Editing CUA: Cryptorchidism (2017)

'''See Original Guideline'''

'''See Undescended Testicle Chapter Notes'''

===== '''*****All of the information below is contained in the more comprehensive Undescended Testicle Chapter Notes*****''' =====

* '''Definition of cryptorchidism: inability to palpate the testicle in the expected normal anatomical position''' (i.e., within its respective hemi-scrotum)
** '''Classified as congenital vs. acquired'''
*** '''Distinction based on findings documented during the neonatal exam.'''
**** In congenital cases, the testicle is not palpable in the scrotum at birth
**** In acquired cryptorchidism (or “ascending” testicle) is in a normal location at birth (or on subsequent well-child exams), but not later in life.
* '''Retractile testes: scrotal testes that retract easily out of the scrotum along the normal path of descent due to a brisk cremasteric reflex but can be manually replaced in a stable scrotal position and remain there at least temporarily until there is recurrent stimulation.'''
* '''“True” undescended vs. ectopic testes:''' Based on location (as determined during physical exam and/or surgery) within or outside the normal path of testicular descent, respectively. An ectopic testicle is unlikely to spontaneously descend or respond to hormonal stimulation.
* '''Palpable vs. non-palpable testicle: Based on ability to feel the testicle during physical exam. If non-palpable, diagnostic considerations include intra-abdominal testicle, inaccurate exam, and testicular absence or atrophy (so-called “nubbin”). The diagnosis is commonly confirmed during exam under anesthesia and surgical exploration'''

== Epidemiology ==

* '''Cryptorchidism is diagnosed in 1.0‒4.6% of full-term and 1.1‒45.3% of preterm male neonates.'''
* Following spontaneous decent, '''often seen in the first 3‒6 months of life, prevalence stabilizes at 0.7–1.0% of one-year-old boys'''
* ≈75% of undescended testes are palpable and unilateral
* '''Risk factors for cryptorchidism (may be incomplete list):'''
*# '''Family history'''
*# '''Prematurity'''
*# '''Prune-Belly syndrome'''
*# '''Down’s syndrome'''
*# '''Prader-Willi syndrome'''
*# '''Noonan’s syndrome'''

== Long-term implications ==

# '''Hypogonadism'''
# '''Reduced fertility'''
#* '''Paternity rates are largely unchanged for men with unilateral cryptorchidism compared to the general population''' (≈90%), '''but are significantly lower (33‒65%)''' '''for those with bilateral UDT'''
#* '''Both location of the testicle and time correlate with Leydig and germ cell loss. Intra-abdominal/non-palpable testes depict severe germ cell loss, as do testes that remain undescended by age 2'''
# '''Risk of testicular cancer'''
#* '''Relative risk (RR) of UDT: 2.75‒8x; risk is slightly increased also in the normally descended testis.'''
#* '''Performing orchiopexy prior to puberty appears to decrease the RR of subsequent testicular cancer to 2.23, but it still remains above that of the normal non-cryptorchid male'''

== Rationale for treatment ==

* '''Surgical correction is offered early after diagnosis'''
* '''Goals of treatment'''
** '''Maximize chances of adequate hormone production and future fertility potential''' by preventing acquired/progressive damage
** '''Prevent testicular torsion'''
** '''Locate testicle(s) in a position amenable to self-exam''' (or caretaker/healthcare provider regular assessment in patients unable to reliably conduct self-examination) which aids in early diagnosis of testicular cancer
** '''Treat associated conditions, such a patent processus vaginalis/inguinal hernia'''
** Avoid missing viable gonadal tissue in an abnormal location (most important intra-abdominal), as it could lead to delayed diagnosis of testicular neoplasm
** Relocate all viable gonad(s) in scrotum to maximize psychological benefits of normal anatomy
** Prevent direct testicular trauma against the pelvic bones during intercourse or sports
** Avoid unnecessary imaging studies
** Minimize parental anxiety
** Consider surgical morbidity, comorbidities, life expectancy, and fertility expectations in special situations

== Diagnosis and Evaluation ==

* '''Physical exam'''
** '''Genital exam by an experienced healthcare provider with good documentation of testicular position should be conducted in all newborn males. In addition, the presence of associated genitourinary abnormalities (such as hypospadias and inguinal hernia) and ipsilateral scrotal hypoplasia should be assessed.'''
*** '''Ultrasound evaluation is not a substitute for a well-performed exam''' '''and it does not add diagnostic accuracy to an evaluation by a less experienced healthcare provider or a limited exam due to an uncooperative child.'''
*** '''A virilized newborn with bilateral non-palpable gonads should be considered to be 46XX with congenital adrenal hyperplasia (CAH) until proven otherwise.'''
** '''Distinguish between a normally located gonad, retractile testicle, palpable undescended/ectopic testicle, and non-palpable testicle. Associated conditions, such as an inguinal hernia, are concomitantly evaluated. The exam should be performed in a quiet, warm environment, assisted with lubrication if needed, and focus on the inguinal canal and scrotum, along with less common ectopic sites (perineal, femoral, prepubic).'''
** '''In patients with unilateral cryptorchidism, evaluation of the contralateral gonad is important in order to detect potential problems with the normally located testicle (such as atrophy, varicocele, abnormal volume, or consistency for age).'''
** '''The presence of testicular hypertrophy, most often suspected when the axial length of the testicle is > 1.8‒2 cm),''' '''is associated with a higher likelihood of an absent or atrophic non-palpable gonad.'''
* '''Imaging studies (no role)'''
** '''Imaging in cryptorchidism is not cost-effective, may delay referral and surgical treatment, and as such cannot be recommended as a standard adjunct to preoperative assessment of these children'''
*** Imaging studies that require sedation or anesthesia (such as MRI), regardless of the diagnostic performance of the test, do not have any therapeutic value. Thus, under most circumstances, surgical exploration is not avoided and a second anesthetic will be required for treatment.
*** The use of imaging modalities that employ ionizing radiation (such as CT scans) should be avoided
*** None of the currently available imaging modalities have sufficient reproducible diagnostic accuracy to confidently rule out the presence of intra-abdominal viable gonadal tissue. Thus, ultimately, in most cases surgical exploration is not avoided.
*** '''Imaging tests may have potential merit solely in directing the best initial approach (e.g. scrotal vs. inguinal vs. laparoscopic exploration).'''
* '''Need for investigation for DSD, karyotype, and other biochemical/genetic studies'''
** '''The incidence of karyotype or other genetic abnormalities in boys with cryptorchidism is low;''' '''routine karyotype or genetic workup of patients with UDT is NOT recommended'''
** '''Karyotype is indicated in patients with (2):'''
**# '''Bilateral non-palpable gonads and a normal phallus with an orthotopic urethral meatus; a phenotypically male newborn with bilateral nonpalpable testicles should be considered to be a genetic female with CAH (21-hydroxylase deficiency) until proven otherwise'''
**#* '''If XX karyotype found, obtain 17-hydroxy-progesterone levels (elevated in congenital adrenal hyperplasia)'''
**#* '''If XY karyotype found, the diagnosis of bilateral vanishing testicles or testicular regression syndrome (TRS) should be considered. In such patients, the combination of high gonadotropins, low testosterone levels (even after stimulation), and very low or undetectable levels of anti-Mullerian hormone may preclude any surgical intervention.'''
**# '''At least one undescended testicle (particularly if non-palpable) and proximal hypospadias'''
**** '''≈1/3 of these patients have a DSD'''
**** '''DSD has not been observed in patients with UDT and distal hypospadias'''
**** WT1 mutations have been identified in 7.5% boys with proximal hypospadias and at least one UDT who were tested. '''Targeted WT1 genetic testing in patients with proximal hypospadias and at least one UDT should be considered'''
** '''Persistent Mullerian Duct Syndrome (PMDS)'''
*** '''Suggested by the presence of Mullerian structures (uterus, fallopian tube) attached to an undescended testicle (more commonly intra-abdominal)'''
*** '''Usually an intraoperative finding'''
*** '''Rarely, can lead to both testicles occupying the same side of the abdomen (transverse testicular ectopia)'''
*** '''Surgical removal of the Mullerian structures seems logical since malignancies have been reported''' and at times their attachments can hinder the performance of a tension-free orchidopexy.
*** '''When Mullerian remnants are found incidentally during an inguinal orchidopexy, the proximal aspect of the fallopian tube can be transected and removed with the uterus, leaving its distal component attached to the vas deferens, allowing the testis to be brought to a scrotal position''' Such a maneuver avoids separation of the tube from the cord structures, protecting the deferential and testicular blood supply.
*** Patients should have AMH levels checked and be referred to endocrinology/genetics for investigation.
** If a DSD is discovered, patients should be followed in a multidisciplinary clinic specific to these complex diagnoses.

== Management ==

* '''See Figure 1 from Original Guideline'''
* '''Hormone therapy has a limited role in the management of cryptorchidism and should not be recommended as first-line therapy'''
** '''Treatment of UDT with either hCG or LHRH does not seem to cause harm and may be effective; however, reported success rates are inconsistent'''
* '''Surgical exploration'''
** '''Timing'''
*** '''Orchidopexy is recommended between 6-18 months of age'''
**** '''Testicular descent is unlikely to occur in full-term babies after 6 months of age'''
*** '''Orchiopexy techniques'''
**** '''Surgical approach to the palpable testicle'''
***** '''Inguinal (most common) or prescrotal/scrotal'''
****** '''High (proximal) ligation of the processus vaginalis is an essential surgical step to allow placement of the testis in a sub-dartos pouch within the hemi-scrotum, without tension'''
**** '''Surgical approach for the non-palpable testicle'''
***** '''If the testicle is not palpable preoperatively, as may occur in up to 20% of UDT cases, examination under anesthesia (EUA) can sometimes allow identification of the testicle. Otherwise, diagnostic laparoscopy is the procedure of choice in most centres.'''
****** '''In certain non-palpable testicle (NPT) cases, confident palpation of an ipsilateral scrotal nubbin and identification of contralateral compensatory testicular hypertrophy may preclude diagnostic laparoscopy by means of initially performing a scrotal incision, which allows for testicular nubbin removal and confirmation of the vanishing testicle diagnosis'''. Inguinal exploration and/or laparoscopy can then be reserved for cases in which the initial scrotal approach is non-diagnostic.
******* '''It is critical to highlight the importance of confidently identifying atrophic testicular tissue with associated vas deferens and gonadal vessels if a scrotal or inguinal approach is chosen, as any doubt should trigger further exploration.''' Presence of a looping vas or incorrectly identifying non-gonadal tissue as a nubbin may lead to misdiagnosis, potentially leaving viable testicular tissue in the abdomen'''. In uncertain cases or when tissue analysis is not consistent with atrophic testicular tissue, laparoscopic exploration should be strongly considered'''
***** '''Diagnostic laparoscopy is the most useful modality for assessing NPT, as it permits identification of three surgical scenarios that will lead to different courses of action:'''
*****# '''Blind-ending vas and vessels indicate a vanishing intra-abdominal testicle (IAT), and no further exploration is necessary''' (10‒30% of cases).
*****# '''Testicular vessels and vas entering the inguinal canal through the internal inguinal ring.'''
*****#* '''Inguinal exploration may find a healthy palpable UDT amenable to standard orchidopexy, or a testicular nubbin either in the inguinal region or, most commonly, in the scrotum.''' Remnant cord structures are usually removed to confirm the diagnosis and because viable residual testicular elements are present in up to 14% of the cases. It should be noted that to date, no cases of intratubular germ cell neoplasia have been reported within these specimens.
*****# '''Peeping''' (just inside internal ring) '''or intra-abdominal testis (50%), which will require either an open or a laparoscopic orchidopexy in one or two stages.'''
***** '''Inguinal approach for the high inguinal canalicular, or intra-abdominal testis'''
******* '''Helpful maneuvers to bring a high testicle down to the scrotum while preserving its blood supply:'''
*******# '''Divide the lateral fibrous attachments of the cord at the internal inguinal ring'''
*******# '''Blunt dissection of the retroperitoneal spermatic vessels''' (which are usually the limiting factor) up to the lower pole of the kidney
*******# '''Mobilization of the cord medial to the inferior epigastric vessels (Prentiss maneuver)'''
*******# '''Despite these steps, if the testicle still does not reach the scrotum, a Fowler-Stephens (FS) orchidopexy may be performed.'''
***** '''Fowler-Stephens orchidopexy'''
****** Originally described as a single-stage open inguinal approach for the IAT in which the testicular artery and veins were too short to allow adequate testicular mobilization into the scrotum through standard orchidopexy
****** '''Principles:'''
******* '''Open approach'''
******** '''Ligating and dividing the testicular vessels'''
******** '''Preserving the''' '''distal gubernacular attachments and the collateral vessels on the floor of the inguinal canal, maintaining the cremasteric blood supply'''
******* '''Laparoscopic approach'''
******** '''Ligating and dividing the testicular vessels and cremasteric collaterals'''
******** '''Preserving the gubernaculum''', mimicking one of the surgical steps of the open FS technique, may help decrease the likelihood of testicular atrophy
******** '''Testicle is advanced medial to the inferior epigastric vessels or obliterated umbilical artery'''
******* '''When the testis is > 2 cm above the internal ring with no vascular redundancy, it is unlikely that the testis will be able to reach the scrotum without dividing the spermatic vessels. In this situation, staged Fowler-Stephens procedure with division of the gonadal vessels at the first stage has a significantly higher success rate than primary Fowler-Stephens procedure'''
**** '''Open vs. laparoscopic orchidopexy for NPT'''
***** Laparoscopic orchidopexy outcomes are comparable to those of open surgery
***** Laparoscopic approach is associated with shorter operative time, shorter return to normal activities, and reduced risk of atrophy at one year (10% laparoscopic vs. 19% open)
**** '''Complications'''
***** '''The most serious complication of inguinal orchidopexy is testicular atrophy, which occurs when the testicular vessels are damaged'''
***** '''Rare complications include''' '''testicular ascent''', where the testicle gets pulled to the entrance of the scrotum, '''and vas deferens injury'''. Other orchidopexy related complications might include those associated with any surgical procedure, such as wound infection, dehiscence, and hematoma.
**** '''Prophylactic contralateral orchidopexy'''
***** In the absence of literature strongly supporting or discouraging prophylactic orchidopexy, '''the decision should be made based on informed discussion of options with the patient parents or legal guardian'''
****** Preventive orchidopexy of the normally descended contralateral testicle in the setting of blind-ending spermatic vessels found upon exploration of a non-palpable testis has been advocated by some authors, based on the reported risk of bell-clapper deformity and abnormal testicular fixation found in the remaining solitary testis.
****** The risk of torsion is admittedly low, conceptually not different from the general population.
** '''Testicular biopsy is not indicated at the time of orchidopexy'''
* '''Conservative management'''
** '''UDT is associated with a multitude of syndromes, some of which can lead to limited life expectancy and/or severe developmental delay (e.g., Down’s, Prader-Willi, and Noonan’s syndromes)'''
** Given the reports of testicular cancer (sometimes at an early age) in these patients, '''we recommend orchidopexy when they are clinically fit for anesthesia for the purpose of surveillance'''
* '''Previous failed orchidopexy'''
** '''We recommend offering redo orchidopexy for cases where inadequate position is detected postoperatively'''

== Follow-up ==

* Although UDT are unquestionably associated with a higher risk for development of testicular cancer, the incidence rates of this type of cancer are small and hence '''no screening policy is justified'''.
* '''There is no need for formal long-term urological follow-up of patients with UDT.'''
* '''Periodic self-exam after puberty is recommended''' with prompt referral to an urologist if an abnormality is noted.

== Age at which orchiectomy is advisable over orchidopexy ==

* '''Orchiectomy remains the treatment of choice for the majority of post-pubertal males presenting with unilateral cryptorchidism, especially when these testicle is small in size (hypotrophic/atrophic).''' Most of these testes have significant malignant potential and cannot contribute to fertility (Sertoli only syndrome).
** '''For patients with unilateral intra-abdominal and inguinal hypotrophic testes identified after puberty, orchiectomy be offered as an option (not mandatory)'''
** '''Observation of a hypotrophic/atrophic UDT is appropriate in patients age > 50'''

== Acquired cryptorchidism ==

* Acquired UDT are diagnosed at an average age of 8‒11 years.
* The percentage of retractile testicles that ascends and requires orchidopexy is difficult to estimate, ranging from 3‒30% in prepubertal children. It is difficult to set a specific age for correction of these cases because it may vary from child to child.

== Questions ==

# What is the prevalence of cryptorchidism at birth in full-term babies? At 12 months?
# List risk factors for cryptorchidism
# What are long term complications of cryptorchidism?
# What are sites of ectopic testicle?
# When is karyotype indicated in patients with UDT?
# At what age should orchidopexy be considered for UDT?
# What are surgical approaches to the palpable testicle?
# Describe the steps to gain length on the spermatic cord for orchidopexy?

== Answers ==

# What is the prevalence of cryptorchidism at birth in full-term babies? At 12 months?
# List risk factors for cryptorchidism
# What are long term complications of cryptorchidism?
# What are sites of ectopic testicle?
# When is karyotype indicated in patients with UDT?
# At what age should orchidopexy be considered for UDT?
# What are surgical approaches to the palpable testicle?
# Describe the steps to gain length on the spermatic cord for orchidopexy?