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1 직장경유전립선초음파로측정한방광내전립선돌출 (Intravesical Prostatic Protrusion) 과저장증상과의연관성분석 The Correlation of Intravesical Prostatic Protrusion with Storage Symptoms, as Measured by Transrectal Ultrasound Jun Min Lee, Hong Chung, Tong-Wook Kim, Hong Sup Kim, Joon Ho Wang 1, Sang-Kuk Yang From the Departments of Urology and 1 Internal Medicine, Chungju Hospital, College of Medicine, Konkuk University, Chungju, Korea Purpose: Intravesical prostatic protrusion (IPP) is a morphological change that's due to excessive growth of the median and lateral lobes of the prostate into the bladder. Few studies have been performed regarding the correlation between IPP and the voiding/storage symptoms. The aim of this study is to identify the clinical significance of IPP by defining its relationship with the prostate volume (PV), the International Prostate Symptom Score (IPSS), the uroflowmetry results and the medication response. Materials and Methods: We performed a retrospective study of 95 male patients who were examined between August 2006 and July The patients were evaluated with the IPSS/quality of life (QoL) test, uroflowmetry (Urodyn-1000 TM ; Medtronic), the post void residual urine (PVR), and IPP and PV by transrectal ultrasound (TRUS) (PROSOUND SSD-3500 TM ; ALOKA). The IPP was compared with the total IPSS, the voiding and storage symptom score, uroflowmetry parameters and the flow patterns (normal, obstructive, detrusor impairment, Valsalva). The patients were classified into two groups (the IPP and non-ipp groups) based on the presence of IPP as identified by TRUS. Results: The PV and IPP showed a significant correlation (r=0.627, p< 0.001). There was no correlation between IPP and total IPSS (p=0.444); however, the storage symptom score was significantly increased in proportion to IPP (p=0.030). With an IPP increase, the Qmax was decreased (r= 0.319, p<0.001) and the PVR was increased (r=0.388, p=0.002). The IPP group showed a lower decrease of the QoL score after 8 weeks of medication, as compared to the non-ipp group (p=0.034). Conclusions: The IPP showed significant correlation with the storage symptoms, but not with the total IPSS. Theoretically, IPP is a unique anatomical configuration of the prostate, and it may worsen the prominent storage symptoms that are the result of irritation of the bladder neck and trigone. IPP should be checked carefully during TRUS as IPP could potentially be a useful marker for the assessment and management of lower urinary tract symptoms. (Korean J Urol 2008;49: ) Key Words: Benign prostatic hyperplasia, Bladder outlet obstruction, Ultrasound 대한비뇨기과학회지제 49 권제 2 호 2008 건국대학교의과대학비뇨기과학교실, 1 내과학교실 이준민ㆍ정홍ㆍ김동욱김홍섭ㆍ왕준호 1 ㆍ양상국 접수일자 :2007년 10월채택일자 :2007년 12월 5일 7일 교신저자 : 양상국건국대학교의과대학충주병원비뇨기과충북충주시교현 2 동 TEL: FAX: yskurol@kku.ac.kr 서 비뇨기과영역에서 transrectal ultrasound (TRUS) 는전립선 론 의용적외에도전립선의모양, 전립선선종의유무, 그리고해부학적구조등을비교적비침습적으로정확히평가할수있으며국내에서널리시행되고있다. Intravesical prostatic protrusion (IPP) 은전립선종이비대화하는과정에서전립선이방광내로밀려들어가발생하는형태적변화 145

2 146 대한비뇨기과학회지 : 제 49 권제 2 호 2008 를말하며, TRUS로정확히측정할수있다. IPP 정도와전립선크기및방광출구폐쇄와의연관성에관한보고는일부있으나, International Prostate Symptom Score (IPSS) 의배뇨증상및저장증상과의상관관계분석을통한임상적의미에대한연구는미비하다. 본연구에서는배뇨및저장증상과요속검사변수및 8주간의전립선비대증약물치료에대한반응을평가하여, TRUS로측정한 IPP 정도와연관성분석을통해임상적의의를알아보고자하였다. 대상및방법 어환자가원하거나급성요폐가발생한경우시행하였다. 요속검사후배뇨곡선의형태에따라나눈 4군에서 IPSS와전립선의크기를비교하였다. 2 통계처리는 SPSS 12.0 version을이용하여처리하였다. 변수들간의연관성분석을위해상관분석을사용하였고, IPP 유무에따른결과비교시 paired Mann Whitney U-test를이용하였다. 요속검사후배뇨곡선형태에따른 4군의비교는일원배치분산분석 (one-way ANOVA) 으로검정하였으며, p값은 0.05 미만인경우를통계적으로유의한것으로판단하였다. 2006년 8월부터 2007년 7월까지하부요로증상으로내원하여직장경유전립선초음파 (PROSOUND SSD-3500 TM ; ALOKA), 요속검사 (Urodyn-1000 TM ; Medtronic), 초음파를통한잔뇨검사 (Biocon-500 TM ; Mcube Technology) 및 IPSS를모두시행한 95명의남자를대상으로하였다. 육안적혈뇨, 요로감염, 요관및방광결석, 골반수술및당뇨의과거력이있거나신경인성방광, 전립선암, 요도협착및항콜린성약물을사용하는환자는제외하였다. IPSS는총점수, 배뇨증상점수및저장증상점수로나누어조사하였고, 외래초진및 8주간약물치료후에추적관찰하여변화정도를측정하였다. 약물치료는환자의전립선및배뇨상태에따라알파차단제 (doxazosin 및 tamsulosin) 와 5-알파환원효소억제제 (finasteride 및 dutasteride) 병합요법또는알파차단제단일요법중선택하여시행하였다. 전립선초음파에서측정된전립선용적이 35g 이상인경우에병합요법을시행하였으며, 35g 이하인경우알파차단제단일요법을적용하였다. 직장경유전립선초음파를통해전립선용적, 전립선이행대용적, 전립선종의성숙유무및방광내돌출정도를측정하였다. IPP는 Nose 등 1 이제시한방법인전립선의최대종축길이를시사하는시상면에서방광목을기준으로방광내로돌출된전립선의첨단부를잇는최단거리로측정하였으며, 방광내돌출정도에따라 5mm 미만, 5-10mm 사이및 10mm 이상의 3가지등급으로분류하였다. 요속검사는배뇨곡선에따라정상, 폐쇄성, 배뇨근저하와복압성배뇨의 4가지형태로분류하였고, 배뇨후잔뇨량을측정하였다. IPP를 IPSS 및전립선용적과비교하여연관정도를분석하였으며, 요속검사결과중실제배뇨량, 최대요속및평균요속과잔뇨량과의연관성을분석하였다. IPP의존재유무에따라나눈두집단에서 IPSS 및 8주동안단일혹은병합약물치료후의 IPSS 변화정도를비교하였으며, 요도경유전립선절제술시행및급성요폐의발생빈도를비교하였다. 요도경유전립선절제술은약물치료에증상호전이없 결과대상환자의평균연령은 64.9±9.0세였으며, 평균전립선용적은 37.9±15.3cc, 평균전립선이행대용적은 18.3±10.6 cc였다. 평균 IPSS는 19.6±8.2점이었으며, 평균배뇨증상점수및평균저장증상점수는각각 12.0±5.4점및 7.7±4.1점이었고, 평균삶의질점수는 3.9±1.1이었다. 평균 IPP는 3.5±4.5mm였고, 10mm 이상의 IPP는 10례 (15.8%) 였다. 상관분석결과전립선용적 (r=0.627, p<0.001) 및전립선이행대용적 (r=0.614, p<0.001) 이클수록 IPP가동반되는경우가유의하게증가되었다. IPSS는전립선용적및전립선이행대용적과연관성을보이지않았다. IPP 실측값은 IPSS (r=0.191, p=0.066), 삶의질 (r=0.051, p=0.624) 및배뇨증상점수 (r=0.144, p=0.168) 와의연관성을보이지않으나, 저장증상점수와는높은상관도를보였다 (r=0.594, p=0.030). IPP Grade는요속검사의배뇨량과는연관성이없었으나, Grade 가높을수록최대요속및평균요속이유의하게낮았으며잔뇨량은증가하는결과를보였다 (Table 1). 전립선종의성숙유무에따른 IPSS, 배뇨증상점수, 저장증상점수및 IPP 의차이는없었다. IPP가존재하는군 (A군) 에서존재하지않는군 (B군) 에비해 8주간약물치료후요도경유전립선절제술을시행하게되는환자들이유의하게많았다 (p<0.001). A군의 63명중 13명 (20.6%) 이요도경유전립선절제술을시행하였으나, B군의 32명은모두 8주간의약물치료이후에도지속적으로보존적치료를유지하였다. A군에서는 5% 의환자 (60명중 3명 ) 에서급성요폐가발생했으며, B군에서는 3.2% 의환자 (31명중 1명 ) 에서발생했고두군간의차이는없었다 (Table 2). 요속검사결과배뇨곡선형태로나뉜 4가지군들을분산분석을통해비교하였을때, IPSS나전립선용적이외에서는각군끼리별다른차이를보이지않았다. 전체 95명중 68.4% 에해당하는 65명의환자가폐쇄성배뇨형태를보였

3 이준민외 : 직장경유전립선초음파로측정한방광내전립선돌출과저장증상 147 으며타군들에비해평균 IPP가높았으나통계적유의성은없었다 (p=0.060). Table 1. Correlation analysis between intravesical prostatic protrusion and the prostate volume/international Prostate Symptom Score/uroflowmetry parameters Parameters IPP & TRUS IPP (mm) & TPV (g) IPP (mm) & TZV (g) TRUS & IPSS TPV(g) & IPSS TPV (g) & Voiding symptom TPV (g) & Storage symptom IPP & IPSS IPP (mm) & IPSS IPP (mm) & QoL IPP (mm) & Voiding symptom IPP (mm) & Storage symptom IPP & Uroflowmetry IPP (Grade) & Voided volume (cc) IPP (Grade) & Qmax (ml/sec) IPP (Grade) & Qavg (ml/sec) IPP(Grade) & PVR(ml) Correlation coefficient p-value * * 0.005* 0.006* Statistical significance was evaluated by correlation analysis, *p <0.05. IPP: intravesical prostatic protrusion, TRUS: transrectal ultrasound, TPV: total prostate volume, TZV: transitional zone volume, IPSS: International Prostate Symptom Score, QoL: quality of life, Qmax: maximal flow rate, Qavg: average flow rate, PVR: post voided residual urine A군과 B군으로나누어 IPSS, 배뇨증상점수및저장증상점수를종속변수로독립표본검정을시행하였을때, IPSS 는차이를보이지않았으나 (p=0.075), A군에서저장증상점수는유의하게증가되었다 (p=0.030). 또한, A군이 B군에비해 8주간의약물치료후삶의질개선이적었다 (p=0.034) (Fig. 1). Table 2. Comparison of occurrence of transurethral resection of the prostate and acute urinary retention during 8 weeks of medication, according to the presence of intravesical prostatic protrusion IPP (+) (n=63) IPP ( ) (n=32) TURP (+) 13 (20.6%, 13/63) 0 (0%, 0/32) TURP ( ) p-value 고 전립선비대증은하부요로증상및방광출구폐쇄를일으키는가장흔한질환중하나이다. 고령화사회로접어들면서유병률도증가하고있는추세로미국에서만매년 100만명 AUR (+) 3 (5.0%, 3/63) 1 (3.2%, 1/32) AUR ( ) p-value Statistical significance was evaluated by paired Mann Whitney U-test, *p<0.05. IPP: intravesical prostatic protrusion, TURP: transurethral resection of prostate, AUR: acute urinary retention 찰 Fig. 1. Comparison of the International Prostate Symptom Score (IPSS) and the quality of life (QoL) according to the presence of intravesical prostatic protrusion at the initial visit (A), Comparison of the change of IPSS and the QoL according to the presence of intravesical prostatic protrusion after 8 weeks of medication (B), *p<0.05.

4 148 대한비뇨기과학회지 : 제 49 권제 2 호 2008 이상의환자가전립선비대증으로치료를받고있다. 3 한국에서도건강보험심사평가원의통계에의하면전립선비대증외래환자는 2000년약 12만명에서 2002년 22만명으로약 2배가늘었고, 2004년 35만명으로 2000년에비해약 3배가증가하는등최근수년간빠르게증가됨을알수있다. 4 하부요로증상이있는환자중 1/3 정도는실제방광출구폐쇄가없는것으로알려져있어약물및수술방법의발전에도불구하고환자의증상이유의하게개선되지않는한계가있다. 5,6 전립선비대증으로요도경유전립선절제술을시행받은환자중 5-35% 정도는증상의개선이뚜렷하지않다고보고되고있으며, 7 특히방광출구폐쇄와급박뇨, 야간뇨등의저장증상은직접적으로관련이없다고알려져있다. 8,9 하부요로증상중저장증상은방광출구폐쇄정도와연관성은있지만반드시일치하지않으므로저장증상과배뇨증상을구분하여평가하고있다. Lim 등 10 은 IPP는전립선의용적, 전립선특이항원과밀접한연관성이있으며방광출구폐쇄를예측할수있는좋은지표로제시하였다. Mariappan 등 11 은급성요폐환자에서알파차단제복용 2주후, 요도도관제거시도 (trial without catheter; TWOC) 를하였을때, IPP 정도가전립선용적에비해배뇨성공여부를판단하는더강력한예시인자임을제시하였다. 저자들의연구에서도 IPP가없는경우모든환자에서 8주동안의단독혹은병합요법의약물치료후에도보존적치료를유지하였으나, IPP가존재하는환자의약 1/5에서요도경유전립선절제술을시행하였다. 또한 IPP 존재시 5% 에서치료중급성요폐가발생했으나, IPP가없는경우 3.2% 로다소낮았다. 이러한결과들은 IPP의존재와약물치료실패의연관성을강력히시사한다. IPSS는하부요로증상의정도를파악하고, 주관적인증상을정량적으로평가하기위하여사용할수있는설문이다. 저장증상 3항목, 배뇨증상 4항목으로구성되어있으며, 각각의증상마다 0-5점으로되어있어총점수에따라 0-7점은경도, 8-19점은중등도, 그이상은중증으로평가하는데경도에서는배뇨증상을추적관찰할수있으나중등도이상에서는약물치료를시작하는것이일반적이다. 12 IPSS의총 7개문항중저장증상이배뇨증상에비해한항목이적은 3문항으로구성되어저장증상이상대적으로저평가될수있는가능성이있으며, 요실금항목이없는한계점이있다. IPSS는방광출구폐쇄의유무및정도와는연관성이적은것으로알려져있어, 증상점수만으로수술적인치료여부를판정할수는없고다른검사방법을통하여방광출구폐쇄유무를판단해야한다. 13 Wadie 등 14 도 IPSS가방광출구폐색과의연관성이적은것이주요결점이라고언급하였다. 기존연구에서는 IPP를방광출구폐쇄의예측인자로서의 가치에초점을맞추었기때문에현재까지 IPP와 IPSS와의상호연관성에대한연구는미비한실정이다. 국내에서처음으로 Kim 등 15 이 IPP를복부초음파로측정하여 Grade에따른 IPSS와의연관성을보고하였다. 이들은저장증상과배뇨증상점수의편중여부에따라 2개의군으로나누어비교하여 IPP가저장증상보다배뇨증상에더많은영향을미칠것이라고하였으나, 이는 IPSS의저장증상점수가배뇨증상점수에비해저평가되어있다는점을고려할때실제환자의저장증상을온전히반영하지못했을가능성이있다. 반면저자들의연구결과상관분석및독립표본검정모두에서, IPP는 IPSS와연관성을보이지않았으나저장증상점수와는높은연관성을보였다. 또한요속검사를배뇨형태에따라 4가지군으로나누어비교한경우, IPP가존재하는대부분의환자들이폐쇄성배뇨형태를보이면서도대체적으로저장증상을호소한다는점에주목할필요가있다. 즉 IPP는단순히방광출구폐쇄를유발하여배뇨증상을일으킬뿐만아니라동시에저장증상을심화시킬수있는요인으로생각할수있으며, 이는 IPP로인한전립선요도신장과방광목및삼각부의자극이증가와관련이있을것으로추정된다. 복부초음파는직장질환이있거나항문수술을받아 TRUS를시행하지못하는환자에서도쉽게시행할수있으며동시에상부요로의상태및복부장기까지확인할수있어 TRUS보다덜침습적인방법으로용이하게진행할수있다는장점이있다. 이러한이유로초기의여러 IPP 관련연구에서는 IPP 측정도구로복부초음파를사용하였다. 복부초음파로 IPP를측정하는방법은기본적으로본연구의 TRUS를이용한측정법과비슷하나충만된방광을창 (acoustic window) 으로하여전립선을관찰하므로방광충만정도에따라영향을받으며, 16 전립선기저부에서방광으로돌출되는환상면부위에서돌출부첨단부까지의수직거리로 IPP를측정한다. 16,17 그러나, Yuen 등 16 은복부초음파를이용한 IPP 측정은방광충만이증가할수록 IPP는상대적으로감소하기때문에 cc 정도의방광충만시에만정확한측정을할수있다고하였으며, 방광이비어있는경우에는 IPP 측정이어려우며측정값의신뢰도가떨어진다고하였다. 실제외래진료실에서 IPP를측정하고자대상환자의방광충만을일정수준으로맞추기는어렵다. 반면, TRUS를이용한 IPP 측정은방광충만을필요로하지않으며, 시행시전립선용적뿐만아니라잔뇨량을동시에측정하면비용및환자의불편감을줄일수있다. 11,18 전립선평가를위한 TRUS 시행중 IPP는전립선용적과함께반드시측정해야할인자로생각한다. 본연구가후향적으로진행되어 IPP group과 non-ipp group의대상환자군

5 이준민외 : 직장경유전립선초음파로측정한방광내전립선돌출과저장증상 149 선택에오차 (selection bias) 가있을수있다. 그러한대상환자군의선택오차를감안하더라도, IPP를단순히방광출구폐쇄를평가하는예시인자로생각하기보다하부요로증상, 특히저장증상과연관성이높으며급성요폐로의진행을더욱빈번하게발생시킬수있으며약물치료에낮은반응을보이게되는원인으로고려할필요가있다. 향후, IPP와저장증상과의연관성에대한더많은전향적연구가필요하며, 저장증상이심한전립선비대증환자에서약물치료시 IPP를고려해야할것으로생각한다. 결 IPP 정도는전립선용적이클수록증가하였다. IPP가증가될수록 IPSS는증가되지않았으나저장증상이현저히증가하여전립선비대에동반된저장증상과밀접한관계가있다고생각하며, 약물치료시반응률이감소하는경우가많았다. IPP가증가됨에따라전립선요도가신장되고방광목및삼각부의자극이증가되어저장증상이심해질가능성이있으므로, IPP는 TRUS 시행시관심있게측정해야할항목으로생각하며이의임상적의의에대한추가적인연구가필요하다. 론 REFERENCES 1. Nose H, Foo KT, Lim KB, Yokoyama T, Ozawa H, Kumon H. Accuracy of two noninvasive methods of diagnosing bladder outlet obstruction using ultrasonography: intravesical prostatic protrusion and velocity-flow video urodynamics. Urology 2005;65: Kelly CE. Evaluation of voiding dysfunction and measurement of bladder volume. Rev Urol 2004;6 (Suppl 1): Woodwell D. Office visit to urologists US, , National Ambulatory Medical Care Survey. In Advance Data from Vital and Health Statistics, no Bethesda, Maryland: National Center for Health Statistics; 1992; Yang SK. How to determine the timing of surgery. J Korean Continence Soc 2005;9 (Suppl): Yalla SV, Sullivan MP, Lecamwasam HS, DuBeau CE, Vickers MA, Cravalho EG. Correlation of American Urological Association symptom index with obstructive and nonobstructive prostatism. J Urol 1995;153: Kaplan SA, Bowers DL, Te AE, Olsson CA. Differential diagnosis of prostatism: a 12-year retrospective analysis of symptoms, urodynamics and satisfaction with therapy. J Urol 1996;155: Bruskewitz RC, Larsen EH, Madsen PO, Dørflinger T. 3-year followup of urinary symptoms after transurethral resection of the prostate. J Urol 1986;136: Tempany CM, Partin AW, Zerhouni EA, Zinreich SJ, Walsh PC. The influence of finasteride on the peripheral and periurethral zones of the prostate in men with benign prostatic hyperplasia. Prostate 1993;22: Abrams PH, Farrar DJ, Turner-Warwick RT, Whiteside CG, Feneley RC. The results of prostatectomy: a symptomatic and urodynamic analysis of 152 patients. J Urol 1979;121: Lim KB, Ho H, Foo KT, Wong MY, Fook-Chong S. Comparison of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of bladder outlet obstruction. Int J Urol 2006;13: Mariappan P, Brown DJ, McNeill AS. Intravesical prostatic protrusion is better than prostate volume in predicting the outcome of trial without catheter in white men presenting with acute urinary retention: a prospective clinical study. J Urol 2007;178: Cho HJ, Kang JY, Yoo TK. The International Prostate Symptom Score: discrepancies between self-administration and physician-administration. Korean J Urol 2007;48: McConnell JD. Why pressure-flow studies should be optional and mandatory studies for evaluating men with benign prostatic hyperplasia. Urology 1994;44: Wadie BS, Ibrahim EH, de la Rosette JJ, Gomha MA, Ghoneim MA. The relationship of the IPSS and objective parameters for diagnosing bladder outlet obstruction. Part I: when statistics fail. J Urol 2001;165: Kim BH, Sohn JC, Park CH, Kim CI. The usefulness of intravesical prostatic protrusion and bladder wall thickness measurement using transabdominal ultrasound in patients with benign prostatic hyperplasia. Korean J Urol 2005;46: Yuen JS, Ngiap JT, Cheng CW, Foo KT. Effects of bladder volume on transabdominal ultrasound measurements of intravesical prostatic protrusion and volume. Int J Urol 2002;9: Chia SJ, Heng CT, Chan SP, Foo KT. Correlation of intravesical prostatic protrusion with bladder outlet obstruction. BJU Int 2003;91: Park SY, Cho JS, Hong CH, Lee KS. The clinical value of residual urine checked by transrectal ultrasonography. Korean J Urol 2007;48:951-5

슬라이드 1

슬라이드 1 Proposed Korean guideline for the diagnosis of BPH Hyun Woo Kim The Catholic University of Korea BPH Guideline AHCPR guideline on BPH (1994) AUA guideline on BPH (2003) EAU guideline on BPH (2004) International