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Testicular Descent and Ascent: A Matter of Timing

Testicular Descent and Ascent: A Matter of Timing . Yegappan Lakshmanan, MD, FAAP Pediatric Urology Children’s Hospital of Michigan. Disclosures. None. Why do testes descend?. 2 to 3 degree F difference in temperature needed for spermatogenesis

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Testicular Descent and Ascent: A Matter of Timing

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  1. Testicular Descent and Ascent: A Matter of Timing Yegappan Lakshmanan, MD, FAAP Pediatric Urology Children’s Hospital of Michigan

  2. Disclosures • None

  3. Why do testes descend? • 2 to 3 degree F difference in temperature needed for spermatogenesis • Only in primates do testes descend at or near birth (hibernating animals descend only during breeding season, whales cooled by water, birds by air during flight)

  4. Testicular Descent: Why the fuss? • A fused scrotum with 2 descended testes is better than any genetic or hormonal test for “manhood” • Porphyry Chair - “La Sedia Gestatoria” • Middle Ages: 1099 (Paschal II) and 1513 (Leo X)

  5. “duo testes bene pendulum” (‘he has 2 testes and they hang well’)

  6. Terminology • Cryptorchidism vs Undescended Testis • Retractile testis • In and out of scrotum but returns to a dependent scrotal position • Ascended testis (acquired) • Documented scrotal position after birth but subsequently not in scrotum

  7. Objectives • Testicular Descent • Current perspectives in treating UDT • Timing of orchidopexy • Bianchi or scrotal approach • Nubbins • Testicular Ascent • Extravaginal torsion

  8. Testicular Descent: Trans-abdominal phase • Gubernaculum – swelling reaction • Cranial suspensory ligament regression • Insl3 from Leydig cells + MIS /DHT • Few mutations of Insl3 / Lgr8 described in patients Klonisch et al, Dev Bio, 270:1-18, 2004; Hutson et al, J Ped Surg, 40:297-302, 2005

  9. Testicular Descent:Inguinoscrotal Phase • Androgen dependent • Deficiency of this phase with retention of CSL in: • LuRKO (LH receptor knockout) • Natural hpg mouse • Natural tfm mouse • Androgens do not suppress CSL in male bats Klonisch et al, Dev Bio, 270:1-18, 2004; Hutson et al, J Ped Surg, 40:297-302, 2005

  10. Epidemiology • Most frequent anomaly of the male GU system • No predilection for race or geographic location • Mostly sporadic but may be associated with genetic disorders

  11. Undescended Testis:Incidence • Newborn:3 to 5% (Full-term, >2500 gm) • At 1 year:0.8 to 1% (after 6 months) • Adults:0.8%

  12. Incidence • By 1 year of age: 0.8-1.5% (constant into adulthood) • 75% of full term and 95% of premature testes will descend (usually in 1st 3 months) • 10% bilateral • 80% of UDT palpable • 20% impalpable (cryptorchid) • Half intra-abdominal • Other half – vanishing or atrophic • 14% of boys have family history of same

  13. Classification • Abdominal • Canalicular • Ectopic- perineum, femoral canal, superficial inguinal pouch, suprapubic, contralateral scrotum (due to gubernacular attachments)

  14. Investigations • Imaging does not influence management (overall accuracy of 44%) • Physical exam is 84% accurate when done by a pediatric urologist • Hormonal workup • Bilateral impalpable testes: HCG stimulation (if normal gonadotrophin levels) • False negatives possible • FSH / MIS / Inhibin B

  15. Histology • The longer the testis is cryptorchid, the more likely it is to be histologically abnormal - changes appear by 1 ½ yrs of age • The higher the testis the more pronounced the abnormality • Hypolasia of Leydig cells, smaller seminiferous tubules, fewer spermatogonia, peritubular fibrosis • Unclear whether changes in testis are due to intrinsic defect or secondary to cryptorchid state (changes often seen in contralateral testis)

  16. Undescended Testis:Histology & Germ Cell maturation • Primary dysgenesis in 20 – 100% • By 2 years, 30 – 40% are aspermatogenic (as early as 15 months) Ong et al, Pediatr Surg Int, 21:240-254, 2005

  17. Undescended Testis:Effects on Fertility - Paternity

  18. Undescended Testis:Fertility – hormone levels • Inhibin B and FSH: • Biomarkers of seminiferous tubule integrity • Correlate well with sperm density • In a cohort of post-op patients, age at orchidopexy was found to correlate • Inversely with Inhibin B levels • Positively with FSH and serum Testosterone levels • Indirect evidence favoring early orchidopexy Lee et al, J Urol, 160:1155-57, 1998 and 167:1824-27, 2002

  19. Current recommendations For truly undescended testes: • Surgical correction anytime after 6 months, preferably before age 1 • Testes that descend are likely to do so by the age of 6 months (Wenzler et al, J Urol, 2004) • Biopsy at orchidopexy has demonstrated more spermatogonia per tubule and larger diameter of seminiferous tubules <1 year of age

  20. Risk of Neoplasia • Testicular Ca incidence 1 in 100,000 • 10% have a H/O UDT • Incidence of Test Ca in UDT is 1 in 2550 (Farrer et al, 1985) for a RR of 40x • Intra-abdominal testes have 6 times greater risk than inguinal testes (half the tumors) • RR 3.6 in contralateral descended normal testis in men with unilateral cryptorchidism

  21. Nubbins? • Remnant gonadal tissue at inguinal exploration should be excised because 13% have viable residual testicular elements • Theoretical risk: • Approx 10% contain residual tubules • 5.6% contain germ cells (De Luna et al, 2003)

  22. Biopsy? • Carcinoma in situ incidence – 1.7% • More common in abdominal testis • But no definite correlation with later development of malignancy • Justifiable in high risk groups: • Danish • Older boys presenting with cryptorchidism • Transplant considerations

  23. Surgical Intervention • EUA to locate testis • Palpable – Inguinal orchidopexy • Impalpable – Laparoscopy

  24. Laparoscopy • For locating non-palpable testes (>95% accuracy) • Findings: • Blind ending vessels above internal ring • Cord structures entering internal ring • Intra-abdominal testis

  25. Surgical Intervention • Nubbin – excise • Contralateral orchidopexy? • Role of Scrotal Orchidopexy • Bianchi approach

  26. Bianchi procedure • Single high scrotal incision – 1980’s • Several large reported series since • Rajimwale et al, Ped Surg Int 2004 (Denver) • Samuel and Izzidien, Ped Surg Int 2008 (Cardiff) • Bassel et al, J Urol, 2007 (Atlanta) • Applicable in UDT situated in the superficial inguinal pouch or lower • Processus vaginalis approachable • Single incision

  27. Extravaginal Torsion • “Bilateral neonatal torsion” – LaQuaglia et al, J Urol, 1987 • 4 cases between 1966-86; 2 asynchronous, 1 salvaged • “Perinatal extravaginal torsion of the testis in the first month of life is a salvageable event” – Sorensen et al, Urology, 2003 • 10 boys < 30 days old, with unilateral torsion – 4 saved

  28. Extravaginal Torsion • “Management of perinatal torsion: today, tomorrow or never?” – Yerkes et al, J Urol, 2005 • 18 pts in 3 institutions over 3 years; 4 had contralateral unsuspected torsion resulting in atrophy (22%) – 2 others in early stages were salvaged • “Perinatal testicular torsion: preoperative radiological findings and the argument for urgent surgical exploration.” – Ahmed et al, J Pediatric Surg 2008 (San Diego – 2 pts) • “Neonatal bilateral testicular torsion: a plea for emergency exploration” – Baglaj and Carachi, J Urol, 2007 (Scotland – 3 cases and lit review)

  29. Extravaginal Torsion • Management: • If diagnosis certain: • Scrotal exploration / orchiectomy / contralateral orchidopexy • If not: • Inguinal exploration • Timing: • If seen immediately: at next available opportunity • If seen later: decide after due counseling

  30. Testicular Ascent • Prevalence of undescended testes stable after age 1 ~ 1% • Reported orchidopexy rates are as high as 2 to 3% of all boys up to age 14 to 17 years • Barthold et al, J Urol, 170:2396-2401, 2003 • Initially thought to be due to treatment of retractile testes

  31. Testicular Ascent • Possible Etiologies: • Persistent processus vaginalis • Ligamentous PV causing tethering • Cremaster spasticity i.e Cerebral Palsy • High scrotal testes (“gliding”) • Mobile superficial inguinal pouch testes • Failure of testicular vessels to elongate • Scarring after groin surgery • Error in diagnosis – missed during infancy

  32. Testicular Ascent: To Pex or Not to Pex? • Dutch ‘national testis registry’ – 1986 • Orchidopexy in ascended testis only for failure to descend at puberty (with testicular volume appropriate for age) • In 2003, of 63 boys with 74 ascended testes: Hack et al, Br J Surg, 90:728-31, 2003 • 15 boys (20 testes) – operated at parental request • 4 boys (4 testes) – lost to followup • 42 of remaining 50 descended at puberty • Recommended conservative management

  33. Testicular Ascent: To Pex or Not to Pex? • Confirm diagnosis by serial examination of “retractile testes” • 5 to 7% incidence of secondary ascent • Conservative management if testicular volume appropriate for age, until puberty • Operate if progressively higher location, or smaller volume • Histological changes and germ cell counts similar to UDT • ? Role of HCG

  34. Conclusions • Testicular location after birth variable • Spontaneous descent & ascent occur • All boys need routine examination throughout childhood • Closer surveillance of ‘retractile testes’ • If undescended, orchidopexy between age 6 to 12 months • Ascended testes may also need orchidopexy

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