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1 Korean J Gastroenterol Vol. 63 No. 2, pissn eissn REVIEW ARTICLE 근거기반위암진료권고안 이준행, 김재규 1, 정혜경 2, 김정훈 3, 정우경 4, 전태주 5, 김준미 6, 김용일 7, 류근원 8, 공성호 9, 김형일 10, 정훈용 11, 김용식 12, 장대영 13, 조재용 14, 박준오 15, 임도훈 16, 정은선 17, 안형식 18, 김현정 18 성균관대학교의과대학삼성서울병원내과, 중앙대학교의과대학내과학교실 1, 이화여자대학교의학전문대학원내과학교실 2, 서울대학교의과대학영상의학과 3, 성균관대학교의과대학삼성서울병원영상의학과 4, 연세대학교의과대학강남세브란스병원핵의학과 5, 인하대학교의과대학병리학교실 6, 이화여자대학교의학전문대학원외과 7, 국립암센터위암센터 8, 서울대학교병원외과 9, 연세대학교의과대학외과 10, 울산대학교의과대학서울아산병원내과 11, 고려대학교의과대학내과 12, 한림대학교의과대학혈액종양내과 13, 연세대학교의과대학종양내과 14, 성균관대학교의과대학삼성서울병원혈액종양내과 15, 성균관대학교의과대학삼성서울병원방사선종양학과 16, 가톨릭대학교의과대학서울성모병원병리과 17, 고려대학교의과대학예방의학교실 18 Synopsis on Clinical Practice Guideline of Gastric Cancer in Korea: An Evidence-Based Approach Jun Haeng Lee, Jae G. Kim 1, Hye-Kyung Jung 2, Jung Hoon Kim 3, Woo Kyoung Jeong 4, Tae Joo Jeon 5, Joon Mee Kim 6, Young Il Kim 7, Keun Won Ryu 8, Seong-Ho Kong 9, Hyoung Il Kim 10, Hwoon-Yong Jung 11, Yong Sik Kim 12, Dae Young Zang 13, Jae Yong Cho 14, Joon Oh Park 15, Do Hoon Lim 16, Eun Sun Jung 17, Hyeong Sik Ahn 18 and Hyun Jung Kim 18 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Department of Medicine, Chung-Ang University College of Medicine, Seoul 1, Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University School of Medicine, Seoul 2, Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 3, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 4, Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 5, Department of Pathology, Inha University School of Medicine, Incheon 6, Department of Surgery, Ewha Womans University School of Medicine, Seoul 7, Center for Gastric Cancer, National Cancer Center, Goyang 8, Department of Surgery, Seoul National University Hospital, Seoul 9, Department of Surgery, Yonsei University College of Medicine, Seoul 10, Department of Internal Medicine, Asan Medical Center, Ulsan University College of Medicine, Seoul 11, Department of Internal Medicine, Korea University College of Medicine, Seoul 12, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang 13, Department of Medical Oncology, Yonsei University College of Medicine, Seoul 14, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 15, Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 16, Department of Pathology, Seoul St. Mary s Hospital, The Catholic University of Korea, Seoul 17, Department of Preventive Medicine, Korea University Medical College, Seoul 18, Korea Although, gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to that of Western countries. However, there is no Korean multidisciplinary guideline for gastric cancer and thus, a guideline adequate for domestic circumstances is required. Experts from related societies developed 22 recommendation statements for the diagnosis (n=9) and treatment (n=13) based on relevant key questions. Evidence levels based on systematic review of literatures were classified as five levels from A to E, and recommendation grades were classified as either strong or weak. The topics of this guideline cover diagnostic modalities (endoscopy, endoscopic ultrasound, radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, radiotherapy) and pathologic evaluation. External review of the guideline was conducted at the finalization phase. (Korean J Gastroenterol 2014;63:66-81) Key Words: Stomach neoplasms; Guidelines 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 : 김재규, , 서울시동작구흑석로 84, 중앙대학교병원소화기내과 Correspondence to: Jae G. Kim, Department of Gastroenterology, Chung-Ang University College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul , Korea. Tel: , Fax: , jgkimd@cau.ac.kr Financial support: None. Conflict of interest: None. Korean J Gastroenterol, Vol. 63 No. 2, February

2 Lee JH, et al. Clinical Practice Guideline of Gastric Cancer in Korea 서론 (Introduction) 1-1. 위암진료권고안개발의필요성, 목적및범위최근국내암발생률이계속높아지고있다. 보건복지부국가암정보센터자료에의하면연도별암발생률이 1999년부터 2008년까지연간 3.3% 씩유의하게증가하였다. 1,2 2008년통계청자료에의하면남자는평균수명 77세까지생존할경우 37.2%, 여자는 83세까지생존할경우 30.5% 에서암발생확률이있어, 국민 3명중한명은암에걸릴수있다. 적극적인치료로인하여위암의생존율이향상되고있으나, 년동안발생한위암의 5년생존율은 63.1% 수준으로아직예후가나쁜암종이다. 1 통계청사망원인통계에따르면 2009 년총사망자 246,942명중 28.6% 가악성신생물로인한사망이었고, 이중위암으로인한사망이가장많았다. 2 국내에서위암으로인한경제적손실규모는매우크다. 2007년도건강보험심사청구원자료에따르면소화기질환으로인한총의료비용 ( 건강보험요양급여에소요되는총비용중식대, 선택진료비, 약제비용을제외한비용 ) 은약 3조 6천 5백억원이었다. 이중소화기악성질환으로인한비용이전체의 36.6% 였고, 단일질환으로는위암이차지하는비율이가장높아 3천 9백억원으로전체소화기질환의 10.9% 를차지했다 ( 미발표자료 ). 본지침은국내외의근거를기반으로우리나라의료실정에적합하고임상적으로널리사용되도록개발하였다. 1차, 2차및 3차의료기관에종사하는모든의료진에게도움이되는권고안을제시하고자하였다. 또한환자및일반인에게는최선의의학정보를제공하여최적의진료를받을수있도록하였다. 나아가본지침의활용및보급으로국내위암치료수준을향상시키고, 이를통하여환자의삶의질을개선하며국민보건향상에이바지하고자하였다. 본진료권고안의대상인구집단은성인남녀위암환자이다. 대상사용자는 1차, 2차및 3차의료기관에서위암환자의진료에임하는의료진 ( 내과의, 외과의, 영상의학과의및병리과의, 가정의학과의, 일반의등 ) 및기관의지도자및관리자이다. 또한전공의및병원근무인력에대해서도진료원칙의길잡이역할을하고자한다. 아울러환자와일반인에대해서도실제적이고표준적인의학정보를제공하고자하였다. 본진료권고안은위암의진단과치료에대한구체적이고포괄적인표준권고안이다. 위암의선별검사에대한부분과소아의위암은제외하였다. 교과서적기술보다분야별핵심질문을통한근거중심의표준권고안으로작성하였다. 비교연구가부족하거나논란이큰분야에대한부분은제외하였다. 다만, 임상적의의가크고전문가들의의견이일치되는일부분야는문헌근거가다소부족하더라도명목집단법으로합의하여권고안을작성하였다. 관련전문분야의완전한합의가이루어지지못한내용은제외하였다 진료권고안개발그룹구성과진행본진료권고안은보건복지부암정복사업지정연구과제 ( 과제번호 ) 로실행되었다. 대한의학회, 대한내과학회, 대한방사선종양학회, 대한병리학회, 대한상부위장관ㆍ헬리코박터학회, 대한소화기내시경학회, 대한소화기학회, 대한암학회, 대한영상의학회, 대한위암학회, 대한핵의학회의다학제적접근을통해통합적이고포괄적으로개발하였고지침개발방법론전문가가포함되었다. 진료권고안개발을위하여소화기암진료권고안조직위원회, 위암표준진료권고안개발위원회및위암표준진료권고안검토위원회를구성하였고위원은각학회의추천을받았다. 각위원회의구체적구성과역할은임상진료지침정보센터 ( 에탑재되어있다 문헌검색, 평가및권고안작성위암의진단및치료에관한기본적이고중요한사항을 patient, intervention, comparator, outcome (PICO) 형식에따라핵심질문으로선정하였다. 각핵심질문에해당하는검색어를미국국립의학도서관에서정한 Medical Subject Headings (MeSH) 용어를이용하여선정하였다. 각핵심질문에대해선택및제외기준을설정하고검색어를적절히조합하여문헌검색을실시하였다. 국외문헌검색의데이터베이스는 MEDLINE과 Cochrane Library를이용하였고, 국내문헌검색의데이터베이스는 KoreaMed를이용하였다. 1980년부터 2011년까지발표된영문혹은우리말문헌을대상으로하였다. 근거에사용될자료로선택된문헌에대한타당성평가를위하여체계적이고일관된평가방법을적용하였다. 연구설계방법에따라문헌을분류하여각각의평가방법을달리적용하였다. 3 무작위비교연구의평가는코크란의 risk of bias (ROB) 법을이용하였다. 4 RevMan 5 프로그램 (The Nordic Cochrane Center, The Cochrane Collaboration, 2012) 과 GRADEpro 프로그램 (Jan Brozek, Andrew Oxman, Holger Schünemann, 2008) 을이용하여근거를정리하고근거표를요약하였다. 5 비무작위연구의평가는 Newcastle-Ottawa assessment scale (NOS) 을이용하였다. 진단연구의평가를위하여 QUADAS 도구를이용하였다. 6 QUADAS 도구의 14개평가항목중실제적으로평가할수있는 11개항목에대하여각각 예, 아니오, 불확실 로평가하였다. 근거요약을위해서는 GRADE 방법을이용하였다. 7,8 문헌의연구유형에따라, 무작위임상시험은높은 (high) 근거수준에서, 관찰연구는낮은 (low) 근거수준에서시작한후연구의질에영향을주는요소를고려하여해당연구의질적수준을올리거나내리는방법을이용하였다. 근거의질수준은높음 (high quality, A), 중등도 (moderate quality, B), 낮음 (low Vol. 63 No. 2, February 2014

3 68 이준행등. 근거기반위암진료권고안 Table 1. Level of Evidence and Grade of Recommendation Level of evidence A. High quality evidence B. Moderate quality evidence C. Low quality evidence D. Very low quality evidence E. No evidence or difficult to analysis Grade of recommendation 1. Strong recommendation 2. Weak recommendation hpylori.or.kr/), 대한소화기내시경학회 ( 대한소화기학회 ( 대한암학회 ( 대한영상의학회 ( radiology.or.kr/), 대한위암학회 ( 대한핵의학회 ( 의홈페이지, 페이스북 (Facebook), 트위터 (Twitter) 등을이용하여무료로제공하고, 진료권고안에대한모니터링및의견을받을예정이다. 임상적근거가축적되면 3-5년후갱신할예정이다. quality, C), 매우낮음 (very low quality, D) 으로구분하였고, 근거가없거나분석하기어려운경우 (no evidence or difficult to analysis, E) 를추가하여사용하였다 (Table 1). 권고의등급은 GRADE 방법론에따라 (1) 바람직한효과와바람직하지못한효과의균형, (2) 근거의질, (3) 가치와선호등의측면을고려하였다. 권고의판단이어려운부분은본진료권고안에서언급하지않았고, 진료권고안의개정단계에서검토하기로하였다. 권고의등급은 (1) 강한권고 (strong recommendation) 와 (2) 약한권고 (weak recommendation) 로구분하였다 (Table 1). 강한권고란특정중재에대해권고를따를경우바람직한효과가바람직하지않은효과보다더크고, 근거의질이높으며, 다른중재와비교하여가치와선호도가우수하기때문에대부분의환자 (most patients) 에서시행할것을권하는등급이다. 약한권고란그근거가다소약하지만바람직한효과가있어다수의환자 (many patients) 에서시행되는것이좋을것으로판단되는등급이다. 약한권고등급에서는일부환자나의료진의가치나선호도에따라다른중재를선택할수있다 내외부검토및승인과정위암표준진료권고안개발위원회에서개발하고위암표준진료권고안검토위원회에서검토한위암표준진료권고안을바탕으로관련전문가, 환자및일반인이참가하는공청회를실시하였다 (2011년 10월 29일 ). 공청회에서제시된의견에따른수정보완을하였다. 본진료권고안은대한내과학회, 대한암학회, 대한병리학회, 대한상부위장관ㆍ헬리코박터학회, 대한소화기학회, 대한소화기내시경학회, 대한영상의학회, 대한외과학회, 대한위암학회, 대한방사선종양학회, 대한핵의학회의인준을받았다 진료권고안의갱신절차및향후모니터링제도개발된위암표준진료권고안은대한의학회 ( or.kr/), 대한내과학회 ( 대한방사선종양학회 ( 대한병리학회 ( pathology.or.kr/), 대한상부위장관ㆍ헬리코박터학회 ( 개발구성원의이해상충위암표준진료권고안은보건복지부암정복사업지정연구과제 ( 과제번호 : ) 인 소화기암진료권고안개발방법및위암 / 대장암진료권고안의개발 의연구로진행되었으며연구과제의연구책임자안형식 ( 고려대학교의과대학예방의학교실 ), 위암표준진료권고안세부연구책임자김재규 ( 중앙대학교의과대학내과학교실 ), 그리고대장암진료권고안세부연구책임자엄준원 ( 고려대학교의과대학외과학교실 ) 으로구성되었다. 재정후원단체의의견이진료권고안의내용에어떠한영향도주지않았다. 진료권고안개발과정에참여한모든구성원은이해상충여부에대해서명이포함된확인서를제출하였고, 참여자전원이이해상충의문제가없었다 위암표준진료권고안의한계본표준진료권고안의가장중요한한계점은국내의근거가충분하지않다는점이다. 국내의근거가부족한영역에대해서는국외의자료를이용할수밖에없었는데, 국외의자료는우리나라와역학적특성, 임상양상등이다르다는문제가있다. 위암은치료역사가깊기때문에치료효과가명확하여윤리적문제로인하여무작위연구를시행하기어려운분야가있음을확인하였다. 2. 내시경검사 (endoscopic diagnosis) 2-1. 광학내시경검사 (conventional endoscopy) 1) 상부위장관내시경과조직검사 (upper gastrointestinal endoscopy and biopsy) 상부위장관내시경검사는위암의가장기본적인검사도구이다. 적절한공기주입과점액제거후위를전체적으로관찰할수있으며위암이의심되는소화성궤양등의병소가발견되면근접하여상세한검사가가능하다. 특히의심되는부위로부터즉시조직검사를할수있다는장점이있다. 최근확대내시경을통하여점막표면변화를자세히관찰함으로써내시경육안진단에도움을받기도한다. 위암의진단을위해서는충분히교육을받은내시경의사가적절한장비로검사를시행해야한다. 내시경육안관찰을통한위암진단의민감도와특 The Korean Journal of Gastroenterology

4 Lee JH, et al. Clinical Practice Guideline of Gastric Cancer in Korea 69 이도에한계가있으므로조직검사가필수적이다. 9 통상적인경우조직검사의진단정확도를높이기위하여 4개이상의조직을얻도록권유하고있다. 그러나작은조기위암의심병소의내시경치료를고려하는상황에서는이보다적은수의조직을얻기도한다. 보만 4형진행성위암의내시경조직검사민감도는낮다. 수술로절제할범위결정을위하여수술전에내시경검사를다시시행하여클립을장착하거나 10 색소를이용할수있다. 위암병소의범위판단이어려운경우에는드물게수술장내내시경검사 (intraoperative endoscopy) 를시행하여도움을받기도한다. 11 내시경과내시경초음파의정확도를비교한최근의국내연구 14 에서조기위암의침윤정도를예측하는데있어서일반내시경의정확도가 73.7%, 내시경초음파의정확도가 67.4% 에불과하였다. 따라서위암내시경치료전내시경초음파의유용성은아직논란이있다. 권고 : 위암의내시경또는수술적절제전일반내시경검사나복부전산화단층촬영에추가하여내시경초음파검사를시행하는것은일부환자에서유용하다. ( 권고등급 2, 근거수준 D) 권고 : 상부위장관내시경검사는위암의진단을위한기본적검사다. ( 권고등급 1, 근거수준 E) 권고 : 상부위장관내시경에서위암이의심되거나암을완전히배제하기어려운병변에서조직검사를실시한다. ( 권고등급 1, 근거수준 E) 2) 색소내시경색소내시경은요철변화가미세하고색조변화가명확하지않은병변을쉽고간단하게관찰할수있는방법이다. 내시경점막하박리절제술을시행하는경우병소의경계를명확히파악하는데도움이된다. 위병변의관찰에유용한색소는 methylene blue, indigo carmine, acetic acid, crystal violet 등이며이중 indigo carmine이흔히사용된다. 12 Indigo carmine을분무하면점막의함몰부위에색소가고여표면의융기와함몰이강조된다. 이러한특징을이용하여조기위암의침윤범위, 심달도를추정하고내시경치료의절제범위를판단하는데응용할수있다. 3. 영상의학검사 (radiologic diagnosis) 3-1. 상부위장관조영술 (upper gastrointestinal series) 상부위장관조영술은안전하고비침습적이며진정 (sedation) 등전처치가필요없어위암의진단에널리이용되고있는검사방법이다. 위암에대한검사의민감도가높고병변의위치를객관적으로정확히알수있어수술전검사로도움을준다. 15,16 상부위장관조영술의진단적정보를충분히얻기위해서는적절한점막도포 (mucosal coating) 와장관팽창 (distention) 이중요하다. 이를위하여일반적으로위장관조영술에는 240% w/v의고밀도바륨을이용한다. 압박검사 (compression study) 와점막이완검사 (mucosal relief study) 를포함한단일조영검사 (single contrast study) 와고농도의바륨을점막에도포한후공기로팽창시켜시행하는이중조영검사 (double contrast study) 를모두병행시행하여야정확한상부위장관조영검사가가능하다. 17 권고 : 위암의진단을위해상부위장관촬영술 (upper gastrointestinal series) 은유용하다. ( 권고등급 1, 근거수준 C) 권고 : 내시경치료의적응증에해당하는조기위암에서색소내시경은치료범위결정에도움이된다. ( 권고등급 2, 근거수준 E) 2-2. 내시경초음파 (EUS) 내시경초음파는위암의심달도와국소림프절전이여부평가를위해사용될수있다. 최근에는위암에서복강경수술과조기위암에대한내시경적절제술이광범위하게시행되고있으므로개복하위절제술만시행되던시절보다치료전위암의병기평가가중요해졌다. 위암환자 5,601명을포함한 54 개의연구에대한최근의메타분석 13 에서내시경초음파가 T1-2 병변을 T3-4 병변과구분하는민감도와특이도는각각 0.86과 0.91로비교적우수하였다. 그러나림프절전이여부에대한민감도와특이도는이보다낮았다 (0.69 및 0.84). 13 일반 3-2. 컴퓨터단층촬영술 (CT) 컴퓨터단층촬영술은 1970년대후반부터위암을비롯한장관계종양의진단과수술전검사로이용되기시작하였고, 위를검사하기위한특수기법이개발된이후최근까지위암의발견, 진단, 정확한병기결정을통한치료방법의결정, 수술후또는항암치료후치료효과판정등에널리이용되고있다. 다중채널 CT 촬영기 (multidetector CT) 의도입으로진단의정확성이높아지고조기위암을비롯한작은병변의발견이개선되었다. 1) 다중채널 CT 촬영기를이용한컴퓨터단층촬영술다중채널 CT 촬영기의도입으로 z-축영상의해상도가개선되었고이에따른기존단일채널나선형 CT의단점인부분체적평균 (partial volume averaging) 에의한병변의불명확성도해소되었다. Vol. 63 No. 2, February 2014

5 70 이준행등. 근거기반위암진료권고안 기존문헌에서나타난위암진단을위한다중채널 CT 검사방법을살펴보면, 적어도 4채널이상의다중채널 CT 촬영기를사용하여 2.5 mm 이하의검출기두께 (detector collimation), 5 mm 이하의재구성영상의절편두께 (section thickness), 그리고 500 ml 가량의물이나상부위장관조영술에사용하는발포제 (effervescent agent) 를투입한후검사부위가적절히팽창되도록환자의체위를바꾸어검사해야한다 또한, 조영증강후역동적 CT 검사를하는것이좋은데, 그이유는동맥기영상을통해조영증강되는위점막병변을발견하기가용이하고, 문맥기영상을통해위벽과주변장기간의구분이뚜렷해지면서위암의침윤깊이를보다정확히알수있고림프절전이에대한평가가용이하기때문이다. 또한지연기영상이도움이될수있는데이는위암주변의섬유화에조영증강되면서위벽침윤을보다정확히평가할수있는경우가있기때문이다. 동맥기와문맥기영상의재구성을통해 CT 혈관촬영술을수행할수있으며위주위의혈관구조에대한수술전평가가가능하다. 다중채널 CT 촬영기를이용하여수술전병기결정 (TNM staging) 을하였던논문을고찰해본결과, T 병기의경우 % ( 중앙값, 82.1%) 의정확도를보였고, N 병기의경우 % ( 중앙값, 69.5%) 의정확도를보였다. 특히, 수술가능여부를결정하는 T4 병변에대한특이도는 % ( 중앙값, 96.5%) 로대체로높았다. 18,20-24 또한수술전 CT를통해위암의복막파급이나원격전이를진단함으로써불필요한수술을막을수있기때문에수술전검사로서의 CT 검사는반드시필요하다. 항암요법시행후치료효과를평가하는데에도역시 CT 검사가유용한데, 고형암의치료반응평가를위한기준인 RECIST criteria에서는 CT가 MR과함께고형암의크기를평가하는데가장유용하고재현가능하다고언급하고있다. 25 권고 : 수술전위암병기의예측을위한 CT 검사를시행한다. ( 권고등급 1, 근거수준 D) 2) 삼차원 CT 위장촬영술 (3-dimensional CT gastrography; virtual gastroscopy) 이기법은 CT 영상의삼차원재구성기법을이용하여상부위장관조영술이나내시경과유사한영상을제공한다. 장점으로는위암의해부학적위치에대해보다직관적으로이해할수있어수술계획을세우는데도움을줄수있고, 단면 CT 영상에서파악하기힘든함몰부나위점막주름변화의발견등을통해조기위암과같은작은위점막표면의병변을찾는데도움을줄수있다 자기공명영상 (MRI) 자기공명영상은장막외침윤이나인접한장기로의침윤을진단하는데도움을줄수있고원위부전이유무를알아내어위암환자의수술전병기결정에유효하다. 특히간전이를보는데널리이용되고있다. 최근에는간세포에만섭취되는간특이성 MR 조영제의개발로이전보다높은정확도의진단을기대할수있게되었다. 26 권고 : 조영제를사용한간 MR 검사는위암의간전이를진단하는데일부환자에서도움이된다. ( 권고등급 2, 근거수준 E) 4. 핵의학검사 (nuclear imaging) 4-1. 위암진단에서 fludeoxyglucose (FDG) PET/CT의역할 FDG PET/CT가다양한암의진단, 병기결정및치료효과판정에그사용빈도가급속히늘고있지만위암에서의역할은아직제한적이다. 지금까지발표된바에의하면 PET에의한조기위암발견율은 50% 미만이며무증상환자에서위암만을스크리닝 (screening) 하기위해서는추천되지않는다. 27 진행성위암의진단에대한연구에있어서 PET의진단능력은 62-98% 의다양한결과를보이는데이는위암의조직학적특성에따라서 FDG의섭취가큰차이를보이기때문이다 즉, 종양의현미경적성장패턴중 intestinal growth type에서는 FDG 섭취가증가하므로높은민감도를보이는반면 diffuse growth type에서는상대적으로낮은민감도를보인다. 32 이상을종합하여볼때, 조기위암의진단을위해서는내시경이나바륨상부위장관조영술등이보다효과적일것으로생각된다 병기결정및예후예측 FDG PET/CT의경우, 위암의원발종양을평가하기에는한계가있으며조영증강 CT 역시위장의특성상원발성위종양의정확한평가가어려운경우도많다. 또한병리조직검사에의하면위암종괴의세포밀도나악성도는균일하지않은경우가많기때문에 32,33 PET/CT가비록위벽침윤정도 (depth of invasion) 를정확히파악하는데한계가있을수있지만, 대사활성도를평가할수있을뿐만아니라조직검사시에악성도가높은부분을표적화 (targeting) 할수있게한다. 다음으로주변림프절의침범을평가하는데있어서 PET 로림프절의당대사를평가하는것은국소림프절로의전이의보다정확한판단을가능하게할것으로기대한바있다. Mochiki 등 31 의연구에의하면 PET를이용한 N1 림프절의진단성능은만족스럽지않지만위암수술시에이들림프절들은기본적으로제거되므로임상에서는큰영향을미치지않을 The Korean Journal of Gastroenterology

6 Lee JH, et al. Clinical Practice Guideline of Gastric Cancer in Korea 71 수도있다. 반면에 15번이상의 N3 group 림프절의침범은원격전이로분류되므로이에대한정확한판정은매우중요하다. Yun 등 34 은이부분에있어서 PET가유용한정보를줄수있다고보고하였다. 다른장기로의원격전이를평가하는데 3,025건의위암환자를대상으로한 Hillner 등 35 의연구에의하면 PET 결과에의하여 37% 에서환자의처치 (management) 가바뀌었다고보고된바있으며간전이의진단에있어서 PET는기존의검사에비하여우월한결과를보였다. 36 골전이의진단에있어서는전신골스캔의역할이여전히중요하며 PET와는상호보완적이다. 29 PET 스캔에서원발성위암의 FDG 섭취정도는해부학적영상을이용한기존의 TNM 병기결정에더하여추가적인예후인자가될수있을것으로기대된다. 32,33 이밖에, 복막전이도예후에많은영향을미치는데 PET의경우 CT에비해특이도는높은 (99%) 반면민감도는낮으며 (35%) 정확도는대등하다. 37 권고 : 위암의병기결정에있어서 FDG PET/CT는일부환자에게도움이된다. ( 권고등급 2, 근거수준 D) 4-3. 재발평가수술후재발평가는위암치료에있어서매우중요한부분이다. 재발경로는인접부위, 림프계, 혈행성, 그리고복막등이있으며결과적으로재발부위는국소부위, 간, 폐, 골격계, 복막및기타여러곳이다. 특히국소부위재발의경우, 수술로인하여변화된해부학적구조는많은경우에서정확한재발의진단을어렵게한다. 일부연구에서 PET가기존의 CT 보다우수한것으로보고하고있으며특히높은특이도와양성예측도를보이는것으로알려졌다. 33,38 물을이용하여위장을팽창시킨후시행한 PET 검사가수술후재발판정에도움이된다는보고도있다. 39 최근의 PET/CT를이용한연구결과들을종합하면전반적으로조영증강 CT에비하여우수한결과를보이고있으며 40 이는해부학적인영상과기능적영상정보를함께비교함으로써보다정확한결과를얻을수있기때문이다. 권고 : 위암수술환자의재발평가에서 FDG PET/CT는일부환자에게도움이된다. ( 권고등급 2, 근거수준 D) 4-4. 치료효과판정위암의치료시환자개인마다위암의세포형, 분화도, 악성도, 침윤정도에차이가있으므로어떠한항암제를치료에 사용할지를결정하는데있어서보다세심한선택이필요하다. Ott 등 39 은기저 PET 스캔을시행하고 2-3 사이클의항암제투여후추적 PET를시행하여항암제치료효과를판정할수있음을제시하였다. 이와같이단순히크기변화뿐만아니라위암병변대사의증감을평가함으로써보다효과적인치료방침을정할수있음을시사하는보고는계속되고있으므로앞으로이분야에서 PET의역할도증가할것이다. 5. 수술 (surgery) 5-1. 위암수술의원칙 (principle of gastric cancer surgery) 1) 위절제 (gastric resection) 위암의표준수술은중하부위암인경우위아전절제술 (distal subtotal gastrectomy, 2/3 절제 ), 중상부위암의경우위전절제술 (total gastrectomy) 이며, 위주위의광범위한림프절절제술을함께시행하는것이다. 축소수술또는기능보존수술에는유문보존위절제술 (pylorus-preserving gastrectomy), 국소절제술 (local resection), 구역절제술 (segmental resection), 근위부위절제술 (proximal gastrectomy) 등이있으며병소의위치, 림프절절제의범위와충분한절제연의확보를고려하여시행한다. 근위부위절제술은상부에위치하는조기위암에서주로시행되며, 역류성식도염이발생할위험성이있어주의가필요하다 권고 : 근치적절제가가능한위암의표준치료는수술이다. 근치적수술이란원발병소의완전절제와위주위의광범위한림프절절제술을시행한후위장관재건을시행하는것이다. ( 권고등급 1, 근거수준 E) 권고 : 근위부위절제술은제한된적응증에서위전절제술을대체할수있다. ( 권고등급 2, 근거수준 D) 2) 림프절절제 (lymphadenectomy) 위주위림프절절제 : 점막및점막하층에국한된조기위암에서시행한다. 위주변림프절 (1군림프절 +LN7, 8, 9, [+11p]) 만을절제한다. 45,46 광범위림프절절제 : 근육층이상을침범하였거나조기위암 ( 점막, 점막하층 ) 이더라도림프절전이가의심되는경우시행한다. 광범위림프절절제술이상 : 확대수술이며아직표준치료법이아니다. 대동맥주변의림프절절제술의치료적효과는없는것으로보고되었다. 47 Vol. 63 No. 2, February 2014

7 72 이준행등. 근거기반위암진료권고안 권고 : 조기위암에서광범위림프절절제대신위주위림프절절제가시행될수있고환자의상태와수술시육안소견에따라달라질수있다. ( 권고등급 2, 근거수준 D) 3) 합병절제원발병소가인접장기로직접침윤하였거나, 상부위대만측에위치한위암이고유근층이상을침윤한경우나비장문부근의림프절전이가의심될경우, 원격전이병변이있는경우, 완전절제또는증상완화를위해침범된장기의합병절제를시행할수있다. 4) 재건술위암수술후재건방법의차이를비교한연구는많지않다. Billroth-I과 Billroth-II를비교한소수의연구에서두문합법간에식사불편감이나치료성적의유의한차이가없다고보고되었으며, 67,68 루와이위-소장문합은 Billroth-I 문합법에비해수술후담즙역류의측면에서는우월할수있다고보고된바있다. 69 권고 : 원위부위절제술시행후위십이지장, 위공장, 루와이문합법은모두사용할수있다. ( 권고등급 2, 근거수준 D) 5-2. 조기위암의수술 (surgery of early gastric cancer) 1) 적응증 (surgical indication of early gastric cancer) 조기위암은림프절전이여부와관계없이점막층과점막하층에국한된경우를말하며, 림프절전이빈도는점막암의경우약 5%, 점막하암의경우약 20% 내이다. 70,71 위선암으로진단되고간, 복막등의원격전이가없는경우모든조기위암환자가위절제술과림프절절제를시행하는수술치료의적응증이된다. 72,73 2) 개복수술과복강경 (open surgery vs. laparoscopic surgery) 조기위암을대상으로한대부분의후향적연구에서복강경수술은개복수술과비교하여열등하지않은치료성적이보고되고있다 그러나아직까지전향적연구는국내외에서부족한상황이다. 85,86 것으로정의한다. 원발병소가주위장기를침윤한경우근치절제를위하여원발병소와침윤장기의합병절제를시행하고, 근치절제가불가능한원격전이가있는경우출혈, 협착등의개선을위하여원발병소만을절제하는고식적수술로삶의질을개선할수있다 절제가곤란한경우위-공장문합술과같은우회수술을시행할수있다 내시경치료 6-1. 절대적응증 (absolute indication) 전통적으로위암의표준치료는외과수술이다. 1984년일본에서처음소개된내시경점막절제술 (endoscopic mucosal resection) 및최근개발된내시경점막하박리절제술 (endoscopic submucosal dissection) 은조기위암중제한된병기에적용할경우표준치료인수술을대체할수있다. 이경우내시경치료는내시경시술만으로병변을절제함으로써수술의합병증과후유증을최소화할수있다. 또한위절제에따른삶의질저하가거의없으며, 다수의후향적연구에서수술과비슷한생존율을보인다 하지만조기위암의내시경치료에대한 Cochrane review에서보듯내시경치료와수술의성적을비교한무작위대조연구는없다. 97 내시경치료의적응증은이론적으로조기위암중림프절전이가없고국소적으로근치가가능한병변이다. 하지만영상진단법이발달된현대에도수술전림프절전이의정확한임상진단은불가능하여과거외과수술로치료받은조기위암의림프절전이여부분석결과를바탕으로내시경치료의적응증이제시되었다 현재조기위암내시경치료의절대적응증은 (1) 점막에국한된분화암 (well and/or moderately differentiated adenocarcinoma), (2) 장경 2 cm 이하, (3) 궤양이나궤양반흔이없고, (4) 암세포의림프혈관침범이없는경우이다. 100 그러나암세포의점막하층침범이나림프혈관침범은시술전정확히확인할수없으므로, 시술후병리검사에서확인되면수술등추가치료가필요하다. 권고 : 조기위암환자중절대적응증에해당하는경우내시경치료를할수있다. ( 권고등급 1, 근거수준 D) 권고 : 조기위암에서복강경수술을시행할수있다. ( 권고등급 2, 근거수준 C) 5-3. 진행위암의수술 (surgery of advanced gastric cancer) 1) 적응증진행위암은근육층또는그이상암세포의침윤이있는 6-2. 확대적응증 (expanded indication) 최근내시경점막하박리절제술과같은내시경치료의기술적발달로내시경치료의적응증을확대하려는시도가있다. 96,103,104 확대적응증이란 (1) 병변의크기와관계없이궤양이없는점막내분화형선암, (2) 궤양이있더라도 3 cm 이하의점막내분화형선암, (3) 2 cm 이하에서궤양이없는점막내미분화형선암, (4) 점막하침윤깊이가 500 μm (SM1) 이하인분화형선암의경우이다. The Korean Journal of Gastroenterology

8 Lee JH, et al. Clinical Practice Guideline of Gastric Cancer in Korea 추적검사 (follow-up) 현재위암의치료후추적관리는 National Comprehensive Cancer Network (NCCN) 가이드라인의경우 R0 resection 은첫 1-3년은 3개월또는 6개월마다, 3-5년째는 6개월마다, 그이후에는매년신체검진및병력청취와같은추적관찰을하고, 일반혈액검사및임상화학검사, 영상의학검사, 내시경검사는임상적으로필요하면시행하는것으로하고있다. 105 조기위암의내시경치료후이시성재발은 % 로보고되고있다. 시술당시발견하지못한동시다발암의가능성도있기때문에적어도매년내시경추적검사를시행할것이추천된다. 권고 : 조기위암으로내시경치료를받은환자에서적어도매년내시경검사를시행한다. ( 권고등급 1, 근거수준 E) trial) 에서는 1,035명의병기 II, IIIa 및 IIIb (T3N2) 환자에서 D2 림프절절제술후 capecitabine과 oxaliplatin 병합요법을시행한군이그렇지않은군에비하여 3년무질병생존율이의미있게높았다 (74% vs. 60%). 114 결론적으로, 표준절제술로 D2 림프절절제술을시행하는우리나라에서효능이입증된표준적으로사용할수있는수술후보조항암화학요법은현재로서는병기 II, III에서 S-1 단독요법과 capecitabine+oxaliplatin 용법이다. 향후, 잘설계된임상연구를통해서보다효과적인수술후보조항암요법을개발하는것이필요하다. 권고 : 위암의근치적수술후보조항암화학요법은유용하며, S-1 단독요법이나 capecitabine과 oxaliplatin 병합요법을사용할수있다. ( 권고등급 1, 근거수준 B) 7. 항암화학요법 (chemotherapy) 7-1. 위암의수술후보조항암화학요법 (postoperative adjuvant chemotherapy for gastric cancer) 위암은완치적으로절제된후에 22-45% 의환자에서재발한다. 106,107 이에, 수술이불가능한진행성위암에서최선의지지요법과비교된항암화학요법의유효성을참작하여, 완치적으로절제된위암의보조적치료로항암화학요법의효과를확립하기위한많은연구들이이루어졌다. 1980년부터 2000년까지발표된임상시험들을분석한여러메타분석들에서, 보조항암화학요법이생존율을향상시키는것으로나타났다. 108, 년 Global Advanced/Adjuvant Stomach Tumor Research International Collaboration (GASTRIC) group에서는 2004년이전에환자모집을끝낸 17개의임상시험들을메타분석하였는데, 보조항암화학요법은생존기간을연장시켰고, fluoropyrimidine을포함한요법이사망의위험도를낮추는것으로나타났다. 110 서구에서는수술전후에 ECF 항암화학요법 (epirubicin+ cisplatin+5-fluorouracil [5-FU]) 을시행한군에서, 수술단독군과비교하여전체생존율 (hazard ratio [HR] 0.75) 과무질병생존율 (HR 0.66) 이유의하게향상됨을보고하였는데, 111 이연구에서는한국에서표준적으로시행되는 D2 림프절절제술이 42.5% 에서만시행되었기때문에, 한국에서의표준치료로받아들이기는어렵다. 일본과한국에서 D2 림프절절제술후의보조항암화학요법의효과를알아보는임상시험들이시행되었다. 총 1,059명의병기 II, III의환자를대상으로 D2 림프절절제술후 S-1 (tegafur+gimeracil+oteracil) 을투여한군과투여하지않은군을비교하였고, 112 S-1을복용한군의 5년생존율은수술단독군에비해유의하게높았다 (71.7% vs. 61.1%, HR 0.669). 113 한국에서주도한임상시험 (CLASSIC 7-2. 재발성및전이성위암의 1차보존적항암화학요법 (first-line palliative chemotherapy for recurrent or metastatic gastric cancer) 1) 재발성및전이성위암에서 1차보존적항암화학요법은유용한가? 재발성및전이성위암에서항암화학요법의주된역할은증상완화와함께생존율을향상시키는것이다. 위암환자에서고식적항암화학요법이과연도움이될수있을지여부에대해서는 1990년도이후에보고된여러임상연구의결과로어느정도규명이되었다고할수있는데, 현재까지총 4개의무작위 3상임상연구결과가발표되어있다. 115 이연구결과들은비록매우적은환자들을대상으로한오래된임상연구이지만, 모든연구에서일관되게항암화학요법을시행받은군이최적의지지요법 (best supportive care) 만받은환자군에비하여생존기간이약 3-7개월증가되었고, 삶의질 (quality of life) 역시향상됨을보고하였다 권고 : 재발성및전이성위암에서 1차보존적항암화학요법은생존연장및삶의질을향상시키므로환자의전신상태등을고려하여시행한다. ( 권고등급 1, 근거수준 B). 2) 재발성및전이성위암에서유용한 1차보존적항암화학요법은? 위암은소화기암중비교적항암화학요법에반응이좋은것으로알려져있으며, 위암의치료에사용되어온항암화학요법제중단독투여로 10% 이상의반응률을보였던것은 5-FU, mitomycin C, cisplatin 및 etoposide 등이있다. 또한새로운약제로는 irinotecan, oral etoposide, paclitaxel, docetaxel 및 pegylated doxorubicine 등이있다. 일반적으로 Vol. 63 No. 2, February 2014

9 74 이준행등. 근거기반위암진료권고안 항암제를단독으로사용하는경우에는반응률이낮고, 반응지속기간도 3-4개월이내로매우짧다. 따라서반응률을증가시키고생존기간을연장하고자하는목적으로이러한약제들을 2제이상동시에사용하는복합항암화학요법 (combination chemotherapy) 들이시도되고있으며, 25-50% 의반응률과 6-12개월의생존기간을보고하고있다 최근의메타분석에의하면위암에서병용항암화학요법은단독항암화학요법혹은보존적치료만받은경우에비하여통계적으로유의하게생존기간을증가시킨다. 115 진행성위암의일차요법으로사용되는표준항암화학요법제는아직완전히확립되어있지않으나, fluoropyrimidine 및 platinum계항암제의 2제병용요법이가장널리사용되고있으며, 여기에제3의약제로 docetaxel 혹은 epirubicin이추가되기도한다. 최근에는재발성및전이성위암에서도역시 trastuzumab, bevacizumab, cetuximab 및 lapatinib 등의분자표적치료제와의병용요법이활발하게연구되고있다. 최근에보고된 ToGA 연구에서는 HER2의과발현혹은증폭이확인된진행성위암환자에서항암화학요법 (5-FU 혹은 capecitabine과 cisplatin) 에 trastuzumab을추가하는경우에생존기간 (13.5 vs. 11.1개월 ) 이유의하게향상됨을보고하여 HER2 의과발현혹은증폭이확인된진행성위암환자에서는새로운표준요법으로여겨지고있다. 123 그러나, bevacizumab, 124 cetuximab 125 및 lapatinib 126 등의표적치료제는 3상임상연구에서는유의한생존율향상을보이지못하였다. 권고 : 재발성및전이성위암의 1차보존적항암화학요법으로사용되는항암제에는 fluoropyrimidines (5-FU, capecitabine, S-1), platinums (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), irinotecan 및 anthracyclines (doxorubicin, epirubicin) 등이있으며, 이들약제의단독혹은병용요법 (2제혹은 3제 ) 이추천된다. ( 권고등급 1-2, 근거수준 B-C) 일반적으로진행성및전이성위암의고식적일차항암화학요법으로추천되는요법으로는 DCF (docetaxel, cisplatin, and 5-FU) 및이의변형요법 (1B), ECF (epirubicin, cisplatin, and 5-FU) 및이의변형요법 (1B), fluoropyrimidines (5-FU, capecitabine or S-1) & cisplatin (1B), fluoropyrimidines (5-FU or capecitabine) & oxaliplatin (2B), fluoropyrimidines (5-FU) & irinotecan (2C), taxanes (docetaxel or paclitaxel) & cisplatin (2C), trastuzumab with fluoropyrimidines (5-FU or capecitabine) & cisplatin for HER2 overexpressing adenocarcinoma (1B) 등이있다. 또한, 전신상태및연령등을고려하여 fluoropyrimidines (5-FU, capecitabine or S-1) (2C) 를단독으로사용할수도있다 재발성및전이성위암의 2차보존적항암화학요법 (second-line palliative chemotherapy for recurrent or metastatic gastric cancer) 재발성 / 전이성위암환자에서완치를기대하기는어렵지만항암화학요법에의해서증세가완화될수있으며, 생존기간의연장을기대할수있다. 그러나 1차보존적항암화학요법을받았던환자의많은수에서질병이진행되지만 2차항암화학요법에대해선정립된바가없었다. 최근의두가지무작위 3상임상시험에서전이성위암에서 1차보존적항암화학요법후에진행된환자를대상으로최적의지지요법에비해서 2차보존적항암화학요법을하는것이유의하게생존기간이연장됨을보여주었다. 127,128 대개 ECOG 수행도 0-2인환자를대상으로 2차보존적항암화학요법으로 irinotecan 또는 docetaxel을투여한환자군이최적의지지요법을받은환자군에비하여유의하게중앙전체생존기간이향상됨을보고하였다. 두연구를메타분석한결과, 전체생존기간에있어서 HR 0.52 (95% CI ) 로 2차항암화학요법을시행하는것이최적의지지요법에비해서유의한효과가있음을보여주었다. 권고 : 재발성및전이성위암에서 1차보존적항암화학요법후진행된경우, 환자의전신상태가양호하면 2차보존적항암화학요법을시행한다. ( 권고등급 1, 근거수준 B) 진행성위암에서표준 2차보존적항암화학요법이아직까지정립되지못하였으나, 2차항암화학요법의용법선택, 약제용량이나투여방법은예상되는약제의독성, 환자간의차이, 1차항암화학요법의종류, 전신수행상태, 동반질환, 사용가능한약제, 경제성등을고려해서결정해야한다. 2차보존적항암화학요법은기존의제2상임상시험의결과를토대로한용법을사용하거나, 잘설계된임상시험에참여하여해당약제를사용할수있다. 임상시험의결과들을토대로권고되는 2 차보존적항암화학요법은 paclitaxel-based chemotherapy (paclitaxel; paclitaxel with doxifluridine, capecitabine, or 5-FU and leucovorin; paclitaxel with cisplatin or carboplatin), docetaxel-based chemotherapy (docetaxel; docetaxel with cisplatin or oxaliplatin; docetaxel with 5-FU or capecitabine; docetaxel with etoposide; docetaxel with epirubicin; DCF [docetaxel, cisplatin and 5-FU: if not used in first line therapy]), irinotecan-based chemotherapy (irinotecan; irinotecan with cisplatin; irinotecan The Korean Journal of Gastroenterology

10 Lee JH, et al. Clinical Practice Guideline of Gastric Cancer in Korea 75 with 5-FU and leucovorin or capecitabine; irinotecan with mitomycin), platinum-based chemotherapy (5-FU or capecitabine with cisplatin; 5-FU or capecitabine with cisplatin and trastuzumab [Her2-neu overexpressing adenocarcinoma if not used in first line therapy]; fluoropyrimidine [capecitabine or 5-FU and leucovorin] with oxaliplatin; pegylated liposomal doxorubicin with oxaliplatin; ECF [epirubicin, cisplatin and 5-FU] or ECX [epirubicin, cisplatin and capecitabine]: if not used in first line therapy), fluoropyrimidine-based chemotherapy (fluoropyrimidine [S-1, capecitabine, or 5-FU and leucovorin]; fluoropyrimidine [S-1 or 5-FU and leucovorin] with mitomycin; 5-FU with methotrexate; capecitabine with doxorubicin) 가있다. 라에적용하기에는한계가있다. 이연구는광범위림프절절제술이시행되지못한위암환자에게는보조항암화학-방사선병용요법이환자의생존기간을증가시킬수있음을보여주었다. 990명의 D2 림프절절제술을시행한환자군을대상으로한 Kim 등 133 의관찰연구에서, 수술후보조항암화학-방사선병용요법군의재발률과생존율이수술단독군에비하여우수하였다. 따라서 D2 림프절절제술을포함한근치적수술후보조요법으로서항암화학-방사선병용요법이고려될수있다. 반면, Dikken 등 134 의관찰연구에서는 D1 림프절절제술후보조항암화학-방사선병용요법은국소재발률을감소시켰으나, D2 림프절절제술을시행한경우에는차이가없었다. 그러므로광범위림프절절제술후추가항암화학-방사선병용요법의효과에대해서는무작위 3상임상연구가필요하다. 8. 방사선치료 (radiation therapy) 8-1. 수술전방사선치료 (neoadjuvant radiation therapy) 수술전방사선치료는국소적으로진행된위암의근치적절제가능성을높이기위해수술전에시행한다. 수술전방사선치료의효과에대한연구는지금까지모두 3개의무작위대조연구가발표되었다. Zhang 등 129 은들문 (gastric cardia) 에위치한위선암환자 370명을대상으로수술단독군과수술전방사선치료군을비교하여절제율과 5년및 10년생존율의유의한향상을보고하였다. Skoropad 등 130,131 은수술전검사에서림프절전이가있거나 T3 이상의병기인환자에서수술전방사선치료가생존율을향상시키는경향을보고하였다. 권고 : 국소적으로진행된위암에서수술전방사선치료는제한적으로시행할수있다. ( 권고등급 2, 근거수준 C) 8-2. 수술후방사선치료 (adjuvant radiation therapy) 수술후방사선치료는위암의근치적절제후재발가능성이있을경우에방사선치료단독혹은항암화학요법과병용하여시행된다. 수술후재발양상은크게국소재발, 영역재발, 원격전이로구분된다. 방사선치료는이중에서국소재발과영역재발의가능성을줄여완치율을높이기위해시행된다. 근치적수술을시행한위암환자에서수술후보조항암화학-방사선치료의효과를수술단독군과비교한몇개의임상연구가있다. Macdonald 등 132 이 556명을대상으로한무작위대조연구에의하면보조항암화학-방사선병용요법군에서수술단독군에비하여생존기간이증가되었다. 그러나약 90% 의환자에서림프절절제술이시행되지않거나부분적으로시행되었으므로, D2 림프절절제술이표준치료로간주되고있는우리나 권고 : 위암의근치적수술후보조요법으로항암화학-방사선병용요법이고려될수있다. ( 권고등급 2, 근거수준 C) 완치는불가능하지만, 환자의고통을완화시키면서삶의질을높이는목적으로시행되는고식적방사선치료가있다. 고식적방사선치료의대상환자는위장내암세포에의해출혈이심하거나음식물연하장애가있을경우, 혹은다른장기 ( 뇌, 뼈, 복부 ) 전이로인해통증이심하거나신경증상이나타날때, 이러한증상의완화를목적으로방사선치료가적용될수있다. 9. 병리학적평가 (pathologic evaluation) 9-1. 위암검체의취급위암조직검체는크기와채취방법에따라내시경생검, 내시경절제조직및수술절제조직등으로분류할수있다. 내시경생검조직채취시반드시채취부위와개수를명기하여야한다. 내시경점막절제술이나내시경점막하박리절제술인경우절제조직의수축을막기위하여, 고정판에펼친후핀으로박아포르말린에담근다. 내시경절제술표본은상기과정으로검체가취급된경우만조직구축학적검사를시행할수있으며조직구축학적검사를한경우만권장된진단항목을언급할수있다. 상기과정을거치지않는경우는조직형분류, 분화도만보고서에기술한다. 수술절제조직은병변이손상되지않도록소만이나대만을통해절개한후수축을막기위하여고정판에펼친후핀으로박는다. 일반광학현미경검사를위한조직은채취즉시 10% 중성포르말린에고정한다. 고정액은검체가충분히잠길정도로하며, 고정시간은생검의경우최소 3-4시간, 절제조직은최소 8시간이상이필요하다. 고정이완료된검체는대한소화기병리학연구회의권고 Vol. 63 No. 2, February 2014

11 76 이준행등. 근거기반위암진료권고안 안에따라절편으로제작한다. 135 동결절편검사및조직은행을위해서는고정하지않은신선검체를채취한다 위암의병리진단위암의조직형분류는 World Health Organization 분류 136 를사용하며 Lauren 분류 137 를추가할수있다. 조직형의분류가어려운경우면역조직화학염색또는조직화학염색을시행하여도움을받을수있다. 관상선암은분화도에따른분류를시행하며 2등급, 3등급, 또는 4등급체계를따를수있다. 일반적으로아래와같은 3등급분류를따른다. 등급 1: 고분화형 - 선구조를만드는면적이 95% 초과등급 2: 중분화형 % 선구조등급 3: 저분화형 - 49% 이하선구조병리진단보고서에는아래와같은항목을포함하는것을권장하며, 대한소화기병리학연구회의권고안에따라추가정보를기재할수있다. 138 다만아래항목을포함하기위해서는적절한방법으로처방, 절편제작, 검경, 진단하는과정이있어야한다. 추가정보를기재할경우그에합당한추가적인처방과검사과정이선행되어야한다. 위암의병리적병기결정은 American Joint Committee on Cancer (AJCC) 매뉴얼 7판 139 을기준으로한다. 생검조직 : 조직형분류, 분화도내시경절제술 *: 조직형분류, 분화도, 종양크기, 침윤깊이, 혈관및림프관침범여부, 절제연의종양유무수술 : 조직형분류, 분화도, 종양크기, 침윤깊이, 근위및원위절제연의종양유무, 절제한국소림프절수, 종양이침범한림프절수 * 내시경절제술표본에대해조직구축학적검사를시행하여상기항목에대한평가가가능한경우에한하여기재할수있다 림프절전이에대한병리학적판정림프절전이는환자의예후와관련된중요요소이며 TNM 병기를결정하게되므로이에대한정확한병리학적판정을시행하여야한다. 위주변림프절을절제하였을때가능한한많은림프절을회수하여현미경검색을시행한다. 위암환자에서 pn 병기는 H&E 염색을통한판독결과에따르며, 림프절전이개수에따른 TNM 병기결정은 AJCC 매뉴얼 7판 139 에의한다 위암의표적치료와관련된병리조직표지자 유전자이상에의한세포내단백질발현의변화는면역조직화학검사를통해관찰할수있으며, 이들여러단백질의발현변화는위암의예후를예측하고치료방침을결정하는중요한표지자로인식된다. 위암및위식도경계암환자에서표적치료를위한환자군을선별하기위해서는 Her2 단백발현또는유전자증폭검사를시행하는것이필요하며, 일차적으로 Her2 면역염색을시행하여 3+ 인경우표적치료의대상으로선별한다. 면역염색 2+ 인경우에는표적치료대상을선별하기위해추가적으로 FISH ( 또는 SISH) 검사를시행하여유전자증폭양성을확인하는것을권장한다. 그러나면역염색 0 또는 1+ 인경우에도 FISH ( 또는 SISH) 검사에서 Her2 유전자증폭양성인경우가 % 로보고되어있으므로, 필요에따라서면역염색 0 또는 1+ 인경우에도 FISH ( 또는 SISH) 검사를시행하여 Her2 유전자증폭유무를확인할수있다 권고 : 위암및위식도경계암환자의위암조직에서 Her2 단 백발현이나유전자증폭검사가유용하다. ( 권고등급 1, 근거 수준 B) REFERENCES 1. Cancer statistics. [Internet]. Goyang (Korea): National Cancer information Center [cited 2014 Feb 5]. Available from: Cause of death statistics. [Internet]. Daejeon (Korea): Korean Statistical Information Service [cited 2014 Feb 5]. Available from: 3. Deeks JJ, Dinnes J, D'Amico R, et al; International Stroke Trial Collaborative Group; European Carotid Surgery Trial Collaborative Group. Evaluating non-randomised intervention studies. Health Technol Assess 2003;7:iii-x, Turk DJ, Kozarek RA, Botoman VA, Patterson DJ, Ball TJ. Disposable endoscopic biopsy forceps: comparison with standard forceps of sample size and adequacy of specimen. J Clin Gastroenterol 1991;13: Dandalides SM, Carey WD, Petras R, Achkar E. Endoscopic small bowel mucosal biopsy: a controlled trial evaluating forceps size and biopsy location in the diagnosis of normal and abnormal mucosal architecture. Gastrointest Endosc 1989; 35: Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003;3: Yang R, Vuitch F, Wright K, McCarthy J. Adequacy of disposable biopsy forceps for gastrointestinal endoscopy: a direct compar- The Korean Journal of Gastroenterology

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