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애윤 태
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1 만성골반통증후군환자에서다중중합효소연쇄반응을이용한미생물검출의결과 Results of Microorganism Detection by Multiplex Polymerase Chain Reaction in Patients with Chronic Pelvic Pain Syndrome Kang Il Seo, Jin Chul Hwang, Tae Wan Kim, Su Hyung Lee, Seo Yong Park, Sang Hue Roh 1 From the Department of Urology, National Medical Center, 1 Hole In One Urologic Clinic, Seoul, Korea Purpose: The aim of this study was to evaluate the results of multiplex polymerase chain reaction (PCR) in patients with chronic pelvic pain syndrome (CPPS) and the significance of microorganisms as the causative factor of CPPS. Materials and Methods: We evaluated the frequency of 19 possible causative microorganisms of prostatitis in 849 patients who had prostatitis symptoms from April 2007 to March 2009 by using multiplex PCR. All of the enrolled patients were category III by the definition of the NIH Chronic Prostatitis Workshop. Results: Of the 849 patients, 414 (49%) and 435 (51%) were categories IIIa (inflammatory CPPS) and IIIb (noninflammatory CPPS). On multiplex PCR, using the third voided urine specimen (VB3), 369 (89%) of the 414 category IIIa and 367 (84%) of the 435 category IIIb cases were found to have positive PCR results for causative microorganisms. The common microorganisms were Enterococcus, Ureaplasma urealyticum, Lactobacillus, Streptococcus agalactiae, and Chlamydia trachomatis in 173 (18%), 144 (15%), 129 (13%), 78 (8%), and 69 cases (7%), respectively. Conclusions: There were too many positive PCR results for causative microorganisms in the CPPS patients despite negative urine culture examination. Therefore, it is necessary to rule out contamination of the specimen to achieve reliable results with multiplex PCR. However, multiplex PCR can detect various unknown microorganisms suggestive of the etiology of CPPS, particularly those that are difficult to cultivate. PCR is expected to play an important role in the diagnosis of CPPS, but further studies will be required to define the usefulness of molecular tests. (Korean J Urol 2009;50: ) Key Words: Prostatitis, Polymerase chain reaction Korean Journal of Urology Vol. 50 No. 11: , November 2009 DOI: /kju 국립의료원, 1 홀인원비뇨기과 서강일ㆍ황진철ㆍ김태완이수형ㆍ박서용ㆍ노상휴 1 Received:July 2, 2009 Accepted:October 16, 2009 Correspondence to: Sang Hue Roh Department of Urology, Hole In One Urologic Clinic, A-314, Woolim Lions Valley, , Gasan-dong, Geumcheon-gu, Seoul , Korea TEL: FAX: nmcuro@hanmail.net C The Korean Urological Association, 2009 서론전립선염은 50세이하의남성에서가장흔한전립선질환으로개원비뇨기과환자의 15-25% 정도가전립선염으로추정될만큼쉽게발견할수있는질환이다 [1,2]. 이처럼전립선염은임상에서흔하게접하는질환이지만전립선의 감염을증명할수있는경우는비교적드물어세균성전립선염은전체전립선염환자의 10% 이하로보고되고있다 [3]. 대부분의전립선염환자들은만성골반통증후군 (category III; chronic pelvic pain syndrome; CPPS) 으로분류되고있으나아직그경로와병인이명확하게규명되지않았으며선별된증상이나객관적인검사소견이없어서, 실제임상에서는환자의증상에의존하여진단과치료효과를판 1120

2 Kang Il Seo, et al:diagnostic Valve of Multiplex PCR in Patients with CPPS 1121 정하는경향이많다 [4-7]. 현재 CPPS의병인으로감염 [8], 자가면역질환 [9], 신경질환 [10] 및정신질환 [11] 등여러원인이거론되고있는데, 많은 CPPS 환자에서항생제투여가효과를보인다는점 [12] 과통상적인배양검사에서확인이어려운세균이나바이러스감염이있을수있다는점 [13] 등에서미생물에의한감염이중요한역할을할것으로추정되고있다. 최근분자생물학적인진단방법들이상용화되면서비뇨기과질환에서도그적용이증가하고있고, 특히요로감염분야에중합효소연쇄반응 (polymerase chain reaction; PCR) 검사법이적용되면서높은민감도및양성예측률을바탕으로원인균의진단에많은도움을주고있다. PCR 검사법은핵산증폭검사법 (nucleic acid amplification tests; NAATs) 중한가지로높은민감도때문에일반적인배양검사로는검출하기힘든 cryptic microorganism의검출에이용되며, 성매개감염 (sexually transmitted infection; STI) 원인균검사에서는이미표준적인검사방법으로인정되고있다 [14]. CPPS의병인을밝혀내려는노력의일환으로 PCR 검사를이용한원인균검출이시도되고있으며, 국내에서도 Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium, Mycoplasma hominis, Trichomonas vaginalis 등의잠복미생물이 CPPS 환자에서검출된바있다 [15-18]. 최근개원가를중심으로상기원인균들과함께세균성전립선염의원인균으로추정되고있는 Escherichia coli, Pseudomonas, Enterococcus, Staphylococcus, Streptococcus agalactiae, Corynebacterium, Proteus, Candida, Klebsiella, Veillonella, Prevotella, Lactobacillus, Peptostreptococcus 등을포함한확대된다중 PCR 검사가 CPPS로진단된환자들에서많이시행되고있다. 이에저자들은 CPPS 환자들의다중 PCR 검사결과를분석하여전립선염의진단에있어서다중 PCR의유용성을알아보고자하였다. 대상및방법 2007년 4월부터 2009년 3월사이에하복부, 회음부통증이나불쾌감등의전립선염증상을주소로내원한환자들에게병력청취와신체검사, 소변검사, 소변배양검사, expressed prostatic secretions (EPS) 및 VB3의배양검사를시행하였으며정액검사, 정액배양검사는시행하지않았다. 이들중소변검사, 소변배양검사에서이상이없고 EPS 및 VB3에서균이자라지않아 CPPS으로진단된 1,178명의환자중최근 3개월이내에성병이나전립선염으로치료받은병력이없고, 증상기간이 6개월이상이며, 만성전립선염증상점수표 (National Institutes of Health Chronic Prostatitis Symptom Index; NIH-CPSI) [19] 에서통증혹은불쾌감의빈도를나타내는 3번문항에서 3점이상이었던 849명을대상으로하였다. 대상환자들의연령분포는 16세부터 68세로평균 36세였으며, 30대가가장높은비율 (436명, 51.4%) 을차지하였다 (Table 1). 전립선마사지와 EPS 검사등모든술기는한명의비뇨기과의사가시행하였다. 대상환자들을 NIH Chronic Prostatitis Work Shop의분류 [20] 에따라 EPS 내의백혈구수가고배율현미경시야에서 10개이상인경우를 category IIIa (inflammatory CPPS) 로, 10개미만인경우를 category IIIb (non-inflammatory CPPS) 로분류하였으며이들은각각 414명, 435명이었다. 모든환자에서전립선마사지후소변 (VB3) 을이용하여 Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium, Mycoplasma hominis, Trichomonas vaginalis, Escherichia coli, Pseudomonas, Enterococcus, Staphylococcus, Streptococcus agalactiae, Corynebacterium, Proteus, Candida, Klebsiella, Veillonella, Prevotella, Lactobacillus, Peptostreptococcus에대한다중 PCR 검사를실시하였다. 검사를위한 DNA는채취된검체 200μl 로부터자동화핵산추출기기인 Chemagic Magnetic separation module I (Chemagen, Baesweiler, Germany) 과 Chemagic Viral DNA/ RNA kit special (Chemagen, Baesweiler, Germany) 을이용하여장비및시약제조사지침에따라추출한후실험에이용하였다. 추출한 DNA는실험에사용하기전까지 -70 o C 에보관하였다. PCR을이용한균주확인과정은 ABI 2720 Thermal cycler (Applied Biosystems, USA) 를사용하여 95 o C에서 pre-denaturation 5분, denaturation 95 o C에서 15초, annealing 62 o C에서 1분 20초, extension 72 o C에서 1분의과정을 40회반복하였고마지막에 final extension은 72 o C에서 5분간반응시켰다. 반응에사용된내용물의구성은삼광의료재단에서자체고 Table 1. Age distribution of the patients with chronic pelvic pain syndrome Age Category IIIa (%) Category IIIb (%) Total (%) (50.0) 1 (50.0) 2 (0.2) (55.4) 95 (44.6) 213 (25.1) (47.0) 231 (53.0) 436 (51.4) (45.6) 81 (54.4) 149 (17.6) (44.9) 27 (55.1) 49 (5.7) Total Category IIIa: inflammatory chronic pelvic pain syndrome, Category IIIb: non-inflammatory chronic pelvic pain syndrome

3 1122 Korean Journal of Urology vol. 50, , November 2009 Table 2. The frequency of species according to polymerase chain reaction findings in patients with inflammatory and noninflammatory chronic pelvic pain syndrome Organism Category IIIa Category IIIb Total Enterococcus (%) 88 (18.4) 85 (17.2) 173 (17.8) Ureaplasma urealyticum (%) 73 (15.2) 71 (14.4) 144 (14.8) Lactobacillus (%) 51 (10.6) 78 (15.8) 129 (13.3) Streptococcus agalactiae (%) 36 (7.5) 42 (8.5) 78 (8.0) Chlamydia trachomatis (%) 62 (12.9) 7 (1.4) 69 (7.1) Prevotella (%) 22 (4.6) 35 (7.1) 57 (5.9) Veillonella (%) 19 (4.0) 27 (5.5) 46 (4.7) Mycoplasma genitalium (%) 25 (5.2) 17 (3.4) 42 (4.3) Escherichia coli (%) 16 (3.3) 24 (4.9) 40 (4.1) Klebsiella (%) 10 (2.1) 12 (2.4) 22 (2.3) Mycoplasma hominis (%) 7 (1.5) 11 (2.2) 18 (1.8) Corynebacterium (%) 9 (1.9) 8 (1.6) 17 (1.7) Candida species (%) 6 (1.3) 3 (0.6) 9 (0.9) Trichomonas vaginalis (%) 6 (1.3) 2 (0.4) 8 (0.8) Pseudomonas (%) 4 (0.8) 3 (0.6) 7 (0.7) Staphylococcus (%) 0 (0) 1 (0.2) 1 (0.1) Neisseria gonorrhoeae (%) 0 (0) 0 (0) 0 (0) Proteus (%) 0 (0) 0 (0) 0 (0) Peptostreptococcus (%) 0 (0) 0 (0) 0 (0) Category IIIa: inflammatory chronic pelvic pain syndrome, Category IIIb: non-inflammatory chronic pelvic pain syndrome 안한 multiplex Primer mix 2μl, Template DNA 4μl, QIAGEN Multiplex PCR Master Mix (Qiagen, Hilden, Germany) 8μl를각각넣고전체반응량을 20μl로맞춘후진행하였다. 이때사용된 primer는 IDT Inc. (Integrated DNA Technologies, Inc., USA) 에서합성하였다. 반응이끝난 PCR 생성물은 ethidium bromide가첨가된 2% agarose gel에 7μl 씩분주하여 200 V로 15분간전기영동하여 UV transilluminator로확인하였다. 19 균주에대한다중 PCR 검사의균검출률을조사하였으며, Category IIIa와 IIIb에서검출률의차이를알아보았다. 또한, 균주에따른검출빈도를분석하여각각의 Category에따른다빈도균주를비교하였다. 통계분석은 SPSS 12.0 for windows의 chi-square test를이용하였으며, p값이 0.05 미만일때통계학적으로유의성이있는것으로판정하였다. 결 총 849명의 CPPS 환자중다중 PCR에의해균주가검출된경우는 736명 (87%) 이었다. Category IIIa에서는 369명 (89%), category IIIb에서는 367명 (84%) 으로비슷한검출률 과 Fig. 1. Graph showing the frequency of species according to polymerase chain reaction findings for each of the chronic pelvic pain syndrome categories. Category IIIa: inflammatory chronic pelvic pain syndrome, Category IIIb: non-inflammatory chronic pelvic pain syndrome, EN: Enterococcus, UU: Ureaplasma urealyticum, LA: Lactobacillus, SA: Streptococcus agalactiae, CT: Chlamydia trachomatis, PR: Prevotella, VE: Veillonella, MG: Mycoplasma genitalium, EC: Escherichia coli, KL: Klebsiella, MH: Mycoplasma hominis, CO: Corynebacterium, CA: Candida, TV: Trichomonas vaginalis, PS: Pseudomonas, ST: Staphylococcus, a : p<0.05. 을보였다. 연령이증가함에따라 category IIIb의비율이높아지는경향이있었으나통계적으로유의하지는않았다 (p=0.291). 검출된균주를보면 Enterococcus가 18% 로가장높은검출률을보였고이어서 Ureaplasma urealyticum (15%), Lactobacillus (13%), Streptococcus agalactiae (8%), Chlamydia trachomatis (7%) 순으로검출빈도를보였다 (Table 2). 각각의 Category를구분하여보았을때, Category IIIa에서는 Enterococcus (18%), Ureaplasma urealyticum (15%), Chlamydia trachomatis (13%), Lactobacillus (11%), Streptococcus agalactiae (8%) 순으로검출빈도수를보였고, category IIIb에서는 Enterococcus (17%), Lactobacillus (16%), Ureaplasma urealyticum (14%), Streptococcus agalactiae (9%), Prevotella (7%) 순으로검출빈도가높게나타났다 (Fig. 1). Neisseria gonorrhoeae, Proteus, Peptostreptococcus는 category IIIa와 category IIIb에서모두검출되지않았으며, Staphylococcus는 category IIIb에서 1건만이검출되었다. 고 현재전립선염의판정을위해 3배분뇨법이나전립선마시지전후의요검사및일반세균배양검사만을시행하는 찰

4 Kang Il Seo, et al:diagnostic Valve of Multiplex PCR in Patients with CPPS 배분뇨법이주로시행되고있으며, 전립선액 (EPS), 전립선마사지후첫소변 (VB3) 혹은정액에서세균이발견되지않으면만성전립선염이나만성골반통증후군으로진단된다 [20]. 그러나투약되어온항생제의영향, 전립선맛사지기술에있어서의개인차, 그리고전립선의국소염증시전립선배출관이폐쇄등으로인해병소의내용물이나미생물의검출이어려워세균성전립선염이 CPPS로오인될수있는가능성이있다 [21]. 또한일반적인배양검사에서는전립선액의세균억제성물질등이존재하여균이잘자라지않을수있으며, 특히 Chlamydia, Mycoplasma 등은일반배양검사에서잘자라지않는다는특징이있다. 그리고균수가적거나, 불완전한균주일경우, 그리고균주가배지로옮기는도중에생존하지못하는경우역시배양검사결과가위음성으로나올수있다. 이러한여러상황을고려할때 VB3나 EPS의배양검사에의존하는진단방법만으로는세균성전립선염의빈도가과소평가될소지가충분히있다고할수있다. 이러한이유로비세균성전립선염에서보이지않는감염을찾기위해 PCR과같은분자생물학적검사방법이시도되었으며, 여러연구에서 Chlamydia trachomatis와같은 cryptic microorganism의존재가증명된바있다 [15-18,22]. 그러나이러한원인균이만성전립선염의확실한원인이될수있는지에대해서는논란이있고, Krieger 등 [22] 을제외한대부분의연구들은검체를환자의요도를통하여얻었기때문에오염되었을가능성을배제할수없어아직까지 PCR 검사법이만성전립선염의표준적인검사방법으로인정되지못하고있는실정이다. 본연구에서는일반배지에서는자라지않는 Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium, Mycoplasma hominis, Trichomonas vaginalis와더불어, 일반배양검사에서검출이가능하며세균성전립선염의원인균으로생각되는 [23,24] 13종의균주 - Escherichia coli, Pseudomonas, Enterococcus, Staphylococcus, Streptococcus agalactiae, Corynebacterium, Proteus, Candida, Klebsiella, Veillonella, Prevotella, Lactobacillus, Peptostreptococcus -를포함한다중 PCR 검사를시행하였으며, 그결과국내에보고된타논문들 [15-18] 에비해 category IIIa에서는 89%, category IIIb에서는 84% 로훨씬높은검출률을확인하였다. 만약본연구의환자들에서도 cryptic microorganism 6종만을검사하였다고가정하였을때 category IIIa에서는 39%, category IIIb에서는 24% 의검출률을보여이전의보고와유사한결과를보임을알수있다. 주목할만한점은세균성전립선염의가능한원인균으로인정되는 Enterococcus, Escherichia coli 등이환자들의소변배양검사에서는동정되지않았으나다중 PCR 검사에서는높은빈도로나타났다 는점이다. 이는 CPPS 환자들의일부에서는만성세균성전립선염임에도불구하고 CPPS로오진되었을가능성도유추해볼수있겠지만, 이전보고들 [15-18] 의경우 category IIIa에서 category IIIb보다더높은검출률을보였으나본연구에서는두그룹이비슷한검출률을나타냈고, cryptic microorganism 6종을제외하였을때 category IIIb에서오히려더높은검출률을보인다는점을고려하면검체채취과정에서오염되었다고판단하는것이더합당하다고생각한다. Chlamydia trachomatis는일반적인배양에서는동정이어려운균주로이미많은보고에서 [15,16,18] CPPS의보이지않는감염의원인으로지목되어왔다. 본연구의경우 Chlamydia trachomatis의검출률은 category IIIa에서 15%, category IIIb에서 2% 로 category IIIa에서유의하게높은빈도로 (p<0.05) 검출되었다. Chlamydia trachomatis의병태생리특성상숙주의변화를초래하지않고장시간에걸쳐숙주세포에기생하면서요도분비물이나심한배뇨통등과같은감염의전형적인증상없이감염이지속될수있다는점 [25] 을고려하면잠행성의요도감염을완전히배제할수없다는문제점이있지만, 여러연구에서유사한결과를도출하였다는점에서염증성비세균성만성전립선염에서 Chlamydia trachomatis의임상적역할은더연구할가치가충분히있다고생각한다. 본연구의제한점으로는 CPPS의진단에정액검사및정액배양검사를포함하지않아 category II와 category IIIa 환자가 category IIIb로분류되었을가능성이있다. 또한 VB3 만을검체로사용하여요도에서의오염의가능성을배제하지못하였다. 그렇지만본연구는요로감염의진단에서그역할이커지고있는 PCR 검사를대단위전립선염환자들에게적용하여 PCR 검사의임상적의미를다시한번평가할수있는기회를제공해주었다고생각한다. PCR 검사는기존의방법들이가질수없었던높은민감도와양성예측률을바탕으로 CPPS에서일반배양검사로는검출되지않는 cryptic microorganism을발견하는데중요한역할을하였으나이를일반배양검사에서검출가능한세균성전립선염의원인균들에게적용하였을때는검체의오염으로인해진단적유용성이없음을알수있었다. 따라서다중 PCR 검사의신뢰도를높이기위해회음부천자를통해검체를얻거나, VB1과 VB3의 PCR 검사를동시에시행하여비교하는방법등요도에서의오염을배제하기위한노력이반드시필요할것이다. 또한통상적인배양검사에서확인이어려운원인균들을밝혀내는데현재 PCR 검사의진단적가치는충분히있다고생각하나 Chlamydia trachomatis 등 PCR 검사로발견된숨은균들의임상적의의에대해서는

5 1124 Korean Journal of Urology vol. 50, , November 2009 추가적인연구가필요하다. 결 만성골반통증후군환자에서다중 PCR을통해상당히높은빈도에서 (87%) 균주를검출할수있었다. 하지만요도를통해검체를채취하였다는점에서오염이상당부분작용하였을것으로생각한다. Chlamydia trachomatis의경우 category IIIa에서 category IIIb에비해유의하게높은빈도로검출되었는데그임상적의의에대해서는추가적인연구가필요할것으로생각한다. PCR과같은분자생물학적방법의이용은전립선염의역학및병태생리를파악하는데새로운시도이며발견된여러 cryptic microorganism이일부에서는중요한역할을하고있을것으로생각된다. 향후더나은진단방법이나오기전까지는현재 PCR 검사가가지고있는문제점들을보완하여높은정확도만큼의신뢰도를높이기위한노력이필요할것이다. 론 REFERENCES 1. Fowler JE Jr. Prostatitis. In: Gillenwater JA, Grayhack JT, Howard SS, Duckett JW, editors. Adult and pediatric urology. 2nd ed. St. Louis: Mosby-Year Book; 1991; Woo YN. Prostatitis. Korean J Urol 1994;35: 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: Alexander RB, Trissel D. Chronic prostatitis: results of an internet survey. Urology 1996;48: Krieger JN, Egan KJ. Comprehensive evaluation and treatment of 75 men referred to chronic prostatitis clinic. Urology 1991;38: Shoskes DA, Hakim L, Ghoniem G, Jackson CL. Long-term results of multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome. J Urol 2003;169: Nickel JC. Effective office management of chronic prostatitis. Urol Clin North Am 1998;25: Berger RE, Krieger JN, Rothman I, Muller CH, Hillier SL. Bacteria in the prostate tissue of men with idiopathic prostatic inflammation. J Urol 1997;157: Ponniah S, Arah I, Alexander RB. PSA is a candidate self-antigen in autoimmune chronic prostatitis/chronic pelvic pain syndrome. Prostate 2000;44: Zermann DH, Ishigooka M, Doggweiler R, Schmidt RA. Neurourological insights into the etiology of genitourinary pain in men. J Urol 1999;161: Mehik A, Hellström P, Sarpola A, Lukkarinen O, Järvelin MR. Fears, sexual disturbances and personality features in men with prostatitis: a population-based cross-sectional study in Finland. BJU Int 2001;88: Bjerklund Johansen TE, Grüneberg RN, Guibert J, Hofstetter A, Lobel B, Naber KG, et al. The role of antibiotics in the treatment of chronic prostatitis: a consensus statement. Eur Urol 1998;34: Batstone GR, Doble A. Chronic prostatitis. Curr Opin Urol 2003;13: 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 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: Heo C, Hong SJ, Gil MC. Diagnostic value of polymerase chain reaction in patients with chronic pelvic pain syndrome: using semen as a specimen. Korean J Urol 2007;48: 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: Litwin MS, McNaughton-Collins M, Fowler FJ Jr, Nickel JC, Calhoun EA, Pontari MA, et al. The National Institutes of Health chronic prostatitis symptom index: development and validation of a new outcome measure. Chronic Prostatitis Collaborative Research Network. J Urol 1999;162: Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282: Blacklock NJ. Anatomical factors in prostatitis. Br J Urol 1974;46: Krieger JN, Riley DE, Roberts MC, Berger RE. Prokaryotic DNA sequences in patients with chronic idiopathic prostatitis. J Clin Microbiol 1996;34: Roberts RO, Lieber MM, Bostwick DG, Jacobsen SJ. A review of clinical and pathological prostatitis syndromes. Urology 1997;49: Lopez-Plaza I, Bostwick DG. Prostatitis. In: Bostwick DG, editor. Pathology of the prostate. 1st ed. New York: Churchill Livingstone; 1990; Moulder JW. Characteristics of Chlamydia. In: Barron AL, editor. Microbiology of chlamydia. Boca Raton: CRC Press; 1988;4-19.

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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