今日の臨床サポート

前立腺肥大症

著者: 野間康央 順天堂大学医学部付属順天堂医院

監修: 堀江重郎 順天堂大学大学院医学研究科 泌尿器外科学

著者校正/監修レビュー済:2021/10/06
患者向け説明資料

概要・推奨   

  1. 多数の中高年男性が下部尿路症状(LUTSを有している。わが国の40歳以上の男性では、その頻度は夜間頻尿、昼間頻尿が特に高く、尿勢低下、残尿感、尿意切迫感、切迫性尿失禁がそれらに続いている。
  1. 前立腺肥大症は中高年男性にみられる進行性の疾患である。有病率は症状・所見の定義によるが、IPSS7前立腺体積20ml、最大尿流量<10ml/秒のすべてを満たすことを条件とすると、60歳代で6%、70歳代で12とされる。
  1. 臨床的進行の危険因子としては、加齢、前立腺腫大、PSA高値、下部尿路症状LUTS、QOL障害尿流量低下などがある。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
野間康央 : 未申告[2021年]
監修:堀江重郎 : 未申告[2021年]

改訂のポイント
  1. 前立腺肥大症の初期治療に対し、PDE5阻害薬(タダラフィル)がα1遮断薬と並んで第1選択薬となった。
  1. β3受容体作動薬にビベグロンが新規追加となった。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 多数の中高年男性が下部尿路症状(LUTS)を有している。わが国の40歳以上の男性では、その頻度は夜間頻尿、昼間頻尿が特に高く、尿勢低下、残尿感、尿意切迫感、切迫性尿失禁がそれらに続いている。
  1. 前立腺肥大症の定義は、「前立腺の良性過形成による下部尿路機能障害を呈する疾患で、通常は前立腺腫大と下部尿路閉塞を示唆する下部尿路症状を伴う」である。
  1. 前立腺肥大症は中高年男性にみられる進行性の疾患である。有病率は症状・所見の定義によるが、IPSS>7、前立腺体積>20ml、最大尿流量<10ml/秒のすべてを満たすことを条件とすると、60歳代で6%、70歳代で12%とされる。
  1. 前立腺の良性過形成(benign hyperplasia)は、尿道周囲から始まり、平滑筋と結合織から成る間質と、腺上皮とその内腔から構成される。間質と腺上皮とは増殖因子を介して相互作用があり、性ホルモン、炎症、アドレナリン作動性神経の刺激で増殖が促進される。
  1. 臨床的な前立腺肥大症は前立腺腫大(benign prostatic enlargement:BPE)、下部尿路症状(LUTS)、前立腺性下部尿路閉塞(膀胱出口部閉塞:BOO)の3つの要素により構成されている。
  1. 臨床的進行の危険因子としては、加齢、前立腺腫大、PSA高値、下部尿路症状(LUTS)、QOL障害、尿流量低下などがある。
  1. 前立腺肥大症の合併症としては尿閉、肉眼的血尿、膀胱結石、反復性尿路感染症、腎後性腎不全が挙げられる。
  1. 前立腺癌との関係は、炎症が共通の病因となっている可能性はあるものの、結論は一致しない。
  1. 前立腺肥大症を想定した場合に必ず行うべき評価としては、病歴聴取、症状・QOL評価(CLSS<図表>、IPSS<図表>、OABSS<図表>)、身体所見、尿検査、尿流測定、残尿測定、血清PSA測定、前立腺超音波検査がある。症例を選択して行う評価としては、排尿記録、尿流動態検査、血清クレアチニン測定、上部尿路超音波検査などがある。
  1. 過活動膀胱症状スコア(Overactive Bladder Symptom Score:OABSS)は過活動膀胱と診断された患者についてその症状の評価が可能である。
 
  1. 前立腺肥大症の明らかな危険因子は加齢である。剖検での検討によると、前立腺重量は性的成熟後40~50歳ごろまでは20ml前後とほぼ一定しているが、その後は加齢に従って増加する。
  1. 前立腺肥大症の明らかな危険因子は加齢である。剖検での検討によると、前立腺重量は性的成熟後40~50歳ごろまでは20ml前後とほぼ一定しているが、その後は加齢にしたがって増加する[1]。組織学的な前立腺肥大症(BPH)は30歳代より認められ、その頻度は加齢に従って増加し、80歳代では約90%になる。この傾向は人種や地域を問わず普遍的に認められることからBPHは生理的な加齢現象であろう[2]
  1. 一般住民を対象に各国で施行されたいずれの横断的研究においても、経直腸的超音波断層法により推定した前立腺体積は、集団全体としては加齢に従って増大する[3][4][5][6]。加齢による前立腺体積の増大は縦断的研究においても確認されており、米国オルムステッド郡での5年間にわたる研究によれば、前立腺体積は年間1.6%の増大を示した[7]。一方、一部の人では加齢に従って前立腺が縮小する。オランダの一般住民を対象にした検討によると観察開始時と比較して10ml以上、あるいは26%以上の前立腺体積の減少を有意な変化と定義した場合、それぞれ、1.4%、1.1%の症例が4.2年後に前立腺体積の減少を示した[8]。剖検による検討によると過形成のない正常前立腺は加齢に従って委縮するのに対し、過形成を有する前立腺は加齢とともに増大していた。このことから、前立腺には萎縮と増大の2通りの自然史があり、いずれをたどるかは40歳代半ばが分岐点と推測されている[9]
 
  1. 前立腺肥大症は中高年男性にみられる進行性の疾患である。有病率は症状・所見の定義によるが、IPSS>7 前立腺体積>20ml、最大尿流量<10ml/秒のすべてを満たすことを条件とすると、60歳代で6%、70歳代で12とされる。
  1. 前立腺肥大症の有病率は症状・所見の設定条件により変動する。わが国におけるcommunity-based study[10][11]の結果をもとにIPSSの重症度・前立腺体積・最大尿流量の3者に基づき前立腺肥大症の有病率を計算したところ、IPSS>7, 前立腺体積>20ml、最大尿流量<10ml/秒のすべてを満たすことを条件とすると、40歳代2%、50歳代2%、60歳代で6%、70歳代で12%と加齢に従って増加した[12]
  1. 前立腺肥大症患者に対してプラセボを投与して経過観察した2つの報告では、2年間の観察で8.9%(初診時の平均前立腺体積39.3ml)[13]、4年間で14%(初診時の平均前立腺体積55ml)[14]の前立腺体積の増大を認めた。前述の一般住民の結果に比較して、前立腺肥大症患者の観察開始時の前立腺体積は大きく、その増大率も急速である。Medical Therapy of Prostatic Symptoms(MTOPS)試験において、4,5年後の前立腺の増大率は初診時の前立腺体積と血清PSA値に規定された[15]。前立腺体積が大きいか血清PSA値が高い症例では、経過中に前立腺体積が増大する危険性が高いと推測される。
 
  1. 前立腺の良性過形成(benign hyperplasia)は尿道周囲から始まり、平滑筋と結合織から成る間質と、腺上皮とその内腔から構成される。間質と腺上皮とは増殖因子を介して相互作用があり、性ホルモン、炎症、アドレナリン作動性神経の刺激で増殖が促進される。
  1. 前立腺は辺縁領域(peripheral zone; PZ)、中心領域(central zone; CZ)、移行領域(transition zone; TZ)および前部線維筋性間質(anterior fibromuscular stroma)から成る。(1)前立腺肥大結節(腺腫)は組織学的に細胞数の増加で肥大(hypertrophy)より過形成あるいは増殖(hyperplasia)が適切な表現である[16]。前立腺腺腫の発生部位は移行領域と尿道周囲組織であり、初期の結節成分は間質のみで構成されている[17]
  1. 前立腺の炎症も過形成に重要な役割を果たしている[18]。5α還元酵素阻害薬の臨床研究では、前立腺の生検標本で炎症所見のある患者は前立腺体積が大きく、症状スコアが高く[19]、また、前立腺切除組織による検討では炎症症例に尿閉のリスクも高かった[18]
  1. アドレナリン作動性神経系は前立腺の平滑筋の緊張も調節している。その受容体は主にα1であり、遺伝子レベルではα1A, α1B, α1Dの3つのサブタイプに分類される。ヒト前立腺ではmRNAの量でα1a 63%、α1b 31%、α1d 6%とα1aが多く、肥大した前立腺ではα1a 85%、α1b14%、α1d 1%とさらにα1aの割合が多くなる[20]
  1. 腺上皮細胞は男性ホルモン支配を受けており、また女性ホルモンの協調作用も肥大結節の発生に重要な役割を果たしている。男性ホルモンを低下させると上皮細胞数は減少するが、α1受容体を介する前立腺収縮力も低下する可能性が示唆されている[21]
 
  1. 臨床的な前立腺肥大症は前立腺腫大(benign prostatic enlargement:BPE)、下部尿路症状、前立腺性下部尿路閉塞の3つの要素により構成されている。
  1. 下部尿路閉塞を伴う前立腺肥大症において、排尿症状は尿流が抵抗を受けた結果で生じるとして理解しやすい。しかし、手術などにより閉塞を解除しても3/1では排尿症状が持続する[22]。特に70歳以上の排尿症状は膀胱収縮障害に起因することが多く(48%)、尿閉の既往を有する症例ではさらに多いとされている[23]
  1. 下部尿路閉塞に対して膀胱平滑筋は肥大し内圧を高めて尿流を維持するようになる[24]。正常に比べ肥大した平滑筋は虚血に対して抵抗性を獲得し、ミオシンのような収縮蛋白の発現に変化が生じて収縮能を維持する一方で刺激に対し過敏となる[25]。閉塞が長時間継続した場合は膀胱平滑筋の収縮障害と加齢変化が重なり、尿道閉塞の解除だけでは症状が改善しないことになる。
  1. 下部尿路閉塞があると二次的に膀胱機能の変化が誘発され、それに伴い蓄尿症状も生じると想定されている。前立腺肥大症では蓄尿・排尿のサイクルごとに膀胱進展・高圧・虚血・再灌流が繰り返され、徐々に上皮・神経・平滑筋にさまざまな変化がもたらされる。前立腺肥大症で経尿道的前立腺切除術(Transurethral resection of prostate:TURP)を施行した後も排尿筋過活動が持続する症例では、下部尿路の血流障害が継続しており、血流障害と蓄尿障害との関連が示唆されている[26]。膀胱壁内神経は虚血に対し特に脆弱で、部分助神経の状態となる。助神経に伴って膀胱平滑筋はアセチルコリンに対し過大な反応を起こすようになる[27]
病歴・診察のポイント  
  1. 前立腺肥大症は、下部尿路症状(LUTS)を主訴に来院する患者が殆どであり、その原因はそれに限られない。そのため、排尿障害の病歴・QOL・排尿状態を評価するとともに、他疾患の鑑別も行う。

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文献 

著者: S J Berry, D S Coffey, P C Walsh, L L Ewing
雑誌名: J Urol. 1984 Sep;132(3):474-9.
Abstract/Text In this study we report the prevalence and growth rate of human benign prostatic hyperplasia with age by combining and analyzing data from 10 independent studies containing more than 1,000 prostates. The normal prostate reaches 20 plus or minus 6 gm. in men between 21 and 30 years old, and this weight remains essentially constant with increasing age unless benign prostatic hyperplasia develops. The prevalence of pathological benign prostatic hyperplasia is only 8 per cent at the fourth decade; however, 50 per cent of the male population has pathological benign prostatic hyperplasia when they are 51 to 60 years old. The average weight of a prostate that is recognized at autopsy to contain benign prostatic hyperplasia is 33 plus or minus 16 gm. Only 4 per cent of the prostates in men more than 70 years old reach sizes greater than 100 gm. An analysis of a logistic growth curve of benign prostatic hyperplasia lesions removed at prostatectomy indicates that the growth of benign prostatic hyperplasia is initiated probably before the patient is 30 years old. The early phase of benign prostatic hyperplasia growth (men between 31 and 50 years old) is characterized by a doubling time for the tumor weight of 4.5 years. In the mid phase of benign prostatic hyperplasia growth (men between 51 and 70 years old) the doubling time is 10 years, and increases to more than 100 years in patients beyond 70 years old.

PMID 6206240  J Urol. 1984 Sep;132(3):474-9.
著者: J T Isaacs, D S Coffey
雑誌名: Prostate Suppl. 1989;2:33-50.
Abstract/Text The natural history of benign prostatic hyperplasia (BPH) involves two phases. The first, or pathological phase of BPH, involves two stages, termed microscopic and macroscopic BPH, neither of which produces symptomatic clinical dysuria. Nearly all men throughout the world will eventually develop microscopic BPH if they live long enough. In only about one-half of the men with microscopic BPH, however, will microscopic BPH grow to produce a macroscopic enlargement of the gland (i.e., macroscopic BPH), suggesting that additional factors are required for the progression of microscopic to macroscopic BPH. Several theories have been proposed to explain the etiology of the pathological phase of BPH. The major theories include the hypotheses that pathological BPH is due to 1) a shift in prostatic androgen metabolism that occurs with aging, which leads to an abnormal accumulation of dihydrotestosterone, thus producing the enlarged prostate (i.e., DHT hypothesis), 2) a change in the prostatic stromal-epithelial interact that occurs with aging, which leads to an inductive effect on prostatic growth (i.e., embryonic reawakening theory), or 3) an increase in the total prostatic stem cell number and/or an increase in the clonal expanding of the stem cells into amplifying and transit cells that occurs with aging (i.e., stem cell theory). The second, or clinical phase of BPH, involves the progression of pathologic BPH to clinical BPH in which the patient develops symptomatic dysuria. Only about one-half the men with macroscopic BPH progress to clinical BPH. Although the macroscopic enlargement of the prostate is a necessary condition for the development of clinical BPH, this enlargement is usually not sufficient by itself for the progression of pathologic BPH to clinical BPH. The etiology of the progression of pathological BPH to clinical BPH requires additional factors (e.g., prostatitis, vascular infarct, tensile strength of the glandular capsule, etc.). A successful treatment for clinical BPH, therefore, does not necessarily require either the prevention or elimination of all degrees of pathologic BPH. Instead, what is needed is a therapy to prevent or reverse the progression of pathologic BPH to the clinical disease.

PMID 2482772  Prostate Suppl. 1989;2:33-50.
著者: W M Garraway, G N Collins, R J Lee
雑誌名: Lancet. 1991 Aug 24;338(8765):469-71.
Abstract/Text There is a strong suspicion among urologists that the prevalence of benign prostatic hyperplasia is higher than has been reported in clinical retrospective and necropsy studies. To find out the prevalence in one community all men aged 40-79 years registered with a group general practice were invited to complete a urinary symptom questionnaire and to undergo uroflowmetry. 705 men (77% of those eligible) participated. 214 men (84% of those invited) with signs and symptoms of prostatic dysfunction subsequently underwent transrectal ultrasonography (TRUS) for assessment of the volume (and by inference weight) of their prostates. The prevalence rate of benign prostatic hypertrophy (BPH), defined as enlargement of the prostate gland of equivalent weight greater than 20 g in the presence of symptoms of urinary dysfunction and/or a urinary peak flow rate less than 15 ml/s and without evidence of malignancy, was 253 (95% CI 221-285) per 1000 men in the community, rising from 138 per 1000 men aged 40-49 years to 430 per 1000 men aged 60-69 years. Thus apparently well men have a much higher frequency of BPH than was previously thought to be the case.

PMID 1714529  Lancet. 1991 Aug 24;338(8765):469-71.
著者: G B Overland, L Vatten, T Rhodes, C DeMuro, G Jacobsen, K Vada, A Angelsen, C J Girman
雑誌名: Eur Urol. 2001 Jan;39(1):36-41. doi: 52410.
Abstract/Text OBJECTIVE: To describe lower urinary tract symptoms, prostate volume and peak urinary flow rate, and investigate the relationships among urological variables in a community sample of Norwegian men.
MATERIALS AND METHODS: A cross-sectional study of 611 men, aged 55-70 years, who underwent a clinical urological examination including uroflowmetry, residual urine measurement, and transrectal ultrasonography of the prostate. All the men completed a questionnaire which included the International Prostate Symptom Score (IPSS).
RESULTS: Severe symptoms were reported by 5%, while 23.6% reported moderate symptoms, and the overall median IPSS was 4 (q1 = 25th percentile, 1; q3 = 75th percentile, 9). The median peak flow rate was 15 ml/s (q1 = 11; q2 = 22) while median prostate volume was 30 cm(3) (q1 = 23; q3 = 38), with little variation evident across the narrow age range of 55-70 years. A positive modest correlation (r = 0.176) was found between IPSS and prostate volume, and a negative correlation between IPSS and peak flow rate (r = -0.278). There was a modest correlation between body mass index (BMI) and prostate size, but no significant correlation between BMI and IPSS.
CONCLUSION: In this population-based study, moderate lower urinary tract symptoms were reported by 24% and severe symptoms by 5% of community men. The distribution of lower urinary tract symptoms, prostate volume and peak urinary flow rate in Norwegian men is comparable to that described in similar studies conducted in Spain, Holland and USA.

PMID 11173937  Eur Urol. 2001 Jan;39(1):36-41. doi: 52410.
著者: J A Chicharro-Molero, R Burgos-Rodriguez, J J Sanchez-Cruz, J M del Rosal-Samaniego, P Rodero-Carcia, J M Rodriguez-Vallejo
雑誌名: J Urol. 1998 Mar;159(3):878-82.
Abstract/Text PURPOSE: We estimate the prevalence of benign prostatic hyperplasia (BPH) according to symptoms as well as prostate obstruction determined by uroflowmetry and prostate size.
MATERIALS AND METHODS: A cross-sectional study was performed at the autonomous community of Andalusia in 1,106 men 40 years old or older. The International Prostate Symptom Score (I-PSS) questionnaire was used to establish symptoms, abdominal and transrectal ultrasonography was done to measure prostate size and uroflowmetry was performed to measure urinary flow obstruction.
RESULTS: The prevalence of moderate or severe symptoms was 24.94% and it increased with age. Of the 1,106 subjects 4.19% had severe prostatism, while 12.45% had poor quality of life (I-PSS greater than 3). Average prostate size was greater than 30 gm. in men 60 years old or older. Maximum urine flow was less than 10 and 15 ml. per second in 25.97 and 55.67% of the men, respectively. The prevalence of BPH, defined as I-PSS greater than 7, maximum flow less than 15 ml. per second and prostate size greater than 30 gm., was 11.77% (range 0.75 to 30 at ages 40 to 49 and greater than 70 years, respectively).
CONCLUSIONS: The prevalence of BPH increases with age. Moderate prostatism is perceived as resulting in poor quality of life by young subjects and good quality of life by some older subjects. In some men there were symptoms and obstruction but no prostate enlargement. This percentage persists with age after 50 years, when the prevalence of BPH starts to increase.

PMID 9474174  J Urol. 1998 Mar;159(3):878-82.
著者: J L Bosch, W C Hop, A Q Niemer, C H Bangma, W J Kirkels, F H Schröder
雑誌名: J Urol. 1994 Nov;152(5 Pt 1):1501-5.
Abstract/Text Parameters of prostate volume and shape were determined in a community based population of 502 men 55 to 74 years old who had not undergone a previous prostate operation and did not suffer from prostatic cancer. The volumes of the total prostate and of the central relatively hypoechoic area of the prostate were determined. Of all men in this age range 95% had a total prostate volume of more than 20 cm3. Moderate correlations between age and both volume measurements were found (r = 0.26, p < 0.0001 and r = 0.34, p < 0.0001, respectively). The percentage increase per year of central hypoechoic volume (3.5%) was higher than that of total prostatic volume (2%). The average doubling time of total prostatic volume and volume of the central hypoechoic prostate was calculated to be 35 and 20 years, respectively. The roundness of the prostate as expressed by width-to-height ratio at the largest transverse section of the prostate correlated poorly with age (r = -0.13, p = 0.004). The average total prostate volumes as measured by transrectal ultrasound were 21 to 28% higher than reported average volumes measured at autopsy in men in the same age range.

PMID 7523706  J Urol. 1994 Nov;152(5 Pt 1):1501-5.
著者: T Rhodes, C J Girman, S J Jacobsen, R O Roberts, H A Guess, M M Lieber
雑誌名: J Urol. 1999 Apr;161(4):1174-9.
Abstract/Text PURPOSE: We estimate the rate of prostate growth in randomly selected healthy community dwelling men.
MATERIALS AND METHODS: Prostate volume in an age stratified random sample of 631 white male residents of Olmsted County, Minnesota 40 to 79 years old without prior prostate surgery or prostate cancer was measured up to 4 times by transrectal ultrasound during a followup period of almost 7 years.
RESULTS: Estimated prostate growth rates increased with increasing age. However, the estimated average annual change was 1.6% across all age groups. Estimated prostate growth rates were high depending on baseline prostate volume with higher growth rates for men with larger prostates.
CONCLUSIONS: While there is wide variability in prostate growth rates on an individual level, prostate volume appears to increase steadily at about 1.6% per year in randomly selected community men.

PMID 10081864  J Urol. 1999 Apr;161(4):1174-9.
著者: J L H R Bosch, A M Bohnen, F P Groeneveld, R Bernsen
雑誌名: Prostate. 2005 Mar 1;62(4):353-63. doi: 10.1002/pros.20144.
Abstract/Text BACKGROUND: Prostate volume and its changes are important parameters in studies of the natural history of benign prostatic hyperplasia (BPH), for prediction of treatment effect and the risk of adverse outcomes. The validity of three calliper-based transrectal ultrasound (TRUS) methods and digital rectal examination (DRE) is compared to transrectal planimetric prostate ultrasonometry.
METHODS: Data were collected from 1,688 population-based men aged 50-78 years. Measurements included DRE, TRUS using the planimetric method, and three different calliper-based TRUS methods for the estimation of prostate volume. After 2.1 and 4.2 years these measurements were repeated. The agreement between these methods and the ability to discriminate between prostates with volumes above or below a certain cut-off was analyzed. The performance of the different methods to measure changes in prostate volume with age was also studied.
RESULTS: All three ultrasound-based methods showed good discrimination compared to the planimetric method. However, the agreement between planimetric volumetry and the other ultrasound methods and DRE is poor. In this study, 22.6% of the men had a real increase in prostate volume after 4.2 years, using the planimetric technique of transrectal ultrasonometry. Only a small percentage of the men (<1.5%) has a real decrease in prostate volume. The alternative measurement methods had a low predictive value for changes in prostate volume with age as measured with the planimetric method.
CONCLUSIONS: Calliper-based ultrasonometry and DRE show poor agreement with planimetric volume measurement of the prostate. Changes in prostate volume as determined by the planimetric method are poorly detected by the alternative methods. (c) 2004 Wiley-Liss, Inc.

PMID 15389783  Prostate. 2005 Mar 1;62(4):353-63. doi: 10.1002/pros.20・・・
著者: G I Swyer
雑誌名: J Anat. 1944 Jul;78(Pt 4):130-45.
Abstract/Text
PMID 17104953  J Anat. 1944 Jul;78(Pt 4):130-45.
著者: N Masumori, T Tsukamoto, Y Kumamoto, H Miyake, T Rhodes, C J Girman, H A Guess, S J Jacobsen, M M Lieber
雑誌名: J Urol. 1996 Apr;155(4):1324-7.
Abstract/Text PURPOSE: We compared prostate volume and peak urinary flow rate in Japanese and American men 40 to 79 years old.
MATERIALS AND METHODS: Prostate volume and peak urinary flow rate were measured in eligible Japanese men and results were compared to those of a randomly selected American cohort.
RESULTS: Mean prostate volume plus or minus standard deviation averaged 20.3 +/- 10.6 ml. in Japanese and 29.6 +/- 13.4 ml. in American men, while predicted cross-sectional increases with age decade were 1.5 and 5.5 ml., respectively. Peak urinary flow rate was higher but the decrease with increasing age was greater in Japanese men.
CONCLUSIONS: Prostate volume is larger and the increase with age is more pronounced in American than in Japanese men. However, Japanese men may have a higher peak urinary flow rate and greater cross-sectional decrease with age.

PMID 8632564  J Urol. 1996 Apr;155(4):1324-7.
著者: T Tsukamoto, Y Kumamoto, N Masumori, H Miyake, T Rhodes, C J Girman, H A Guess, S J Jacobsen, M M Lieber
雑誌名: J Urol. 1995 Aug;154(2 Pt 1):391-5.
Abstract/Text PURPOSE: We estimate the prevalence of urinary symptoms in Japanese men.
MATERIALS AND METHODS: A total of 289 eligible residents 40 to 79 years old completed a questionnaire with questions worded similarly to those of the international prostate symptom score (response rate 42%).
RESULTS: The ratio of moderate-to-severe symptoms was 41%, 29%, 31% and 56% for each age decade from ages 40 to 79 years, respectively, after adjusting for nonresponse. Within each age decade the median international prostatic symptom score was higher for Japanese men than for United States men with little difference in rates of increase with participant age or bother.
CONCLUSION: Lower urinary tract symptoms were common in Japanese men, with age-related increases similar to those of United States men.

PMID 7541852  J Urol. 1995 Aug;154(2 Pt 1):391-5.
著者: M J Marberger
雑誌名: Urology. 1998 May;51(5):677-86.
Abstract/Text OBJECTIVES: To compare the long-term effects of finasteride (5 mg/day) and placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH).
METHODS: Patients aged 50 to 75 years, with at least two urinary symptoms indicating moderate BPH, and an enlarged prostate, were followed in a 2-year double-blind, randomized, placebo-controlled multicenter study. The effects of finasteride versus placebo were assessed by total symptom score (modified Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume, and urologic end points (acute urinary retention, BPH-related surgical intervention).
RESULTS: Of the 3270 men enrolled, 3168 contributed data to the safety analysis, and 2902 to the efficacy evaluation. Significantly greater improvement with finasteride compared to placebo was observed at 12 and 24 months for total symptom score (mean -2.9 versus -1.9 at 12 months, P < or =0.001; -3.2 versus -1.5 at 24 months, P < or =0.001), obstructive symptom score (mean -1.9 versus -1.3 at 12 months, P < or =0.001; -2.1 versus -1.1 at 24 months, P < or =0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P = 0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean -14.2 versus +5.4% at 12 months, P < or =0.01; -15.3 versus +8.9% at 24 months, P < or =0.001). Greater improvements in placebo-adjusted total symptom score occurred in men with large prostates than in men with small prostates (mean -2.4 versus -1.1 at 12 months; -3.2 versus -1.3 at 24 months, placebo-adjusted data, P = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of 1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log-rank statistic, decreased by 57% for acute urinary retention and by 40% for surgery accompanied by finasteride therapy compared to placebo.
CONCLUSIONS: Finasteride causes long-term symptomatic improvement and reduces the risk of acute urinary retention or surgery. Men with enlarged prostates benefit most from finasteride treatment.

PMID 9610579  Urology. 1998 May;51(5):677-86.
著者: J D McConnell, R Bruskewitz, P Walsh, G Andriole, M Lieber, H L Holtgrewe, P Albertsen, C G Roehrborn, J C Nickel, D Z Wang, A M Taylor, J Waldstreicher
雑誌名: N Engl J Med. 1998 Feb 26;338(9):557-63. doi: 10.1056/NEJM199802263380901.
Abstract/Text BACKGROUND: Finasteride is known to improve urinary symptoms in men with benign prostatic hyperplasia, but the extent to which the benefit is sustained and whether finasteride reduces the incidence of related events, including the need for surgery and the development of acute urinary retention, is not known.
METHODS: In this double-blind, randomized, placebo-controlled trial, we studied 3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands who were treated daily with 5 mg of finasteride or placebo for four years. Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence of outcome events were assessed every four months in 3016 men. Prostate volume was measured in a subgroup of the men. Complete data on outcomes were available for 2760 men.
RESULTS: During the four-year study period, 152 of the 1503 men in the placebo group (10 percent) and 69 of the 1513 men in the finasteride group (5 percent) underwent surgery for benign prostatic hyperplasia (reduction in risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65 percent). Acute urinary retention developed in 99 men (7 percent) in the placebo group and 42 men (3 percent) in the finasteride group (reduction in risk with finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent). Among the men who completed the study, the mean decreases in the symptom score were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001). Treatment with finasteride also significantly improved urinary flow rates and reduced prostate volume (P<0.001).
CONCLUSIONS: Among men with symptoms of urinary obstruction and prostatic enlargement, treatment with finasteride for four years reduces symptoms and prostate volume, increases the urinary flow rate, and reduces the risk of surgery and acute urinary retention.

PMID 9475762  N Engl J Med. 1998 Feb 26;338(9):557-63. doi: 10.1056/N・・・
著者: John D McConnell, Claus G Roehrborn, Oliver M Bautista, Gerald L Andriole, Christopher M Dixon, John W Kusek, Herbert Lepor, Kevin T McVary, Leroy M Nyberg, Harry S Clarke, E David Crawford, Ananias Diokno, John P Foley, Harris E Foster, Stephen C Jacobs, Steven A Kaplan, Karl J Kreder, Michael M Lieber, M Scott Lucia, Gary J Miller, Mani Menon, Douglas F Milam, Joe W Ramsdell, Noah S Schenkman, Kevin M Slawin, Joseph A Smith, Medical Therapy of Prostatic Symptoms (MTOPS) Research Group
雑誌名: N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056/NEJMoa030656.
Abstract/Text BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown.
METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia.
RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone.
CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

Copyright 2003 Massachusetts Medical Society
PMID 14681504  N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056・・・
著者: J E McNeal
雑誌名: Invest Urol. 1978 Jan;15(4):340-5.
Abstract/Text Important features of the origin and evolution of benign prostatic enlargement (BPH) remain unclarified, partly because of imprecision in previous morphologic observations. Precise, quantitative analysis was applied to BPH development in 63 autopsy prostates. BPH nodules originated selectively from a very small region, near a cylindrical urethral sphincter above the verumontanum, and usually on the outer aspect of that sphincter laterally. They arose in a newly described transition zone, in which the unique mingling of prostatic glands with sphincteric stroma may be implicated in BPH pathogenesis. Nodules originate through eccentric duct budding toward a focus, suggesting local stromal inductive effects. BPH evolved through three processes: early diffuse gland growth, small nodule proliferation, and later nodule enlargement. If these are independent processes, BPH etiology may be multifactorial.

PMID 75197  Invest Urol. 1978 Jan;15(4):340-5.
著者: J McNeal
雑誌名: Urol Clin North Am. 1990 Aug;17(3):477-86.
Abstract/Text Morphometric studies of prostates with benign hyperplasia (BPH) have revealed features that may help clarify the disease's natural history and biologic behavior. Hyperplasia arises within a small anatomic region having precise boundaries and containing an unusual juxtaposition of glandular and stromal elements. Diffuse non-nodular enlargement of the transition zone is the commonest morphologic feature of BPH, but nodules show a greater potential for growth and comprise most of the tissue in large (more than 50-gm) resection specimens. Most nodules are predominantly glandular, with features that suggest a pathogenetic role of induction of embryonic-type stroma.

PMID 1695776  Urol Clin North Am. 1990 Aug;17(3):477-86.
著者: Vibhash C Mishra, Darrell J Allen, Christophoros Nicolaou, Haytham Sharif, Charles Hudd, Omer M A Karim, Hanif G Motiwala, Marc E Laniado
雑誌名: BJU Int. 2007 Aug;100(2):327-31. doi: 10.1111/j.1464-410X.2007.06910.x.
Abstract/Text OBJECTIVE: To compare the incidence of acute and/or chronic intraprostatic inflammation (ACI) in men undergoing transurethral resection of the prostate (TURP) for urinary retention and lower urinary tract symptoms (LUTS), as recently a role was suggested for ACI in the pathogenesis and progression of BPH, and urinary retention is considered an endpoint in the natural history of this condition.
PATIENTS AND METHODS: Details of TURPs done between January 2003 and December 2005 at one institution were obtained from the operating theatre database. Patients were divided by indication (retention/LUTS). Clinical data and histology reports were then reviewed and bivariate and logistic regression used to compare the pathological features between these groups.
RESULTS: Of 406 patients, 374 had evaluable data; 70% of men with urinary retention had ACI, vs 45% of those with LUTS (P < 0.001). On logistic regression, the pathological factors associated with TURP for acute retention compared to that for LUTS were ACI, old age, and resection weight to a lesser degree.
CONCLUSION: Inflammation appears to be important in the pathogenesis and progression of BPH. In this study, the risk of urinary retention due to BPH was significantly greater in men with ACI than in those without, and the association of TURP for retention with ACI was stronger than that with prostate weight. This finding might offer new avenues for the medical treatment of men with LUTS due to BPH.

PMID 17617139  BJU Int. 2007 Aug;100(2):327-31. doi: 10.1111/j.1464-41・・・
著者: J Curtis Nickel, Claus G Roehrborn, Michael P O'Leary, David G Bostwick, Matthew C Somerville, Roger S Rittmaster
雑誌名: Eur Urol. 2008 Dec;54(6):1379-84. doi: 10.1016/j.eururo.2007.11.026. Epub 2007 Nov 20.
Abstract/Text OBJECTIVE: The ongoing REDUCE trial is a 4-yr, phase 3, placebo-controlled study to determine if daily dutasteride 0.5mg reduces the risk of biopsy detectable prostate cancer. Prostate biopsies performed in all men prior to entry were centrally reviewed, thus allowing an examination of the relationship between inflammatory changes and lower urinary tract symptoms (LUTS).
METHODS: Eligible men were aged 50-75 yr, with serum prostate-specific antigen >or=2.5 ng/ml and or=3.0 ng/ml and 60 yr) and an International Prostate Symptom Score (IPSS)<25 (or <20 if already on alpha-blocker therapy). Acute prostatitis was an exclusion criterion. For a given individual, inflammation was assessed across all cores and the amount of inflammation scored as none (0), mild (1), moderate (2), or marked (3). LUTS was assessed with the use of the IPSS. The relationship between inflammation scores (averaged over all cores) and total IPSS; grouped IPSS (0-3, 4-7, 8-11, 12-15, 16-19, >/=20); and irritative, obstructive, and nocturia subscores was determined by Spearman rank correlations. The relative contribution of inflammation, age, and body mass index was then examined with the use of linear regression analyses.
RESULTS: Data were available for 8224 men. Statistically significant but relatively weak correlations were found between average and maximum chronic inflammation and IPSS variables (correlation coefficients, 0.057 and 0.036, respectively; p < 0.001 for total IPSS). Both age and average chronic inflammation were significant in the linear regression after adjustment for other covariates; for both variables, more severe inflammation was associated with higher IPSS scores.
CONCLUSIONS: In the REDUCE population, there is evidence of a relationship between the degree of LUTS and the degree of chronic inflammation. Study entry criteria that selected older men and decreased enrolment of men with a greater degree of inflammation and LUTS may have limited the strength of this relationship. The impact of baseline prostate inflammation on progression of LUTS and/or associated complications will be determined during 4-yr longitudinal follow-up.

PMID 18036719  Eur Urol. 2008 Dec;54(6):1379-84. doi: 10.1016/j.eururo・・・
著者: K Nasu, N Moriyama, K Kawabe, G Tsujimoto, M Murai, T Tanaka, J Yano
雑誌名: Br J Pharmacol. 1996 Nov;119(5):797-803.
Abstract/Text 1. There are at least three alpha 1-adrenoceptor subtypes, alpha 1a, alpha 1b and alpha 1d, in human tissues. Using an RNase protection assay, we have now determined the amount of each subtype mRNA in human prostatic tissue, for both benign prostatic hypertrophy (BPH) and non-BPH. In all tissue samples examined, the predominant subtype mRNA was alpha 1a. The total abundance of alpha 1-adrenoceptor mRNA in BPH samples was over six times that in non-BPH samples. This increase was mostly accounted for by alpha 1a, which was almost nine times as abundant in BPH samples as in non-BPH samples. The abundance of alpha 1b was almost the same between BPH and non-BPH samples, and the abundance of alpha 1d in BPH samples was about three times that in non-BPH samples. The ratio of the numbers of the subtype mRNAs, alpha 1a: alpha 1b: alpha 1d, was 85:1:14 in BPH samples and 63:6:31 in non-BPH samples. 2. In situ hybridization studies showed no significant differences in the tissue localization of alpha 1-adrenoceptor subtype mRNAs between BPH and non-BPH samples. alpha 1a and alpha 1d were clearly detected in the interstitium of the prostate, where alpha 1a was stained more intensely than alpha 1d, and the positive sites were primarily smooth muscle cells. In contrast, alpha 1b staining was very faint. 3. This increase in mRNA abundance may be directly related to the contraction of prostatic tissue that leads to obstruction of the urinary tract in BPH patients. Specifically, our data suggest that increased expression of the alpha 1a subtype may be primarily responsible for the contraction of the prostate.

PMID 8922723  Br J Pharmacol. 1996 Nov;119(5):797-803.
著者: Y Homma, K Hamada, Y Nakayama, G Tsujimoto, K Kawabe
雑誌名: Br J Pharmacol. 2000 Dec;131(7):1454-60. doi: 10.1038/sj.bjp.0703706.
Abstract/Text 1. The prostate function is regulated by androgens and alpha-adrenergic activity. Clinically, antiandrogens and/or alpha(1)-adrenergic antagonists are commonly used to treat symptomatic prostatic hypertrophy. To elucidate the effects of androgen deprivation on prostate contractility via alpha(1)-adrenoceptor, the characteristics and expression of alpha(1)-adrenoceptors were examined in castrated rats. 2. Isolated prostate strips from intact and castrated rats were subjected to a phenylephrine stimulated contraction. Prazosin (10 nM), [(3)H]-prazosin and phenoxybenzamine (3 - 300 nM) were used for inhibition assay, receptor characterization and partial alkylation of alpha-adrenoceptor, respectively. The mRNA content of three subtypes of alpha-adrenoceptors was determined by reverse transcription combined with polymerase chain reaction (RT - PCR). 3. Contractile response to phenylephrine increased in castrated rats, which could be explained by a relative increase of the stromal component. A lowered contraction potency was also noted in castrated rats. Receptor binding assay indicated minimal changes in the affinity or density of alpha(1)-adrenoceptor. Escalating alkylation of the alpha(1)-adrenoceptor population resulted in a rightward shift in the contraction-response curves before depressing maximal contractile force, and the suppression was detected at lower doses in castrated rats. RT - PCR study confirmed the expression of three types of alpha(1)-adrenoceptor, alpha(1a), alpha(1b) and alpha(1d)-adrenoceptors, in intact rat prostate, and revealed that alpha(1a)-adrenoceptor, but not alpha(1b) or alpha(1d)-adrenoceptors, was down-regulated in castrates. 4. The results show that androgen deprivation suppressed alpha(1)-adrenergic contractility of rat prostate strips, and the suppression was associated with down-regulation of receptor reserve for the alpha(1a)-adreneroceptor population expressed in intact rat prostate.

PMID 11090120  Br J Pharmacol. 2000 Dec;131(7):1454-60. doi: 10.1038/s・・・
著者: P H Abrams, D J Farrar, R T Turner-Warwick, C G Whiteside, R C Feneley
雑誌名: J Urol. 1979 May;121(5):640-2.
Abstract/Text There were 152 patients with prostatism investigated by inflow cystometry and pressure flow analysis of micturition before and after elective prostatectomy. Many symptoms attributed to obstruction were found to be owing to bladder instability, which was demonstrated in 60 per cent of the patients. The symptomatic improvement postoperatively was accompanied by a decrease in the incidence of instability to 25 per cent. The repeat urodynamic studies and symptom analysis demonstrated a surgical success rate of 88 per cent.

PMID 86617  J Urol. 1979 May;121(5):640-2.
著者: Joseph Abarbanel, Esther-Lee Marcus
雑誌名: Urology. 2007 Mar;69(3):436-40. doi: 10.1016/j.urology.2006.11.019.
Abstract/Text OBJECTIVES: To determine the prevalence of impaired detrusor contractility (IDC) with and without detrusor hyperactivity (DH) among community-dwelling elderly with lower urinary tract symptoms and to identify which patients are at a greater risk of having a hypocontractile detrusor.
METHODS: We performed a retrospective chart review of all patients 70 years old or older with storage and/or voiding lower urinary tract symptoms who had undergone urodynamic pressure-flow studies in a urodynamic referral center during a 2-year period.
RESULTS: During the study period, 181 patients (82 men [45%] and 99 women [55%]), aged 70 years or older (mean age 75.7 +/- 4.8), underwent urodynamic studies. IDC was detected in 39 (48%) of the 82 men and in 12 (12%) of the 99 women. Two thirds of the men and one half of the women with IDC also had involuntary detrusor contractions during the filling phase and/or low bladder compliance. The prevalence of IDC/DH-IDC was significantly greater in those with a history of urinary retention and an indwelling urethral catheter.
CONCLUSIONS: Detrusor-impaired contractility is an important pathophysiologic mechanism in older patients with lower urinary tract symptoms, especially in men. Establishing the diagnosis by urodynamic pressure-flow studies is crucial for determining treatment--potentially harmful to this vulnerable population--from objective parameters rather than by empirical decisions.

PMID 17382138  Urology. 2007 Mar;69(3):436-40. doi: 10.1016/j.urology.・・・
著者: R M Levin, M English, M Barretto, M Dubuc, L O'Connor, R Leggett, C Whitbeck
雑誌名: Neurourol Urodyn. 2000;19(6):701-12.
Abstract/Text Partial outlet obstruction results in marked metabolic as well as contractile alterations. Specifically, the ratio of anaerobic to oxidative metabolism is significantly greater in hypertrophied than normal bladder smooth muscle, lactate dehydrogenase (LDH) and lactic acid production are increased, and the contractile apparatus is altered to allow for metabolically more efficient tension generation. In addition, contractile responses of hypertrophied bladder are apparently more resistant than those of normal bladder to hypoxia. In the current experiment, we studied the effects of in vitro ischemia (hypoxia + substrate deprivation) followed by an in vitro model of reperfusion (re-oxygenation + substrate replacement) on contractile responses of normal and hypertrophied urinary bladder strips. We used repetitive field stimulation (FS) during the hypoxic period as a model for hyperreflexia. The purpose of the current study was to compare the responses of normal and hypertrophied bladder smooth muscle to repetitive stimulation in the presence of in vitro ischemia followed by re-oxygenation and substrate replacement. Thirty-two rats were separated into four groups of eight each. The rats in groups 1 and 3 were subjected to partial outlet obstruction. Two weeks later, all rats were anesthetized; their bladders were isolated and cut into four strips. Each strip was mounted in an isolated bath, and after 1-hour incubation in Tyrode's solution containing glucose (in the presence of O(2)), contractile responses to FS, carbachol, and KCl were determined. After this first set of stimulations, the strips were incubated without glucose and in the presence of N(2) for 30 minutes and 1 hour (groups 1 and 2); and for 2 and 4 hours (groups 3 and 4). For groups 1 and 2, the tissues were stimulated at 5-minute intervals with FS at 32 Hz, 1-millisecond duration, 3-second trains (in vitro model of hyperreflexia). For groups 3 and 4, no stimulations were performed during the ischemic period. At the end of the ischemic period, all strips were washed and incubated for 1 hour in the presence of O(2) and with glucose. At the end of this incubation, all strips received a second set of stimulations. a) Partial outlet obstruction resulted in a significant increase in bladder weight. b) Responses to in vitro ischemia: After in vitro ischemia, contractile responses of both normal and hypertrophied tissues to FS were reduced to a significantly greater degree than were responses to carbachol and KCl. The rate of development of contractile dysfunction was significantly greater in normal bladder tissue strips than in hypertrophied bladder strips. c) Responses to repetitive stimulation: The rate of development of contractile dysfunction was significantly greater in all strips subjected to repetitive stimulation than in those not repetitively stimulated; in addition, normal bladder strips were more sensitive than hypertrophied strips to hypoxia and substrate deprivation-induced contractile dysfunction. The rate of contractile failure induced by in vitro ischemia followed by re-oxygenation and substrate replacement was significantly greater for normal bladder strips than for hypertrophied bladder strips. These results indicate that, after partial outlet obstruction, the hypertrophied tissue is more resistant than normal tissue to hypoxia and substrate deprivation.

PMID 11071701  Neurourol Urodyn. 2000;19(6):701-12.
著者: Anita S Mannikarottu, Joseph A Hypolite, Stephen A Zderic, Alan J Wein, Samuel Chacko, Michael E Disanto
雑誌名: J Urol. 2005 Jan;173(1):302-8. doi: 10.1097/01.ju.0000142100.06466.49.
Abstract/Text PURPOSE: Smooth muscle (SM) myosin (SMM) isoform composition is altered in response to partial bladder outlet obstruction (PBOO). A recent study showed that during PBOO the upper dome region of the bladder is subjected to greater expansion pressure than the base and regional differences in contractility exist in the detrusor of PBOO rabbits. We hypothesized that alteration in SMM isoform composition in response to PBOO may show regional heterogeneity.
MATERIALS AND METHODS: Detrusor samples were obtained from 9 defined regions of the bladders from dysfunctional PBOO rabbits (greater than 30 voids per 24 hours) and sham operated adult New Zealand White rabbits. Reverse transcriptase-polymerase chain reaction, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were used to determine the relative levels of SMM isoform expression at the mRNA and protein levels. Contractile responses to bethanechol and KCl were also determined.
RESULTS: Myosin isoform expression was uniform throughout the detrusor from sham operated subjects with all regions expressing SM-B almost completely. However, in response to PBOO the dome region showed approximately 70% SM-B and 30% SM-A isoforms, whereas the base region expressed only 35% SM-B and, thus, 65% SM-A. This change also correlated with an approximately 2-fold higher protein level expression of SM-B in the dome region of PBOO rabbit bladders. Expression of the SMemb SMM isoform was significantly increased in PBOO rabbits at the mRNA and protein levels but only in the dome region. Regional differences in SMM isoform expression in the PBOO rabbit bladders correlated with altered contractility.
CONCLUSIONS: Alteration in SMM isoform composition in response to PBOO shows regional heterogeneity and may be involved in the mechanism responsible for regional localized differences in detrusor contractility in PBOO rabbits.

PMID 15592101  J Urol. 2005 Jan;173(1):302-8. doi: 10.1097/01.ju.00001・・・
著者: Michael Mitterberger, Leo Pallwein, Johann Gradl, Ferdinand Frauscher, Hannes Neuwirt, Nicolai Leunhartsberger, Hannes Strasser, Georg Bartsch, Germar-Michael Pinggera
雑誌名: BJU Int. 2007 Apr;99(4):831-5. doi: 10.1111/j.1464-410X.2006.06735.x. Epub 2007 Jan 22.
Abstract/Text OBJECTIVES: To elucidate, in patients with benign prostatic hyperplasia (BPH), how often detrusor overactivity (DOA) is persistent after transurethral resection of the prostate (TURP) and if perfusion of the lower urinary tract influences postoperative outcomes.
PATIENTS AND METHODS: Fifty men with urodynamically confirmed DOA and bladder outlet obstruction due to BPH had a TURP. Before and 1 year after TURP the International Prostate Symptom Score (IPSS), quality of life (QoL) score, prostate-specific antigen (PSA) level and total prostatic volume (TPV) were evaluated. Also, the lower urinary tract was evaluated using pressure-flow studies and transrectal colour Doppler ultrasonography to assess the vascular resistive index (RI) as a variable of the perfusion of the lower urinary tract.
RESULTS: After TURP the IPSS, QoL score, PSA level and TPV decreased. Cystometric measurements showed that in 15 (30%) patients DOA was persistent after TURP. The mean (sd) maximum urinary flow rate increased from 9.20 (4.03) to 15.98 (4.62) mL/s and postvoiding residual urine volumes decreased from 109.38 (73.71) to 29.24 (45.00) mL. When men with persistent DOA (15 patients; group 1) were compared with those with no DOA after TURP (35; group 2) there was a statistically significantly higher RI of the bladder vessels in group 1, at 0.86 (0.068) than in group 2, at 0.68 ( 0.055) (P < 0.001).
CONCLUSIONS: Persistent DOA in men after TURP seems to be associated with increased vascular resistance of the bladder vessels with subsequent reduced perfusion and hypoxia.

PMID 17244278  BJU Int. 2007 Apr;99(4):831-5. doi: 10.1111/j.1464-410X・・・
著者: M J Speakman, A F Brading, C J Gilpin, J S Dixon, S A Gilpin, J A Gosling
雑誌名: J Urol. 1987 Dec;138(6):1461-6.
Abstract/Text Eighteen Landrace pigs and 12 Göttingen mini-pigs were evaluated in a study of experimental bladder outflow obstruction. Twenty-two of the animals underwent partial bladder outflow obstruction for periods up to 12 months. The subsequent changes were assessed using cystometric, physiological and morphological means. There was a consistent increase in the voiding pressures and a concomitant reduction in the flow rates in all the obstructed animals. Seventy-seven per cent of the obstructed animals showed cystometric evidence of bladder instability. In vitro studies showed an increase in sensitivity to exogenously applied agonists and a reduction in sensitivity to intramural nerve stimulation. Morphological studies showed an inverse correlation between neuronal density and the duration of obstruction. These changes are typical of post-junctional supersensitivity secondary to partial denervation. These results suggest that agents capable of stabilising the bladder smooth muscle membrane may be useful in the treatment of detrusor instability secondary to bladder outflow obstruction.

PMID 3682077  J Urol. 1987 Dec;138(6):1461-6.
著者: P Abrams, C Chapple, S Khoury, C Roehrborn, J de la Rosette, International Scientific Committee
雑誌名: J Urol. 2009 Apr;181(4):1779-87. doi: 10.1016/j.juro.2008.11.127. Epub 2009 Feb 23.
Abstract/Text PURPOSE: The 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases met from June 24-28, 2005 in Paris, France to review new developments in benign prostatic disease.
MATERIALS AND METHODS: A series of committees were asked to produce recommendations on the evaluation and treatment of lower urinary tract symptoms in older men. Each committee was asked to base recommendations on a thorough assessment of the available literature according to the International Consultation on Incontinence level of evidence and grading system adapted from the Oxford system.
RESULTS: The Consultation endorsed the appropriate use of the current terminology lower urinary tract symptoms/benign prostatic hyperplasia/benign prostate enlargement and benign prostatic obstruction, and recommended that terms such as "clinical benign prostatic hyperplasia" or "the benign prostatic hyperplasia patient" be abandoned, and asked the authorities to endorse the new nomenclature. The diagnostic evaluation describes recommended and optional tests, and in general places the focus on the impact (bother) of lower urinary tract symptoms on the individual patient when determining investigation and treatment. The importance of symptom assessment, impact on quality of life, physical examination and urinalysis is emphasized. The frequency volume chart is recommended when nocturia is a bothersome symptom to exclude nocturnal polyuria. The recommendations are summarized in 2 algorithms, 1 for basic management and 1 for specialized management of persistent bothersome lower urinary tract symptoms.
CONCLUSIONS: The use of urodynamics and transrectal ultrasound should be limited to situations in which the results are likely to benefit the patient such as in selection for surgery. It is emphasized that imaging and endoscopy of the urinary tract have specific indications such as dipstick hematuria. Treatment should be holistic, and may include conservative measures, lifestyle interventions and behavioral modifications as well as medication and surgery. Only treatments with a strong evidence base for their clinical effectiveness should be used.

PMID 19233402  J Urol. 2009 Apr;181(4):1779-87. doi: 10.1016/j.juro.20・・・
著者: C G Roehrborn, P C Peters
雑誌名: Urology. 1988 May;31(5):445-9.
Abstract/Text In 81 outpatients the postvoiding residual urine (PVR) using real-time B-mode ultrasonography (3.5 MHz transducer) was measured. For the calculation of the bladder volume the formula for an ellipsoid (V = 4/3 pi X r1 X r2 X r3) was found to be most accurate in predicting the actual volume measured by in-and-out catheterization (r = 0.982). Other volume formulas, using only one diameter of the bladder, were found to be much less accurate. For any arbitrary value of PVR, used in determining clinical management, the incidence of misjudgment by ultrasound was negligibly low. We conclude, that sonographic measurement of the PVR as a quick, noninvasive method, should replace catheterization, if the basic equipment is available. Additional information, e.g., prostate size, bladder configuration, diverticula, etc., can be obtained during the procedure without additional costs or loss of time.

PMID 3284155  Urology. 1988 May;31(5):445-9.
著者: W J Catalona, J P Richie, F R Ahmann, M A Hudson, P T Scardino, R C Flanigan, J B deKernion, T L Ratliff, L R Kavoussi, B L Dalkin
雑誌名: J Urol. 1994 May;151(5):1283-90.
Abstract/Text To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandem-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 micrograms/l or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 micrograms/l, 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 micrograms/l or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.

PMID 7512659  J Urol. 1994 May;151(5):1283-90.
著者: E David Crawford, Shandra S Wilson, John D McConnell, Kevin M Slawin, Michael C Lieber, Joseph A Smith, Alan G Meehan, Oliver M Bautista, William R Noble, John W Kusek, Leroy M Nyberg, Claus G Roehrborn, MTOPS RESEARCH Group
雑誌名: J Urol. 2006 Apr;175(4):1422-6; discussion 1426-7. doi: 10.1016/S0022-5347(05)00708-1.
Abstract/Text PURPOSE: We analyzed data from the placebo arm of the MTOPS trial to determine clinical predictors of BPH progression.
MATERIALS AND METHODS: A total of 3,047 patients with LUTS were randomized to either placebo, doxazosin (4 to 8 mg), finasteride (5 mg), or a combination of doxazosin and finasteride. Average length of followup was 4.5 years. The primary outcome was time to overall clinical progression of BPH, defined as either a confirmed 4-point or greater increase in AUA SS, acute urinary retention, incontinence, renal insufficiency, or recurrent urinary tract infection. We analyzed BPH progression event data from the 737 men who were randomized to placebo.
RESULTS: The rate of overall clinical progression of BPH events in the placebo group was 4.5 per 100 person-years, for a cumulative incidence (among men who had at least 4 years of followup data) of 17%. The risk of BPH progression was significantly greater in patients on placebo with a baseline TPV of 31 ml or greater vs less than 31 ml (p <0.0001), a baseline PSA of 1.6 ng/dl or greater vs PSA less than 1.6 ng/dl (p = 0.0009), a baseline Qmax of less than 10.6 ml per second vs 10.6 ml per second or greater (p = 0.011), a baseline PVR of 39 ml or greater vs less than 39 ml (p = 0.0008) and baseline age 62 years or older vs younger than 62 years (p = 0.0002).
CONCLUSIONS: Among men in the placebo arm, baseline TPV, PSA, Qmax, PVR and age were important predictors of the risk of clinical progression of BPH.

PMID 16516013  J Urol. 2006 Apr;175(4):1422-6; discussion 1426-7. doi:・・・
著者: L H Spiro, G Labay, L A Orkin
雑誌名: Urology. 1974 Mar;3(3):345-7.
Abstract/Text
PMID 4132103  Urology. 1974 Mar;3(3):345-7.
著者: M Ohmura, A Kondo, M Saito
雑誌名: Int J Urol. 1997 May;4(3):295-9.
Abstract/Text BACKGROUND: Acute ethanol ingestion increases the risk of urinary retention in patients with benign prostatic hyperplasia (BPH). To elucidate the mechanism of this effect, we investigated the in vitro effects of ethanol on lower urinary tract function in rabbits.
METHODS: The responses to various stimuli of muscle strips isolated from male rabbit bladder and urethra were determined in the presence of 0%, 0.5%, 1.0%, and 3.0% ethanol.
RESULTS: Basal tension of tissue strips taken from the bladder and the urethra was reduced by ethanol in a dose-dependent manner, as were bladder contractions induced by field stimulation, bethanechol, and ATP. Ethanol also reduced phenylephrine-induced contractions of the prostatic urethra. A high (3%) concentration of ethanol significantly reduced KCl-induced contraction of both the bladder and urethra, as well as urethral relaxation induced by field stimulation following contraction with 200 mumol/L phenylephrine.
CONCLUSION: Responsiveness of the rabbit lower urinary tract was significantly reduced by exposure to ethanol. A similar decrease in tonus and contractility of the detrusor and inhibition of relaxation in the prostatic urethra may lead to urinary retention in men following acute ingestion of ethanol.

PMID 9255670  Int J Urol. 1997 May;4(3):295-9.
著者: W K Mebust, H L Holtgrewe, A T Cockett, P C Peters
雑誌名: J Urol. 1989 Feb;141(2):243-7.
Abstract/Text The mortality rate for transurethral prostatectomy was 0.2 per cent in 3,885 patients reviewed retrospectively. The immediate postoperative morbidity rate was 18 per cent. Increased morbidity was found in patients with a resection time of more than 90 minutes, gland size of more than 45 gm., acute urinary retention and patient age greater than 80 years, and in the black population. Of the patients 77 per cent had significant pre-existing medical problems. Operative mortality, significant morbidity and hospital stay were reduced in comparison to studies done 15 and 30 years ago.

PMID 2643719  J Urol. 1989 Feb;141(2):243-7.
著者: S J Foley, D M Bailey
雑誌名: BJU Int. 2000 Jan;85(1):70-3.
Abstract/Text OBJECTIVES: To examine the prostates from patients with haematuria associated with benign prostatic hyperplasia (BPH) to determine their microvascular anatomy and thus assess histopathological differences in patients with significant haematuria.
PATIENTS AND METHODS: Prospectively, 11 patients with BPH and haematuria (mean age 70 years) and 19 control patients with BPH alone (mean age 72 years) were identified. Neither group had received hormone manipulation or had been catheterized. The sub-urothelial compartment of the prostatic urethra in subsequent specimens from transurethral resection was examined using factor VIII/CD-34 immuno-histochemistry. The microvessel density (MVD) was calculated by counting vascular cross-sectional profiles within a 0.81-mm2 grid. The pathologist studying the specimens was unaware of the patients' symptoms.
RESULTS: The median (range) MVD in the haematuria group was 64 (28-137) and in the controls was 27 (14-39) (P < 0.001).
CONCLUSION: The MVD was significantly greater in the patients with haematuria, suggesting that suburothelial microvessel proliferation may play an important role in mediating haematuria associated with BPH. This is the first time that a difference has been shown at the cellular level in patients with haematuria and could form an important foundation for subsequent research.

PMID 10619949  BJU Int. 2000 Jan;85(1):70-3.
著者: R Corey O'Connor, Brett A Laven, Gregory T Bales, Glenn S Gerber
雑誌名: Urology. 2002 Aug;60(2):288-91.
Abstract/Text OBJECTIVES: To assess the outcome of men with bladder calculi who did not undergo transurethral resection of the prostate after endoscopic stone removal. Bladder calculi associated with benign prostatic hyperplasia (BPH) have historically been an absolute indication for transurethral resection of the prostate.
METHODS: A retrospective analysis of the results of 23 men who underwent endoscopic removal of bladder calculi with subsequent medical management of BPH symptoms was performed. Inclusion criteria included men with bladder stones secondary to BPH, serum creatinine 1.6 mg/dL or less, no evidence of hydronephrosis, and no history of acute urinary retention or neurogenic bladder. The International Prostate Symptom Score and postvoid residual urine volume before and after treatment and the incidence of bladder stone recurrence and associated complications were recorded. All patients were treated with either an alpha-receptor blocker or alpha-receptor blocker and finasteride after bladder stone removal.
RESULTS: The follow-up after endoscopic removal of the bladder calculi averaged 30.0 months (range 6 to 96). The International Prostate Symptom Score before and after treatment was 18.3 and 9.4 (P <0.01), respectively. The postvoid residual urine volume before and after treatment was 354 and 179 mL (P <0.01), respectively. Urinary tract infection, acute urinary retention, recurrent calculi, chronic renal insufficiency, or renal failure developed in 21.7% (n = 5), 17.4% (n = 4), 17.4% (n = 4), 4.3% (n = 1), and 0% (n = 0) of the 23 men, respectively. Overall, 18 (78%) did not have any complications.
CONCLUSIONS: Many men with bladder stones can be successfully and safely treated with transurethral stone removal and medical management of BPH.

PMID 12137828  Urology. 2002 Aug;60(2):288-91.
著者: M J Barry, F J Fowler, M P O'Leary, R C Bruskewitz, H L Holtgrewe, W K Mebust, A T Cockett
雑誌名: J Urol. 1992 Nov;148(5):1549-57; discussion 1564.
Abstract/Text A symptom index for benign prostatic hyperplasia (BPH) was developed and validated by a multidisciplinary measurement committee of the American Urological Association (AUA). Validation studies were conducted involving a total of 210 BPH patients and 108 control subjects. The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's alpha = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p < 0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols.

PMID 1279218  J Urol. 1992 Nov;148(5):1549-57; discussion 1564.
著者: Naoya Masumori, Daiichi Homma, Taiji Tsukamoto
雑誌名: BJU Int. 2005 May;95(7):1013-22. doi: 10.1111/j.1464-410X.2005.05457.x.
Abstract/Text OBJECTIVE: To investigate the distribution of lower urinary tract symptoms (LUTS) in elderly Japanese men, to clarify which variables contributed to medical care-seeking behaviour, and to construct a structural-equation model (SEM) to explain overall quality of life (QoL).
SUBJECTS AND METHODS: A dataset was obtained from 662 Japanese men aged 50-79 years who participated in the programme by accessing a website via the Internet between 10.30 hours on 19 February 2003 and 10.30 hours on 24 February 2003. The participants were queried about their International Prostate Symptom Score (IPSS), bother, QoL index and medical care-seeking behaviour.
RESULTS: Of the 662 participants, 314 reported intending to seek medical care for LUTS (intention group); the remaining 348 answered that they did not intend to see a doctor (no-intention group). The characteristic of weak stream had the strongest correlation with the QoL index, not only in the intention (r = 0.58) but also in the no-intention group (r = 0.48). Among several SEMs proposed, one that included a latent variable termed 'QoL sensitivity' was the most appropriate to explain overall QoL. In this model it was assumed that 'QoL sensitivity' was affected by other latent variables, termed the 'voiding symptom factors' and 'storage symptom factors', and affected the degree of bother related to each symptom.
CONCLUSION: In Japanese men, voiding symptoms, especially weak stream, contributed to overall QoL for medical care-seeking behaviour. Differences in 'QoL sensitivity' among men may be one of the reasons why symptomatic severity is not always correlated with symptom-related bother.

PMID 15839923  BJU Int. 2005 May;95(7):1013-22. doi: 10.1111/j.1464-41・・・
著者: R Takei, I Ikegaki, K Shibata, G Tsujimoto, T Asano
雑誌名: Jpn J Pharmacol. 1999 Apr;79(4):447-54.
Abstract/Text The pharmacological profiles of the alpha1-adrenoceptor antagonists naftopidil, tamsulosin and prazosin were studied in an anesthetized dog model that allowed the simultaneous assessment of their antagonist potency against phenylephrine-mediated increases in prostatic pressure and mean blood pressure. The intravenous administration of each of these compounds dose-dependently inhibited phenylephrine-induced increases in prostatic pressure and mean blood pressure. To further assess the ability of the three compounds to inhibit phenylephrine-induced responses, the doses required to produce a 50% inhibition of the phenylephrine-induced increases in prostatic and mean blood pressure and the selectivity index obtained from the ratio of those two doses were determined for each test compound. Forty minutes after the intravenous administration of naftopidil, the selectivity index was 3.76, and those of tamsulosin and prazosin were 1.23 and 0.61, respectively. These findings demonstrated that naftopidil selectively inhibited the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure in the anesthetized dog model. The selectivity of naftopidil for prostatic pressure was the most potent among the test compounds. In addition, using cloned human alpha1-adrenoceptor subtypes, naftopidil was selective for the alpha1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha1a- and alpha1b-adrenoceptor subtypes, respectively. The selectivity of naftopidil for prostatic pressure may be attributable to its high binding affinity for alpha1a- and alpha1d-adrenoceptor subtypes.

PMID 10361884  Jpn J Pharmacol. 1999 Apr;79(4):447-54.
著者: K Shibata, R Foglar, K Horie, K Obika, A Sakamoto, S Ogawa, G Tsujimoto
雑誌名: Mol Pharmacol. 1995 Aug;48(2):250-8.
Abstract/Text alpha 1-Adrenoceptors (ARs) comprise a heterogeneous family, and subtype-selective ligands are valuable for studying the functional role of each receptor subtype. We characterized a newly synthesized, alpha 1-AR antagonist, KMD-3213, by using Chinese hamster ovary cells stably expressing the three cloned human alpha 1-ARs (alpha 1a, alpha 1b, and alpha 1d), as well as native rat and human tissues. KMD-3213 potently inhibited 2-[2-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]-alpha-tetralone binding to the cloned human alpha 1a-AR, with a Ki value of 0.036 nM, but had 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively. KMD-3213 inhibited norepinephrine-induced increases in intracellular Ca2+ concentrations in alpha 1a-AR-expressing Chinese hamster ovary cells with an IC50 of 0.32 nM but had a much weaker inhibitory effect on the alpha 1b- and alpha 1d-ARs. Using pharmacologically well characterized native rat tissues [submaxillary gland (alpha 1A-AR-expressing tissue), liver (alpha 1B-AR-expressing tissue), and heart (mixed alpha 1A- and alpha 1B-AR-expressing tissue)], binding studies showed that inhibition curves for KMD-3213 in submaxillary gland and liver best fit a one-site model (with Ki values of 0.15 and 16 nM, respectively), whereas KMD-3213 had high and low affinity sites in heart membranes. Chloroethylclonidine treatment of rat heart membranes completely eliminated the low affinity sites for KMD-3213. Furthermore, in human liver and prostate KMD-3213 could identify high and low affinity sites, the Ki values of which corresponded well to those for the cloned human alpha 1a- and alpha 1b-ARs, respectively. Moreover, the affinity of KMD-3213 was found to be approximately 10-fold higher at the cloned human alpha 1a-AR than at the cloned rat alpha 1a-AR. KMD-3213 is a potent and highly selective antagonist for the human alpha 1a-AR and would be useful for studying the physiological roles of human alpha 1-AR subtypes.

PMID 7651358  Mol Pharmacol. 1995 Aug;48(2):250-8.
著者: Taiji Tsukamoto, Yukihiro Endo, Michiro Narita
雑誌名: Int J Urol. 2009 Sep;16(9):745-50. doi: 10.1111/j.1442-2042.2009.02357.x. Epub 2009 Aug 5.
Abstract/Text OBJECTIVES: To assess the efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia (BPH).
METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group study. A total of 378 subjects with clinical BPH having an International Prostate Symptom Score (IPSS) of 8 points or greater, a prostate volume of 30 mL or greater, and a maximal urinary flow rate (Qmax) of 15 mL/s or less were randomized to receive placebo or dutasteride once daily for 52 weeks. Subjects were stratified according to tamsulosin use at baseline. The numbers of subjects with and without tamsulosin use were 242 and 136, respectively. IPSS, Qmax, prostate volume and drug safety were evaluated.
RESULTS: Continued improvement in IPSS was noted in the dutasteride group, and dutasteride significantly decreased IPSS compared with placebo. At week 52, dutasteride significantly improved Qmax and prostate volume compared with placebo. Drug-related sexual function events in the dutasteride group were infrequent and generally were not treatment limiting.
CONCLUSIONS: Dutasteride improves urinary symptoms and flow rate and reduces prostate volume. In Japanese men with BPH, it is effective and generally well tolerated during the one-year treatment period.

PMID 19674165  Int J Urol. 2009 Sep;16(9):745-50. doi: 10.1111/j.1442-・・・
著者: Jean-Nicolas Cornu, Sascha Ahyai, Alexander Bachmann, Jean de la Rosette, Peter Gilling, Christian Gratzke, Kevin McVary, Giacomo Novara, Henry Woo, Stephan Madersbacher
雑誌名: Eur Urol. 2015 Jun;67(6):1066-1096. doi: 10.1016/j.eururo.2014.06.017. Epub 2014 Jun 25.
Abstract/Text CONTEXT: A number of transurethral ablative techniques based on the use of innovative medical devices have been introduced in the recent past for the surgical treatment of benign prostatic obstruction (BPO).
OBJECTIVE: To conduct a systematic review of the literature and a meta-analysis of available randomized controlled trials (RCTs), and to evaluate the efficacy and safety of transurethral ablative procedures for BPO.
EVIDENCE ACQUISITION: A systematic literature search was performed for all RCTs comparing any transurethral surgical technique for BPO to another between 1992 and 2013. Efficacy was evaluated after a minimum follow-up of 1 yr based on International Prostate Symptom Score, maximum flow rate, and postvoid residual volume. Efficacy at midterm follow-up, prostate volume, perioperative data, and short-term and long-term complications were also assessed. Data were analyzed using RevMan software.
EVIDENCE SYNTHESIS: A total of 69 RCTs (8517 enrolled patients) were included. No significant difference was found in terms of short-term efficacy between bipolar transurethral resection of the prostate (B-TURP) and monopolar transurethral resection of the prostate (M-TURP). However, B-TURP was associated with a lower rate of perioperative complications. Better short-term efficacy outcomes, fewer immediate complications, and a shorter hospital stay were found after holmium laser enucleation of the prostate (HoLEP) compared with M-TURP. Compared with M-TURP, GreenLight photoselective vaporization of the prostate (PVP) was associated with a shorter hospital stay and fewer complications but no different short-term efficacy outcomes.
CONCLUSIONS: This meta-analysis shows that HoLEP is associated with more favorable outcomes than M-TURP in published RCTs. B-TURP and PVP have resulted in better perioperative outcomes without significant differences regarding efficacy parameters after short-term follow-up compared with M-TURP. Further studies are needed to provide long-term comparative data and head-to head comparisons of emerging techniques.
PATIENT SUMMARY: Bipolar transurethral resection of the prostate, photovaporization of the prostate, and holmium laser enucleation of the prostate have shown efficacy outcomes comparable with conventional techniques yet reduce the complication rate. The respective role of these new options in the surgical armamentarium needs to be refined to propose tailored surgical treatment for benign prostatic obstruction relief.

Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 24972732  Eur Urol. 2015 Jun;67(6):1066-1096. doi: 10.1016/j.euru・・・
著者: Sascha A Ahyai, Peter Gilling, Steven A Kaplan, Rainer M Kuntz, Stephan Madersbacher, Francesco Montorsi, Mark J Speakman, Christian G Stief
雑誌名: Eur Urol. 2010 Sep;58(3):384-97. doi: 10.1016/j.eururo.2010.06.005. Epub 2010 Jun 11.
Abstract/Text CONTEXT: There is a continuous decline in the number of transurethral resections of the prostate (TURP) and an increase use of minimally invasive surgical therapy (MIST) for lower urinary tract symptoms resulting from benign prostatic enlargement. Current results from randomised controlled trials (RCT) and methodologically sound prospective studies suggest that some of the proposed procedures have the potential to replace TURP.
OBJECTIVE: To determine the contemporary status of TURP and of the currently most commonly applied transurethral MISTs: (1) bipolar TURP, (2) bipolar transurethral vaporisation of the prostate (bipolar TUVP), (3) holmium laser enucleation of the prostate (HoLEP), and (4) potassium-titanyl-phosphate (KTP) laser vaporisation of the prostate.
EVIDENCE ACQUISITION: This meta-analysis was based on a systematic Medline search assessing the period 1997-2009. All RCTs comparing TURP and the most commonly discussed ablative treatments were included. The end points of our analyses were functional outcomes and treatment-related adverse events.
EVIDENCE SYNTHESIS: Twenty-seven publications involving 23 different RCTs with a total of 2245 patients provided the highest level of evidence available (level 1b) and were fully assessed. Meta-analysis was conducted with SAS v.9.1.3 (SAS Institute, Cary, NC, USA). Forest plots were produced using the R software. Pooled odds ratios and 95% confidence intervals were calculated between various operative techniques versus TURP. Functional results between the specific transurethral procedures versus TURP were summarised as differences in means.
CONCLUSIONS: This meta-analysis demonstrates statistically comparable efficacy and overall morbidity for MISTs versus contemporary TURP. Type, category (minor vs major), and the number of complications (safety profile) vary specifically for each of the different transurethral techniques. We feel that the individual patient's clinical profile should be carefully assessed to identify the most appropriate transurethral technique.

(c) 2010 European Association of Urology. All rights reserved.
PMID 20825758  Eur Urol. 2010 Sep;58(3):384-97. doi: 10.1016/j.eururo.・・・
著者: Alexander Bachmann, Andrea Tubaro, Neil Barber, Frank d'Ancona, Gordon Muir, Ulrich Witzsch, Marc-Oliver Grimm, Joan Benejam, Jens-Uwe Stolzenburg, Antony Riddick, Sascha Pahernik, Herman Roelink, Filip Ameye, Christian Saussine, Franck Bruyère, Wolfgang Loidl, Tim Larner, Nirjan-Kumar Gogoi, Richard Hindley, Rolf Muschter, Andrew Thorpe, Nitin Shrotri, Stuart Graham, Moritz Hamann, Kurt Miller, Martin Schostak, Carlos Capitán, Helmut Knispel, J Andrew Thomas
雑誌名: Eur Urol. 2014 May;65(5):931-42. doi: 10.1016/j.eururo.2013.10.040. Epub 2013 Nov 11.
Abstract/Text BACKGROUND: The comparative outcome with GreenLight (GL) photoselective vaporisation of the prostate and transurethral resection of the prostate (TURP) in men with lower urinary tract symptoms due to benign prostatic obstruction (BPO) has been questioned.
OBJECTIVE: The primary objective of the GOLIATH study was to evaluate the noninferiority of 180-W GL XPS (XPS) to TURP for International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) at 6 mo and the proportion of patients who were complication free.
DESIGN, SETTING, AND PARTICIPANTS: Prospective randomised controlled trial at 29 centres in 9 European countries involving 281 patients with BPO.
INTERVENTION: 180-W GL XPS system or TURP.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Measurements used were IPSS, Qmax, prostate volume (PV), postvoid residual (PVR) and complications, perioperative parameters, and reintervention rates. Noninferiority was evaluated using one-sided tests at the 2.5% level of significance. The statistical significance of other comparisons was assessed at the (two-sided) 5% level.
RESULTS AND LIMITATIONS: The study demonstrated the noninferiority of XPS to TURP for IPSS, Qmax, and complication-free proportion. PV and PVR were comparable between groups. Time until stable health status, length of catheterisation, and length of hospital stay were superior with XPS (p<0.001). Early reintervention rate within 30 d was three times higher after TURP (p=0.025); however, the overall postoperative reintervention rates were not significantly different between treatment arms. A limitation was the short follow-up.
CONCLUSIONS: XPS was shown to be noninferior (comparable) to TURP in terms of IPSS, Qmax, and proportion of patients free of complications. XPS results in a lower rate of early reinterventions but has a similar rate after 6 mo.
TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01218672.

Copyright © 2013. Published by Elsevier B.V.
PMID 24331152  Eur Urol. 2014 May;65(5):931-42. doi: 10.1016/j.eururo.・・・
著者: Hazem Elmansy, Abdulaziz Baazeem, Ahmed Kotb, Hesham Badawy, Essam Riad, Ashraf Emran, Mostafa Elhilali
雑誌名: J Urol. 2012 Jul;188(1):216-21. doi: 10.1016/j.juro.2012.02.2576. Epub 2012 May 15.
Abstract/Text PURPOSE: To our knowledge we report the first single center, prospective, randomized study comparing holmium laser enucleation and high performance GreenLight™ prostate photoselective vaporization as surgical treatment of prostatic adenomas greater than 60 ml.
MATERIALS AND METHODS: A total of 80 patients with a large prostatic adenoma were randomly assigned to surgical treatment with holmium laser enucleation or photoselective vaporization. International Prostate Symptom Score, International Index of Erectile Function-15, maximum flow rate, post-void residual urine, serum prostate specific antigen and transrectal ultrasound volume were recorded.
RESULTS: Patient baseline characteristics were similar for holmium laser enucleation and photoselective vaporization. Operative time and catheter removal time were almost equal in the 2 groups (p = 0.7 and 0.2, respectively). Eight vaporization cases were converted to transurethral prostate resection or holmium laser enucleation intraoperatively due to bleeding. A significantly higher maximum flow rate and lower post-void residual urine were noted in holmium laser cases during the entire followup (at 1 year each p = 0.02). However, no significant difference in International Prostate Symptom Score, quality of life or International Index of Erectile Function-15 was detected. Prostate volume and serum PSA decreased 78% and 88% in the holmium laser group, and 52% and 60% in the vaporization group, respectively.
CONCLUSIONS: Holmium laser enucleation and photoselective vaporization are effective for lower urinary tract symptoms due to a large prostatic adenoma. Early subjective functional results (maximum flow rate and post-void residual urine) of holmium laser enucleation appear to be superior to those of photoselective vaporization. In our hands cases intended to be treated with photoselective vaporization were at 22% risk of conversion to another modality. This could reflect our determination to vaporize to the capsule in all vaporization cases.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 22591968  J Urol. 2012 Jul;188(1):216-21. doi: 10.1016/j.juro.201・・・
著者: Kang Sup Kim, Jin Bong Choi, Woong Jin Bae, Su Jin Kim, Hyuk Jin Cho, Sung-Hoo Hong, Ji Youl Lee, Sang Hoon Kim, Hyun Woo Kim, Su Yeon Cho, Sae Woong Kim
雑誌名: PLoS One. 2016;11(5):e0156133. doi: 10.1371/journal.pone.0156133. Epub 2016 May 26.
Abstract/Text OBJECTIVE: Photoselective vaporization of the prostate (PVP) using GreenLight and Holmium laser enucleation of the prostate (HoLEP) is an important surgical technique for management of benign prostate hyperplasia (BPH). We aimed to compare the effectiveness and safety of PVP using a 120 W GreenLight laser with HoLEP in a small prostate volume.
METHODS: Patients who underwent PVP or HoLEP surgery for BPH at our institutions were reviewed from May 2009 to December 2014 in this retrospective study. Among them, patients with prostate volumes < 40 mL based on preoperative trans-rectal ultrasonography were included in this study. Peri-operative and post-operative parameters-such as International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), and complications-were compared between the groups.
RESULTS: PVP was performed in 176 patients and HoLEP in162 patients. Preoperative demographic data were similar in both groups, with the exception of PVR. Operative time and catheter duration did not show significant difference. Significant improvements compared to preoperative values were verified at the postoperative evaluation in both groups in terms of IPSS, QoL, Qmax, and PVR. Comparison of the postoperative parameters between the PVP and HoLEP groups demonstrated no significant difference, with the exception of IPSS voiding subscore at 1 month postoperatively (5.9 vs. 3.8, P< 0.001). There was no significant difference in postoperative complications between the two groups.
CONCLUSION: Our data suggest that PVP and HoLEP are efficient and safe surgical treatment options for patients with small prostate volume.

PMID 27227564  PLoS One. 2016;11(5):e0156133. doi: 10.1371/journal.pon・・・

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