대한내과학회지 : 제 90 권제 4 호 2016 http://dx.doi.org/10.3904/kjm.2016.90.4.307 의학강좌 - 개원의를위한모범처방 (Current Clinical Practice) 위용종의진단및치료 가톨릭대학교의과대학대전성모병원내과 이승우 Diagnosis and Management of Gastric Polyps Seung Woo Lee Department of Internal Medicine, Daejeon St. Mary`s Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea A gastric polyp is defined as a proliferative or neoplastic lesion from the mucosal membrane. Rates of gastric polyp detection are increasing due to widespread use of gastrointestinal endoscopy in Korea. There are many types of gastric polyps; the most common are fundic gland, hyperplastic, and adenomatous polyps. This article reviews the clinical and histologic features of these polyps and provides recommendations for management. (Korean J Med 2016;90:307-312) Keyword: Stomach; Polyps; Diagnosis; Disease management 서론국내에서는최근국가암검진프로그램으로인하여위내시경검사가보편화되어무증상의위용종이발견되는경우가많아지고있다. 넓은의미의용종이란위장관의내강쪽으로돌출된병변을의미하나엄격하게는위의점막층에서발생된과증식성또는종양성병변으로정의할수있다 [1]. 위용종은상피성용종과비점막성벽내용종으로크게분류되며 (Table 1) [2] 상피성용종에는위저선용종 (fundic gland polyp), 과증식성용종 (hyperplastic polyp), 위선종 (Gastric adenoma) 등이대표적이다. 이외에도다양한종류의용종이있지만임상양상이나악성화비율등이각각다르기때문에일률적인치료 방법을선택하기어렵다. 본고에서는위용종중에서내시경검사중흔히관찰할수있는상피성용종을중심으로진단및치료에대해기술하고자한다. 역학위용종의발생률은연구자마다 1-9% 정도로다양하게보고하고있다. 가장흔하게발견되는용종은위저선용종, 증식성용종, 위선종이다. 전통적으로가장흔하게발견되는용종은과증식성용종으로알려져있으나발생률에지역적인차이가있어서서구에서시행된연구에서는위저선용종이가장흔한것으로나타났지만국내연구에서는과증식성용종 Correspondence to Seung Woo Lee, M.D., Ph.D. Department of Internal Medicine, Daejeon St. Mary`s Hospital, College of Medicine, The Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon 34943, Korea Tel: +82-42-220-9501, Fax: +82-42-252-6808, E-mail: leeseungw00@hanmail.net Copyright c 2016 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 307 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- The Korean Journal of Medicine: Vol. 90, No. 4, 2016 - Table 1. Classification of gastric polyps Epithelial polyps Non mucosal intramural polyps Fundic gland polyp Gastrointestinal stromal tumor Hyperplastic polyp Leiomyoma Adenomatous polyp Inflammatory fibroid polyp Hamartomatous polyp Fibroma and fibromyoma - Juvenile polyp Lipoma - Peutz-Jeghers syndrome Ectopic pancreas - Cowden s syndrome Neurogenic and vascular tumors Polyposis syndrome (non hamartomatous) Neuroendocrine tumors (carcinoids) - Juvenile polyposis - Familial adenomatous polyposis A B Figure 1. Fundic gland polyp. (A) Endoscopic finding showing a small smooth, translucent, round polyp in the gastric body. (B) Histological finding showing cystically dilated fundic glands lined by normal cells in the oxyntic mucosa, which consists of parietal cells, chief cells, and mucous neck cells. The lamina propria is scant, with mixed inflammatory cells. Cells are stained with Hematoxylin & Eosin. 100 magnification. 이가장흔하고다음으로위저선용종과선종성용종의순으로많은것으로나타났다 [3]. 최근중국에서시행된연구에서 10년전과비교하여위용종의분포양상을비교하였는데과증식성용종은감소하는추세인반면에위저선용종의비율은점차증가하고있는것으로나타났다 [4]. 이는장기간의양성자펌프억제제 (proton pump inhibitor) 의사용과 Helicobacter pylori 감염률의감소에기인한것으로추정하고있다. 위저선용종 (fundic gland polyp) 위저선용종은산발적으로발생되는용종 (sporadic fundic gland polyp) 과가족성선종성용종증 (Familial adenomatous polyposis symdrome) 과동반된용종그리고장기간의양성자펌프억제제사용과연관된용종이있다. 위저선용종의발생원인은명확하지않지만 β-catenin 유전자의변형과연관되어있는것으로알려져있다 [5]. 산발성위저선용종 (sporadic fundic gland polyp) 위저선용종은부드럽고투명하며, 무경성의융기된형태 로보이며단독혹은다발성으로나타나지만다발성인경우가많으며대부분 5 mm 이내의크기이다 (Fig. 1A). 주변점막과비슷한색조를띄며내시경소견만으로도진단이가능한경우가많다. 조직학적소견은특징적으로위저샘들의증식과소낭형성을볼수있으며바탕질 (lamina propria) 에서염증세포의침윤은거의관찰되지않는다 (Fig. 1B). 산발성용종에서이형성 (dysplasia) 은 1% 미만에서나타나며 H. pylori 감염과의연관성은낮고시간이지나면서크기가줄어들거나사라지기도한다. 이형성을보이는경우는매우드물지만보고가되고있으며 [6] 한증례보고에서작은크기의위저선용종에서인환세포암이발생되었던예를보고하여용종의표면이불규칙하거나미란이있을경우이형성변화의가능성을생각하여야되겠다 [7]. 양성자펌프억제제와연관된위저선용종 1992년에양성자펌프억제제사용후발생한위저선용종에대한증례들이보고된이후로양성자펌프억제제사용과위저선용종과의연관성에대한연구들이발표되었다. 양성자펌 - 308 -
- Seung Woo Lee. Benign gastric polyps - 프억제제의사용후에발생하는위저선용종의발생기전은명확하지는않으나다음과같은기전이제시되고있다. 첫번째로약물로인한위산분비의억제나고가스트린수치 (high gastric level) 에의한영양효과 (trophic effect) 에의해벽세포의돌출 (parietal cell protrusion) 이발생한다는것과두번째로이런돌출이선협부 (glandular isthmus) 의폐색을유발하여유출로 (outflow) 를차단하게되고이로인해위저선낭종 (fundic gland cyst) 이발생되고이런낭종이커지면서위저선용종으로진행될수있다는기전이제시되고있다 [8]. 한연구에따르면 1년이상양성자펌프억제제를장기복용하는환자에서위저선용종의발생률은 4배까지증가하는것으로나타났고특히 5년이상복용하는경우발생률이높게나타났다 [9]. 다른연구에서용종은대부분크기가 1 cm 미만이었고근위또는중체부에서발생된경우가많았다. 용종발생의평균시간은 32.5개월이었고양성자펌프억제제를중단후 3개월후에사라졌다 [10]. 양성자펌프억제제의사용과위저선용종과의관계를증명한연구들이많지만일부연구에서는양성자펌프억제제와위저선용종과의명확한연관성을증명하지못하여향후더연구가필요한상태이다. 가족성선종성용종증 (familial adenomatous polyposis) 에서위저선용종가족성선종성용종증환자에서위저선용종이다수생길수있으며이는 adenomatous polyposis coli 유전자의변형에의한다. 또한이형성발생률이 25-41% 정도발생될수있다 [11]. 한연구에서가족성선종성용종증환자에서위저선용종에대해조사한결과 88% 의환자에서위저선용종이발견되었고이중 41% 는이형성을포함하고있었다는보고를하였다 [12]. 이형성이있는경우는크기가 1 cm 이상크거나, 십이지장용종증의정도가심하거나전정부의위염이있는경우와연관이있었다 [12]. 따라서이형성이발견되거나 40세미만의환자에서다수 (20개이상 ) 의위저선용종이발견되는경우가족성선종성용종증이동반되어있을가능성을생각하여대장내시경검사를해보는것이권장된다. 치료위저선용종을처음발견한경우한개이상의대표적인용종에서조직검사를시행하여확진해야한다. 크기가 1 cm 이상인경우제거하는것이좋은데위저선용종은 1 cm 이상자라는경우가드물고조직채취가불충분하여이형성이있는부위를놓칠수있기때문이다. 또한철저한관찰을통해다른 용종들과다르게보이거나크기가 1 cm 이상인경우나, 미란이나궤양이형성되어있는경우그리고전정부와같이전형적인위치에있지않은경우용종절제를고려한다. 20개이상의용종이발견되거나 1 cm 이상의용종이발견된경우양성자펌프억제제를사용중이라면중지하여용종이줄어드는지관찰하고다른양성자펌프억제제로변경하거나최소한의용량으로사용하는것을고려해야한다 [13]. 위저선용종은다른용종들에비해악성화비율이낮아상대적으로중요성이떨어질수있지만가족성선종성용종증을의심해볼수있는단서가될수있으므로가족력을확인해보는것이필요하고위저선용종의개수나성상뿐만이아니라위산분비억제치료의병력등도확인해보는것이좋겠다. 과증식성용종 (hyperplastic polyp) 과증식성용종은육안적으로부드러운돔형태를띄고발적을띄며반구상과아유경성인형태가흔하다 (Fig. 2A). 크기는수 cm까지커지기도하지만 0.5-1.5 cm가보통이고단독으로나타날경우전정부에다발성으로나타날경우위에전체적으로분포된다. 위축성위염, H. pylori 연관성위염, 위궤양이나미란의주변부그리고담즙역류에지속적으로노출되는 Billroth I 또는 II 수술을받은환자에서문합부위에잘발생된다. 보통증상이없는환자에서우연히발견되지만크기가큰경우표면상피가손상되면서만성적인실혈로인해철분결핍성빈혈이발생될수있고큰용종에의해위출구폐색이발생되기도한다. 조직학적으로주로위소와 (foveolae) 상피의증식및확장, 위샘의과형성과확장등의소견을보이며과증식된상피세포들로인하여주름이잡히고내강표면이 corkscrew 모양을보인다 [14] (Fig. 2B). 바탕질에는부종, 염증세포의침윤및산재된평활근이관찰되는데염증성침윤 (inflammatory infiltrate) 이현저한경우염증성용종 (inflammatory polyp) 으로불리기도하며크기가클수록미란을동반하는경우가많다. 발생기전은명확하지않으나과증식성용종은현저한점막의재생에의한결과로발생되는것으로제시되고있는데점막의손상이나미란후에치유와재생이소와의증식 (foveolar hyperplasia) 의형태로발생될수있고이런과증식된조직들은자연적으로소실되기도하지만지속적으로남아있거나과증식성용종으로진전되기도한다 [15]. 과증식성용종은 H. pylori 감염또는자가면역성위염등과관련이많은데전암성상태인위축성위염과같이배경이 - 309 -
- 대한내과학회지 : 제 90 권제 4 호통권제 668 호 2016 - A B Figure 2. Hyperplastic polyp with dysplastic foci. (A) Endoscopic finding showing a smooth and dome-shaped polyp. (B) Histological finding showing the hyperplastic foveolar epithelium and cystically dilated glandular tissue with inflammatory cells and smooth muscle in the lamina propria. The focal proliferative dysplasic epithelium is shown in the box. Cells are stained with Hematoxylin & Eosin. 100 magnification. A B Figure 3. Gastric adenoma and hyperplastic polyps. (A) Multiple hyperplastic polyps and a synchronous gastric adenoma in the antrum are shown (arrow). (B) A close-up view of the gastric adenoma. 되는위점막에이상소견이있다는점이중요하다. 과증식성용종에서이형성이발생되는확률은 1.9-19% 까지다양하게보고되고있으며암이발생되는경우는 0.6-2.1% 로보고되고있고크기가 2 cm 이상큰경우에더흔하게나타난다 (Fig. 2). 용종주변점막에서종양이발생될위험이증가되는것으로알려져있고 (Fig. 3) 용종자체에서발생되는것보다주변점막에서암이발생될위험이더높다 [2,16]. 따라서주변점막을자세히관찰하여이상이있을경우조직검사를하는것이필요하겠다. 치료과증식성용종은일부에서악성화가능성이있기때문에 1 cm 이상의용종은절제가필요하며절제된조직에대한철저한병리검사가필요하다. 서구의가이드라인에서는주변정상점막을조직검사하여위암의전구병변인위축성위염의범위와정도를검사해보는것을권장하고있다 [2]. 절제이외에다른치료방법으로 H. pylori 제균치료를들수가있는데과증식성용종이 H. pylori 와연관되어있으므로점막손상을일으키는기저상태를없애주는것이효과를볼수가있겠다. 국외의연구에서 H. pylori 제균치료로 70% 까지과증식성용종이감소되었다는보고가있었고 [17] 국내보고 에서는과증식성용종의크기가 10 mm 이내인경우와무경성형태를보이는경우 H pylori 제균후에용종의소실률이높았다는보고를하였으며제균치료에성공한경우 90% 정도의부분또는완전소실을보고하였다 [18]. 최근의국내연구에서도 H. pylori 제균치료가과증식성용종의소실을 85% 까지유도한다는보고가있었다 [3]. 서구의가이드라인에서는과증식성용종이있는경우 H. pylori 제균치료를권장하고있지만 [2] 현재국내의제균치료가이드라인에과증식성용종에대한 H. pylori 제균치료는아직포함되어있지않은상태이다. 선종성용종 (adenomatous polyp; gastric adenoma) 위선종의유병률은서구에서는 0.5-3.75% 로보고되었고위암이많이발병하는지역에서는 9-20% 정도로높게보고되고있다 [19]. 위선종은위암의전구병변이되는신생물성병변으로 50-60대에가장흔히발생된다. 위축성위염이나장상피화생이있는경우에더흔하게발생되며위치는위의전정부에서주로발견되고단독으로생기는경우 (> 82%) 가많다. 육안소견은주로퇴색조를띄는경우가흔하고표면은균일하며분엽 - 310 -
- 이승우. 위용종의진단및치료 - 상을보인다 (Fig. 3). 조직학적으로는관상, 융모상, 관-융모상형태로분류된다. 대장의선종과마찬가지로암으로진행하는단계로생각해야하며크기가커질수록암을포함하고있을확률이증가되며동시성암의가능성도있으므로내시경관찰시염두에두어야겠다. 조직검사결과가위선종병변전체를대변할수없기때문에내시경절제후병리검사결과와일치하지않는경우가많이있으므로주의를요한다. 위선종점막에함몰성병변, 발적, 미란, 궤양, 불균일함, 결절성등이관찰될때는위암이나고등급선종과연관된소견이므로적극적인치료가필요하겠다. 치료 위선종은위암의전구병변이면서동시에위암을포함할수있기때문에안전하게시행할수있다면완전절제를해주는것이권장된다. 동시성병변이존재할수있으므로위점막전체를철저히검사하여이상이있는부위에서조직검사가필요하다. 위선종의내시경절제후이시성병변이발견될수있는데최근의연구에서 H. pylori 제균치료가이시성병변의발생을예방할수있다는결과를보고하였다 [20,21]. 국내의가이드라인에서는위선종이있는환자에서 H. pylori 치료에대한지침은아직없는상태이나유럽과미국의가이드라인에서는 H. pylori 제균치료를권장하고있다 [22,23]. 결 위용종은육안적소견및조직검사결과로진단이가능하지만조직검사만으로용종안에포함된이형성이나암을확인할수없다는문제가있어서크기가 1 cm 이상인경우는용종절제술이추천된다. 하지만안전하게절제가시행될수있도록내시경을시행하는의사는합병증에충분히대처할수있어야하겠다. 용종의육안형태가비전형적인경우이형성이나암이포함되어있을가능성이있으므로신중한접근이필요하다. 론 중심단어 : 위 ; 용종 ; 진단 ; 치료 REFERENCES 1. Crawford JM. The gastrointestinal tract. In: Cotran RS, Kumar V, Robbins SL, eds. In: Robbins pathologic basis of disease. 6th ed. Philadelphia: W. B. Saunders Company, 775-843. 2. Goddard AF, Badreldin R, Pritchard DM, Walker MM, Warren B; British Society of Gastroenterology. The management of gastric polyps. Gut 2010;59:1270-1276. 3. Nam SY, Park BJ, Ryu KH, Nam JH. Effect of Helicobacter pylori infection and its eradication on the fate of gastric polyps. Eur J Gastroenterol Hepatol 2016;28:449-454. 4. Cao H, Wang B, Zhang Z, Zhang H, Qu R. Distribution trends of gastric polyps: an endoscopy database analysis of 24 121 northern Chinese patients. J Gastroenterol Hepatol 2012;27: 1175-1180. 5. Abraham SC, Nobukawa B, Giardiello FM, Hamilton SR, Wu TT. Sporadic fundic gland polyps: common gastric polyps arising through activating mutations in the beta-catenin gene. Am J Pathol 2001;158:1005-1010. 6. Levy MD, Bhattacharya B. Sporadic fundic gland polyps with low-grade dysplasia: a large case series evaluating pathologic and immunohistochemical findings and clinical behavior. Am J Clin Pathol 2015;144:592-600. 7. Jeong YS, Kim SE, Kwon MJ, et al. Signet-ring cell carcinoma arising from a fundic gland polyp in the stomach. World J Gastroenterol 2014;20:18044-18047. 8. Zelter A, Fernández JL, Bilder C, et al. Fundic gland polyps and association with proton pump inhibitor intake: a prospective study in 1,780 endoscopies. Dig Dis Sci 2011;56: 1743-1748. 9. Jalving M, Koornstra JJ, Wesseling J, Boezen HM, S DE Jong S, Kleibeuker JH. Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy. Aliment Pharmacol Ther 2006;24:1341-1348. 10. Choudhry U, Boyce HW Jr, Coppola D. Proton pump inhibitor-associated gastric polyps: a retrospective analysis of their frequency, and endoscopic, histologic, and ultrastructural characteristics. Am J Clin Pathol 1998;110:615-621. 11. Burt RW. Gastric fundic gland polyps. Gastroenterology 2003;125:1462-1469. 12. Bianchi LK, Burke CA, Bennett AE, Lopez R, Hasson H, Church JM. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin Gastroenterol Hepatol 2008;6:180-185. 13. Shaib YH, Rugge M, Graham DY, Genta RM. Management of gastric polyps: an endoscopy-based approach. Clin Gastroenterol Hepatol 2013;11:1374-1384. 14. Jain R, Chetty R. Gastric hyperplastic polyps: a review. Dig Dis Sci 2009;54:1839-1846. 15. Orlowska J, Jarosz D, Pachlewski J, Butruk E. Malignant transformation of benign epithelial gastric polyps. Am J Gastroenterol 1995;90:2152-2159. - 311 -
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