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1 A-IV. 상부위장관치료내시경 : 기본에서고급술기까지 Room A 고려대학교의과대학내과학교실 Polypectomy/Mucosal Resection Eun Sun Kim Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea 서론 위용종은상부위장관내시경을하는동안우연히발견되는경우가대부분이며증상을동반하는경우는매우드물지만일부의위용종은악성의가능성이있으므로적합한진단과처치는매우중요하다. 본저자는위용종에대하여전반적인내용및위용종을안전하게제거할수있는절제술의방법과적용에대하여소개하고자한다. 위용종은상부위장관내시경검사도중약 6% 에서발견이된다. 1 3 헬리코박터필로리감염이높은지역에서는증식성용종및선종이더흔하며 2 4 헬리코박터감염률이낮고양성자펌프억제제투약빈도가높은서구에서는위바닥샘용종 (fundic gland polyp) 의빈도가더높다. 1,4 본론 1. 용종의초기평가 1) 용종의조직학적평가작은단발위용종이발견되면조직검사혹은용종절제술을시행하여현미경적조직형태를확인해야한다 cm 이상크기의위용종은조직검사만으로는국소고도이형성및조기암병변을완전히배제할수없기때문에모두용종절제술을시행해야한다. 7 다발성용종을가진환자에서는가장큰용종에대하여용종절제술을시행하고다른대표용종들에서조직검사를시행하도록한다. 10,11 목없는용종 (sessile polyp) 에대하여는조직확진과완전제거를위하여내시경적점막절제술 (endoscopic mucosal resection) 을시행한다. 12 2) 주변점막의평가용종의조직검사와함께주변점막의조직검사도함께병행하는것이좋다. 전정부와위몸통에서조직검사를시행하여장상피화생위축및헬리코박터필로리감염이동반되었는지확인한다. 11 Operative Link on Gastritis Assessment (OLGA) staging system 등을이용하여위염을분류하고위암의위험인자인위점막위축정도를평가한다. 13,14 2. 위용종의타입분류에따른향후관리및치료 1) 증식성용종헬리코박터필로리감염이높은지역에서는증식성용종이전체위용종의 75% 를차지한다. 증식성용종은만성염증자극으로인한과다 재생점막상피 (hyper regenerative epithelium) 의결과로발생한다. 따라서만성위축성위염과같은만성염증, 헬리코박터필로리감염, 악성빈혈, 궤양주변, 위소장연결술부위에서주로발견된다. 15 남녀에서비슷한빈도로발생하며중장년층이후에주로발생한다. 증식성용종은무증상인경우가많고우연히발견된다. 증식성용종은시간이경과함에따라변화가없기도하고, 크기가증가하거나헬리코박터필로리제균에의해소실되기도한다. 16,17 무증상이대부분이지만증식성용종에생긴미란부위에서출혈이발생하기도하고드물지만유경성인경우위유문부위에서협착증상을보이기도한다. 18,19 내시경검사소견에서매끈하고반구형태, 혹은줄기가있으며 cm 크기가흔하다. 증식성용종은다발성인경우가많고위전정부, 몸통, 기저부, 분문에생길수있다. 2,20 조직학적소견은다음과같다 : elongated, dilated, and/or cystic, architecturally distorted, foveolar epithelium within 64 Korean Society of Gastrointestinal Endoscopy

2 an edematous, congested, and often actively and chronically inflamed lamina propria. 21,22 Other features that may be seen include epithelial regenerative changes, dystrophic goblet cells, intestinal metaplasia, pyloric metaplasia (in corpus and fundic lesions), surface erosion, and ulceration. 증식성용종에서이형성 / 선암의순서를통해악성병변이발생할수있다. 1,23, % 의증식성용종에서이형성의국소잠복부위가보고되고있다 cm 이상의유경성증식성용종에서는악성의위험도가높지만고유근이상침범의가능성은매우낮다. 23 증식성용종의크기가 0.5 cm 보다크면완전절제가필요하며헬리코박터필로리균이양성인모든증식성용종환자에서제균치료가권유된다. 17 위증식성용종의추적관찰은이형성이나선암이없는경우그외의위암위험도에따라시행하도록한다. 고위험군 ( 예 ; Operative Link on Gastritis Assessment [OLGA] stage 3 or 4 with moderate diffuse or severe atrophy in the corpus or antrum usually accompanied by extensive intestinal metaplasia, migrants from areas with high gastric cancer incidence, family history of gastric cancer) 에서는 1,2년마다정기적으로상부위장관내시경검사를시행한다. 위암발생저위험군에서는 ( 예 ; OLGA stage 1 or 2) 헬리코박터필로리제균치료후 3 6개월사이에추적상부위장관내시경검사를시행하여새로운용종이나절제가필요한용종이남아있는지확인하도록한다. 2) 위바닥샘용종 (fundic gland polyp) 헬리코박터필로리감염이적고양성자펌프억제제사용이많은나라에서흔히관찰된다. 위바닥샘용종은대부분산발적으로발생하지만, 가족성용종증후군 (familial adenomatous polyposis, FAP), MUTYH 연관용종증 (MAP), gastric adenocarcinoma and proximal polyposis of stomach (GAPPS) 환자에서도관찰된다 FAP 의경우 % 의환자에서위바닥샘용종이관찰된다. 30,31 가스트린종에동반된고가스트린혈종, 졸링거엘리슨증후군, 양성자펌프억제제장기간투약이위바닥샘용종과관련이있다. 4,32 34 양성자펌프억제제를 5년이상투약시위바닥샘용종발생위험도가 4배증가하지만 1년미만투약시에는관련이없다. 4 헬리코박터필로리감염과는역의관계가있으며감염에의해위바닥샘용종이소실될수있다. 32,35 산발적으로발생하는위바닥샘용종은여자에더호발하고중년층에주로생기며 40% 의환자에서다수의용종을갖고있다. FAP 환자들에서는남녀모두비슷한빈도로발생하고 40세이전에주로발생하며 90% 의환자에서다발성으로생긴다. 위바닥샘용종의내시경소견은주로작은크기의 ( cm) 울혈성, 무경성, 매끈한표면으로관찰된다. 주로위몸통에서생기고협대역내시경으로관찰시혈관이밀집된벌집모양으로보인다. 병리소견은다음과같다 : be composed of normal gastric corpus type epithelium, arranged in a disorderly and/or microcystic configuration. 3 증후군관련위바닥샘용종에서 APC 유전자체세포변이가 70% 이상관찰되지만산발성인경우 10% 미만으로발생한다. 36 양성자펌프억제제관련위바닥샘용종의악성가능성은거의없는것으로여겨지고있다. 37 하지만 FAP 환자의위바닥샘용종은드물게악성으로진행하기도하며 30 50% 의환자에서는저도이형성이동반되기도한다. 38,39 위바닥샘용종은대부분다발성이므로하나이상의대표적인병변에서조직검사를시행하는것이좋다. 남아있는용종들을주의깊게관찰하고육안적소견이두드러지게다른부분에서조직검사를추가로시행하고가능하다면절제를하도록한다. 1 cm 이상의위바닥샘용종및궤양을동반한경우및위전정부에발생한경우에는확진및이형성혹은신생물을배제하기위해절제를시행하도록한다. 용종의개수가 20개이상인경우, 전정부에발생한위닥샘용종, 40세이전에발생한경우, 십이지장의선종이동반된경우에는 FAP의가능성을고려하도록하고대장내시경을시행한다. FAP 환자를제외하고는이형성이동반되지않다면정기적인상부위장관내시경검사는권유되지않는다. 3) 염증성섬유소모양용종 (inflammatory fibroid polyps) 매우드문병변이며전체위용종의 0.1% 미만이다. 염증성섬유소모양용종은중간엽종양 (mesenchymal tumor) 으로위장관점막, 점막하부위에발생한다. 면역조직화학염색에서수지상 (dendritic) 세포유래인것으로여겨진다. 40 대부분무증상이지만크기가큰경우에복통, 조기팽만, 빈혈, 위출구폐색증상이생길수있다. 내시경소견으로단단하고단발성, 무경성혹은유경성, 간헐적으로궤양이동반되는경우가있다. 초음파내시경검사에서저에코의균일한병변으로경계가불명확하고주로 2( 점유근 ), 3( 점막하층 ) 번째층에존재한다. 병리소견은다음과같다 : be characterized by submucosal proliferations of spindle cells with vessels surrounded by a characteristic circumferential deposition of fibroblasts giving it an onion skin appearance, and an inflammatory infiltrate with a predominance of eosinophils. 염증성섬유소모양용종은신생물이아닌반응성 (reactive) 병변으로여겨진다. 절제후에는대개의경우재발하지않으므로추적검사는권유되지않는다. 제 51 회대한소화기내시경학회세미나 65

3 3. 용종절제술환자준비용종절제술은출혈고위험시술이므로항응고제, 항혈소판제를복용하는환자들은투약중지를고려하도록한다. 예방적항생제의투약은필요하지않다. 4. 시술도구준비기본적인내시경도구와더불어다음과같은도구를준비하도록한다. 1) Poypectomy snares 2) Electrosurgical generators 3) Injection needles 4) Saline or hyaluronic acid 5) Methylene blue or indigo carmine dye for staining 6) India ink or other dye for tattooing 7) Retrieval nests 8) Hemoclips 9) Nylon loops 10) Argon plasma coagulation (APC) probes 11) Argon gas 5. 위용종절제술술기용종절제술의목적은크게두가지로생각해볼수있다. 첫번째는완전한절제이며두번째는병리검사를위한조직획득이다. 위용종을절제하는방법은용종의크기와형태, 위치, 시술자의숙련도나경험에따라서다르게선택할수있다. 1) 올가미폴립절제술 (snare polypectomy) 크기가큰유경성용종에사용할수있는방법으로전기지짐 (electrocautery) 을이용하여용종의줄기 (stalk) 부위를절제한다. 또한, 무경성용종을절제할수도있으며 1 cm 미만의작은용종인경우전기지짐을이용하지않고절제할수도있다. 1 cm 이상크기의용종은전기지짐을시행하여주로제거한다. 점막하주입은 1.5 cm 이상크기의용종에서주로시행하도록한다. 다양한올가미들이시판되고있으며전통적인큰사이즈의연성 (soft) 올가미, 경성 (stiff) 올가미, 작은사이즈의올가미, 육각형의올가미등이있다. 2) 내시경적점막절제술 (endoscopic musical resection, EMR) EMR 은크기가비교적큰무경성용종을절제할수있는방법이다. 점막과점막하층을고유근층과분리시키기위하여점막하주입을시행한후절제하는소위 lift and cut 방법으로시행한다. 점막하주입후에올가미와전기지짐을이용하여절제 한다. 크기가큰경우 ( cm 이상 ), 일괄절제가아닌단편절제 (piecemeal resection) 이되는경우가발생하는데, 이러한경우절제된조직의경계와여백 (margin) 상태를알수없으며또한, 국소적인조기암이나이형성을찾기에어려움이있으므로일괄절제가되도록하는것이중요하다. 하지만 2 cm 이상의경우올가미를이용한일괄절제시천공등의위험이있으며이러한경우내시경적점막하박리술 (endoscopic submucosal dissection) 을고려하도록한다. 3) 용종경계, 여백의결정용종절제전용종의경계를명확히살피는것이중요하다. 이를위해 0.1 1퍼센트의인디고카민색소를살포하여관찰하거나협대역내시경으로용종과정상점막의경계를자세히관찰할수있다. 메틸렌블루색소를첨가한식염수를점막하주입하여경계를관찰할수도있다. 4) 점막하주입식염수혹은다른액체를용종하부의점막하에주입하여용종이액체쿠션위로들어올려지도록한다. 이로인해내시경적절제를용이하게할수있으며천공의위험을줄일수있다. 41 점막하주입을할때에는내시경과먼위용종의원위부에서부터시작하는것이좋다. 내시경과가까운근위부부터점막하주입을하여근위부가먼저융기하게되면시야에서용종이잘보이지않고용종의원위부로접근이어렵게된다. 점막하주입으로들어올려지지않는병변은섬유화혹은악성병변일가능성이있음에도유의한다. 식염수를이용한점막하주입으로인해전기지짐이통과하는깊이가얕아지며이로인해천공의위험을줄일수있을것으로여겨진다. 식염수주입의문제점은빠른흡수이다. 점막의융기가빠른시간내에다시가라앉기때문에이에대한대안으로히알루론산 (hyaluronic acid), 42,43 포도당용액, 44 숙시닐젤라틴 (succinylated gelatin), 45 하이드록시에틸전분 (hydroxyethyl starch) 46 을쓸수있다. 점막하주입액에에피네프린을시술후지혈의목적으로함께섞어서사용하기도한다. 희석된에피네프린 (1:10,000~1:20,000) 을용종의줄기나용종의기저부에주사한다. 하지만아직이방법이단순히식염수나히알루론산주입보다용종절제술후출혈을효과적으로줄이는지에대한데이터는확립된바없다. 5) 용종절제용종은겸자구의위치에따라내시경의 6시방향에위치하도록한다. 용종을올가미를이용하여잡은다음전기지짐을시행하여절제를한다. 응고 (coagulation) 모드혹은응고 / 절제 (coagnlation and cutting) 혼합모드를사용할수있다. 반드시올가미로잡은용종을들어올리면서전기지짐을시행해야만 66 Korean Society of Gastrointestinal Endoscopy

4 전기가깊이통과되어천공이발생하는것을예방할수있다. 용종을제거한바닥이남은조직없이모두제거되었음을확인해야한다. 6) 용종절제후잔류병변이남은경우의처치절제후용종의병변잔류가의심되는경우조직겸자를이용하여추가로제거를하거나아르곤플라즈마응고 (argon plasma coagulation, APC, power limit 60W, argon flow 1 to 2L per minute) 혹은모노폴라 (monopolar) 응고 (pure coagulation, power limit 60W) 를시행할수도있다. 7) 출혈의예방출혈의위험을감소시키기위하여용종절제술부위에에피네프린주사법, 지혈클립으로봉합, 유경성용종의줄기부분을클립으로결찰혹은나일론고리로결찰하는방법중에선택할수있다. 결론 이상으로위용종과용종절제술에대한내용을살펴보았다. 위용종을치료함에있어서용종절제술의술기와기술을익히는것에못지않게위용종의조직학적분류에따른특성및향후악성화가능위험도의파악, 추적검사의적절한계획수립또한매우중요하다고생각한다. 따라서본원고가이에조금이나마도움이되기를바란다. 참고문헌 1. Carmack SW, Genta RM, Schuler CM, et al. The current spectrum of gastric polyps: a 1 year national study of over 120,000 patients. Am J Gastroenterol 2009;104: Archimandritis A, Spiliadis C, Tzivras M, et al. Gastric epithelial polyps: a retrospective endoscopic study of symptomatic patients. Ital J Gastroenterol 1996;28: Morais DJ, Yamanaka A, Zeitune JM, et al. Gastric polyps: a retrospective analysis of 26,000 digestive endoscopies. Arq Gastroenterol 2007;44: Jalving M, Koornstra JJ, Wesseling J, et al. Increased risk of fundic gland polyps during long term proton pump inhibitor therapy. Aliment Pharmacol Ther 2006;24: Ginsberg GG, Al Kawas FH, Fleischer DE, et al. Gastric polyps: relationship of size and histology to cancer risk. Am J Gastroenterol 1996;91: Papa A, Cammarota G, Tursi A, et al. Management of gastric polyps: the need of polypectomy also for small polyps. Am J Gastroenterol 1997;92: Muehldorfer SM, Stolte M, Martus P, et al. Diagnostic accuracy of forceps biopsy versus polypectomy for gastric polyps: a prospective multicentre study. Gut 2002;50: Yoon WJ, Lee DH, Jung YJ, et al. Histologic characteristics of gastric polyps in Korea: emphasis on discrepancy between endoscopic forceps biopsy and endoscopic mucosal resection specimen. World J Gastroenterol 2006;12: Akahoshi K, Yoshinaga S, Fujimaru T, et al. Endoscopic resection with hypertonic saline solution epinephrine injection plus band ligation for large pedunculated or semipedunculated gastric polyp. Gastrointest Endosc 2006;63: Hirota WK, Zuckerman MJ, Adler DG, et al. ASGE guideline: the role of endoscopy in the surveillance of premalignant conditions of the upper GI tract. Gastrointest Endosc 2006; 63: Committee ASoP, Sharaf RN, Shergill AK, et al. Endoscopic mucosal tissue sampling. Gastrointest Endosc 2013;78: Carmack SW, Genta RM, Graham DY, et al. Management of gastric polyps: a pathology based guide for gastroenterologists. Nat Rev Gastroenterol Hepatol 2009;6: Rugge M, Meggio A, Pennelli G, et al. Gastritis staging in clinical practice: the OLGA staging system. Gut 2007;56: Rugge M, Correa P, Di Mario F, et al. OLGA staging for gastritis: a tutorial. Dig Liver Dis 2008;40: Dirschmid K, Platz Baudin C, Stolte M. Why is the hyperplastic polyp a marker for the precancerous condition of the gastric mucosa? Virchows Arch 2006;448: Ljubicic N, Banic M, Kujundzic M, et al. The effect of eradicating Helicobacter pylori infection on the course of adenomatous and hyperplastic gastric polyps. Eur J Gastroenterol Hepatol 1999;11: Ohkusa T, Takashimizu I, Fujiki K, et al. Disappearance of hyperplastic polyps in the stomach after eradication of Helicobacter pylori. A randomized, clinical trial. Ann Intern Med 1998;129: Al Haddad M, Ward EM, Bouras EP, et al. Hyperplastic polyps of the gastric antrum in patients with gastrointestinal blood loss. Dig Dis Sci 2007;52: Kumar A, Quick CR, Carr Locke DL. Prolapsing gastric polyp, an unusual cause of gastric outlet obstruction: a review of the pathology and management of gastric polyps. Endoscopy 1996;28: Stolte M, Sticht T, Eidt S, et al. Frequency, location, and age and sex distribution of various types of gastric polyp. Endoscopy 1994;26: Snover DC. Benign epithelial polyps of the stomach. Pathol Annu 1985;20 Pt 1: Hattori T. Morphological range of hyperplastic polyps and carcinomas arising in hyperplastic polyps of the stomach. J Clin Pathol 1985;38: Antonioli DA. Precursors of gastric carcinoma: a critical review with a brief description of early (curable) gastric cancer. Hum Pathol 1994;25: Dijkhuizen SM, Entius MM, Clement MJ, et al. Multiple hyperplastic polyps in the stomach: evidence for clonality and neoplastic potential. Gastroenterology 1997;112: Daibo M, Itabashi M, Hirota T. Malignant transformation of 제 51 회대한소화기내시경학회세미나 67

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<303520C0C7C7D0B0ADC1C220C0CCBDC2BFEC2E687770> 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