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1 Korean J Urol Oncol 2014;12(1):23-28 만성전립선염 / 만성골반통증증후군치료법의최신경향 한양대학교의과대학비뇨기과학교실 김규식ㆍ이승욱 Manegement of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) Kyu Shik Kim, Seung Wook Lee Department of Urology, Hanyang University College of Medicine, Seoul, Korea Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition; however, many of the traditional therapies like monotherapy used in clinical practice fail to show efficacy. There is no one particular treatment to be recommended as a mono-therapy for CP/CPPS. New concept of treatment which is `UPOINT' is introduced. The major barrier in treating men with CP/CPPS is the heterogenous nature of this syndrome. In order to treat appropriately patient should be evaluated individually to assess the nature of symptoms. To evaluate patients chronic urologic pelvic pain, six-point clinical phenotyping system is developed. The clinical domains are urinary symptoms, psychosocial dysfunction, organ-specific findings, infection, neurologic/systemic, and tenderness of muscles, which produces the acronym UPOINT. This clinical phenotyping system may provide a useful and clinically relevant framework for multimodal therapy for the treatment of CP/CPPS. However, concept of UPOINT needs randomization, placebo or sham control studies to show verified treatment. (Korean J Urol Oncol 2014;12:23-28) Key Words: Prostatitis, Chronic Prostatitis with Chronic Pelvic Pain Syndrome 서 20여년전만성전립선에대한치료는질병의원인이되는세균을찾아내고항생제를사용하여치료하였다. 원인을알아내기위해소변검사와전립선액을채취하여배양검사를하였으며그에맞는항생제치료를시행하였다. 그러나몇몇연구에서특정항생제의치료가증상호전에효과가없음을발표하였다 년국립보건원은 NIDDK consenus meeting에서전립선염증상으로전립선염에대한분류표를발표했었다. 세 Received March 19, 2014, Revised April 7, 2014, Accepted April 8, 2014 Corresponding Author: Seung Wook Lee, Department of Urology, Hanyang University Guri Hospital, 249-1, Gyomun-dong, Guri , Korea. Tel: , Fax: , swleepark@hanyang.ac.kr 론 번째분류인 chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) 은만성골반통과함께요로감염없이배뇨증세를갖고있는것이다. 이정의와분류는 1999년 chronic prostatitis syptom index (CPSI) 를발표하여이전의치료결과를바탕으로더항목을보강하여 CP/CPPS의치료법을보강하였다. 2,3 1900년대말에서 2000년대에들어서면서항생제외다른약물치료및여러가지방법의치료들이 CP/CPPS에좋은성과를가져온다는연구들이발표되었으며, 일부치료에대해서 Randomized placebo- or sham-controlled treatment trials등연구를하였다. 전립선비대증, 전립선암은전립선의대표적인질환으로진단, 치료방법또한많은발전을이루어왔으며, 지금도지속적으로연구하고있다. 3번째의전립선질환인전립선염은전립선비대증과전립선암에비해연구가활발하지않으며, 아직도개척해야할분야가많이있다. 최근들어전립선염특히 CP/CPPS에대한새로운치료방법을제시하는연 23

2 24 대한비뇨기종양학술지 : 제 12 권제 1 호 2014 구들이있다. 어떤방법들이제시되고연구되고있는지보겠다. 본론 1. CPPS의요인 CP/CPPS는질병의증상으로인해삶의질에악영향을미치고, 지속적인치료로재정적인부담을안겨주고있다. 4 여러가지의요인이병태생리학적으로영향을복합적으로미친다. 요로감염, 전립선요도역류, 5 Cytokines, 6 pelvic floor spasm, 7 전신성신경성혹은내분비요인 8 그리고신경정신학적인 [9] 요인이복합적으로병인에영향을미친다 (Fig. 1). 대게이런요인들이하나로나타나지않으며복합적으로나타나므로, 단일요법으로치료되었던치료법이최근에는환자에게나타난여러원인을찾고, 표현하고있는증상을동시에치료하자는 UPOINT phenotyping system이소개되었다. 2. 단일치료법 CP/CPPS에대한많은종류의단일치료법이소개되었으며연구되었다. 이치료법의종류로알파차단제, 항생제, 호르몬치료, 항염증치료, 식물치료, 항경련제그리고비약물치료가있다. 이치료법들은 CP/CPPS치료에긍정적인효과를가져온다는논문도있지만효과가없다는논문들도있으며치료법에대한연구의수가부족하거나연구가없는치료방법도있었다. 알파차단제는단일치료법에대해많은연구가되어 CP/CPPS증상치료의효과에대한논문이다수발표되었다. Nickel et al. 은 Silodosin이 CP/CPPS환자의증상호전과삶의질에개선을가져왔다는연구를발표하였다. 9 그리고다른알파차단제 terazosin, 11 alfuzosin 12 도 CP/CPPS에효과가있다는연구들이있었다. 그러나두곳에서실시한다기관연구에의하면그반대의 CP/CPPS에효과가없다는결과를보여주고있다. Alexander et al. 의연구에의하면 6주간의 tamsulosin치료에대한 NIH-CPSI점수는아무런개선이없었으며 13 또다른대규모 alfuzosin연구에서는증상개선이없어 CP/CPPS치료에알파차단제의이점이없음을보고하기도하였다. 14 항생제는배양검사에서음성인경우에도세균성전립선염에거의필수적으로사용되어왔다. 15 그리고 CP/CPPS에항생제를이용한단일치료법이증상에효능이있다는연구결과를보인연구들도있었다. Tetracycline연구에서는 12주간사용하여대조군과비교했을때증상호전이있었으나삶의질에관한연구조사는부족하였다. 16 한Randomized controls trial연구에서 6주간 levofloxacin을사용하여 placebo 와비교하였고 NIH-CPSI 총점수에두군간의호전된점수를보였으나두군간의차이는없었다. 17 NIDDK-후원연구에서는 Ciprofloxacin이 placebo에비해더나은점이없음을발표하였다. 13 항생제사용에대한메타분석에서통계학적으로임상적호전이뚜렷하게개개인마다효과가있을수도있고없을수도있다는연구결과가나왔다. 18,19 이는 CP/CPPS가일부환자에게세균이배양이안되거나, 배양이안되는세균, 또는항염증 cytokine이항생제를막아서생길수있다는결과라고발표하였다. 19,20 이는항생제치료가 Fig. 1. Multifactorial etiology of chronic prostatitis/chronic pelvic pain syndrome.

3 김규식ㆍ이승욱 : 만성전립선염 / 만성골반통증증후군치료법의최신경향 25 CP/CPPS 환자에게단일치법으로권장되지않으며, 특히이전에항생제치료에실패했던환자에게해당한다고한다. 항염증치료제역시 CPPS에여러증상에다양하게사용되었으며, 여러가지약물들이연구되었다. 특히 rofecoxib, 22 celecoxib, 23 pentosanpolysulfate, 24 zafirlukast (a leukotriene antagonist), 25 prednisone, 26 그리고 tanezumab 27 을들수있다. Rofecoxib와 celecoxib는고농도투여시증상의호전이있었고 Pentosanpolysulfate도고농도시증상의호전은있었으나, CPSI점수에서는대조군에비해눈에띄게호전을가져오진않았다. Zafirlukast와 prednisone는증상에호전을가져오지않았고 tanezumab 또한효과가없었다. 항염증치료제역시큰증상호전은보이지않았으며단일치료법으로권장되지않는다. 식물치료에서는 Quercetin이효과가있었다. 28 이는항산화제와항염증기능을하는물질이들어있기때문이라고한다. randomized, double-blind, placebo-controlled trial에서 NIH-CPSI를 7.9점이나대조군 (1.4) 과비교하여낮추었으며부작용도거의없었다. Quercetin는단일치료법으로어느정도효능이있었다. Neuromodulatory 치료에있어서 Pregabalin은 NIH-CPSI총점수및통증점수에서호전을보였으나통계학적으로는의미가없었다. 호르몬치료에서는 estrogen수치를낮추는 mepartricin을이용한연구 29 와 finasteride를이용한연구가있었다. 30 Mepartricin 연구는총 NIH-CPSI 점수에호전이있었으나연구수가적었고, finasteride연구에서는대조군에비에증상의호전이있었으나통계학적으로의미가없었다. 이로인해호르몬치료도단일요법으로기대하는바가크지않다. Physical therapies로 Myofascial trigger point release를이용한연구결과가있었다. 만성골반통환자에게적용하였으나통계학적으로결과가의미없었고, 적은수로연구가진행되었다. 31 단일요법치료는각각의장단점이있고활발한연구를통해효능이있는반면없는경우도있었다. 그리고활발한연구가이루어지지않은분야에서는아직임상적으로적용시킬수없는치료들이있어 CP/CPPS 환자에게단일요법으로치료하기에는다소무리가있다. 3. UPOINT의발전단일치료법이효과없다는몇몇의연구가나온이후여러가지치료를동시에했을때단일치료법으로치료했을때보다효과가있었다는연구가발표되었다. Nickel et al. 은알파차단제와항생제또는진통소염제를동시에치료했을때대조군보다임상점수가더많이호전되었고, 32 또 다른연구에서는항생제, 알파차단제, 그리고진통소염제를함께사용했을때단일치료법보다효과가있다는논문을발표하였다. 33 CP/CPPS를이해하고발전시킨것은 NIH classification이다. CP/CPPS는다양한요인들에의한 Syndrome으로단일치료법으로는증상호전에효과를못봤다. 그러므로 CP/CPPS 는여러증상의요인 (Fig. 1) 을모두밝히도록접근하고적절하게동시에치료해야한다는주장이제기되었다. 그주장은 2009년 Nickel과 Shoskes가표현형대로 CP/ CPPS를접근하고치료해야한다는논문을발표했다. 34 그리고 volkan et al. 은단일치료법만큼복합치료도안전하다는연구논문을발표하였으며, 35 Nickel et al. 은 CP/CPPS review논문에서환자가호소하는모든증상에대해복합적으로치료해야한다는 UPOINT에대한개념을자세히설명하였다 UPOINT관점치료법 CPPS를적절하고직접적으로치료하기위해서환자에게 6가지임상적표현형시스템을진단하는것이필요하다고한다. 임상적인 6개의영역은 urinary symptoms, psychosocial dysfunction, organ-specific findings, infection, neurologic/systemic, and tenderness of muscles로앞글자를따서 UPOINT 로명명하였다. 37 평가방법은 NIH-CPSI를이용하여각영역별로평가하고 NIH-CPSI로영역별표시하여총합을산출하는데이것은환자가호소하는증상의기간과연관되어있다고한다. UPOINT는임상적인표현형을이용하여 multimodal therapy로환자를치료한다. 최근유럽, 독일, 캐나다에서성기능장애항목을삽입하여 UPOINTS에대한평가를했을때 NIH-CPSI 평가가좀더자세하게이루어지는것을볼수있었다. 38,39 이는 CP/CPPS 가발기부전에도영향을미칠수있다고주장한다. 그러나 Nickel et al. 이발표한논문에서는성기능장애를 UPOINT 에같이평가하는것이의미없다고발표하였다. 40 UPOINT에대한임상적인연구가많지않으나최근에 Prospective 연구를보면각항목별로평가한뒤동시에치료했을때 6개월뒤 NIH-CPSI점수가 84% 의환자에서적어도 6점감소했고평균점수는 12점감소하였다. 41 UPOINT directed therapy는 CP/CPPS를진단받고고생하는환자들에게매력적인치료방법이다. 치료의각항목과그항목에대한치료는 Table 1에정리하였다. 각항목별로해당하는지알아보고해당항목에대해치료를해야한다. 예를들어환자가소변증상그리고장기통증이있을경우에알파차단제와 Quercetin으로치료해야하며또다른신경학적인통증이동반되었을경우 Pregabalin과골반PT처

4 26 대한비뇨기종양학술지 : 제 12 권제 1 호 2014 Table 1. Diagnostic criteria for UPOINT phenotypes and treatments Domain Diagnostic criteria Potential treatments Urinary Psychosocial Organ specifi (bladder or prostate) Infection Neurologic/Systemic Tenderness Bothersome irritative or obstructive urinary symptoms High postvoid residual Clinical depression Catastrophizing (verbalized helplessness and hopelessness) Specific prostate tenderness Hematospermia Symptom relief with voiding Positive cultures of prostatic fluid in absence of UTI Concomitant urethritis Pain outside pelvis Systemic pain syndrome Pelvic floor spasm Muscle trigger points Alpha-blockers Antimuscarinics Psychologic or Psychiatric counseling Cognitivebehavioral therapy Quercetin (e.g., Prosta-Q) Pollen extract (e.g., Q-Urol) Pentosan Polysulfate Antibiotics Pregabalin Amitriptyline Pelvic physical therapy Myofascial Release 방을한다. 지난 15년간 CP/CPPS에대한치료법이많이연구되어왔으나임상적으로그에대한치료는환자나의사에게실망감을안겨주었다. CP/PPS는특정단일요법의치료는효능이떨어지며권장되지못하고있다. 그러므로개개인에게어떤치료법이더효과적인지 randomized placebo- and sham-controlled trials가더많이연구되어야하며환자의임상적인표현형증상을자세히밝혀내어동시다발적으로치료하는것이효과적일것이다 UPOINT의제한점 UPOINT에대한접근은기존의단일요법으로사용되었던약제 ( 알파차단제, 항생제, 항소염제등 ) 들이 CP/CPPS 치료에효과가없는일부연구들그리고단일치료가효과가없다는연구에의해힘들얻게되었다. 그러나 UPOINT는많은임상적인연구가이루어지지않았으며 mechaistic하게어떠한원리로치료되는지원리가밝혀지지않았다. 그리고환자가증상을나타내는항목내에혹은 domain간의연구도이루어지지않았다. 그리고치료에대한장기간평가또한이루어지지않아앞으로연구해야할과제가많이남아있고효능에대한검증도필요할것이다. 42 결론최근까지 CP/CPPS에대한치료는단일치료법으로환자에게적용하였으나여러연구에서치료의효과및단일치료법으로의미가없음을발표하였다. 최근 CP/CPPS에대한원인이여러가지요인이복합적으로연계되어있음이밝 혀지면서치료도환자가호소하는표현형그대로모두동시에치료하자는 UPOINT개념의치료법이소개되었다. 개개인에게어떤치료법이더효과적인지 randomized placeboand sham-controlled trials가더많이연구되어야하며환자의임상적인표현형증상을자세히밝혀내어동시다발적으로치료하는것이효과적일것이다 REFERENCES 1. Nickel JC. Prostatitis: lessons from the 20th century. BJU Int 2000;85: Krieger JN, Nyberg L, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282: Schaeffer AJ Chronic prostatiitis and chronic pelvic pain syndrome. NEJM 2008;355: He L, Wang Y, Long Z, Jiang C. Clinical significance of IL-2, IL-10, and TNF-alpha in prostatic secretion of patients with chronic prostatitis. Urology 2010;75: Persson BE, Ronquist G. Evidence for a mechanistic association between nonbacterial prostatitis and levels of urate and creatinine in expressed prostatic secretion. J Urol 1996;155: He L, Wang Y, Long Z, Jiang C. Clinical significance of IL-2, IL-10, and TNF-alpha in prostatic secretion of patients with chronic prostatitis. Urology 2010;75: Westesson KE, Shoskes DA. Chronic prostatitis/chronic pelvic pain syndrome and pelvic floor spasm: can we diagnose and treat? Curr Urol Rep 2010;11: Pontari MA, McNaughton-Collins M, O leary MP, Calhoun EA, Jang T, Kusek JW, et.al. A case-control study of risk factors in men with chronic pelvic pain syndrome. BJU Int 2005;96:

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( )Kju269.hwp 만성세균성전립선염모델흰쥐에서 의항염효과 Anti-inflammatory Effect of Lycopene on Chronic Bacterial Prostatitis Rat Model Cho Hwan Yang, Dong Wan Sohn, Yong-Hyun Cho From the Department of Urology, The Catholic University