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1 Original Article ISSN (Print) / ISSN: X(Online) Korean J Urogenit Tract Infect Inflamm 2013;8(2): Chronic Prostatitis Category IIIa 와 IIIb 환자에서 Polymerase Chain Reaction 을이용한 Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum 의유병률 조인창, 김유석, 김성빈, 김순기, 이경인 1, 민승기 국립경찰병원비뇨기과, 1 진단검사의학과 Prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum in Chronic Prostatitis Category IIIa and IIIb Patients Using Polymerase Chain Reaction In-Chang Cho, Yoo Seok Kim, Sung Bin Kim, Soon Ki Kim, Gyeong In Lee 1, Seung Ki Min Departments of Urology and 1 Laboratory Medicine, National Police Hospital, Seoul, Korea Purpose: The aim of this study was to report on the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), and Ureaplasma urealyticum (UU) in patients with chronic prostatitis (CP) IIIa and CP IIIb using PCR and correlations between four microorganisms and other clinical parameters. Materials and Methods: The medical charts of 206 Patients who visited National Police Hospital and were diagnosed with CP IIIa and CP IIIb between January 2011 and December 2012 were reviewed. We investigated white blood cell (WBC) counts on expressed prostatic secretion (EPS) samples and the frequency of four possible causative microorganisms of prostatitis, CT, NG, MG, and UU, using PCR techniques on first voided urine samples (VB1). Results: Of 206 patients, 88 patients were CP IIIa and 118 were CP IIIb, with a mean age of 33.8±12.9 and 34.6±11.3, respectively. CT, NG, MG, and UU were detected in 13.6%, 0%, 4.5%, and 14.8% of CP IIIa patients and in 0.8%, 0%, 3.4%, and 11.9% of CP IIIb patients, respectively. Among men aged 19-30, detection of CT was significantly greater in the CP IIIa group than in the CP IIIb group (p=0.002). CT showed a positive association with EPS or the third voided urine (VB3) WBC count grade (p<0.01), however, MG and UU did not. The relationship between numbers of detected microorganisms and WBC counts was statistically insignificant. Conclusions: In subgroup analyses, microorganisms were detected in by PCR in 29 CP IIIa patients (32.9%) and 19 CP IIIb patients (16.1%). Young aged men in the CP IIIa group showed high prevalence of CT, and patients in whom CT was detected in urine PCR had high EPS WBC counts. Keywords: Polymerase chain reaction; Prevalence; Chlamydia Copyright 2013, Korean Association of Urogenital Tract Infection and Inflammation. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 30 September, 2013 Revised: 14 October, 2013 Accepted: 14 October, 2013 Correspondence to: Seung Ki Min Department of Urology, National Police Hospital, 123, Songi-ro, Songpa-gu, Seoul , Korea Tel: , Fax: msk0701@hanmail.net No potential conflict of interest relevant to this article was reported. 102

2 In-Chang Cho, et al. CP IIIa 와 CP IIIb 환자를대상으로한 PCR 연구 103 서 론 만성전립선염 (chronic prostatitis, CP) 은성인남성의약 50% 가일생에한번정도는그증상을경험할정도로흔한질환이며, 1 그특징적증상인비뇨생식기의통증및사정시통증은생활할때의불편감, 성욕감소, 발기부전을유발하여삶의질저하를초래하는것으로알려졌다. 2 현재까지의보고에의하면만성전립선염은세균성에비해비세균성원인이월등히많으며 3 이로인해아직까지병리학적기전은거의알려지지않은상태로이전의감염병력, 골반저고혈압, 국소적화학변화, 관류장애등이가설로등장하였지만여전히논의중이며 4 또한싸이토카인레벨의증가및염증, 배뇨시신경근부조화와관계된비정상적방광기능, 호르몬의불균형, 전립선내역류, 정신적문제등이영향을미치는것으로알려졌다. 5 그래서만성전립선염은대부분만성골반통증후군 (chronic pelvic pain syndrome, CPPS) 의증상군에포함되는경우가많으며실제임상에서는환자의증상에의존하여진단과치료효과를판정하는경향이많고증후군의개념에서치료의목적은증상의개선에초점이맞추어져있다. 전립선염은미국국립보건원 (National Institutes of Health, NIH) 분류에따라크게네가지유형으로분류되는데, category I은급성세균성전립선염, II는만성세균성전립선염이며이두 category는전체의 5-10% 에지나지않는다. Category IV는무증상염증성전립선염을일컫는데전립선비대증, 전립선암, 불임등다른비뇨기과질병에대해경직장전립선침생검, 전립선적출술후조직, 또는정액검사시우연히발견되는소견이다. 6 Category III의전립선염은만성전립선염 / 만성골반통증후군 (CP/CPPS) 이라는용어로도사용되는데, 지난 6개월간 3개월이상의요로생식기계통증을호소하며정액과전립선염검사에서원인균의검출이되지않는경우이며해외의보고에의하면전립선염의 90% 이상이이 category 에속한다. 7,8 Category III, 즉 CP/CPPS는 IIIa와 IIIb로다시분류되는데 IIIa는현미경고배율하에정액, 전립선액 (expressed prostatic secretion, EPS) 에서백혈구가 10배이상으로관찰되거나, 전립선마사지후채취한소변 (third voided urine, VB3) 에서고배율하에서 4개이상의백혈구가관찰되는경우이다. 이를염증성만성골반통증증후군 (inflammatory CPPS) 이라말하며, 그이하의백혈구가관찰될때를 IIIb, 비염증성만성골반통증증후군 (non-inflammatory CPPS) 라부른다. 9 만성전립선염의대부분을차지하는 CP/CPPS의병인이불명확한이유는이전연구에의하면약 8% 에서의환자에서만감염의원인이밝혀지고나머지에서는확고한요로계병원균이배양되지않기때문이다. 10 하지만몇몇연구들에서 hidden bacterial infection 이전립선염의병인임을시사하는증거들이 제시되고있고 11 많은임상의들이배양검사에서발견되지않는감염이 CP/CPPS 의병인에중요한역할을할것이라생각하고있다. 네덜란드의일반의 (63%) 와위스콘신의일차진료의 (78%) 는세균의감염을만성전립선염의가장중요한병인으로보고있고, 12,13 한국에서는약반수 (52%) 의비뇨기과전문의가만성비세균성전립선염의병인을 hidden bacterial infection 으로꼽았다. 14 최근 CPPS의병인을밝혀내려는노력의일환으로분자생물학적인진단방법들이상용화되고특히요로감염분야에중합효소연쇄반응 (polymerase chain reaction, PCR) 검사법이적용되면서높은민감도및양성예측률을바탕으로원인균의진단에많은도움을주고있다. PCR 검사법은핵산증폭검사법 (nucleic acid amplification tests, NAATs) 중한가지로높은민감도때문에일반적인배양검사로는검출하기힘든 cryptic microorganism 의검출에이용되며, 성매개감염 (sexually transmitted infection, STI) 원인균검사에서는이미표준적인검사방법으로인정되고있다. 15 국내에서도 Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Mycoplasma genitalium (MG), Mycoplasma hominis, Trichomonas vaginalis 등의잠복미생물이 CPPS 환자에서검출된바있다. 16,17 특히 CT, Neisseria gonorrhoeae (NG), MG, UU 등은전립선염의원인균으로생각되는 cryptic microorganism 이며통상적인배양검사에서잘자라지않아 PCR 검사를통해야보다정확한검출률을확인할수있는균주들이다. 본연구는본원을방문한만성비세균성전립선염환자들을 CP/CPPS IIIa와 CP/CPPS IIIb 환자군으로나누어 EPS 및 VB3를 PCR을이용하여흔한 cryptic microorganism인 CT, NG, UU, MG의검출률을조사하여이들간의상관관계를연구하고자하였다. 대상및방법 20011년 1월에서 2012년 12월까지본원에서 chronic non-bacterial prostatitis로진단받은 206명의환자를후향적으로조사하였다. 환자군은 3개월이상의하복부, 회음부통증이나불쾌감등의전립선염증상을호소하였던환자들로병력청취, 신체검사, 소변검사, EPS, VB3를시행하였다. NIH Chronic Prostatitis Work Shop의분류 18 에따라 EPS 및 VB3 내의백혈구수가현미경 400 배의시야당 10개이상인경우를 CP IIIa 로, 10개미만인경우를 CP IIIb 로분류하였으며이들은각각 88명, 118명이었다. 모든환자를대상으로소변검체를채취하여상온에서안정화한후 15분간 5,000g로원심분리한뒤상층액을제거하고재부유시킨후 DNA를추출하였다. DNA 검출은 real-time

3 104 In-Chang Cho, et al. CP IIIa 와 CP IIIb 환자를대상으로한 PCR 연구 PCR DNA detection method를이용하였으며검체로부터자동화핵산추출기기인 ExiPrep 16 Dx (Cat. No. A-5050, Bioneer Co., Daejeon, Korea) 와 ExiPrep Dx Bacteria Demonic DNA Kit (Cat. No. K-4414, Bioneer Co.) 를이용하여장비및시약제조사지침에따라추출한후실험에이용하였다. PCR 이전에준비된원심분리액튜브에 44 μl의 PCR-grade water와 1 μl의 internal positive control을혼합하고 5 μl의핵산추출물은대조군튜브에추가하였다. 튜브를막은후 DNA extracts에 premix pellet을녹이기위해 ExiSpin (Cat. No. A-7040, Bioneer Co.) 을사용하였다. PCR을이용한균주확인과정은 Exicycler 96 Real-Time Quantitative Thermal Block (Cat. No. A-2060M, Bioneer Co.) 과 AccuPower CT & NG Real-Time PCR Kit (Cat. No. STD2A-1111, Bioneer Co.), AccuPower MG Real-Time PCR Kit (Cat. No. MPG-1111, Bioneer Co.), AccuPower UU Real-Time PCR Kit (Cat. No. UUU11, Bioneer Co.) 를사용하여 chromosome을증폭시키고확인하였다. PCR 진행과정의평가는 tabocco mosaic virus genome 을증폭하여 internal positive control을측정하였다. Positive control은 microorganism이명확히확인된배양배지에서추출한 DNA를사용하였고 negative control은건강한환자의정상소변을증류수에희석하여추출한 DNA를사용하였다. 교차오염및위양성결과를막기위해모든검사시마다환자에게검체의정확한채취에대한설명을고지하였다. 만성전립선염 IIIa와 IIIb 환자의 PCR 결과를나이와 EPS 또는 VB3에서의백혈구개수등에따라 Student s t-test 와 chi-square test 및 fisher s exact test를이용하여비교하였다. 통계분석은 PASW Statistics 18.0 (IBM Co., Armonk, NY, USA) 을이용하여수행하였으며 p-value 가 0.05 미만일경우를통계적으로유의성이있다고판정하였다. 결과 총 206명의환자중 CP IIIa 환자군은 88명, IIIb 환자군은 118명이었으며각군의평균연령은각각 33.8±12.9세, 34.6±11.3세였다. CP IIIa 환자군에서 CT 검출수는 12 (13.6%), NG 0 (0%), MG 4 (4.5%), UU 13 (14.8%) 였고 CP IIIb 환자군에서의각균주의검출수는각각 CT 1 (0.8%), NG 0 (0%), MG 4 (3.4%), UU 14 (11.9%) 였다 (p=0.677, Table 1). 연령에따른각균주의검출률을비교해보았을때 세의연령대의 CT의검출률에서 CP IIIa 환자군은 23.8% (10/42), CP IIIb 환자군은 2.1% (1/48) 로유의한차이를보였으나 (p=0.002), 다른세가지균주에서는각각 NG 0% (0/42)/0% (0/48), MG 7.1% (3/42)/2.1% (1/48), UU 19% (8/42)/12.5% (6/48) 로유의한차이를보이지않았다. 30대에서는 UU만이 CP IIIb 군에서만 16% (4/24) 검출되었고, 40대에서는 CT 7.1% (2/28)/0% (0/40), NG 0% (0/28)/0% (0/40), MG 3.6% (1/28)/5.0% (2/40), UU 17.9% (5/28)/7.5% (3/40) 의검출률을, 50대에서는 MG 0% (0/7), 16.7% (1/6)/UU 0% (0/7)/16.7% (1/6) 의검출률을보여, 30대, 40대, 50대에서는각균주의검출률에대한 CP IIIa 환자군과 CP IIIb 환자군의유의한차이를발견할수없었다 (Fig. 1). EPS 또는 VB3에서검출된 white blood cell (WBC) counts 에따른각균주의검출률을비교해본결과 WBC counts 0-2개가 0% (0/58), 3-5개 2.9% (1/35), 6-8개 0% (0/25), 10-15개 11.8% (2/17), 20-25개 5.6% (1/18), 다수개 17% (9/53) 으로 WBC counts와 CT의검출률이통계적으로유의하게양의상관관계를보였으며 (p=0.002) 다른균주에대해서는 NG는전혀검출되지않았고 MG는 WBC counts 0-2개가 3.4% (2/58), 3-5개 2.9% (1/35), 6-8개 4% (1/25), 10-15개 0% (0/17), 20-25개 5.6% (1/18), 다수개 5.7% (3/53) 였으며 UU는 0-2개가 12.1% (7/58), 3-5개 11.4% (4/35), 6-8개 12.0% (3/25), 10-15개 11.8% (2/17), 20-25개 22.2% (4/18), 다수개 13.2% (7/53) 의결과를보여 WBC counts 와균주의검출률과의상관관계가통계적으로유의하지않는것으로나타났다 (Fig. 2). 그리고 EPS 또는 VB3에서검출된 WBC counts와 PCR을통해검출된균주의총개수와의상관관계를조사한결과로는최대 2개까지의균주가검출되었으며, 균주가전혀검출되지않은경우는 WBC counts 0-2개가 84.5% (49/58), 3-5개 82.9% (29/35), 6-8개 88.0% (22/25), 10-15개 76.5% (13/17), 개 66.7% (12/18), 다수개 71.7% (38/53) 였다. 균주가 1개만검출된경우는 WBC counts 0-2개가 15.5% (9/58), 3-5개 17.1% (6/35), 6-8개 8.0% (2/25), 10-15개 23.5% (4/17), 20-25개 33.3% (6/18), 다수개 20.8% (11/53) 였으며, 균주가 2개검출된경우는 WBC counts 0-2개가 0% (0/58), 3-5개 0% (0/35), 6-8개 4.0% (1/25), 10-15개 0% (0/17), 20-25개 Table 1. Baseline characteristics of CPIIIa and CP IIIb patients (n=206) Age (year) CT positivity NG positivity MG positivity UU positivity CP IIIa (n=88) 33.8± (13.6) 0 (0) 4 (4.5) 13 (14.8) CP IIIb (n=118) 34.6± (0.8) 0 (0) 4 (3.4) 14 (11.9) Values are presented as mean±standard deviation or number (%). CP: chronic prostatitis, CT: Chlamydia trachomatis, NG: Neisseria gonorrhoeae, MG: Mycoplasma genitalium, UU: Ureaplasma urealyticum. Positivity for microorganisms was detected using polymerase chain reaction methods in urine samples.

4 In-Chang Cho, et al. CP IIIa 와 CP IIIb 환자를대상으로한 PCR 연구 105 Fig. 1. (A) Detected microorganisms according to age subgroup in CP IIIa and CP IIIb patients (age years). (B) Detected microorganisms according to age subgroup in CP IIIa and CP IIIb patients (age years). (C) Detected microorganisms according to age subgroup in CP IIIa and CP IIIb patients (age years). (D) Detected microorganisms according to age subgroup in CP IIIa and CP IIIb patients (age years). CT: Chlamydia trachomatis, MG: Mycoplasma genitalium, UU: Ureaplasma urealyticum. 0% (0/18), 다수개 7.5% (4/53) 의결과를보였으며통계적으로유의하지는않았다 (Table 2). 고찰 만성전립선염은다양한임상경과를나타내는비뇨기계질환으로최근증가추세이며연구마다차이는있지만성인남성에서의 4-16% 의유병률을나타내는질환이다. 만성전립선염의 category III 에해당하는만성전립선염 / 만성골반통증후군 (CP/CPPS) 은만성전립선염의대부분을차지하며현미경고배율하에 EPS 또는 VB3에서백혈구가일정수이상관찰되느냐에따라 IIIa와 IIIb로분류된다. 만성전립선염의병인은아직까지많은논란이있지만몇몇병원균과관련이있는데이중특정병원균은다른균에비해서수정능력에더큰영향을미치는것으로알려졌다. 기존의국내외보고에서국내외투약되어온항생제의영향, 전립선마사지기술에있어서의개인차, 그리고전립선의국소염증시전립선배출관폐쇄등으로인해병소의내용물이나미생물의검출이어려워세균성전립선염이 CPPS로오인될수있는가능성이있으며일부 균주는일반배지에서균이자라지않는관계로비세균성전립선염에서보이지않는감염을찾기위해 PCR과같은분자생물학적검사방법이시도되었으며, 여러연구에서 CT, MG, NG, UU 같은 STI 의원인균이되며일반배양검사로관찰하기힘든 cryptic microorganism의존재가증명된바있다 본연구에서는총 206명의 CP/CPPS 환자중 PCR에의해원인균주가확인된경우가 category IIIa에서는 29명 (32.9%), category IIIb에서는 19명 (16.1%) 으로국내에서 Ha 등 20 이 5종류의균주 (CT, MG, NG, UU, Mycoplasma hominis, Trichomonas vaginalis) 에대한단독 PCR을각각시행하여 category IIIa에서 16.8%, category IIIb에서 8.1% 의검출률을보인것과 Kim 등 16 이 6종류의균주 (CT, MG, M. hominis, NG, T. vaginalis, UU) 에서 category IIIa 에서 39.1%, category IIIb에서 17.4% 의검출률을보인것과유사하게 category IIIb 에비해 IIIa에서 2배정도많은균주가검출되었다. Category IIIa와 category IIIb의환자군을연령대로나누어분석한결과 19-30세의연령대에서 CT 검출률에서 CP IIIa 환자군은 23.8% (10/42), CP IIIb 환자군은 2.1% (1/48) 로

5 106 In-Chang Cho, et al. CP IIIa 와 CP IIIb 환자를대상으로한 PCR 연구 Fig. 2. Positivity of microorganisms according to WBC counts in EPS or VB3. CT: Chlamydia trachomatis, MG: Mycoplasma genitalium, UU: Ureaplasma urealyticum, WBC: white blood cell, EPS: expressed prostatic secretion, HPF: high power field. Table 2. Number of detected microorganism according to WBC counts in EPS or VB3 Number of microorganisms WBC counts Many 49/58 (84.5) 9/58 (15.5) 0/58 (0.0) 0/58 (0.0) 0/58 (0.0) 29/35 (82.9) 6/35 (17.1) 0/35 (0.0) 0/35 (0.0) 0/35 (0.0) 22/25 (88.0) 2/25 (8.0) 1/25 (4.0) 0/25 (0.0) 0/25 (0.0) Values are presented as number/hpf (%). WBC: white blood cell, EPS: expressed prostatic secretion, HPF: high power field. 13/17 (76.5) 4/17 (23.5) 0/17 (0.0) 0/17 (0.0) 0/17 (0.0) 12/18 (66.7) 6/18 (33.3) 0/18 (0.0) 0/18 (0.0) 0/18 (0.0) 38/53 (71.7) 11/53 (20.8) 4/53 (7.5) 0/53 (0.0) 0/53 (0.0) p-value 유의한차이를보였는데 (p=0.002) 이는이연령대의환자군이성적으로활발한시기이므로성매개감염균의검출빈도가높게나온것으로생각된다. 또한 MG, UU도 CP IIIa 환자군에서검출률이높게나왔으나통계적으로유의하지는않았다. 특히 Chlamydia는성매개감염에서가장흔한박테리아감염으로아직논란의여지가있지만만성전립선염의원인이되는것으로생각되고있으며남성에서는요도, 부고환, 전립선질환을, 여성에서는질, 요도및상부요로의질환과더불어 자궁경부염, 요도염, 난관염, 자궁내막염등을일으키는중요한원인균으로여성의경우자궁외임신및불임과남성불임의원인이되기도한다. 23 Chlamydia는약 75% 의여성과절반이상의남성에있어감염되어있어도증상이없고정액이나전립선액에서감염의증거가있어도일반배양검사로는배양되지않기때문에특수배양이나 PCR 을통해서만균주를확인할수있는특성을가지고있다. 24 따라서성적으로활발한연령대의만성전립선염환자군에서 PCR 검사와함께

6 In-Chang Cho, et al. CP IIIa 와 CP IIIb 환자를대상으로한 PCR 연구 107 Clamydia에대한경험적항생제로 azithromycin과 doxycycline의투여및파트너에대해서도 PCR 등의정밀검사시행과항생제사용을고려해볼필요가있다고생각된다. 또한 EPS 또는 VB3에서현미경고배율로관찰한 WBC counts 와각균주의검출률을비교해보았을때 CT의검출률이통계적으로유의하게양의상관관계 (p=0.002) 를보였으며이는 Clamydia 감염환자의절반이상은무증상인경우가많기때문에 Kim 등 25 이제시하였듯이증상이드러나지않은환자에서도 WBC counts가높은의심되는환자군에대해적극적인 PCR 검사를시행하고항생제치료후원인균의박멸여부를추적관찰하기위한도구로서 PCR 검사가의미를가진다고본다. 또한 Lee 와 Lee 24 는항생제치료후최소 3-5 주후핵산증폭검사법 (NAATs) 을권장하고있다는점도이를뒷받침하는부분이라하겠다. WBC conuts와 multi-organism infection은관련성이없었고총 206명의환자가운데 CP IIIa 환자 118명중에서 4명, CP IIIb 환자 88명중 1명에서 multi-organism infection이관찰되어 CP IIIb 환자군에서는 multi-organism infection을무시할만하다고생각된다. Multi-organism이관찰된 5명은 CT-UU 가 4명, MG-UU 1명으로대체로 CT와 UU가동시감염될가능성이높은결과를보였다. 본연구는국내에서 PCR을통한 cryptic microorganism 의검출결과및임상적의의를기술한기존자료들이많지않아 CPPS 환자군의 cryptic microorganism 의연령별특징및치료에도움이되리라생각되며특정연령대의 EPS 및 VB3의 WBC counts 가낮은환자에게서는 CT나 MG의검출이되지않아불필요한 PCR 검사의생략도고려해볼만하다고생각한다. 본연구의제한점으로는총환자군의수가많지않아 PCR 에서균주가검출된환자수가적은관계로통계상의근거가약한점이있다. 또한 CPPS 의진단에정액검사및정액배양검사를포함하지않아 category II와 category IIIa 환자가 category IIIb로분류되었을가능성이있다. 다음연구에서는 EPS 나정액의 culture, PCR 등의검사를동반하여비교분석하면좀더세부적인연관성을찾을수있을것이며, 또한 CPSI 등의설문지를통해증상점수와비교하였으면임상적으로더밀접한연관이있는연구가될수있었다고생각한다. 마지막으로만성전립선염의전통적인분류인 NIH classification외에새로이고안된 UPOINT (Urinary, Psychosocial, Organ specific infection, Neurologic/systemic, Tenderness of skeletal muscles) 의도메인을이용한치료효과분석에대해서는다른추가연구가필요하다고생각된다. 결론 만성전립선염 / 만성골반통증후군환자에서 PCR을통해 cryptic microorganism 을검출한결과 대나이의연령군에서 category IIIa이 category IIIb에비해 CT 검출이유의하게높았고 MG, UU도통계적으로유의하지는않지만높은빈도수로검출되었으며, EPS 또는 VB3에서관찰된 WBC counts 와 CT가양의상관관계를나타내었다. 이를통해연령대및 ESP, VB3를통해관찰된 WBC counts에따라 Chlamydia 등의 hidden cryptic microorganism 을예측하여검사및치료여부결정에도움을줄수있을것이라생각하며, category III prostatitis 에서 PCR 을통해균이배출되는경우가적지않으므로특히젊은연령에서는 PCR 검사시행이필요할것으로생각된다. REFERENCES 1. Ku JH, Lee SH, Jeon YS, Kim ME, Lee NK, Park YH. Epidemiologic study of chronic prostatitis-like symptoms surveyed among young men in the area of Taejeon and Chung-nam: prevalence and influence of weather. Korean J Urol 2002;43: Shoskes DA, Landis JR, Wang Y, Nickel JC, Zeitlin SI, Nadler R; Chronic Prostatitis Collaborative Research Network Study Group. Impact of post-ejaculatory pain in men with category III chronic prostatitis/chronic pelvic pain syndrome. J Urol 2004;172: Krieger JN, Egan KJ, Ross SO, Jacobs R, Berger RE. Chronic pelvic pains represent the most prominent urogenital symptoms of chronic prostatitis. Urology 1996;48: Pontari MA. Chronic prostatitis/chronic pelvic pain syndrome. Urol Clin North Am 2008;35: Schaeffer AJ. Epidemiology and evaluation of chronic pelvic pain syndrome in men. Int J Antimicrob Agents 2008;31(Suppl 1):S Cho IC, Min SK. Asymptomatic prostatitis: clinical significances and management. Korean J Urogenit Tract Infect Inflamm 2013;8: Nickel JC, Nyberg LM, Hennenfent M. Research guidelines for chronic prostatitis: consensus report from the first National Institutes of Health International Prostatitis Collaborative Network. Urology 1999;54: Nickel JC, Downey J, Hunter D, Clark J. Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health chronic prostatitis symptom index. J Urol 2001;165: Nadler RB, Schaeffer AJ. Lower urinary tract cultures. In: Nickel JC, ed. Textbook of prostatitis. 1st ed. Oxford, England: Isis

7 108 In-Chang Cho, et al. CP IIIa 와 CP IIIb 환자를대상으로한 PCR 연구 Medical Media, 1999: Schaeffer AJ, Landis JR, Knauss JS, Propert KJ, Alexander RB, Litwin MS, et al; Chronic Prostatitis Collaborative Research Network Group. Demographic and clinical characteristics of men with chronic prostatitis: the national institutes of health chronic prostatitis cohort study. J Urol 2002;168: Krieger JN, Riley DE. Chronic prostatitis: charlottesville to Seattle. J Urol 2004;172: de la Rosette JJ, Hubregtse MR, Karthaus HF, Debruyne FM. Results of a questionnaire among Dutch urologists and general practitioners concerning diagnostics and treatment of patients with prostatitis syndromes. Eur Urol 1992;22: Moon TD. Questionnaire survey of urologists and primary care physicians' diagnostic and treatment practices for prostatitis. Urology 1997;50: Lee KS, Choi JD. Chronic prostatitis: approaches for best management. Korean J Urol 2012;53: Johnson RE, Green TA, Schachter J, Jones RB, Hook EW 3rd, Black CM, et al. Evaluation of nucleic acid amplification tests as reference tests for Chlamydia trachomatis infections in asymptomatic men. J Clin Microbiol 2000;38: Kim TH, Kim TH, Kim HR, Lee MK, Myung SC, Kim YS. Detection of cryptic microorganisms in patients with chronic prostatitis by multiplex polymerase chain reaction. Korean J Urol 2007;48: Seo KI, Hwang JC, Kim TW, Lee SH, Park SY, Roh SH. Results of microorganism detection by multiplex polymerase chain reaction in patients with chronic pelvic pain syndrome. Korean J Urol 2009;50: Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282: Kim SW, Lee JY, Park WJ, Cho YH, Yoon MS. The diagnostic values of the polymerase chain reaction in prostatitis. Korean J Infect Dis 2000;32: Ha JS, Kim SW, Cho YH. Detection of cryptic microorganisms by polymerase chain reaction assay in chronic pelvic pain syndrome. Korean J Urol 2002;43: Krieger JN, Riley DE, Roberts MC, Berger RE. Prokaryotic DNA sequences in patients with chronic idiopathic prostatitis. J Clin Microbiol 1996;34: Brookings C, Goldmeier D, Sadeghi-Nejad H. Sexually transmitted infections and sexual function in relation to male fertility. Korean J Urol 2013;54: Mouton JW, Verkooyen R, van der Meijden WI, van Rijsoort-Vos TH, Goessens WH, Kluytmans JA, et al. Detection of Chlamydia trachomatis in male and female urine specimens by using the amplified Chlamydia trachomatis test. J Clin Microbiol 1997; 35: Lee YS, Lee KS. Chlamydia and male lower urinary tract diseases. Korean J Urol 2013;54: Kim SJ, Lee DS, Lee SJ. The prevalence and clinical significance of urethritis and cervicitis in asymptomatic people by use of multiplex polymerase chain reaction. Korean J Urol 2011; 52:703-8.

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