UROLOGIC PROBLEMS UPDATE: Practical, Evidence-Based, Clinical Pointers

1. UROLOGIC PROBLEMS UPDATE:Practical, Evidence-Based, Clinical Pointers B. WAYNE BLOUNT, MD, MPH PROFESSOR, EMORY UNIVERSITY SOM

2. Objectives • Urinary Incontinence Prostate diseases • Prostatitis • BPH • Cancer Erectile dysfunction

3. QUESTION # 1 • 64 YO WF C/O sudden losses of large amounts of urine, not always with urgency. you can diagnose this patient by history alone. • A. True • B. False

4. Symptom Description Stress Leakage with physical exertionor upon sneezing or coughing Urge Leakage with a strongand urgent desire to void Mixed Combination of stress and urge Urinary Incontinence Symptoms

5. Urge Incontinence • Detrusor instability Urge Stress Incontinence • Diminished urethralsphincter function and/or • Urethra hypermobility Stress Primary Underlying Causesof Incontinence

6. Other Causes of Accidental Urine Loss • Overflow • Functional

7. Basic Approach • Identify and treat reversible causes • Identify complicating factors - • that need specialized treatment or additional evaluation • Exclude overflow • Distinguish stress vs urge • Treat Urinary Incontinence in Adults. AHCPR/AHRQ Clinical Practice Guideline, 2009

8. DDelirium I Infection A Atrophy PPharmaceuticals P Psychological E Endocrine R Restricted mobility S Stool impaction Transient Urinary Incontinence

9. Distinguish Stress from Urge

10. Urinalysis • Bacteriuria • Hematuria • Pyuria • Glycosuria • Proteinuria

11. Other Basic Tests • Postvoid residual • Distinction is > 150-200 ml • Don’t forget that kidneys make about 1 ml per minute

12. Treatment Strategies • Increase urethral resistance • Exercises, injections, medications • Electrical stimulation, biofeedback, surgery • Urethral obstruction • Plugs, patches, continence pessary • Decrease magnitude of stress on bladder • Cough control, exercise modification, weight loss

13. Behavioral Therapy • Bladder retraining • Strongly recommended for treatmentof urge and mixed incontinence : ‘A’ NIH, 2009 • Pelvic floor muscle training (pelvic muscle or Kegel exercises) • Strongly recommended for thetreatment of stress incontinence ‘A’ NIH, 2009 • May be augmented by biofeedbackor vaginal weights

14. Other Therapies • All with inconsistent results in trials : • Electrostimulation • Magnet Therapy (Works for UUI) • Medical devices : pessaries, plugs, etc. • Injectable bulking agents • Local estrogen • NIH Consensus Conference on Urinary Incontinence, 2008

15. Procedure Goal Surgery Colposuspension(Burch; MMK) Elevates and stabilizes urethra by suspending anterior vaginal wall toiliopectineal (Cooper’s)ligaments/pubic symphysis Suburethral sling(fascial; TVT) Stabilizes urethra by placing it withina sling suspending it from rectus fasciaor pubic bone Urethral bulking(collagen; carbon) Injection of bulking materials abouturethra to increase outlet resistance MMK = Marshall-Marchetti-Krantz.TVT = transvaginal tape.

16. Medications • Currently, there is no medication approved for the treatment of SUI

17. Off-Label Medications Pharmacological Action Classification Examples -adrenergic agonists Increase urethral tone and closure pressure by direct stimulation of -adrenergic receptors EphedrineMidodrinePseudoephedrine Thickens urethral mucosa for a better seal; increases -adrenergic response; directly affects all lower urinary tract tissues; may increase sensory threshold of bladder and increase bladder relaxation Estrogen Estradiol Tricyclic antidepressants ImipramineAmitriptyline These agents have anticholinergic,direct smooth muscle relaxant, and norepinephrine-reuptake inhibition properties This information concerns a use that has not been approved by the US FDA.

18. QUESTION # 2 • A patient with urge incontinence cannot be effectively treated with which of the following : • A. Behahioral therapy • B. Oxybutinin • C. Hyoscyamine • D. Tolterodine • E. Imipramine

19. URGE INCONTINENCE (OAB, DETRUSOR INSTABILITY) • All of the answers except hyoscyamine are correct. • Anticholinergics & meds with such side effects are used to treat oab. • Oxybutynin and tolterodine are the 2 most commonly used meds. Level “A” Rec • Propanthaline & imipramine are 2nd line agents. B Rec • Behavioral therapy; e.g. bladder training, is effective. A Rec

20. Referral/Consultation Criteria • Uncertain diagnosis • Uncertain treatment plan • Failure to respond to therapy • Consultation regarding surgery • Hematuria • Recurrent urinary tract infections • Abnormal PVR PVR=postvoid residual.

21. # 4 62 YO WM C/0 2 MOs WORSENING DIFFICULTY STARTING URINATION WITH LESS FORCE OF STREAM & SOME DRIBBLING. • PMH: Negative • PE: 30 cc prostate; rest: WNL • The next recommended step in managing this patient is • A. PSA level • B. Ultrasound of prostate • C. Empiric treatment • D. Prostatic biopsy • E. All of the above

22. BENIGN PROSTATIC HYPERPLASIA • Prevalence : 8% 31-40; 45% 51-60, & >80% 80 yo • SX: LUTS: reduced force of stream, hesitancy, terminal dribbling, sense of incomplete emptying, urgency, nocturia, frequency. • Complications: acute urinary retention, recurrent UTIs, hydronephrosis & Renal failure

23. BENIGN PROSTATIC HYPERPLASIA • Lifetime risk of surgery = 29% • 2 Components: Dynamic muscle tension & Bulky structural • Use AUA symptom scoring index * ‘C’ Rec • Mild (Score < 7) : Watchful waiting • Moderate (Score 8 – 19) : Medical RX • Severe (Score > 20): Surgery • SEE www.aafp.org/afp/20020701/77.html & end of H.O.

24. BPH Symptom score

25. BPH Symptom Score www.aafp.org/afp/20020701/77.html

26. QUESTION # 3 • Which of the following meds would be inappropriate for this patient? • A. Saw palmetto • B. Alpha-1-antagonist • C. 5-alpha-reductase inhibitor • D. Ciprofloxacin

27. BPH MEDS • Alpha-1-antagonists (5 approved) : Similar efficacy; different side effect profiles: Terazosin & Doxazosin more SEs; Dynamic component; They work: “A” Rec; Cochrane, 2008 • 5-Alpha-reductase inhibitors (2 approved): Reduce size; Need 6-12 mo.s RX for full effect; 2 approved with similar efficacy & Ses; • They work: “A” Rec, Cochrane, 2008 • NNT for hematuria = 2; NNT to prevent a TURP = 6

28. BPH MEDS • Combination RX MAY help: ‘A’ Rec; Cochrane, Level “B”. (esp when > 30 cc volume) • Saw Palmetto is as effective as 5-alphas ‘A’ Rec (Cochrane Review)

29. Other BPH Treatments • TUMT: Transurethral Microwave Thermotherapy • Is effective when there is • No urinary retention • No previous prostate procedures • Prostate volumes between 30 – 100 ml • Not as effective as TURP • Cochrane, 2007 • Serenoa repens (Am. Dwarf Palm) does NOT work : “A” ;Cochrane, 2009 • Beta-sitosterols are effective: “B”; Cochrane 2008

30. QUESTION # 4 • 54 YO WM C/O 6 days of perineal pain, urgency & frequency, fever & myalgias. never had before. the most likely Dx. is • A. Acute prostatitis • B. Cystitis • C. Chronic bacterial prostatitis • D. Chronic nonbacterial prostatitis • E. Urethritis

31. PROSTATITIS • Acute Bacterial • Chronic bacterial • Chronic Nonbacterial (CPPS) : Inflammatory & Noninflammatory

32. PROSTATE DX TESTS • Traditional 4-glass test not done much anymore: not validated & too cumbersome • Alternative is the Pre- & Post-massage test (PPMT): As good as 4-glass test, but also not validated

33. ACUTE PROSTATITIS • A type of UTI • SX: fever, chills, LBP, perineal pain, dysuria, urgency, frequency, myalgias, ? Obstructive sx • P.E.: Tender, warm, swollen, firm & irregular • UA & C&S sans massage

34. ACUTE PROSTATITIS RX • MEDS: ‘C’ Rec • TCN • TMP-SMX • Quinolone • Duration: 3-4 weeks; ‘C’ Rec

35. CHRONIC BACTERIAL PROSTATITIS (CBP) • Source of recurrent UTIs • Similar SX as Acute c ASX intervals • WBCs + on pre- & post-massage UAs • - C&S on pre- & + on post-massage

36. CBP RX • TMP-SMX as 1st line: ‘C’ Rec • Quinolone for RX failures: ‘C’ Rec • Rarely: TUP of infected tissue for very sx complete failures on Abx

37. Erectile Dysfunction • Definition: The inability to achieve or maintain an erection sufficient for satisfactory sexual performance • 18 million men in US

38. Erectile Dysfunction • ED is a robust predictor of all-cause mortality & CV events in men. • Hazard ratio for mortality = 2.04 • Hazard ratio for CV event = 1.62 • With a “dose-response” increase with ED severity • Bohm, Circulation, March 15, 2010

39. Erectile Dysfunction • 1st line therapy should consist of oral phosphodiesterase 5 inhibitors (PD5s): NNT = 2.1, A Rec, Cochrane, 2007 • PD5s are most effective in ED assoc with DM, spinal cord dysfunction and ED caused by antidepressants: A Rec Cochrane, 2007 • PD5s can help in ED in nerve-sparing prostatectomy: B Rec, Bandolier, 2005 • PD5 efficacy & side effects among the 3 are similar, but drop-out rates are lower for sildenafil, A Rec Bandolier, 2005

40. Phosphodiesterase 5 Inhibitors :Adverse Effects • Vision disturbances • Priapism • Angina • Sudden, Permanent sensorineural hearing loss ( May, 2010)

41. Erectile Dysfunction • Vacuum Devices : B Rec, Bandolier, 2005 • Yohimbine : NNT = 6.4, A Rec, Bandolier, 2000 • Testosterone works in men with low testosterone (<12 nmol/L), NNT = 2.1 Bandolier, 2005 • Alprostadil works: NNT = 3.5; Is not a 1st line agent 2/2 side effects : A Rec, Bandolier, 2005 • We don’t know about apomorphine, phentolamine, or intracavernosal VIP: I Rec, bandolier,

42. Erectile Dysfunction : What Doesn’t Work • Trazodone : A Rec, Bandolier, 2005 • Fibrates & statins may contribute to ED: B Rec,Bandolier, 2007 • Having a BMI > 30 is a risk factor for ED, B Rec, Bandolier, 2000 • Losing weight in obese patients improves erectile function, B Rec, Bandolier, 2005

43. BIBLIOGRAPHY • USPSTF. SCREENING FOR PROSTATE CANCER. 2005.WWW.ahrq.gov/clinic/3rduspstf/prostatescr/prostaterr.htm • Weiss BD. Selecting Medications for the Treatment of Urinary Incontinence. AFP 2005;71:315-22. • Burgio KL, et al. Combined behavioral & drug therapy for urge incontinence. J Am Geriatr Soc 2000;48:370-4 • Burgio,KL, et al. Behavioral training with & without biofeedback in the treatment of urge incontinence. JAMA Nov 13, 2002; 288:2293-9. • AAFP. Urinary Incontinence: Assessment & management in Family Practice. Video: http:/www.aafp.org/x17358.xml • Stevermer JJ, Easley SK. Treatment of Prostatitis. AFP 2000;61:3015-22. • NJAFP. CME Report: Diagnosis & Management of Overactive Bladder in Family Medicine. 2007; 2:1-14. • Stenardo S. Caring for Patients Who have BPH. AAFP CME Bulletin. 2007;6:1-6.

44. BIBLIOGRAPHY • Stern JA, Schaeffer AJ. Chronic Prostatitis. West J Med Feb. 2000; 172:98-101. • Jang T, Schaeffer A. Chronic Prostatis. (Clinical Evidence Concise). AFP Aug 1, 2005 • Shamliyan et al. Trials of Nonsurgical Treatments for Urinary Incontinence in Women. Ann Int Med 2008,148. • Amer. Cancer Soc. Guideline for the Early detection of prostate cancer: Update 2010. Cancer J Clin 2010. • Wilbur J. Prostate Cancer Screening. Am Fam Physician. 2008;78:1377-84. • Edwards J. Diagnosis & Management of Benign Prostatic Hyperplasia. Am Fam Physician. 2008;77:1403-10.

45. EXTRAS

46. Prevalence of Urinary Incontinencein Women Women Under 60 Years Old Women Over 60 Years Old Stress55% Stress30% Mixed35% Urge35% Urge20% Mixed25% .

47. Initial Assessment for Urinary Incontinence • History • Voiding diary • Physical/pelvic exam • Urinalysis and other basic tests

48. Stress and Urge IncontinenceScreening Questions • During the last week, how many timesdid you accidentally leak urine with • A physical activity like coughing, sneezing,lifting, or exercising? • A feeling of strong, sudden need to pass your urine that did not allow you to get to the toilet fast enough?

49. Urine Voiding Diary Time Amount Voided Activity Leakage*(0-3 scale) Urge Present (yes/no) Fluid IntakeAmount/Type 16 oz. coffee6 oz. orange juice 6:50AM 425 mL Getting up/breakfast 0 Yes 7:45AM 150 mL Leaving for work 0 Slight – 8:20AM 350 mL At work 0 Yes 8 oz. coffee 9:10AM – Cough 2 Yes – 9:15AM 300 mL Working 0 Yes 10 oz. water 12:25PM 275 mL Working/at lunch 0 Yes 8 oz. water 2:45PM 400 mL Bending 1 Yes 4 oz. water 5:30PM 250 mL Leaving work 0 Yes – 6:30PM 125 mL Exercise class 2 Slight 12 oz. water 7:45PM – Dinner 0 No 4 oz. wine, 8 oz. water 8:20PM 375 mL At home 0 Yes 4 oz. water 10:50PM 250 mL Getting ready for bed 0 Yes – *Leakage: 0=no leakage; 1=drops; 2=wet underwear or light pad; 3=soaked pad or clothing.

50. a. Diminished urethral sphincter function b. Increased afferent stimulation from the bladder c. Contractile dysfunction of the bladder d. Detrusor muscle instability/overactivity ? What Is a Primary Cause of SUI?