慢性前列腺炎研究進(jìn)展

1、慢性前列腺炎研究進(jìn)展,,歷史回顧,1850-1920發(fā)現(xiàn)時(shí)代建立概念和認(rèn)識(shí)病因（19世紀(jì)初）前列腺液檢查（1906）治療策略1921-1955啟蒙時(shí)代認(rèn)識(shí)微生物學(xué)病因（1920s）肯定前列腺液白細(xì)胞的重要性（1920s）前列腺按摩是主要治療方法（1940s前）應(yīng)用抗生素（1940s后）,J. C. Nickel. Prostatitis: Evolving Managemen

2、t Strategies. Urol. Clin. North Am.: 1999, 26 (4): 737-751Nickel JC.Prostatitis: lessons from the 20th century. BJU Int 2000 Jan;85(2):179-85,歷史回顧,1956-1967質(zhì)疑時(shí)代發(fā)現(xiàn)無(wú)菌性前列腺炎（1950s）質(zhì)疑前列腺液白細(xì)胞和細(xì)菌培養(yǎng)的意義1968-1995現(xiàn)代

3、科學(xué)時(shí)代/停滯時(shí)代Mears-Stamey 技術(shù)（1968）Drach提出傳統(tǒng)的分類（1978）提出合理應(yīng)用抗菌藥研究相對(duì)停滯,J. C. Nickel. Prostatitis: Evolving Management Strategies. Urol. Clin. North Am.: 1999, 26 (4): 737-751Nickel JC.Prostatitis: lessons from

4、the 20th century. BJU Int 2000 Jan;85(2):179-85,歷史回顧,1996-今新啟蒙時(shí)代前列腺炎研究重新活躍NIH慢性前列腺炎研討會(huì)（1995）前列腺炎的NIH定義和分類（1995）北美慢性前列腺炎臨床研究組織（1997）NIH國(guó)際前列腺炎協(xié)作組織（1998）,J. C. Nickel. Prostatitis: Evolving Management S

5、trategies. Urol. Clin. North Am.: 1999, 26 (4): 737-751Nickel JC.Prostatitis: lessons from the 20th century. BJU Int 2000 Jan;85(2):179-85,前列腺炎分類,急性細(xì)菌性前列腺炎慢性細(xì)菌性前列腺炎慢性非細(xì)菌性前列腺炎（64%）前列腺痛（31%）,傳統(tǒng)分類,Brunner H, Weidner W,

6、Schiefer HG. Studies of the role of Ureaplasma urealyticum and Mycoplasma hominis in prostatitis. J Infect Dis 1983, 147: 807,,,5%,前列腺炎NIH分類（1998）,Acute bacterial prostatitis 急性細(xì)菌性前列腺炎Chronic bacterial prostatitis 慢性細(xì)菌性

7、前列腺炎Chronic prostatitis/chronic pelvic pain syndrome慢性前列腺炎/慢性骨盆疼痛綜合征IIIA. Inflammatory 炎癥性IIIB. Noninflammatory 非炎癥性IV.Asymptomatic inflammatory prostatitis 無(wú)癥狀炎癥性前列腺炎,Krieger, J. N., Nyberg, L., Jr. and Nickel,

8、 J. C.: NIH consensus definition and classification of prostatitis. JAMA, 282: 236,1999,各類前列腺炎的特征,慢性前列腺炎/慢性骨盆疼痛綜合征,90%以上有癥狀的患者名稱揭示了認(rèn)識(shí)的不足對(duì)大多數(shù)患者的病因認(rèn)識(shí)有限前列腺以外的器官可能很重要泌尿系疼痛是首要癥狀，且除外正在發(fā)作的尿道炎泌尿生殖系腫瘤尿路疾病功能性尿道狹窄(functiona

9、l urethral stricture)影響膀胱的神經(jīng)疾病IIIA型患者前列腺按摩液、按摩后尿液、精液中有白細(xì)胞,Krieger, J. N., Nyberg, L., Jr. and Nickel, J. C.: NIH consensus definition and classification of prostatitis. JAMA, 282: 236,1999,慢性前列腺炎/慢性骨盆疼痛綜合征與慢性非細(xì)菌性前列腺炎和

10、前列腺痛的差異 IIIA+IIIB=CNP+PdyIIIA=CNP & IIIB=Pdy,有癥狀但無(wú)尿道炎、急性或慢性細(xì)菌性前列腺炎的140名患者EPS、按摩后尿(POST-M)、精液 共420份標(biāo)本73人的111 份(26%)標(biāo)本有炎癥證據(jù)EPS白細(xì)胞> 500/mm3, 39份POST-M尿白細(xì)胞>1/mm3, 32份精液白細(xì)胞>1?106/mm3，40份 根據(jù)不同的診斷標(biāo)準(zhǔn)，

11、140名患者中IIIA 73（52%）CNP 39 (28%)IIIB 67（48%）Pyd101(72%),Krieger JN, Jacobs RR, Ross SO. Does the chronic prostatitis/pelvic pain syndrome differ from nonbacterial prostatitis and prostatodynia? J Urol 2000 Nov;1

12、64(5):1554-8,？,？,無(wú)癥狀炎癥性前列腺炎在前列腺癌篩查中的意義,Potts JM. Prospective identification of National Institutes of Health category IV prostatitis in men with elevated prostate specific antigen. J Urol 2000 Nov;164(5):1550-3,無(wú)癥狀炎癥性前列腺

13、炎在前列腺癌篩查中的意義,PSA的下降在良性組遠(yuǎn)較前列腺癌者明顯 (-21.32 versus -1.33%, p = 0.001)隨訪1-2年前列腺炎組未發(fā)現(xiàn)PSA波動(dòng)篩除前列腺炎減少了活檢的病例數(shù)18% (22 of 122)提高了PSA篩查的活檢陽(yáng)性率 (45 of 122 cases or 37% versus 36 of 71 or 51%),Potts JM. Prospective identification o

14、f National Institutes of Health category IV prostatitis in men with elevated prostate specific antigen. J Urol 2000 Nov;164(5):1550-3,NIH第一屆國(guó)際前列腺炎協(xié)作組織會(huì)議 International Prostatitis Collaborative Network (IPCN)（1998年11月5-

15、6日，華盛頓）,慢性前列腺炎是一重要健康問題在前列腺炎的臨床試驗(yàn)中應(yīng)采納NIH慢性前列腺炎/慢性骨盆疼痛綜合征的定義NIH1995年分類系統(tǒng)應(yīng)廣泛應(yīng)用于慢性前列腺炎/慢性骨盆疼痛綜合征的研究和臨床試驗(yàn)NIH慢性前列腺炎臨床研究組織提出的入選和排除標(biāo)準(zhǔn)應(yīng)為前列腺炎臨床研究所采納NIH慢性前列腺炎癥狀評(píng)分應(yīng)為前列腺炎臨床試驗(yàn)所采納臨床治療研究的規(guī)范,Nickel JC, Nyberg LM, Hennenfent M.Resear

16、ch guidelines for chronic prostatitis: consensus report from the first National Institutes of Health International Prostatitis Collaborative Network. Urology 1999 Aug;54(2):229-33,流行病學(xué),前列腺炎患病率為5-8%1前列腺炎是50歲以下患者就診泌尿外科的最常

17、見原因，占美國(guó)泌尿外科門診總量的8%2對(duì)31681名男性專業(yè)技術(shù)人士的調(diào)查3年齡40-75歲，平均63.2歲調(diào)查方法：?jiǎn)栴}和問卷（AUA癥狀評(píng)分）16% 報(bào)告有前列腺炎病史，除外BPH患者則為9%接受治療的年齡60歲2.8%6.1% 9.5%12.3%6.8%,Nickel JC.Prostatitis: lessons from the 20th century. BJU Int 2000 Jan;85

18、(2):179-85 Collins MM, Stafford RS, O’Leary MP, et al. How common is prostatitis? A national survey of physician visits. J Urol. 1998, 159: 1224-8Collins MM, Meigs JB, Barry MJ, et al. Prevalence and correlates of pros

19、tatitis in the health professionals follow-up study cohort. J Urol 2002 Mar;167(3):1363-6,Collins MM, Meigs JB, Barry MJ, et al. Prevalence and correlates of prostatitis in the health professionals follow-up study cohort

20、. J Urol 2002 Mar;167(3):1363-6,,,,,危險(xiǎn)因素,慢性前列腺炎與性功能障礙,早泄患者中慢性前列腺炎的患病率1前列腺炎癥 56.5%慢性細(xì)菌性前列腺炎47.8% 1832名前列腺炎患者243%勃起功能障礙24%性欲減退,Screponi E, Carosa E, Di Stasi SM, Pepe M, Carruba G, Jannini EA.Prevalence of chronic pro

21、statitis in men with premature ejaculation. Urology 2001 Aug;58(2):198-202Mehik A, Hellstrom P, Sarpola A, et al. Fears, sexual disturbances and personality features in men with prostatitis: a population-based cross-sec

22、tional study in Finland. BJU Int 2001 Jul;88(1):35-8,尿液返流交感神經(jīng)興奮免疫反應(yīng)細(xì)菌感染,機(jī)制研究,神經(jīng)與理化研究,慢性骨盆疼痛可見于間質(zhì)性膀胱炎、結(jié)腸易激綜合征、前列腺炎等炎癥性疾病，但無(wú)明確病因神經(jīng)原炎癥(neurogenic inflammation)1前列腺液和精液中的氧化張力(Oxidative stress)2-3前列腺組織內(nèi)壓力4前列腺炎>對(duì)照II

23、IA>IIIB,Wesselmann U. Neurogenic inflammation and chronic pelvic pain. World J Urol 2001 Jun;19(3):180-5Shahed AR, Shoskes DA.Oxidative stress in prostatic fluid of patients with chronic pelvic pain syndrome: correl

24、ation with gram positive bacterial growth and treatment response. J Androl 2000 Sep-Oct;21(5):669-75Pasqualotto FF, Sharma RK, Potts JM, et al. Seminal oxidative stress in patients with chronic prostatitis. Urology 2000

25、 Jun;55(6):881-5Mehik A, Hellstrom P, Nickel JC, Kilponen A, et al. The chronic prostatitis-chronic pelvic pain syndrome can be characterized by prostatic tissue pressure measurements. J Urol 2002 Jan;167(1):137-40,免疫學(xué)研

26、究,IIIB患者血液、精漿和前列腺組織中白介素、補(bǔ)體和免疫球蛋白的變化1精漿Il-1? 、TNF-?、IL-6、IL-8水平比對(duì)照組顯著增高，IIIA與IIIB組間無(wú)顯著差別2IIIA和IV類的EPS中Il-1? 、TNF-?增高，IIIB不增高3III類精漿中?干擾素、 IL-2 、IL-10水平增高4 II、IIIA者EPS或POST-M尿液中內(nèi)毒素水平增高，IIIB同對(duì)照5,John H, Barghorn A, Funk

27、e G, et al. Noninflammatory chronic pelvic pain syndrome: immunological study in blood, ejaculate and prostate tissue. Eur Urol 2001 Jan;39(1):72-8Orhan I, Onur R, Ilhan N, Ardicoglu A. Seminal plasma cytokine levels in

28、 the diagnosis of chronic pelvic pain syndrome. Int J Urol 2001 Sep;8(9):495-9Nadler RB, Koch AE, Calhoun EA, et al. IL-1beta and TNF-alpha in prostatic secretions are indicators in the evaluation of men with chronic p

29、rostatitis. J Urol 2000 Jul;164(1):214-8Miller LJ, Fischer KA, Goralnick SJ, et al. Interleukin-10 levels in seminal plasma: implications for chronic prostatitis-chronic pelvic pain syndrome. J Urol 2002 Feb;167(2 Pt 1)

30、:753-6Li LJ, Shen ZJ, Lu YL, Fu SZ. The value of endotoxin concentrations in expressed prostatic secretions for the diagnosis and classification of chronic prostatitis. BJU Int 2001 Oct;88(6):536-9,細(xì)菌核糖體編碼DNA(165 rDNA)

31、序列1107例前列腺癌標(biāo)本中 21 (19. 6%)例陽(yáng)性170例慢性前列腺炎/骨盆疼痛綜合征標(biāo)本中 79 (46.4%)例陽(yáng)性 細(xì)菌包括泌尿生殖系病原菌及以前未報(bào)道的微生物細(xì)菌16S rRNA 序列214例前列腺癌標(biāo)本中 9例可見炎癥，PCR均陽(yáng)性65%慢性前列腺炎前列腺液16S rRNA 陽(yáng)性3陰性者抗生素治療無(wú)效細(xì)菌譜廣，棒狀桿菌、葡萄球菌、鏈球菌、大腸桿菌等,Krieger JN, Riley DE, Vesel

32、la RL, et al. Bacterial DNA sequences in prostate tissue from patients with prostate cancer and chronic prostatitis. J Urol 2000 Oct;164(4):1221-8Hochreiter WW, Duncan JL, Schaeffer AJ.Evaluation of the bacterial flora

33、of the prostate using a 16S rRNA gene based polymerase chain reaction. J Urol 2000 Jan;163(1):127-30Tanner MA, Shoskes D, Shahed A, Pace NR.Prevalence of corynebacterial 16S rRNA sequences in patients with bacterial and

34、 "nonbacterial" prostatitis. J Clin Microbiol 1999 Jun;37(6):1863-70,分子生物學(xué)研究,診斷與評(píng)估,生活質(zhì)量及對(duì)患者身心健康影響的客觀評(píng)價(jià)1Chronic Prostatitis Collaborative Research Network功能評(píng)估2,McNaughton Collins M, Pontari MA, et al. Qualit

35、y of life is impaired in men with chronic prostatitis: the Chronic Prostatitis Collaborative Research Network. J Gen Intern Med 2001 Oct;16(10):656-62Zernann DH, Ishigooka M, et al. The male chronic pelvic pain syndrome

36、. World J Urol, 2001, 19: 173-179,簡(jiǎn)化的細(xì)菌定位實(shí)驗(yàn)按摩前后試驗(yàn)（PPMT）,標(biāo)本按摩前按摩后II類白細(xì)胞 ? +培養(yǎng) ? +IIIA類白細(xì)胞 - +培養(yǎng) - -IIIB類白細(xì)胞 - -培養(yǎng) - -,

37、NIH慢性前列腺炎癥狀評(píng)分（CPSI）----疼痛或不適,1、在上一周里，在下列部位是否感到疼痛和不適------------ 是 否 a.肛門與陰囊間 □.1 □.0b.睪丸 □.1 □.0c.陰莖頭 □.1 □.0d.腰骶部、膀胱區(qū) □.1 □.0,2、 上一周是否經(jīng)歷過 -------

38、 是 否 a.排尿時(shí)疼痛或燒灼感 □.1 □.0b.射精時(shí)或其后感到 疼痛或不適 □.1 □.0,3 、上一周，上述部位疼痛或不適的頻度 □.0 從不 □.1偶爾 □.2 有時(shí) □.3 經(jīng)常 □.4 多數(shù)時(shí)候

39、 □.5 總是,4、您覺得用哪個(gè)數(shù)字來描述您的疼痛或不適最合適？□0 □1 □2 □3 □4 □5 無(wú)痛□6 □7 □8 □9 □10 最痛,,,,5、上一周里排尿不凈的感覺頻度 □.0 從不□.1 少于１／５的次數(shù) □.2少于１／２的次數(shù)□.3 大約半數(shù)

40、□.4 半數(shù)以上 □.5 幾乎總有,6、上一周中，排尿后不到２小時(shí)又有排尿的感覺的頻度□.0 從沒有□.1 ５次中不到１次□.2 不足半數(shù)□.3 大約半數(shù)□.4 多于半數(shù)□.5 幾乎總是,NIH慢性前列腺炎癥狀評(píng)分（CPSI）----排尿,7、上述癥狀是否影響你日常生活□.0 無(wú)影響□.1 僅有一點(diǎn) □.2 有一些 □.3 很多9、如不治療就這樣過以后的生活 ，你怎么想?□.0 非常滿意 □.1 滿意

41、□.2 基本滿意□.3 滿意與不滿意差不多各半□.4 基本上不滿意□.5 不滿意□.6 非常不滿意,8、你是否總在考慮著你的癥狀□.0 沒有□.1 僅有一點(diǎn)□.2 有些時(shí)侯□.3 不時(shí)地在想,NIH慢性前列腺炎癥狀評(píng)分（CPSI）----癥狀的影響和生活質(zhì)量,NIH-CPSI得分計(jì)算,疼痛或不適癥狀: 項(xiàng)目1+2+3+4=排尿癥狀：項(xiàng)目5+6=生活質(zhì)量影響：項(xiàng)目7+8+9=癥狀嚴(yán)重程度（疼痛+排尿癥狀）：1+2+

42、3+4+5+6=輕度0-9中度10-18重度18-31總體評(píng)分：1+2+3+4+5+6+7+8+9=輕度1-14中度15-29重度30-43,慢性前列腺炎的治療,J. C. Nickel. Prostatitis: Evolving Management Strategies. Urol. Clin. North Am.: 1999, 26 (4): 737-751,保守治療-慢性細(xì)菌性前列腺炎,選擇長(zhǎng)期足量抗

43、生素治療，療程至少6周，少見的細(xì)菌感染應(yīng)治療12周癥狀緩解可停藥觀察癥狀部分緩解，可用抑菌劑量的抗生素復(fù)發(fā)時(shí)可使用預(yù)防劑量的抗生素癥狀無(wú)緩解，再次前列腺按摩并換用抗生素耐藥菌：MRSA,高解離系數(shù)pKa和高脂溶性的藥物易于穿透前列腺組織，喹諾酮類、大環(huán)內(nèi)酯類、四環(huán)素類、磺胺喹諾酮類環(huán)丙沙星對(duì)大腸桿菌引起的慢性細(xì)菌性前列腺炎有效1Clarithromycin在前列腺組織內(nèi)有較高的濃度2Gatifloxacin對(duì)前列腺液

44、和精囊液有良好的穿透，抗菌譜廣3 Levofloxacin 對(duì)未發(fā)生炎癥的前列腺組織穿透良好4,Shoskes DA.Use of antibiotics in chronic prostatitis syndromes. Can J Urol 2001 Jun;8 Suppl 1:24-8Giannopoulos A, Koratzanis G, et al. P harmacokinetics of clarithromycin

45、 in the prostate: implications for the treatment of chronic abacterial prostatitis. J Urol 2001 Jan;165(1):97-9Naber CK, Steghafner M, et al. Concentrations of gatifloxacin in plasma and urine and penetration into prost

46、atic and seminal fluid, ejaculate, and sperm cells after single oral administrations of 400 milligrams to volunteers. Antimicrob Agents Chemother 2001 Jan;45(1):293-7Drusano GL, Preston SL, Van Guilder M, et al. A popul

47、ation pharmacokinetic analysis of the penetration of the prostate by levofloxacin. Antimicrob Agents Chemother 2000 Aug;44(8):2046-51,抗菌治療-慢性細(xì)菌性前列腺炎,TURP或前列腺切除手術(shù)是最后選擇膀胱頸梗阻和尿道狹窄者有手術(shù)適應(yīng)癥理想的受術(shù)者為反復(fù)前列腺液培養(yǎng)為同一細(xì)菌感染前列腺活檢肯定細(xì)菌來自

48、前列腺內(nèi)前列腺結(jié)石合并持續(xù)細(xì)菌感染者也適于手術(shù)手術(shù)前必須讓患者了解手術(shù)的并發(fā)癥以及手術(shù)不一定能緩解癥狀,手術(shù)治療-慢性細(xì)菌性前列腺炎,慢性骨盆疼痛綜合征的診治,考慮神經(jīng)心理因素除外惡性疾病、急/慢性感染除外下尿路功能異常、骨盆底功能異常和盆腔神經(jīng)反射異常推薦的診治程序立即對(duì)癥治療解除疼痛進(jìn)行診斷程序?qū)σ蛑委?Zermann DH, et al. The male chronic pelvic pain syndrome.

49、World J Urol 2001 Jun;19(3):173-9,IIIA類的治療,可能有潛在的一般培養(yǎng)方法陰性的細(xì)菌感染，故可采用抗生素試驗(yàn)治療6周，如反應(yīng)良好，可再用6周選擇抗生素時(shí)需兼顧衣原體等的感染其他同IIIB此類患者不宜手術(shù)治療，可能導(dǎo)致持續(xù)疼痛。,IIIB類的治療,治療目標(biāo)是減輕癥狀、提高生活質(zhì)量，比治愈更重要治療選擇?受體阻滯劑，至少使用3個(gè)月鎮(zhèn)痛藥或非甾體類抗炎藥（口服或局部用藥）植物藥（舍尼通）其它

50、治療安定解痙藥抗抑郁藥雄激素支持療法：鍛煉、心理治療、改變生活方式,對(duì)癥治療-慢性骨盆疼痛綜合征,Terazosine可明顯改善慢性骨盆疼痛綜合征的癥狀，治療應(yīng)至少持續(xù)3個(gè)月1Quercetin（櫟精）可明顯改善慢性骨盆疼痛綜合征的癥狀2小規(guī)模雙盲實(shí)驗(yàn)發(fā)現(xiàn)，非那甾胺可減輕炎癥性慢性骨盆綜合征的排尿癥狀但不能緩解疼痛3Pentosan polysulfate sodium (PPS)治療IIIA 患者，癥狀的頻率和程度、疼

51、痛的程度均較基線明顯減輕，患者生活質(zhì)量提高4舍尼通（裸麥花粉提取物）可改善排尿和疼痛癥狀,Gul O, Eroglu M, Ozok U. Use of terazosine in patients with chronic pelvic pain syndrome and evaluation by prostatitis symptom score index. Int Urol Nephrol 2001;32(3):433-6

52、Shoskes DA, Zeitlin SI, Shahed A, Rajfer J.Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology 1999 Dec;54(6):960-3Leskinen M, Lukkarinen O,

53、 Marttila T. Effects of finasteride in patients with inflammatory chronic pelvic pain syndrome: a double-blind, placebo-controlled, pilot study. Urology 1999 Mar;53(3):502-5Nickel JC, Johnston B, Downey J, et al. Pentos

54、an polysulfate therapy for chronic nonbacterial prostatitis (chronic pelvic pain syndrome category IIIA): a prospective multicenter clinical trial. Urology 2000 Sep 1;56(3):413,舍尼通活性成分---P5與EA10,Habib FK. Ross M Buck. In

55、 vitro elaluation of the pollen extract cernitin T-60 in the regulation of prostate cell growth. Br J Urd, 1990;66:393.Kimura M et al. Activity of pollen extract: contractile effect on bladder and inhibitory effects

56、on urethral smooth muscle of mouse and pig. Planta Medica. 1989;2:148.G. Loschen, et al. Inhibition of the arachidonic acid metabolism by an extract fron rye pollen. Arzneim.-Forsch,1991,41:162-167.Poltit Review. Phar

57、macia Allergon,1994.,舍尼通治療CNP和前列腺痛的機(jī)制和療效,國(guó)外報(bào)道有效率78%（n=90）1治愈36%有效率72.5% （n=40）2治愈32.5%脂溶性EA10抑制白三烯和前列腺素的合成水溶性P5松弛尿道平滑肌,Rugendorff EW, Weidner W, Ebiling L, et al. Results of treatment with pollen extracts (cernilton