ORIGINAL ARTICLE ISSN 1738-3331, http://dx.doi.org/10.7704/kjhugr.2015.15.3.166 The Korean Journal of Helicobacter and Upper Gastrointestinal Research, 2015;15(3):166-173 Borrmann 4 형위암의다양한내시경소견과임상적특성 장지영, 심기남, 태정현, 최아름, 문창모, 김성은, 정혜경, 정성애 이화여자대학교의학전문대학원내과학교실, 의과학연구소 Variable Endoscopic Findings and Clinicopathological Characteristics of Borrmann Type 4 Advanced Gastric Cancer Ji Young Chang, Ki-Nam Shim, Chung Hyun Tae, A Reum Choe, Chang Mo Moon, Seong-Eun Kim, Hye-Kyung Jung, Sung-Ae Jung Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea Background/Aims: Borrmann type 4 advanced gastric cancer (AGC) is difficult to diagnose. There are no typical endoscopic findings. Endoscopic biopsies have a high false negative rate because Borrmann type 4 AGC frequently resides below the submucosal cells from which it develops. The aim of this study was to investigate the endoscopic findings of Borrmann type 4 AGC in order to improve diagnosis rates. Materials and Methods: A total of 24 patients with pathologically proven Borrmann type 4 AGC at the Ewha Womans University Medical Center between January 2008 and May 2013 were included. We divided the cases according to their distinguishing endoscopic findings. The diagnostic yield for endoscopic biopsies was evaluated. Results: The most common endoscopic findings were cases with Bormann type 4 AGC like lesions (diffuse infiltrative, n=10), followed by Bormann type 3 AGC like lesions (ulceroinfiltrative, n=9), Borrmann type 2 AGC like lesions (ulcerofungating, n=4) and early gastric cancer like lesion (n=1). Among the 23 cases in which endoscopic biopsies was performed, the diagnostic yield for the first endoscopic biopsy was 87.0% (n=20). All of the second endoscopic biopsies failed to diagnose the malignancy. Conclusions: The endoscopic findings of Borrmann type 4 AGC are atypical and diverse. In cases where negative results are accompanied by a malignant impression, further meticulous evaluation should be performed with careful targeting. (Korean J Helicobacter Up Gastrointest Res 2015;15:166-173) Key Words: Stomach neoplasms; Endoscopy, gastrointestinal 서 론 위암은국내암발생률 2위로남성의암발생률 1위, 여성의암발생률 4위 (2011년기준 ) 1 를차지하며새로진단되는위암환자의 50 60% 는조기위암이다. 2 림프절전이가없는조기위암의경우내시경적절제술만으로도완치를기대할수있으며, 진행성위암역시보조적항암요법과방사선요법의발전으로치료성적및환자의삶의질이현저히향상되었다. 2 그러나진행성위암중 Borrmann 4형위암은진단시림프절전이, 복막전이, 장막침윤의정도가높아치료방법이제한적이고, 진행이빠른생물학적특성때문에여전히치료성적이좋지않다. 3,4 이러한불량한예후는위내시경검사에서점막병변이간과되거나점막하침윤으로조직검사에서위음성으로나와 5 Received: March 6, 2015 Accepted: August 1, 2015 Corresponding author: Ki-Nam Shim Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea Tel: +82-2-2650-2632, Fax: +82-2-2655-2076, E-mail: shimkn@ewha.ac.kr 진단및치료가지연되기때문이며, 이는윤리적, 법적문제를야기하기도한다. 따라서 Borrmann 4형위암의치료성적을향상시키기위해서는내시경검사를통한조기진단이필수적이다. 기존에알려진 Borrmann 4형위암의기본적인내시경소견은점막주름의비대와위벽의경화이다. 그러나최근연구에의하면조기위암의형태등다양한소견으로나타날수있다고한다. 6,7 본연구에서는 Borrmann 4형위암의내시경소견과임상적특성을알아봄으로써 Borrmann 4형위암의진단율을향상시킬수있는인자들을찾아보고자한다. 대상및방법 1. 대상 2008년 1월부터 2013년 5월까지이화여자대학교의료원에서위암으로진단받고수술또는내시경적치료를받은 596명중수술후병리조직학적소견을바탕으로 Borrmann 4형위암 Copyright 2015 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 (http://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.
Ji Young Chang, et al: Variable Gastroscopic Findings in Borrmann Type 4 AGC 으로진단되고, 진단당시내시경사진이남아있는 24명의환자들을대상으로 2014년 7월을추적종점으로하여후향적으로조사하였다. 이번연구는이화여자대학교목동병원임상시험심사위원회의승인을통과하였다 (IRB No. 2014-10-011-001). 2. 방법대상환자의의무기록을통하여성별, 연령, 위내시경, 복부컴퓨터단층촬영, 양전자방출컴퓨터단층촬영 (PET-CT) 소견을조사하였다. 그리고내시경을이용한조직검사결과와수술후의병리학적조직학적분류, 분화도, 침윤깊이, 정맥관, 림프관, 신경조직침윤유무를확인하였으며수술후생존기간을분석하였다. 생존기간은수술시행일로부터사망일까지의기간또는환자가생존해있는경우에는마지막내원일까지의기간으로정의하였다. TNM stage는 2010년발행된 American Joint Committee for Cancer Staging 7판에의한분류 8 를사용하였으며암종의크기는최장직경으로대표하였다. 병리학적구분은분화조직형군과미분화조직형군으로구분하였다. 분화조직형군은고분화형위선암, 중등도분화형위선암을포함하며, 미분화조직형군은저분화형위선암과인환세포암을포함하였다. 광범위위전절제술은위전절제술과함께비장, 대장, 췌장, 소장, 간, 신장등의주변장기를함께절제하는경우로정의했다. 3. 통계분석통계분석은 PASW Statistics ver. 18.0 (IBM Co., Armonk, NY, USA) 을이용하였다. 모든측정값들에대해연속형변수들은평균 ± 표준편차로표시하였으며, 기간에대한변수에대해서는중앙값및범위로제시하였다. 생존기간은 Kaplan-meier 방법을이용하여추정하였다. 비연속형범주형변수들은표본의수와백분율로나타냈다. 변수들은소수점첫째자리까지반올림하여나타냈다. 결과 1. 임상적특성 2008년 1월부터 2013년 5월까지이화여자대학교의료원에서위암으로진단받고수술또는내시경적치료를받은 596명의환자중진행성위암환자는 219명 (36.7%) 이었으며, 이중 25명 (11.4%) 의환자들이 Borrmann 4형위암으로진단되었으나진단당시내시경소견이남아있지않은 1명은분석에서제외했다. Borrmann 4형위암환자들의평균연령은 57.8±12.4 세 ( 중앙값, 57세 ; 범위, 39 89세 ) 였으며, 남자가 13명 (54.2%), Table 1. Clinical Characteristics of the Study Subjects Characteristic Value 4 (1~144) Age (yr) 57.8±12.4 (39 89) Gender Male 13 (54.2) Female 11 (45.8) Past history None 13 (54.2) Hypertension 7 (29.2) Chronic liver disease 3 (12.5) Coronary artery disease/ 3 (12.5) cerebral vascular disease Diabetes mellitus 2 (8.3) Other cancer 1 (4.2) Other neurologic disease 1 (4.2) Symptom a None 5 (20.8) Epigastric pain 7 (29.2) Dyspepsia 7 (29.2) Weight loss 6 (25.0) Anemia 2 (8.3) Nausea/vomiting 2 (8.3) Melena 2 (8.3) Interval from symptoms to gastroscopy (wk) (n=19) b Values are presented as mean±sd (range), n (%), or median (range). a Symptoms can be multiple in one patient. b Five patients who had gastroscopy for routine health evaluation was excluded. 여자가 11명 (45.8%) 으로나타났다. 위암이진단되기전 13명 (54.0%) 의환자들은특별한과거력을갖고있지않았으며, 고혈압을진단받았던경우가 7명 (29.1%) 으로가장많았다. 진단전환자들이호소했던증상은상복부통증과소화불량이각각 7예 (29.1%) 로가장높았으며, 특별한증상없이건강검진목적으로시행한내시경검사에서우연히위암이진단된경우도 5예 (20.8%) 가있었다. 증상이발생한후내시경을시행하기까지기간의중앙값은 4주 (1 144주) 였다 (Table 1). 2. 위내시경소견 내시경소견은 Borrmann 형에따라분류하였다 (Fig. 1). Ulceroinfiltrative mucosa (Borrmann 3형 ) 는 9예 (37.5%), diffuse infiltrative mucosa (Borrmann 4형 ) 는 10예 (41.7%) 로높은비율을차지했으며 1예 (4.1%) 는조기위암의육안적형태를보이고있었다 (Table 2). 내시경에서 Borrmann 4형위암의소견을보인 10예중 3예 (30.0%) 는점막주름의비대또는위벽의경화와같은일반적으로알려진소견단독으로나타났으나 7예 (70.0%) 에서는점막주름의비대와함께궤양성병변을동반하고있었다. 167
Korean J Helicobacter Up Gastrointest Res: Vol 15, No 3, September 2015 Fig. 1. Variable gastroscopic findings of Borrmann type 4 advanced gastric cancer (AGC). (A) An early gastric cancer-mimicking, superficial depressed ulcerative lesion with irregular margins was observed at the lesser curvature of the antrum. (B) An ulcerofungating mass similar to Borrmann type 2 AGC was observed on the prepyloric antrum. (C) A huge infiltrative ulcer with nodular lesions similar to Borrmann type 3 AGC was seen at the anterior wall of the low body. (D) An encircling infiltrative lesion consistent with Borrmann type 4 AGC with friable mucosa was noted at the prepyloric antrum. Table 2. Gastroscopic Findings of the Study Subjects (n=24) Gastroscopic finding Value Fungating mass (Borrmann type 1) 0 (0) Ulcerofungating mass (Borrmann type 2) 4 (16.7) Ulceroinfiltrative mucosa (Borrmann type 3) 9 (37.5) Diffuse infiltrative mucosa (Borrmann type 4) 10 (41.7) Only hypertrophied mucosal fold 3 (30.0) Hypertrophied mucosal fold with combined ulcer 7 (70.0) Early gastric cancer-mimicking lesion 1 (4.1) Values are presented as n (%). 활동성출혈위험으로조직검사를시행하지못한 1예를제외한 23예중 1차조직검사에서암이진단된경우는 20예 (87.0%), 음성으로나온경우는 3예 (13.0%) 였다. 이들 3예는내시경에서 Borrmann 4형위암으로분류되었던경우로, 이중 2 명은 2차조직검사를시행하였으나 2차검사에서도모두음성소견을보였다 (Table 3). 1차조직검사에서는음성이나왔으나 2차조직검사에서암으로진단된 1예는위전반에점막비대가동반되어있어 Borrmann 4형위암에합당했으나, 국소적으로 IIc형또는 III형의얕은궤양성병변을동반하고있었다. 궤양주변의비대된점막, 궤양이없는곳의비대된점막그리고궤 양주변에서각각 1개씩총 3개의조직검사를시행하였으나궤양주변에서시행한조직검사에서만악성세포가확인되었다. 2 차조직검사에서도음성소견을보인 2예는모두기저부및전정부를제외한위전반에점막비대를보이고있었으나궤양또는종괴의형성은보이지않았다. 이중 1예는 2차조직검사시보다많은조직을얻기위하여내시경적점막절제술 (endoscopic mucosal resection, EMR) 을이용하여조직을확보하였으나역시악성세포는발견되지않았다 (Fig. 2). 조직검사가불가능했던 1예와 2차조직검사에서도음성이나온 1예는모두수술을통해 Borrmann 4형위암으로진단되었다. 전체 24예중초기양성병변이장시간에걸쳐악성화한 2 예를확인할수있었다. 첫번째증례는빈혈을주소로내원한 85세남자환자로, 광범위한침윤성점막, 점막비대및얕은궤양성병변을보여내시경에서 Borrmann 4형위암으로분류되었으나출혈위험으로조직검사를시행하지못했다. 위암이진단되기 7년전시행한내시경에서는중간부체부후벽에장상피화생이관찰되었으며, 당시시행한조직검사에서편평선종이확인되었으나환자가자의적으로병원을내원하지않아 7 년간추가적인검사나치료는이루어지지않았다 (Fig. 3). 두번째증례는흑색변을주소로내원한 61세남자환자로, 168
Ji Young Chang, et al: Variable Gastroscopic Findings in Borrmann Type 4 AGC Table 3. Pathological Diagnostic Rate according to Gastroscopic Findings Gastroscopic finding Total First biopsy Second biopsy False negative True positive False negative True positive Ulcerofungating mass (Borrmann type 2) 4 0 (0) 4 (100) Ulceroinfiltrative mucosa (Borrmann type 3) 9 0 (0) 9 (100) Diffuse infiltrative mucosa (Borrmann type 4) 10 a 3 (33.3) 6 (66.7) 2 (66.7) 1 (33.3) Only hypertrophied mucosal fold 3 2 (66.7) 1 (33.3) 2 (100) 0 (0) Hypertrophied mucosal fold with combined ulcer 7 a 1 (16.7) 5 (83.3) 0 (0) 1 (100) Early gastric cancer-mimicking lesion 1 0 (0) 1 (100) Total 24 3 (13.0) 20 (87.0) 2 (66.7) 1 (33.3) Values are presented as n (%). a In one case, biopsy could not be done due to active bleeding. Fig. 2. Second gastroscopic finding of 2 cases of Borrmann type 4 advanced gastric cancer with negative results from at second biopsy. (A) Diffuse marked wall thickening with edematous mucosal changes were noted in the entire stomach. Diagnostic endoscopic mucosal resection was performed at the great curvature of high body; however, the biopsy result was negative. (B) We observed hypertrophy of mucosal folds with hyperemic mucosal changes. The biopsy was performed at the great curvature of the high body. No malignant cells were identified. Fig. 3. Development of Borrmann type 4 advanced gastric cancer (AGC) from an adenoma with high-grade dysplasia at the posterior wall of the mid-body. (A) Initial gastroscopic findings revealed gray-white patches and slightly opalescent nodularity at the posterior wall of the mid-body. The biopsy result was adenoma with high-grade dysplasia. (B) Five months later, gastroscopic images showed nearly the same findings. The biopsy result was a flat adenoma and chronic gastritis with focal intestinal metaplasia. (C) Follow-up gastroscopic findings after 7 years showed hypertrophied mucosa from the high body to the low body with a focal shallow ulcerative lesion, similar to Borrmann type 4 AGC. The biopsy result was adenocarcinoma. 169
Korean J Helicobacter Up Gastrointest Res: Vol 15, No 3, September 2015 Fig. 4. Development of Borrmann type 4 advanced gastric cancer (AGC) from gastritis with Helicobacter pylori infection at the antrum and the angle. (A, B) An initial gastroscopy revealed multiple benign gastric ulcers at the antrum and the angle. The biopsy result was chronic and acute gastritis with H. pylori infection. (C, D) One year later, a large excavating ulceration was observed at the angle and another active ulcer was seen at the antrum. The biopsy result was chronic gastritis. (E, F) A follow-up gastroscopy after 3 months showed a round active ulceration at the angle and multiple small erosions at the antrum. A biopsy was not performed at that time. (G, H) Two years and 3 months later, multiple ulcers were seen at the lesser curvature of the low body, antrum, and angle with congestive gastropathy. The biopsy result was chronic gastritis with intestinal metaplasia. (I, J) Follow-up gastroscopic findings after 9 months showed diffuse infiltrative-type AGC with hypertrophied mucosa at the lesser curvature of the low body that extended from the high body to the proximal antrum. Small ulcerative lesions were observed between the hypertrophied mucosa. The biopsy result was poorly differentiated adenocarcinoma. 위암이진단되기약 4년전시행한내시경에서는전정부와각부에다발성궤양이관찰되었고조직검사에서 Helicobacter pylori 감염이동반된급만성위염이진단되었다. 그후 12개월, 15개월, 42개월째시행한내시경모두에서전정부와각부에활동성궤양이보였으나조직검사에서악성세포는보이지않았다. 그러나 51개월째시행한내시경에서궤양성병변과함께상체부에서전정부까지점막비대가새롭게관찰되고, 조직검사에서선암이확인되어최종적으로 Borrmann 4형위암으로진단되었다 (Fig. 4). 3. 방사선학적특성복부 CT에서는위벽의조영및위주위침윤소견이각각 18예 (78.0%) 로높은소견을보였고림프절전이는 20예 (83.3%) 로실제림프절전이가확인된 21예 (87.5%) 와유사한값을보였다. 그외종괴가 5예 (20.8%) 에서확인되었다. 전체 24예중 4예를제외한 20예에서는 PET-CT 를시행하였고, 이중 2예 (10.0%) 에서는위주변부 18F-fluorodeoxy-glucose (FDG) 섭취음성소견을보였다. 위주변부 FDG 섭취양성을보인 18예중 12예 (66.7%) 는림프절 FDG 섭취음성소견을보였으나수술후병리조직에서는이중 10예에서림프절전이소견을보였다. 반면위주변부및림프절 FDG 섭취모두양성을보였던 6예 (33.3%) 중 1예는수술후병리검사에서는림프 Table 4. Radiologic Findings of the Study Subjects Variable Value Abdominal pelvic CT (n=24) a Negative 1 (4.2) Lymph node metastasis 20 (83.3) Gastric wall enhancement 18 (78.0) Perigastric infiltration 18 (78.0) Mass 5 (20.8) PET (n=20) b Perigastric FDG uptake(+) Lymph node uptake(+) 6 (30.0) Lymph node uptake( ) 12 (60.0) Perigastric FDG uptake( ) c 2 (10.0) Values are presented as n (%). FDG, 18F-fluorodeoxyglucose. a Abdominal pelvic CT findings can be overlapped in one case. b Only 20 patients had PET-CT. c All cases of negative perigastric FDG uptake showed negative lymph node FDG uptake. 절전이가관찰되지않았다 (Table 4). 4. 병리학적특성 병변의발병부위는광범위한침윤을보이는경우가 10 예 (41.7%) 로가장많았으며단일병소인경우에는체부중간에위치한경우가 9예 (37.5%) 로가장많았다. 병변의크기는 170
Ji Young Chang, et al: Variable Gastroscopic Findings in Borrmann Type 4 AGC 10.2±6.2 cm ( 중앙값, 8.5 cm; 범위, 2.5 25.0 cm) 로나타났다. 세포분화도는 24건모두에서미분화조직형군으로확인되었다. 정맥침윤은 10예 (41.7%), 림프관침윤은 18예 (75.0%), 신경침윤은 16예 (66.7%) 에서확인되었다. 위벽침윤도는장막층까지침범한경우 (T4a) 가 13예 (54.2%) 로가장많았고, 비장, 횡행결장등의주변조직까지침범한경우 (T4b) 는 5예 (20.8%) 로 T4a 와 T4b를합한전체 T4는 18예 (75.0%) 를차지했다. 림프절전이는 7개이상의림프절을침범한경우 (N3) 가 14예 Table 5. Pathological Characteristics of the Study Subjects Variable Value Location Upper 1/3 1 (4.1) Middle 1/3 9 (37.5) Lower 1/3 4 (16.7) Whole stomach 10 (41.7) Tumor size (cm) 10.2±6.2 Histologic type Differentiated type 0 (0) Undifferentiated type 24 (100) Venous invasion Negative 14 (58.3) Positive 10 (41.7) Lymphatic invasion Negative 6 (25.0) Positive 18 (75.0) Neural invasion Negative 8 (33.3) Positive 16 (66.7) Depth of invasion T3 6 (25.0) T4a 13 (54.2) T4b 5 (20.8) Lymph node metastasis N0 3 (12.5) N1 5 (20.8) N2 2 (8.3) N3 14 (58.3) Distant metastasis M0 18 (75.0) M1 6 (25.0) Peritoneal metastasis Negative 19 (79.2) Positive 5 (20.8) Hepatic metastasis Negative 24 (100) Positive 0 (0) Stage II 3 (12.5) III 15 (62.5) IV 6 (25.0) Values are presented as n (%) or mean±sd. (58.3%) 로가장높은비율을나타냈다. 원격전이 (M1) 는 6예 (25.0%) 에서나타났으며, 복막전이는 5예 (20.8%) 에서확인됐다. 병기 III기가 15예 (62.5%) 로가장많았고, 병기 IV기는 6예 (25.0%) 로전체적으로상당히진행된병기에서진단됨을확인할수있었다 (Table 5). 5. 치료및임상경과위부분절제술을시행한경우는 8예 (33.3%), 전절제술을시행한경우는 7예 (29.2%), 광범위위전절제술을시행한경우는 9 예 (37.5%) 였으며, 중앙생존기간은 36.0 개월 (22.3 49.7) 로나타났다. 내시경에서 Borrmann 4형위암소견을보였으나활동성출혈로조직검사를시행하지못한 1예는임상적으로위암이강력히의심되어조직학적확진없이수술적치료를시행했다. 수술후추가적인치료는받지않았으며, 8.5 개월뒤사망하였다. 2 차조직검사에서도악성세포가나오지않았던 2예는모두위전절제술을시행받았으며, 각각병기 IV기 (T3N3M0), 병기 IIIA 기 (T3N1M0) 로진단되었다. 고찰 Borrmann 4형위암은전체진행성위암중약 11 13% 를차지하며젊은여성에서의발생률이높은것으로알려져있다. 9-11 이번연구에포함된 Borrmann 4형위암환자들의평균연령은 57.8 세로다른논문 4,12 에서보고된 53.2세, 54.0세보다다소연령이높았으며, 남자가 54.0% 로남자의비율이높았다. 그러나전체위암환자를대상으로조사했을때남자가 66.4%, 여자가 33.6% 였던것 1 을고려해보면기존에알려졌던바와같이여성에서의비율이상대적으로높은것을알수있다. 또한 Borrmann 4형위암은진단당시림프절전이의수와빈도가많고복막전이및간전이와같은원격전이가많아근치적수술이어려운경우가많으며, 근치적수술을한경우에도복막전이로재발하는경우가많아예후가불량한것으로알려져있다. 4,9-13 국내에서수행된 Borrmann 4형위암에대한연구에서는비교적조기에진단된병기 1, 2기환자의 5년생존율은각각 50.0%, 56.0% 였으나 3기환자는 31.0%, 4기환자는 0% 로다른육안형암의병기에따른 5년생존율에비해현저히낮다고보고되었다. 14 또한 Borrmann 1, 2, 3형의환자의 5 년생존율이각각 74.2%, 64.6%, 59.0% 인데비해 Borrmann 4형의경우 27.6% 로다른육안형에비해상대적으로낮음이보고되었다. 12 본연구에서는병기 III기가 15예 (62.5%) 로가장많았으며병기 IV기는 6예 (25.0%) 로전체적으로상당히진행된병기에서진단됨을확인할수있었다. 또한각병기별환자수가 171
Korean J Helicobacter Up Gastrointest Res: Vol 15, No 3, September 2015 작고, 대다수가 5년이전에사망하여 5년생존율을구할수는없었으나중앙생존기간은 36.0개월 (22.3 49.7) 로나타나나쁜예후를보였다. 이처럼 Borrmann 4형위암은진행된병기에서진단되고예후도불량하기때문에내시경검사에서 Borrmann 4형위암으로진단하거나이를의심할수있는소견을발견하는것이중요하다. Borrmann 4형위암은섬유성증식에의해주름의수가증가하고거대해지며, 위벽의경화로진행한다. 이로인해정상점막은송기시주름이잘펴지고주름과주름사이가분명하고넓은것에비해 Borrmann 4형위암의주름은송기시에도잘펴지지않고두꺼워진경우가많다. 15 그러나최근점막주름의비대및위벽의경화와같은전형적소견외에도다양한소견을보인 Borrmann 4형위암의예들이보고되고있다. 예를들어위점막은결절상발적을보일수있고, 전정부를침윤하는경우에는특별한점막병소없이위벽이두꺼워보이고음식물이내려가지않는소견만보일수도있으며경우에따라국소적종괴형병변이관찰될수도있다. 15,16 또한조기위암의형태인 IIc형또는 III+IIc 형함몰및 6 부정형의작은미란성병변등다양한소견으로나타날수도있다. 7 본연구에서는전형적인 Borrmann 4형위암소견이동반된경우가 10 예로가장많았으며, 이중 3예 (30.0%) 만이점막주름의비대또는위벽의경화만으로발현되었고, 7예 (70.0%) 에서는점막주름의비대와함께궤양성병변을동반하고있었다. 또한내시경에서 Borrmann 3형위암의소견인 ulceroinfiltrative mucosa 로나타난경우는 9예 (37.5%) 로상당히많은부분을차지하고있었다. 그리고 1예 (4.1%) 는조기위암의육안적형태를보이고있어 Borrmann 4형위암이상당히다양한소견으로나타날수있음을확인할수있었다. Borrmann 4형위암은조기에원발병소가점막하층이하에서광범위하게침윤하여내시경및조직검사에서위음성률이높아진단이지연되고진행된병기에서진단되는경우가많다. 내시경을통한조직생검이나 brushing 에서의진단율은 30 70% 로연구마다큰차이를보이고있으며, 17-20 최근발표된연구에따르면첫조직검사의위음성률이 10.8% 에이르는것으로보고되고있다. 21 또한 EMR 을시행하거나미세침흡인술을포함한 8회의조직검사에도악성세포가나오지않았던증례들이보고된바있으며, 21,22 본연구에서도 2회이상의조직검사가필요한경우가 3예있었다. 이들은모두내시경에서전형적인 Borrmann 4형위암의소견을보였던경우이며, 1차조직검사의위음성률은 13.0% 로다른연구에서나타난결과와유사하였다. 원발병소인 IIc 또는 III형의궤양성병변을발견하는것이중요한또다른이유는이부위에서조직검사를시행하면암세 포를진단할수있는가능성이높기때문이다. 반면주름종대를보이는부위나협착이있는부위에서조직검사를시행하면암세포가점막하층보다깊이침윤해있어위음성이나오는경우가발생할수있다. 3,15 본연구의 2차조직검사에서암으로진단된경우에도궤양주변의비대된점막, 궤양이없는곳의비대된점막그리고궤양주변에서각각 1개씩조직검사를시행하였으나궤양주변에서시행한조직검사에서만암세포가확인되었다. 2차조직검사에서도음성소견을보인 2예는위전반에점막비대만을보이고있어비대된점막에서조직검사를시행했던경우로조직검사를시행하는병소의내시경적소견이중요함을확인할수있었다. 따라서 Borrmann 4형위암의진단율을높이기위해서는 Borrmann 4형위암의다양한내시경소견을숙지하고, 조직검사시최대한주의를기울여야한다. 조직검사는점막병변이있는곳에서시행하고, 점막병변이없는경우에는점막주름이가장두껍고유약한부분에서반복적으로시행해야한다. 15 임상적으로위암의가능성이높을것으로보이나조직검사결과가음성으로나온경우에는반복적인조직검사를시행하거나진단적 EMR 을고려할수있다. 본연구는아래의몇가지제한점이있다. 우선연구의전체표본수는 24개로이는정확한분석을위해수술후얻은병리조직에서 Borrmann 4형위암으로확진된경우만연구에포함시켰기때문이다. 그러나대부분의 Borrmann 4형위암은임상병리적특성으로인해진단이지연되어진행된병기에서진단된경우가많아진단당시수술이불가능한경우가많을수있다. 따라서수술이가능했던환자들은상대적으로조기진단이용이했던집단으로볼수있어본연구에서나타난 Borrmann 4형위암의특성을전체 Borrmann 4형위암의특성으로일반화시키는데는제한이있다. 본연구에서간전이가동반된예가없었던것역시같은이유로생각된다. 마지막으로본연구는후향적연구이기때문에송기시위의신전여부및점막병변이없는경우조직검사를시행한정확한위치등일부정보를파악하는데제한이있었다. 현재 Borrmann 4형위암에대해정립된치료방법은없는상태로치료성적을높이기위해서는병변을조기에발견하는것이가장중요하다. 점막비대및위벽경화가 Borrmann 4형위암의특징적인내시경소견중하나이나, 모든경우에서나타나는소견은아니며다양한형태로보여질수있기때문에내시경시행시각별한주의가필요하며, 조직검사를시행하는부위또한신중하게결정해야할것이다. 또한임상적으로암이의심되나조직검사에서음성이나올경우에는반복적으로조직검사를시행하거나진단및치료목적의수술적치료를고려하는등적극적인대처가필요하다. 172
Ji Young Chang, et al: Variable Gastroscopic Findings in Borrmann Type 4 AGC REFERENCES 1. Jung KW, Won YJ, Kong HJ, Oh CM, Lee DH, Lee JS. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2011. Cancer Res Treat 2014;46:109-123. 2. Choi JY, Shim KN. Diagnosis of advanced gastric cancer. Korean J Helicobacter Up Gastrointest Res 2013;13:133-137. 3. Jee SR. Borrmann type 4 AGC. Paper presented at: the 46th Korean Society of Gastrointestinal Endoscopy Seminar; 2012 Mar 25; Goyang, Korea. p.82-84. 4. Kang TH, An JY, Kim YS, et al. Clinicopathological features of borrmann type IV gastric carcinomas. J Korean Gastric Cancer Assoc 2006;6:270-276. 5. Lee JH. Hypertrophic gastritis and Borrmann type IV. Korean J Gastrointest Endosc 2010;40:83-85. 6. Kohli Y, Takeda S, Kawai K. Earlier diagnosis of gastric infiltrating carcinoma (scirrhous cancer). J Clin Gastroenterol 1981; 3:17-20. 7. Park MI. The development of Linitis plastic gastric cancer and similar lesions. Paper presented at: the 13th Korean Society of Gastrointestinal Endoscopy Seminar; 2006 Jul 9; Busan, Korea. p.57-61. 8. Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol 2010;17:3077-3079. 9. Kwon SJ, Lee GJ. Clinicopathologic characteristics of Borrmann type IV gastric cancer. J Korean Surg Soc 2003;64:127-133. 10. Kim DY, Kim HR, Kim YJ, Kim S. Clinicopathological features of patients with Borrmann type IV gastric carcinoma. ANZ J Surg 2002;72:739-742. 11. Yook JH, Oh ST, Kim BS. Clinicopathological analysis of Borrmann type IV gastric cancer. Cancer Res Treat 2005;37: 87-91. 12. An JY, Kang TH, Choi MG, Noh JH, Sohn TS, Kim S. Borrmann type IV: an independent prognostic factor for survival in gastric cancer. J Gastrointest Surg 2008;12:1364-1369. 13. Otsuji E, Kuriu Y, Okamoto K, et al. Outcome of surgical treatment for patients with scirrhous carcinoma of the stomach. Am J Surg 2004;188:327-332. 14.Ryu JH, Yook JH, Kim BS, Oh ST, Jung ST, Choi WY. Clinicopathologic characteristics and prognostic factors of long-term survivors of Borrmann Type 4 gastric cancer. Korean J Gastroenterol 2003;41:9-14. 15. Jeoung HY. AGC Borrmann type IV cancer. Korean J Gastrointestinal Endosc 2011;43 Suppl 2:S215-S217. 16. Korean Society of Gastrointestinal Endoscopy. Atlas of Gastrointestinal Endoscopy: upper gastrointestinal endoscopy, colonoscopy. Seoul: Daehan Medical Book Publishing, 2011. 17. Winawer SJ, Posner G, Lightdale CJ, Sherlock P, Melamed M, Fortner JG. Endoscopic diagnosis of advanced gastric cancer. Factors influencing yield. Gastroenterology 1975;69:1183-1187. 18. Evans E, Harris O, Dickey D, Hartley L. Difficulties in the endoscopic diagnosis of gastric and oesophageal cancer. Aust N Z J Surg 1985;55:541-544. 19. Balthazar EJ, Rosenberg H, Davidian MM. Scirrhous carcinoma of the pyloric channel and distal antrum. AJR Am J Roentgenol 1980;134:669-673. 20. Levine MS, Kong V, Rubesin SE, Laufer I, Herlinger H. Scirrhous carcinoma of the stomach: radiologic and endoscopic diagnosis. Radiology 1990;175:151-154. 21. Song W, Chen CY, Xu JB, et al. Pathological diagnosis is maybe non-essential for special gastric cancer: case reports and review. World J Gastroenterol 2013;19:3904-3910. 22. Ahn JB, Ha TK, Lee HR, Kwon SJ. An insufficient preoperative diagnosis of Borrmann type 4 gastric cancer in spite of EMR. J Gastric Cancer 2011;11:59-63. 173