05 KJG (이선영)-332.hwp

Transcription

1 Korean J Gastroenterol Vol. 73 No. 6, pissn eissn ORIGINAL ARTICLE 위축성위염과화생성위염의전구병변으로서결절성위염의의의 김영중, 이선영, 양호준, 김정환, 성인경, 박형석 건국대학교의학전문대학원내과학교실 Nodular Gastritis as a Precursor Lesion of Atrophic and Metaplastic Gastritis Young Jung Kim, Sun-Young Lee, Hojun Yang, Jeong Hwan Kim, In-Kyung Sung and Hyung Seok Park Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea Background/Aims: Chronic atrophic gastritis (CAG) and metaplastic gastritis (MG) are precancerous conditions of Helicobacter pylori (H. pylori)-related gastric cancer. This study aimed to identify the characteristics of nodular gastritis (NG) showing CAG or MG after nodule regression. Methods: H. pylori-infected patients with NG were included after upper gastrointestinal endoscopy. Patients were excluded if their latest endoscopy had been performed 36 months after the initial diagnosis of NG. Small-granular-type NG was defined as the condition with 1-2 mm regular subepithelial nodules. Large-nodular-type NG was defined as those with 3-4 mm, irregular subepithelial nodules. The endoscopic findings after nodule regression were recorded. Results: Among the 97 H. pylori-infected patients with NG, 61 showed nodule regression after a mean follow-up of 73.0±22.0 months. After nodule regression, 16 patients showed a salt-and-pepper appearance and/or transparent submucosal vessels, indicating CAG. Twenty-nine patients showed diffuse irregular elevations and/or whitish plaques, indicating MG. Sixteen patients with other endoscopic findings (14 normal, one erosive gastritis, and one chronic superficial gastritis) showed a higher proportion of H. pylori eradication (12/16, 75.0%) than those in the CAG group (5/16, 31.3%) and MG group (6/29, 20.7%; p=0.001). Patients with small-granular-type NG tended to progress toward CAG (14/27, 51.9%), whereas those with large-nodular-type NG tended to progress toward MG (25/34, 73.5%; p<0.001). Conclusions: In patients with a persistent H. pylori infection, NG tended to progress to CAG or MG when the nodules regressed. Small-granular-type NG tended to progress to CAG, whereas large-nodular-type NG tended to progress to MG. (Korean J Gastroenterol 2019;73: ) Key Words: Gastritis; Lymphoid tissue; Atrophy; Metaplasia 서론 결절성위염 (nodular gastritis) 은위내시경검사시전정부에닭살모양의점막하결절들이보이면진단할수있는내시경소견으로, 헬리코박터파일로리 (Helicobacter pylori, H. pylori) 감염이가장흔한원인으로알려져있다. 1,2 결절들은 H. pylori 감염으로인하여점막하에형성된림프여포 (lymphoid follicle) 와림프혈장계세포의응집 (lymphoplasma cell aggregate) 으로인하여형성된다. 3 림프여포와림프혈장계세포의응집이점막고유층 (lamina propria) 의상부에몰려있으면 1-2 mm의작은과립형 (small-granular type) 으로보이고, 점막고유층의하부에몰려있으면 3-4 mm의납작한모양인 Received March 22, Revised April 20, Accepted April 28, 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 : 이선영, 05030, 서울시광진구능동로 120-1, 건국대학교의학전문대학원내과학교실 Correspondence to: 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, ORCID: Financial support: This study was supported by the Korean National Research Foundation (NRF 2016R1D1A1B ). Conflict of interest: None. Korean J Gastroenterol, Vol. 73 No. 6, June

2 Kim YJ, et al. Nodular Gastritis as a Precursor Lesion of Atrophic and Metaplastic Gastritis 333 큰결절형 (large-nodular-type) 으로보인다. 4 아직도육안적소견으로진단하는결절성위염과병리학적소견으로진단하는림프여포구성위염 (lymphofollicular gastritis) 을혼동하여사용하는경향이있으나, 실제로림프여포구성위염중에서내시경검사시결절성위염으로보이는경우는소수 (13%) 에불과하므로다르게취급해야한다. 5 반대로위내시경검사시채취할수있는검체깊이의한계때문에 H. pylori 감염으로인한결절성위염환자의조직검사검체에서림프여포와림프혈장계세포의응집이보이지않는경우도흔하다. 3,4,6 H. pylori 감염이흔한지역에서는성인의약 2% 에서결절성위염이관찰되며, 콜라겐성위염 (collagenous gastritis), 아밀로이드증 (amyloidosis), 유육종증 (sarcoidosis) 등다른원인에의한결절성위염은드물다. 7,8 H. pylori 제균치료는결절성위염을호전시킬수있는가장중요한인자로서, 균이사라지고난후수개월에걸쳐서결절이사라진다. 9,10 그러나현재우리나라국민건강의료보험인정기준으로는위암, 위의말트림프종, 소화성궤양, 특발성혈소판감소성자반증이진단된경우에만 H. pylori 제균치료의적응증에해당된다. 따라서보건복지부공고 호에의거하여결절성위염환자에서는제균치료제를 100/100 급여로처방해야하는데, 감염자가항생제값에대한본인부담을거부할경우에는 H. pylori 감염이지속된상태에서경과를관찰하는수밖에없다. 결절성위염환자를장기간추적검사하다보면 H. pylori 감염이지속됨에도불구하고일부에서는결절이사라지고위축성위염이나화생성위염등의다른위염이관찰된다. 이는결절성위염이다른위염의전구병변일가능성을시사하지만아직까지어떤결절성위염환자가어떤위염으로진행하는지에대해서는알려진바가없다. 이에본연구에서는결절성위염에서결절이사라진후에관찰되는내시경소견과그와연관된인자에대하여조사하였다. 대상및방법 2. 결절성위염의진단과분류결절성위염은위내시경검사시전정부에서무색의다발성점막하결절들이닭살처럼보이면진단하였다. 결절성위염의분류는규칙적인 1-2 mm의결절들로구성된작은과립형 (small-granular type) 과 3-4 mm의납작한결절들로구성된큰결절형 (large-nodular-type) 으로분류하였다 (Fig. 1). 상부위장관내시경검사는본원의소화기내과전문의가 GIF-H260 또는 GIF-H290 (Olympus, Tokyo, Japan) 이나 EG-2990i (Pentax, Tokyo, Japan) 로시행하였으며, 관찰자간의차이를줄이기위하여최종진단은두연구자 (YJK와 SYL) 의동의하에내려졌다. 3. H. pylori 감염에대한진단과치료내시경검사시채취된위점막을포르말린에고정하여표본을제작한뒤, H&E 염색과 Giemsa 염색을시행하였다. H&E 염색에서 H. pylori가관찰되고 Giemsa 염색양성소견을보이면 H. pylori 감염이있다고진단하였다. 결절성위염으로진단된 H. pylori 감염자가제균치료에동의한경우, 국내지침에맞추어일차제균치료 (amoxicillin 1 g, clarithromycin 500 mg, lansoprazole 15 mg [ 또는 pantoprazole 20 mg] 모두하루 2회 ) 를일주일간하였다. 12 약물복용이끝난 4주뒤에는요소호기검사로제균여부를확인하였다. 제균실패시에는이차제균치료 (metronidazole 500 mg 하루 3회, tetracycline 500 mg 하루 4회, tripotassium bismuth dicitrate 300 mg 하루 4회, lansoprazole 15 mg [ 또는 pantoprazole 20 mg] 하루 2회 ) 를일주일간하였으며, 복용을마친 4주뒤에요소호기검사로확인하였다. 4. 추적위내시경검사결절소실후의위내시경소견에대한기술은배경위점막의색과모양의변화로판단하였다. 점막하혈관상이투영되어보이거나소금과후추를뿌려놓은듯한희끗희끗한양상 1. 연구대상자선정본원에서 2008년부터 2014년사이에위내시경검사시결절성위염으로진단된 H. pylori 감염자중본원에서 3년이상위내시경추적검사를받은만 18세이상의성인을대상으로하였다. 위점막에서조직검사를하지않아 H. pylori 감염이외의다른원인에의한결절성위염을배제할수없는경우는연구대상에서제외하였다. 이연구는결절성위염환자를대상으로한전향적코호트연구로서, 기존의결절성위염의후속연구로진행되었다. 11 본원임상윤리위원회의승인을받았으며 (KUH ), 헬싱키선언의윤리기준을준수하였다. A Fig. 1. Two main subtypes of nodular gastritis. (A) Small-granular-type nodular gastritis consisting of multiple 1-2 mm subepithelial nodules in the antrum. (B) Large-nodular-type nodular gastritis consisting of multiple 3-4 mm subepithelial nodules in the antrum. B Vol. 73 No. 6, June 2019

3 334 김영중등. 만성위염의전구병변 (salt-and-pepper appearance, 소금-후추가루양상 ) 이보이면위축성위염군으로분류하였다 (Fig. 2A-D). 불규칙한흰색융기나광범위한불규칙적인융기 (diffuse irregular elevation) 가관찰되면화생성위염군으로분류하였다 (Fig. 2E-H). 전정부의대만측이나체부의소만측에긴일직선상의규칙적인발적이여러개보이면표재성위염으로진단하였다. 전정부에붉은색의융기형미란이균일한크기로여러개보이면미란성위염으로진단하였다. 배경위점막의색이나모양에이상이없으면정상소견으로판정하였다. correction으로분석하였다. 내시경진단에대한관찰자간의차이는 kappa 분석으로조사하였다. Kappa 수치 (κ) 가 >0.80 이면매우높은일치도 (excellent agreement), κ> 이면높은일치도 (good agreement), κ> 이면중등도의일치도 (moderate agreement), κ> 이면낮은일치도 (fair agreement), κ 0.20이면매우낮은일치도 (poor agreement) 로판단하였으며, standard error와함께기술하였다. PASW Statistics version 17.0 (SPSS Inc., Chicago, IL, USA) 을사용하였으며, 유의수준은 p<0.05로하였다. 5. 통계분석연속형변수는 Student s t-test로분석한뒤, 평균과표준편차 (SD) 로표시하였다. 범주형변수는 Chi-square test로분석한뒤, 빈도 (%) 로표시하였다. 정규분포를하지않는경우연속형변수는 Kruskal-Wallis test로분석한뒤중간값과범위로표시하였으며, 범주형변수는 Fisher s exact test로분석한뒤빈도 (%) 로표시하였다. 세군간의차이를알기위하여연속형변수는 ANOVA와 Bonferroni correction으로분석하였으며, 범주형변수는 Chi-square test와 Bonferroni 결과 1. 결절성위염환자들의경과본원에서 3년이상위내시경추적검사를받은 H. pylori 감염성결절성위염환자 99명중에서진단당시위점막에서조직검사를하지못한 2명을제외한 97명을분석하였다. H. pylori 감염이증명된 97명의결절성위염환자중 73.0±22.0개월의관찰기간동안결절이사라진사람은 61명이었다. 결절성위염의호전여부는나이나성별과무관하였다 (Table 1). A B C D E F G H Fig. 2. Follow-up endoscopic findings after nodule regression. (A) Small-granular-type nodular gastritis with whitish discoloration was observed in the antrum. With the progress of nodule regression, a salt-and-pepper appearance was observed in the antrum. (B) The salt-and-pepper appearance extended up to the lesser curvature side of the body, which is consistent with the atrophic border. (C) With the progression of the salt-and-pepper appearance, whitish discoloration with transparent submucosal vessels was visible in the antrum. An atrophic border was found at the greater curvature side of the proximal antrum. (D) Prominent submucosal vessels were observed from the antrum extending up to the lower body. The endoscopic diagnosis was consistent with chronic atrophic gastritis. (E) Large-nodular-type nodular gastritis was noticed in the distal antrum. (F) The nodules extended up to the proximal antrum. Some of the large nodules were closer to the diffuse irregular mucosal elevations observed in metaplastic gastritis than the nodules observed in nodular gastritis. (G) On a retroflexed view, diffuse irregular elevations were observed on the lesser curvature side of the body. A villous appearance was noted on the surface of whitish elevated lesions. (H) Diffuse irregular elevations were observed with whitish discoloration, indicating intestinal metaplasia. The endoscopic diagnosis was consistent with metaplastic gastritis. The Korean Journal of Gastroenterology

4 Kim YJ, et al. Nodular Gastritis as a Precursor Lesion of Atrophic and Metaplastic Gastritis 335 제균치료를받은 25명중 7명은일차제균치료에실패하였으며, 이차제균치료후에성공하였다. 이중에서일차제균치료시속쓰림증을호소하였던 1명은이차제균치료시 pantoprazole 40 mg을하루두번복용하였다. 제균치료에성공한 25명중 23명 (92%) 에서결절성위염이호전되어제균치료여부에따른차이를보였다. 제균치료 Table 1. Characteristics of 97 H. pylori-infected Patients with Nodular Gastritis Variable All (n=97) Regression of nodules (n=61) Persistent nodules (n=36) Age (years) 40.3± ± ± Female 68 (70.1) 44 (72.1) 24 (66.7) Successful H. pylori eradication 25 (25.8) 23 (37.7) 2 (5.6) <0.001 Total follow-up period (months) 73.0± ± ± Initial endoscopic findings Small-granular-type 48 (49.5) 27 (44.3) 21 (58.3) Antrum only 53 (54.6) 36 (59.0) 17 (47.2) Multiple hemorrhagic spots in the corpus 29 (30.0) 15 (24.6) 14 (38.9) Updated Sydney system scores (no:mild:moderate:marked) Inflammation 0:6:77:14 0:6:47:8 0:0:30: Activity 1:30:54:12 1:15:36:9 0:15:18: Atrophy 78:17:2:0 49:10:2:0 29:7:0: Intestinal metaplasia 89:6:1:1 55:4:1:1 34:2:0: H. pylori infiltration 2 a :8:43:44 2 a :5:28:26 0:3:15: The differences between the two were analyzed using a t-test and chi-square test for the continuous and categorical variables, respectively. The continuous variables are presented as the mean±standard deviation, and the categorical variables are presented as the number of patients with the proportion (%). H. pylori, Helicobacter pylori. a Two patients did not show H. pylori infiltration at the time of the biopsy because they were on medication for H. pylori eradication. p-value Fig. 3. Study flow of the 97 H. pylori-infected patients with nodular gastritis. The asterisks in parenthesis indicate the numbers of patients in whom H. pylori was eradicated. In total, 25 patients with large-nodular-type nodular gastritis (including six patients in whom H. pylori was eradicated) showed metaplastic gastritis on follow-up endoscopy, whereas 14 patients with small-granular-type nodular gastritis (including five patients in whom H. pylori was eradicated) showed chronic atrophic gastritis. Most of the patients with persistent nodules showed the same pattern on follow-up endoscopy; however, two patients with small-granular-type nodular gastritis progressed to large-nodular-type nodular gastritis. H. pylori, Helicobacter pylori. Vol. 73 No. 6, June 2019

5 336 김영중등. 만성위염의전구병변 후에도결절성위염이지속된감염자 2명중 1명은 40세여자로, 결절성위염을진단받고 4년이지나서야제균치료를하였다. 따라서총추적기간은 61개월이었으나, 마지막내시경추적검사는제균치료 12개월후에불과하였다. 다른 1명은 38세여자로결절성위염을진단받고 3년이지나서야제균치료를하여, 마지막내시경추적검사는제균치료 22개월후였다 ( 총추적기간 59개월 ). 2. 결절성위염호전후의추적내시경검사소견추적위내시경검사에서결절이사라진 61명중에소금-후추가루양상이나점막하혈관상을보인경우는 16명이었으며, 불규칙한점막의융기나흰색의색조변화를보인경우는 29명이었다 (Fig. 3). 나머지 14명은정상위점막을시사하는규칙적인혈관상을보였으며, 1명 (40세남자 ) 은미란성위염으로진단되었다. 마지막 1명 (41세여자 ) 은결절이사라진후에만성표재성위염으로진단되었다 (Fig. 4A-D). 정상소견을보인군 (n=14) 과표재성위염군 (n=1), 미란성위염군 (n=1) 간의나이, 성별, 추적기간, 제균치료율, 진단당시의조직검사및내시경소견에통계학적으로유의한차이는없었다. 두관찰자간의내시경적진단차이는총 8예 (8.2%) 에서 관찰되었으며, Kappa 수치 (κ) 는 (standard error=0.058, p<0.001) 으로측정되었다. 첫번째관찰자 (YJK) 가큰결절형결절성위염으로진단한 3예를두번째관찰자 (SYL) 는화생성위염군으로진단하였다. 또한, 첫번째관찰자가화생성위염군으로진단한 5예를두번째관찰자는큰결절형결절성위염으로진단하였다. 3. 위축성위염군으로진행한경우추적위내시경검사에서소금-후추가루양상이나점막하혈관상을보인경우는총 16명으로, 위축성위염군으로분류되었다. 결절이호전된작은과립형결절성위염환자 27명중 14명이위축성위염군으로진행하여, 결절의크기가작은작은과립형결절성위염은위축성위염으로진행하는경향을보였다 (Table 2). 16명중에서점막하혈관상은 2명에서만관찰되었는데, 나머지 14명과진단당시의성별, 나이, 제균치료여부, 관찰기간, 내시경소견, 조직검사소견 ( 시드니체계의측정항목 5가지 ) 을비교한결과, 통계학적으로유의한차이는없었다. 명확한점막하혈관상을보인 2명은 40세남자와 34세여자로, 둘다제균치료에성공하였음에도불구하고각각제균치료 17개월과 52개월후에위축성위염소견을보였다. A B C D E F G H Fig. 4. Different prognosis of small-granular-type nodular gastritis according to the presence of a H. pylori infection. (A) Small-granular-type nodular gastritis was diagnosed along with a H. pylori infection in a 42-year-old woman. (B) Salt-and-pepper appearance was observed at the lesser curvature side of the lower body. (C) Four years after the H. pylori eradication, several linear hyperemic streaks were observed at the greater curvature side of the antrum. The endoscopic diagnosis was consistent with chronic superficial gastritis. (D) A salt-and-pepper appearance was no longer observed in the lower body. (E) Small-granular-type nodular gastritis was diagnosed along with a H. pylori infection in a 36-year-old man. (F) Small- and regular-sized nodules were extending up to the proximal antrum. (G) After eight years of persistent H. pylori infection, the nodules showed irregularity. (H) The size of the nodules increased with irregular changes. The endoscopic diagnosis was large-nodular-type nodular gastritis. H. pylori, Helicobacter pylori. The Korean Journal of Gastroenterology

6 Kim YJ, et al. Nodular Gastritis as a Precursor Lesion of Atrophic and Metaplastic Gastritis 337 Table 2. Characteristics of 61 Patients with Nodular Gastritis according to the Findings of the Follow-up Endoscopy after Nodule Regression Variable CAG group showing salt-and-pepper appearance and/or transparent vessels (n=16) MG group showing diffuse irregular elevations and/or whitish plaques (n=29) Other endoscopic findings (n=16) Age (years) 42.1± ± ±7.8 Female 11 (68.8) 21 (72.4) 12 (75.0) Follow-up period (months) 76.1± ± ±23.9 Successful H. pylori eradication 5 (31.3) 6 (20.7) 12 (75.0) a,b Nodule regression after eradication (months) 36.0 (9-110) 47.3 (13-90) 23.7 (5-57) Initial endoscopic findings Small-granular-type 14 (87.5) 4 (13.8) a 9 (56.3) a,b Antrum only 10 (62.5) 16 (55.2) 10 (62.5) Multiple hemorrhagic spots in the corpus 5 (31.3) 8 (27.6) 2 (12.5) Updated Sydney system scores (no:mild:moderate:marked) Inflammation 0:0:13:3 0:5:20:4 0:1:14:1 Activity 0:3:11:2 1:8:16:4 0:4:9:3 Atrophy 15:0:1:0 22:6:0:0 11:4:1:0 Intestinal metaplasia 15:0:0:1 26:2:1:0 14:2:0:0 H. pylori infiltration 0:1:10:5 1:1:12:15 1:3:6:6 Other endoscopic findings consisted of 14 normal findings, one of erosive gastritis, and one of chronic superficial gastritis. The differences among the three groups were analyzed by post-hoc analysis for the continuous variables, and a chi-square test with a Bonferroni correction for the categorical variables. Continuous variables are presented as the mean±standard deviation, and categorical variables are presented as the number of patients with proportion (%). CAG, chronic atrophic gastritis; MG, metaplastic gastritis; H. pylori, Helicobacter pylori. a Significant difference (p<0.05) compared to the patients showing salt-and-pepper appearance and/or transparent vessels; b Significant difference (p<0.05) compared to the patients showing diffuse irregular elevations and/or whitish plaques. Table 3. Differences among 29 Patients Showing Diffuse Irregular Elevations after Nodule Regression Variable Diffuse irregular elevations only (n=27) Diffuse irregular elevations with whitish plaques (n=2) p-value Age (years) 40.5± ± Female 19 (70.4) 2 (100) Total follow-up period (months) 79.9± ± H. pylori eradication 5 (18.5) 1 (50) Follow-up period after eradication (months) 47.3 (13-90) 40.5 (13-68) Initial endoscopic findings Small-granular-type 3 (11.1) 1 (50) Antrum only 16 (59.3) Multiple hemorrhagic spots in the corpus 7 (25.9) 1 (50) Updated Sydney system scores (no:mild:moderate:marked) Inflammation 0:4:20:3 0:1:0: Activity 1:8:14:4 0:0:2: Atrophy 23:4:0:0 0:2:0: Intestinal metaplasia 26:1:0:0 0:1:1:0 <0.001 H. pylori infiltration 0:1:12:14 1:0:0: The differences between the two groups were analyzed using a t-test and chi-square test for the continuous and categorical variables, respectively. The continuous variables are presented as the mean±standard deviation, and the categorical variables are presented as the number of patients with the proportion (%). H. pylori, Helicobacter pylori. Vol. 73 No. 6, June 2019

7 338 김영중등. 만성위염의전구병변 4. 화생성위염군으로진행한경우추적위내시경검사에서불규칙한점막의융기와흰색의색조변화를보인경우는 29명이었다. 결절이호전된큰결절형결절성위염환자 34명중 25명이화생성위염군으로진행하여, 결절의크기가큰경우에는화생성위염으로진행하는경향을보였다 (Table 2). 흰색변화가동반된장상피화생을보인화생성위염은단 2명 (47세여자, 71세여자 ) 에서만관찰되었다. 71세여자는결절성위염으로진단받고 3년후에제균치료를하였음에도불구하고, 제균치료 13개월후에화생성위염이진단되었다. 제균치료를하지않아서 68개월관찰기간내내감염이지속된 47세여자는명확한흰색융기가있는화생성위염소견을보였다. 화생성위염이진단된 2명은불규칙한점막의융기만보인 27명에비하여나이가많았다 (Table 3). 또한, 이 2명은처음진단시림프여포와함께위축과장상피화생소견이조직검사에서증명되었다. 5. 결절성위염이지속된환자들의추적위내시경검사소견추적검사기간동안결절이사라지지않은 36명은작은과립형결절성위염환자 21명과큰결절형환자 15명로구성되어있었다 (Fig. 3). 큰결절형결절성위염환자 15명은모두추적검사에서큰결절형을유지하였으나, 작은과립형결절성위염환자 21명중 2명 (9.5%) 은추적검사에서큰결절형으로변형된모습을보였다 (Fig. 4E-H). 고찰 결절성위염환자에서결절이사라진후위축성및화생성위염의전구병변으로진행하는데관여하는주요인자는지속되는 H. pylori 감염과결절의크기였다. 작은과립형의결절성위염은소금-후추가루양상을거쳐위축성위염으로진행하는경향을보였으며, 큰결절형은불규칙한점막의융기로구성된화생성위염으로진행하는경향을보였다. 또한, 결절이지속된작은과립형결절성위염환자중일부는큰결절형으로진행하였다. 이연구를통하여결절성위염환자에서제균치료를하지않을경우결절성위염이지속되거나, 서서히위축성위염이나화생성위염으로진행한다는것을확인할수있었다. 위각부에서체부의소만측으로진행되는소금-후추가루양상들은내시경검사시흔히관찰되는소견임에도불구하고, 그의의에대해서는정확히알려진바가없다. 이연구에서는활동성 H. pylori 감염이있는상태에서결절성위염이수년간지속되면점차점막하결절로튀어나왔었던부분이납작해지면서희끗희끗하게탈색되고, 점막하층이투영되는것이보였다. 나아가서소금-후추가루양상을보인점막의희끗희끗 한부분들이융합되면서점막하혈관상이관찰되는전형적인만성위축성위염소견을보였다. 또한, 이러한변화는전정부에서시작하여위각과체부의소만측으로진행하였다. 이는 Kimura와 Takemoto 13 의위축성위염에대한분류중위각을지나체부의소만측으로진행하는폐쇄형 2형의위축성위염의경로와일치하며, 개방형위축성위염으로진행하기전의만성위염소견과일치한다 장상피화생의내시경소견은울퉁불퉁한점막표면 (rough mucosal surface), 융모상모양 (villous appearance), 흰색융기 (whitish mucosa), 광범위하고납작한발적 (patchy redness), 비전형적인혈관상 (atypical collecting venule) 등으로다양하게관찰될수있다. 16 이중에서흰색융기나융모상모양은주변점막과다르게보여서진단하기가쉬우며 (Fig. 2G), 특수광에서도옅은푸른색문양 (light blue crest) 으로관찰되거나특수면역염색에서 CDX2 양성소견을보이는등화생성위염의특징이비교적쉽게관찰된다. 14,16 반면에나머지소견들은국소병변없이광범위하게관찰되어 (Fig. 2H), 이연구에서는흰색융기처럼장상피화생변화가명확한증례들과아닌증례들을분류하여추가로비교하였다. 후자의경우에는납작한발적, 울퉁불퉁한점막, 비전형적인혈관상이전정부에서체부로퍼지는소견을보였는데, 관찰자간불일치를보인 8예가모두여기에해당되어큰결절형결절성위염에서화생성위염으로진행하는연장선상임을알수있었다. 반면에흰색융기를보인 2예는결절성위염과분류하기가쉽고평균연령도유의하게높아서, 화생성위염으로진행된기간이상대적으로길었을것으로추정되었다. 이연구에서결절성위염은제균치료를하지않은상태에서결절이사라질경우, 위축성이나화생성위염으로진행하였다. 이두가지만성위염은결절성위염처럼전정부에서먼저발생한뒤에체부로진행하는대표적인 H. pylori 감염성위염이다. 17,18 나아가서결절성위염은이형성증과장상피화생변화가발생할수있으며, 고령에서의결절성위염도젊은연령에서의결절성위염처럼위암과연관이있다. 19,20 이연구에서도화생성위염으로진행한환자들은나이가많고, 결절성위염진단당시에이미조직검사에서장상피화생이동반된소견을보였다. 하지만결절성위염은위축성위염이나화생성위염과달리위산분비능이상승되어있는활동성감염상태에해당하며, 제균치료를하면비대성위염 (hypertrophic gastritis) 이나미만성발적 (diffuse redness) 처럼거의정상화된다. 9,11 또한, 결절성위염은미만형위암을유발할수있으므로장형위암으로진행하는위축성이나화생성위염과달리만성비활동성감염상태가아닌, 그전단계에해당한다 즉, 결절성위염은위축성이나화생성위염의전구병변에해당하므로, 위암화과정이진행되는것을막 The Korean Journal of Gastroenterology

8 Kim YJ, et al. Nodular Gastritis as a Precursor Lesion of Atrophic and Metaplastic Gastritis 339 기위하여제균치료를적극적으로시행해야한다. 우리나라를제외한다른국가들지침서에는 H. pylori 감염이진단되면제균치료를하도록되어있다 따라서결절성위염환자가장기간감염된채다른위염으로진행해가는과정을보고한연구는희귀하다. 한일본연구에서는여성에서작은결절형이더흔하며, 전정부에만국한된결절성위염이위축성위염으로진행한다고하였다. 32 결절성위염자체가여성에서더흔하고, 위축성변화는화생성변화를동반하면서전정부에서체부로진행되기에그런경향을보일수도있겠지만, 이번연구에서성별이나결절의위치는위축성이나화생성위염으로의진행에영향을주지않았다. 결절성위염환자에서감염이장기간지속되면성별이나결절의위치와무관하게위축성및화생성위염으로진행하므로, H. pylori 감염이진단된결절성위염환자는성별이나결절의크기와무관하게제균치료를해야한다. 33,34 이연구는단일기관연구로장기간추적위내시경검사를본원에서시행한환자만선별하였기에연구대상자가 97명으로적다는한계점이있다. 그러나적은숫자에도불구하고, 통계학적으로유의한인자를찾을수있었다. 아울러감염이지속되면소금-후추가루양상들이나불규칙한점막의융기들을보이면서위축성및화생성위염으로진행한다는것을확인할수있었기에, 연구대상자를더늘려도결과는달라지지않을것으로예상된다. 또다른한계점으로는위내시경검사로진단한위축성위염을조직검사로증명하지못하였다는것이다. 위축과장상피화생은위내시경소견과조직검사소견의일치도가낮아, 점막하혈관상이명확히보이는경우에도조직검사에서증명되지않을수있다. 15 이는조직을고정하여슬라이드를제작하는과정에서조직이줄어들기때문으로추정되며, 이미고정된조직을다시펴서현미경으로관찰할수는없기에위점막조직검사로정확하게진단하는것에한계가있다. 위축성위염이나화생성위염의진단에있어서조직검사소견보다위내시경소견이정확할수있으며, 이연구에서관찰된소금-후추가루양상들은조직검사로도진단하기어려운초기소견에해당한다. 따라서위내시경검사시에위각에서소금-후추가루양상이보이면만성위암화과정의초기단계로간주하고, 진행을막기위하여 H. pylori 감염여부를확인하고치료해야한다. 결론적으로, 결절성위염은 H. pylori 감염이지속되면결절이사라진후에위암의전구병변인위축성이나화생성위염으로진행한다. 작은과립형의결절성위염은폐쇄형위축성위염으로변해가는경향을보였으며, 이는납작해진결절후에보이는소금-후추가루양상의희끗희끗한점막들이융합되면서점막하혈관상이관찰되는위축성위염으로진행하였다. 큰결절형결절성위염은불규칙한점막의융기들이점차 체부로퍼지면서화생성위염으로진행하는경향을보였다. 결절성위염이위축성및화생성위염으로진행하는것을막기위해서라도 H. pylori 제균치료가필요하다. 요 약 목적 : 위축성위염과화생성위염은 H. pylori 감염으로인한전암성병변으로알려졌으나, 만성위염의전구병변에대한연구는희박하다. 이연구에서는결절성위염환자들중에서위축성및화생성위염으로진행하는환자들의특징및이와연관된인자들을규명하고자하였다. 대상및방법 : 상부위장관내시경검사시결절성위염으로진단된 H. pylori 감염자를대상으로하였다. 결절성위염진단부터마지막내시경검사를받은기간이 36개월미만인경우에는대상에서제외하였다. 내시경상 1-2 mm의균일한점막하결절을보이는경우작은과립형결절성위염으로정의하였고, 3-4 mm의불규칙적인점막하결절이있는경우를큰결절형결절성위염으로정의하였다. 결절이사라진후관찰되는배경위점막의내시경소견을기록하였다. 결과 : 추적내시경검사를시행한 97명의결절성위염환자를 73.0±22.0개월간관찰한결과, 61명에서결절이소실되었다. 결절성위염이호전된 61명중 16명은소금과후추를뿌려놓은듯한소금-후추가루양상 (salt-and-pepper appearance) 과점막하혈관상이투영되는위축성위염군으로진행하였다. 다른 29명은불규칙한점막의융기 (diffuse irregular elevation) 와흰색융기가광범위하게관찰되는화생성위염군으로진행하였다. 나머지 16명중 14명은정상내시경소견을보였으며, 제균치료율 (12/16, 75.0%) 이위축성위염군 (5/16, 31.3%) 이나화생성위염군 (6/29, 20.7%) 보다유의하게높았다 (p=0.001). 작은과립형결절성위염은위축성위염군 (14/27, 51.9%) 으로진행하는경향을보인반면, 큰결절형은화생성위염 (25/34, 73.5%) 으로진행하는경향을보였다 (p<0.001). 결론 : H. pylori 감염이지속되면결절성위염은전암성병변인위축성이나화생성위염으로진행한다. 작은결절형은위축성위염으로진행하는경향을보이며, 큰결절형은화생성위염으로진행하는경향을보인다. 색인단어 : 위염 ; 림프조직 ; 위축성 ; 화생성 REFERENCES 1. Miyamoto M, Haruma K, Yoshihara M, et al. Nodular gastritis in adults is caused by Helicobacter pylori infection. Dig Dis Sci 2003;48: Chen MJ, Wang TE, Chang WH, Liao TC, Lin CC, Shih SC. Nodular Vol. 73 No. 6, June 2019

9 340 김영중등. 만성위염의전구병변 gastritis: an endoscopic indicator of Helicobacter pylori infection. Dig Dis Sci 2007;52: Okamura T, Sakai Y, Hoshino H, Iwaya Y, Tanaka E, Kobayashi M. Superficially located enlarged lymphoid follicles characterise nodular gastritis. Pathology 2015;47: Nakashima R, Nagata N, Watanabe K, et al. Histological features of nodular gastritis and its endoscopic classification. J Dig Dis 2011;12: Kim YJ, Lee SY, Lee SP, et al. Identification of nodular gastritis among patients diagnosed with lymphofollicular gastritis on gastric biopsied specimen. Korean J Gastroenterol 2018;71: Al-Enezi SA, Alsurayei SA, Aly NY, et al. Endoscopic nodular gastritis in dyspeptic adults: prevalence and association with Helicobacter pylori infection. Med Princ Pract 2010;19: Hong SN, Jo S, Jang JH, et al. Clinical characteristics and the expression profiles of inflammatory cytokines/cytokine regulatory factors in asymptomatic patients with nodular gastritis. Dig Dis Sci 2012;57: Ebert EC, Hagspiel KD. Gastrointestinal and hepatic manifestations of rheumatoid arthritis. Dig Dis Sci 2011;56: Chen MJ, Shih SC, Wang TE, Chan YJ, Chen CJ, Chang WH. Endoscopic patterns and histopathological features after eradication therapy in Helicobacter pylori-associated nodular gastritis. Dig Dis Sci 2008;53: Nishikawa I, Kato J, Terasoma S, et al. Nodular gastritis in association with gastric cancer development before and after Helicobacter pylori eradication. JGH Open 2018;2: Kim JW, Lee SY, Kim JH, et al. Nodule regression in adults with nodular gastritis. Gastroenterology Res 2015;8: Kim SG, Jung HK, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. J Gastroenterol Hepatol 2014;29: Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy 1969;1: Ahn SY, Lee SY, Hong SN, et al. Endoscopic diagnosis of open-type atrophic gastritis is related to the histological diagnosis of intestinal metaplasia and Cdx2 expression. Dig Dis Sci 2011;56: Nomura S, Ida K, Terao S, et al. Endoscopic diagnosis of gastric mucosal atrophy: multicenter prospective study. Dig Endosc 2014;26: Fukuta N, Ida K, Kato T, et al. Endoscopic diagnosis of gastric intestinal metaplasia: a prospective multicenter study. Dig Endosc 2013;25: 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: 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: Niknam R, Manafi A, Maghbool M, Kouhpayeh A, Mahmoudi L. Is endoscopic nodular gastritis associated with premalignant lesions? Neth J Med 2015;73: Kitamura S, Yasuda M, Muguruma N, et al. Prevalence and characteristics of nodular gastritis in Japanese elderly. J Gastroenterol Hepatol 2013;28: Lee SP, Lee SY, Kim JH, Sung IK, Park HS, Shim CS. Link between serum pepsinogen concentrations and upper gastrointestinal endoscopic findings. J Korean Med Sci 2017;32: Hayashi S, Imamura J, Kimura K, Saeki S, Hishima T. Endoscopic features of lymphoid follicles in Helicobacter pylori-associated chronic gastritis. Dig Endosc 2015;27: 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): Japan Helicobacter Society Guideline Committee. Guidelines for diagnosis and treatment of H. pylori infection. Tokyo: Sentan Igaku-sha, Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol 2017;112: Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut 2017;66: Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 2016;151:51-69.e Smith S, Boyle B, Brennan D, et al. The Irish Helicobacter pylori working group consensus for the diagnosis and treatment of H. pylori infection in adult patients in Ireland. Eur J Gastroenterol Hepatol 2017;29: Sheu BS, Wu MS, Chiu CT, et al. Consensus on the clinical management, screening-to-treat, and surveillance of Helicobacter pylori infection to improve gastric cancer control on a nationwide scale. Helicobacter 2017;22:e Mahachai V, Vilaichone RK, Pittayanon R, et al. Helicobacter pylori management in ASEAN: the Bangkok consensus report. J Gastroenterol Hepatol 2018;33: International Agency for Research on Cancer, World Health Organization. Helicobacter pylori eradication as a strategy for preventing gastric cancer. IARC working group reports volume 8. Lyon: International Agency for Research on Cancer, Shiotani A, Kamada T, Kumamoto M, et al. Nodular gastritis in Japanese young adults: endoscopic and histological observations. J Gastroenterol 2007;42: Sokmensuer C, Onal IK, Yeniova O, et al. What are the clinical implications of nodular gastritis? Clues from histopathology. Dig Dis Sci 2009;54: Dwivedi M, Misra SP, Misra V. Nodular gastritis in adults: clinical features, endoscopic appearance, histopathological features, and response to therapy. J Gastroenterol Hepatol 2008;23: The Korean Journal of Gastroenterology