AUA: Cryptorchidism (2018)

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• See Guideline Algorithm
• Literature search up to October 2018

Definitions

• Cryptorchidism, or undescended testis (UDT): failure of a testis to descend into a scrotal position
  • Classified as congenital vs. acquired
    • Congenital cryptorchidism: testes that are extrascrotal from the time of birth
    • Acquired cryptorchidism: testes are intrascrotal at birth but subsequently identified in an extrascrotal position
      • Classified as ascending vs. entrapped
        • Ascending: spontaneous change from an intrascrotal to an extrascrotal position occurs at some point after birth
          • Generally unilateral and most likely located distal to the inguinal ring
        • Entrapped: change from an intrascrotal to an extrascrotal position occurs after prior inguinal surgery
      • At risk for developing the same adverse histologic changes seen in primary cryptorchid testes
  • Retractile testis: testis that is initially extrascrotal on examination or moves easily out of scrotal position, (often associated with a vigorous cremasteric reflex), but that can be manually replaced in stable, dependent scrotal position and remain there without tension at least temporarily
• Atrophic testis: testis that suffers significant volume loss due to
  1. Prior inguinal or testicular surgery OR
  2. Due to prolonged location in an extrascrotal position OR
  3. Primary developmental failure
• Vanished testis: testis was present initially but disappeared during development most likely due to spermatic cord torsion or vascular accident.

Background

• Epidemiology
  • Most common genital disorder identified at birth
    • Prevalence among newborns:
      • 1-3% in full-term
      • 15-30% in premature male infants
  • Spontaneous descent of congenitally cryptorchid testes occurred in 35-43% of newborn boys followed longitudinally, usually prior to 3 months of age
    • Descent of the testes into the scrotum is probable in premature boys during the first months of life, but is unlikely after 6 months of corrected age
      • Obtaining the gestational age is thus critical to the proper and timely referral of a child with persistent undescended testes to a surgical specialist
• Normal Testicular Descent
  • Occurs in 2 phases:
    1. Transabdominal descent
    2. Inguinoscrotal migration
  • Transabdominal descent
    • occurs in the first trimester of gestation
    • At approximately 22-25 weeks of gestational age, the testes are located at the internal ring
  • Inguinoscrotal migration
    • Occurs between 25-30 weeks
    • Androgen dependent
• Usually unilateral (70-80%)
  • Approximately 20-30% of all patients with cryptorchidism have bilateral UDTs.
• Potential location of cryptorchid testes (4):
  1. Prescrotal (above or at the scrotal inlet)
  2. In the superficial inguinal pouch (distal and lateral to the external inguinal ring, anterior to the rectus muscle), at the external ring (or prepubic)
  3. Within the inguinal canal
  4. Ectopic
     • Most commonly perineal
     • Abdominal
       • "Peeping" through or proximal to the internal inguinal ring
       • Near the bladder, iliac vessels or kidney
• A genital examination should be performed at least annually at every well-child visit in accordance with Bright Futures AAP recommendations.
  • Testicular position may change as infants and children grow.

Risk factors

• Congenital
  • Gestational history
    • Prematurity
    • Low-birth weight
      • Prevalence of cryptorchidism in infants <900g is approximately 100%
  • Family history
    • 7x risk with affected brother
    • 5x risk with affected father/uncle
    • Molecules involved
      • Insulin-like 3 (INSL3) and its receptor relaxin/insulin-like family peptide receptor 2 (RXFP2)
      • Leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8)
  • Maternal environment
    • Potentially associated
      • Maternal hypertension
      • Maternal diabetes
      • Smoking
      • Analgesic exposure
      • Estrogen
    • No significant association
      • Obesity
  • Environment exposures
    • Endocrine-disrupting chemicals
      • Pesticides
• Acquired
  • Prior inguinal surgery

Diagnosis and Evaluation

History and Physical Exam

History

• Risk factors (see above)

Physical Exam

• Genital exam
  • Ipsilateral gonad
    • Infants should be examined in the supine position with legs gently frog-legged, or sitting on the lap of the parent
      • Older children may be examined in the upright cross-legged or supine position
    • Apply gentle downward pressure along the inguinal canal from the anterior iliac spine to the scrotum and counter palpation with the opposite hand
      • Helps to identify the lowest position of a palpable testis
    • If the testis is palpated, gently grasp it with the dominant hand and continue to sweep the testis toward the scrotum with the other hand.
      • In palpable testes that can be manipulated into the scrotum, it is important to maintain the position of the testis in the scrotum for approximately 30 seconds in order to fatigue the cremaster muscle. This will allow differentiation of a retractile testis from a UDT.
        • Release the testis, and if it remains in place, it is a retractile testis.
        • If it immediately retracts to a prescrotal position, it is a UDT.
    • Repeated examinations, patient distraction techniques, a warm environment, and use of a lubricant for the examiner's hands facilitate the physical examination
  • Scrotum
    • A hypoplastic hemiscrotum may imply that the testis is not present.
    • A vanishing testis may manifest as a testicular "nubbin," which can be palpated in the scrotum, and is representative of a completely atrophic testis
  • Contralateral gonad
    • Size and location should be noted as it may increase the ability to predict the status of the UDT.
      • The presence of compensatory hypertrophy (length > 2 cm in prepubertal young boys) is highly associated with monorchia.
• Careful examination of the (5):
  1. Groin
  2. Femoral region
  3. Perineum
  4. Contralateral hemiscrotum (to detect the rare cases of transverse testicular ectopia)
  5. Pubic areas
• Classify a testis as palpable or nonpalpable
  • Approximately 70% of UDTs are palpable
    • For testes that are not palpable, approximately 30% will be found in the inguinal-scrotal area, 55% will be intra-abdominal, and 15% will be absent or vanishing.
  • Surgical approach is based on the palpability of the UDT
  • If bilateral, nonpalpable testes, consider possible disorder of sex development (DSD)
    • CAUTION: A newborn with a male phallus and bilateral nonpalpable gonads is potentially a genetic female (46 XX) with congenital adrenal hyperplasia until proven otherwise.
      • Failure to diagnose congenital adrenal hyperplasia can result in serious harm, as a high proportion of patients with this condition are unable to regulate their electrolyte levels and may present with shock, hyponatremia and hyperkalemia.
        • Serum electrolytes should be monitored.
        • Additionally, karyotype and a hormonal profile (including 17-hydroxyprogesterone levels, LH, FSH, testosterone and androstenedione) must be obtained with simultaneous consultation with a pediatric endocrinologist and a pediatric urologist.
      • Circumcision should not be performed until after the workup is complete, even if a completely normal phenotypic penis is documented on examination
      • The possibility of DSD, or other syndromes should also be entertained when unilateral or bilateral cryptorchidism is present with phallic anomalies, such as hypospadias or micropenis.
      • Radiological, genetic and endocrinological evaluations are indicated in cryptorchid males with disorder of sex development, in conjunction with hormone levels discussed in guideline statement 8 below.
    • If the infant with bilateral nonpalpable testes has normal penile development or micropenis and 46 XY karyotype, an evaluation to distinguish vanishing testis syndrome (bilateral congenital anorchia (rare)) versus bilateral abdominal testes is warranted.
      • In order to avoid surgical exploration in the 46 XY male with anorchia, studies to assess for the presence of any viable testicular tissue should include serum MIS and consider additional hormone testing (inhibin B, FSH, LH, and testosterone).
        • Within the testis,
          • Leydig cells respond to endogenous LH or exogenous hCG by producing testosterone
          • Sertoli cells respond to endogenous FSH by producing MIS and inhibin B.
        • hCG stimulation
          • The failure of testosterone to increase after hCG stimulation alone is not diagnostic of anorchia; testicular dysgenesis with UDT may fail to respond to hCG stimulation.
          • If the hCG stimulation test is used, it must be confirmed with a significant elevation in serum FSH and LH.
          • If the patient has anorchia and is less than 12 months of age, serum LH is high, FSH is high, MIS and inhibin B are undetectable, and testosterone is low. In infants with anorchia, the postnatal testosterone surge will be absent.
          • most recent studies suggest that a phenotypic 46 XY male with bilateral nonpalpable testes has isolated anorchia if undetectable levels of MIS and inhibin B with an elevated FSH level are present,155 making neither hCG stimulation testing nor surgical exploration necessary for the diagnosis of isolated anorchia
        • If the endocrine markers of Sertoli and Leydig cell function are normal, then testicular tissue is present despite being not palpable and warrants surgical therapy.

Imaging

• Ultrasound (US) or other imaging modalities should not be performed in the evaluation of boys with cryptorchidism prior to referral
  • In the hands of an experienced provider or specialist, more than 70% of cryptorchid testes are palpable by physical examination and need no imaging.
  • US is non-contributory in routine use, with sensitivity and specificity to localize nonpalpable testis at 45% and 78%, respectively.
  • The cost and ionizing radiation exposure associated with CT scanning precludes its use.
  • MRI with or without angiography has been more widely used with greater sensitivity and specificity but is deterred by cost, low availability and need for anesthesia.

Other

Diagnostic laparoscopy

• Gold standard with high sensitivity and specificity
• Indications
  • All nonpalpable unilateral
  • Many bilateral cryptorchid patients
• If a testis is found, the surgery continues and laparoscopic or open orchidopexy is completed, thereby providing diagnosis and therapy simultaneously
• Technique
  • Exhaustive search from the level of the kidney to the internal ring
  • In situations where the testis is identified, a decision is made to proceed with either orchidopexy or orchiectomy.
  • When the testis is not identified, the surgeon must identify the vessels. The vessels may end blindly within the abdomen or exit the internal ring.
    • The identification of the vas deferens should not guide management as it is of distinct embryologic origin and may not be fused to the testis.
  • In cases of vanishing testes that have descended distal to the internal ring, the testicular vessels typically are less robust as they enter the internal ring as compared to the normal descended side.
  • When the vessels end blindly in the retroperitoneum, the surgeon may terminate the procedure or explore distal to the internal ring to confirm the absence of testicular tissue or remove a vanishing testis.
  • In situations where the vessels clearly enter the internal ring, the surgeon must explore either the inguinal canal or the scrotum, depending on the surgeon's preference.

Management

Benefits of Treatment

1. Improve fertility potential
2. Improve testicular growth
3. Reduce risk of testicular malignancy
4. Reduce risk of torsion
5. Treat potential associated inguinal hernia

Timing

• Infants with a history of cryptorchidism (detected at birth) who do not have spontaneous testicular descent by 6 months (corrected for gestational age) should be referred to an appropriate surgical specialist for timely evaluation.
  • Spontaneous descent of testes may occur in the first 6 months of life.
  • Testes that remain undescended by six months (corrected for gestational age) are unlikely to descend spontaneously.
  • Longer duration of testis undescent correlates with higher rates of germ cell loss and adult infertility
• In the absence of spontaneous testicular descent by 6 months (corrected for gestational age), surgery should be performed within the next year (first 18 months of life).
  • While it is optimal to perform surgery for the cryptorchid testis by 18 months of age, there are clear benefits to performing orchidopexy in all prepubertal boys at the time of diagnosis of a cryptorchid testis
    • Progressive and adverse histologic changes will occur in the cryptorchid testis prior to puberty
  • In the post pubertal child with cryptorchidism, consideration should be given to performing an orchiectomy or biopsy, although there needs to be careful consideration of other factors including associated medical conditions, anesthetic risk, and status of the contralateral testis.

Options

• Orchidopexy/orchiopexy
  • Refers to surgical repositioning of the testis within the scrotal sac
  • Current standard of therapy in the United States
• Primary hormonal therapy
  • Historically used for many years
  • Using hCG or luteinizing hormone-releasing hormone (LHRH or gonadotropin-releasing hormone (GnRH))
  • Should not be used to induce testicular descent
    • Evidence shows low response rates and lack of evidence for long-term efficacy.

Approach

• Palpable
  • Standard technique: two-incision approach (inguinal and scrotal)
    • The inguinal portion of the procedure is performed to mobilize the cord structures and gain adequate length for repositioning the testis in the scrotum, along with closure of a patent processus vaginalis, when present. The secondary scrotal incision is performed to create a subdartos pouch for placement and fixation of the testis.
  • If low lying, single incision orchidopexy is also a viable option.
    • Potential advantages with respect to enhanced recovery and cosmesis, as well as reduced operative time. This technique can be effective even when there is a patent processus/hernia sac present
  • If a palpable nubbin is present, in the scrotum, potentially representing a vanishing testis, then scrotal or inguinal exploration can safely be performed.
    • Regardless of the approach, the specimen should be sent for pathologic confirmation, to confirm a vanishing testis and no presence of malignancy.
• Non-palpable
  • Perform examination under anesthesia to reassess for palpability of testes
    • If the testis is palpable, open orchidopexy should be undertaken
  • If nonpalpable, surgical exploration (laparoscopic or open) and, if indicated, abdominal orchidopexy should be performed.
    • Surgical options if an intrabdominal testis is found with anatomy that is felt to be appropriate for salvage (3):
      1. Orchidopexy
      2. One-stage Fowler Stephens (FS) orchidopexy
      3. Two-stage FS orchidopexy
    • The identification of the testicular vessels should be the end point of any exploration for a nonpalpable testis.
    • If the testicle warrants salvage and tesicular vessels are long enough to reach into the scrotum, then the vascular supply should be spared and a primary orchidopexy is performed in preference to FS orchidopexy
    • In the FS approach, the testicular vessels are divided and the blood supply to the testis is maintained through collaterals, including the artery of the vas deferens.
      • When the FS orchidopexy is done in one stage, the testicular vessels are ligated and the testicle is immediately moved down into the scrotum;
      • In the two-stage approach, only ligation is done at the time of the first stage, without mobilization of the testis. The patient is then followed for three to six months, to presumably allow for improved collateral circulation to develop. A second stage repair is then undertaken with repositioning of the testis in to the scrotum.
      • When a primary orchidopexy cannot be performed in cases where the testicular vessels are too short, the decision to perform a one-stage or two-stage FS orchidopexy is left to the discretion for the surgeon based on the location of the testis, associated vascular supply to the testis, and the anatomy of the peritesticular structures.
    • Situations where orchiectomy may be preferred in the presence of a normal contra-lateral descended testis (4)
      1. Atretic and/or short vas deferens
      2. Very short testicular vessels that place the testis high within the retroperitoneum
      3. Dysmorphic testis
      4. Testis in a postpubertal male
    • If an orchiectomy is performed, then the patient and family should be counseled about the importance of wearing protective gear during sporting activity.

Special Scenarios

Retractile testes

• Do not require surgical correction
• Children with retractile testes should be monitored at least annually to assess for secondary "ascent" of the affected testis.
  • Risk of testicular ascent (between 2-45%) may be higher in boys with retractile testes
  • Potential mechanisms related to ascent
    • Hyperactive cremasteric reflex
    • Foreshortened patent processus vaginalis
    • Entrapping adhesions

Acquired cryptorchidism

• Risk factors
  • History of proximal hypospadias
  • History of retractile testes
• Children with a newly diagnosed non-scrotal testis found after six months of age should be referred to a surgical specialist.
  • the same adverse histologic features (e.g. loss of germ cells) found in primary UDTs are also found in acquired cryptorchid testes.

Peeping testis

• May occur when a patent processus vaginalis prevents palpation of the testis. When the abdomen is insufflated with laparoscopy, the testis travels through the internal ring and can be palpated.
• Can be managed safely with either laparoscopic orchidopexy or inguinal orchidopexy.

Follow-up

• Major long-term concerns for patients with a history of cryptorchidism
  • Risk of testicular cancer
    • The increase in the incidence of malignancy in the cryptorchid testis warrants close follow-up, especially after puberty.
    • Every previously cryptorchid boy should be taught how to perform a monthly testicular self-examination after puberty to potentially facilitate early cancer detection.
  • Infertility
    • Formerly bilateral cryptorchid men have greatly reduced fertility
    • Unilaterally cryptorchid men had a paternity rate similar to the level of fertility found in general population

Questions

1. When should patients with cryptorchidism be referred for surgical management?

Answers

1. When should patients with cryptorchidism be referred for surgical management?

References

• Kolon, Thomas F., et al. "Evaluation and treatment of cryptorchidism: AUA guideline." The Journal of urology 192.2 (2014): 337-345.