Benign Prostatic Hyperplasia Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital

Bladder Outlet obstruction Bladder neck dysfunction Prostatic enlargement Urethral stricture External sphincter dyssynergia Urethral meatal stenosis BOO is a condition of progressive degree

Lower urinary tract symptoms IPSS & AUA symptom score Frequency Urgency Nocturia Small caliber of urine Dysuria Intermittency Residual urine sensation

LUTS and BOO 1/3 of men with LUTS do not have BOO 5% - 35% of patients with BPH & LUTS do not improve symptoms after TURP LUTS have a poor diagnostic specificity for BOO Prostate size and uroflowmetry have better correlation with urodynamic study than symptoms alone

Pathogenesis of Bladder outlet obstruction Progressive increased urethral resistance High voiding pressure and low flow Bladder compensation in energy Increased residual urine volume Elevated intravesical pressure at end-filling Bladder stone, diverticulum, UTI Hydroureter, hydronephrosis, azotemia

Reduction in AChE-positive nerve fibers after BOO

Differential diagnosis of male BOO and LUTS Benign prostatic enlargement Bladder neck dysfunction Spastic urethral sphincter Poor relaxation of urethral sphincter Urethral stricture Low detrusor contractility Pseudodyssynergia due to neuropathy

Relation of prostate and urethra

Benign prostatic hyperplasia Prostatic enlargement – benign or malignant, a sign Prostatic hyperplasia – histological term Prostatic obstruction – a clinical diagnosis Bladder outlet obstruction – an urodynamic term Lower urinary tract symptoms – symptom

Anatomy of Prostate gland

Anatomy of Prostate gland

Prostatic glandular anatomy

Cystoscopic Prostatic obstruction

Benign Prostatic Hyperplasia BPH requires testicular androgen during prostatic development Basic fibroblast growth factor, epidermal growth factor, keratinocyte growth factor, transforming growth factor-beta play some part in prostate growth Decreased endogenous apoptosis in prostate cause abnormal tissue growth in prostate

Histology of Benign prostatic hyperplasia

Clinical BPH LUTS ( storage or empty symptoms) due to histological benign prostatic hyperplasia and urodynamical bladder outlet obstruction which has been proven by urodynamic pressure flow study as prostatic obstruction Treatment for LUTS and restoration of normal storage and empty function by reducing prostatic enlargement either medically or surgically

Pathophysiology of BPH and LUTS Nodular proliferation of prostate gland Increased stroma to epithelial ratio to 2:1 to 5:1 in benign prosatic hyperplasia Increased smooth muscle component Detrusor compensatory change and bladder dysfunction, detrusor overactivity LUTS may related to BPH or detrusor dysfunction,or combination

Symptom scores of BPH as treatment guideline 1970 Boyarsky and Madsen-Iverson 1992 AUA symptom index International prostatic symptom score adds quality of life index Bothersomeness and health related quality of life (HRQOL) Symptom problem index BPH impact index (BII)

Clinical evaluation of BPH Digital rectal examination of prostate -- Prostate size, consistency, surface nodularity, tenderness Bladder palpation – residual urine volume Cystography, Intravenous pyelography Transrectal sonography of prostate Cystourethroscopy

Cystography of Bladder base elevation indicating BPH

Sonography of BPH

Clinical evaluation of BPH Uroflowmetry, prstatic volume Postvoid residual urine volume Prostatic specific antigen (PSA) Pressure flow study improves in diagnosis and aid in selection for specific invasive treatment Videourodynamic study is helpful in determining complicated case

Uroflowmetry in BPH without or with obstruction

Pressure flow study in BPH with Obstruction

Videourodynamic study in BPH with Obstruction

Causes of non-obstructive Men with LUTS Normal bladder and urethra 25 Bladder hypersensitivity 17 Detrusor instability 6 Detrusor underactivity 3 Poor relaxed urethral sphincter 61

Videourodynamic study in Man with normal bladder and urethra

Videourodynamic study in Man with low detrusor contractility

Videourodynamic study in Man with Poor relaxation of sphincter

Subjective improvement rate in patients after prostatectomy HPOB LPOB LPNOB Qmax <10 10-15 >15 Total Irritative symptoms good 23 2 1 10 9 7 26(52%) fair 4 12 21(42%) Got worse - 3 3(2%) Obstructive symptoms 28 5 21 35(70%) 13(26%) 2(4%) Subjective results Successful 31 18 14 34(68%) Unchanged 6 10(20%) Failed 6(12%)

Improvement in Qmax after Prostatectomy

Causes of 185 Men with LUTS after prostatectomy Normalbladder and urethra 17 Detrusor instability 18 Low detrusor contractility 35 Poor relaxation of urethral sphincter 36 Detrusor instability and low contractility 27 Bladder outlet obstruction 52

Prostate volume, Qmax, resected prostate weight in patients with LUTS after prostatectomy prostatic weight,g Preoperative prostatic vol, ml PreoperativQmax, ml/s Normal tracing(n=17) 12.3 ± 7.4 22.5 ± 14.2 11.0 ± 5.2 DI (n=18) 14.3 ± 15.4 26.5 ± 21.7 10.9 ± 4.0 LC (n=35) 8.9 ± 8.7 17.6 ± 13.8 9.6 ± 4.5 PRS (n=35) 9.2 ± 5.2 17.6 ± 8.8 8.4 ± 4.6 DHIC (n=27) 10.3 ± 7.1 19.9 ±10.3 10.5 ± 4.5 BOO (n=52) 14.4 ± 12.6 25.6 ± 18.7 9.7 ± 4.5 Statistics (ANOVA) P=0.131 P=0.140 P=0.559

Urodynamic parameters in BPH Age N FSF Capacity Pves Voided Qmax CQmax MUCP PPA ≦45 9 77.5±24.9 238.4±87.4 106.2±31.3 173.6±73.2 12.5±3.6 0.99±0.25 86.7±12.5 87.5±0 46-55 30 95.8±28.4 263.3±98.5 84.5±36.3 240.7±123.6 10.8±3.9 0.74±0.24 82.5±21.6 111.4±32 56-65 156 116.2±49.8 263.4±103.1 92.0±38.4 215.9±113.4 10.2±3.3 0.74±0.23 90.0±35.1 107.8±90.1 66-75 159 129.7±74.4 256.6±116.8 85.9±35.9 186.7±103.2 9.9±5.9 0.78±0.53 99.4±46.2 137.9±84.5 ≧76 64 128.9±81.1 214.9±115.5 90.7±44.4 166.4±76.6 9.3±4.1 0.74±0.28 96.7±45.3 126.±112.3 All 418 124.2±70.8 244±114.3 89±39.6 198.1±109.9 10.1±4.6 0.76±0.38 94.8 ±41.8 125.1±91.4

Relationship of Qmax and Age in BPH patients

Clinical Prostate Score in BPH Clinical prostate scoring system for patients with lower urinary tract symptoms Uroflowmentry (ml/s) Residual urine (mL) Qmax ≧ 15 -1 < 100 10 Qmax <15 ≧ 100 2 Qmax ≦ 10 1 Voided volume (mL) Flow pattern ≧ 250 Normal < 250 Compressive obstructive TZI Comstrictive obstructive ≦ 0.3 Intermittent > 0.3 but < 0.5 TPV (mL) ≧ 0.5 ≦ 20 Median lobe enlargement > 20 but <40 Presence ≧ 40 Absence

Calculation of Clinical Prostate Score for Diagnosis of BPO Prostate score = Qmax + TPV + voided volume + residual urine Score ≧ 3: sensitivity = 90.7%, specificity = 33% Prostate score = Qmax + flow pattern + voided volume + residual urine + TPV + TZI + prostatic configuration Score ≧ 3: sensitivity of BPO = 87.2%, specificity = 60.8% Score ≧ 4: sensitivity of BPO = 90.7%, specificity = 50.5% Score ≧ 5: sensitivity of BPO = 97.6%, specificity = 38.2% Sensitivity and specificity of BPO diagnosis in patients with at least 1 favorable predictive factor (n = 148) Score ≧ 3: sensitivity of BPO = 91.6%, specificity = 87.27% Exclusion of patients with at least 1 favorable predictive factor (n=176) Score ≧ 3: sensitivity of BPO = 68.9%, specificity = 23.0%

Prostatic Transition Zone Index

A-G Number in Diagnosis of BPO

Treatment of BPH Treating an enlarged prostate ? Treating lower urinary tract symptoms? Treating bladder outlet obstruction? Can LUTS disappear after treatment? Can BOO be relieved after treatment? Any complication may occur? Is the treatment cost- effective ?

Therapeutic modalities for LUTS ascribed to the prostate Watchful waiting and fluid restriction, natural history of BPO may wax and wan Medical treatment to reduce prostate size or decrease intraprostatic resistance Surgical treatment to remove prostatic obstruction or reduce urethral resistance Minimally invasive therapies

Surgical Treatment for BPH Suprapubic & retropubic prostatectomy Transurethral prostatectomy (TUR-Prostate) Laser interstitial prostatectomy Transurethral incision of prostate Intraprostatic stent Balloon dilatation of prostatic urethra Prostatic hyperthermia

Prostate Resectoscope and TURP

Complications of TUR-Prostate Peri-operative bleeding Urinary tract infection and urosepsis Electrolyte imbalance, hemolysis, acute tubular necrosis Acute pulmonary edema Bladder neck or urethral contracture Retrograde ejaculation and erectile dysfunction Urge or stress urinary incontinence

Minimally invasive procedure Transurethral vaporization- resection of prostate (TUVRP) Ho-YAG laser coagulation of prostate Visual laser ablation of prostate (VLAP) Transurethral needle ablation (TUNA) High intensity focused ultrasound (HIFU) Microwave hyperthermia Minimally invasive = minimally effective? A higher re-treatment rate than TURP although less complication occurs

Intra-Prostatic Stent

Interstitial Laser Coagulation

Hyperthermia of BPH

Transurethral Dilatation of Prostate

Medical Therapy for BPH Prostatic smooth muscle tension was mediated by alpha 1-adrenoreceptors Smooth muscle contractions contribute 40% of outflow obstruction Alpha 1- blockers can rapidly improve Qmax and relieve LUTS Phenoxybenzamine, terazosin, doxazosin have side effect of dizziness and hypotension

Prostatic specific alpha- adrenoreceptor Alpha 1A- AR subtype comprises 70% of all alpha-1 receptors Alpha 1A-AR agonist – tamslosin has 13 x more affinity to prostatic smooth muscle than urethral muscle , 10 x than vascular smooth muscle Side effects are still reported Long-acting (once daily) dose

Hormone based medical therapy 5-alpha-reductase catalyzes conversion of testosterone to dihydrotestosterone Inhibition of 5-alpha-reductase can arrest prostatic growth and relieve obstruction Finasteride can improve symptom score,Qmax, QOL score Effective especially in prostatic weight of >40 gm and effective in prostatic hematuria

Combination therapy with alpha-blocker and finasteride Terazosin is effective therapy, finasteride was not, combination was no more effective than terazosin alone (Lepor, N Engl J Med 1996; 335: 533) Combined dibenyline and finasteride has an additive effect than dibenyline or finasteride alone in improvement of Qmax and prostatic size

Consideration in treating BPH Patients are old in symptomatic BPH Too early surgery may lead to undesired sequalae such as erectile dysfunction Too late surgery cannot reverse detrusor overactivity and leads to urge incontinence Etiology of LUTS (DI? DHIC? BOO?) should be clarified to prevent unsuccessful surgical results

Therapeutic guideline for BPO Calculation of clinical prostatic score and QOL index, medical treatment for BPO Monitoring Qmax, residual urine volume, and prostate volume during treatment If obstructive or irritative symptom exacerbate, detailed pressure flow study to confirm the BOO diagnosis Surgery for patients with poor QOL index