1. Disease review Benigh Prostatic Hyperplasia GU PK19 조 51 번 오민주

2. Benigh Prostatic Hyperplasia  Microscopic BPH : proliferative process of the stromal and epithelial elements of the prostate  Macroscopic BPH : “enlarged” prostate  Clinical BPH Benign prostatic enlargement (BPE) bladder outlet obstruction (BOO) lower urinary tract symptoms (LUTS)

3. Etiology  Hyperplastic process Androgens Estrogens Stromal-epithelial interactions Growth factors and neurotransmitters

4. Etiology 1. Hyperplasia Androgen, GF → cell porliferation increase (experimental) Androgen → normal cell proliferation & differentiation, cell death inhibition 2. Androgen role BPH development, puberty aging 90% Androgne in prostate = Dihydrotestosterone form Androgne withdrawal → gene activation →programmed cell death 3. Estrogen role 4. Regulation of Programmed cell death (apoptosis) : grandular homeostasis

5. Etiology 5. Stromal - epithemial interaction → maintain sophisticated paracrine type of communication New gland - reawakening of embryonic process 6. GF (GF & steroid interaction ) VEGF, IGF, FGF (1,2,7,17) TGF-β : inhibition 7. Inflammatory pathway and cytokine role IL 2,4,7,17 IFN-γ 8. Genetic factor Inheritable gene component Familiar BPH : large prostate size

6. Pathophysiology increases urethral resistance compensatory changes in bladder function

7. Area density of BPH

8. Clinical manifestations of BPH  LUTS (Low urinary tract symptoms) urinary frequency urgency nocturia decreased & intermittent force of stream sensation of incomplete bladder emptying  poor bladder emptying  urinary retention  detrusor instability  urinary tract infection  hematuria and renal insufficiency

9. Useful predictors of the risk progression  Age  Symptom severity  Flow rate  Prostate size  Serum PSA

10. Complication of BPH 1. Motality : more than 10/100,000 2. Bladder stone (kidey, urethral stone risk = normal) 3. UTI 4. Bladder decompensation 5. Urinary incontinence 6. Upper Urinary Tract Deterioration and Azotemia 7. Hematuria 8. Acute urinary retention (AUR)

11. Acute urinary retention  Etiology : Prostate infection, bladder overdistention,excessive fluid intake, alcohol consumption, sexual activity, debility, and bed rest prostitic infarction  Precipitated AUR => inability to urinate after a triggering event non-prostate-related surgery catheterization, anesthesia ingestion of medication (sympathomimetics, anticholinergics, antihistamine)  All other AUR episodes are classified as spontaneous

12. Diagnosis  Initial Evaluation Medical History Physical Examination Urinalysis Serum Creatinine Measurement Serum Prostate-Specific Antigen Symptom Assessment  Additional diagnosis Postvoidal residual (PVR) urine, urinary flow rate Pressure-flow urodynamic study Filling Cystometry (Cystometrography) Urethrocystoscopy Imaging of the Urinary Tract

13. Diagnosis  Medical History : History or hematuria, UTI, diabetes, nervous system disease (e.g.,Parkinson’s disease or stroke), urethral stricture disease, urinary retension, aggravation of symptoms by cold or sinus medication Anti cholinergics : impair bladder contraction α sympathomimetics: out flow resistence increase Previous lower urinary tract surgery history Void diary (volume, time record)  Physical Examination DRE, abdominal examination  Urinalysis Dipstick test or microscopic exam (severe irritable symptoms & dysuria, especially with smoking hx)  Serum Creatinine Measurement : no standard

14. Diagnosis  Serum Prostate-Specific Antigen (PSA,< 4.0 ng/mL) prostate cancer check : LUTS by producing bladder outflow obstruction commonly coexists with BPH PSA test and DRE ->increase the detection rate of prostate cancer  Symptom assement The International Prostate Symptom Score(IPSS) : No diagnosis Used for the baseline assessment symptom severity (mild 0-7, moderate 8-19, sever 20-35)  Additional diagnosis IPSS 0-7 = no need IPSS ≥8 : Postvoidal residual (PVR) urine, urinary flow rate,Pressure-flow urodynamic study

16. Algorithm for management of BPH

17. The choice of treatment

18.  First-line management of uncomplicated BPH 1. α-adrenergic blockers (if the prostate is larger) 2. 5α-reductase inhibitor 3. Combination therapy (α-adrenergic blockers+5α-reductase inhibitor) : most effective means of preventing disease progression Medical therapies for BPH

19.  Contraindication (may develop life-threatening consequences) Recurrent urinary retention Recurrent UTIs Renal insufficiency Bladder calculi Recurrent gross hematuria

20. α-adrenergic blockers  Rationale clinical BPH caused by bladder oulet obstruction, α1 adrenoceptors (α1 AR) associated with prostatic smooth muscle  Α1blockers : Provide symptomatic relief of BPH symptoms  Available drugs : doxazosin, terazosin, alfuzosin, tamsulosin (Older drugs, Phenoxybenzamine and Prazosin are not recommended)  long-acting α1 blockers well tolerated Terazocin, doxazosin coexisting BPH and hypertension -significantly lower blood pressure only in hypertensive subjects Class of α Blocker Nonselective Phenoxybenzamine α1α1 Prazosin IR Alfuzosin Indoramin Long-Acting α 1 Terazosin Doxazosin Alfuzosin SR

21. Androgen Suppression  Rationale Embryonic development of the prostate is dependent on the androgen dihydrotestosterone (DHT) Testosterone is converted to DHT by the enzyme 5α- reductase The genetic deficiency of 5α-reductase in males : rudimentary prostate and in feminized external genitalia

22. Androgen Suppression  Most extensively characterized in BPH  Benefits on LUTS associated demonstrable prostatic enlargement  Maximal reduction of prostate volume achieved within 6 months  Finasteride The long-term safety and durability of efficacy Adverse clinical events : minimal and are related primarily to sexual function. Very effective in the management of gross hematuria associated with BPH Drugs GnRH Analogues Leuprolide Nafarelin acetate Cetrorelix Progestational Agents 17α-Hydroxycortisone Megestrol Antiandrogens Flutamide Oxandolone Bicalutamide (Casodex) Zanoterone 5α-Reductase Inhibitors Finasteride

23. Combination therapy   -adrenergic blocker and 5  -reductase inhibitor  Most effective means of preventing disease progression

24. Minimally invasive & endoscopic management  Intraprostatic Stents : management of patients who were unfit for surgery  Transurethral Needle Ablation of the Prostate : management of patients who had lateral lobe enlargement and a prostate of 60 g or less complication : post-treatment urinary retention irritative voiding symptoms Urinary tract infection Urethral strictures  Transurethral Microwave Therapy

25. Minimally invasive & endoscopic management  Lasers  Transurethral Prostatectomy(TURP) : Gold standard for the surgical management of BPH Improving symptoms up to 95% : Indication acute urinary retention recurrent infection recurrent hematuria and azotemia.  Transurethral Vaporization of the Prostate Transurethral Incision of the Prostate : effective particularity for small prostates

26. Open prostatectomy  considered when the obstructive tissue is estimated to weigh more than 75 g or sizable bladder diverticula or calculi exist.  Retropubic and suprapubic prostatectomy  Suprapubic prostatectomy : Ideal for men with a large median lobe, significant bladder diverticulum, or large bladder calculi

27. Open prostatectomy  Advantages of open prostatectomy over TURP lower retreatment rate more complete removal of the prostatic adenoma under direct vision No risk of dilutional hyponatremia (the TURP syndrome)  Disadvantages of open prostatectomy over TURP lower midline incision longer hospitalization increased potential for perioperative hemorrhage

28. Complications of open prostatectomy 1. Urinary incontinence 2. Erectile dysfunction 3. Retrograge ejaculation 4. UTI 5. Bladder neck contracture 6. Urethral stricture 7. Deep Vein Thrombus 8. Pulmonary Embolus

29. Reference  Campbell's Urology, 9th ed. - Walsh  전립선비대증 : 대한전립선학회