전립선비대증환자에서전립선염 동반유무가수술결과에미치는영향 연세대학교대학원 의학과 전희종
전립선비대증환자에서전립선염 동반유무가수술결과에미치는영향 지도김광진교수 이논문을석사학위논문으로제출함 2007 년 6 월 연세대학교대학원 의학과 전희종
전희종의석사학위논문을인준함 심사위원 심사위원 심사위원 인 인 인 연세대학교대학원 2007 년 6 월 20 일
감사의글 본논문이완성되기까지각별한지도와격려, 그리고세심한배려를아끼지않으신은사김광진교수님과연구과정이진행되는동안많이도와주시고격려해주신김성진, 김춘배교수님께진심으로감사를드립니다. 또한학위과정에서많은도움을주신송재만, 정현철교수님과비뇨기과전공의들에게도깊은감사를드립니다. 끝으로오늘에이르기까지넓은사랑과이해로뒷받침하여주신어머니에게이조그마한영광을드립니다. 2007 년 6 월 저자씀
차 례 그림및표차례 ⅱ 국문요약 ⅲ 제 1 장서론 1 제 2 장대상및방법 3 제 3 장결과 8 제 4 장고찰 11 제 5 장요약및결론 13 참고문헌 14 영문요약 18 - i -
그림및표차례 Fig. 1. Flow of patients throughout the trial 5 Fig. 2. Microscopic features of benign prostatic hyperplasia with prostatitis 6 Fig. 3. Microscopic features of benign prostatic hyperplasia without prostatitis 7 Table 1. General characteristics, prostate volume, and PSA of study population 9 Table 2. Comparison of the preoperative and postoperative clinical outcome between two groups 9 Table 3. Comparison of IPSS, QoL, Qmax between two groups 10 Table 4. Comparison of complications between two groups 10 - ii -
국문요약 전립선비대증환자에서전립선염동반여부가수술결과에미치는영향 최근전립선비대증에동반된전립선염의임상적중요성이강조되면서이에대한여러연구가보고되었는데, 그중두질환이동반된경우전립선비대증에대한약물치료후전립선염이동반된군과동반되지않은군간에하부요로증상의개선효과에대한연구는있으나, 경요도전립선절제술후전립선염의동반이하부요로증상의개선에어떤영향을주는지에대한연구는보고되지않았다. 이에전립선비대증환자에서전립선염의동반이경요도전립선절제술후하부요로증상개선에어떠한영향을주는지를알아보고자하였다. 1996년 3월부터 2006년 12월까지경요도전립선절제술을시행받고추적관찰이가능하였던 237명의환자들을대상으로수술후전립선조직의병리결과에따라전립선염군과비전립선염군으로분류하였으며, 수술전후의국제전립선증상점수, 삶의질지수, 요속의변화, 합병증유무를조사분석하였다. 전립선염군과비전립선염군의경요도전립선절제술후최고요속및합병증동반률은통계학적으로유의한차이를보이지않았으나 (p>0.05), 국제전립선증상점수및삶의질지수의변화는유의한차이를보였다 (p<0.05). 즉, 임상적으로전립선염군은비전립선염군에비해객관적지표인최고요속은차이가나지않았으나, 주관적지표인국제전립선증상점수및삶의질지수가유의하게낮았다. 따라서전립선염은경요도전립선절제술의하부요로증상개선효과를저해시키는것으로생각되며, 수술전전립선염이진단된경우에전립선염에대한치료를먼저시행하고, 수술후조직검사에서전립선염이진단된경우에도전립선염에대한치료를시행하면환자의술후만족도를더욱증가시킬수있을것으 - iii -
로판단된다. 핵심되는말 : 전립선비대증, 전립선염, 경요도전립선절제술 - iv -
제 1 장. 서론 비뇨기과전문의들이외래에서가장흔하게접하게되는염증성질환중의하나인전립선염은빈뇨, 잔뇨감, 요지연, 요급등의배뇨증상과회음부, 치골상부및음낭부위등에통증을유발하는데, 이는우리나라에서전체남성비뇨기질환의 25% 를차지할정도로그발생빈도가높다 (Lee 1992; Woo 1994). 전립선비대증역시흔한남성노인성질환중의하나로부검결과에의하면, 50대이후남성의 50%, 70대이후에는 75% 에서전립선의비대소견이관찰된다고한다 (Holtgrewe 1998; Roehrborn and McConnell 2002). 남성노인환자에서삶의질을저하시키는하부요로증상을유발시키는질환중전립선비대증과전립선염의영향에대한관심이증가하고있으나, 현재까지두질환의상관관계에대해서는정확히밝혀지지않고있다 (Kohen and Dratch 1979; Nickel et al. 1999). 하부요로증상은그동안전립선증으로불리면서염증에의한방광자극증상과하부요로폐색으로인한방광폐색증상으로나누어서기술하였으나, 그증상과원인간의상관관계는뚜렷치않다고하였다 (Chaikin and Blaivas 2001). 이런하부요로증상의원인중전립선폐색이 2/3를차지하며, 이로인해반수에서배뇨근의과항진성이, 나머지에서는배뇨근수축력부전, 감각성요급, 괄약근부전에의한요실금, 빈뇨또는야간빈뇨등이발생한다. Abrams 등 (1979) 은하부요로증상의완화를위해전립선절제술을받는경우성공률이 70-90% 로 10-30% 에서는증상이잔존한다고하였고, Ball과 Smith(1986) 는경요도전립선절제술후에도배뇨근수축력저하나불안정성방광이있는경우술후배뇨증상이개선되지않았다고하였다. 전립선비대증수술후실패원인으로배뇨근실조와불안정이중요한요인이며, 배뇨근실조의기전에대해서비교적잘알려진반면배뇨근불안정에대해서는아직논란이많다. 전립선비대증환자에서배뇨근불안정의여러원인중전립선염동반여부가관련되어있을것으로생각되나아직확실하게밝혀진적이없다. 이러한불안정성방광의원인을 Kang 등 (2003) 은전립선염이라고생각하였으며, - 1 -
전립선염이동반된전립선비대증환자에서전립선비대증의치료약물로사용되는 α1-교감신경차단제와 5α-환원효소억제제를사용한경우전립선염이동반되지않은환자군에비해국제전립선증상점수가덜호전되었다고하였다. 이에본연구에서는전립선비대증환자의치료에있어전립선염존재여부가전립선비대증치료전후에영향을미친다는가정하에경요도전립선절제술후전립선염존재여부에따른하부요로증상및요속의차이를비교하고자하였다. - 2 -
제 2 장. 대상및방법 이연구에서는 1996년 3월부터 2006년 12월까지원주기독병원에서전립선비대증으로진단받고입원치료를받은 461명의환자를대상으로하였다. 이중수술을거부하거나신경인성방광, 요도협착, 당뇨, 요로감염등의병력이있는환자및다른술자에의한경우를제외한 271명이연구대상으로최종선정되었다. 환자들은모두경요도전립선절제술을받고 3개월후에삶의질을포함한임상결과지표를전향적으로추적관찰하여측정받았다. 이중 34명은술후 3개월에추적관찰이불가능하여연구대상에서제외되었으며, 조직검사에서전립선비대증과전립선염이동반된군이 82명 (34.6%), 전립선염이동반되지않은군이 155명 (65.4%) 이었다 (Fig. 1). 경요도전립선절제술후얻은병리조직을분석하여전립선조직내에백혈구나임파구의침윤이있을경우전립선염군으로, 이러한소견이없는경우비전립선염군으로나누었다 (Fig. 2,Fig. 3). 술전경직장초음파 (7.5MHz, Aloka) 를통해전립선전체크기를종경ⅹ횡경ⅹ전후경ⅹ(π/6) 로산정하였으며, 경요도전립선절제술의효과를분석하기위하여전립선비대증에의한방광자극증상과요로폐색증상등의주관적증상을술전과술후 3개월에국제전립선증상점수로측정하여평가하였다. 객관적평가로서는술전후요속검사를시행하였으며, 최대요속측정은배뇨량의차이에의한오차를줄이기위해단회배뇨량이 150ml 이상인경우로하였다 (Siroky, Olsson and Krane 1979). 요속비교는급성요폐나이로인한도뇨관삽입으로요속측정이불가능한환자는제외하였다. 경요도절제술에의한합병증을파악하기위해술전및수술직후혈색소치, 혈중전해질수치의변화등생화학적검사를시행하였으며, 요검사와요배양검사를시행해요로감염여부를조사하였다. 이외술후요실금, 요도협착등에대해서도관찰하였다. 수술은방광경부에서정구사이의비대된전립선조직의절제를원칙으로하였으며, 마취방법은척추마취를우선적으로시행하였으며, 절제경은 26Fr. Storz 절제경을, 관류액은 Urione용액 (d-manntol 0.54g, d-sorbitol 2.7g/100ml, 3,000ml, - 3 -
중외제약 ) 을각각사용하였다. 절제후에는 22Fr. 3-way 30cc balloon Foley 카테터를유치하여출혈정도에따라도뇨관을견인할수있도록하였다. 통계분석은 SPSS 12.0 for Windows를이용하였으며, 통계적유의성은독립표본 t 검정및대응표본 t 검정을이용하였으며, p값이 0.05 미만인경우를통계학적으로유의하다고판정하였다. - 4 -
Figure 1. Flow of patients throughout the trial - 5 -
Figure 2. Microscopic features of benign prostatic hyperplasia with prostatitis A B A. Note the glandular hypertrophy and sparse infiltration of inflammatory cells. (haematoxylin eosin stain; original magnification 40) B. Numerous small dark blue lymphocytes are seen in the stroma between the glands. (haematoxylin eosin stain; original magnification 200) - 6 -
Figure 3. Microscopic features of benign prostatic hyperplasia without prostatitis A B A. Notice the large number of complex, infolded glands without inflammatory cells. (haematoxylin eosin stain; original magnification 40) B. Notice that its epithelium is infolded even within the glands, the cells are too numerous. (haematoxylin eosin stain; original magnification 200) - 7 -
제 3 장. 결과 237명의환자중전립선염군은 82명 (34.6%) 으로평균나이는 67.6±6.2세였으며, 비전립선염군은 155명 (65.4%) 으로평균나이는 69.6±7.8세로두군간에유의한차이를보이지않았다 (p=0.058). 전립선초음파검사에서전체전립선용적은전립선염군에서 56.8±25.6cc, 비전립선염군에서 52.7±25.1cc로평균의차이는있었으나통계학적유의성은없었다 (p=0.238). 혈중전립선특이항원수치도각각평균 7.1±10.5ng/ml, 5.2±6.7ng/ml로두군간에유의한차이를보이지않았다 (p=0.093)(table 1). 국제전립선증상점수및삶의질지수, 최대요속은술후평균 3개월에추적조사되었는데, 술전평균국제전립선증상점수는전립선염군과비전립선염군에서유의한차이를보였으며 (p=0.018), 술후에도두군간에유의한차이를보였다 (p<0.01). 술전및술후평균삶의질지수역시전립선염군과비전립선염군에서유의한 차이를보였다 (p<0.01). 그러나평균최대요속은술전및술후두군간에차 이를보이지않았다 (p>0.05)(table 2). 두군간에최대요속값의변화는통계학적으로유의성이없었으나 (p=0.805), 국제전립선증상점수및삶의질지수의변화는술전및술후유의한차이를보였다 (p<0.01). 전립선염군이평균국제전립선증상점수는 8.4점낮았으며, 평균삶의질지수도 2.03점낮아술후주관적인환자의만족도가유의하게낮았다 (Table 3). 합병증은전립선염군에서 17례 (17/82, 21%), 비전립선염군에서 34례 (34/155, 22%) 였으며출혈, 요도협착, 요로감염의순으로두군간에유의한차이는보이지않았다 (p=0.831) (Table 4). - 8 -
Table 1. General characteristics, prostate volume, and PSA of study population (unit : Mean±SD) BPH patients prostatitis + prostatitis - Total p value Number 82 155 237 Age 67.6±6.2 69.6±7.8 68.9±7.3 0.058 Prostate volume(cc) 56.8±25.6 52.7±25.1 54.1±25.3 0.238 PSA(ng/ml) 7.1±10.5 5.2±6.7 5.9±8.2 0.093 Table 2. Comparison of the preoperative and postoperative clinical outcome between two groups (unit : Mean±SD) BPH patients prostatitis + prostatitis - P value of prostatitis + vs prostatitis - Test Preop Postop Preop Postop Preop Postop IPSS(score) 22.7±7.4 18.1±9.4 25.1±7.2 12.1±7.1 0.018 <0.01 QoL(score) 4.5±1.3 3.5±1.6 5.1±1.2 2.1±1.3 <0.01 <0.01 Qmax(ml/s) 6.8±3.6 14.9±7.9 7.1±3.9 15.0±6.8 0.545 0.932-9 -
Table 3. Comparison of IPSS, QoL, Qmax between two groups (unit : Mean±SD) BPH patients prostatitis (+) (n=82) prostatitis (-) (n=155) p value IPSS (score) 4.6±10.4 13.0±7.5 < 0.01 QoL (score) 1.0±2.1 3.0±1.6 < 0.01 Qmax (ml/s) 8.1±7.7 7.8±6.4 0.805 : IPSS = preoperative IPSS - postoperative IPSS : QoL = preoperative QoL - postoperative QoL : Qmax = postoperative Qmax - preoperative Qmax Table 4. Comparison of complications between two groups prostatitis (+) (%) n=82 prostatitis (-) (%) n=155 Total(%) Hemorrhage 5(6.1) 11(7.1) 16(6.7) Urethral stricture 5(6.1) 9(5.8) 14(5.9) Infection 4(4.9) 8(5.2) 12(5.1) Urinary retention 2(2.4) 5(3.2) 7(2.9) Urinary incontinence 1(1.2) 1(0.6) 2(0.8) Total (n=51) 17(20.7) 34(21.9) 51(21.5) - 10 -
제 4 장. 고찰 1945년 Barnes와 Nesbit에의해경요도전립선절제술이하부요로증상을호소하는전립선비대증환자의수술적치료로정착하게된이후현재까지황금률로자리잡고있다. 그러나경요도전립선절제술후에도하부요로증상이개선되지않고지속되는경우가많았으며, 많은학자들이그원인중의하나로전립선염을지목하고있다. Nickel 등 (1999) 은전립선비대증으로경요도전립선절제술을시행받은환자 100명의조직을백혈구공통항원으로면역염색을시행하고컴퓨터이미지분석을시행한결과, 모든조직에서염증소견을보였다고하였다. 전립선염에이환된경우그기전은정확히밝혀지지않았지만대개전립선관내로의요의역류, 골반근육의습관적인수축, 감염등이알려져있고, 일단전립선내염증이생기면외요도괄약근이나요도를자극하여요도내압은더욱증가하여요역류가더욱심해지는악순환을하게된다 (Kirby et al. 1982). 이는전립선비대증으로인한방광출구폐색이방광의허혈을유발하여배뇨근의변화와함께배뇨근과항진이일어나는기전과상이한점을보인다 (Thomas,and Abrams 2000). Jensen(1989) 은하부요로증상을호소하는환자의 1/3에서압력-요속검사에서폐색이없었으며, 이경우경요도전립선절제술후에 25% 에서는증상의호전율이낮았다고보고하였다. Kim 등 (2002) 은전립선비대증환자에서전립선염의동반에따른하부요로증상및요역동학검사의비교에서전립선염동반시에하부요로증상중요급같은방광자극증세가더우세하였고, 폐색군보다는비폐색군이더많았으며배뇨근불안정등의배뇨장애를보이는빈도가높다고하였다. 그러나실제로경요도전립선절제술후에요역동학검사를시행하는경우는드물며, 전향적연구로술전및술후요역동학검사를비교할수있으면하부요로증상의병태생리를밝히는데도움이될것으로생각한다. 하부요로증상을측정할수있는증상점수및삶의질지수는기본검사로사용하 - 11 -
고있으며, 전립선비대증에대한치료시방향설정과치료후예후판정에유용하게사용되고있다 (Ko et al. 1995). 그러나증상점수의문제점은환자가자신의증상정도를점수표에정확하게표현하는데오차가있고, 증상점수정도와폐색의유무및정도와는연관성이낮은것으로알려져있다 (Barry et al. 1995). Kang 등 (2003) 이전립선염이동반된전립선비대증환자에서 α1-교감신경차단제와 5α-환원효소억제제를사용하여투약 12개월후두군간의하부요로증상의호전율을비교한전향적연구에서두군모두증상점수및요속, 잔뇨등의증상호전을보였으나, 두군간에호전되는양상은전립선염군에서비전립선염군보다증상점수의호전율이낮다고하였다. 본연구에서는경요도전립선절제술후증상점수및삶의질지수, 최대요속이두군모두호전을보였으나, 두군간의호전율은증상점수및삶의질지수가비전립선염군에서더높았고, 최대요속은차이를보이지않았다. 또한본연구에서는술후병리학적으로전립선염을진단하였으나전립선액채취를통해임상적으로전립선염을진단하여연구를시행할경우의미있는연구결과를얻을수있을것으로생각하며, 추적관찰기간이 3개월로짧아향후장기간의추적관찰이필요할것으로생각한다. - 12 -
제 5 장. 요약및결론 전립선비대증으로경요도전립선절제술을시행받은환자중 1/3 이상에서전립선비대증과동반된전립선염의병리학소견이관찰되었으며, 이경우비전립선염군에비해증상점수및삶의질지수의호전율이낮았다. 그러므로전립선염은경요도전립선절제술의하부요로증상개선효과를저해시키는것으로생각되며, 술전전립선염의적극적인진단이필요하며전립선염이진단된경우에는전립선염에대한치료가필요할것으로생각한다. 또한전립선수술후조직검사에서전립선염이진단된경우에도술후지속적으로전립선염에대한치료를시행하면환자의술후만족도를증가시킬것으로판단된다. - 13 -
참고문헌 1. Abrams PH, Farrar DJ, Turner-warwick RT, Whiteside CG, Feneley RCL.1979. The results of prostatectomy: a symptomatic and urodynamic analysis of 152 patients. J Urol 640-2 2. Ball AJ, Smith PJB. 1986. Urodynamic factors in relation to outcome of prostatectomy. Urology 28:256-9 3. Barry MJ, Fowler FJ Jr, O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. 1992. The American Urological Association symptom index for benign prostatic hyperplasia. the measurement committee of the American Urological Association. J Urol 148:1549-57 4. Barry NK, Williford WO, Chang Y, Machi M, Jones KM, Walkwe-Corkery E, et al. 1995. BPH-specific health status measures in clinical research: How much change in AUA symptom index and BPH impact index is perceptible to patients? J Urol 154:1770-4 5. Berry SJ, Coffey DS, Walsh PC, Ewing LL. 1984. The development of human benign prostatic hyperplasia with age. J Urol 132:474-9 6. Chaikin DC, Blaivas JG. 2001. Voiding dysfunction: definitions. Curr Opin Urol 11:395-8 - 14 -
7. Collins MM, Stafford RS, O'Leary MP, Barry MJ. 1999. Distinguishing chronic prostatitis and benign prostatic hyperplasia symptoms: results of a national survey of physician visits. Urology 53:921-5 8. Cunha GR. 1994. Role of mesenchymal-epithelial interactions in normal and abnormal development of the mammary gland and prostate. Cancer 74:1030-44 9. Holtgrewe HL. 1998. Current trends in management of men with lower urinary tract symptoms and benign prostatic hyperplasia. Urology 51:1-7 10. Jensen KM. 1989. Clinical evaluation of routine urodynamic investigations in prostatism. Neurourol Urodyn ;8:545-78 11. Kang TW, Oh BR, Kim KW, Min KD, Kwon DD, Ryu SB. 2003. Clinical significance of prostatitis in patients with benign prostatic hyperplasia Korean J Urol 44:278-82. 12. Kessler OJ, Keisari Y, Servadio C, Abramovici A. 1998. Role of chronic inflammation in the promotion of prostatic hyperplasia in rats. J Urol 159:1049-53 13. Kim KW, Kwon DD, Park YI. 2002. Comparison of lower urinary tract symptoms and urodynamic study in BPH patients with or without prostatitis Korean J Urol 43:578-83 - 15 -
14. Kirby RS, Lowe D, Bultitude MI, Shuttleworth KED. 1982. Intraprostatic urinary reflux: an aetiological factor in bacterial prostatitis. BR J Urol 54:729-31 15. Ko DSC, Fenster HN, Chambers K, Sullivan LD, Jens M, Goldenberg SL. 1995. The correlation of multichannel urodynamic pressure-flow studies and American Urological Association voiding symptom index in the evaluation of benign prostate hyperplasia. J Urol 154:396-8 16. Kohnen PW, Dratch GW. 1979. Patterns of inflammation in prostatic hyperplasia; a histologic & bacteriologic study. J Urol 121:755-60 17. Krieger JN, Egan KJ, Ross SO, Jacobs R, Berger RE. 1996. Chronic pelvic pains represent the most prominent urogenital symptoms of chronic prostatitis. Urology 48:715-22 18. Lee MS.. 1992. Prostatitis. J Korean Med Sci 35:1066-70 19. McNicholas TA. 2001. Lower urinary tract symptoms suggestive of benign prostatic obstruction: what are the current practice patterns? Eur Urol 39:26-30 20. National Institutes of Health Summary Statement. National Institute of Diabetes and Digestive and Kidney disease workshop on chronic prostatitis. Bethesda. December 1995-16 -
21. Nickel JC, Downey J, Young I, Boag S. 1999. Asymptomatic inflammation and infection in benign prostatic hyperplasia. BJU Int 84:976-81 22.. Roehrborn CG, McConnell JD. 2002. Etiology, pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ, editors. Campbell's urology. 8th ed. Philadelphia: Saunders 1297-336 23. Sheckter CB, Matsumoto AM, Bremner WJ. 1989. Testosterone administration inhibits gonadotropin secretion by an effect directly on the human pituitary. J Clin Endocrinol Metab 68:397-401 24. Siroky MB, Olsson CA, Krane RJ. 1979. The flow rate nomogram: I. Development. J Urol 122:665-8 25. Thomas AW, Abrams P. 2000. Lower urinary tract symptoms, benign prostatic obstruction and the overactive bladder. BJU Int suppl 85:57-68 26. Woo YN. 1994. Prostatitis. Korean J Urol 35:575-85 - 17 -
ABSTRACT The effect of prostatic inflammation on the operation outcome in patient with benign prostatic hyperplasia Hee-Jong Jeon Dept. of Medicine The Graduate School Yonsei University Benign prostatic hyperplasia (BPH) and prostatitis may present similar clinical manifestations, although the severity of their symptoms is different. From march 1993 to december 2006, 237 patients with symptomatic BPH, who had undergone TURP by one surgeon, were enrolled in this study. Among total of 237 patients, 82 patients (34%) had prostatitis and 155 patients (66%) were free of prostatitis in pathologic diagnosis after TURP. We investigated the differences between BPH patients with prostatitis and those without prostatitis after TURP through International Prostate Symptom Score (IPSS), maximal urine flow rate (Qmax) and Quality of Life scale (QoL). Statistical analysis was performed using the independent t test and paired t test. Prostate volume, PSA, Qmax, complications have no differences between two groups (p>0.05), but IPSS and QoL have a - 18 -
significance differences between two groups (p<0.05). So BPH patients with prostatitis who are planning to transurethral prostate surgery should be treated before or after surgery in order to improve their satisfaction after surgery. Key words : Benign Prostate Hyperplasia (BPH), Prostatitis, Transurethral resection of the prostate (TURP) - 19 -