1.  The Status of UDT Management in The State of WV in The Light of AUA Guidelines. West Virginia Chapter on AAP, 4/15/2016 Osama AL-Omar, M.D., FEBU. Assistant Professor of Surgery. Director of Pediatric Urology. West Virginia University.

2. UDT and AUA guidelines (2014)  Terminology.  Epidemiology.  AUA guideline on UDT (16 statements):  Standard  Option  Clinical principle

3. Terminology: UDT vs Ectopic

4. Ectopic Testicle

5. Terminology: More ….  Retractile testicle: one that is initially extra-scrotal, but can be manually replaced in the scrotum without tens, at least temporarily.  Ascending (Acquired) testicle: Cryptorchid testicle that is documented as in scrotal position at a previous examination without intervening inguinal surgery.  Vanishing testicle: present initially in development but are lost owing to vascular accident or torsion unilaterally ( monorchia ) or, very rarely, bilaterally ( anorchia ).  Testicular Agenesis: refers to a testis that was never present and therefore associated with ipsilateral müllerian duct persistence.

6. Epidemiology:  Cryptorchidism is one of the most common congenital anomalies, occurring in 1% to 4% of full-term and up to 45% of preterm male neonates.  The prevalence decreases to 0.8% at age 6 month old.  It is a component of over 390 syndromes (like Prune-belly syndrome).  The majority of cases are isolated, with the ratio of non- syndromic to syndromic cryptorchidism reported as greater than 6 : 1. Campbell-Walsh, 11 th edition, 2015

8. AUA guideline Statements: Statement#1 (Risk factors)  “Providers should obtain gestational history at initial evaluation of boys with suspected cryptorchidism”. (Standard; Evidence Strength: Grade B).  The prevalence of cryptorchidism is higher in premature boys in the first months of life (1-3% in full-term and 15-30% in premature male infants)  Low birth weight for gestational age: the prevalence of cryptorchidism in infants <900g is approximately 100%, while decreases to 3% in infant weighing 2.7-3.6 kg. AUA guidelines, 2014

9. AUA guideline Statements: Statement#2 (Child Well Visit)  “Primary care providers should palpate testes for quality and position at each recommended well-child visit.” (Standard; Evidence Strength: Grade B) AUA guidelines, 2014 To determine : The current position of UDT or in an ectopic location. Spontaneous descent of testes may occur in the first six months of life. Additionally, testes may "ascend" out of the scrotum (acquired cryptorchidism).

10. AUA guideline Statements: Statement#3 (Time of Referral)  “Providers should refer infants with a history of cryptorchidism (detected at birth) who do not have spontaneous testicular descent by six months (corrected for gestational age) to an appropriate surgical specialist for timely evaluation.” (Standard; Evidence Strength: Grade B)  Rate of spontaneous descending is 50-87%, based on location (extra-scrotal vs high scrotal testes, respectively).  Descending happens in the first 6 months of life (corrected age)  The rationale for referral by six months is the low probability of spontaneous descent and the probable continued damage to testes that remain in a non-scrotal location. AUA guidelines, 2014

11. AUA guideline Statements: Statement#4 (Ascending Testicle)  “Providers should refer boys with the possibility of newly diagnosed (acquired) cryptorchidism after six months (corrected for gestational age) to an appropriate surgical specialist.” (Standard; Evidence Strength: Grade B)  Acquired or ascending testicle: Cryptorchid testicle that is documented as in scrotal position at a previous examination.  The prevalence of acquired cryptorchidism is (1-7%) and peaks around 8 years of age  Reason : fibrous persistence of the processus vaginalis, which limits the growth of the spermatic cord.  Risk Factor: Retractile testicles (34%), Hypospadias and Hx of contralateral UDT.* * Agarwal PK, Diaz M, Elder JS., JUrol. 2006 AUA guidelines, 2014

12. AUA guideline Statements: Statement#5 (UDT & DSD)  “Providers must immediately consult an appropriate specialist for all phenotypic male newborns with bilateral, nonpalpable testes for evaluation of a possible disorder of sex development (DSD).” (Standard; Evidence Strength: Grade A)  A newborn with a male phallus and bilateral nonpalpable gonads is potentially a genetic female (46 XX) with CAH until proven otherwise.  Karyotype, serum electrolytes and a hormonal profile (LH, FSH, testosterone) should all be done. AUA guidelines, 2014

13. Bilateral Nonpalpable UDT

14. AUA guideline Statements: Statement#6 (Imaging)  “Providers should not perform ultrasound (US) or other imaging modalities in the evaluation of boys with cryptorchidism prior to referral, as these studies rarely assist in decision making.” (Standard; Evidence Strength: Grade B).  Factors that influence this recommendation against imaging (US, CT scan or MRI) include:  imaging accuracy,  cost, availability,  rate of false positives,  radiation and need for anesthesia.  At this time, there is no radiological test that can conclude with 100% accuracy that a testis is absent.  Diagnostic laparoscopy is the gold standard with high sensitivity and specificity. AUA guidelines, 2014

15. AUA guideline Statements: Statement#7 (UDT & Hypospadias)  “Providers should assess the possibility of a disorder of sex development (DSD) when there is increasing severity of hypospadias with cryptorchidism. (Recommendation; Evidence Strength: Grade C).  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.  Cox et al, (2008) : 32% risk of DSD in patient who has proximal hypospadias and UDT (mixed gonadal dysgenesis, Autosomal translocations, and 48XY aneuploidy). AUA guidelines, 2014

16. Mixed Gonadal Dysgenesis (MGD)

18. AUA guideline Statements: Statement#8  “In boys with bilateral, nonpalpable testes who do not have congenital adrenal hyperplasia (CAH), providers should measure Müllerian Inhibiting Substance (MIS or Anti- Müllerian Hormone [AMH]) and consider additional hormone testing to evaluate for anorchia.” (Option; Evidence Strength: Grade C).  Patient who has bil nonpalpable UDT with 46 XY karyotype, may have hormonal workup or wait until age 6 months to undergo laparoscopic exploration.  Hormonal workup: Tes, LH, FSH, hCG stimulation test, and MIS. AUA guidelines, 2014

19. AUA guideline Statements: Statement#9 (Retractile Testes)  “In boys with retractile testes, providers should assess the position of the testes at least annually to monitor for secondary ascent.” (Standard; Evidence Strength: Grade B).  Testicular examination is recommended at least annually at every well-child visit in accordance with Bright Futures AAP recommendations (2014).  Etiology: presence of a hyperactive Cremasteric reflex.  Why: Retractile testes are at increased risk for testicular ascent (34%) AUA guidelines, 2014

20. AUA guideline Statements: Statement#10 (Hormonal Therapy)  “Providers should not use hormonal therapy to induce testicular descent as evidence shows low response rates and lack of evidence for long-term efficacy.” (Standard; Evidence Strength: Grade B).  The overall review of all available studies fails to document long-term efficacy.  Success rates: 6-21% in randomized, blinded studies (mostly distal inguinal UDT).  Side effects of hCG treatment seen in up to 75% of boys include:  Increased scrotal wrinkles, pigmentation, and pubic hair.  Penile growth.  Inducing epiphyseal plate fusion and retard future somatic growth. AUA guidelines, 2014

21. AUA guideline Statements: Statement#11 (Time of Surgery)  “In the absence of spontaneous testicular descent by six months (corrected for gestational age), specialists should perform surgery within the next year.” (Standard; Evidence Strength: Grade B).  Time of surgery: between age 6 and 18 months, to preserve available fertility potential.  After 15 to 18 months of age some cryptorchid boys will have decreased number of germ cells, Leydig and Sertoli cells in the testes. AUA guidelines, 2014

22. AUA guideline Statements: Statement#12 (Surgical Approach)  “In prepubertal boys with palpable, cryptorchid testes, surgical specialists should perform scrotal or inguinal orchidopexy.” (Standard; Evidence Strength: Grade B).  Outpatient procedure with minimal morbidity.  There are cosmetic, fertility and cancerous advantages.  Success rate is greater than 96%. AUA guidelines, 2014

23. AUA guideline Statements: Statement#13 (Surgical Approach)  “In prepubertal boys with nonpalpable testes, surgical specialists should perform examination under anesthesia to reassess for palpability of testes. If nonpalpable, surgical exploration and, if indicated, abdominal orchidopexy should be performed.” (Standard; Evidence Strength: Grade B).  Advantage: diagnostic and treatment procedure at the same time. AUA guidelines, 2014

24. AUA guideline Statements: Statement#14  “At the time of exploration for a nonpalpable testis in boys, surgical specialists should identify the status of the testicular vessels to help determine the next course of action." (Clinical Principle)  Results of exploration:  Vanishing testicle: do nothing further.  Intraabdominal viable testicle: Primary vs FS orchiopexy. AUA guidelines, 2014

25. Normal Laparoscopic view of Cord structures

26. Vanishing Testicle

27. Video:

28. AUA guideline Statements: Statement#15 (Orchiectomy)  “In boys with a normal contralateral testis, surgical specialists may perform an orchiectomy (removal of the undescended testis) if a boy has a normal contralateral testis and either very short testicular vessels and vas deferens, dysmorphic or very hypoplastic testis, or postpubertal age.” (Clinical Principle) AUA guidelines, 2014

29. AUA guideline Statements: Statement#16 (Cancer & Infertility)  “Providers should counsel boys with a history of cryptorchidism and/or monorchidism and their parents regarding potential long-term risks and provide education on infertility and cancer risk.” (Clinical Principle).  UDT and testicular cancer:  Risk of Testicular Ca in normal men is 1:500  The increased incidence of malignancy in cryptorchid testes varies from (0.05%) to (1%).  The RR of testicular cancer in UDT is 2.75-8, which decreased to 2-3 in patients who underwent orchiopexy before puberty (age 10-12 years).  UDT and fertility:  Risk of infertility: normal men (7%), unilateral UDT (10%) and bilateral UDT (33%). * * 2009 Pediatric review Syllabus, volume 1 of 2, AUA publication

31.  THE PATTERN OF REFERRAL FOR UNDESCENDED TESTICLES IN WEST VIRGINIA AND OUR ADHERENCE TO THE AUA GUIDELINES Chad Morley, MD; Dana Point, MD; Osama Al-Omar, MD Division of Urology/Pediatric Urology, West Virginia University Robert C. Byrd Sciences Center, Morgantown, WV, USA

32. Objectives  Determine compliance with current guidelines of pediatric patients requiring surgical intervention for cryptorchidism in West Virginia  Statement 3 – Referral time  Statement 6 – Scrotal US  Statement 11 – Orchiopexy before 18 months  Determine referring provider characteristics  Comparisons with a more urban center, Johns Hopkins University

33. Background  It has been proposed that the age at time of intervention for cryptorchidism serves as an indicator of medical awareness, access and overall quality of health care  The Urologic Diseases in America Project (UDAP) in 2012  87% of American children with cryptorchidism underwent between 6-12 months of age.  Data taken from only children with private insurance  Pediatric Health and Information System (PHIS) in 2013  61% of children with private insurance coverage underwent timely intervention compared to 54 % of those without private insurance

34. Methods  Retrospective review of all pediatric patients who underwent surgical management of UDT or non-palpable testicles  Age at time of surgery in months  Single Surgeon and Institution  Only Pediatric Urology referral center in state  January 2013 through March 2014.  Surgical Intervention (N=100)  Inguinal Orchiopexy  Laparoscopic Orchiopexy  Exclusion Criteria:  Torsion  Diagnostic laparoscopy and orchiectomy for non-UDT  Multiple complex urologic issues  Severe VUR requiring re-implantation  Hypospadias  Bladder Exstrophy

35. Age at time of Orchiopexy Number of Patients Mean Age at Referral +/- SD (months) Avg Age at Referral 6.45 (+/-3.64) Avg Age at Surgery 11.36 (+/-3.35) Time from Referral to Surgery 4.91 (+/-2.22) 18 – 48 mos 25 Avg Age at Referral 24.37 (+/-10.94) Avg Age at Surgery 31.34 (+/-8.32) Time from Referral to Surgery 6.97 (+/-5.77) 48 – 132 mos 25 Avg Age at Referral 90.70 (+/-23.29) Avg Age at Surgery 96.07 (+/-23.98) Time from Referral to Surgery 5.10 (+/-3.83) Avg Age at Referral 154.16 (+/-21.24) Avg Age at Surgery 158.86 (+/-22.44) Time from Referral to Surgery 4.69 (+/-2.28) 39 11 < 18 mos > 132 mos

36. Age Group at Time of SurgeryWVU N(%) JHU N (%)p Value Group 1 39 (39.0)38 (29.0)0.0552 Group 2 25 (25.0)25 (19.0)0.1396 Group 3 25 (25.0) 53 (40.5) 0.0069* Group 4 11 (11.0) 15 (11.5) 0.4574

38. Scrotal Ultrasound

39. Referring Provider Characteristics by Age Group Number of Patients (%) < 18 mos 39 (39.0) A. Private vs Academic Private 29 (74.4) Academic 10 (25.6) B. Specialty Pediatrics 29 (74.4) Family 5 (12.8) Other 5 (12.8) Number of Patients (%) 18 – 48 mos 25 (25.0) A. Private vs Academic Private 18 (72.0) Academic 7 (28.0) B. Specialty Pediatrics 14 (56.0) Family 6 (24.0) Other 5 (20.0) Number of Patients (%) 48 – 132 mos 25 (25.0) A. Private vs Academic Private 24 (96.0) Academic 1 (4.0) B. Specialty Pediatrics 22 (88.0) Family 3 (22.0) Other 0 (0.0) Number of Patients (%) > 132 mos 11 (11.0) A. Private vs Academic Private 9 (81.8) Academic 2 (18.2) B. Specialty Pediatrics 6 (54.5) Family 2 (18.2) Other 3 (27.3)

40. Referring Provider Characteristics

42. Conclusions  Average age at time of orchiopexy was 48.3 months  Need to improve referral time and time from referral to surgery  39 % of patients underwent surgical intervention within the recommended timeframe of less than 18 months.  Unsure of the true rate of ascending testicles, so annual exam is necessary  Overuse of scrotal ultrasounds for diagnosis  If any uncertainty, please refer

43. Questions? Thank You

44. Thank you. Questions….