BPH

1. BPH

2. Benign Prostatic Hyperplasia

3. PROSTATE GLAND • a walnut-sized gland found in the true pelvis of males just behind the symphysis pubis. • composed of several regions or lobes that are enclosed by an outer layer of tissue (capsule) • Three distinct zones: • peripheral zone (PZ) • central zone (CZ) • transitional zone (TZ)

4. PROSTATE GLAND • Benign prostatic hyperplasia uniformly arise in the transitional zone • 60-70% of carcinomas originate in the peripheral zone • 10-20% in the TZ • 5-10% in the CZ

5. Benign Prostatic Hyperplasia • Characterized by hyperplasia of prostatic stromal and epithelial cells, resulting in the formation of large, fairly discrete nodules in the periurethral region of prostate • With sufficient growth the nodules can compress the urethral canal causing partial, or sometimes complete obstruction of urethra inhibiting urine flow • Not considered as a premalignant tumor [ PSA]

7. Incidence & Epidemiology • Most common benign tumor in men • Incidence is age-related • 20% - men aged 41-50 • 50% - men aged 51-60 • 90% - men older than 80

8. ETIOLOGY • Risk factors are poorly understood [multifactorial] • BPH involves both the stromal and epithelial elements of the prostate undergoing hyperplastic changes • Seems strongly tied to endocrine control [levels of free testosterone and estrogen] • As men age the androgen receptors of the prostate becomes increasingly sensitive/hormonally dependent on testosterone and dihydrotestosterone (DHT) production

9. Dihydrotestosterone (DHT) • In both cell types (stroma/epithelial), DHT binds to nuclear androgen receptors and signals the transcription of growth factors that are mitogenic • Though testosterone can also bind to androgen receptors and cause growth stimulation, DHT is 10x more potent because it dissociates from androgen receptors more slowly

10. PATHOLOGY • BPH originates from the transition zone • Hyperplastic process resulting from increase number of cells

11. PATHOLOGY • Nodular growth pattern composed of stroma and epithelium • BPH nodules in the transition zone enlarge and compress the outer zones of the prostate  formation of surgical capsule

12. PATHOPHYSIOLOGY • Symptoms are either obstructive or secondary response of the bladder to the outlet resistance • As enlargement ensues, mechanical obstruction may result from intrusion into the uretheral lumen or bladder neck  high bladder outlet resistance

13. PATHOPHYSIOLOGY • Stroma composed of smooth mm and collagen is rich in adrenergic nerve supply  autonomic stimulation sets a tone to the prostatic urethra • Irritative voiding complaints are secondary response of the bladder to increased outlet resistance

14. Clinical Findings of BPH

15. Symptoms • Obstructive • Hesitancy •  Force and caliber of stream • Sensation of incomplete bladder emptying • Double voiding • Straining to urinate • Post-void dribbling • Irritative • Urgency • Frequency • Nocturia

16. Symptoms • AUA (American Urological Association) Symptom Score questionnaire • Single most important tool to evaluate patients with BPH • Recommended for all patients before initiating therapy • Self-administered • Identifies the need to treat • Monitors therapeutic response • Scoring: 0-35

17. Source: Smith’s General Urology, 17th ed.

18. Signs • Physical examination • DRE • Focused neurologic examination

19. Signs • Size and consistency • Smooth, firm, elastic enlargement of the prostate=BPH • Induration=CA? • Further evaluation: PSA, transrectal US, biopsy

20. Laboratory Findings • Assessment of renal function • Urinalysis • Serum creatinine • Renal insufficiency: • 10% of patients with prostatismupper-tract imaging •  Risk of postoperative complications from surgical intervention for BPH • Serum PSA: Optional

21. Imaging • Upper-tract imaging (intravenous pyelogram or renal US) • Recommended only in the presence of concomitant urinary tract disease or complications from BPH

22. Cystoscopy • Not recommended to determine need for treatment • Assist choosing surgical approach for invasive therapy

23. Additional Tests • Cystometrograms and urodynamic profiles • Tests for bladder capacity & pressure, and lower urinary tract symptoms (bladder, urethra) respectively • Suspected neurologic disease • Failed prostate surgery • Flow rate measurement, post-void residual urine, pressure-flow studies • Optional

24. Differential Diagnosis: • Urethral Stricture • Bladder Neck Obstruction • hx of previous urethral instrumentation, urethritis or trauma • Bladder Stones- Hematuria and pain • UTI- Mimics the irritative symptoms of BPH • Urinalysis and culture • Neurogenic Bladder- hx of neurologic problems, stroke, dm, or back injury. • PE: diminished perineal or lower extremity sensation or alteration in bulbocavernous reflex

25. Treatment: • Mild symptoms (score 0-7)- watchful waiting • Surgical indications • refractory urinary retention • recurrent UTI • recurrent gross hematuria • bladder stones • renal insufficiency • large bladder diverticula

26. Medical Therapy: • Alpha blockers • alpha-1-adrenoreceptors located in the prostate and bladder • Contractile response of prostate to agonists • Selective blockade of α1a receptors = fewer A.E. • 5α-reductase inhibitors (Finasteride) • blocks conversion of testosterone to dihydrotestosterone • ↓ size of prostate • Improvement of symptoms (>40cm)

27. Medical Therapy: • Combination therapy • Alpha blockers + 5α-reductase inhibitors • Phytotherapy • use of plants or plant extracts for medicinal purposes • MOA, efficacy and safety unknown

28. Conventional Surgical Therapy: • Transurethral resection of the prostate (TURP) • Done endoscopically • Symptom score and flow rate improvement • Longer hospital stay • TUR syndrome • Transurethral incision of the prostate • More rapid less morbid • Open Simple Prostatectomy • Done when the prostate is too large to be removed endoscopically

29. Conventional Surgical Therapy: • Open Simple Prostatectomy • Glands >100g • With concomitant bladder diverticulum or bladder stone or dorsal lithotomy position is not possible

30. Conventional Surgical Therapy: • Simple Suprapubic Prostatectomy • Procedure of choice in dealing with concomitant bladder pathology • Simple Retropubic Prostatectomy • The bladder is not entered

31. Minimally Invasive Therapy: • Laser Therapy • Transurethral Electrovaporization of the Prostate • Hyperthermia • Transurethral Needle Ablation of the Prostate • High Intensity Focused Ultrasound • Intraurethral Stents • Transurethral Balloon • Dilation of the Prostate

32. Prostate Cancer

33. Molecular genetics, Pathophysio

34. Prostate Cancer Prostate Cancer • most common cancer diagnosed & is the 2nd leading cause of cancer death in American men • Incidence continues to  with advancing age (no peak) • Lifetime risk of a 50-yr old man for latent CaP: 40%; clinically apparent: 9.5%; death from CaP: 2.9%

35. Risk factors: • Increasing age • Race • Family history • High dietary fat intake • Exposure to chemicals (e.g. cadmium)

36. Molecular genetics • Chromosome 1 • Gene responsible for familial prostatic cancer • Tumor suppressor genes (8p, 10q, 13q, 16q, 17p, 18q) • Found in the regions human genome

37. Pathology • Nature : • More than 95% are adenocarcinomas • 5% are transitional cell carcinomas • 90% are neuroendocrine (“small cell”) carcinomas or sarcomas

38. Histologic characteristics • - hyperchromatic, enlarged nuclei, w/ prominenent nucleoli • - cytoplasm abundant & slightly blue-tinged or basophilic • - absent basal cell layer • - HMW keratin immunohistochemical staining

39. Origin of Prostatic cancer • Peripheral zone- 70% • Transitional zone- 10 to 20% • Central zone- 5 to 10%

40. Prostatic Intraepithelial Neoplasia (PIN) • - Precursor to invasive prostatic cancer • - Basal cell layer of the glandular architecture is present • Classifications: • High grade PIN • - associated with invasive Prostatic cancer in 50-80% of cases • Low grade PIN • - ~20% of the cases

41. Prostatic Intraepithelial Neoplasia (PIN) classic histologic features: - intermediate-to-large size preexisting glands displaying nuclear and nucleolar enlargement and fragmented basal cell layer

42. Grading and Staging • Gleason score or Gleason sum • primary grade + secondary grade • Gleason grades: 1- 5 • Gleason scores: 2 - 10 • Tumor Grade Score • Well-differentiated 2 - 4 • Moderately-differentiated 5 - 6 • Poorly-differentiated 8-10

43. Gleason grades 1 & 2 • - small, uniformly shaped glands, closely packed, w/ little infiltrating stroma

44. Gleason 1 • The most important difference between Gleason pattern 1 and 2 is the presence or absence of circumscription

45. Gleason 2 • The glands are round to oval and uniformly placed. There are no sharply-angulated or distorted glands. 

46. Gleason 3 • - Variable-sized glands that percolate between normal stroma • Cribriform pattern • - a small mass of cells is perforated by several gland lumens w/ no intervening stroma  cookie-cutter-like appearance of cell nests • - smooth border

47. This example of Gleason grade 3 cancer shows abundant amphophilic cytoplasm, enlarged nuclei with prominent nucleoli. Higher magnification view of the previous slide. Most glands have occluded lumens. The nuclei are hyperchromatic.

48. Gleason 4 • - Incomplete gland formation • Several histological appearances: • - sometimes glands appear fused, sharing a common cell border • - sheets of cell nests or long cords of cells • - cribriform glands (large masses, ragged borders w/ infiltrating fingerlike projections

49. The glands are fused and there is no intervening stroma. Glandular fusion is a hallmark of Gleason grade 4. Higher magnification view of the previous slide. Most glands have occluded lumens. The nuclei are hyperchromatic.

50. Gleason 5 • - single infiltrating cells, no gland formation or lumen appearance • comedocarcinoma •  cribriform glands w/ central areas of necrosis