02 KJCP (종설)-81.hwp

Transcription

1 REVIEW ISSN , The Korean Journal of Helicobacter and Upper Gastrointestinal Research, 2019;19(2):81-87 헬리코박터파일로리감염과위염의 Kyoto 분류 이선영 건국대학교의학전문대학원내과학교실 Helicobacter pylori Infection and the Kyoto Classification of Gastritis Sun-Young Lee Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea Estimating the risk of Helicobacter pylori (H. pylori)-induced gastric cancer during endoscopic examination is important. Owing to recent advances in gastrointestinal endoscopy, the gross appearance of the background gastric mucosa has enabled discrimination of subjects with active, chronic, and past H. pylori infection from those with no history of infection. To provide subjective criteria for H. pylori infection-related endoscopic findings with increased risk of gastric cancer, the Kyoto classification of gastritis was proposed at the 85th annual meeting of the Japanese Society for Gastrointestinal Endoscopy in May 2013 in Kyoto. The main contents focus on determining the gastric cancer risk by scoring the endoscopic findings of the background gastric mucosa from 0 to 8. These important findings are not described in the Kyoto Global Consensus Conference proceedings published in English. To better estimate the gastric cancer risk during screening endoscopy in an H. pylori-prevalent population, knowledge of the Japanese version of the Kyoto classification is important. This new classification emphasizes the discrimination of subjects with H. pylori infection by assessing 19 endoscopic findings (presence of atrophy, intestinal metaplasia, diffuse redness, spotty redness, mucosal swelling, enlarged folds, sticky mucus, chicken skin-like nodularity, foveolar-hyperplastic polyp, xanthoma, depressed erosion, regular arrangement of collecting venules, fundic gland polyp, linear red streak, raised erosion, hematin deposit, multiple white and flat-elevated lesions, patchy redness, and map-like redness). In this review, the validity of the Kyoto classification is summarized in conjunction with several suggestions to resolve emerging H. pylori infection-related problems in Korea. (Korean J Helicobacter Up Gastrointest Res 2019;19:81-87) Key Words: Classification; Endoscopy; Gastritis; Helicobacter pylori; Stomach neoplasms 서 론 위염의 Kyoto 분류는 2013년 5월에 Kyoto에서개최된제 85회일본소화기내시경학회에서언급된내용으로, 내시경검사시관찰되는육안적소견만으로위염을분류하는차별화된내시경적분류이다. 1 위염의내시경소견에객관적인점수를부여하여위암으로진행할위험성을 0~8 점사이로채점하는방법이다. 2,3 나아가서 Helicobacter pylori (H. pylori) 에감염되어있는위 ( 현감염 ), 감염된적이있는위 ( 과거감염 ), 한번도감염된적이없는위 ( 미감염 ) 를위내시경소견으로감별하여미감염자보호, 현감염자치료, 과거감염자추적검사를유도하는괄목할만한업적이다. 하지만 2015년에영문으로발표된위염의 Received: January 16, 2019 Revised: January 21, 2019 Accepted: January 21, 2019 Corresponding author: Sun-Young Lee Department of Internal Medicine, Konkuk University School of Medicine, Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea Tel: , Fax: , sunyoung@kuh.ac.kr This study was supported by the Korean National Research Foundation (NRF2016R1D1A1B ). Kyoto 협의안에서는이러한새로운내용들이언급되지않았다. 4 대신만성위염과십이지장염에대한진단방법, 기능성소화불량증과 H. pylori 감염으로인한소화불량증의감별법, 위염의올바른진단접근법, H. pylori 제균치료의대상, 시기, 방법에대한전문가들의투표결과를실었으며, 원인학적위염분류표가함께게재되었다. 따라서일본밖에서알려진위염의 Kyoto 협의안은일본에서출판된 Kyoto 분류보다오히려기존의서양의위염분류에가깝다. 영문본만읽으면위염의 Kyoto 분류가위내시경소견으로 H. pylori 감염상태를진단하고, 위암의위험성을예측하는점수체계였다는사실조차알수없다. 우리나라처럼위내시경검사가빈번하게이루어지는곳에서는내시경소견만으로미감염자, 현감염자, 과거감염자를감별하고, 위암의위험성을예측하는것이중요하다. 이에본론에서는 Kyoto 분류의탄생배경과 H. pylori 감염과의연관성에대하여알아보고, 현재우리나라에서직면한 H. pylori 감염성위염에대한문제점들과해결책에대하여고민해보고자한다. Copyright 2019 Korean College of Helicobacter and Upper Gastrointestinal Research The Korean Journal of Helicobacter and Upper Gastrointestinal Research is an Open-Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License ( creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 Korean J Helicobacter Up Gastrointest Res: Vol 19, No 2, June 2019 본 1. Kyoto 분류의탄생배경 론 내시경으로관찰되는위점막의해상도가좋아지면서이전에는조직검사로만진단할수있었던병변들을내시경소견만으로도예측할수있게되었다. 하지만국소병변이아닌광범위한배경위점막의내시경소견들을모두포괄하는위염분류가없어서관찰된소견들을 H. pylori 감염이나위암과연관지어표기할방법이없었다. 비록 updated Sydney system 에서이전보다 H. pylori 감염의중요성을강조하였지만, 다양한위내시경소견을기술하는데한계가있다. 5 이에 2013년 5월에 Kyoto 에서 3일간개최된일본소화기내시경학회에서하루마켄학회장은위내시경검사를시행하는의사들의눈높이에맞춘새로운위염분류법을제안하였다. 배경위점막의내시경소견으로 H. pylori 감염상태와위암에대한위험성을채점하는 Kyoto 분류는 Sydney system 을기본으로하되, 보다객관적인시각에서위내시경소견을표준화한것이다. 2,3 표준화에앞서 2008년에결성된일본소화기내시경학회의부속기구인 만성위염의내시경진단확립을위한연구회 에서논의된내용을중심으로위염의내시경소견, 위암과연관된내시경소견과점수, 내시경소견의표기방법을 개발하였다. 이후에소화기내시경전문의 5인 ( 가와사키대학의하루마켄교수, 카마다토모아키선생, 이노우에카즈히코선생, 삿포로대학의카토모토츠구교수, 오카야마대학의무라카미카즈나리교수 ) 에의하여 120쪽에달하는 위염의 Kyoto 분류 가완성되었다. 6 그리고 2018년 10월에는 160쪽에달하는개정판으로거듭났다. 2. 위내시경소견을통한 H. pylori 감염상태의진단 Kyoto 분류의주요내용은국소병변이아닌배경위점막의내시경소견으로 H. pylori 감염상태를판단하고, 위암에대한위험성을 0~8 점사이로채점하는것이다. 관찰한의사개개인의주관적소견을배제하기위하여 Kyoto 분류에서는 H. pylori 미감염, 현감염, 과거감염상태를시사하는각각의내시경소견들과약물로인한위점막손상시관찰되는내시경소견들을 19개의객관적인지표로개발하였다 (Table 1). 1) H. pylori 감염상태에따른위내시경소견활동성감염시관찰되는내시경소견은전정부보다체부와기저부에서더뚜렷하다. 7 호중구와단핵구침윤으로인하여위점막이빨갛게붓는급성염증소견이전정부보다체부에서더명확하게관찰되기때문이다. 위축과장상피화생에의한만성위염의위암화과정이강조되었던기존분류와달리, Kyoto 분 Table 1. Subjective Criteria Listed in the Kyoto Classification Endoscopic finding Location H. pylori infection Increase the risk of intestinal-type gastric cancer 1. Atrophy All Active or past 2. Intestinal metaplasia All Active or past Increase the risk of diffuse-type gastric cancer 3. Diffuse redness (translucency of collecting venules) Body Active 4. Enlarged gastric folds 5 mm Body Active 5. Chicken skin-like nodularity Antrum Active >> past No comment on the risk of gastric cancer 6. Spotty redness Fundus > body Active >> past 7. Sticky mucus Body Active 8. Mucosal swelling All Active 9. Foveolar-hyperplastic polyp All Active > past 10. Xanthoma All Past > active 11. Map-like redness All Past 12. Depressed erosion All All 13. Patchy redness All All 14. Multiple white and flat elevated lesions Fundus > body Past or never >> active 15. Regular arrangement of collecting venules Angle > body Never >> past 16. Fundic gland polyp Fundus > body Never > past 17. Linear red streak All Never > Past >> active 18. Raised erosion Antrum Never > past >> active 19. Hematin deposit All Never > Past >> active H. pylori, Helicobacter pylori. 82

3 Sun-Young Lee: Helicobacter pylori Infection and the Kyoto Classification of Gastritis 류에서는위축이발생하기전활동성감염상태에서의급성위염중요성을강조하였다. 이는만성위염없이도 H. pylori 감염이위암을유발할수있으며, 활동성감염상태에서발생한위암은예후가불량하다는사실에착안한것이다. 1-3 급성활동성 H. pylori 감염을치료하지않으면거의모든예에서만성위염으로진행하므로위내시경검사시아직만성화되지않은비위축성 H. pylori 감염성위염을진단하고치료하는것이중요하다. 2) H. pylori 감염력이없을때관찰되는위내시경소견내시경검사시위각이나체부의소만측에서보이는균일한세정맥집합 (regular arrangement of collecting venules, RAC) 은손상되지않는위점막을가리킨다. 6 RAC 소실은 H. pylori 감염이외에다른원인에의해서도발생할수있으나드물다. RAC 외에미감염자에서더흔한내시경소견들로는전정부의대만측이나체부소만측의규칙적인선상발적, 체부에서보이는 5 mm 미만의다발성상피하용종 ( 위저선용종 ) 등이있다. 6 기저부에만국한된위축성변화를보이는 A형자가면역성위염도미감염자에서더흔하다. 3) 약물손상으로인한위내시경소견 H. pylori 감염으로인한위축이나궤양이위각부나소만측에서흔한것과달리, 약물로인한위점막손상은위전반에걸쳐다발성으로발생하기쉽고증상이있는경우가많다. 8 아스피린이나비스테로이드성항염증제 (nonsteroidal anti-inflammatory drug) 는점막을헐게하여궤양, 미란, 발적, 헤마틴침착등을유발하지만, 양성자펌프억제제 (proton pump inhibitor) 는융기형병변을유발한다. 9 히스타민2 억제제와달리양성자펌프억제제를장기복용할때는기저부와체부에서흰색융기가관찰될수있는데, Kyoto 의위염분류에서는이를위의조약돌모양병변 (gastric cobblestone-like lesion) 이라고부른다. 10 4) Kyoto 분류의개정판에새로추가된소견 2018년 11월에나온 Kyoto 분류의개정판에서는기존의 19개의위내시경소견에 4개의소견 ( 가성용종, 흑점, 서리내린모양, 조약돌모양 ) 이추가되었다. 개정판에추가된내용은대부분 H. pylori 감염과무관한위염으로, 상대적으로드물어서진단하기어려운위염의내시경소견들이다. H. pylori 이외의감염성위염으로결핵, 거대세포바이러스, 매독, 아니사키시스 (anisakiasis), Helicobacter suis에의한위염이추가되었다. 그밖에약제연관성위염, 자가면역성위염, 호산구성위염, 콜라겐성위염 (collagenous gastritis), 염증성장질환과동반된위염에대한내용도추가되었다. 3. 위내시경소견을통한위암발생의위험성예측 H. pylori 감염성위염이궤양, 선종, 선암, 림프종으로진행할가능성은 10% 미만이지만, 우리나라와일본에서만동아시아형 Cytotoxin associated gene A를지닌 H. pylori 의감염율이전체 H. pylori 감염자의 95% 에달하기때문에위염, 위궤양, 위암의발생률이높다 Kyoto 분류에서는 H. pylori 감염과무관한위암이드물다는사실에착안하여, 위암의위험성에대한지표를 H. pylori 감염성위염의 5대내시경소견인위축, 장상피화생, 결절, 주름비대, 미만성발적 ( 점상출혈 ) 으로정하였다. 6,14 따라서기존의위염분류에서중요하게여기는원인 (H. pylori 감염 ), 형태 ( 내시경소견 ), 위치 ( 병변의발생부위 ) 에대한내용이포함되었으나병리소견은누락되었다. 2,3 기존의위염분류들이 H. pylori 감염과무관한원인이나많은수의조직검사를요하는병리학적소견에치중되었다는점을감안할때, Kyoto 분류는내시경검사를하면서바로사용할수있는, 내시경시행의들을위한맞춤형분류이다. 1) 미만형위암으로진행할위험성이높은체부위염지금까지의위염분류는 H. pylori 감염에의한장기간위암화과정에맞추어져서만성위염에발생하는예후가좋은장형위암이나선종에적용할수있었으나, 젊은위암환자에서발생하는미만형위암을설명하기에는부족하였다. 실제로심각한위암은미만형위암임에도불구하고이에대한전암성병변에대한정보가부족하였었다. 나아가서 H. pylori 감염에의한위암이적은서양에서는미만형위암의원인을유전자이상으로분류하지만, 우리나라와일본에서진단되는젊은위암환자들은대부분 H. pylori 감염자들이다. 11,14 이에 Kyoto 분류에서는미만형위암의전암성병변으로체부위염으로나타나는활동성감염성위염소견을강조하였다. 미만형위암은만성위염으로진행할틈도없이급성활동성감염상태에서 H. pylori 에의하여암이발생한것이기에, 체부의 H. pylori 감염성위염은빠른위암화과정으로진행하기전에제균치료하는것이중요하다. 15,16 대표적인체부위염은주름비대로나타나는비후성위염과기저부의점상출혈로관찰되는미만성발적이다. 17 비후성위염은 H. pylori 감염으로인한점막부종때문에위주름이 5 mm 이상으로두꺼워지는것으로미만형위암과의연관성이잘알려져있다. 18,19 미만성발적은기저부와체부대만측에서보이는위점막자극소견으로, 1 mm 미만의다발성점상출혈부터광범위한발적까지다양하게관찰될수있다. 20 2) 미만형위암으로진행할위험성이높은결절성위염결절성위염은위점막이닭살처럼보일때진단하는내시경적진단명으로, Kyoto 분류에서처음으로전암성병변으로분 83

4 Korean J Helicobacter Up Gastrointest Res: Vol 19, No 2, June 2019 류되었다. 21 위축이없는위점막일수록 H. pylori 감염성위염으로인한상피하림프성여포가뚜렷하게관찰되기에, 결절성위염은젊은여성에서흔하다. 22 그동안미만형위암의주요전암성병변임에도불구하고소아에서도흔히관찰된다는이유로과소평가되어왔으나, Kyoto 분류에서는 H. pylori 감염으로인한결절성위염과젊은환자에서발생한미만형위암에대한연구결과들을바탕으로이를 5대전암성병변으로추가하였다 ) 장형위암으로진행할위험성이높은만성위염화생성위염은장상피화생의내시경소견으로, 불규칙하고납작한흰색융기나함몰형미란으로관찰되며만성감염이나과거감염에서흔한황색종이나위축성위염과함께진단된다. 26 H. pylori 감염성위염이비교적드문서양에서는위염분류로 Operative Link for Gastritis Assessment 와 Operative Link for Gastric Intestinal Metaplasia Assessment 를사용한다. 27,28 하지만이는위염의병리학적분류로조직검사를반드시필요로하므로, 위내시경검사를자주하는지역에서는검사할때마다 Operative Link for Gastritis Assessment 와 Operative Link for Gastric Intestinal Metaplasia Assessment를측정하기는어렵다. 또한만성위염이흔한지역에서는 H. pylori 감염여부를조직검사로만판단하면위음성으로나올확률이높으므로, 우리나라에서는병리학적위염분류로만위내감염상태나위암화과정을판단하기가어렵다. 29 Kyoto 분류는이러한조직검사의한계점들을감안하여제작된내시경소견을기반으로한위염분류이다. Kyoto 분류에서위축성위염의진단은 Kimura-Takemoto 분류에준하여폐쇄형 (closed-type, C1~3) 과개방형 (open-type, O1~3) 의 6단계로분류한다. 30 전정부에만국한된위축은 H. pylori 감염없이도나타날수있는노화현상으로전암성병변이아니기에, Kyoto 분류에서폐쇄 I형의위축성위염은 0점에해당한다. 31 즉, 위축이전정부에국한된폐쇄 I형은위암의위험성을높이지않지만, 위축의경계선이위각을넘어체부에있는폐쇄 II형부터는위암의위험성이높아진다. 32 그러므로위축성위염은위암발생의위험성에준하여전정부에국한된위축 (C1), 위축경계선이체부에있는위축 (C2~3), 분문부와기저부까지침범한개방형 (O) 의세종류로만나누는것이바람직하다. 4. Kyoto 분류의활용과우리나라에서해결해야할문제점들 Kyoto 분류가정기적인위내시경검사로시행하는지역에서도움이되는이유는 H. pylori 감염상태와위암발생에대한위험성을알려주기때문이다. 현감염자는미감염자에비하여 위암발생률이약 150배높고, 과거감염자는미감염자에비하여약 50배높기때문에위내시경소견으로위암의위험성이높은 H. pylori 를감별하는것이중요하다. 33 1) H. pylori 전염으로부터보호 40세이상의모든성인에게일괄적으로위암검진을권하는것은과거감염자의추적검사를우선시하는구세대적인발상으로, 미감염자가점차증가하는우리나라현실에부적합하다. 34,35 위암가족력이나 H. pylori 감염력조차없는미감염자들이감염자들과함께일괄적으로위암검진을자주받으면오히려위험하기때문이다. 아무리소독을제대로하여도내시경기기를통한전염률은 0% 가될수없기에, 이전에같은기기로검사받은감염자의균이전염될수있다 특히 H. pylori 유병률이 50% 가넘는지역에서는위내시경 1,000건당 4건의비율로 H. pylori 가전염될수있으며, 내시경전용소독기를사용하지않을경우에는더욱높다 따라서 H. pylori 감염자에게제균치료를강요하지않은채모든국민에게일괄적으로위암검진을받게하는현정책은바뀌어야한다. 과거에는 H. pylori 감염이주로가족내수직전염으로인하여발생하였으나위생상태개선으로가족내미감염자가증가하면서, 타인으로부터의수평전염이증가하고있다 실제로 H. pylori 감염자와결혼한사람은감염자일가능성이 6배높다는독일의연구결과가있으며, H. pylori 의 DNA 를분석한일본연구에서는부부나직장동료가같은균에감염되어있었다. 45,46 H. pylori 는타액과치석에도존재하므로식사나음주를자주같이하는사이일수록전염의기회가증가하는것으로추정된다 ) 감염자에대한신속한진단과치료위암의일차예방책은위내시경검사를하는것이아니라위암의발암인자인 H. pylori 를치료하는것이다. 50 그러나우리나라에는제균치료를하지않은채위암검진만열심히받는감염자들이많다. H. pylori 는위점막과치석에서증식하므로, 식기나술잔뿐만아니라치과시술이나위내시경검사를통해서도전염될수있다 따라서제균치료를하지않고위암검진에만주력하면조기위암진단율증가와위암으로인한사망률감소만가져올뿐, 위암발생률자체는줄이기가어렵다. 일본에서는 2013년 12월 21일부터전감염자에게제균치료를시행하고있으며, 개정된학회의지침서에서도위암예방을위한 H. pylori 제균치료의중요성을강조하였다. 55 청소년기, 위암의저위험기 (50세미만의성인 ), 고위험기 (50세이상 ) 에서각각위암을예방하는방법이정리되어있는데, 모두 H. pylori 감염진단과치료에대한내용이다. 대부분의위암이 H. pylori 감염때문에발생하기에, 위암의원인을음식이나특정유전자로설명하는것은외국에서는통 84

5 Sun-Young Lee: Helicobacter pylori Infection and the Kyoto Classification of Gastritis 하지않는다. 14,50,55 유독우리나라에서만위암의원인을 H. pylori 감염이아닌음식이라고믿는경향이있는데이는외국의최신문헌들이경외시되고있다는간접적인증거로, 위암 1위국가를벗어나는데걸림돌이되고있다. 위암으로부분위절제술을받은감염자들조차제균치료를하지않고음식조절만하면서여러병원에서검사를받고다니기도한다. 감염자치료없이는미감염자보호가되지않아위암을결코줄일수없기에, 서양처럼 H. pylori 를에이즈나결핵환자와같이감염자로취급하여별도의공간에서치과시술이나내시경검사를받게하는방안이검토되어야한다. 3) 과거감염자에대한추적검사위축성위염이나장상피화생이있는감염자도균이사라지면위암의발생률과위염진행이감소하기때문에제균치료를먼저시행한뒤정기적인추적검사를권한다 일부에서는균이사라진후에도만성위염이지속적으로관찰되며위암이발생할수있지만제균치료시위암의발생률은감염자들보다월등히낮다. 60 감염이오래지속된고령의환자일수록이시성위암의발생률이높지만, 대부분천천히자라는장형위암이라서다소늦게발견되더라도예후가좋기에, 더잦은추적검사를권하지않는다. 61,62 5. Kyoto 분류의한계점과추후전망 Kyoto 분류는 H. pylori 감염상태를진단하는데있어서훌륭한객관적인지표이다 그러나국제화지표로거듭나기위해서는세분화된내시경지표와위암발생위험성채점비중의근거부족에대한검토가필요하다. 예를들면, Kyoto 분류의첫문장에나오는위축성위염의 6단계분류가위암발생위험성에맞춘 3단계분류로개편된다면보다많은외국의사들이공감할것이다. 아울러 19개의내시경지표와새로추가된 4개지표중단독소견으로관찰되는빈도나의미가적은것은과감히정리하여부가적인지표로만나열하면국제화에도움이될것이다. 예를들면, 지도상발적은대부분장상피화생과동반되기에개별지표로책정하지않는편이사용하기편하다. 현재일본에서사용중인 Kyoto 분류는 H. pylori 감염상태를감별하는데탁월하여, 이러한단점들만보완된다면전세계어느곳에서위내시경검사를할때마다간편하게사용할수있는국제적인위염분류로거듭날수있을것이다. 결 론 위염의 Kyoto 분류는 H. pylori 감염으로인한위암이흔한지역일수록위내시경검사시유용하게사용할수있는체계적 인분류법이다. 그러나영문판만볼수있는대부분의외국의사들은 Kyoto 분류의내용이 Kyoto 협의안과다르며, 위내시경소견으로 H. pylori 감염상태를파악하고위암의위험성을예측하는점수체계 였다는사실조차알수없다. H. pylori 감염성위염의내시경적분류에초점을맞추어만든본래의의도와가치를제대로알리기위해서라도원문제작과무관한제3자가중심이된영문판은차라리위염의 Kyoto 협의안이아닌다른제목으로발표하는것이나았을것이다. 이를타산지석으로삼아우리사회에서도실무자의중요성을깨닫고, 나아가서원문에서강조한 H. pylori 감염성위염의위내시경소견과전암성병변으로서의중요성을깨달았으면좋겠다. 또한, 이렇게새로운분류까지나오게된이유가 H. pylori 감염자를빨리진단하고치료하여전염을줄이기위해서라는것도상기해야한다. 위암의궁극적인일차예방법은위내시경검사나음식조절이아닌 H. pylori 제균치료이기때문이다. 지금처럼지위와나이를막론하고논문을읽고쓰기싫어하는의사들의비중만날로늘어간다면쏟아지는위염관련문헌을제대로이해할수있는국내전문가들도점차줄어들것이다. 최신지식을습득하려는능동적이고적극적인태도만이왜내시경도못만드는나라에서 H. pylori 제균치료를강요하지않은채정기적인위내시경검진을하는것이외국에서는웃음거리가되는지, 위암 1위국가에서벗어나는데걸림돌이되는지깨닫게해줄것이다. CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported. Sun-Young Lee ORCID REFERENCES 1. Kamada T, Haruma K. Diagnosis of the chronic gastritis. Jpn J Helicobacter Res 2013;14(Suppl 1): Kamada T, Inoue K, Haruma K. Kyoto classification of gastritis. Jpn J Helicobacter Res 2015;16: Kamada T, Haruma K, Inoue K, Shiotani A. Helicobacter pylori infection and endoscopic gastritis -Kyoto classification of gastritis. Nihon Shokakibyo Gakkai Zasshi 2015;112: Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015;64: Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International 85

6 Korean J Helicobacter Up Gastrointest Res: Vol 19, No 2, June 2019 workshop on the histopathology of gastritis, Houston Am J Surg Pathol 1996;20: Haruma K, Kato M, Inoue K, Murakami K, Kamada T. Kyoto classification of gastritis. Tokyo: Nihon Medical Center, Tsai YC, Hsiao WH, Yang HB, et al. The corpus-predominant gastritis index may serve as an early marker of Helicobacter pylori-infected patients at risk of gastric cancer. Aliment Pharmacol Ther 2013;37: Kim Y, Yokoyama S, Watari J, et al. Endoscopic and clinical features of gastric ulcers in Japanese patients with or without Helicobacter pylori infection who were using NSAIDs or low-dose aspirin. J Gastroenterol 2012;47: Hongo M, Fujimoto K; Gastric Polyps Study Group. Incidence and risk factor of fundic gland polyp and hyperplastic polyp in long-term proton pump inhibitor therapy: a prospective study in Japan. J Gastroenterol 2010;45: Takahari K, Haruma K, Ohtani H, et al. Proton pump inhibitor induction of gastric cobblestone-like lesions in the stomach. Intern Med 2017;56: Abe T, Kodama M, Murakami K, et al. Impact of Helicobacter pylori CagA diversity on gastric mucosal damage: an immunohistochemical study of East-Asian-type CagA. J Gastroenterol Hepatol 2011;26: Choi KD, Kim N, Lee DH, et al. Analysis of the 3' variable region of the caga gene of Helicobacter pylori isolated in Koreans. Dig Dis Sci 2007;52: Matsuhisa T. Asian Helicobacter pylori infection and gastritis. Jpn J Helicobacter Res 2013;14: Matsuo T, Ito M, Takata S, Tanaka S, Yoshihara M, Chayama K. Low prevalence of Helicobacter pylori-negative gastric cancer among Japanese. Helicobacter 2011;16: Egi Y, Kim S, Ito M, et al. Helicobacter pylori infection is the major risk factor for gastric inflammation in the cardia. Dig Dis Sci 2006;51: Kamada T, Sugiu K, Hata J, et al. Evaluation of endoscopic and histological findings in Helicobacter pylori-positive Japanese young adults. J Gastroenterol Hepatol 2006;21(1 Pt 2): Kato T, Yagi N, Kamada T, et al. Diagnosis of Helicobacter pylori infection in gastric mucosa by endoscopic features: a multicenter prospective study. Dig Endosc 2013;25: Watanabe M, Kato J, Inoue I, et al. Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis. Int J Cancer 2012;131: Nishibayashi H, Kanayama S, Kiyohara T, et al. Helicobacter pylori-induced enlarged-fold gastritis is associated with increased mutagenicity of gastric juice, increased oxidative DNA damage, and an increased risk of gastric carcinoma. J Gastroenterol Hepatol 2003;18: Kato M, Terao S, Adachi K, et al. Changes in endoscopic findings of gastritis after cure of H. pylori infection: multicenter prospective trial. Dig Endosc 2013;25: Shichijo S, Hirata Y, Niikura R, Hayakawa Y, Yamada A, Koike K. Association between gastric cancer and the Kyoto classification of gastritis. J Gastroenterol Hepatol 2017;32: Shiotani A, Kamada T, Kumamoto M, et al. Nodular gastritis in Japanese young adults: endoscopic and histological observations. J Gastroenterol 2007;42: Kamada T, Shiotani A, Haruma K. Nodular gastritis and gastric cancer in young adult. Nihon Rinsho 2012;70: Miyamoto M, Haruma K, Yoshihara M, et al. Nodular gastritis in adults is caused by Helicobacter pylori infection. Dig Dis Sci 2003;48: Kamada T, Tanaka A, Yamanaka Y, et al. Nodular gastritis with Helicobacter pylori infection is strongly associated with diffusetype gastric cancer in young patients. Dig Endosc 2007;19: Fukuta N, Ida K, Kato T, et al. Endoscopic diagnosis of gastric intestinal metaplasia: a prospective multicenter study. Dig Endosc 2013;25: Rugge M, Correa P, Di Mario F, et al. OLGA staging for gastritis: a tutorial. Dig Liver Dis 2008;40: Capelle LG, de Vries AC, Haringsma J, et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc 2010;71: Kim JH, Lee SY, Lee SP, et al. The histologic detection of Helicobacter pylori in seropositive subjects is affected by pathology and secretory ability of the stomach. Helicobacter 2018;23:e Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy 1969;1: Okamura T, Iwaya Y, Kitahara K, Suga T, Tanaka E. Accuracy of endoscopic diagnosis for mild atrophic gastritis infected with Helicobacter pylori. Clin Endosc 2018;51: Sugimoto M, Ban H, Ichikawa H, et al. Efficacy of the Kyoto classification of gastritis in identifying patients at high risk for gastric cancer. Intern Med 2017:56: Nakajima S, Kato M. Follow-up after the sanitization of the Helicobacter pylori infection in chronic gastritis. Jap J Helicobacter Res 2013;14(Suppl 1): Lee JH, Choi KD, Jung HY, et al. Seroprevalence of Helicobacter pylor in Korea: a multicenter, nationwide study conducted in 2015 and Helicobacter 2018;23:e Lee SP, Lee SY, Kim JH, et al. Correlation between Helicobacter pylori infection, IgE hypersensitivity, and allergic disease in Korean adults. Helicobacter 2015;20: Graham DY, Alpert LC, Smith JL, Yoshimura HH. Iatrogenic Campylobacter pylori infection is a cause of epidemic achlorhydria. Am J Gastroenterol 1988;83: Sugiyama T, Naka H, Yachi A, Asaka M. Direct evidence by DNA fingerprinting that endoscopic cross-infection of Helicobacter pylori is a cause of postendoscopic acute gastritis. J Clin Microbiol 2000;38: Bai H, Li Q, Liu X, Li Y. Characteristics and interactions of Helicobacter pylori and H. pylori-infected human gastro- 86

7 Sun-Young Lee: Helicobacter pylori Infection and the Kyoto Classification of Gastritis duodenal epithelium in peptic ulcer: a transmission electron microscopy study. Dig Dis Sci 2010;55: Tytgat GN. Endoscopic transmission of Helicobacter pylori. Aliment Pharmacol Ther 1995;9 Suppl 2: Kim DH, Moon JH, An JK, et al. Importances of the endoscope cleaning and disinfecion techniques in the prevention of endoscopic transmission of Helicobacter pylori. Korean J Gastrointest Endosc 2001;23: Nürnberg M, Schulz HJ, Rüden H, Vogt K. Do conventional cleaning and disinfection techniques avoid the risk of endoscopic Helicobacter pylori transmission? Endoscopy 2003;35: Breckan RK, Paulssen EJ, Asfeldt AM, Kvamme JM, Straume B, Florholmen J. The all-age prevalence of Helicobacter pylori infection and potential transmission routes. A population-based study. Helicobacter 2016;21: Mamishi S, Eshaghi H, Mahmoudi S, et al. Intrafamilial transmission of Helicobacter pylori: genotyping of faecal samples. Br J Biomed Sci 2016;73: Osaki T, Konno M, Yonezawa H, et al. Analysis of intra-familial transmission of Helicobacter pylor in Japanese families. J Med Microbiol 2015:64: Brenner H, Weyermann M, Rothenbacher D. Clustering of Helicobacter pylori infection in couples: differences between high- and low-prevalence population groups. Ann Epidemiol 2006;16: Yokota S, Konno M, Fujiwara S, et al. Intrafamilial, preferentially mother-to-child and intraspousal, Helicobacter pylori infection in Japan determined by mutilocus sequence typing and random amplified polymorphic DNA fingerprinting. Helicobacter 2015;20: Cellini L, Grande R, Artese L, Marzio L. Detection of Helicobacter pylori in saliva and esophagus. New Microbiol 2010;33: Jung JH, Choi KD, Han S, et al. Seroconversion rates of Helicobacter pylori infection in Korean adults. Helicobacter 2013;18: Kwon HG, Lee SY, Kim JH, et al. Effect of alcohol consumption on seroconversion in Helicobacter pylori-seronegative Koreans. Korean J Med 2018;93: International Agency for Research on Cancer. World Health Organization. Helicobacter pylori eradication as a strategy for preventing gastric cancer. Lyon: International Agency for Research on Cancer, Al-Hawajri AA, Keret D, Simhon A, et al. Helicobacter pylori DNA in dental plaques, gastroscopy, and dental devices. Dig Dis Sci 2004;49: Amiri N, Abiri R, Eyvazi M, Zolfaghari MR, Alvandi A. The frequency of Helicobacter pylori in dental plaque is possibly underestimated. Arch Oral Biol 2015;60: Kamada T, Hata J, Manabe M, et al. Can dental treatment be the infection route of H. pylori transmission in adults? Three cases of acute gastric mucosal lesions after dental treatment. Dig Endosc 2007;19: Kikuchi S, Ohgihara A, Hasegawa A, Miki K, Kaneko E, Mizukoshi H. Seroconversion and seroreversion of Helicobacter pylori antibodies over a 9-year period and related factors in Japanese adults. Helicobacter 2004;9: The committee of the Japanese Society for Helicobacter Research. Guidelines for diagnosis and treatment of H. pylori infection. Tokyo: Sentan Igaku-sha, Hwang YJ, Kim N, Lee HS, et al. Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years. Aliment Pharmacol Ther 2018;47: Ito M, Haruma K, Kamada T, et al. Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis. Aliment Pharmacol Ther 2002;16: Toyokawa T, Suwaki K, Miyake Y, Nakatsu M, Ando M. Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: a long-term prospective cohort study. J Gastroenterol Hepatol 2010;25: Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med 2018;378: Bae SE, Choi KD, Choe J, et al. The effect of eradication of Helicobacter pylori on gastric cancer prevention in healthy asymptomatic populations. Helicobacter 2018;23:e Kamada T, Hata J, Sugiu K, et al. Clinical features of gastric cancer discovered after successful eradication of Helicobacter pylori: results from a 9-year prospective follow-up study in Japan. Aliment Pharmacol Ther 2005;21: Moribata K, Iguchi JK, Nakachi K, et al. Endoscopic features associated with development of metachronous gastric cancer in patients who underwent endoscopic resection followed by Helicobacter pylori eradication. Dig Endosc 2016;28: Nakmaura Y, Somary U. Exploring the potential of endoscopic examinations using the Kyoto scoring system for risk evaluation of gastric carcinoma in patients with gastritis. Int J Oncol Res 2017;1: Nomura S, Terao S, Adachi K, et al. Endoscopic diagnosis of gastric mucosal activity and inflammation. Dig Endosc 2013;25: Watanabe K, Nagata N, Nakashima R, et al. Predictive findings for Helicobacter pylori-uninfected, -infected and -eradicated gastric mucosa: validation study. World J Gastroenterol 2013; 19: