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1 C-IV. 대장폴립절제술, 그것이알고싶다. Room C 폴립절제후추적내시경은언제? 인제대학교의과대학해운대백병원내과학교실 Optimal Colonoscopy Surveillance Interval after Polypectomy So Chong Hur, Tae Oh Kim Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea 서론대장암은전세계적으로유병률이증가추세이며, 우리나라에서도식생활의서구화로매년대장암의발생률은매우빠르게증가하고있다. 대장암의발생은대장암이양성선종에서시작하여암으로변화되는 adenoma-carcinoma sequence설과정상점막내에서암이발생한다는 de novo설로나뉘며 2/3 이상은선종에서기인하여선암으로발생하는것으로알려져있어대장내시경을통해대장암의전구병변인샘종을발견하고제거하는것이대장암예방을위해최선의방법이다. 2008년미국보고에따르면검진목적의선별검사에서 9 mm 이상의용종이발견된경우가 6-7% 정도라고보고하고있고, 국내에서도보고에따라다르지만선별검사에서선종의발견빈도는 9% 정도이다. 1,2 최근대장암선별검사로대장내시경검사가보편화되면서대장폴립의진단과절제가급격히증가하고있으며, 1,2 이에따라폴립절제후추적검사에대한수요도가파르게증가하고있다. 대장선종의내시경절제술이후발생가능한대장암을줄이기위해추적대장내시경검사가요구된다. 실제로한개이상의대장선종을제거받은환자의경우 3-5년내추적내시경을시행한결과약 20-30% 에서이시성병변 (metachronous lesion) 이발견되었으며, 3-7 약 20% 의환자들은직경이 10 mm 이상, 융모성분이 25% 이상, 또는고도이형성을갖는것으로정의되는진행성선종이발견되었고, 3-8 비록적은비율이지만침습적대장암또한발생하였다. 5,9-14 또한, 대장암의선별검사로시행한대장내시경후적절한추적기간내에진단되는중간암에대한보고도있으며, 이러한중간암의원인중약 19-27% 정도는불완전하게절제된폴립으로부터발생하는것으로알려져있다 만약이러한진행성대장종양의발생을예측하고불완전절제된폴립에대해대처하고적절한추적내시경을할수있다면대장암발생위험이큰환자들을선별하여추적내시경검사를더엄격하게시행할수있을것이다. 본론대장용종을절제한경우용종이없는군과비교하여향후대장용종과대장암이발생할위험성이증가하기때문에대장내시경을이용한추적검사가필요하다. 21 대장내시경에서발견된폴립의특징과환자의특성중폴립절제후추적검사시기를결정하는데반영되어야할진행신생물발생위험요인들을결정하고, 이들위험요인에근거한진행신생물발생위험정도에따라적절한폴립절제후추적대장내시경검사시기를 2012년국내에서가이드라인을제정하여발표한바있다. 대장용종절제후추적대장내시경검사를결정하는데고려해야하는점은선종의개수와크기, 조직학적특성으로알려져있다. 폴립절제후추적검사시기결정에반영되어야할위험인자로서우선절제한선종의개수가 3개이상인경우에는추적대장내시경검사에서진행성용종이나암이발견될위험이증가한다. 샘종의개수에따라추적검사에서진행신생물발생위험을평가한연구들에따르면 선종의개수가증가할수록추적검사에서진행신생물이발생할위험은통합교차비 1.93 (95% CI, ) 과통합위험비 2.20 (95% CI, ) 으로증가하였다. 특히 3개이상의 176 Korean Society of Gastrointestinal Endoscopy

2 폴립절제후추적내시경은언제? 샘종이진단된환자에서폴립절제후진행신생물이발생할위험은통합교차비 2.84 (95% CI, ) 와통합위험비 2.20 (95% CI, ) 으로의미있게증가하였다. 이러한이유로기존각국의가이드라인에서는 3개이상의선종을제거하였을경우 3년추적검사를시행하기를권유하고있다. 또한, 다수의샘종이발견된경우에는일부가이드라인에서는조기에추적검사를시작할것을권고하여 British Society of Gastroenterology ()-Association of Coloproctology for Great Britain and Ireland (ACPGBI) 는 5개이상의샘종또는 1 cm 이상의샘종이있으면서 3개이상의샘종이발견된경우고위험군으로 1년후추적검사를시행할것을권고하고있고, 31 USMSTF-ACS 는 10개이상의샘종이발견된경우 3년이내에추적검사를시행하고가족성폴립증의가능성도고려할것을권고하고있다. 32 기준샘종의크기에따라폴립절제후진행신생물의발생위험을평가한연구에따르면 22-26,28-30 기준샘종의크기가 5-10 mm인경우는 5 mm 이하인경우보다진행신생물의발생위험이의미있게증가하지않았지만절제한용종의크기가 10 mm 이상인경우에는 10mm 이하의경우보다약 2배가량추적검사시에진행성신생물이발견될위험이크다고보고하였다. 샘종은크기가클수록많은융모조직을포함하고진행된조직형을보일가능성이커져 20 mm 이상의폴립은악성화된부위가포함된경우가많게는 32% 까지보고되고있다. 33,34 따라서, 크기가큰목없는폴립을제거할때병리학적인완전절제여부의평가는중요하나, 일반적으로 20 mm 이상의목없는폴립은전통적인올가미폴립절제술로한번에제거하기어려워분할절제 (piecemeal resection) 로제거되는경우가많다 따라서, 크기가큰목없는폴립을제거할때병리학적인완전절제여부의평가는중요하다. 따라서 1 cm 이상이며 2 cm 이하의용종이하나있는경우라면반드시 1 년후추적검사를시행할필요는없으나완전절제가되지않았다는판단이든다면경우에따라서 1년전후로추적검사가필요하다. 또한, 2 cm 이상의무경성용종의경우완전절제여부의판단이중요한데이경우병리적, 임상적완전절제를획득하지못하였다면 6개월에서 12개월사이에추적검사를시행하는것이필요하다. 절제한용종조직이관상선종이냐융모선종이냐에따라서는다소이견이있었다. 그러나기준샘종의융모조직이 20-25% 를초과하는경우를관융모또는융모샘종으로정의하였고여러연구관융모또는융모샘종이발견된환자는추적대장내시경검사에서진행신생물의발생위험이관샘종만발견된환자에비해통합교차비 1.51 (95% CI, ), 통합위험비 1.83 (95% CI, ) 로의미있게증가하였 다. 22,23,25,28 국내의한연구에서는기준샘종에융모샘종조직이존재하여도진행샘종의발생위험이증가하지는않았지만 ( 위험비, 1.48; 95% CI, ), 30 Yang 등 37 은구불창자내시경검사를이용하여샘종을제거한후 16년동안추적관찰결과기준샘종이관융모또는융모샘종인경우진행신생물의발생위험이유의하게증가하여 ( 교차비, 8.1; 95% CI, ) 고도이형성과함께관융모또는융모샘종을폴립절제후진행신행물발생위험을예측하는가장중요한인자로제시하였다. 또한, 대장내시경에서고도이형성을동반한경우는저도이형성을동반한경우에비해추적대장내시경검사에서진행신생물의발생위험은통합교차비 1.33 (95% CI, ) 으로증가추세가관찰되었고, 통합위험비 1.69 (95% CI, ) 로의미있게증가하였다. 22,23,29 경우에따라검사시기를조절할필요는있겠으나 Martínez 등 38 에따르면그위험이크지않다는보고도있으며 Saini 등 39 은메타분석에서는샘종의개수와더불어고도이형성만이기준대장내시경검사 3년후에시행한추적대장내시경검사에서진행샘종의발생위험증가를예측할수있는의미있는위험인자로 ( 통합상대위험도, 1.84; 95% CI, ) 3년이후추적검사를권하고있다. 최근에톱니모양용종 (serrated polyp) 의경우선종-암연쇄경로를밟지않고다른톱니모양경로 (serrated pathway) 를통해대장암으로진행한다는것이밝혀졌다. 40 증식폴립을포함하여목없는톱니샘종 (sessile serrated adenoma), 전통톱니샘종 (traditional serrated adenoma), 증식폴립과샘종의혼합폴립 (mixed adenomatous and hyperplastic polyp) 등병리학적으로톱니모양의구조 (serrated architecture) 를가지는경우톱니모양폴립으로분류한다. 41 톱니모양용종은주로우측대장에많이발생하고, BRAF 돌연변이, 현미위성체불안정 (MSI-high) 과연관된대장암이많고대장암이빠르게진행될수있을것으로예상된다. 연구에따르면톱니모양용종이발견된경우진행성신생물이발견될경우는통합교차비는 1.98 (95% CI, ) 로 10 mm 이상의톱니모양폴립이발견된경우는진행신생물의발생위험이증가하였다 샘종의위치에따른진행신생물발생위험에대한연구는최근에많이이루어졌으며우측결장을맹장에서횡행결장혹은비만곡부까지로정의하였을때샘종이좌측결장에국한하여존재했던경우에비해우측결장에서발견되었던경우는추적대장내시경검사에서진행신생물이발견될위험의통합교차비가 1.73 (95% CI, ) 으로증가하였다. 24,28,38 우측결장의굴곡이심하고결장팽대가뚜렷한해부학적특성으로내시경검사상종양을간과할위험이있고우측결장에발생하는대장암은톱니모양경로를 제 54 회대한소화기내시경학회세미나 177

3 폴립절제후추적내시경은언제? Table 1. 용종절제후추적검사지침요약 (Summary of Guidelines for Postpolypectomy ) Guideline society Low risk 1-2 small aenomas * Intermediate risk Advanced neoplasm or 3-10 small adenomas High risk Small adenomas >10 Large sessile adenoma Initial interval 5-10 yrs or no < < 1 yrs 2-6 months 3-6 months 2-6 months 3 months Subsequent interval if FU colonoscopy shows only low-risk adenomas 5-10 yrs or no Subsequent interval if FU colonoscopy shows no adenomas no 1 yr By US Multi-Society Task Force on Colorectal Cancer (Task Force), American College of Gastroenterology (ACG), American Society of Gastrointestinal Endoscopy (), and British Society of Gastroenterology (). * Small adenomas are defined as tubular adenomas <1 cm in size; ACG guidelines note that selected low-risk patients might not need at all, but do not further elaborate; Advanced neoplasm is defined as villous or tubulovillous adenoma, adenoma with high-grade dysplasia, or a tubular adenoma 1 cm in size; ACG guidelines consider patients with 1-2 small adenomas and positive family history in first-degree relative to be at intermediate risk; guidelines define intermediate-risk patients as those with 3-4 small adenomas or at least one adenoma 1 cm in size; guidelines recommend ceasing if two consecutive follow-up colonoscopies are negative; ** guidelines define high risk patients as those with 5 adenomas or 3 adenomas, at least one of which is 1 cm in size; guidelines recommend repeating colonoscopy in 1 year after confirmation of complete removal, then every ; FU, follow-up. 통해발생할수있으며환자의특징및환경적요인에많은영향을받으므로우측결장샘종이진행신생물의위험요인이라고결론내리기는추가적인연구가필요할것으로보인다. 폴립절제후추적검사시기에대해서는우리나라 2012년가이드라인 42 에서는폴립절제후진행신생물발생의고위험군에해당되지않는경우는추적대장내시경검사를폴립절제후 5년에시행하고, 기준대장내시경이고위험군에해당되지않더라도이전의대장내시경검사에서고위험군에해당하는소견을보였던경우에는추적검사기간을단축할것을권고하였다. 앞서언급하였던폴립절제후진행신생물발생위험이증가하는고위험군의경우에는추적대장내시경검사를폴립절제후 3년에시행할것을권고한다. 그러나상기의전제조건이만족되지않거나기준대장내시경검사소견, 샘종의절제상태, 환자의전신상태, 가족력및과거력등을고려하여추적검사기간을단축할수있다고권고하였다 (Table 1). Table 2. 용종절제후추적대장내시경시진행성신생물발견가능성이높은경우 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 결론 대장암의유병률은증가하는추세에있으며대장내시경상폴립을제거한환자는제거하지않은환자에비해진행신생물의발생위험이높으므로적절한추적검사가요구된다. 추적대장내시경검사시에진행성신생물이발견될위험이큰경우는 3개이상의선종이제거된경우, 10 mm 이상의선종을제거한경우, 관융모또는융모샘종, 고도이형성을동반 178 Korean Society of Gastrointestinal Endoscopy

4 폴립절제후추적내시경은언제? 한샘종, 10 mm 이상의톱니모양용종을제거한경우로요약할수있겠다 (Table 2). 이중한가지라도해당되는경우는고위험군에해당되며추적대장내시경검사를폴립절제후 3 년에시행할것을권고하였다. 그외이전대장내시경소견, 샘종의절제상태, 환자의전신상태, 가족력및과거력을고려하여추적검사기간을단축할수있으며고위험군에해당되지않는경우폴립절제후 5년에추적검사를시행하도록권고하였다. 우리나라의대장내시경검사는외국과수가가달라서구의비용-효과분석을적용하기에는적절치않아앞으로국내대장폴립연구결과를바탕으로비용-효과분석이더이루어져야할것으로보인다. 참고문헌 1. The National Health Insurance Corporation. National Health Insurance Statistical Yearbook for kr/portal/site/main/menuitem.e0e5d150f021cfe46e 20bbb5b210101c, Health Insurance Policy Research Institute, The National Health Insurance Corporation. Trend of studies about economic evaluation of the cancer screening programs. f8c38b31148b a0/, Martinez ME, Sampliner R, Marshall JR, et al. Adenoma characteristics as risk factors for recurrence of advanced adenomas. Gastroenterology 2001;120: Schatzkin A, Lanza E, Corle D, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med 2000;342: Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348: 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: Lieberman DA, Weiss DG, Harford WV, et al. Five-year colon after screening colonoscopy. Gastroenterology 2007;133: Winawer SJ, Zauber AG, O Brien MJ, et al. Randomized comparison of intervals after colonoscopic removal of newly diagnosed adenomatous polyps. N Engl J Med 1993;328: Robertson DJ, Greenberg ER, Beach M, et al. Colorectal cancer in patients under close colonoscopic. Gastroenterology 2005;129: Alberts DS, Martinez ME, Roe DJ, et al. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians Network. N Engl J Med 2000;342: Bertagnolli MM, Eagle CJ, Zauber AG, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 2006;355: Arber N, Eagle C, Spicak J, et al. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 2006;355: Pabby A, Schoen RE, Weissfeld JL, et al. Analysis of colorectal cancer occurrence during colonoscopy in the Dietary Polyp Prevention Trial. Gastrointest Endosc 2005;61: Farrar WD, Sawhney M, Nelson DB, et al. Colorectal cancers found after a complete colonoscopy. Lancet 2006;4: Rabeneck L, Paszat LF, Saskin R, Stukel TA. Association between colonoscopy rates and colorectal cancer mortality. Am J Gastroenterol 2010;105: Singh H, Turner D, Xue L, et al. Risk of developing colorectal cancer following a negative colonoscopy examination: evidence for a 10-year interval between colonoscopies. JAMA 2006;295: Singh H, Nugent Z, Demers AA, et al. Rate and predictors of early/missed colorectal cancers after colonoscopy in Manitoba: a population-based study. Am J Gastroenterol 2010;105: Robertson DJ, Greenberg ER, Beach M, et al. Colorectal cancer in patients under close colonoscopic. Gastroenterology 2005;129: Leung K, Pinsky P, Laiyemo AO, et al. Ongoing colorectal cancer risk despite colonoscopy: the Polyp Prevention Trial Continued Follow-up Study. Gastrointest Endosc 2010;71: Robertson DJ, Lieberman DA, Winawer SJ, et al. Interval cancer after total colonoscopy: results from a pooled analysis of eight studies. Gastroenterology 2008;134(abstr):111A. 21. 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: Jørgensen OD, Kronborg O, Fenger C. A randomized 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: Martínez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology 2009;136: Noshirwani KC, van Stolk RU, Rybicki LA, Beck GJ. Adenoma size and number are predictive of adenoma recurrence: implications for colonoscopy. Gastrointest Endosc 2000;51: Nusko G, Mansmann U, Kirchner T, Hahn EG. Risk related following colorectal polypectomy. Gut 2002; 51: Kim JB, Han DS, Lee HL, et al. The recurrence rate of colon polyp after polypectomy and the interval of co- 제 54 회대한소화기내시경학회세미나 179

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untitled Korean J Gastroenterol Vol. 59 No. 2, 99-117 http://dx.doi.org/10.4166/kjg.2012.59.2.99 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