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1 Korean J Gastroenterol Vol. 70 No. 3, pissn eissn REVIEW ARTICLE 위선종의내시경치료 허철웅, 김병욱 가톨릭대학교의과대학인천성모병원소화기내과 Endoscopic Treatment of Gastric Adenoma Cheal Wung Huh and Byung-Wook Kim Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea Gastric adenoma (dysplasia) is a precancerous lesion. Therefore, managements of gastric adenomas are important for preventing the development of gastric cancers and for detecting gastric cancers at earlier stages. The Vienna classification divides gastric adenomas into two categories: high-grade dysplasia and low-grade dysplasia. Generally, endoscopic resection is performed for adenoma with high-grade dysplasia due to the coexistence of carcinoma and the potential of progression to carcinomas. However, the treatments of adenoma with low-grade dysplasia remain controversial. Currently two treatment strategies for the low-grade type have been suggested; First is the wait and see strategy; Second is endoscopic treatment (e.g., endoscopic mucosal resection, endoscopic submucosal dissection, or argon plasma coagulation). In this review, we discuss the current optimal strategies for endoscopic management of gastric adenoma. (Korean J Gastroenterol 2017;70: ) Key Words: Gastric adenoma; Dysplasia; Endoscopic treatment 서론 위암은전세계에서네번째로흔히발생하는암으로, 한국을포함한동아시아국가에서특히그발생빈도가높다. 1 위선종 (gastric adenoma) 또는위이형성 (gastric dysplasia) 은위암의전구병변으로, 이에대한진단및치료는위암의조기발견및예방에매우중요하다. 2 현재대부분의임상의사들은위선종과위이형성을비슷한의미로혼용하여사용하고있다. 하지만엄밀하게위선종은주변점막의위축성위염과같은염증과관련없이발생한양성신생물로정의할수있는반면, 위이형성은주변점막의염증과관련이있는양성신생물이라는차이가있다. 3 병리학적으로는위선종의경우주변점막에비해융기되어있는병 변을일컬으며, 위이형성은주변점막과동일한높이의병변을일컫는다. 4 이에본고에서는저도이형성선종 (gastric adenoma with low grade dysplasia), 고도이형성선종 (gastric adenoma with high grade dysplasia) 으로통일하여사용하고자한다. 위암과고도이형성선종을감별할때일본병리학자들과서양병리학자들사이에이견이있다. 일본병리학자들은점막고유층의침범여부에관련없이세포학적구조의변화에따라암을진단하는반면, 서양병리학자들은점막고유층의침범여부에따라서암을진단하였다. 5 이에대한혼돈을줄이고자 1998년에 Vienna 분류를발표하였고, 2000년에수정된 Vienna 분류법을발표하였다 (Table 1). 6,7 현재고도이형성선종의치료는이견이없는반면에저도 Received August 9, Revised September 1, Accepted September 5, CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright Korean Society of Gastroenterology. 교신저자 : 김병욱, 21431, 인천시부평구동수로 56, 가톨릭대학교의과대학인천성모병원소화기내과 Correspondence to: Byung-Wook Kim, Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 56 Dongsu-ro, Bupyeong-gu, Incheon 21431, Korea. Tel: , Fax: , Financial support: None. Conflict of interest: None. Korean J Gastroenterol, Vol. 70 No. 3, September

2 116 허철웅, 김병욱. 위선종의내시경치료 Table 1. Classification Systems of Gastric Epithelial Neoplasia Revised Vienna 15 Japanese 56 WHO 57 Category 1: Negative for dysplasia Group I: Normal or benign No intraepithelial neoplasia/dysplasia Category 2: Indefinite for dysplasia Group II: Benign with atypia Indefinite for intraepithelial neoplasia/dysplasia Category 3: Mucosal low-grade neoplasia Group III: Borderline Low-grade intrae pithelial neoplasia/dysplasia (low-grade adenoma/dysplasia) Category 4: Mucosal high-grade neoplasia Group IV: Strongly suspicious for invasive carcinoma High-grade intraepithelial neoplasia/dysplasia 4.1: High-grade adenoma/dysplasia 4.2: Noninvasive carcinoma (CIS) 4.3: Suspicious for invasive carcinoma 4.4: Intramucosal carcinoma Category 5: Submucosal invasion by carcinoma Group V: Definitive for invasive carcinoma Intramucosal invasive carcinoma WHO, World Health Organization; CIS, carcinoma in situ. 이형성선종의치료는논란이있다. 본고에서는고도및저도이형성선종의치료, 특히내시경적치료에초점을맞추어살펴보고자한다. 본론 고도이형성선종과저도이형성선종은모두암으로진행될가능성이있다. 여러보고에따르면고도이형성선종은약 60-85% 이상에서악성변화를보였다 따라서, 고도이형성선종은반드시내시경치료를통하여제거할것을권유하고있다. 15 하지만저도이형성선종은현재까지치료에대해이견이있다. 저도이형성선종은암으로진행될가능성이 10% 미만으로낮고, 8,16 일부에서는추적관찰중자연적으로소실되기도한다. 11,17-19 고도및저도이형성선종의치료에대해여러가이드라인이제시되었는데, 개정된 Vienna 분류에서는고도이형성선종은내시경치료를권유하고, 저도이형성선종은내시경치료혹은추적관찰을권유하고있다. 15 최근 American Society for Gastrointestinal Endoscopy 가이드라인과 British Society of Gastroenterology 가이드라인은위선종의크기및분화도와상관없이가능하면내시경절제를권고하고있다. 20,21 유럽가이드라인역시고도이형성선종은반드시내시경절제가필요하며, 저도이형성선종이라고하더라도정확한병리학적진단을위해내시경절제를시행할것을권고하고있다 내시경점막절제술 (endoscopic mucosal resection, EMR) 내시경점막절제술은선종의치료뿐만아니라진단목적으로도사용된다. 선종의진단에있어서생검겸자를이용한조직검사와내시경절제후조직검사결과의불일치가비교적높은것으로알려져있다. 최근한메타분석은생검겸자를이용한조직검사에서저도이형성선종으로진단되어내 시경절제를받은환자들을분석하였을때, 약 25% 의환자에서고도이형성선종이나조기위암이관찰되었다. 23 이러한불일치는고도이형성선종의경우에는더욱심하게나타나, 약 80% 의환자에서내시경절제후조기위암이관찰되었다. 24 따라서내시경점막절제술은선종에대한치료목적뿐만아니라생검겸자의조직학적불일치를극복할수있는진단적목적, 즉 total biopsy 측면에서도의미가있을수있다. 내시경점막절제술은고식적점막절제술 (conventional EMR, snaring technique) 뿐만아니라점막층절개후점막절제술 (EMR with circumferential precutting, EMR-P), 이중겸자공내시경을이용한점막절제술 (EMR using a dual-channel endoscope, EMR-D), 내시경선단에캡을씌운점막절제술 (cap-assisted EMR, EMR-C), 밴드로묶은후점막절제술 (ligation-assisted EMR, EMR-L) 등여러변형된점막절제술방법이사용되고있다 내시경점막절제술은내시경점막하박리술 (endoscopic submucosal dissection) 에비해시술시간이짧고, 출혈이나천공과같은합병증이적다는장점이있다. 29 하지만내시경점막절제술은내시경점막하박리술에비해서일괄절제율, 완전절제율이낮다는단점이있다 (Table 2). 특히, 병변의크기가 2 cm 이상으로큰경우나병변의위치에따라서일괄절제율과완전절제율은크게감소하는것으로알려져있다 이로인해불완전절제와분할절제가많아져국소재발률이높아질수있는단점이있다. 34 따라서, 내시경점막절제술은위암의가능성이높은고도이형성선종의치료에는효과적이지못하다. 또한생검겸자를이용한조직검사에서저도이형성선종으로진단된경우라도병변의크기가 2 cm 이상인경우, 함몰이동반된경우, 표면이거칠거나붉은색으로보이는경우, 자발적출혈등내시경절제후고도이형성선종이나암으로진단될가능성이높은병변의치료에는내시경점막절제술이효과적 The Korean Journal of Gastroenterology

3 Huh CW and Kim BW. Endoscopic Treatment of Gastric Adenoma 117 Table 2. Treatment Outcomes and Complications of Endoscopic Mucosal Resection for Gastric Adenoma Author Year Number of patients Complete resection rate (%) En bloc Procedure time resection rate (%) (mins) Complication Bleeding (%) Perforation (%) Local recurrence (%) Kim et al ± Park et al Table 3. Treatment Outcomes and Complications of Endoscopic Submucosal Dissection for Gastric Adenoma Author Year Number of patients Complete resection rate (%) En bloc resection rate (%) Procedure time (mins) Complication Bleeding (%) Perforation (%) Local recurrence (%) Kato et al N/A Choi et al N/A Kim et al ± Jung et al ± Lee et al N/A N/A, not available. Table 4. Treatment Outcomes and Complications of Argon Plasma Coagulation for Gastric Adenoma Author Year Number of patients Hospital days Need to admission (%) Procedure time (mins) Complication Bleeding (%) Perforation (%) Local recurrence (%) Lee et al N/A N/A 15.0± Jung et al ± ± Ahn et al N/A N/A N/A Lee et al ± N/A N/A, not available. 이지못할수있다 내시경점막하박리술 (endoscopic submucosal dissection) 내시경점막하박리술은내시경점막절제술과는달리병변의크기와위치에관계없이일괄절제, 완전절제를할수있다는장점이있다. 따라서, 내시경점막하박리술은조기위암과동일하게치료를권고하는고도이형성선종의치료에있어가장효과적인치료라고할수있다. 하지만저도이형성선종의내시경치료에있어서는아직명확히정립된바없다. 현재까지의보고를종합해보면고도및저도이형성선종에대한내시경점막하박리술의치료성적은매우우수하다 (Table 3). 또한, 내시경점막하박리술은내시경점막절제술에비해일괄절제율, 완전절제율이높고국소재발률이낮다고알려져있다. 하지만내시경점막하박리술은내시경점막절제술에비해서출혈, 천공등과같은합병증의발생빈도가높고시술시간이많이소요된다는단점이있다. 39,40 또한내시경점막하박리술은시술자의숙련도에따라시술의성공이크게좌우된다는제한점이있다. 41,42 출혈, 천공과같은대부분의내시경점막하박리술의합병증은내시경적으로치료가 가능하고, 내시경점막하박리술로인한심각한합병증은매우적다고알려져있다. 고도및저도이형성선종의생검겸자를이용한조직검사와내시경절제후조직검사결과의불일치가높다는점을고려하면내시경점막하박리술은고도이형성선종과저도이형성선종중에내시경절제후고도이형성선종이나암으로불일치될가능성이높은병변에대해서효과적인치료방법이라고할수있다. 3. 아르곤플라즈마응고술 (argon plasma coagulation) 아르곤플라즈마응고술은이온화된아르곤가스를통하여조직으로전해지는에너지를이용하여조직과직접닿지않고전기소작을하는방법이다. 43,44 아르곤플라즈마응고술은이론적으로는점막층뿐아니라점막하층의표층까지도근절할수있다고알려져있다. 45 아르곤플라즈마응고술은내시경절제에비해시술시간이짧고, 출혈이나천공의위험이적으며, 입원이필요없고, 시술비용이적게들며, 시술자의숙련도가크게중요하지않다는장점이있다 (Table 4) 여러보고에따르면, 아르곤플라즈마응고술은 1-2 cm 미만의크기가작은육안적으로편평한고도및저도이형성선종의 Vol. 70 No. 3, September 2017

4 118 허철웅, 김병욱. 위선종의내시경치료 치료에효과적이라고알려져있다. 하지만크기가 2 cm 이상일경우, 육안적으로융기형이나점막하식염수주입시병변이떠오르지않는경우, 40 W 등낮은전압으로아르곤플라즈마응고술을시행하였을경우에는그효과가떨어져재발률이상승하는것으로알려져있다 또한아르곤플라즈마응고술은내시경절제와다르게선종전체의조직검사결과를확인할수없기때문에고도이형성선종이나고위험저도이형성선종의치료에는제한적이다. 따라서육안적으로평면형인 1 cm 크기미만의작은저도이형성선종의치료에는아르곤플라즈마응고술로치료를시도해볼수있겠지만충분한 W의높은전압으로충분한시간동안치료하여야한다. 또한국소재발률이높은점을감안하여정기적인내시경추적관찰이반드시필요하다. Fig. 1. Proposed treatment strategy algorithm for gastric adenoma diagnosed by endoscopic biopsy; * low risk lesion: size<2 cm, grossly flat type, whitish color with smooth surface; high risk lesion: size 2 cm, grossly depressed type, surface erythema or unevenness, presence of spontaneous bleeding. EMR, endoscopic mucosal resection; APC, argon plasma coagulation; ESD, endoscopic submucosal dissection. 4. 단순추적관찰 (wait and see) 고도이형성선종의경우에는반드시내시경절제술이필요하다. 하지만일부연구에서저도이형성선종의경우에는추적기간동안자연적으로소실되었고, 11,17,19 Helicobacter pylori (H. pylori) 균이있는경우제균치료후저도이형성선종이소실되었음을보고한바있다. 17,49 이를근거로일부에서는저도이형성선종에서는치료없이 1년마다조직검사를동반한내시경추적관찰을추천하였다. 50,51 하지만이러한반복적인위내시경검사는환자입장에서육체적, 정신적부담및경제적부담이커질수있다. 또한무엇보다저도이형성선종의생검겸자조직과내시경적절제술이후조직간의심한불일치와저도이형성선종의암발전가능성등을고려하면단순추적위내시경검사만은위험부담이클수밖에없다. 그리고내시경절제술을이용한치료가보급되고기술이발전한국내에서는단순추적관찰은좋은치료전략이라고보기는어렵다. 5. 내시경절제후추적관찰 (follow up after endoscopic resection) 생검겸자로위선종이발견된경우, 동시성병변의선종이나암이존재할위험이있기때문에반드시전체위를다시한번자세히관찰하여야한다. 또한고도및저도이형성선종에대한내시경치료후에는이시성병변의발생위험이높으므로주기적인내시경추적관찰이필요하다. 36,52 American Society for Gastrointestinal Endoscopy 가이드라인은내시경절제후 1년뒤추적내시경검사를권고하고있으며, British Society of Gastroenterology 가이드라인은고도이형성선종이나불완전절제후에는 6개월, 그외의경우에는 1년뒤추적내시경검사를권고하고있다. 또한이러한환자군에서 H. pylori가있을경우제균치료하는것이이시성병 변의발생을줄일수있다고알려져있기때문에가능한 H. pylori 제균치료를하는것이좋다 결 론 고도이형성선종의경우에는조기위암에준한내시경절제등적극적인치료가반드시필요하다. 반면에저도이형성선종의치료에는이견이있는실정이다. 하지만생검겸자를이용한조직검사와내시경절제후조직검사결과의불일치가능성이있으므로진단목적및치료목적으로내시경절제를시행하는것이좋겠다. 현재까지의연구를근거로생검겸자를이용한조직검사결과에따른치료전략을 Fig. 1에정리하였다. 고도및저도이형성선종에대한내시경절제후 H. pylori가검출되는경우, 이시성병변의발생위험을낮추기위해제균치료를시행하는것이좋을것으로생각한다. REFERENCES 1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006;24: Lauwers GY, Riddell RH. Gastric epithelial dysplasia. Gut 1999; 45: Lewin KJ. Nomenclature problems of gastrointestinal epithelial neoplasia. Am J Surg Pathol 1998;22: Iacobuzio-Donahue CA, Montgomery EA. Gastrointestinal and liver pathology. 2nd ed. Philadelphia: Saunders, Schlemper RJ, Kato Y, Stolte M. Review of histological classifications of gastrointestinal epithelial neoplasia: differences in diagnosis of early carcinomas between Japanese and Western pathologists. J Gastroenterol 2001;36: Stolte M. The new Vienna classification of epithelial neoplasia of The Korean Journal of Gastroenterology

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Meta-analysis of endoscopic submucosal dissection versus endoscopic mucosal resection for tumors of the gastrointestinal tract. Endoscopy 2009; 41: Oda I, Odagaki T, Suzuki H, Nonaka S, Yoshinaga S. Learning Vol. 70 No. 3, September 2017

6 120 허철웅, 김병욱. 위선종의내시경치료 curve for endoscopic submucosal dissection of early gastric cancer based on trainee experience. Dig Endosc 2012;24 Suppl 1: Sakamoto T, Saito Y, Fukunaga S, Nakajima T, Matsuda T. Learning curve associated with colorectal endoscopic submucosal dissection for endoscopists experienced in gastric endoscopic submucosal dissection. Dis Colon Rectum 2011;54: Grund KE. Argon plasma coagulation (APC): ballyhoo or breakthrough? Endoscopy 1997;29: Grund KE, Storek D, Farin G. Endoscopic argon plasma coagulation (APC) first clinical experiences in flexible endoscopy. Endosc Surg Allied Technol 1994;2: Lee DH, Bae WK, Kim JW, et al. The usefulness of argon plasma coagulation compared with endoscopic submucosal dissection to treat gastric adenoma. Korean J Gastroenterol 2017;69: Jung SJ, Cho SJ, Choi IJ, et al. Argon plasma coagulation is safe and effective for treating smaller gastric lesions with low-grade dysplasia: a comparison with endoscopic submucosal dissection. Surg Endosc 2013;27: Ahn JY, Choi KD, Na HK, et al. Clinical outcomes of argon plasma coagulation for the treatment of gastric neoplasm. Surg Endosc 2013;27: Lee KM, Kim YB, Sin SJ, et al. Argon plasma coagulation with submucosal saline injection for gastric adenoma on outpatient basis. Dig Dis Sci 2009;54: Gotoda T, Saito D, Kondo H, et al. Endoscopic and histological reversibility of gastric adenoma after eradication of helicobacter pylori. J Gastroenterol 1999;34 Suppl 11: Rugge M, Nitti D, Farinati F, di Mario F, Genta RM. Non-invasive neoplasia of the stomach. Eur J Gastroenterol Hepatol 2005;17: Weinstein WM, Goldstein NS. Gastric dysplasia and its management. Gastroenterology 1994;107: Kim MK, Jang JY, Kim JW, et al. Is lesion size an independent indication for endoscopic resection of biopsy-proven low-grade gastric dysplasia? Dig Dis Sci 2014;59: Shin SH, Jung DH, Kim JH, et al. Helicobacter pylori eradication prevents metachronous gastric neoplasms after endoscopic resection of gastric dysplasia. PLoS One 2015;10:e Bae SE, Jung HY, Kang J, et al. Effect of helicobacter pylori eradication on metachronous recurrence after endoscopic resection of gastric neoplasm. Am J Gastroenterol 2014;109: Chon I, Choi C, Shin CM, Park YS, Kim N, Lee DH. Effect of helicobacter pylori eradication on subsequent dysplasia development after endoscopic resection of gastric dysplasia. Korean J Gastroenterol 2013;61: Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer 2011;14: Yakirevich E, Resnick MB. Pathology of gastric cancer and its precursor lesions. Gastroenterol Clin North Am 2013;42: Kim SY, Sung JK, Moon HS, et al. Is endoscopic mucosal resection a sufficient treatment for low-grade gastric epithelial dysplasia? Gut Liver 2012;6: Park SM, Kim JS, Ji JS, Choi H, Lee BI, Kim BW. Efficacy of endoscopic mucosal resections for the management of small gastric adenomas with low-grade dysplasia. Scand J Gastroenterol 2015;50: Choi CW, Kang DH, Kim HW, Park SB, Kim S, Cho M. Endoscopic submucosal dissection as a treatment for gastric adenomatous polyps: predictive factors for early gastric cancer. Scand J Gastroenterol 2012;47: The Korean Journal of Gastroenterology

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