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  • LUTS can arise from a variety of causes, for example as a consequence of prolonged urinary obstruction due to BPH. LUTS are categorised as being obstructive (voiding) or irritative (storage) symptoms. Obstructive symptoms include hesitancy, weak stream, straining to pass urine, prolonged micturition, feeling of incomplete bladder emptying, and urinary retention. Irritative symptoms include urgency, frequency, nocturia, and urge incontinence. LUTS may also be due to inflammatory or infectious processes.
  • The initial evaluation can be done either by a Primary Care Practitioner (PCP) or by a urologist. If the initial evaluation suggests a diagnosis of BPH, the physician can proceed to develop an appropriate treatment plan. The physical examination should include specific attention to the presence or absence of a distended bladder, urethral discharge, genital abnormalities, and neurologic abnormalities that can affect voiding. A digital rectal examination (DRE) is considered an important part of the physical examination of any patient complaining of symptoms of prostatism. This examination is conducted with a well-lubricated, gloved index finger, which is used to palpate the prostate gland and the surrounding tissues through the wall of the rectum. Because of the prevalence of prostatic disease in older men, many physicians conduct DREs as part of the routine annual physical examination of any man over the age of 50 years. The size, consistency, shape, and symmetry of the prostate gland can be felt through the rectal wall during a DRE. Several questionnaires are used to assess the severity of symptoms and their impact on a patient’s QoL. American Urology Association-Symptom Score (AUA-SI) or International Prostate Symptom Score (IPSS), QoL score and BPH-II. In men with symptoms of BPH, a urine sample should be examined for signs of a urinary tract infection or haematuria, both of which suggest a non-BPH cause for the LUTS. Both urinary tract infections and bladder cancer can produce symptoms similar to those produced by BPH.
  • Relaxation of these muscle bundles lessens the resistance to outflow during urination.α
  • Medications address the desire we all have to find a “cure” to fix the problem. We all like a “quick and easy” solution. They can, however, become less effective over time. Studies have shown that people tend to become less careful about following directions regarding the dose and/or frequency of taking their medication.
  • Relaxation of these muscle bundles lessens the resistance to outflow during urination.
  • [Dr. McVary, transcript page 26] Prostate smooth muscle tone is mediated via  1 -adrenergic receptors. Increased tone of the prostate smooth muscle leads to BOO and a reduction in urinary flow rate. Blockage of the  1 -adrenergic receptor relaxes prostate smooth muscle and relieves BOO. 1 Studies indicate that, overall,  1 -adrenergic receptor expression doubles with age (<55 y vs  65 y). 2 To date, three  1 -adrenergic receptor subtypes have been identified:  1A ,  1B , and  1D . 1 Schwinn DA. Novel role for  1 -adrenergic receptor subtypes in lower urinary tract symptoms. BJU Int. 2000;86(suppl 2):11-22. Rudner XL, Berkowitz DE, Booth JV, et al. Subtype specific regulation of human vascular  1 -adrenergic receptors by vessel bed and age. Circulation. 1999;100:2336-2343.
  • Alpha-1 Blockers: Conclusions In conclusion, all alpha blockers currently available induce fast improvement in LUTS and flow rate parameters, with similar efficacy across all alpha blockers These agents are all well tolerated; however, the adverse event spectrum differs between the agents with Terazosin and doxazosin inducing more dizziness, fatigue and asthenia Tamsulosin inducing more ejaculatory disturbances Nevertheless, none of the alpha blockers alter prostate volume or serum PSA, and none have been shown to significantly change the rate of AUR/surgery
  • Dutasteride was associated with a significant reduction in the risk of AUR (57%) compared to placebo during the first 2 years of the studies Between 2-4 years, when all patients are receiving dutasteride, AUR occurred at a lower rate in the switchers than observed for these patients in years 0-2, and at a rate consistent with that seen in dutasteride-treated patients between 0-2 years.
  • Dutasteride was associated with a significant reduction in the risk of BPH-related surgery (48%) compared to placebo during the first 2 years of the studies Between 2-4 years, when all patients are receiving dutasteride BPH-related surgery occurred in a small percentage of men, at slightly lower rates than seen in dutasteride-treated men between 0-2 years
  • As this is not comparator data patient populations from the various studies may differ. dutasteride data for 1, 2 and 4 years is shown in yellow. Continuing improvement in symptoms over the 4 years is seen. Finasteride data for 1, 4 and 5 years is shown red, including that from PLESS & MTOPS. Alpha blocker data for 13 weeks to 5 years in shown in green. dutasteride symptom improvement at 4 years is comparable to that seen for alpha blockers.
  • SMART-1 was a randomised, blinded, parallel group, multi-centre pilot study in male subjects with symptomatic BPH. Eligible subjects were entered into a four week single-blind placebo run-in phase prior to randomisation to Avodart 0.5mg plus tamsulosin 0.4mg combination therapy for 24 weeks. At the 24-week time-point, approximately half of the subjects had tamsulosin removed from their treatment regimen in a double-blinded manner. These subjects received Avodart monotherapy for a further 12 weeks (to week 36). The other group of subjects continued to receive Avodart plus tamsulosin combination therapy for a further 12 weeks (to week 36).
  • Approx 1/10 patients responded that they were worse at week 30, after withdrawal of the alpha blocker at week 24. As could be expected those patients who responded that they were worse following withdrawal of the alpha blocker were likely to have a severe IPSS score at baseline.
  • No change requested.
  • Until recently, the only option we could offer patients for treatment of their symptoms was either an open abdominal surgical procedure, or a trans-urethral resection of the prostate.
  • [Dr. McVary, transcript page 24] Treatment options for BPH include watchful waiting, medical therapy, and various surgical procedures. 1-3 About 42% of patients treated with placebo or watchful waiting report symptomatic improvement compared with about 98% for open prostatectomy. 2 Symptom improvement with medical treatment is less than that with surgical procedures. The mean probability of symptomatic improvement is 74% with an  -adrenergic blocker versus 98% with an open prostatectomy. 2 However, disadvantages of surgery include invasiveness, a period of recuperation and, in the case of open surgery, a comparatively prolonged hospitalization. 3 Watchful waiting is a strategy of management/monitoring in which patients receive no active treatment. 2 Phytotherapy involves the use of plant extracts for medicinal uses. 4 Today,  -adrenergic blockers, which inhibit contraction of prostatic smooth muscle, are first-line treatment for LUTS/BPH. Another pharmacologic option is the 5ARI, finasteride, which lowers prostatic androgen levels and can result in some decrease in prostate size. Office-based procedures include transurethral microwave thermotherapy (TUMT) and transurethral needle ablation (TUNA). Transurethral resection of the prostate (TURP), the gold standard and most common active treatment, is the surgical removal of the prostate ’ s inner portion, using an endoscopic approach through the urethra. 2,3 Transurethral incision of the prostate (TUIP) is also an endoscopic surgical procedure. Patients with smaller prostates ( < 30 g) have an instrument inserted through the urethra to make one or two cuts in the prostate that reduce urethral constriction. 2,3 Open surgery (prostatectomy) is the surgical removal of the prostate via an incision in the lower abdomen. 2,3 Transurethral vaporization of the prostate (TUVP or TVP) applies electrical energy to electrosurgically vaporize the obstructive enlarged prostatic tissue. The laser is inserted under direct vision into the prostate and activated to destroy the surrounding tissue. 3 With visual laser ablation of the prostate (VLAP), a laser fiber is passed into the prostatic channel under telescopic guidance to destroy the obstructing portions of the prostate. Stents are wire devices shaped like small springs or coils, which are placed within the prostate channel to keep the channel open. 3 Chatelain C, Denis L, Foo JKT, et al. 5th International Consultation on BPH. Recommendations of the International Scientific Committee: Evaluation and treatment of lower urinary tract symptoms (LUTS) in older men. In: Chatelain C et al, eds. Benign Prostatic Hyperplasia . Plymouth, UK: Health Publication Ltd; 2001:519-534. McConnell JD, Barry MJ, Bruskewitz RC, et al. Benign Prostatic Hyperplasia: Diagnosis and Treatment . Clinical Practice Guideline, Number 8. AHCPR Publication No. 94-0582. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services. February 1994. Columbia University website. Therapies for the treatment of benign prostatic hyperplasia (BPH). Available at http://cpmcnet.columbia.edu/dept/urology/bphtherapy.html#translas. Accessed 8/23/01. Dreikorn K, Lowe I, Borkowski A, et al. Other medical therapies. In: Chatelain C et al, eds. Benign Prostatic Hyperplasia . Plymouth, UK: Health Publication Ltd; 2001;479-511.
  • BPH

    1. 1. BenignProstatic Hyperplasia
    2. 2. Understanding the prostate Walnut-shaped gland that forms part of the male reproductive system Surrounds the urethra - the tube that carries urine from the bladder out of the body
    3. 3. Understanding the prostate Secretes semen which carries sperm Duringorgasm, prostate muscles contract and propel ejaculate out of the penis
    4. 4. BPH The size of prostate enlarged microscopically since the age of 40.Half of all men over the age of 60 will develop an enlarged prostate By the time men reach their 70’s and 80’s, 80% will experience urinary symptoms But only 25% of men aged 80 will be receiving BPH treatment
    5. 5. What is Benign Prostatic Hyperplasia? Peripheral zone Transition zone Urethra
    6. 6. Peripheral zone Transition zone Urethra
    7. 7. What causes BPH? BPH is part of the natural aging process, like getting gray hair or wearing glasses BPH cannot be prevented BPH can be treated
    8. 8. What’s LUTS? Voiding (obstructive) Storage (irritative or symptoms filling) symptoms • Hesitancy • Urgency • Weak stream • Frequency • Straining to pass urine • Nocturia • Prolonged micturition • Urge incontinence • Feeling of incomplete bladder emptying • Urinary retention LUTS is not specific to BPH – not everyone withLUTS has BPH and not everyone with BPH has LUTSBlaivas JG. Urol Clin North Am 1985;12:215–24
    9. 9. Diagnosis of BPH• Symptom assessment – the International Prostate Symptom Score (IPSS) is recommended as it is used worldwide – IPSS is based on a survey and questionnaire developed by the American Urological Association (AUA). It contains: • seven questions about the severity of symptoms; total score 0–7 (mild), 8–19 (moderate), 20–35 (severe) • eighth standalone question on QoL• Digital rectal examination(DRE) – inaccurate for size but can detect shape and consistency• PV determination- ultrasonography• Urodynamic analysis – Qmax >15mL/second is usual in asymptomatic men from 25 to more than 60 years of age• Measurement of prostate-specific antigen (PSA) – high correlation between PSA and PV, specifically TZV – men with larger prostates have higher PSA levels 1 – PSA is a predictor of disease progression and screening tool for CaP – as PSA values tend to increase with increasing PV and increasing age, PSA may be used as a prognostic marker for BPH
    10. 10. Interfere with sexual life Sexual Activity Decreases with Average sex intercourse/activity/ month 9 8.5 n=12,815 Age and LUTS: MSAM-7 Survey 8 7.6 IPSS = 0 7 6.6 IPSS 1–7 5.7 5.7 IPSS 8–19 6 4.9 IPSS 20–35 5 4.6 4.0 4 3.7 3.5 2.6 3 1.7 2 1 0 50–59 years 60–69 years 70–79 yearsRosen et al. Eur Urol 2003 n=12815
    11. 11. When should BPH be treated?BPH needs to be treated ONLY IF: Symptoms are severe enough to bother the patient and affect his quality of life Complications related to BPH
    12. 12. Choosing the right treatment Consider risks, benefits and effectiveness of each treatment Consider the outcome and lifestyle needs
    13. 13. Treatment options “Watchful waiting” Medication Surgical approaches Minimal invasive TURP Invasive “open” procedures
    14. 14. “watchful waiting” For mild symptoms. follow up1 to 2 times yearly Offer suggestions that help reduce symptoms  Avoid caffeine and alcohol  Avoid decongestants and antihistamines
    15. 15. Medication First line of defense against bothersome urinary symptoms Two major types:  α blockers - relax the smooth muscle of prostate and provide a larger urethral opening (Hytrin,Doxaben, Harnalidge) 5 α reductase inhibitor - Shrink the prostate gland (Proscar, Avodart)
    16. 16. Medication Benefits Disadvantages Convenient  Drug Interactions No loss of work  Must be taken every day time  Manages the problem Minimal risk instead of fixing it
    17. 17. Possible side effects of medication • Impotence  • Dizziness  • Headaches  • Fatigue  • Loss of sexual drive 
    18. 18. α-Adrenergic Blockers: Rationale • Prostate smooth muscle tone is mediated via α1-adrenergic receptor • Blockage of the receptor leads to improvement of flow rate and LUTS1 • Central α-receptors and the effect of agents on these receptors likely play an additional role • Density of adrenergic receptors changes with prostate size and age • Three α1-adrenergic receptor subtypes have been identified (A, B, D)Schwinn DA. BJU Int. 2000;86(suppl 2):11-22.
    19. 19. Distribution of α1-Adrenergic Receptors
    20. 20. Localization of α1-Adrenergic Receptors (α1-ARs)
    21. 21. α-Blockers• Nonselective – Phenoxybenzamine• Short-acting selective α1-blocker – Prazosin, Alfuzosin• Long-acting selective α1-blockers – Terazosin – Doxazosin• Long-acting selective α1A-subtype – Tamsulosin – Alfuzosin-SR
    22. 22. α1-Adrenergic Blockers: Summary• All currently available α1-blockers induce fast improvement in LUTS and flow rate parameters with similar efficacy• They are all well tolerated; however, the adverse event spectrum differs between the agents – Terazosin and doxazosin induce more dizziness, fatigue, and asthenia – Tamsulosin induces more ejaculatory disturbances• None of the α1-blockers alter urodynamic parameters, prostate volume or serum PSA• None have been shown to alter the natural history of the disease or prevent AUR / Surgery
    23. 23. 5α-Reductase Inhibitor: Rationale • Prostatic differentiation & growth depend on androgenic stimulation • Testosterone is converted to dihydrotestosterone (DHT) within the prostatic stromal & basal cells facilitated by 5α-reductase enzyme • 5α-reductase inhibitor: deprive the prostate of its testosterone support • 5α-reductase enzyme: Type I: skin & liver Type II: stromal & basal cells of prostate, seminal vesicle, epididymisKirby RS et al. Br J Urol. 1992;70:65-72Tammela TLJ et al. J Urol. 1993;149:342-344
    24. 24. Regulation of cell growth in the prostate in BPHSerum testosterone (T) Serum Dihydrotestosterone (DHT) T Prostate 5AR (1 and 2) DHT cell Growth DHT-androgen factors receptor complex Cell death Increased Unbalanced Cell growth
    25. 25. 5α-reductase inhibition Mode of action OH OH 5 α-reductase type 1 and 2O O NADPH NADP H Testosterone Dihydrotestosterone Avodart (dutasteride) - Dual (type 1&2) 5ARI Proscar(finasteride) - Only type 2 5ARI
    26. 26. Greater and more consistent suppression of DHT observed with dutasteride versus finasteride (n=399) DHT (% change from baseline) 40 Treatment withdrawn Placebo 20 Fin 5.0 mg Dut 0.5 mg 0 -20 -40 -60 100% Dut patients>70% 49% Fin patients -80>90% 85.4% Dut patients -100 2.2% Fin patients 0 4 8 12 16 20 24 28 32 36 40 Time (weeks)Richard V. Clark et al. J Clin Endocrinol Metab 89:2179-2184, 2004Roehrborn et al (2003)
    27. 27. Comparison of adverse events: Dutasteride vs. finasteride vs. placebo (n=399) Patients (%) 100 Placebo Dutasteride 0.5 mg 80 Dutasteride 5.0 mg Finasteride 5.0 mg 60 40 20 0 Any AE Drug-related Serious AE Withdrawal AE due to AERichard V. Clark et al. J Clin Endocrinol Metab 89:2179-2184, 2004
    28. 28. Dutasteride 4-year studies (2-year double-blind and 2-year open-label) Randomised to double-blind phase n=4325 Key inclusion criteria: aged ≥ 50 years, diagnosis of BPH, PV ≥ 30 cc, AUA-SI score ≥ 12, Qmax ≤ 15 mL/sec, PSA ≥ 1.5 ng/mL Placebo Dutasteride n=2158 n=2167 Entered open-label phase Entered open-label phase on dutasteride n=1152 on dutasteride n=1188 P/D D/DRoehrborn CG et al Urol 63:709-15,2004
    29. 29. Dutasteride therapy results in reductions in total prostate volume from 1– 24 months that are sustained to 4 years Placebo Dutasteride Open-label dutasteride after placebo Mean change (%) 5 * * *† *‡ 1.4 0.2 0 -0.6 -1.5 -2.1 -5 -5.2 -10 -15 -13.8 -20 -19.9 -21.7 -25 -23.6 -26.0 -30 -27.3Treatment month 1 3 6 12 24 48*p<0.001 for differences between treatment groups†p<0.001 for change from Month 24 to Month 48‡p=0.07 for change from Month 24 to Month 48Roehrborn CG et al Urol 63:709-15,2004; Debruyne F et al, Euro Urol 2004;46: 488-495
    30. 30. Dutasteride therapy results in symptom improvements from 6 months, with continuing improvements over 4 years (completers) Change in AUA-SI (units) 0 Double-blind Open-label -1 P/D (n=1152) -2 D/D (n=1188) * -3 -2.7 -4 -5 *† -5.0 -5.6 -6 -6.5 -7 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48*p<0.001 between treatment groups Treatment month†p<0.001 for differences within treatment groups from Month 24Roehrborn CG et al Urol 63:709-15,2004; Debruyne F et al, Euro Urol 2004;46: 488-495
    31. 31. Dutasteride therapy results in improvements in urinary flow from 1 month, with continuing improvements over 4 years Mean change P/D (n=1152) (mL/sec) D/D (n=1188) 3.0 † * × 2.7 2.5 2.2 2.0 ¤ 1.9 1.5 1.0 0.5 0.6 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Treatment month *p<0.001 between treatment groups †p=0.042 between treatment groups ¤p<0.001 vs. Month 24 ×p=0.007 vs. Month 24Roehrborn CG et al Urol 63:709-15,2004; Debruyne F et al, Euro Urol 2004;46: 488-495
    32. 32. Acute urinary retention Kaplan-Meier estimates: time to first event Patients (%) 7 Double-blind Open-label 6.7% 6 5 P/D 4 D/D 57 3 3.3% % 2 1 0 0 6 12 18 24 30 36 42 48 Treatment monthRoehrborn CG et al Urol 63:709-15,2004; M.Emberton et al. 2004 EAU Abstract
    33. 33. BPH-related surgery Kaplan-Meier estimates: time to first event Patients (%) 7 Double-blind Open-label 6 5.6% 5 P/D 4 D/D 48 3 3.3% % 2 1 0 0 6 12 18 24 30 36 42 48 Treatment monthRoehrborn CG et al Urol 63:709-15,2004; M.Emberton et al. 2004 EAU Abstract
    34. 34. PSA is reduced in a predictable manner preserving its prostate cancer screening utility Double-blind Open-label 20 Mean (+/- SE) % Change 10 0 -10 -20 -30 -40 -50 -60 -57.2 0 6 12 18 24 30 36 42 48 Treatment Month Placebo n=1152 Dutasteride n=1188Data on File GlaxoSmithKline
    35. 35. Long-term change in prostate volume Indirect comparison of dutasteride, finasteride and a-blockers% Change in prostatevolume from baseline Dutasteride 30 Finasteride α-blockers 20 10 0 -10 -20 -30 2 yr 4 yr PLESS MTOPS 6 yr MTOPS DB OL 4 yr 4 yr OL Dox 4 yrMcConnell et al. (1998); McConnell et al. (2003); Roehrborn et al. (2002); Lowe et al. (2003)
    36. 36. Symptom improvement Indirect comparison of a-blockers, finasteride and dutasteride Mean AUA-SI score Dutasteridereduction from baseline Finasteride 9 α-blockers 8 7 6 5 4 3 2 1 0 1y 2y 4y AUA PLESS MTOPS 5y Tam Tam Tam Alf Tera Dox Dox DB DB OL 1y 4y 4y OL label label 5y 1y AUA AUA 4y 13 wk 13 wk OL OL 1y 1 y MTOPS study 1 study 2 McConnell et al. (1998); McConnell et al. (2003); Roehrborn et al. (2002); AUA (2003)
    37. 37. Combination therapy with 5aRIs and a1 blockers
    38. 38. Rationale for Combination Therapy Alpha blockers relax the smooth muscle of bladder neck and prostatic capsule/adenoma, thereby improving symptoms and flow rates, relieving obstruction 5 ARIs reduce the action of androgens in the prostate, inducing apoptosis, atrophy, and, by shrinking the prostate improve symptoms, relieve obstruction and prevent AUR & prostate surgery 5ARIs α1-adrenergic ? blockers Arrest disease progression Rapidly relieve symptoms
    39. 39. Medical Therapy of Prostatic Symptoms (MTOPS)
    40. 40. Change in AUA Symptom Score at Year 4 Placebo 4.0 Doxazosin 6.0 (p<0.001) Finasteride 5.0 (p<0.047) Combination 7.0 (p<0.001) 2 4 6 8 10 Median point decrease from baselineMedian baseline AUA SS = 17.0
    41. 41. Change in Qmax at Year 4 Placebo 1.4 Doxazosin 2.5 (p<0.001) Finasteride 2.2 (p<0.047) Combination 3.7 (p<0.001) 1 2 3 4 5 Median point decrease from baselineMedian baseline Qmax = 10.6
    42. 42. Conclusions Single arm therapy with alpha blocker  Improve symptoms and prevent symptom progression  Does not alter natural history or cross over to invasive therapy Single arm therapy with 5 ARI  Treats symptoms only when LUTS associated with BPH (ie enlargement or high PSA)  Alters natural history in pts at risk (large gland, high PSA) Combination (doxazosin+finasteride) therapy is the most effective form of treatment for LUTS and BPH  Improve symptoms and flow rate  Prevent AUR and/or surgery  Alter the natural history of the disease
    43. 43. Symptom Management After Reducing Therapy: SMART–1SMART–1 was designed to examineshort-term dutasteride and a1-blockercombination therapy, followed bydutasteride monotherapyEntry criteria: IPSS ≥ 12 PV ≥ 30 cc, estimated by DRE PSA 1.5 – 10.0 ng/ml Barkin et al (2002)
    44. 44. SMART-1: study design DT24 + D12 DT36 dutasteride 0.5mg Combination + placebo Placebo Placebo dutasteride 0.5mg (tamsulosin) run-in + tamsulosin 0.4mg once daily Combination 4 weeks 24 weeks 12 weeks 1 week Single Single Double blind Single blind blind blind Wk 30 Wk 36Barkin et al (2002)
    45. 45. SMART-1: primary endpoint question at week 30 by baseline IPSS Moderate Severe (baseline IPSS <20) (baseline IPSS ≥20) (n=220) (n=82) 100 93% 84% 86% 80Patients (%) 57.5% 60 40 Severe pts need longer AB treatment 20 0 DT36 DT24 + D12 DT36 DT24 + D12 % patients better/same Barkin et al (2002)
    46. 46. 5 α Reductase Inhibitors 成份 Finasteride Dutasteride* Compared to PROWESS1 PLESS2 MTOPS3 2yrs4 4yrs5,6,7 Baseline Duration (yr) 2 4 4 2 4Total Prostate Volume -15.3% -18% -19% -25.7% -27.3% Symptoms -2.1 -3.3 -5.6 -4.5 -6.5 Urinary Flow Rate 1.5 1.9 3.2 2.2 2.7 Continue Risk of AUR -57% -57% -68% -57% Reduction Continue Risk of BPH Surgery -40% -55% -64% -48% ReductionNote: Not from a comparative trial, all result abstracted from treatment group.PROWESS=Proscar Worldwide Efficacy and Safety Study; PLESS=Proscar Long-term Efficacy and Safety Study;MTOPS=Medical Therapy of Prostatic Symptoms*: Avodart Phase III trial 為在 2 年的 double blind 後再延長 2 年至 4 年的 open-label studyReferences:1. Marberger MJ. Urol.51:677-86,1998 。 2. McConnell JD et al. N Engl J Med 338(9):577-63,1998 。 3. McConnell JD etal. N Engl J Med 349(25):2387-98,2003 。 4. Roehrborn CG et al.Urol.60:434-41,2002 。 5. T.Tammela et al. 2004 EAUAbstract 。 6. F.Debruyne et al. 2004 EAU Abstract 。 7.M.Emberton et al. 2004 EAU Abstract 。
    47. 47. Conclusions In MTOPS study, finasteride afforded long-term reduction in risk of AUR on surgery when combined with alpha 1- blocker doxazosin  In SMART-1 study, dutasteride can be used in combination with tamsulosin to achieve fast symptom relief that is maintained with alpha 1- blocker is removed after 6 months
    48. 48. Medical Therapy Algorithm Patient IPSS IPSS ≤7 >7 No or Moderate to little severe bother botherProstate Prostate Prostate Prostate small large small largePSA low PSA high PSA low PSA high No α- Preventive therapy 5α-ReductaseTreatment Adrenergic 5α-Reductase Inhibitor Inhibitor Blocker Combination Rx IPSS <19 IPSS >19 (Moderate) (Severe) Short term Long term
    49. 49. Surgical treatment
    50. 50. Treatment Modalities for BPH  Watchful waiting  Surgicenter/Hospital-based  Medical therapy treatment  Phytotherapy  TURP (gold standard)  α-adrenergic blockers  TUIP  5α-reductase inhibitors  Open surgery (prostatectomy)  Combination therapy  TUVP  Office-based treatment  ILC  TUMT  VLAP  TUNA  Prostatic stents  WITChatelain C et al. In: Chatelain C et al, eds. Benign Prostatic Hyperplasia. Plymouth, UK: HealthPublication Ltd; 2001;519-534. McConnell JD et al. Benign Prostatic Hyperplasia: Diagnosis andTreatment. Clinical Practice Guideline, Number 8.
    51. 51. Indication of surgical intervention• Acute urinary retention• Gross hematuria• Frequent UTI• Vesical stone• BPH related hydronephrosis or renal function deterioration• Obstruction IPSS≧8, prostate size, image study, UFR cystoscopic findings, residual urine
    52. 52. Conventional Surgical Therapy• Transurethral resection of the prostate (TURP)• Open simple prostatectomy
    53. 53. TURP (transurethral resection of the prostate) “Gold Standard” of care for BPH Uses an electrical “knife” to surgically cut and remove excess prostate tissue Effective in relieving symptoms and restoring urine flow
    54. 54. TURP• “Gold standard” of surgical treatment for BPH• 80~90% obstructive symptom improved• 30% irritative symptom improved• Low mortality rate 0.2%
    55. 55. The “gold standard”- TURP Benefits Disadvantages Widely available  Greater risk of side effects and complications Effective  1-4 days hospital stay Long lasting  1-3 days catheter  4-6 week recovery
    56. 56. Complication of TURP• Immediate complication bleeding capsular perforation with fluid extravasation TUR syndrome• Late complication urethral stricture bladder neck contracture (BNC) retrograde ejaculation impotence (5-10%) incontinence (0.1%)
    57. 57. Open Simple Prostatectomy• “too large prostate” -- >100 gm• Combined with bladder diverticulum or vesical stone surgery• Suprapubic or retropubic method
    58. 58. Minimally invasive therapy• During the last decade, numerous amounts of minimally invasive therapy modalities have been developed to challenge the traditional surgery of TURP• The aim of these therapies is to achieve results similar to TURP but with minimal anesthesia, complication, risk and hospital stay.
    59. 59. Minimally invasive therapy for BPH• transurethral balloon dilatation of the prostate (TUBDP)• transurethral incision of the prostate (TUI)• intraprostatic stent• transurethral microwave thermotherapy (TUMT)• transurethral needle ablation of the prostate (TUNA)• transurethral electrovaporization of the prostate (TUVP)• photoselective vaporization of the prostate (PVP),• Cryotherapy• Transurethral ethanol ablation of the prostate (TEAP),
    60. 60. Minimally invasive therapy for BPH• transurethral laser-induced prostatectomy (TULIP)• visual laser ablation of the prostate (VLAP)• contact laser prostatectomy (CLP)• interstitial laser coagulation of the prostate (ILC)• holmium:YAG laser resection of the prostate (HoLRP)• holmium:YAG laser enucleation of the prostate (HoLEP)• high-intensity focused ultrasound (HIFU) coagulation• botulinum toxin-A injection of the prostate
    61. 61. HoLEP Vs. TURP • IPSS & urodynamic findings: no statistically significant differences • Operation time: HoLEP 74 +/- 19.5 vs. TURP 57 +/- 15 mins (p <0.05) • Catheterization time: 31 +/- 13 vs 57.78 +/- 17.5 hours (p <0.001) • Hospital stay: 59 +/- 19.9 vs 85.8 +/- 18.9 hours (p <0.001) • Urge incontinence: more common in the HoLEP group • The overall complication rate was comparable in the 2 groupsJournal of Urology. 172(5, Part 1 of 2):1926-1929, November 2004
    62. 62. TURP vs HIGH POWER (80 W) POTASSIUM TITANYL PHOSPHATE (KTP) LASER VAPORIZATION • Hemostasis: standardized ablation volume of 16 cm 3 tissue (23.3 vs 2.1 ml per minute, p <0.0001). • Tissue ablation: more rapid in the resection group (100 vs 20 seconds, p <0.001). • Histological examinations: larger coagulation zones for the KTP group compared to conventional tissue resection (0.9 vs 0.6 mm, p <0.01). • 80 W KTP laser vaporization: bloodless ablative procedure, but more time-consumingJournal of Urology. 171(6, Part 1 of 2):2502-2504, June 2004
    63. 63. How does PVP work? Uses a very high powered green laser and a thin, flexible fiber Fiber is inserted into the urethra through a cystoscope
    64. 64. How does PVP work? Quickly and precisely vaporizes and removes the enlarged prostate tissue The green laser energy is hemostatic, so there is almost no bleeding
    65. 65. Enlarged Prostate After GreenLight PVP Urethra is obstructed  Urethra is open Urine flow blocked  Normal urine flow is restored
    66. 66. Summary• Minimally invasive therapies for the treatment of BPH has the advantages such as less blood loss, less occurrence of hyponatremia, quicker recovery, and reduced risk of urethral stricture.• However, it also has the disadvantages such as long- lasting bladder irritation owing to higher temperature during therapy and possible longer catheterization period due to swelling of the prostate.• It is still too early to make a definitive conclusion concerning the future role of these minimally invasive therapies for the treatment of BPH.