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Urology Update Douglas C. Bauer, MD University of California, San Francisco No disclosures Overview • Microscopic hematuria • Urinary incontinence • Benign prostatic hypertrophy • Impotence • Prostatitis • Prostate cancer treatment Cases • 26 WF, 3rd episode of gross hematuria, one following URI • 77 BM, microscopic hematuria. Smoker. Asymptomatic. Microscopic hematuria • Defined as >3-5 RBC/HPF • Common (even in young) – Yearly UAs in soldiers for 16 yr: 39% – Fear of malignancy Etiology: age dependent • Glomerular: IgA, thin basement (<50), Alport’s (>50), other GN • Non-glomerular (upper): nephrolith, renal cell CA (>50), polycystic kidney • Non-glomerular (lower): cytitis, prostatitis, urethritis, bladder CA (>50) • Other: exercise, anti-coag, factitious Diagnostic evaluation • Repeat dipstick unless risk factors • Rule out proteinuria, azotemia, infection • Imaging: helical CT vs. sono • Procedures: cystoscopy if risk factors for cancer or >50 Other issues • Cytology not recommended • Phase contrast microscopy identifies glomerular source (dysmorphic) • Screening not cost-effective • Natural history of IgA uncertain –Fish oil? Cases • 56 female, 30+ years of worsening UI with cough, exercise. • 40 female, several years of episodic urgency, occasional UI. Worse with coffee, EtOH Urinary incontinence • Common – 25% reproductive age women – 40% postmenopausal women • Chronic - social seclusion – Falls & Fractures – 3x Nursing home admits • Costly – $26 billion annually – More than all cancer care for women Incontinence definitions • Overactive Bladder (OAB) - urge incontinence , frequency, nocturia • Stress -coughing, sneezing, straining, exercise • Mixed - both urge and stress • Other - neurologic, obstruction Stress vs. urge incontinence Symptom • Precipitant Stress activity Urge urge • Timing immediate delayed • Amount small-mod large • Nocturia rare common • Remissions rare common Evidence-based guidelines 1996 AHRQ Clinical Practice Guidelines: Primary Care diagnosis & treatment History, neurologic & pelvic exam, PVR, U/A 10 years later, where are we? Barriers for Primary Care: • Work up too time consuming & complex • No pelvic exam tables • PVR frequently not possible Diagnostic Aspects of Incontinence Study (DAISy) • Cross-sectional study (N = 301), 6 US centers – 3 incontinence questions (3 IQ) vs. full evaluation • 3 questions 1. During the last 3 months, have you leaked urine, even a small amount? If yes: 2. Stress UI: physical activity, coughing, sneezing, lifting, or exercise Urge UI: urge, feeling need to empty but could not get to the toilet fast enough 3. Type of UI most often: Stress, Urge, Mixed, Other Brown Annals 2006 Accuracy of 3 IQ compared to full evaluation Sensitivity Specificity PPV LR+ Urge 3IQ 0.75 0.77 0.79 3.26 0.86 0.60 0.74 2.13 Stress 3IQ Summary: screening for incontinence Primary Care Clinicians: 3 IQ to classify type of UI DAISy Take Home Message: 3 IQ is a good test for type of UI, especially because the risk of missed Dx and Rx low Indentification is critical to reducing burden of UI! Initial visit • Clinical diagnosis - 3 IQ, UA • Patient information • Urinary diary • Bedside commode • Topical estrogens? • Weight loss? • Consider Rx Behavioral vs. meds • 197 women with Urge UI; RCT UI • Biofeedback/behavioral 81% • Medication 69% • Placebo 40% Greater satisfaction in behavioral group Burgio 1998 Patient information • 222 women with Urge UI: RCT Improved • Biofeeback 63% • Verbal/vaginal instruct 69% • Self-help booklet 59% Not statistically different Burgio JAMA 2002 Urinary diary • Simple form for recording voids, incontinent episodes, fluid intake • Excellent education & intervention! • Very useful in planning therapy -fluid adjustment -timing and type of medications Incontinence treatment • Initial Rx similar for stress & urge • Behavioral Management - Fluids modification - Pelvic Floor Exercises - Bladder training • Verbal and written instructions Successful pelvic floor exercises • Strengthen levator ani and sphincter • Two fingers in the vagina, one hand on the abdomen • Two types: rapid and prolonged • Individualized program • Coughing Bladder training • Re-establishing voluntary control • Schedule voids q 30-60 minutes • Diary, relaxation, urge suppression • RCT demonstrated: ≥ 50% improvement in 75% of participants • Stress and Urge UI (Fantyl 1991) OAB medication effectiveness • Subjective cure vs. placebo • Long-term “success” • Side effects • Discontinuation 40-60% 20-40% 50% 50% 10-65% Bottom line: Medications very similar! OAB medications Side effects: dry mouth constipation drowsiness blurred vision dizziness Contraindications: narrow angle glaucoma hepatic/renal disease Medication prescribing guideline Immediate Release Extended release • Darifenacin (Enablex) • Oxybutynin (Ditropan) • Ditropan XL • Solifenacin (Vesicare) • Tolterodine (Detrol) • Detrol LA • Trospium (Santura) • Oxybutynin transdermal (Oxytrol) Case • 63 WM, progressive nocturia, hesitancy. PSA 6. Benign prostatic hypertrophy • 80% by age 80 years –50% have had a prostatectomy • Prostate grows throughout life –Until (unless) testosterone is gone • Two components of BPH –Dynamic –Mechanical Assessing BPH severity • 0 to 35 AUA scale (7 questions) • Moderate symptoms = 8 to 18 • Peak urine flow < 10 ml/sec (requires 150cc) Dynamic therapy of BPH • Contraction = adrenergic-mediated • blockers relax smooth muscle –prostate, blood vessels –prazosin, terazosin • 1A receptors in prostate only –tamsulosin = specific 1A blocker Mechanical therapy of BPH • Curious genetic abnormality – 5-reductase deficiency – fail to convert T to DHT – no baldness, prostatic hypertrophy • Finasteride – specific 5-reductase blocker – marked reduction in DHT levels Finasteride and BPH • Somewhat better than placebo (1.5 points!) • Not as good as -blockers in VA study • Combined with -blockers (NEJM, 12/03) – Slower progression vs. either one alone – Retention, surgery similar to finasteride • May depend upon gland size – works better in large glands, higher PSA Herbs and BPH • Beta-sitosterol (plant phytosterol) – 1 RCT • Saw palmetto – 18 RCTs • Both better than placebo Surgery (TUR-P) and BPH • Works better than watchful waiting – RCT of 556 men • Especially if sx moderate or severe • Surgery group had less –urinary retention, urinary symptoms • No diff. in impotence, incontinence Cases • 38 WM with impotence. Gradual worsening. Poor libido, no depression. • 58 male, 3 year S/P total prostatectomy, impotent ever since. Intact libido. Impotence • No new developments in diagnosis • Common (25% >65), iatrogenic causes • Laboratory evaluation – not evidence-based – glucose or glycosylated hemoglobin – TSH – testosterone x 2, then LH/FSH, prolactin – ? free testosterone if boarderline Hypogonandism and impotence • Testosterone falls with age (nl >325 ng/dl) – low in 40% age 50-60, 70% age 70-80 • Little evidence that low testosterone is a common cause of impotence • Long-term effects of testosterone replacement still unknown (IOM report) Sildenafil • Phosphodiesterase (PDE)-5 inhibitor – PDE’s normally breaks down cGMP – PDE-5 localizes in prostate • cGMP is a second messenger • Sexual stimulation–> nitric oxide release – > cGMP release –> vasodilation –> obstructs venules –> erection • Sildenafil prolongs half-life of cGMP Nitrates and nitric oxide • Nitrates are metabolized to nitric oxide • Nitric oxide regulates resting vascular tone • cGMP is a common second messenger for nitric oxide • Inhibition of cGMP prolongs nitric oxide action… Clinical implications • Basal NO release means that sildenafil normally reduces BP by 10-20 mm Hg – developed as an anti-anginal • Exogenous nitrates = substantial effects – 25 - 50 mm Hg drop in SBP – sildenafil half-life of 4 hours • Bottom line: nitrates, no sildenafil; & viceversa Sildenafil practicalities • $10 per pill (25, 50, 100 mg size) • Easy to split in half • “Works” in 30 minutes • Requires NO release • Prescribe 3 x 50 mg –try 25 mg first, then 50, then 75 Me too drugs • Vardenafil (Levitra) – similar efficacy, no direct comparisons – less effect on PDE-6 (fewer visual effects?) • Tadalafil (Cialis, “Le Weekend pill”) – up to 36 hr. of efficacy Other modalities • Erec-Aid suction device • Alprostadil intra-urethral pellets – smooth muscle relaxant (direct) – determine dose (125, 250, 500, 1000 ug) – Success in 65% – Penile pain in one-third • Yohimbine ( 2 antagonist) ? Case • 66 male with urgency, hesitancy, nocturia Prostatitis • Ascending infection • Often with partner’s GU organism(s) • Zinc levels low; ?value of supplements • Symptoms variable • Pain between umbilicus and knees Prostatitis diagnosis Type Rectal exam EPS white cells EPS Cult. UA Urine cult. Acute Tender DON’T ++ WBCs e.coli Chronic bacterial Usu. nl. Yes ++ WBCs e.coli Chronic nonbact. Normal Yes — nl — Prostadynia Normal nl — — — Common errors • Using normal exam, UA to r/o prostatitis • Overdiagnosis of acute prostatitis • Undertreatment (time-wise) • Extra-prostatic sources • Unusual organisms with Foley • Diagnosis w/o leukocytes Treatment of prostatitis • Bacterial – Acute for 4 weeks • TMX/Sulfa, CBCN, quinolone – Chronic for 2 to 4 months • TMX/Sulfa, nitrofurantoin • Non-bacterial (2, then + 4 weeks) • Erythromycin, TCN or doxycycline • Prostadynia = ? Prostate cancer • 350,000 new cases in U.S. each year • 50,000 deaths per year • 8.5 million men with the disease (30%) • Leveling off now (PSA penetration) • Average age 73 years • One in six dx’ed, one in thirty die Is early detection and treatment good? • Early detection = early treatment • Early treatment = early side effects • Early side effects = loss of quality-of-life – Loss of 2 to 7 days of QA life • Early treatment =? late benefit • If Tx works & pt. lives long enough Prostate cancer classification • Official system, Stages 0 to IV • Most pathologist still use dual Gleason • Worst Gleason is 10 =5 + 5, written 5/5 Localized disease: 15-year mortality in untreated 55-year-old men Mortality 100% 80% 60% 40% 20% 0% 2 to 4 5 6 7 Gleason score 8+ Prostate cancer treatment (usual) • Stage 0 = watch • Stage I, II = surgery (?radiation) • Stage III = radiation • Stage IV = hormonal therapy Early prostate cancer treatment, ? needed • Initial non-randomized studies: watchful waiting as good as treatment for most localized dz. • Therapies have complications –Radical prostatectomy • 8% incontinence • 60% (55%) impotent Does surgery improve outcomes? • RCT of watchful waiting vs. surgery in 695 men with local dz (Holmberg, 2002) – 75% had palpable dz, 10% detected from PSA – Mean age 64, 6.2 years follow up • Prostate cancer death RR = 0.50 (0.27, 0.91) • Distant metastases RR = 0.63 (0.41, 0.96) • Ongoing trials in US Advanced cancer: hormonal treatment • Surgical or medical castration – LHRH agonists (leuprolide, goserelin) – Constant stimulation of LH = tachyphylaxis – No LH = no testosterone – Suppress early LH surge • Androgen receptor blockade (flutamide) • Adrenal androgen production (ketoconazole) Confusing results • Waiting = hormones = orchiectomy • Flutamide + orchiectomy > orchiectomy – 5-year survival: 28% vs. 25% • Radiation + goserelin > radiation – Hit advanced disease early and hard Summary • Urologic conditions are common in primary care • Many can be successfully managed, at least initially, without referral