Prostate anatomy, structure & function – define BPH & BOO, which terminology?

1. Prostate anatomy, structure & function – define BPH & BOO, which terminology? Kieran Jefferson Consultant Urological Surgeon

3. Biography 08 - Partner, Warwickshire Urology 06 - Consultant, UHCW 05-06 Fellow in uro-oncology, Bristol 98-05 SpR urology, Southwest deanery 94-98 Basic surgical training, Bristol 90-93 BM BCh, Oxford 87-90 BA (Nat Sci), Cambridge

4. Potential conflict of interest • Ipsen (Decapeptyl) Paid consultant; principal trial investigator; book sponsorship; meeting sponsorship • Wyeth/Takeda (Prostap) Trial co-investigator; meeting sponsorship; paid lecturer; book sponsorship • Glaxo (Dutasteride) Trial co-investigator, meeting sponsorship, paid lecturer • Astrazeneca(Zoladex) Principal trial investigator; meeting sponsorhip; paid lecturer • Novartis (Zoledronate) Trial co-investigator; meeting sponsorship • Sanofi Synthelabo (Docetaxel) Meeting sponsorship; book sponsorship

5. What is a prostate? • prostate = ‘protector’ gr. • exocrine gland • reproductive role

7. Who needs a prostate? • Phylogenetic conservation in mammals • Wide variation in ejaculatory volumes • human 3ml, boar 250ml! • Ejaculate nourishes sperm & ↑motility • fructose, citrate, spermine, prostaglandins, Zinc • Optimises fertility • acid-base buffering, antibacterial

8. Semen • Spermatozoa (100 million)+ seminal plasma • Plasma from SVs and prostate • PSA – serine protease; ? lyses seminal clot • Seminogelins – coagulation and capacitation

9. Embryology • Wolffian ducts form SV, epididymis, vas • requires testosterone (not DHT) • Prostate develops from urogenital sinus • requires DHT/5-AR • glands bud from urogenital sinus • reciprocal induction • Stromal-epithelial interaction • endoderm/mesenchyme

10. Androgen dependent (DHT) Differentiation vs proliferation vs apoptosis Testicular androgens from Leydig Cells Prostatic 5-AR converts to DHT Adult prostate

11. Gross anatomy • 20g; 3 x 4 x 2 cm • Ovoid; narrow apex and broad base • Apex continuous with rhabdosphincter • Inf vesical, int pudendal and mid rectal arteries • Lymphatic drainage to obturator/iliac nodes

14. Sagittal section • B = bladder; CS = verumontanum; DVC = dorsal venous complex; PS = pubic symphysis; • pPF/SVF = Denonvilliers’ fascia; R = rectum; RU = rectourethralis; SS = striated (rhabdo) sphincter; VEF = visceral endopelvic fascia

15. Axial section mid-prostate • DVC = dorsal vascular complex; ED = ejaculatory ducts • NVB = neurovascular bundle; PEF/VEF = parietal/visceral endopelvic fascia; PF = prostatic fascia; pPF/SVF = Denonvilliers’ fascia; R = rectum; U = urethra

16. Axial section at sphincter • DVC = dorsal venous complex; MDR = median dorsal raphe; NVB = neurovascular bundle; PB = pubis; PPL = puboprostatic ligament • SS = striated (rhabdo) sphincter; U = urethra; VEF = visceral endopelvic fascia.

17. McNeal’s Zones • Transition Zone (TZ; 5-10%) • BPH & excess cancers (20%) • Surrounding stroma • Central Zone (CZ; 25%) • ? Wolffian Duct origin • surrounds ejaculatory ducts • Peripheral zone (PZ; 70%) • Most prostate cancers • Most prostatitis • Anterior fibromuscular stroma (AFS)

18. McNeal’s Zones TZ TZ CZ PZ PZ

19. Histology 70% glandular structures; 30% stroma Thin fibromuscular capsule Surrounds urethra lined with transitional epithelium

20. Stromal-epithelial interaction • Details complex (if at all understood) • and constantly changing • Androgen actions on stromal cells • trigger paracrine release of growth • factors, which act on epithelial cells, • regulating differentiation, proliferation • and apoptosis

21. Nomenclature • Benign prostatic hyperplasia (BPH) • histological diagnosis • cellular proliferation (epithelium & stroma) • Transition zone predominantly • Benign prostatic enlargement (BPE) • clinical/radiological diagnosis • Lower urinary tract symptoms (LUTS) • does not presume cause cf ‘prostatism’ • Bladder outlet obstruction (BOO) • cystometric finding • low flow despite high detrusor pressure

22. Benign Prostatic Hyperplasia • Overgrowth of epithelium and stroma • SM hypertrophy and increased tone • Predominantly TZ change of unknown aet • Imbalance of proliferation/apoptosis • May cause BOO, LUTS and complications • Near ubiquitous in old men (90% > 80y/o)

23. LUTS • Possible to have any combination of LUTS, BPH and BOO • Reasonable association between LUTS, prostate volume and PSA • Storage vs voiding symptoms • IPSS score increases with age • Degree of bother important

24. BOO • No population level stats for cystometric BOO • Qmax < 10ml/s – likely to have BOO • Qmax > 15ml/s – unlikely to have BOO • Flow rates decline with age

25. Complications of BPH/BOO • Incomplete bladder emptying/OAB • Bladder stones • (0.1% per year) • UTI • unusual in RCTs • Obstructive uropathy • rare in RCTs; no case in 3000 MTOPs patients in 4 years • Acute retention of urine • 2% per year in PLESS study

26. Conclusions • Prostate essential for reproduction • BPH is almost universal in older men • LUTS and complications are common but most men do not experience them • Degree of enlargement does not equate to severity of LUTS