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1 Korean J Gastroenterol Vol. 59 No. 2, SPECIAL REVIEW 폴립절제후추적대장내시경검사가이드라인 홍성노 1, 양동훈 2, 김영호 3, 홍성필 4, 신성재 5, 김성은 6, 이보인 7, 이석호 8, 박동일 3, 김현수 9, 양석균 2, 김효종 10, 김세형 11, 김현정 12 ; 다학회기반대장폴립진료가이드라인개발실무위원회 건국대학교의학전문대학원 1, 울산대학교의과대학 2, 성균관대학교의과대학 3, 연세대학교의과대학 4, 아주대학교의과대학 5, 이화여자대학교의학전문대학원 6, 가톨릭대학교의과대학 7, 순천향대학교의과대학 8, 연세대학교원주의과대학 9, 경희대학교의과대학 10 내과학교실, 서울대학교의과대학영상의학교실 11, 고려대학교의과대학예방의학교실 12 Korean Guidelines for Post-polypectomy Colonoscopic Surveillance Sung Noh Hong 1, Dong-Hoon Yang 2, Young-Ho Kim 3, Sung Pil Hong 4, Sung Jae Shin 5, Seong-Eun Kim 6, Bo In Lee 7, Suck-Ho Lee 8, Dong Il Park 3, Hyun-Soo Kim 9, Suk-Kyun Yang 2, Hyo Jong Kim 10, Se Hyung Kim 11, Hyun Jung Kim 12 ; Multi-Society Task Force for Development of Guidelines for Colorectal Polyp Screening, Surveillance and Management Department of Internal Medicine, Konkuk University School of Medicine 1, Seoul, University of Ulsan College of Medicine 2, Seoul, Sungkyunkwan University School of Medicine 3, Seoul, Yonsei University College of Medicine 4, Seoul, Ajou University School of Medicine 5, Suwon, Ewha Womans University School of Medicine 6, Seoul, The Catholic University of Korea College of Medicine 7, Seoul, Soonchunhyang University College of Medicine 8, Cheonan, Yonsei University, Wonju College of Medicine 9, Wonju, Kyunghee University College of Medicine 10, Seoul, Department of Radiology, Seoul National University College of Medicine 11, Seoul, Department of Preventive Medicine, Korea University College of Medicine 12, Seoul, Korea Post-polypectomy surveillance has become a major indication for colonoscopy as a result of increased use of screening colonoscopy in Korea. However, because the medical resource is limited, and the first screening colonoscopy produces the greatest effect on reducing the incidence and mortality of colorectal cancer, there is a need to increase the efficiency of postpolypectomy surveillance. In the present report, a careful analytic approach was used to address all available evidences to delineate the predictors for advanced neoplasia at surveillance colonoscopy. Based on the results of review of the evidences, we elucidated the high risk findings of the index colonoscopy as follows: 1) 3 or more adenomas, 2) any adenoma larger than 10 mm, 3) any tubulovillous or villous adenoma, 4) any adenoma with high-grade dysplasia, and 5) any serrated polyps larger than 10 mm. In patients without any high-risk findings at the index colonoscopy, surveillance colonoscopy should be performed five years after index colonoscopy. In patients with one or more high risk findings, surveillance colonoscopy should be performed three years after polypectomy. However, the surveillance interval can be shortened considering the quality of the index colonoscopy, the completeness of polyp removal, the patient s general condition, and family and medical history. This practical guideline cannot totally take the place of clinical judgments made by practitioners and should be revised and supplemented in the future as new evidence becomes available. (Korean J Gastroenterol 2012;59:99-117) Key Words: Colorectal polyp; Colonoscopy; Polypectomy; Surveillance; Guideline CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 교신저자 : 김영호, , 서울시강남구일원동 50번지, 성균관대학교의과대학삼성서울병원내과학교실소화기내과 Correspondence to: Young-Ho Kim, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul , Korea. Tel: , Fax: , younghokim@skku.edu Financial support: This study was initiated with the support of the Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, and the Korean Association for the Study of Intestinal Diseases. This study was supported by a grant from the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A ). Conflict of interest: None. 이가이드라인은원활한보급을위하여대한소화기학회지, 대한장연구학회지및 Clinical Endoscopy 에공동게재됨. These guidelines are being co-published in the Korean Journal of Gastroenterology, the Intestinal Research, and the Clinical Endoscopy for the faciliated distribution. Korean J Gastroenterol, Vol. 59 No. 2, February

2 100 홍성노등. 폴립절제후추적대장내시경검사가이드라인 서론 대장내시경을이용하여전암병변인대장폴립을제거하는것은대장암의발생과대장암관련사망을줄이는가장효과적인방법이다. 1-5 대장폴립을절제한환자는향후대장폴립과대장암이발생할위험성이증가하기때문에대장내시경을이용한추적검사 (surveillance) 가필요하다. 2,3,6-11 최근대장암선별검사로대장내시경검사가보편화되면서대장폴립의진단과절제가급격히증가하고있으며, 12,13 이에따라폴립절제후추적검사에대한수요도가파르게증가하고있다. 폴립절제후추적검사로대장암발생률과사망률감소를기대할수있지만, 선별대장내시경검사보다는예방효과가작아서, 제한된의료자원을효율적으로사용하고불필요한추적검사로인한의료비용과합병증을줄이기위해서는폴립절제후적절한간격의대장내시경추적검사전략이필요하다. 6,9,14 이러한목적으로대장폴립과대장암의발생이높은서구에서는대장폴립절제후추적검사가이드라인을제정하고새로이도출되는근거에따라개정을거듭해왔다 우리나라에서도생활습관이서구화됨에따라대장폴립의발생이서구에필적할정도로증가하였지만, 22,23 아직국내실정에적합한폴립절제후추적대장내시경검사가이드라인은없는실정으로적정한진료를위한통일된가이드라인의필요성이제기되어왔다. 이러한공감대를토대로대한소화기학회, 대한소화기내시경학회, 대한장연구학회, 대한복부영상의학회는다학회기반의대장폴립진료가이드라인개발실무위원회를구성하여현재까지국내외에서발표된연구자료들을검토하고정리하여, 임상에서대장폴립진료를담당하는의사가양질의기준대장내시경검사 (index colonoscopy) 가시행되었을경우를전제로추적검사시기를결정하는데참고할수있는근거중심의가이드라인을제시하고자한다. 하지만, 이진료가이드라인은실제임상에서의료진이환자를진료하고다양한임상적요인을고려하여결정하는추적검사에대한임상적판단을대신할수없으며, 더욱이우선시될수는없다. 폴립절제후추적대장내시경검사가이드라인은국내에서처음으로제정되는것이므로, 앞으로새로운국내외연구결과에따라수정, 보완되어야할것이다. 1. 목적이가이드라인은일선에서대장폴립진료를담당하고대장내시경검사를수행하는의료진이대장폴립환자에게양질의진료를제공하는데도움이될수있도록현재까지알려진국내외문헌을체계적으로고찰하고메타분석을통해기준대장내시경검사에서발견된폴립의특징과환자의특성에따라대장암과대장암의대리표지자 (surrogate marker) 인진행샘 종 (advanced adenoma) 의발생위험도를구분 (risk stratification) 하여추적대장내시경검사시기를제안하였다. 그러나아쉽게도국내연구는충분치않아한국인의특성과국내의료현실을반영하기위해국내전문가의의견을수렴하여동의수준을제시하였다. 2. 가이드라인의필요성대장암의발생이급격히증가하는 50세이상의성인에서는대장내시경을이용한선별검사가권장되며, 선별검사에서폴립이진단되어제거한환자는대장암발생위험이증가하므로주기적인추적검사를받도록권고하고있다. 15,16,18-20,24 국내의인구고령화는계속심해져서통계청장래인구추계결과에따르면선별대장내시경검사가필요한 50세이상인구가전체인구에서차지하는비율이 2010년 29% 에서 2020년 40%, 2050년 60% 로급격히증가할것으로예상되지만, 25 대장내시경검사를수행할수있는전문인력과시설의확충은제한적일수밖에없다. 따라서, 한정된의료자원을효율적으로사용하기위해서는대장암예방효과가큰선별검사에자원이집중될수있도록추적검사간격을합리적으로유지하는것이필요하다. 또한, 이러한노력은추적검사로인한의료비용상승과합병증발생위험을예방할수있다. 3. 대장폴립절제후추적대장내시경검사가이드라인의한계체계적인문헌검색을통해근거로사용된문헌대부분이서구의자료로국내자료는매우제한적이었다. 따라서, 국내의료환경을반영하기위해인터넷기반의설문조사를통해실제임상에서대장폴립을진료하는의료진의진료행태를파악하였고, 델파이방법을이용하여국내임상전문가들의합의도출과정을거쳤다. 또한, 근거로사용된서구의연구들도무작위대조연구 (randomized controlled trial) 보다는대부분관찰연구 (observational study) 였기에도출된권고안의근거의질 (quality of evidence) 이낮게평가되었다. 4. 가이드라인의제작진과제작과정가이드라인의제작을위해대한소화기학회, 대한소화기내시경학회, 대한장연구학회, 대한복부영상의학회에서추천한전문가와임상진료지침개발전문가로구성된다학회기반대장폴립진료가이드라인개발실무위원회를 2010년 6월발족하였다. 대장폴립진료가이드라인은선별검사, 추적검사및치료로구분하여개발되었으며, 각각의운용팀이구성되어가이드라인개발을수행하였다. 진료가이드라인개발과정에참여한모든구성원은이해상충의문제가없었다. The Korean Journal of Gastroenterology

3 Hong SN, et al. Korean Guidelines for Post-polypectomy Colonoscopic Surveillance 가이드라인의보급및실행발표된가이드라인은참여학회의학술지와홈페이지에게재하고, 주요권고안을담은요약본을작성하여무료로일선의의료진에게보급할예정이다. 본론 1. 방법 1) 정의이가이드라인에서는국내외의연구들을참고하여가장보편적으로사용되는다음의정의를사용하였다. (1) 폴립절제후추적검사 (postpolypectomy surveillance): 폴립절제당시에미처발견되지못했던폴립 (synchronous polyp) 을찾아제거하고새로이발생한폴립 (metachronous polyp) 이악성화되기전발견하여제거하기위해서대장을검사하는것으로대장암치료후재발을평가하기위한검사는제외함. (2) 진행샘종 (advanced adenoma): 샘종의크기가 1 cm 이상이거나고도이형성또는 25% 이상의융모조직을포함하는샘종. (3) 진행신생물 (advanced neoplasia): 진행샘종과샘암종을통칭함. (4) 기준대장내시경검사 (index colonoscopy): 추적대장내시경검사를시행하기전가장최근에시행된검사로대장암검진질지침에따라대한의학회회원학회중대장내시경연관전문학회에서인정하는전문의로수련병원에서지도하에일정수준이상의대장내시경검사 (supervised endoscopy) 수련을받은대장내시경의사가양호한대장정결상태에서시행한양질의대장내시경검사. 26 (5) 기준샘종 (index adenoma): 기준대장내시경검사에서발견된샘종중크기가큰샘종을기준으로하되모든샘종의크기가 1 cm 미만이면고도이형성또는 25% 이상의융모조직을포함하는샘종을기준으로삼음. 폴립절제후추적검사의효과평가를위한결과지표 (outcome measure) 로대장암발생및이로인한사망률을평가하는것이이상적이다. 하지만, 대장암을결과지표로채택할경우, 매우오랜기간동안추적해야추적검사의효과평가가가능하다는현실적인제약이있기때문에대장암의생물학적대리표지자인진행샘종을포함하는진행신생물을초기결과지표 (early outcome measure) 로삼았다. 1,21 2) 핵심질문 (key question) 의선정폴립절제후추적대장내시경검사가이드라인을도출하기위해서첫째, 폴립절제후추적검사시기를결정하는데반영 되어야할진행신생물의발생위험인자로는어떤것이있는지, 둘째, 분석된위험인자에근거하여폴립절제후진행신생물의발생고위험군을어떻게분류할수있는지, 셋째, 폴립절제후고위험군에해당하는소견이없는경우적절한추적검사시기가언제인지, 넷째, 폴립절제후진행신생물의위험이증가하는고위험군에서의적절한추적검사시기가언제인지를핵심질문으로선정하였다. 3) 문헌검색이가이드라인개발전발표된대장폴립절제후감시가이드라인은 MEDLINE, Cochrane Library 및 National Guideline Clearinghouse를이용하여 2000년이후발표된가이드라인을검색하였다. 2006년 US Multi-Society Task Force on Colorectal Cancer와 American Cancer Society (USMSTF- ACS) 의폴립절제후추적대장내시경검사가이드라인과 년 European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE II) 의대장폴립과대장암절제후감시가이드라인은 15 권고안도출을위해마련된근거표 (evidence table) 가제시되어있으며이들근거표에포함된문헌은전문을검토하였다. 체계적인문헌고찰을위해국외문헌검색은 MEDLINE 및 Cochrane Library를이용하여 2000년 1월부터 2010년 9월까지영문으로발표된임상연구 (clinical trial) 와무작위대조연구 (randomized controlled trials) 를검색하였다. 영문검색에사용한주제어는 colonoscopy AND colon OR colonic OR colorectal AND polyp OR neoplasm OR neoplasia 였다. 한글로발표된모든국내문헌에대해서는 Korean Studies Information Service System ( 및한국의학논문데이터베이스 (Korean Medical Database; 를이용하여검색하였다. 국내문헌검색에서사용한주제어는 대장내시경 AND 대장폴립 과 대장내시경 AND 대장용종 이었다. 문헌선정기준은 (1) 사용언어 : 한글또는영어, (2) 전문발간, (3) 발행연도 : 1991년부터 2010년, (4) 연구설계 (study design): 코호트연구, 무작위대조연구및분석연구 (pooled analysis), (5) 연구대상 : 한개이상의대장폴립이있는 18세이상의성인, (6) 중재 (intervention): 기준대장내시경검사와 6 개월이상의간격을두고추적대장내시경검사를시행한연구, (7) 결과 : 폴립절제후진행신생물의발생률또는발생위험요인을제시하였거나, 추적대장내시경검사시기를근거를바탕으로제안한연구로하였으며, 린치신드롬 (Lynch Syndrome, 유전성비폴립대장암 ), 가족성폴립증, 염증성장질환및대장암을절제한환자를대상으로한연구는제외하였다. 검색된문헌은국외문헌 884건, 국내문헌 391건이었다. 논문제목과초록을통해선정기준에맞지않는문헌을배제 Vol. 59 No. 2, February 2012

4 102 홍성노등. 폴립절제후추적대장내시경검사가이드라인 Fig. 1. Flow chart outlining search process used to identify articles for inclusion in systematic review and meta-analysis. 하였으며필요시논문전문을검토하였다. 국외문헌 833건, 국내 389건을배제하고, 국외 51건, 국내 3건을선택하여논문전문을자세히검토하여핵심질문에해당하는자료를추출하기위해표준화된근거표를작성하였다. 논문전문을검토하던중인용된참고문헌에서문헌선정기준에해당하는논문 1편이추가로발견되어전문을검토하여문헌선정에포함하였고, 검색기간이후이지만한국인을대상으로한대규모의전향적코호트연구가발표되어문헌선정에포함하였다 (Fig. 1). 4) 메타분석전문을검토한문헌중폴립절제후추적대장내시경검사에서진행신생물발생의위험요인에대한교정교차비 (adjusted OR), 교정상대위험도 (adjusted RR) 또는교정위험비 (adjusted hazard ratio, HR) 와 95% 신뢰구간 (95% CI) 을제시한 17개문헌을대상으로폴립절제후추적대장내시경검사시기를결정하는데반영되어야할진행신생물의발생위험인자에대한메타분석을수행하였다 (Supplementary Table 1). 통합분석 (pooled analysis) 은포함된개별연구의가공되지않은자료를제공받아개별위험인자의독립적인영향을분석한연구이므로개별연구에우선하여메타분석을위한자료를추출하였고, 이러한경우통합분석에포함된개별연구에서추출된자료는메타분석에서배제하였다. 연구설계는무작위대조연구이지만, 치료군과대조군모두를종합하여단일코호트로간주하고자료추출이시행되어무작위할당의의미가소실된경우관찰연구로평가하였다. 메타분석을위해선정된연구사이에는대상환자군, 연구설계, 추적대장내시경검사기간, 목표점의정의등에대한임상적이질성 (heterogeneity) 이존재하므로통계적모형으로는변량효과모형 (random-effects model) 을적용하였고, 효과성측정은역분산가중추정법 (inverse variance weighted estimation method) 을사용하여효과추정치 (pooled estimates) 를산출하였다. 효과추정치의결과는상대위험도는교차비보다위험도가보수적으로평가되고질병의유병률이낮은경우교차비에근접하기때문에교정교차비와교정상대위험도를제시한연구들에대해서는추정된결합교차비 (pooled estimated OR) 로결과를제시하였고, 27 사건의발생시까지의시간이관련된통계적분석인위험비로결과를제시한연구들에대해서는추정된결합위험비 (pooled estimated HR) 를제시하였다. Cochran의 Q-검정결과 p<0.1인경우통계적이질성 (statistical heterogeneity) 이존재하는것으로평가하였다. 메타분석은 Review Manager (version 5.1; Cochrane Collaboration, Oxford, UK) 을이용하여실시하였다. 5) 근거의질및권고의강도최종선정된문헌을체계적으로검토하고메타분석등을통해종합한근거를바탕으로권고안을제시하였다. 권고안이어느정도의과학적근거를가지고있는지를나타내는근거의질 (quality of evidence) 과권고안을어느정도의강도로권고할것인가를나타내는권고의강도 (strength of a recommendation) 는 Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group에서제안한방법론을따랐다 (Table 1). 28,29 근거의질은근거가무작위대조연구로구성된경우 높음 (high quality) 으로평가하였고, 근거에관찰연구가포함된경우 낮음 (low quality) 으로평가하였다. 하지만, 근거로사용된연구들에설계또는수행의제약 (limitation in study design or execution), 결과의불일치 (inconsistency of results), 중재효과비교의간접성 (indirectness of evidence), The Korean Journal of Gastroenterology

5 Hong SN, et al. Korean Guidelines for Post-polypectomy Colonoscopic Surveillance 103 Table 1. Quality of Evidence and Strength of a Recommendation Quality of evidence High quality Moderate quality Low quality Very low quality Strength of a recommendation Strong recommendation Weak recommendation Further research is very unlikely to change our confidence in the estimate of effect Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Any estimate of effect is very uncertain Most or all individuals will be best served by the recommended course of action Not all individuals will be best served by the recommended course of action. There is a need to consider more carefully than usual individual patient s circumstances, preferences, and values. 결과의부정확성 (imprecision of results), 또는출판오류 (publication bias) 가존재하는경우에는근거의질을하향조정하였다. 근거의질평가에서근거의질이하향조정되지않은관찰연구에서효과의크기가크거나 (large effect), 가능한교란변수 (plausible confounding) 에의해보고된효과가감소되었을가능성이있거나, 용량-반응관계 (dose-response gradient) 가존재하는경우에는근거의질을상향조정하였다. 권고의강도는바람직한효과와바람직하지못한효과의균형 (balance of desirable and undesirable consequences), 근거의질, 가치와선호에대한확신 (confidence in values and references), 의료비용및자원의효과적인배분을고려하여 강력히권고함 (strong recommendation) 으로또는 권고함 (Weak recommendation) 으로평가하였다. 즉, 대부분의환자에게권고를따랐을때중요한건강상의이득또는손실이있음이확실하다고판단되는경우 강력히권고함 으로하였고, 권고를따랐을때중요한건강상의이득또는손실이있을것으로판단되나환자에따라차이가존재하여환자개개인의환경과선호, 가치에대한고려가필요한경우 권고함 으로하였다. 2. 폴립절제후추적대장내시경검사가이드라인폴립절제후추적대장내시경검사가이드라인은기준내시경검사에서발견된폴립의특징과환자의특성중폴립절제후추적검사시기를결정하는데반영되어야할진행신생물발생위험요인들을결정하고, 이들위험요인에근거한진행신생물발생위험정도에따라적절한폴립절제후추적대장내시경검사시기를제시하였다. 1) 폴립절제후추적검사시기결정에반영되어야할위험인자 (1) 기준대장내시경검사에서제거된샘종의개수에따라추적검사에서진행신생물이발견될위험이증가하는가? 기준대장내시경검사에서 3개이상의샘종을제거한환자는추적대장내시경검사에서진행신생물이발견될위험이증 가한다. 근거의질 : 높음 (high quality) 동의수준 : 전적으로동의함 (74%), 대체로동의함 (24%), 일부동의함 (3%), 대체로동의하지않음 (0%), 전적으로동의하지않음 (0%) 기준대장내시경검사에서발견된샘종의개수에따라추적검사에서진행신생물발생위험을평가한연구는한개의통합분석과 30 2개의국내연구를포함한 9개의관찰연구가있었다 (Supplementary Table 2). 9,10,30-36 연구사이에통계적이질성이존재하였지만, 샘종의개수가증가할수록진행신생물이발생할위험은통합교차비 1.93 (95% CI, ) 과통합위험비 2.20 (95% CI, ) 으로증가하였다 (Fig , 2.2.1). 부집단분석 (subgroup analysis) 에서샘종이한개진단된환자에비해 2개이상진단된환자의통합교차비는 2.18 (95% CI, ) 로통계학적유의성을보이지못한반면 (Fig ), 32,33 3개이상의샘종이진단된환자에서폴립절제후진행신생물이발생할위험은통합교차비 2.84 (95% CI, ) 와통합위험비 2.20 (95% CI, ) 으로의미있게증가하였다 (Fig , 2.2.2). 국내에서시행된전향적코호트연구에서도 3개이상의샘종이진단된환자는진행신생물의발생위험이 1개또는 2개의샘종이발견된환자에비해위험비 3.06 (95% CI, ) 으로메타분석의결과와유사한결과를보였다. 36 북미에서시행된 8개의대규모무작위대조연구및전향적코호트연구를대상으로한통합분석에서도기준대장내시경검사에서발견된샘종의개수는환자의나이와더불어진행신생물의발생위험을예측할수있는가장강력한위험인자로, 샘종의개수가증가함에따라진행신생물의발생위험은비례하여증가하는용량-반응관계를보였고 (P trend<0.0001), 기준대장내시경검사에서진단된샘종이 5개이상이면진행신생물발생위험의교차비는 3.87 (95% CI, ) 까지증가하였다. 30 또한, 3년후추적대장내시경검사를시행한 4개의무작위대조연구를분석한메타분석에서도기준내시경에서 3개이 Vol. 59 No. 2, February 2012

6 104 홍성노등. 폴립절제후추적대장내시경검사가이드라인 Fig. 2. Forest plot for the number of colorectal adenomas as a risk factor for advanced neoplasia. SE, standard error; IV, inverse variance; df, degrees of freedom; HR, hazard ratio. 상의샘종이발견된경우 1-2개의샘종이발견된경우에비해 3년후진행신생물재발위험의통합상대위험도는 2.52 (95% CI, ) 로이번분석결과와유사하였다. 37 한편, 기준대장내시경검사에서발견되는폴립의개수가증가할수록폴립간과율 (polyp miss rate) 이의미있게증가하는것이여러국내외연구에서보고되고있다 Kim 등 41 은 The Korean Journal of Gastroenterology

7 Hong SN, et al. Korean Guidelines for Post-polypectomy Colonoscopic Surveillance 105 Fig. 3. Forest plot for the size of colorectal adenomas as a risk factor for advanced neoplasia. SE, standard error; IV, inverse variance; df, degrees of freedom; HR, hazard ratio. 5개이상의폴립이발견된경우에는폴립을간과할위험이교차비 4.48 (95% CI, ) 로의미있게증가한다고보고하였다. 하지만, 간과된폴립대부분은비진행샘종 (non-advanced adenoma) 이거나비종양성폴립 (non-neoplastic polyp) 으로 39,42-45 양질의대장내시경검사가시행되었다면간과되는대부분의폴립이악성화되기에는오랜시간이필요하다 이러한요인등을반영하여기존의각국의가이드라인에서는 3개이상의샘종이기준대장내시경검사에서발견된경우 3년후추적검사를시행할것을권고하고있다. 또한, 다수의샘종이발견된경우에는일부가이드라인에서는조기에추적검사를시작할것을권고하여 British Society of Gastroenterology (BSG)-Association of Coloproctology for Great Britain and Ireland (ACPGBI) 는 5개이상의샘종또는 1 cm 이상의샘종이있으면서 3개이상의샘종이발견된경우고위험군으로 1년후추적검사를시행할것을권고하고있고, 17 USMSTF-ACS는 10개이상의샘종이발견된경우 3년이내에추적검사를시행하고가족성폴립증의가능성도고려 Vol. 59 No. 2, February 2012

8 106 홍성노등. 폴립절제후추적대장내시경검사가이드라인 할것을권고하고있다. 21 (2) 기준대장내시경검사에서제거된샘종의크기에따라추적검사에서진행신생물이발견될위험이증가하는가? 기준대장내시경검사에서 1 cm 이상크기의샘종을제거한환자는추적대장내시경검사에서진행신생물이발견될위험이증가한다. 근거의질 : 보통 (moderate quality) 동의수준 : 전적으로동의함 (59%), 대체로동의함 (35%), 일부동의함 (5%), 대체로동의하지않음 (0%), 전적으로동의하지않음 (0%) 기준샘종의크기에따라폴립절제후진행신생물의발생위험을평가한연구는 1개의통합분석과 30 1개의국내연구가포함된 8개의관찰연구가있었다 (Supplementary Table 3). 9,10,31,32,34-36,49 대부분의연구는생검겸자등을이용하여대장내시경검사도중평가된크기를기준으로하였다. 6,31,49-53 연구사이에통계적이질성이존재하였지만, 기준샘종의크기가증가하면진행신생물의발생위험에대한통합교차비는 1.78 (95% CI, ) 로증가하였다 (Fig ). 부집단분석에서기준샘종의크기가 5-10 mm인경우는 5 mm 이하인경우보다진행신생물의발생위험이의미있게증가하지않았지만 ( 통합교차비, 1.17; 95% CI, ; Fig ), 9,30 기준샘종의크기가 10 mm 이상이면 10 mm 이하인경우에비해통합교차비 1.59 (95% CI, ) 와통합위험비 2.04 (95% CI, ) 로진행신생물의발생위험이의미있게증가하였다 (Fig , 3.2.1). 이러한결과는국내에서시행된전향적코호트연구에서도유사한결과를보여 10 mm 이상의샘종이진단된환자에서진행신생물이발생할위험비는 3.02 (95% CI, ) 였다. 36 또한, Martínez 등 30 의통합분석에서는폴립절제후진행신생물의발생위험은샘종의크기가증가할수록비례하여증가하는용량-반응관계를보이기도하였다 (P trend<0.0001). 샘종은크기가클수록많은융모조직을포함하고진행된조직형을보일가능성이커져 20 mm 이상의폴립은악성화된부위가포함된경우가많게는 32% 까지보고되고있다. 54,55 따라서, 크기가큰목없는폴립을제거할때병리학적인완전절제여부의평가는중요하다. 하지만, 일반적으로 20 mm 이상의목없는폴립은전통적인올가미폴립절제술로한번에제거하기어려워분할절제 (piecemeal resection) 로제거되는경우가많다. 56,57 점막하박리술 (endoscopic submucosal dissection) 을이용하면큰목없는폴립도일괄절제가가능하지만, 숙련된기술이필요하고천공과같은심각한합병증이 % 로높게보고되고있어, 실제임상에서는분할 Fig. 4. Forest plot for villous/tubulovillous adenomas as a risk factor for advanced neoplasia. SE, standard error; IV, inverse variance; df, degrees of freedom; HR, hazard ratio; TA, tubular adenoma; TVA, tubulovillous adenoma; VA, villous adenoma. The Korean Journal of Gastroenterology

9 Hong SN, et al. Korean Guidelines for Post-polypectomy Colonoscopic Surveillance 107 절제가광범위하게시행되고있다. 56,57 하지만, 분할절제를시행한경우에는병리학적으로완전절제여부를평가하는것이불가능하며, 폴립을절제한부위에서국소재발이 12-55% 로높게보고된다. 55,58-61 이러한요인등을반영하여기존의가이드라인에서는큰목없는폴립을분할절제로제거한경우 2-6개월후추적대장내시경검사로폴립절제부위에종양조직이남아있는지를확인할것을권고하고있다 ,21 (3) 기준대장내시경검사에서관융모또는융모샘종을제거한환자는관샘종만을제거한환자에비해추적대장내시경검사에서진행신생물이발견될위험이증가하는가? 기준대장내시경검사에서관융모또는융모샘종을제거한환자는추적대장내시경검사에서진행신생물이발견될위험이증가한다. 근거의질 : 낮음 (low quality) 동의수준 : 전적으로동의함 (26%), 대체로동의함 (53%), 일부동의함 (16%), 대체로동의하지않음 (5%), 전적으로동의하지않음 (0%) 관융모혹은융모샘종절제후진행신생물발생위험을평가한연구는 1개의통합분석과 30 1개의국내연구가포함된 7개의관찰연구가있었다 (Supplementary Table 4). 9,10,31,34,36,49,62 대부분의연구에서기준샘종의융모조직이 20-25% 를초과하는경우를관융모또는융모샘종으로정의하였다. 이연구들을대상으로메타분석을시행한결과관융모또는융모샘종이발견된환자는추적대장내시경검사에서진행신생물의발생위 험이관샘종만발견된환자에비해통합교차비 1.51 (95% CI, ), 통합위험비 1.83 (95% CI, ) 로의미있게증가하였다 (Fig. 4). 국내의전향적코호트연구에서는기준샘종에융모샘종조직이존재하여도진행샘종의발생위험이증가하지는않았지만 ( 위험비, 1.48; 95% CI, ), 36 Yang 등 63 은구불창자내시경검사 (sigmoidoscopy) 를이용하여지역사회기반선별검사 (population based screening program) 를실시하여샘종을제거한후 16년동안추적관찰결과기준샘종이관융모또는융모샘종인경우진행신생물의발생위험이유의하게증가하여 ( 교차비, 8.1; 95% CI, ) 고도이형성과함께관융모또는융모샘종을폴립절제후진행신행물발생위험을예측하는가장중요한인자로제시하였다. 한편, Bertario 등 10 과 Martínez 등 51 은관융모샘종과융모샘종을구분하여관샘종과비교하여평가하였으나진행신생물발생위험에는차이가없었다. (4) 기준대장내시경검사에서고도이형성을동반한샘종이제거된환자는저도이형성을동반한샘종만을제거한환자에비해추적대장내시경검사에서진행신생물이발견될위험이증가하는가? 기준대장내시경검사에서고도이형성을동반한샘종을제거한환자는추적대장내시경검사에서진행신생물이발견될위험이증가한다. 근거의질 : 낮음 (low quality) Fig. 5. Forest plot for adenomas with high grade dysplasia as a risk factor for advanced neoplasia. SE, standard error; IV, inverse variance; df, degrees of freedom; HR, hazard ratio; LGD, low grade dysplasia; HGD, High grade dysplasia. Vol. 59 No. 2, February 2012

10 108 홍성노등. 폴립절제후추적대장내시경검사가이드라인 Fig. 6. Forest plot of the large ( 10 mm) serrated polyps at index colonoscopy as a risk factor for advanced neoplasia. SE, standard error; IV, inverse variance; df, degrees of freedom. 동의수준 : 전적으로동의함 (34%), 대체로동의함 (55%), 일부동의함 (11%), 대체로동의하지않음 (0%), 전적으로동의하지않음 (0%) 1992년 Atkin 등 11 이경성구불창자내시경검사를통해제거한샘종의이형성정도가심할수록결장암및직장암의위험이증가한다는사실을보고한이후, 1개의통합분석과 4개의관찰연구에서 9,10,35,49 기준대장내시경검사에서고도이형성동반샘종여부와추적대장내시경검사에서진행신생물의발생위험과의관련성이보고되었다 (Supplementary Table 5). 이연구들을대상으로메타분석을시행한결과기준대장내시경에서저도이형성을동반한경우에비해고도이형성을동반한경우추적대장내시경검사에서진행신생물의발생위험은통합교차비 1.33 (95% CI, ) 으로증가추세가관찰되었고 (Fig ), 통합위험비 1.69 (95% CI, ) 로의미있게증가하였다 (Fig ). Martínez 등 51 의통합분석에서는기준샘종이고도이형성이면저도이형성인경우보다진행신생물의발생위험이증가하지않는다고 ( 통합교차비, 1.05; 95% CI, ) 하였지만, Saini 등 37 의메타분석에서는샘종의개수와더불어고도이형성만이기준대장내시경검사 3년후에시행한추적대장내시경검사에서진행샘종의발생위험증가를예측할수있는의미있는위험인자였다 ( 통합상대위험도, 1.84; 95% CI, ). (5) 기준대장내시경검사에서톱니모양폴립 (serrated polyp) 이발견된환자는추적대장내시경검사에서진행신생물의발생위험이증가하는가? 기준대장내시경검사에서 10 mm 이상의톱니모양폴립이발견된환자는추적대장내시경검사에서진행신생물의발생위험이증가한다. 근거의질 : 매우낮음 (very low quality) 동의수준 : 전적으로동의함 (3%), 대체로동의함 (61%), 일부동의함 (34%), 대체로동의하지않음 (3%), 전적으로동의하지않음 (0%) 최근에는증식폴립을포함하여목없는톱니샘종 (sessile serrated adenoma), 전통톱니샘종 (traditional serrated adenoma), 증식폴립과샘종의혼합폴립 (mixed adenomatous and hyperplastic polyp) 등병리학적으로톱니모양의구조 (serrated architecture) 를가지는경우톱니모양폴립으로분류한다. 64 톱니모양폴립의임상적인중요성은기존의샘종암종연쇄 (adenoma-carcinoma sequence) 와는다른톱니모양경로 (serrated pathway) 를통해대장암으로진행한다는것이분자생물학적인연구를통해증명되었다. 65 톱니모양경로를통해발생하는대장암은우측결장에잘발생하며, BRAF 돌연변이가많고현미위성체불안정 (microsatellite instability, MSI-high) 과 CpG island methylator phenotype과연관된대장암이많아비교적빠르게악성화가진행될수있을것으로생각되며, 이러한임상적특징은대장내시경검사로예방에실패한중간암 (interval cancer) 의임상적특성과도유사하여많은주목을받고있다. 66,67 체계적인문헌고찰을위해 MEDLINE 및 Cochrane Library 에서 2000년 1월부터 2010년 12월까지 serrated AND polyp OR adenoma 를주제어로발표된임상연구와무작위대조연구를검색하였으며, 검색된 52편의문헌에서기준대장내시경검사에서톱니모양폴립이발견된환자에서진행신생물의발생위험을평가한연구를검토하였다. 10 mm 이상의톱니모양폴립이발견된경우진행신생물위험을평가한 3개의관찰연구가있었으며 (Supplementary Table 6), 이들연구결과를메타분석한결과통합교차비는 1.98 (95% CI, ) 로 10 mm 이상의톱니모양폴립이발견된경우는진행신생물의발생위험이증가하였다 (Fig. 6). 기존에는화학예방 (chemoprevention) 의효과를규명하기위한 2개의무작위연구를통합분석한결과에서증식폴립을제거한후 3년후시행한추적대장내시경검사에서전체샘종의발생이증가하지않았음을근거로 71 증식폴립만진단된환자에서대장종양의발생위험은폴립이진단되지않은평균위험군과동일하게간주하였다. 15,17,21 하지만, Schreiner 등 69 은 Veteran s Affairs Cooperative Study Group 380의자료를재분석하여우측결장에서이형성을동반하지않은폴립, 즉 The Korean Journal of Gastroenterology

11 Hong SN, et al. Korean Guidelines for Post-polypectomy Colonoscopic Surveillance 109 증식폴립또는목없는톱니샘종이발견된경우동시성진행샘종이존재할위험 ( 교차비, 1.90; 95% CI, ) 과추적대장내시경검사에서샘종이발생할위험 ( 교차비, 3.14; 95% CI, ) 이모두증가함을보고하였다. 또한, Lu 등 72 은과거에증식폴립으로진단되었던환자의조직소견을재검토하였을때 5.8% 는목없는톱니샘종이었으며, 이환자들을추적한결과 12.5% 에서대장암이발생하여증식폴립이나샘종을가진환자의 1.8% 에서대장암이발생하는것에비하여유의하게높은대장암의발생률을보고하였다. 한국인을대상으로한연구에서는 Lim 등 73 이 6 mm 이상의증식폴립이발견된경우진행샘종의위험이증가한다고 ( 교차비, 4.75; 95% CI, ) 보고했다. 이러한근거를종합하면기준대장내시경검사에서 5 mm 이하의증식폴립이좌측결장에국한되어발견된경우는추적검사에서진행신생물의발생위험이증가하지않으나, 기준대장내시경검사에서 10 mm 이상의톱니모양폴립이발견된환자는추적대장내시경검사에서 진행신생물의발생위험이증가한다. (6) 기준대장내시경검사에서진단된샘종의위치에따른진행신생물발생위험샘종의분포에따라추적대장내시경검사에서진행신생물의발생위험을평가한연구는비교적최근에많이이루어졌으며 1개의통합분석과 30 3개의관찰연구가있었다 (Supplementary Table 7). 34,35,51 모든연구에서우측결장은맹장에서횡행결장혹은비만곡부까지로정의하였고, 30,35,49,51 이연구들을대상으로시행한메타분석에서샘종이좌측결장에국한하여존재했던경우에비해우측결장에서발견되었던경우는추적대장내시경검사에서진행신생물이발견될위험의통합교차비가 1.73 (95% CI, ) 으로증가하였다 (Fig. 7). 폴립예방연구의전향적자료를바탕으로연구한결과에서도우측결장의진행샘종간과율및재발률이높게나왔다. 74 우측결장에발생하는대장암은톱니모양경로를통해발생할수도있고, 75,76 굴곡이심하고결장팽대가뚜렷한우측결장 Fig. 7. Forest plot for the location of index polyps as a risk factor for advanced neoplasia. SE, standard error; IV, inverse variance; df, degrees of freedom. Fig. 8. Forest plot for the gender as a risk factor for advanced neoplasia. SE, standard error; IV, inverse variance; df, degrees of freedom; HR, hazard ratio. Vol. 59 No. 2, February 2012

12 110 홍성노등. 폴립절제후추적대장내시경검사가이드라인 Fig. 9. Forest plot for the family history of colorectal cancers as a risk factor for advanced neoplasia. SE, standard error; IV, inverse variance; df, degrees of freedom; HR, hazard ratio; FHx, family history. 의해부학적특성으로대장내시경검사에서종양을간과할위험이높아대장내시경검사를이용한우측결장암의예방효과는상대적으로낮다 하지만, 우측결장의종양은연령과성별같은환자의특징과다양한환경적요인에많은영향을받으며, 국내에서샘종을진단받는환자의 2/3 가량에서우측결장샘종이진단될정도로흔하다. 85 델파이미팅에서도기준대장내시경검사에서우측결장샘종이진행신생물의위험요인이라는데에대한동의수준은높지않았다. 따라서, 아직우측결장샘종이진행신생물의위험요인이라고결론내리기는조심스러우며추가적인연구가진행되어야할것으로생각된다. (7) 환자의나이, 성별, 대장암가족력, 흡연력과비만정도에따른진행샘종발생위험대장폴립을제거한환자의나이에따라진행신생물의발생위험을평가한연구는 1개의통합분석과 30 6개의관찰연구가있었다. 9,10,31,35,81,86 하지만, 이들연구에서나이의기준과분류가각기달라근거를종합하기어려워권고를도출할수없었다 (Supplementary Table 8). 한편, Martínez 등 30 은통합분석에서나이가증가할수록진행신생물의발생위험이증가한다고하였으나, 국내의전향적연구에서는 50-59세의환자군에비해 60-69세의환자군에서진행신생물의발생위험은크지않았다 ( 위험비, 1.51; 95% CI, ). 36 성별과진행신생물의발생위험성에대해서는다양한연구가있다 (Supplementary Table 9). 9,30,31,34,36,86 Martínez 등 30 은통합분석에서남자에서진행신생물의발생위험이증가하였지만, 국내의전향적코호트연구에서는성별에따라진행신생물의발생위험은차이를보이지않는등 36 연구와분석방법에따라일치되지않는결과를보여, 성별에따라폴립절 제후추적검사시기를다르게제시할수있는근거는부족하다 (Fig. 8). 국내의전향적코호트연구에서는성별에따라진행신생물의발생위험은차이를보이지않았다 ( 교정위험비, 1.00; 95% CI, ). 36 대장암의가족력은일부연구에서는진행신생물의위험증가와연관이있었지만, 32 대부분의연구에서는연관이없었다고보고하였다 (Supplementary Table 10). 10,30,36,86 이들연구의메타분석에서도통합교차비 1.20 (95% CI, ) 으로증가하는추세는보였지만통계학적의미는없었고 (Fig. 9), 국내의전향적코호트연구에서는대장암가족력에따라진행신생물의발생위험은차이를보이지않았다 ( 교정위험비, 1.14; 95% CI, ). 36 최근대장암의위험요인으로인정되는흡연과비만이추적대장내시경검사에서진행신생물의발생위험에어떠한영향을미치는지를평가한연구는많지않았다. 하지만, Martínez 등 30 의통합분석과국내의전향적코호트연구 36 에서흡연력 (Supplementary Table 11) 과체질량지수 (Supplementary Table 12) 로평가한비만정도에따라진행신생물의발생위험은증가하지않았다. 2) 폴립절제후추적검사에서진행신생물발생고위험군폴립을제거한환자는대장샘종과진행신생물의발생위험이폴립이없는환자에비해증가함은잘알려져있다. 2,3,6-11 폴립을제거한환자중에서진행신생물의발생위험이높은경우를구분하는것은효과적인추적검사전략을수립하고추적검사순응도를향상시키는데효과적이다. 15,21 체계적인문헌검색과메타분석결과추적검사에서진행신생물의발생위험을증가시키는소견으로는기준대장내시경검사에서샘종의개수가 3개이상, 가장큰샘종의크기가 10 The Korean Journal of Gastroenterology

13 Hong SN, et al. Korean Guidelines for Post-polypectomy Colonoscopic Surveillance 111 Table 2. Patients with a High Risk of Subsequent Advanced Neoplasia at Post-polypectomy Surveillance Colonoscopy Index colonoscopy findings related to an increased risk of subsequent neoplasia, any of the followings 1. Three or more adenomas 2. Any adenoma(s) larger than 10 mm 3. Any tubulovillous or villous adenoma(s) 4. Any adenoma(s) with high-grade dysplasia 5. Any serrated polyp(s) larger than 10 mm mm 이상, 관융모또는융모샘종, 고도이형성을동반한샘종, 또는크기 10 mm 이상의톱니모양폴립이진단된경우였다. 따라서, 이다섯가지항목중어느한가지라도해당하는경우폴립절제후추적대장내시경검사를시행하였을때진행신생물의발생위험이증가하는고위험군으로분류할수있을것이다 (Table 2). 3) 폴립절제후추적검사시기 (1) 폴립절제후진행신생물발생의고위험소견이없는경우적절한추적대장내시경검사시기는언제인가? 일정한자격을갖춘대장내시경의사가양호한대장정결 상태에서양질의기준대장내시경검사를시행하였음을전제 로기준대장내시경검사소견이폴립절제후진행신생물발생 의고위험군에해당되지않는경우, 추적대장내시경검사를 폴립절제후 5 년에시행할것을권고한다. 그러나, 상기의전 제조건이만족되지않거나기준대장내시경검사이전의대장 내시경검사에서고위험군에해당하는소견을보였던경우에 는기준대장내시경소견이고위험군에해당되지않더라도추 적검사기간을단축할것을권고한다. 근거의질 : 낮음 (low quality) 동의수준 : 전적으로동의함 (23%), 대체로동의함 (41%), 일부동의함 (31%), 대체로동의하지않음 (5%), 전적으로동의하지않음 (0%) 권고수준 : 권고함 (weak recommendation) 폴립절제후적절한추적검사시기에대한근거가없던 1990년대이전에는서구에서도 1년마다폴립절제후추적대장내시경검사를시행하는것이일반적이었다. 1993년발표된 National Polyp Study는미국내 7개기관이참여한무작위대조군연구로 1,418명의폴립절제를시행받은환자들을대상으로폴립절제후 1년째및 3년째추적검사를시행받는군과 3년째한차례추적검사를시행받는군으로나누었을때, 두군모두에서 3.3% 라는낮은진행샘종발생률을보여이를토대로폴립절제후적절한추적검사시기를 3년으로제시한바있다. 6 그결과 1993년이후수행된대부분의폴립예방임상연구는추적검사간격을 3년또는 4년으로설계하였다. 1992년 Atkin 등 11 은경성구불창자내시경검사를받은 1,618 명의환자들을대상으로평균 13.8년동안추적관찰한결과 10 mm 미만크기의관샘종을제거한경우는그개수와무관하게일반인구와비교하여대장암발생위험이증가하지않는다고보고하였다. 1995년에발표된 Funen Adenoma Follow-up Study에서는폴립절제후추적검사시기를 2년및 4년후두차례시행받는군과 4년후한차례시행받는군으로무작위로나누어진행신생물의누적발생률을평가한결과각각 5.2% ( %) 와 8.6% ( %) 로의미있는차이를보이지않았다. 9 이를근거로폴립을절제하였지만향후진행신생물의위험이상대적으로낮을것으로보이는 1-2개의 10 mm 미만의관샘종의경우, 추적검사시기를 3년이후로좀더연장해도될것으로생각하게되었다. 2007년 Lieberman 등 52 은 1-2개의 10 mm 미만의관샘종을제거한후추적대장내시경검사간격에대한무작위대조연구결과를발표했는데, 이연구에서는 10 mm 미만의관샘종을제거했던환자를기준대장내시경검사 2년후및 5년후에두차례검사를시행하는군 (n=300) 과 5년후에한차례만추적검사를시행하는군 (n=294) 에서진행신생물누적발생률은각각 4.9%, 6.4% 로의미있는차이가없었다 (p=0.55). 또한, 최근발표된국내의전향적코호트연구에서기준대장내시경검사에서샘종이발견되지않은정상군 (n=1,242) 과 1-2 개의 1 cm 미만의관샘종만발견된환자군 (n=671) 에서진행샘종의 5년누적발생률은각각 2.4% 와 2.0% 로차이가없었다 ( 교정위험비, 1.14; 95% CI, ). 36 한편, 서론에서언급한것처럼기준대장내시경검사를추적대장내시경검사시행전가장최근의검사로정의할경우, 실제임상에서는기준대장내시경검사전시점에이미 1회이상대장내시경검사를시행받은경험이있는환자, 즉추적대장내시경검사시행전이미 2회이상대장내시경검사를시행받은환자를종종경험하게되는데기존대부분의연구에서는추적대장내시경검사바로전대장내시경검사의소견에대한분석만이시행되었다. 최근 Robertson 등 87 은아스피린및엽산을통한폴립예방연구참여자를대상으로시행된 3번의연속적인대장내시경검사결과를분석하여발표하였는데, 흥미롭게도이연구에서는첫번째대장내시경검사에서진행샘종또는 3개이상의샘종이진단된경우에는두번째대장내시경검사가정상혹은 1-2개의비진행샘종만진단되었더라도각각평균 44개월및 51개월후에시행한세번째대장내시경검사에서고위험소견을보일확률이각각 12.3%, 13.6% 로상당히높았다. 또한, 첫번째대장내시경검사에서저위험샘종만진단된경우라도두번째대장내시경검사에서고위험샘종이진단된경우에는세번째대장내시경검사에서고위험샘종이진단될확률이 20% 에달했다. 87 한편, 비슷한시기에 Laiyemo 등 86 은폴립예방연구참여자들을대상으로시행한추적연구 Vol. 59 No. 2, February 2012

14 112 홍성노등. 폴립절제후추적대장내시경검사가이드라인 에서첫번째대장내시경검사에서저위험샘종만진단되고두번째대장내시경검사에서고위험샘종이진단된경우두번째검사로부터평균 4.7년경과후시행한세번째대장내시경검사에서진행샘종이발견될확률을 13.8% 로보고하였고, 첫번째검사에서고위험샘종이진단되고두번째검사에서저위험샘종이진단된경우평균 4.8년후시행한세번째검사에서진행샘종발견확률이 11.9% 로 Robertson 등의연구결과와유사하였다. 반면, 첫번째대장내시경검사에서고위험샘종이진단되고두번째대장내시경검사가정상이면평균 4.7 년후시행한세번째검사에서진행샘종발견확률이 6.8% 로 Robertson 등의연구에비해낮았다. 86 이러한연구결과는추적대장내시경검사시행바로전의대장내시경검사결과뿐만아니라그이전의대장내시경검사결과역시추적검사시기결정에고려해야함을시사하나, 아직적절한세번째대장내시경검사의시기를제시할만한연구결과가부족하다. (2) 폴립절제후진행신생물발생위험이증가하는고위험군의적절한추적대장내시경검사시기는언제인가? 일정한자격을갖춘대장내시경의사가양호한대장정결상태에서양질의기준대장내시경검사를시행하였음을전제로기준대장내시경검사소견이폴립절제후진행신생물발생의고위험군에해당하는경우는추적대장내시경검사를폴립절제후 3년에시행할것을권고한다. 그러나, 상기의전제조건이만족되지않거나기준대장내시경검사소견, 샘종의절제상태, 환자의전신상태, 가족력및과거력등을고려하여추적검사기간을단축할수있다. 근거의질 : 낮음 (low quality) 권고의강도 : 권고함 (weak recommendation) 동의수준 : 전적으로동의함 (21%), 대체로동의함 (44%), 일부동의함 (23%), 대체로동의하지않음 (10%), 전적으로동의하지않음 (3%) 진행신생물발생위험인자와관련한양질의연구대부분은폴립예방임상연구의참여자로구성된코호트를대상으로수행한후속연구들이다. 이들연구는 National Polyp Study 후진행되었으며기준대장내시경검사시행후 3년후추적검사를진행하였다. 10,30-32,34-36,49,51,88 이들연구에서 3년후시행한추적검사에서진행샘종의위험은고위험군에서증가하였지만, 실제대장암의발생은드물었기때문에이를근거로고위험군의적절한추적검사시기를 3년으로제시할수있을것으로생각된다. 그러나, National Polyp Study 및그외의임상연구에참여한환자들은대장내시경전문가로부터양질의대장내시경검사를받았거나, 연구포함전폴립의완전절제를확인하고간과된폴립을제거하기위해추가적인대장내시경검사 (clearing colonoscopy) 를받은경우가많았으며, 상당수의연구는대장암가족력이있는환자를연구대상에서제 외하였다는점을고려할때, 실제임상에서추적검사시기를정함에기준대장내시경검사에서관찰되었던샘종의개수나크기, 조직학적특징, 분포외에도대장내시경검사의질과대장암가족력및병력에대한자세한정보를참고할것을덧붙여권고하는바이다. 한편, 폴립절제후추적대장내시경검사에서진행신생물이발견될위험이증가하는고위험군에해당하는소견중두가지이상의중복된소견이있을경우진행신생물발생위험이가중되는지에대한연구는많지않은데, 1992년경성구불창자내시경검사를이용한 Atkin 등 11 의연구에따르면, 초기검사에서융모 / 관융모샘종또는 10 mm 이상크기의샘종이있었던고위험군내에서샘종이 1개였던군의대장암표준화발생비 (standardized incidence ratio) 가 2.9 (95% CI, ) 인데비해샘종이 2개이상이었던군은대장암표준화발생비가 6.6 (95% CI, ) 으로증가하였다. 2000년 Noshirwani 등 31 이기준대장내시경검사에서 10 mm 미만크기의샘종이 3개있었던경우 42개월후시행한추적검사에서진행샘종이발생할확률이 8.5% 로추정되는데비해샘종이 3개이상이면서그중가장큰샘종이 10 mm 이상이었던경우에는 21.3% 로증가하였다. 또한, 10 mm 미만크기의샘종이 4개이상있었던경우추적검사시진행샘종발생확률이 15.3% 로추정되지만, 샘종이 4개이상이면서그중가장큰샘종이 10 mm 이상이었던경우에는진행샘종발생확률이 34.5% 까지증가한다고제시한바있다. 이러한결과는고위험군에해당하는소견이중복될경우진행샘종발생위험이가중됨을시사한다. 이에근거하여고위험군에해당하는소견이두가지이상이면추적검사시기를앞당겨야할개연성이있으나, 아직관련연구가부족하여명확한추적검사시기를제시하기에는어려움이있다. 고찰 폴립을제거한환자는대장암과샘종의발생위험이폴립이없는환자에비해증가하기때문에주기적인추적검사가필요하다. 2,3,6-11 이렇게폴립을제거한환자중에서도추적검사에서진행신생물발생위험이증가하는경우는기준대장내시경검사에서 (1) 샘종의개수가 3개이상, (2) 샘종의크기가 10 mm 이상, (3) 관융모또는융모샘종, (4) 고도이형성을동반한샘종, (5) 10 mm 이상크기의톱니모양폴립이진단된경우로, 이중한가지라도해당하는경우폴립절제후추적대장내시경검사를하였을때진행신생물발생위험이증가하는고위험군으로분류하도록제안한다. 본위원회에서는문헌고찰을토대로, 한국의대장폴립환자에대한폴립절제후추적대장내시경검사의추적시기를기 The Korean Journal of Gastroenterology

15 Hong SN, et al. Korean Guidelines for Post-polypectomy Colonoscopic Surveillance 113 Table 3. Prerequisite to Determine the Surveillance Colonoscopy Interval Based on the Guideline 1. The index colonoscopy should reach the cecal base with adequate bowel preparation. If the cecal intubation failed or if bowel preparation was inadequate during the index colonoscopy, significant colorectal lesions may be missed, and a repeat colonoscopy is recommended. 2. Because the quality of the index colonoscopy may vary significantly among endoscopists, screening and surveillance colonoscopies should only be conducted by qualified endoscopists. 3. If any polyps, especially adenomas with high-grade dysplasia, may have been incompletely removed, the completeness of the resection should be confirmed by a repeat colonoscopy. 4. The surveillance interval proposed in this guideline is applicable to asymptomatic adults. The necessity of a diagnostic colonoscopy in any symptomatic patients should be assessed by a physician, regardless of the recommended surveillance interval. 준대장내시경소견에근거하여고위험군은폴립절제후 3년에시행할것을제안하고, 고위험군에해당하는소견이없는경우에는추적대장내시경검사를폴립절제후 5년에시행할것을제안한다. 그러나, 추적대장내시경검사시기를정하기에앞서다음의사항은반드시고려되어야한다 (Table 3). 우선기준대장내시경검사는양호한대장정결상태에서맹장까지완전히관찰할것이요구된다. 폴립절제후추적대장내시경검사를계획하기전에대장정결상태가불량하거나맹장까지완전히관찰하지못했다면의미있는대장종양을간과할수있어반복적인검사를시행하는것이권장된다. 89 또한, 기준대장내시경검사의질은검사를수행한내시경의사에따라많은차이가있기에선별및추적대장내시경검사는대장암검진질관리지침에따라자격을갖춘내시경의사에의해시행될것을권장한다 기준대장내시경검사에서발견된폴립의절제가내시경적또는병리학적으로불완전하다고판단되는경우추가적인대장내시경검사로완전절제여부를확인하고잔존하는폴립은제거해야하며, 특히고도이형성을동반한샘종의경우에는더욱중요하다. 55,58-61 마지막으로이가이드라인에서제안하는추적검사시기는무증상성인을대상으로적용할수있으며, 추적검사시기이전이라도증상등이발생하여임상의가필요하다고판단하는경우에는대장내시경검사를시행해야한다. 따라서, 의사는기준대장내시경검사의질, 장정결상태, 샘종의절제상태, 환자의전신상태, 가족력및과거력등을함께고려하여개별환자에서의추적대장내시경검사시기를판단하여야한다. 한편, 샘종의개수가 10개를넘는경우는진행신생물의발생위험의증가와높은폴립간과율등을고려하여외국의가이드라인에서는 1년또는 3년이내의짧은추적검사간격을 제시하고있으나, 적절한추적검사시기에대한권고를도출하기위한연구는부족한상태이다. 15,17-21 또한, 조직학적으로불완전절제된경우또는분할절제된경우에도병변의재발위험등을고려하여 2개월에서 6개월이내에추적검사를시행할것을권고하고있지만, 이가이드라인에서는구체적인추적대장내시경검사시기를제시할수없었으며, 그검사시기는의사의판단에맡겨야할것으로생각한다. 과거여러차례대장내시경을시행받은환자에서각각의검사소견을추적검사시기에어떻게반영할것인지에대해서도아직은연구가부족하여구체적인권고안을제시하기어려웠다. 고위험군에해당하는소견중두가지이상의소견이중복되어관찰되는경우에고위험군소견이한가지만동반된경우와동일한추적검사시기를적용해야하는지도잘알려진바는없다. 이가이드라인은국내에서처음으로제정되는것이며, 국내의폴립절제후추적대장내시경검사에대한자료가매우제한적이어서많은부분을우리나라와의료환경이다른서구의연구자료에근거하여제안하였다. 특히, 우리나라의대장내시경검사는외국보다수가가낮아서구의비용-효과분석을적용하기에는적당하지않으므로앞으로국내의대장폴립연구결과를바탕으로한비용-효과분석이수행되고이결과가가이드라인에반영되어야할것으로보인다. 끝으로, 이가이드라인에서는임상에서발생하는다양한상황을모두고려할수없기에실제임상에서의료진이환자를진료하고임상적요인을고려하여결정하는추적검사방법과시기에대한임상적판단을대신할수는없음을강조하는바이다. 요약 1. 기준대장내시경검사에서샘종이 3개이상발견된환자는추적대장내시경검사에서진행신생물이발견될위험이증가한다. 2. 기준대장내시경검사에서 10 mm 이상크기의샘종이발견된환자는추적대장내시경검사에서진행신생물이발견될위험이증가한다. 3. 기준대장내시경검사에서관융모또는융모샘종이발견된환자는관샘종이발견된환자에비해추적대장내시경검사에서진행신생물이발견될위험이증가한다. 4. 기준대장내시경검사에서제거한샘종이고도이형성을동반한경우, 저도이형성을동반한경우에비해추적대장내시경검사에서진행신생물이발견될위험이증가한다. 5. 기준대장내시경검사에서 10 mm 이상의톱니모양폴립이발견된환자는추적대장내시경검사에서진행신생물의발생위험이증가한다. 6. 추적검사에서진행신생물발생의고위험군은기준대장 Vol. 59 No. 2, February 2012

16 114 홍성노등. 폴립절제후추적대장내시경검사가이드라인 내시경검사에서샘종의개수가 3개이상, 가장큰샘종의크기가 10 mm 이상, 관융모또는융모샘종, 고도이형성을동반한샘종, 또는크기 10 mm 이상의톱니모양폴립중한가지이상의소견이진단된경우이다. 7. 일정한자격을갖춘대장내시경의사가양호한대장정결상태에서양질의기준대장내시경검사를시행하였음을전제로, 기준대장내시경검사소견이폴립절제후진행신생물의발생고위험군에해당되지않는경우추적대장내시경검사를폴립절제후 5년에시행할것을권고한다. 그러나, 상기의전제조건이만족되지않거나기준대장내시경검사이전의대장내시경검사에서고위험군에해당하는소견을보였던경우에는기준대장내시경소견이고위험군에해당되지않더라도추적검사기간을단축할것을권고한다. 8. 일정한자격을갖춘대장내시경의사가양호한대장정결상태에서양질의기준대장내시경검사를시행하였음을전제로, 기준대장내시경검사소견이폴립절제후진행신생물의발생고위험군에해당하는경우는추적대장내시경검사를폴립절제후 3년에시행할것을권고한다. 그러나, 상기의전제조건이만족되지않거나기준대장내시경검사소견, 샘종의절제상태, 환자의전신상태, 가족력및과거력등을고려하여추적검사기간을단축할수있다. 감사의글 이번대장폴립선별검사가이드라인논문에아낌없는조언을주신가톨릭의대채현석교수님, 한양의대한동수교수님, 그리고고려의대진윤태교수님께깊은감사를표합니다. 또한이가이드라인의최종안에동의해주신대한내과학회와대한내과개원의사회에도감사드립니다. REFERENCES 1. Thiis-Evensen E, Hoff GS, Sauar J, Langmark F, Majak BM, Vatn MH. Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study I. Scand J Gastroenterol 1999;34: Citarda F, Tomaselli G, Capocaccia R, Barcherini S, Crespi M; Italian Multicentre Study Group. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001;48: Loeve F, van Ballegooijen M, Snel P, Habbema JD. Colorectal cancer risk after colonoscopic polypectomy: a population-based study and literature search. Eur J Cancer 2005;41: Stryker SJ, Wolff BG, Culp CE, Libbe SD, Ilstrup DM, MacCarty RL. Natural history of untreated colonic polyps. Gastroenterology 1987;93: Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329: Winawer SJ, Zauber AG, O'Brien MJ, et al. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. N Engl J Med 1993;328: Meagher AP, Stuart M. Does colonoscopic polypectomy reduce the incidence of colorectal carcinoma? Aust N Z J Surg 1994;64: Lund JN, Scholefield JH, Grainge MJ, et al. Risks, costs, and compliance limit colorectal adenoma surveillance: lessons from a randomised trial. Gut 2001;49: Jørgensen OD, Kronborg O, Fenger C. A randomized surveillance study of patients with pedunculated and small sessile tubular and tubulovillous adenomas. The Funen Adenoma Follow-up Study. Scand J Gastroenterol 1995;30: Bertario L, Russo A, Sala P, et al. Predictors of metachronous colorectal neoplasms in sporadic adenoma patients. Int J Cancer 2003;105: Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992;326: The National Health Insurance Corporation. National Health Insurance Statistical Yearbook for nhic.or.kr/ portal/site/main/menuitem.e0e5d150f021cfe46e20bbb5b210101c, Health Insurance Policy Research Institute, The National Health Insurance Corporation. Trend of studies about economic evaluation of the cancer screening programs. portal/site/main/menuitem.42a779d76d7f8c38b31148b a0/, Rapuri S, Spencer J, Eckels D. Importance of postpolypectomy surveillance and postpolypectomy compliance to follow-up screening--review of literature. Int J Colorectal Dis 2008;23: Arditi C, Peytremann-Bridevaux I, Burnand B, et al; EPAGE II Study Group. Appropriateness of colonoscopy in Europe (EPAGE II). Screening for colorectal cancer. Endoscopy 2009; 41: Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 2000;95: Cairns SR, Scholefield JH, Steele RJ, et al; British Society of Gastroenterology; Association of Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut 2010;59: Davila RE, Rajan E, Baron TH, et al; Standards of Practice Committee, American Society for Gastrointestinal Endoscopy. ASGE guideline: colorectal cancer screening and surveillance. Gastrointest Endosc 2006;63: Levin B, Lieberman DA, McFarland B, et al; American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. Screening and surveillance for the early detection The Korean Journal of Gastroenterology

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