대한남성과학회지 : 제 29 권제 2 호 2011 년 8 월 Korean J Androl. Vol. 29, No. 2, August 2011 http://dx.doi.org/10.5534/kja.2011.29.2.161 술전 5-알파환원효소억제제의투여가 120W Greenlight TM HPS 레이저를이용한광선택적전립선기화술에미치는영향 부산대학교의과대학비뇨기과학교실 박현준ㆍ김현우ㆍ김태남ㆍ박남철 The Effect of 5-alpha Reductase Inhibitors on the Efficacy of Photoselective Vaporization of the Prostate with 120 W GreenLight HPS Laser Hyun Jun Park, Hyun Woo Kim, Tae Nam Kim, Nam Cheol Park Department of Urology, Pusan National University School of Medicine, Busan, Korea =Abstract= Purpose: To evaluate the effect of preoperative 5-alpha reductase inhibitor (ARI) administration on the operative results of photoselective vaporization of prostate with 120W GreenLight HPS laser. Materials and Methods: Data were collected from 98 benign prostatic hyperplasia (BPH) patients who underwent transurethral electrovaporization of prostate by 120W Greenlight HPS laser between Jan. 2010 and Dec. 2010. We compared the time of operation, the energy required in lasering, postoperative maximum uroflow velocity, change in residual urine volume and complications between 5-ARI administrating group and control group. Results: 56 patients administrated 5-ARI at least 3 months before surgery. 30 and 26 patients administrated finasteride and dutasteride, respectively. Mean follow up period was 4.1±1.8 months. Mean age of the subjects and mean prostate volume were not different. Mean change of postoperative hemoglobin, lasing time and energy required in lasering were greater in 5-ARI administrating group. There were 3 and 1 cases of acute urinary retension in 5-ARI administrating group and control group, respectively. Conclusions: The mean change of hemoglobin and mean energy required in lasering were greater and mean lasing time was longer in the patients who administrated 5-ARI before photoselective vaporization of prostate by 120W Greenlight HPS laser. Further investigation and extensive study will be needed to confirm these results. Key Words: Prostate hyperplasia, 5-alpha reductase inhibitors, Transurethral vaporesection of prostate 서 론 접수일자 : 2011 년 4 월 4 일, 수정일자 : (1 차 ) 2011 년 6 월 21 일, (2 차 ) 2011 년 7 월 19 일, 게재일자 : 2011 년 7 월 21 일교신저자 : 박남철, 부산대학교병원비뇨기과부산시서구아미동 1 가 10 번지 602-739 Tel: 051-240-7347, Fax: 051-247-5443 E-mail: pnc@pusan.ac.kr * 본연구는 2011 년부산대학교병원임상연구비지원에의해수행되었음. 전립선비대증은고령사회로접어드는현재, 가장흔한노인성질환의하나로서진단및치료기술의발달과의료기관으로의접근성이향상되어, 전립선비대증으로수술치료를받는환자수도증가하고있다. 전립선비대증의수술치료에서특히, 레이저 161
162 대한남성과학회지 : 제 29 권제 2 호 2011 를이용한비교적저침습적수술이차지하는비율이점점높아지고있으며, 이들중일부술식은전립선비대증의표준수술법으로알려져있는경요도전립선절제술 (transurethral resection of prostate; TURP) 과비슷한결과를보이고, 합병증은오히려적은것으로여러연구에서확인되었다. 1 이중대표적인수술법중의하나로 1998년 Malek 2 에의해 60W 광선택적전립선기화술이소개된이후 532 nm 파장의레이저를이용한광선택적전립선기화술 (photoselective vaporization of prostate, PVP) 은수술결과가좋고합병증도적은장점을바탕으로국내외에서시술빈도가증가하고있다. 1,3 80W 광선택적전립선기화술의 5년간추적연구에서수술전보다최고요류속도 (peak urinary flow rate, Qmax) 에서 90%, 배뇨후잔뇨 (post void residual, PVR) 에서 89% 의호전이보고되었다. 4 국내에서도최근 GreenLight high-performance (HPS) system 120W 레이저가도입되어빠르게보급되고있으며만족할만한초기연구결과가보고되고있다. 5 수술전전립선비대증의약물치료제로널리사용되는 5-알파환원효소억제제 (5-alpha reductase inhibitor, 5-ARI) 는전립선의크기를감소시켜급성요폐의발생률을저하시키며, 경요도전립선절제술시출혈감소, 혈청 PSA 수치를감소시키는효과를보인다. 이는전립선으로의혈류를감소시키는효과와관련이있다. 6 이러한 5-ARI 제제의약물특성상전립선조직내적혈구의헤모글로빈에흡수되어기화를시키는 120W HPS 레이저를이용할경우조직의기화되는효율에영향을주고, 이에따른수술소요시간이증가할수있다. 이에저자들은전립선의혈류를감소시키는 5-알파환원효소억제제의술전복용이적혈구의헤모글로빈에흡수되어조직을기화시키는 120W Green- Light HPS 레이저를이용한광선택적전립선기화술의시행과술후결과에미치는영향을알아보고자한다. 기화술을시행받은 98 명의환자들을대상으로하였다. 술전에 5-ARI 제제를복용한적이없는환자들을대조군으로, 술전에 5-ARI 제제를최소 3 개월이상복용한환자들을복용군으로나누어각군별로수술전과후의평가지표를비교하였다. 양군모두에서평가지표에영향을최소화하기위해술전평가최소 1 주전부터, 그리고술후평가시에알파차단제는복용하지않은환자를대상으로하였다. 수술은전례에서단일술자에의해시술되었다. 2. 평가지표 평가지표로는수술시의평균나이, 술전전립선및전환대 (Transition zone) 의크기, 최고요속과배뇨후잔뇨량, 국제전립선증상점수 (International Prostate Symptom Score, IPSS) 및 quality of life (QoL) 7 을사용하였다. 시술에관련된평가지표로는레이저사용시간및에너지량, 전립선전체및전환대의단위용적당레이저사용시간및에너지량을조사하였다. 술후평가지표로는술후최고요속및잔뇨량의변화, 혈색소수치의변화및합병증을비교하였다. 혈색소치의변화는수술직후에측정한수치를, 술후최고요속및잔뇨량의변화, IPSS 및 QoL 은술후 3 개월째측정한지표를사용하였다. 5-ARI 제제를복용한 56 명의환자에서는약제의종류에따른차이를알아보기위해 finasteride 와 dutasteride 를복용한환자, 각각 36 명및 20 명에서술중및술후평가지표를비교하였다. 3. 통계처리 통계처리는 SPSS 12.0 을이용하였다. 각군간의수술전후의지표차이는 Student's t-test 를사용하였으며, p 값이 0.05 미만을통계적으로의미있는것으로간주하였다. 결 과 1. 대상환자 대상및방법 2010 년 1 월부터 2010 년 12 월까지부산대학교병원비뇨기과를방문하여전립선비대증으로 120W Greenlight HPS 레이저를이용한광선택적전립선 술전 5-ARI 제제를최소 3 개월이상복용한환자는 56 명이었고복용하지않은환자는 42 명이었다. 술후평균추적관찰기간은 4.1±1.8 개월이었으며, 복용군의술전 5-ARI 제제복용기간은평균 34.4± 35.0 개월이었다. 두군사이에술전평균혈청전립선특이항원 (Prostatic specific antigen, PSA) 치를제외한평균나이, 전립선및선종의용적, IPSS 및
박현준외 : 5-α Reductase Inhibitors and PVP 163 Table 1. Preoperative characteristics of the 98 patients 5-ARI group (n=56) Control group (n=42) Age (yrs) Prostate volume (cc) TZ volume (cc) IPSS QoL PSA (ng/ml) Qmax (ml/s) PVR (ml) 68.6±6.1 42.7±12.7 22.0±9.1 24.4±4.1 4.6±0.7 1.1±3.1 11.7±6.1 33.5±35.7 66.3±8.2 36.9±16.0 17.0±13.2 24.1±3.6 4.4±0.6 2.0±2.4 11.5±7.9 48.3±71.3 0.16 0.08 0.07 0.27 0.37 0.04 0.87 0.08 5-ARI: 5-alpha reductase inhibitor, TZ: transition zone, IPSS: international prostate symptom score, QoL: quality of life, PSA: prostate-specific antigen, PVR: post void residual. Table 2. Operative end point and postoperative outcomes of the 98 patients 5-ARI group (n=56) Control group (n=42) Operative end point Hb. (g/dl) Lasing time (min) Energy (kj) Lasing time/prostate volume (min/cc) Lasing time/tz volume (min/cc) Energy/Prostate volume (kj/cc) Energy/TZ volume (kj/cc) Postoperative outcomes Qmax (ml/s) PVR (ml) IPSS QoL 0.53±0.94 38.4±23.1 183.3±102.6 0.88±0.34 1.75±0.68 4.2±1.8 9.1±3.4 +11.2±1.5 15.8±13.9 14.0±3.3 2.1±0.4 0.36±0.90 27.7±16.0 124.6±86.2 0.74±0.22 1.61±0.75 3.5±1.6 10.3±7.7 +10.9±1.4 18.2±16.3 14.2±2.6 2.0±0.3 0.02 0.02 0.009 0.02 0.03 0.07 0.39 0.53 0.27 0.33 0.17 5-ARI: 5-alpha reductase inhibitor, Hb: hemoglobin, TZ: transition zone, PVR: post void residual, IPSS: international prostate symptom score, QoL: quality of life. QoL, 최고요속및잔뇨량은차이가없었다 (Table 1). 수술후두군모두에서최고요속의증가, 잔뇨량의감소및 IPSS 와 QoL 의호전을보였다. 5-ARI 복용군과대조군의비교에서술후평가지표에서는두군사이에술후혈색소치의감소, 레이저사용시간, 소요된에너지량, 전립선및전환대의단위용적당레이저사용시간이 5-ARI 군에서유의하게증가하였으며, 그외지표에서는두군사이에차이가없었다 (Table 2). 술후역행성사정을제외한술후합병증으로는급성요폐가 5-ARI 군에서 3 예, 대조군에서 1 예가있었다. 술전 5-ARI 제제를복용한환자중 finasteride 및 dutasteride 를복용한군간에비교시술후혈색소치의변화량, 레이저사용시간, 에너지소요량등의 술중지표와술후평가지표인최고요속및잔뇨량의변화, IPSS 및 QoL 은두군에서유의한차이는없었다 (Table 3, 4). 고 최근의전립선비대증의치료로는 5-ARI 제제등의약물요법에서수술요법까지다양하게존재한다. 수술적치료로는 TURP, 광선택적전립선기화술, 개복전립선절제술, 홀뮴레이저나툴리움레이저를이용한전립선절제술등이이용되고있다. 8,9 여러종류의수술적요법중그동안표준으로제시되어왔던 TURP와광선택적전립선기화술을비교한여러연구들에서는그치료효과에서거의차 찰
164 대한남성과학회지 : 제 29 권제 2 호 2011 Table 3. Comparison of preoperative characteristics between finasteride and dutasteride group Finasteride group (n=30 ) Dutasteride group (n=26 ) Age (yrs) Prostate volume (cc) TZ volume (cc) IPSS QoL PSA (ng/ml) Qmax (ml/s) PVR (ml) 68.0±8.2 44.7±16.1 24.6±7.7 23.9±3.8 4.5±0.6 1.0±0.6 9.9±8.1 32.6±41.3 68.8±5.2 42.0±11.4 21.2±9.5 24.5±4.0 4.6±0.7 1.0±0.5 12.4±5.4 33.8±34.8 0.79 0.63 0.32 0.32 0.38 0.39 0.44 0.94 TZ: transition zone, IPSS: international prostate symptom score, QoL: quality of life, PSA: prostate-specific antigen, PVR: post void residual. Table 4. Comparison of operative end point and postoperative outcomes between finasteride and dutasteride group Finasteride group (n=30) Dutasteride group (n=26) Operative end point Hb (g/dl) Lasing time (min) Energy (kj) Lasing time/prostate volume (min/cc) Lasing time/tz volume (min/cc) Energy/Prostate volume (kj/g) Energy/TZ volume (kj/g) Postoperative outcomes Qmax (ml/s) PVR (ml) IPSS QoL 0.52±0.83 39.5±14.6 167.1±92.9 0.88±0.23 1.64±0.66 3.9±2.3 8.3±3.4 10.6±2.6 15.1±12.2 13.9±3.1 2.1±0.3 0.53±1.0 38.0±25.6 189.8±107.3 0.90±0.41 1.78±0.86 4.1±1.6 9.4±3.4 9.7±2.1 15.9±11.4 14.1±3.3 2.1±0.4 0.98 0.29 0.54 0.42 0.27 0.78 0.47 0.63 0.72 0.25 0.57 Hb: hemoglobin, TZ: transition zone, PVR: post void residual, IPSS: international prostate symptom score, QoL: quality of life. 이가없음이보고되고있다. 10 그리고수술시간, 도뇨관유치기간, 출혈등에서광선택적전립선기화술이 TURP 에비해우수하다는연구결과도보고되고있다. 10 120W Greenlight HPS 레이저를이용한광선택적전립선기화술은조직내모세혈관에분포하는혈색소에선택적으로흡수되어이로인해발생되는열에너지로주위조직을기화시키는수술이다. 또한 Park 등 11 의연구에의하면광선택적전립선기화술과 TURP 간에수술과관련된합병증을비교하였을때전립선피막천공이 TURP 에서유의하게많은것을확인할수있었는데이는 TURP 가전립선의전환대, 피막조직에관계없이절제가가능한수술이라는점에반해광선택적전립선기화술은전립선선종조직에비해상대적으로혈류가 적은피막조직은기화가잘되지않기때문으로생각된다. 이에광선택적전립선기화술은거의출혈을일으키지않고전립선피막천공확률이적은안전하고비침습적인수술적치료법으로널리보급되었다. 11-14 5-ARI 제제중대표적인약제인 finasteride는테스토스테론을디하이드로테스토스테론 (dihydrotestosterone, DHT) 으로변환되는것을막으며세포고사억제유전자인 survivin과 bcl-2의발현을감소시킨다. 감소된 DHT는인슐린유사성장인자 (insulinlike growth factor, IGF) 와상호작용하여전립선상피의증식을억제하며, 전립선상피세포의고사를통해전립선의크기를줄일수있다. 15,16 Dutasteride의경우 finasteride가 II형 5-알파환원효소만을억제하
박현준외 : 5-α Reductase Inhibitors and PVP 165 는반면 I 형과 II 형 5- 알파환원효소를모두억제하므로 17 finasteride 와비교하여 DHT 억제가더강하고지속적이며전립선용적감소율과 PSA 감소율이큰것으로보고되었다. 18 이러한과정과더불어, 5-ARI 제제는전립선요도의미세혈관밀도 (microvessel density, MVD) 및혈관형성을자극하는혈관내피성장인자 (vascular endothelial growth factor, VEGF) 의발현을감소시킨다는것이일부에서보고된바있다. 19,20 특히, Puchner 와 Miller 21 은 5-ARI 제제가 testosterone 이 DHT 로변환되는것을막아서혈관형성을관장하는남성호르몬에의해조절되는성장인자의활성이감소하고, 이로인해전립선출혈이감소하게된다고보고하였다. 반면, Hagerty 등 22 은 5-ARI 제제에의한전립선크기감소효과로전립선의대사요구량이감소하여이차적으로혈류량이감소하게된다고하였다. 또한, Canda 등 23 은쥐의전립선을사용한실험을통하여 5-ARI 제제가전립선비대증에서출혈을감소시키는효과는전립선의증식부위가위축되면서전립선의전체적인혈관분포도를감소시키기보다는혈관벽의안정성을증진시키기때문이라고하였다. 이렇듯 5-ARI 제제가전립선비대증에서출혈을감소시키는효과를일으키는기전에대해서는연구자에따라여러가지견해가있지만 5-ARI 제제를술전전립선비대증의치료제로복용하고있는환자들에서 120W Greenlight HPS 레이저를이용한광선택적전립선기화술을이용할경우조직의기화되는효율에영향을주고, 이에따른수술소요시간이증가할수있다고 Bepple 등 6 의연구에서제시하고있다. 이에저자들은본연구에서 5-ARI 제제의술전복용이 120W Greenlight HPS 레이저를이용한광선택적전립선기화술의결과에미치는영향을알아보았다. 그결과술전 5-ARI 제제를복용한환자의경우, 120W Greenlight HPS 레이저를이용한광선택적전립선기화술의시행후혈색소감소량이많고, 평균수술시간이길며, 평균에너지소요량이많은경향을보였다. 그러나 5-ARI 제제에따른차이는없었다. 술후합병증의경우역행성사정을제외하면 4 예에서발생하였고모두급성요폐였다. 이들 4 명중 3 명에서 5-ARI 제제를복용한환자였으며이는약제에의한영향이라기보다는술중생리식염수세척액의방광내주입으로발생한지속적인방광팽창으로인한방광배뇨근의허탈이나술후전립 선요도내부종으로인한것으로추측되었다. 급성요폐가생긴모든환자들은그처치로도뇨관을재삽입하였고 1 2 일후도뇨관을제거하고나서는배뇨가원활히되는것을확인하였다. Bepple 등 6 은 59 명의환자들중술전 3 개월부터 5-ARI 제제인 dutasteride 를복용한 30 명과 Placebo 를복용한 29 명을대상으로수술시지표및술후지표를비교한결과통계적으로유의하지는않았지만술중출혈량, 수술시간, 레이저사용에의한에너지량이 dutasteride 를복용하는환자군에서감소하는경향을보고하였다. 이는 5-ARI 제제를술전에복용한환자군에서평균레이저사용시간이길며, 평균에너지소요량도많다는저자들의연구결과와상반되었다. 양연구모두두군간의술중평가지표의차이가실제시술에미치는영향은크지않은수준이지만 5-ARI 제제의복용이수술에미치는영향이상반되므로이에대한보다면밀한검토와추가연구가있어야할것으로생각된다. 본연구는대상환자의수가적고추적관찰기간이짧은점이제한점이다. 또한수술시절제한전립선용적을정확히산출하지못해실제절제된전립선조직의용적당레이저사용시간이나에너지소요량을비교하지못한점도본연구의제한점이분명하다. 술전 5-ARI 제제의복용에따른수술지표의변화를더욱정확하게평가하기위해선추후보다많은환자를대상으로한추가연구가이루어져야할것으로생각된다. 결 술전 5-ARI 제제를복용한경우, 120W Greenlight TM HPS 레이저를이용한광선택적전립선기화술의시행후혈색소감소량이많고, 레이저사용시간이길어지며, 에너지소요량이많은경향을보였다. 그러나 5-ARI 제제에따른차이는없었다. 본연구에서나온결과를확인하기위해서는향후장기간의조사및대규모연구를통하여이러한경향에대한확인이필요할것으로생각된다. 론 REFERENCES 1) Yu X, Elliott SP, Wilt TJ, McBean AM. Practice patterns in benign prostatic hyperplasia surgical therapy: the dramatic increase in minimally invasive
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