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3 Clinical Guideline for Benign Prostatic Hyperplasia Committee Members: Yukio Homma, Osamu Ishizuka, Seiichiro Ozono, Toshiyuki Kamoto, Akihiro Kawauchi, Momokazu Gotoh, Narihito Seki, Atsushi Nagai, Naoya Masumori, Tomonori Yamanishi, Osamu Yokoyama 2011 The Japanese Urological Association All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright holder. The Japanese Urological Association Saito Bldg. 5F, Yushima, Bunkyo-ku, Tokyo Japan Tel: Fax: Publisher: RichHill Medical Inc Kanda-jimbocho, Chiyoda-ku, Tokyo Japan Tel: Fax: ISBN

4 QOL iii

5 iv

6 BPH benign prostatic hyperplasia IPSS international prostate symptom score LUTS lower urinary tract symptoms OAB overactive bladder PSA prostate specific antigen QOL quality of life RCT randomized controlled trial TURP transurethral resection of the prostate PubMed MEDLINE Epub AUA EAU 8 9 International Consultation on Urological Diseases ICUD Male Lower Urinary Tract Dysfunction. Evaluation and Management p. 47 Consensual recommendation 2 3 v

7 EBM EBM AUA Guideline on the Management of Benign Prostatic Hyperplasia BPH. 9 EAU Guidelines on Benign Prostatic Hyperplasia McConnell J, Abrams P, Denis L, Khoury S, Roehrborn C eds. Male Lower Urinary Tract Dysfunction. Evaluation and Management. Edition Paris: Editions 21, Minds vi

8 vii

9 ... iii... iv viii

10 QOL PSA urodynamic study: UDS Clinical Questions CQ1?? CQ2? CQ3?? CQ4 PSA? PSA? anti-androgen drugs ix

11 open prostatectomy sub-capsular enucleation transurethral resection of the prostate: TURP transurethral incision of the prostate: TUIP bipolar-turp holmium laser enucleation of the prostate: HoLEP photoselective vaporization of the prostate by KTP laser: PVP, holmium laser ablation of the prostate: HoLAP transurethral detachment of the prostate transurethral enucleation with bipolar system: TUEB interstitial laser coagulation of the prostate: ILCP high-intensity focused ultrasound: HIFU transurethral needle ablation: TUNA transurethral microwave thermotherapy: TUMT urethral stent transurethral ethanol ablation of the prostate: TEAP botulinum toxin watchful waiting Clinical Questions CQ5 1? CQ6 1? CQ7 1 5? x

12 CQ8? CQ9 TURP? CQ10? CQ11? CQ12? CQ13? Clinical Questions CQ14? xi

13

14 CQ1 CQ2 CQ3 CQ4 CQ5 CQ6 CQ7 CQ8 CQ9 CQ10 CQ11 CQ12 CQ13 CQ14

15

16 1 QOL CLSS IPSS OABSS PSA CQ1 CQ2 CQ3 CQ4 p.42 p.45 PSA CQ10 CQ11 CQ12 CQ13 CQ14 p.109 p.114 p ml 5 OABSS 6 CQ5 CQ6 CQ7 p.98 p.104 CQ8 p.106 CQ9 p.108 3

17 2 A disease that manifests as a lower urinary tract dysfunction due to benign hyperplasia of the prostate, usually associated with enlargement of the prostate and lower urinary tract symptoms suggestive of lower urinary tract obstruction 1 benign prostatic hyperplasia BPH th International Consultation on BPH 1 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases 2 BPH BPH patient symptomatic BPH clinical BPH BPH treatment International Continence Society: ICS prostatism prostatism lower urinary tract symptoms: LUTS BPH hyperplasia benign prostatic enlargement BPE benign prostatic obstruction BPO BPH lower urinary tract symptoms suggestive of bladder outlet 4

18 2 obstruction 2 BPH Hald 3 Hald s ring BPE BPO LUTS BPH BPE BPO BPO LUTS LUTS BPO 3 BPO pressure flow study: PFS PFS PFS LUTS BPH

19 BPH BPH BPH BPH BPH BPH BPH Roehrborn CG. Focus on lower urinary tract symptoms: nomenclature, diagnosis, and treatment options. Highlights from the 5th International Consultation on Benign Prostatic Hyperplasia. June 25-27, 2000, Paris, France. Rev Urol 2001; 3: McConnell J, Abrams P, Denis L, Khoury S, Roehrborn C eds. Male Lower Urinary Tract Dysfunction. Evaluation and Management. Edition Paris: Editions 21, Hald T. Urodynamics in benign prostatic hyperplasia: a survey. Prostate 1989; 15 Suppl 2 :

20 3 3 benign prostatic hyperplasia natural history PubMed AUA 1 EAU 2 Male Lower Urinary Tract Dysfunction. Evaluation and Management IPSS 7 20 ml 10 ml/ 60 6% 70 12% PSA QOL

21 6 5 LUTS 2 7 LUTS 3 8 LUTS ,815 9 LUTS LUTS a community-based study populationbased study 11 8

22 3 b g BPH % 13 BPH c % 30 ml ml 40 ml 1.4% 1.9% 2.3% ml 26% 1.4% 1.1%

23 10 26 d LUTS IPSS 8 LUTS LUTS LUTS IPSS 32 5 IPSS 2 LUTS LUTS e % % f LUTS LUTS 3 PSA LUTS 35 IPSS 21 g 2 36 community-based study IPSS 3 1 IPSS 7 20 ml 10 ml/ 40 2% 50 2% 60 6% 70 12% 10

24 % Q max 10 ml/ Q max 15 ml/ QOL 3 30 ml IPSS 7 50 ml 20 ml 50 ml IPSS: Q max : % IPSS 7 2 % PV 20 3 % Q max IPSS: PV: ml Q max : ml/ 2 health-care seeking behavior 37 IPSS Community-based study 242 LUTS IPSS 63 65% 36 57% QOL 11

25 LUTS QOL 3 a , , /1,000 IPSS 12 ml/ 30 ml b Baltimore Longitudinal Study of Aging 40 3% 1 8.9% % % TURP LUTS TURP 30 ml 30 ml 9.2 PSA 1.4 ng/ml 1.4 ng/ml TURP IPSS 0% 4% 21% TURP 53.9 ml 19.8 ml LUTS QOL 4 12

26 3 2 III a % 39.3 ml % 55 ml % 20 3, Medical Therapy of Prostatic Symptoms MTOPS 4.5 PSA 45 PSA b LUTS LUTS IPSS LUTS 10% 24% 39% 47 LUTS / 350 ml / 2 TURP 3/ /100 24% 3 16% 31% PSA ml ng/ml ml ng/ml ml ng/ml 8.9% 11.7% 22.0% MTOPS ml 1.6 ng/ml PSA 4 IPSS 13

27 51 LUTS PSA LUTS PSA 52 c , % 1/4 1/3 53 3% MTOPS AUA Guideline on the Management of Benign Prostatic Hyperplasia BPH. 2 EAU Guidelines on Benign Prostatic Hyperplasia. 3 McConnell J, Abrams P, Denis L, Khoury S, Roehrborn C eds. Male Lower Urinary Tract Dysfunction. Evaluation and Management. Edition Paris: Editions 21, Sanda MG, Beaty TH, Stutzman RE, Childs B, Walsh PC. Genetic susceptibility of benign prostatic hyperplasia. J Urol 1994; 152: Partin AW, Page WF, Lee BR, Sanda MG, Miller RN, Walsh PC. Concordance rates for benign prostatic disease among twins suggest hereditary influence. Urology 1994; 44: Turkes A, Griffiths K. Molecular control of prostatic growth. In: Kirby RS, McConnell JD, Fitzpatrick JM, Roehrborn CG, Boyle P eds. Textbook of Benign Prostatic Hyperplasia. UK: Taylor and Francis, 2005: Roberts RO, Tsukamoto T, Kumamoto Y, Rhodes T, Masumori N, Miyake H, Girman CJ, Jacobsen SJ, Lieber MM. Association between cigarette smoking and prostatism in a Japanese community. Prostate 1997; 30: Nandeesha H. Benign prostatic hyperplasia: dietary and metabolic risk factors. Int Urol Nephrol 14

28 3 2008; 40: Rosen R, Altwein J, Boyle P, Kirby RS, Lukacs B, Meuleman E, O Leary MP, Puppo P, Robertson C, Giuliano F. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male MSAM-7. Eur Urol 2003; 44: McVary K. Lower urinary tract symptoms and sexual dysfunction: epidemiology and pathophysiology. BJU Int 2006; 97 Suppl 2 : Guess HA, Girman CJ. Descriptive epidemiology of benign prostatic hyperplasia. In: Kirby RS, McConnell JD, Fitzpatrick JM, Roehrborn CG, Boyle P eds. Textbook of Benign Prostatic Hyperplasia. UK: Taylor and Francis, 2005: Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human benign prostatic hyperplasia with age. J Urol 1984; 132: Isaacs JT, Coffey DS. Etiology and disease process of benign prostatic hyperplasia. Prostate 1989; 15 Suppl 2 : Garraway WM, Collins GN, Lee RJ. High prevalence of benign prostatic hypertrophy in the community. Lancet 1991; 338: Øverland GB, Vatten L, Rhodes T, DeMuro C, Jacobsen G, Vada K, Angelsen A, Girman CJ. Lower urinary tract symptoms, prostate volume and uroflow in Norwegian community men. Eur Urol 2001; 39: Chicharro-Molero JA, Burgos-Rodriguez R, Sanchez-Cruz JJ, del Rosal-Samaniego JM, Rodero- Carcia P, Rodriguez-Vallejo JM. Prevalence of benign prostatic hyperplasia in Spanish men 40 years old or older. J Urol 1998; 159: Bosch JLHR, Hop WCJ, Niemer AQHJ, Bangma CH, Kirkels WJ, Schröder FH. Parameters of prostate volume and shape in a community based population of men 55 to 74 years old. J Urol 1994; 152: Masumori N, Tsukamoto T, Kumamoto Y, Miyake H, Rhodes T, Girman CJ, Guess HA, Jacobsen SJ, Lieber MM. Japanese men have smaller prostate volumes but comparable urinary flow rates relative to American men: results of community based studies in 2 countries. J Urol 1996; 155: Wei JT, Schottenfeld D, Cooper K, Taylor JM, Faerber GJ, Velarde MA, Bree R, Montie JE, Cooney KA. The natural history of lower urinary tract symptoms in black American men: relationships with aging, prostate size, flow rate and bothersomeness. J Urol 2001; 165: Rhodes T, Girman CJ, Jacobsen SJ, Roberts RO, Guess HA, Lieber MM. Longitudinal prostate growth rates during 5 years in randomly selected community men 40 to 79 years old. J Urol 1999; 161: Bosch JLHR, Bangma CH, Groeneveld FPMJ, Bohnen AM. The long-term relationship between a real change in prostate volume and a significant change in lower urinary tract symptom severity in population-based men: the Krimpen study. Eur Urol 2008; 53: Bosch JLHR, Bohnen AM, Groeneveld FP, Bernsen R. Validity of three calliper-based transrectal ultrasound methods and digital rectal examination in the estimation of prostate volume and its changes with age: the Krimpen study. Prostate 2005; 62: Swyer GIM. Post-natal growth changes in the human prostate. J Anat 1944; 78: Masumori N, Tsukamoto T, Kumamoto Y, Miyake H, Rhodes T, Girman CJ, Guess HA, Jacobsen SJ, Lieber MM. Age-related differences in internal prostatic architecture on transrectal ultrasonography: results of a community based survey in Japan. J Urol 1997; 157: Fukuta F, Masumori N, Muto M, Miyamoto S, Igarashi M, Tsukamoto T. Does the prostate internal architecture on transrectal ultrasound predict future prostate growth? A 15-year longitudinal community-based study of benign prostatic hyperplasia in Japan. Eur Urol Suppl 2008; 7: 128 abstr Lieber MM, Rhodes T, Jacobson DJ, McGree ME, Girman CJ, Jacobsen SJ, St Sauver JL. Natural history of benign prostatic enlargement: long-term longitudinal population-based study of prostate volume doubling times. BJU Int 2010; 105: Epub 2009 Jul 7 27 Tsukamoto T, Masumori N. Epidemiology and natural history of benign prostatic hyperplasia. Int J 15

29 Urol 1997; 4: Tsukamoto T, Kumamoto Y, Masumori N, Miyake H, Rhodes T, Girman CJ, Guess HA, Jacobsen SJ, Lieber MM. Prevalence of prostatism in Japanese men in a community-based study with comparison to a similar American study. J Urol 1995; 154: Homma Y, Kawabe K, Tsukamoto T, Yamanaka H, Okada K, Okajima E, Yoshida O, Kumazawa J, Fang-Liu G, Lee C, Hsu TC, dela Cruz RC, Tantiwang A, Lim PHC, Sheikh MA, Bapat SD, Marshall VR, Tajima K, Aso Y. Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the International Prostate Symptom Score. Int J Urol 1997; 4: Homma Y, Yamaguchi O, Hayashi K; Members of the Neurogenic Bladder Society Committee. Epidemiologic survey of lower urinary tract symptoms in Japan. Urology 2006; 68: Jacobsen SJ, Girman CJ, Guess HA, Rhodes T, Oesterling JE, Lieber MM. Natural history of prostatism: longitudinal changes in voiding symptoms in community dwelling men. J Urol 1996; 155: Lee AJ, Garraway WM, Simpson RJ, Fisher W, King D. The natural history of untreated lower urinary tract symptoms in middle-aged and elderly men over a period of five years. Eur Urol 1998; 34: Masumori N, Tsukamoto T, Rhodes T, Girman CJ. Natural history of lower urinary tract symptoms in men results of a longitudinal community-based study in Japan. Urology 2003; 61: Roberts RO, Jacobsen SJ, Jacobson DJ, Rhodes T, Girman CJ, Lieber MM. Longitudinal changes in peak urinary flow rates in a community based cohort. J Urol 2000; 163: St Sauver JL, Jacobson DJ, Girman CJ, Lieber MM, McGree ME, Jacobsen SJ. Tracking of longitudinal changes in measures of benign prostatic hyperplasia in a population based cohort. J Urol 2006; 175: Bosch JLHR, Hop WCJ, Kirkels WJ, Schröder FH. Natural history of benign prostatic hyperplasia: appropriate case definition and estimation of its prevalence in the community. Urology 1995; 46 Suppl 3A : Jacobsen SJ, Guess HA, Panser L, Girman CJ, Chute CG, Oesterling JE, Lieber MM. A populationbased study of health care-seeking behavior for treatment of urinary symptoms: the Olmsted County Study of Urinary Symptoms and Health Status among Men. Arch Fam Med 1993; 2: Masumori N, Tanaka Y, Takahashi A, Itoh N, Ogura H, Furuya S, Tsukamoto T. Lower urinary tract symptoms of men seeking medical care comparison of the symptoms found in the clinical setting and in a community study. Urology 2003; 62: Jacobsen SJ, Jacobson DJ, Girman CJ, Roberts RO, Rhodes T, Guess HA, Lieber MM. Natural history of prostatism: risk factors for acute urinary retention. J Urol 1997; 158: Arrighi HM, Guess HA, Metter EJ, Fozard JL. Symptoms and signs of prostatism as risk factors for prostatectomy. Prostate 1990; 16: Arrighi HM, Metter EJ, Guess HA, Fozard JL. Natural history of benign prostatic hyperplasia and risk of prostatectomy: the Baltimore Longitudinal Study of Aging. Urology 1991; 38 Suppl 1 : Jacobsen SJ, Jacobson DJ, Girman CJ, Roberts RO, Rhodes T, Guess HA, Lieber MM. Treatment for benign prostatic hyperplasia among community dwelling men: the Olmsted County study of urinary symptoms and health status. J Urol 1999; 162: Marberger MJ on behalf of the PROWESS Study Group. Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. Urology 1998; 51: McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, Albertsen P, Roehrborn CG, Nickel JC, Wang DZ, Taylor AM, Waldstreicher J for the Finasteride Long-term Efficacy and Safety Study Group. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med 1998; 338: Roehrborn CG, McConnell J, Jacobs S, Slawin K, Kreder K, Foley J, Bautista OM. Baseline prostate volume and serum PSA predict rate of prostate growth: analysis of the MTOPS data. J Urol 2003; 16

30 3 169 Suppl : 364 abstr Lee AJ, Russell EBAW, Garraway WM, Prescott RJ. Three-year follow-up of a community-based cohort of men with untreated benign prostatic hyperplasia. Eur Urol 1996; 30: Barry MJ, Fowler FJ, Bin L, Pitts JC 3rd, Harris CJ, Mulley AG Jr. The natural history of patients with benign prostatic hyperplasia as diagnosed by North American urologists. J Urol 1997; 157: Wasson JH, Reda DJ, Bruskewitz RC, Elinson J, Keller AM, Henderson WG for the Veterans Affairs Cooperative Study Group of Transurethral Resection of the Prostate. A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. N Engl J Med 1995; 332: Flanigan RC, Reda DJ, Wasson JH, Anderson RJ, Abdellatif M, Bruskewitz RC. 5-year outcome of surgical resection and watchful waiting for men with moderately symptomatic benign prostatic hyperplasia: a Department of Veterans Affairs Cooperative Study. J Urol 1998; 160: Roehrborn CG, McConnell JD, Lieber M, Kaplan S, Geller J, Malek GH, Castellanos R, Coffield S, Saltzman B, Resnick M, Cook TJ, Waldstreicher J for the PLESS Study Group. Serum prostatespecific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. Urology 1999; 53: Crawford ED, Wilson SS, McConnell JD, Slawin KM, Lieber MC, Smith JA, Meehan AG, Bautista OM, Noble WR, Kusek JW, Nyberg LM, Roehrborn CG for the MTOPS RESEARCH Group. Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol 2006; 175: Roehrborn CG, Boyle P, Bergner D, Gray T, Gittelman M, Shown T, Melman A, Bracken RB, devere White R, Taylor A, Wang D, Waldstreicher J for the PLESS Study Group. Serum prostate-specific antigen and prostate volume predict long-term changes in symptoms and flow rate: results of a fouryear, randomized trial comparing finasteride versus placebo. Urology 1999; 54: Koyanagi T, Artibani W, Correa R, Desgranchamps F, De Reijke TM, Govier F, Hanash K, Hirao Y, Hoisaeter PA, Kobayashi S, Kurth KH, Marshall VR, Palmtag H, Wasserman N, Zerbib M. Initial diagnostic evaluation of men with lower urinary tract symptoms. In: Denis L, Griffiths K, Khoury S, Cockett ATK, McConnell J, Chatelain C, Murphy G, Yoshida O eds. 4th International Consultation on Benign Prostatic Hyperplasia BPH. UK: Plymbridge Distributors, 1998: McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, Lepor H, McVary KT, Nyberg LM Jr, Clarke HS, Crawford ED, Diokno A, Foley JP, Foster HE, Jacobs SC, Kaplan SA, Kreder KJ, Lieber MM, Lucia MS, Miller GJ, Menon M, Milam DF, Ramsdell JW, Schenkman NS, Slawin KM, Smith JA for the Medical Therapy of Prostatic Symptoms MTOPS Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349: Levi F, Lucchini F, Negri E, Boyle P, La Vecchia C. Recent trends in mortality from benign prostatic hyperplasia. Prostate 2003; 56:

31 4 benign prostatic hyperplasia pathophysiology lower urinary tract symptoms bladder outlet obstruction overactive bladder complication 1,325 benign hyperplasia dihydrotestosterone: DHT 35 Denonvilliers prostate specific antigen: PSA 18

32 4 PSA PSA 0.1% PSA 4 ng/ml PSA PSA PSA peripheral zone: PZ central zone: CZ transition zone: TZ anterior fibromuscular stroma 3 3 hypertrophy hyperplasia DHT CZ PZ TZ anterior fibromuscular stroma 3 McNeal 3 19

33 7 6 8 IL-1 FGF fibroblast growth factor A 1B 1D 3 mrna 1a 63% 1d 31% 1b 6% 1a 1a 85% 1d 14% 1b 1% 1a a 41% 1d 49% 1a 1d 13 1a 1a 1A 1L 2 1L 14 1D 15 1D 1 1D 16 1d mrna D 1A 1L a 1L

34 4 3 22% 53% 16% 9% benign prostatic enlargement: BPE 3 1 p I II III 21

35 % % gap junction connexin TURP 39 22

36 a partial denervation b 44 gap junction connexin supersensitivity 47 RhoA/Rho-kinase pathway 48 NGF 49 c 50 ATP NO transient receptor potential vanilloid 1 TRPV1 51 epithelial sodium channel ENaC 52 acid-sensing ion channels ASIC C 55 23

37 d botulinum toxin type A 57 botulinum toxin type A ED 60 ED ED NO RhoA/Rho-kinase ED ml PSA 1.6 ng/ml % 3% 24

38 % 65 VEGF vascular endothelial growth factor % , % 28 2% % 6.5% % EAU

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40 4 Epub 2009 Oct Homma Y, Hamada K, Nakayama Y, Tsujimoto G, Kawabe K. Effects of castration on contraction and 1 -adrenoceptor expression in rat prostate. Br J Pharmacol 2000; 131: Shapiro E, Hartanto V, Lepor H. Quantifying the smooth muscle content of the prostate using doubleimmunoenzymatic staining and color assisted image analysis. J Urol 1992; 147: Hald T. Urodynamics in benign prostatic hyperplasia: a survey. Prostate 1989; 15 Suppl 2 : Rosier PFWM, de la Rosette JJMCH. Is there a correlation between prostate size and bladder-outlet obstruction? World J Urol 1995; 13: el Din KE, Kiemeney LALM, de Wildt MJAM, Rosier PFWH, Debruyne FMJ, de la Rosette JJMCH. The correlation between bladder outlet obstruction and lower urinary tract symptoms as measured by the International Prostate Symptom Score. J Urol 1996; 156: van Venrooij GEPM, Boon TA. The value of symptom score, quality of life score, maximal urinary flow rate, residual volume and prostate size for the diagnosis of obstructive benign prostatic hyperplasia: a urodynamic analysis. J Urol 1996; 155: Chia SJ, Heng CT, Chan SP, Foo KT. Correlation of intravesical prostatic protrusion with bladder outlet obstruction. BJU Int 2003; 91: Oelke M, Baard J, Wijkstra H, de la Rosette JJ, Jonas U, Höfner K. Age and bladder outlet obstruction are independently associated with detrusor overactivity in patients with benign prostatic hyperplasia. Eur Urol 2008; 54: Romanzi LJ, Groutz A, Heritz DM, Blaivas JG. Involuntary detrusor contractions: correlation of urodynamic data to clinical categories. Neurourol Urodyn 2001; 20: Hyman MJ, Groutz A, Blaivas JG. Detrusor instability in men: correlation of lower urinary tract symptoms with urodynamic findings. J Urol 2001; 166: Abrams PH, Farrar DJ, Turner-Warwick RT, Whiteside CG, Feneley RCL. The results of prostatectomy: a symptomatic and urodynamic analysis of 152 patients. J Urol 1979; 121: Abarbanel J, Marcus E-L. Impaired detrusor contractility in community-dwelling elderly presenting with lower urinary tract symptoms. Urology 2007; 69: Madersbacher S, Klingler HC, Schatzl G, Stulnig T, Schmidbauer CP, Marberger M. Age related urodynamic changes in patients with benign prostatic hyperplasia. J Urol 1996; 156: Levin RM, English M, Barretto M, Dubuc M, O Connor L, Leggett R, Whitbeck C. Normal detrusor is more sensitive than hypertrophied detrusor to in vitro ischemia followed by re-oxygenation. Neurourol Urodyn 2000; 19: Mannikarottu AS, Hypolite JA, Zderic SA, Wein AJ, Chacko S, Disanto ME. Regional alterations in the expression of smooth muscle myosin isoforms in response to partial bladder outlet obstruction. J Urol 2005; 173: Mori K, Noguchi M, Matsuo M, Nomata K, Suematsu T, Kanetake H. Decreased cellular membrane expression of gap junctional protein, connexin 43, in rat detrusor muscle with chronic partial bladder outlet obstruction. Urology 2005; 65: Mirone V, Imbimbo C, Sessa G, Palmieri A, Longo N, Granata AM, Fusco F. Correlation between detrusor collagen content and urinary symptoms in patients with prostatic obstruction. J Urol 2004; 172: Elbadawi A, Diokno AC, Millard RJ. The aging bladder: morphology and urodynamics. World J Urol 1998; 16 Suppl 1 : S10 S34 39 Mitterberger M, Pallwein L, Gradl J, Frauscher F, Neuwirt H, Leunhartsberger N, Strasser H, Bartsch G, Pinggera G-M. Persistent detrusor overactivity after transurethral resection of the prostate is associated with reduced perfusion of the urinary bladder. BJU Int 2007; 99: Azadzoi KM, Tarcan T, Kozlowski R, Krane RJ, Siroky MB. Overactivity and structural changes in the chronically ischemic bladder. J Urol 1999; 162: Azadzoi KM, Radisavljevic ZM, Golabek T, Yalla SV, Siroky MB. Oxidative modification of 27

41 mitochondrial integrity and nerve fiber density in the ischemic overactive bladder. J Urol 2010; 183: Epub 2009 Nov Speakman MJ, Brading AF, Gilpin CJ, Dixon JS, Gilpin SA, Gosling JA. Bladder outflow obstruction a cause of denervation supersensitivity. J Urol 1987; 138: Azadzoi KM, Radisavljevic ZM, Siroky MB. Effects of ischemia on tachykinin-containing nerves and neurokinin receptors in the rabbit bladder. Urology 2008; 71: Coolsaet BLRA, Van Duyl WA, Van Os-Bossagh P, De Bakker HV. New concepts in relation to urge and detrusor activity. Neurourol Urodyn 1993; 12: Christ GJ, Day NS, Day M, Zhao W, Persson K, Pandita RK, Andersson KE. Increased connexin43- mediated intercellular communication in a rat model of bladder overactivity in vivo. Am J Physiol Regul Integr Comp Physiol 2003; 284: R1241 R de Jongh R, van Koeveringe GA, van Kerrebroeck PEV, Markerink-van Ittersum M, de Vente J, Gillespie JI. Alterations to network of NO/cGMP-responsive interstitial cells induced by outlet obstruction in guinea-pig bladder. Cell Tissue Res 2007; 330: Sibley GNA. The physiological response of the detrusor muscle to experimental bladder outflow obstruction in the pig. Br J Urol 1987; 60: Takahashi N, Shiomi H, Kushida N, Liu F, Ishibashi K, Yanagida T, Shishido K, Aikawa K, Yamaguchi O. Obstruction alters muscarinic receptor-coupled RhoA/Rho-kinase pathway in the urinary bladder of the rat. Neurourol Urodyn 2009; 28: Steers WD, Ciambotti J, Etzel B, Erdman S, de Groat WC. Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction. J Comp Neurol 1991; 310: Birder LA, de Groat WC. Mechanisms of disease: involvement of the urothelium in bladder dysfunction. Nat Clin Prac Urol 2007; 4: Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, de Groat WC, Apodaca G, Watkins S, Caterina MJ. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV 1. Nat Neurosci 2002; 5: Araki I, Du S, Kamiyama M, Mikami Y, Matsushita K, Komuro M, Furuya Y, Takeda M. Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction. Urology 2004; 64: Sadananda P, Shang F, Liu L, Mansfield KJ, Burcher E. Release of ATP from rat urinary bladder mucosa: role of acid, vanilloids and stretch. Br J Pharmacol 2009; 158: Kim JC, Yoo JS, Park EY, Hong SH, Seo SI, Hwang T-K. Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction. BJU Int 2008; 101: Masuda H, Kihara K, Saito K, Matsuoka Y, Yoshida S, Chancellor MB, de Groat WC, Yoshimura N. Reactive oxygen species mediate detrusor overactivity via sensitization of afferent pathway in the bladder of anaesthetized rats. BJU Int 2008; 101: Yokoyama O, Nagano K, Kawaguchi K, Ueki O, Ohkawa M. The influence of prostatic urethral anesthesia in overactive detrusor in patients with benign prostatic hyperplasia. J Urol 1994; 151: Chen J-L, Chen C-Y, Kuo H-C. Botulinum toxin A injection to the bladder neck and urethra for medically refractory lower urinary tract symptoms in men without prostatic obstruction. J Formos Med Assoc 2009; 108: Chuang Y-C, Chiang P-H, Yoshimura N, De Miguel F, Chancellor MB. Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia. BJU Int 2006; 98: McVary KT, Rademaker A, Lloyd GL, Gann P. Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005; 174: Becker AJ, Ückert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Jonas U. Cavernous and 28

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43 5 benign prostatic hyperplasia diagnosis initial evaluation symptom score questionnaire frequency volume chart physical examination ultrasound prostate specific antigen urinalysis urodynamic study postvoid residual urine cystoscopy retrograde urethrography renal function 6, QOL CLSS IPSS OABSS PSA 1 1 a CLSS QOL 3 QOL 1 b 4 30

44 ? CLSS 10 31

45 4 1 2QOL aipss QOL IPSS QOL 4 7 IPSS QOL IPSS 8 9 QOL 32

46 5 5IPSS QOL IPSS QOL IPSS QOL

47 6 BPH Impact Index: BII b BII c CLSS d OAB OABSS 10 OAB OAB-q 11 QOL International Consultation on Incontinence-Questionnaire-Short Form ICIQ-SF 12 King s Health Questionnaire: KHQ DRE 34

48 ml ml PSA PSA th International Consultation on New Developments in Prostate Cancer and Prostate Diseases 15 35

49 EAU 7 PSA 27 PSA PSA PSA 32 PSA PSA % % mg PSA % % PSA 2 PSA PSA

50 th International Consultation on New Developments in Prostate Cancer and Prostate Diseases EAU 7 micturition time chart frequency volume chart: FVC FVC bladder diary 37

51 2urodynamic study: UDS apressure flow study: PFS PFS ml/ PFS 5 15 b DO 1 5 DO

52 International Prostate Symptom Score BPH Impact Index 2002; 93: International Prostate Symptom Score BPH Impact Index 2003; 94: Barry MJ, Fowler FJ Jr, O Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, Cockett ATK; and the Measurement Committee of the American Urological Association. The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 1992; 148: , EBM AUA Guideline on the Management of Benign Prostatic Hyperplasia BPH. 7 EAU Guidelines on Benign Prostatic Hyperplasia. 8 Johnson TV, Schoenberg ED, Abbasi A, Ehrlich SS, Kleris R, Owen-Smith A, Gunderson K, Master VA. Assessment of the performance of the American Urological Association symptom score in 2 distinct patient populations. J Urol 2009; 181: Masumori N, Homma D, Tsukamoto T. Web-based research of lower urinary tract symptoms that affect quality of life in elderly Japanese men: analysis using a structural equation model. BJU Int 2005; 95: Overactive bladder questionnaire OAB-q 2006; 17: Donovan J, Corcos J, Badia X, Kelleher CJ, Naughton M, Shaw C, Avery K, QOL ICIQ-SF International Consultation on Incontinence- Questionnaire: Short Form 2001; 12:

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54 5 in patients with prostate specific antigen levels 10 ng/ml. Cancer 2003; 98: Gretzer MB, Partin AW. Prostate cancer tumor markers. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA eds. Campbell-Walsh Urology. 9th ed. Philadelphia: Saunders, 2007: D Amico AV, Roehrborn CG. Effect of 1 mg/day finasteride on concentrations of serum prostatespecific antigen in men with androgenic alopecia: a randomised controlled trial. Lancet Oncol 2007; 8: Tsukamoto T, Endo Y, Narita M. Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia. Int J Urol 2009; 16: Andriole GL, Kirby R. Safety and tolerability of the dual 5 -reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol 2003; 44: Andriole GL, Marberger M, Roehrborn CG. Clinical usefulness of serum prostate specific antigen for the detection of prostate cancer is preserved in men receiving the dual 5 -reductase inhibitor dutasteride. J Urol 2006; 175: Fujimoto K, Hirao Y, Masumori N, Arai Y, Yamanaka H, Kato T, Miyazawa K. Prostate-specific antigen changes as a result of chlormadinone acetate administration to patients with benign prostatic hyperplasia: a retrospective multi-institutional study. Int J Urol 2006; 13: Marks LS, Andriole GL, Fitzpatrick JM, Schulman CC, Roehrborn CG. The interpretation of serum prostate specific antigen in men receiving 5 -reductase inhibitors: a review and clinical recommendations. J Urol 2006; 176: Grossfeld GD, Coakley FV. Benign prostatic hyperplasia: clinical overview and value of diagnostic imaging. Radiol Clin North Am 2000; 38: Roehrborn CG. Accurate determination of prostate size via digital rectal examination and transrectal ultrasound. Urology 1998; 51 Suppl 4A : Marks LS, Roehrborn CG, Wolford E, Wilson TH. The effect of dutasteride on the peripheral and transition zones of the prostate and the value of the transition zone index in predicting treatment response. J Urol 2007; 177: Wasserman NF. Benign prostatic hyperplasia: a review and ultrasound classification. Radiol Clin North Am 2006; 44: Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 1996; 48: Kojima M, Inui E, Ochiai A, Naya Y, Ukimura O, Watanabe H. Noninvasive quantitative estimation of infravesical obstruction using ultrasonic measurement of bladder weight. J Urol 1997; 157: Kessler TM, Gerber R, Burkhard FC, Studer UE, Danuser H. Ultrasound assessment of detrusor thickness in men can it predict bladder outlet obstruction and replace pressure flow study? J Urol 2006; 175: Tan YH, Foo KT. Intravesical prostatic protrusion predicts the outcome of a trial without catheter following acute urine retention. J Urol 2003; 170: Mariappan P, Brown DJG, McNeill AS. Intravesical prostatic protrusion is better than prostate volume in predicting the outcome of trial without catheter in white men presenting with acute urinary retention: a prospective clinical study. J Urol 2007; 178: Lieber MM, Jacobson DJ, McGree ME, St Sauver JL, Girman CJ, Jacobsen SJ. Intravesical prostatic protrusion in men in Olmsted County, Minnesota. J Urol 2009; 182: Homma Y, Ando T, Yoshida M, Kageyama S, Takei M, Kimoto K, Ishizuka O, Gotoh M, Hashimoto 41

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