Objectives Benign Prostate Disorders ƒ To review the causes and symptoms of prostatitis FkPBFrank P. Begun, MDM.D. ƒ TdtdthdiidTo understand the diagnosis and Associate Professor, Urology management of prostatitis and Medical Director, Urological Services at OSU East Hospital Pelvic Pain Syndrome The Ohio State University

Objectives/Goals Benign Prostate Disorders ƒ To understand the causes of BPH ƒ To review the symptoms related to BPH ƒ Benign Prostatic ƒ To gai n k nowl ed ge of th e diff eren t Hyperplasia (BPH) forms of treatment for bladder outlet ƒ Prostatitis obstruction due to BPH Medical management ƒ Pelvic Pain Syndrome (PPS) Surgical options Other treatments

1 BPH BPH/BPE Role of Androgens ƒ Epidemiology ƒ Post natal androgen surges are critical ƒ Etiology ƒ Imprinting of prostate cells ƒ Symptoms ƒ Affects maturation process and cell ƒ Objective Data death ƒ Necessary during puberty and aging ƒ Nonsurgical/Medical ƒ Prostatic levels of dihydrotestosterone Management (DHT) and androgen receptors play a ƒ Surgical Management key role

BPH BPH Role of Androgens ƒ Exact molecular etiology is unknown ƒ Prostate retains ability to respond to androgens throughout ones life ƒ Androgens and estrogens ƒ Concentration of androgens does not ƒ Growth factors increase with age ƒ Cell-cell interactions ƒ Stromal cell – 5 alpha reductase Type 2 ƒ Impaired programmed cell death interaction seems to be key event in (apoptosis) the development of BPH ƒ Neurotransmitters ƒ Role of estrogens is unclear

2 BPH BPH Other Factors ƒ Inheritable component: earlier ƒ Stromal events induce glandular onset, larger gland size, autosomal proliferation dominant ƒ Interaction between growth ƒ Sympathetic nerve pathways factors, GF receptors, and steroid hormones ƒ Inflammation ƒ Programmed cell death/apoptosis ƒ Reflux ƒ Environmental

Pathophysiology of Obstruction ƒ BPH develops in the Transition and Periurethral Zones : central prostate ƒ Prostate Cancer develops in the Peripheral Zone : posterior prostate ƒ Static component of obstruction ƒ Dynamic component of obstruction

From: Campbell-Walsh Urology, 9th edition

3 BPH ƒ Obstructive uropathy/Urinary obstruction ƒ Bladder outlet obstruction (BOO) ƒ LUiTtS(LUTS)Lower Urinary Tract Sx (LUTS) ƒ Prostatism

ƒ BPH ≠ Urinary obstruction

ƒ Urinary obstruction ≠ BPH From: Campbell-Walsh Urology, 9th edition

BPE Size Doesn’t Matter

ƒ Not critical when deciding whether or ƒ Explanation of increased urethral not to Rx resistance due to BPE is too ƒ Not well correlated with Sx severity, simplistic degree of obstruction, or Rx outcome ƒ Must factor in age related detrussor ƒ Important wrt deciding mode of Rx and bladder neck dysfunction ƒ However, size does correlate with ƒ Static and dynamic factors disease progression and risk of acute retention

4 BPH Evaluation ƒ History ƒ Microscopic BPH: stromal and epithelial cellular proliferation ƒ AUA/IPSS Symptom Score ƒ DRE ƒ Macroscopic BPH: increase in the size of the prostate as a result of ƒ Urinalysis (r/o UTI) microscopic BPH (BPE) ƒ Uroflow and Post Void Residual ƒ Clinical BPH: signs and Sx of (PVR) obstruction due to BPE (LUTS, BOO, ƒ Imaging : Transrectal U/S (TRUS) Prostatism) with volume measurement ƒ Urodynamic Testing

Clinical Manifestations of International Prostate Symptom BPH Score (IPSS) ƒ Hematuria ƒ 7 questions + QOL assessment Microscopic ƒ Considered “Gold Standard” Gross ƒ NtitNot intend ddted to est tblihthDablish the Dx of ƒ LUTS BPE ƒ UTI ƒ Urinary retention ƒ Initial assessment of severity of Sx ƒ Hydronephrosis ƒ Determinant of Rx response ƒ Renal Insufficiency ƒ Determinant of Sx progression

5 IPSS Post Void Residual (PVR)

ƒ 0-7 Mild Sx ƒ High intra-individual variability 8-19 Moderate Sx ƒ Poor correlation with other signs 20-35 Severe Sx and Sx ƒ Degree of “bothersomeness” ƒ Measured by U/S or catheterization ƒ ? Predictor of Rx outcome ƒ Need to consider patient’s ƒ Increasing PVRs may be an lifestyle, performance status indicator of the need for intervention

Uroflow Cystoscopy

ƒ Non invasive ƒ Not indicated to determine the need ƒ Inaccurate for voided volumes <150mL for treatment ƒ Max flow rate (Qmax) ƒ Poor correlation between visual ƒ No definite cutoff as a determinant for appearance and treatment outcome Rx ƒ Indicated to determine the most ƒ No age or voided volume adjustment appropriate type of treatment for ƒ Low flow does not differentiate BOO those who have opted for surgical from detrussor hypocontractility management

6 Surgical Rx: Indications Urinary Obstruction ƒ Patient preference ƒ Static Component: ƒ Recurrent urinary retention BPH/mechanical obstruction ƒ Recurrent UTI’s ƒ Dynamic Component: smooth ƒ Recurrent gross hematuria muscle function at bladder ƒ Bladder calculus outlet ƒ Large bladder diverticula ƒ Renal insufficiency due to BPE

Medical Management Nonsurgical Management of BPH ƒ Preferred treatment for those men ƒ Alpha Adrenergic Blockers lacking absolute indications for ƒ Androgen Suppression/Ablation surgical intervention. ƒ Combination Therapy ƒ US Medicare Database: 250,000 prostate surgeries in 1987 ƒ Aromatase Inhibitors 116,000 in 1996 ƒ Phytotherapy 88,000 in 2000

7 Alpha Adrenergic Alpha Blocker Therapy Receptors Side Effects ƒ Dizziness ƒ Orthostatic hypotension ƒ Fatigue/somnolence ƒ Headache ƒ Rhinitis ƒ Nausea

From: Campbell-Walsh Urology, 9th edition ƒ Retrograde ejaculation

Alpha Blocker Therapy Androgen Ablation ƒ Agents causing a loss of ƒ Selective α1 Adrenergic receptor Testosterone or DHT action result in a blockade decrease in the volume of the ƒ Several medications available: prostate. Doxazosin (Cardura) ƒ Primarily an epithelial regression. ƒ Maximum results occur within 6 Terazosin (Hytrin) months Tamsulosin (Flomax) ƒ Treats static component of BPH Alfuzosin (Uroxatrol) ƒ 5 alpha reductase inhibitors

8 Androgen Ablation Androgen Ablation ƒ 5 alpha reductase converts T Æ ƒ DHT Decreased risk of urinary retention ƒ Decreased need for prostate surgery ƒ DHT is pppredominant intraprostatic androgen ƒ VlVolume red ucti on of prost ttate ƒ Finasteride (Proscar) Type 1 ƒ Can lower PSA – effect on cancer detection ƒ Dutasteride (Avodart) Type 1 and 2 ƒ Side effects : impotence ƒ ~30% volume reduction

Combination Therapy

ƒ Theory: synergistic effects of alpha blocker and antiandrogen ƒ Treats both components of prostate obstruction: static and dynamic ƒ VA Coop Study

From: Campbell-Walsh Urology, 9th edition

9 Phytotherapy Phytotherapy ƒ Serenoa repens Saw palmetto berry ƒ Little is know about active ƒ Sabal serrulata American dwarf palm compounds ƒ Hypoxis rooperi South African star grass ƒ Pygeum africanum African plum tree ƒ Little is know about dosage ƒ Urtica dioica Stinging nettle ƒ Little is know about mechanism of ƒ Secale cereale Rye pollen action ƒ Cucurbita pepo Pumpkin seed ƒ Paucity of double blinded ƒ Opuntia Cactus flower ƒ Pinus Pine flower prospective comparative studies ƒ Picea Spruce ƒ Almost all data is anecdotal.

Phytotherapy Surgical Treatment Dosages of Common Phytotherapeutic Options Preparations ƒ Intraprostatic Stents ƒ Serenoa repens (Permixon)160 mg ƒ Transurethral Needle Ablation (TUNA) bid Pygeum africanum (Tadenan )50 ƒ Transurethral Microwave (TUMT) mg bid Secale cereale (Cernilton)6 ƒ Transurethral Laser Therapy capsules ƒ TURP : Gold Standard β-Sitosterol (Harzol)20 mg tid ƒ Transurethral Incision (TUIP) β-Sitosterol (Azuprostat)65 mg tid ƒ Transurethral Vaporization ƒ Open Prostatectomy

10 Intraprostatic Stents TUNA

ƒ Primary indication is in patients who are unfit for surgery ƒ Temporary vs . Permanent ƒ Complications: migration, pain ƒ May be useful as a temporary measure after Laser Rx or TUMT

From: Campbell-Walsh Urology, 9th edition

TUNA Transurethral Laser Therapy ƒ Heats prostate tissue to >60°C ƒ Greenlight Laser ƒ Uses radiofrequency (RF) energy ƒ RltidtiResults in deep tissue necrosi s ƒ Spares the prostatic urethra ƒ Doesn’t require anesthesia, ƒ Holmium Laser (HoLEP) therefore, office procedure

11 TURP Benign Prostate Disorders ƒProstatitis ƒChroni c P el vi c P ai n Syndrome (CPPS)

From: Campbell-Walsh Urology, 9th edition

Transurethral Prostatitis Vaporization ƒ Most common GU Dx in men <50 yrs old ƒ Principle similar to TURP ƒ 3rd most common GU Dx in men >50 ƒ Removal of central prostate yrs tissue ƒ (BPH, prostate cancer) ƒ No specimen for path analysis ƒ 2-10% of men have prostatitis-like Sx ƒ 9-16% have had the Dx of prostatitis ƒ Less blood loss ƒ Accounts for 3-12% of male GU office visits

12 Prostatitis Bacterial Prostatitis Classification ƒ Acute Bacterial ƒ Gold Standard for Dx is the Meares Stamey “4 Glass” collection ƒ Chronic Bacterial thitechnique ƒ Non-bacterial ƒ 1st described in 1968 ƒ Prostatodynia ƒ Can use pre and post massage “2 Glass” collection

Prostatitis Classification Acute Bacterial NIH System Prostatitis/UTI ƒ E coli accounts for 65-80% of infections ƒ Category I : Acute bacterial ƒ Pseudomonas, Klebsiella, Serratia, ƒ Category II : Chronic bacterial Enterobacter account for another 10- ƒ CCCategory III : Chronic Pelvic Pain 15% Syndrome (CPPS) ƒ Enterococci 5-10% IIIA : Inflammatory CPPS IIIB : Non-inflammatory CPPS ƒ Urovirulence : p-fimbri, biofilms ƒ Reflux of urine into the intraprostatic ƒ Category IV : Asymptomatic ducts

13 Bacterial Prostatitis Bacterial Prostatitis Treatment Etiologies ƒ Most antibiotics achieve poor ƒ UTI intraprostatic ƒ Transurethral surgery concentrations and yet antibiotics are ƒ Indwelling catheter the mainstay of treatment ƒ Fluoroquinolones ƒ Dysfunctional voiding/neurogenic bladder ƒ Trimethoprim-sulfa ƒ Macrolides : erythromycin, ƒ Phimosis azithromycin ƒ Altered host immune response ƒ Tetracycline/doxycycline ƒ Idiopathic ƒ No standard treatment durations

Prostatitis Chronic Bacterial Prostatitis Other Organisms Treatment ƒ Duration of optimal Rx is unknown ƒ Corynebacterium ƒ Sulfa-trimethoprim remains primary ƒ Chlamydia agent ƒ Ureaplasma ƒ 30-50% efficacy rates ƒ Candida ƒ Fluoroquinolones also useful ƒ Trichamonas ƒ 1 month vs. 3 month Rx ƒ Differential Dx = CPPS

14 CPPS CPPS ƒ Absence of bacteria in prostatic ƒ Intraductile reflux secretions ƒ Common presenting Sx is pain Chemical prostatitis ƒ Perineal, suprapubic, penile ƒ Immunological Alterations ƒ Can also be groin, testicular, low back ƒ Neurological ƒ Pain during and after ejaculation (50%) ƒ Pelvic floor muscle dysfunction ƒ Irritative or obstructive voiding Sx ƒ Psychological factors

CPPS CPPS Treatment ƒ 40% achieve benefit from antibiotic Rx ƒ >3 months Sx = CPPS ƒ Long duration Rx not recommended ƒ SStedtoaadaex tend to wax and wane ƒ Alpha blocker Rx ƒ Up to 33% will resolve over 1 ƒ Anti-inflammatory Rx year’s time ƒ Biofeedback ƒ Pelvic muscle relaxation ƒ Antidepressants ƒ Psych

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