대한외과학회지 : 제74권제5호 Vol. 74, No. 5, May, 2008 원 저 분문부위암 : Personal Experience 연세대학교의과대학외과학교실, 1 국민건강보험공단일산병원외과 윤호영ㆍ김국진ㆍ이상훈 1 ㆍ김충배 Cardia Cancer: Personal Experience Ho Young Yoon, M.D., Kook Jin Kim M.D., Sang Hoon Lee, M.D. 1 and Choong Bai Kim, M.D., FACS. Department of Surgery, Yonsei University College of Medicine, Seoul, 1 Department of Surgery, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea Purpose: Due to the biological characteristics of cardia cancer, prognosis is poor. It is therefore essential to achieve a sufficient proximal resection margin to maximize survival. The authors studied gastric cardia cancer, focusing on adenocarcinoma. Methods: One-hundred fifty patients who were diagnosed with gastric cardia cancer and underwent surgery between January 1990 and December 2006 by a single surgeon were included in this study. Results: Of the 150 cases, 141 were adenocarcinomas, 4 were carcinomas, and 3 were leiomyosarcomas. In the adenocarcinoma group, the male-to-female ratio was 2.62:1. There were 2, 60, and 79 (56.0%) cases of adenocarcinoma type I, II, and III, respectively, and there were 32 (22.7%), 18 (12.8%), 70 (49.6%), and 21 (14.9%) cases of stage I, II, III, and IV tumors, respectively. The mean distance from the proximal tumor to the resection margin was 1.93±1.72 cm pathologically, and there was tumor invasion of the resection margin in 4 cases (2.8%). In the 10 cases of extended surgery in type II, the mean distance was 5.85±3.67 cm, with no tumor invasion of the resection margin. Recurrence occurred in 30 (21.3%) cases, and 5 of those cases were local anastomotic site recurrences. Cumulative survival was 81.3%, 77.8%, 51.4%, and 28.6% for stage I, II, III, and IV tumors, respectively. Conclusion: Although it is possible to remove the tumor with 책임저자 : 김충배, 서울시서대문구신촌동 134 번지 120-752, 연세대학교의과대학외과학교실 Tel: 02-2228-2113, Fax: 02-313-8289 E-mail: cbkimmd@yuhs.ac 접수일 :2007 년 11 월 21 일, 게재승인일 :2008 년 2 월 28 일본논문의요지는 2007 년대한위암학회추계학술대회에서포스터구연발표되었음. 중심단어 : 분문부암, Siewert 분류, 위 - 식도경계 an appropriate resection margin by only an abdominal incision, the surgeon should always keep in mind the possibility of a thoracoabdominal incision when operating on a patient with esophageal infiltration. (J Korean Surg Soc 2008;74:341-346) Key Words: Cardia cancer, Siewert classification, Gastroesophageal junction 서 위암은세계에서사망빈도가두번째로높은암이다. 우리나라에서는전체암에서차지하는비중이점차감소하는추세이나아직까지는악성종양중가장빈도가많다. 분문부위선암은서구에서발생률이상대적으로높으나국내에서는원위부위선암이다수를차지하고있고종양학적특성상광범위하게림프배출이되어예후가나쁘고, 하부식도를잘침범하며점막하림프선을통해전이가이루어지기때문에국소재발과사망률이높다. 생존율을높이기위해많은노력이이루어지고있지만분문부의정의, 분문부위선암의분류가아직까지명확하지가않아독립질환군으로보아야한다는의견도제시되고있는것이사실이다.(1,2) 분문부는병리조직학적으로식도의편평상피세포와위의원주상피세포간의전이가일어나는부위로정의되지만 International Gastric Cancer association (IGCA) 은분문부위선암의분류를선암이발생한위치에따라나누는데동의한바즉, 위-식도경계부위를기준으로상하 5 cm를분문부로정의하였고경계부위에서상부 1 cm에서 5 cm까지를 type I, 하부 2 cm에서 5 cm까지를 type III 그리고중간부분을 type II로분류하였다.(3) 이분류법은수술방법과치료결과에대한평가를비교할수있게함으로써비교적유용한분류로받아들여지고있다. 저자들은분문부위암으로진단받고수술을받은환자들의임상적특성, 병리조직학적특성, 수술방법과재발여부그리고생존율등을선암을위주로검토하여분문부위암의치료에도움이되고자한다. 론 341
342 J Korean Surg Soc. Vol. 74, No. 5 방법 1990년 1월부터 2006년 12월까지분문부위암으로진단되어연세대학교의과대학외과학교실에서한외과의에게수술을받은환자 150예를대상으로하였고, 임상기록을선암을중심으로후향적으로검토하여생존에영향을줄수있다고추정되는성별, 연령, 수술방법, 병리조직결과와병기그리고수술합병증등의요인에대해 Fisher s exact test 또는 Chi-square test와 independent t-test 그리고 logistic regression model을이용하여분석하였다. 술식은 Siewert 분류에따라달라 type I은식도수술에준해서 type II와 III는개복을하여 ( 확대 ) 위전절제술및제2군림프절절제술을원칙으로하되근위부절제연확보가충분하지않을때개흉술이나열공을통해서확대위-식도절제술을시행하였는데본연구에서 Siewert 분류는종양의종축중심의위치를기준으로병리조직결과지에근거하여분문부위선암을분류하였다. 병기는 AJCC/IUAC(4) 를기준으로하였으며생존여부는 2007년 6월 30일을기준으로알아보았고추적은 93% 에서이루어졌는데추적기간의중앙값은 28개월이었다. 생존율분석은 SPSS program을사용하여 Kaplan- Table 1. Type of operation Operation No. of cases (%) Fig. 1. Distribution of cardia cancer by age. Total or extended total gastrectomy Esophagogastrectomy with colon interposition Tranhiatal Thoracoabdominal Three stage (Mckweon) Proximal gastrectomy with distal esophagectomy Transhiatal esophagectomy with proximal gastrectomy 122 (86.7) 4 (2.8) 5 (3.5) 1 (0.7) 8 (5.6) 1 (0.7) Fig. 2. According to the extension of esophageal invasion, it is needed thoracoabdominal (A) or transhiatal (B) approach in type II cardia cancer.
Ho Young Yoon, et al:cardia Cancer: Personal Experience 343 Meier method 를이용하였다. Table 2. Clinicopathologic findings and univariative analysis of prognostic factors Variables 결 150예중 141예가선암이었고나머지중미분화상피암 (undifferentiated carcinoma) 이 4예, 평활근육종 2예, 위장관기저종양 (GIST) 2예그리고기타 1예였다. 선암에서남녀별발생빈도는남자가 102예 (72.3%) 로비율은 2.62:1이었고, 연령별로는 16세에서 86세까지분포를보였으며 60대에서가장많이호발하였다 (28.4%)(Fig. 1). 수술시접근방법은 122예 (86.7%) 가복부절개만으로충분하였고그외에도식도침윤정도에따라좌, 우흉복부절개, 경열공절개, three stage 절개 (Mckweon 술식 ) 를사용하였다 (Table 1, Fig. 2). 139예에서근치적수술이그리고 2예에서고식적수술이이루어졌다. Siewert 분류에따른 type I은 2예, type II은 60예, type III 가 79예 (56.0%) 로가장많았고, 병기는 Ia 19예 (13.5%), Ib 13예 (9.2%), II 18예 (12.8%), IIIa 45예 (31.9%), IIIb 25예 (17.7%) 그리고 IV 21예 (14.9%) 였다. 합병절제는 59.6% 에서이루어졌는데그중비장절제가 70예로가장많고, 종양의 과 P-value 주위장기와유착으로췌미절제 7예, 부신절제 3예, 횡행결장부분절제 2예, 횡격막절제 1예, 그리고동반질환으로인한 8예에서이루어졌다. 비장절제의빈도에대해서는각각을여러요인으로비교하였을때통계학적인유의한차이는없었지만 T3 이상군과 T2 이하군으로나누어비교하면 T3 군에서빈도수는현저히컸고통계학적인의미는부여할수없었다 (53 vs 17, P=0.323). 종양의근위부에서절제연까지의조직학적거리는평균 1.93±1.72 cm였고절제연암침윤은 5예 (3.5%) 였는데그중한예는동결절편조직에서는음성이었으나최종결과가양성인경우였다. 그러나 type II에서위-식도절제술후대장간치를한 10예에서는평균거리가 5.85±3.67 cm로위전절제술만을시행한군간에유의한차이를가졌으며절제연암침윤은한예도없었다. 또한근위부문합은대부분 (140예) EEA 자동문합기를사용하였는데보통약 0.5 cm 정도가절제되므로실제는절제연의거리가더길다고볼수있다. 단변량분석에서생존에영향을준요소로는종양의위벽침윤도, 분화도그리고림프절침윤정도였고 (Table 2) 다변량분석을하였을때위벽침윤도, 림프절침윤정도, 종양크기가영향을주는요소들이었다 (Table 3). 재발은 30예인 21.3% 에서발생하였고 5예가문합부국소재발이었는데종양으로부터근위부절제연까지의거리와국소재발과의연관성은없었고절제연침윤과도관계가없었다 (Table 4). 위선암환자중 58.2% 인 82예가생존해있으며누적생존율은 Age (mean, SD) Sex (%) Male Female Depth of invasion (%) T1 T2 T3 T4 Lauren s type (%) Intestinal Diffuse Mixed Differentiation (%) Well Moderate Poor Signet ring cell Mucinous Others Nodal status (%) N0 N1 N2 N3 Tumor size (mean, SD) 55.49±13.84 yrs 102 (72.3) 39 (27.7) 21 (14.8) 17 (12.1) 93 (66.0) 10 (7.1) 57 (40.4) 75 (53.2) 9 (6.4) 15 (10.4) 48 (34.0) 57 (40.4) 17 (12.1) 3 (2.1) 1 (0.7) 46 (32.6) 53 (37.6) 25 (17.7) 17 (12.1) 5.72±3.28 cm ( ) NS <0.001 NS 0.048 0.050 ( ) Table 3. Multivariative analysis of prognostic factors affecting to survival Variable Odds ratio 95% CI for odds ratio P-value Sex Differentiation Lauren s type Margin Tumor size Depth of invasion Nodal status 0.879 1.313 0.879 1.174 1.206 2.405 1.682 0.354 2.183 0.779 2.214 0.433 1.785 0.938 1.417 1.072 1.357 1.189 4.865 1.058 2.674 Table 4. Recurrence sites of the cardia cancer Type No. of cases (%) Local Peritoneal seeding Metastasis Bone Kidney Ovary Liver Brain Lung 3 (10) 16 (53.5) 3 (10) 2 (6.6) 1 (3.3) 3 (10) 1 (3.3) 1 (3.3) 0.781 0.307 0.722 0.161 0.002 0.015 0.028
344 J Korean Surg Soc. Vol. 74, No. 5 Fig. 3. Five (A) & overall (B) survival rate according to Siewert s classification (P=0.3508, 0.4233). Fig. 4. Five (A) & overall (B) survival rate according to the stage (median survival time; 46 & 44, respectively). type II, III에서각각 60.00%, 55.70% 로각군간에유의한차이는없었으며 (Fig. 3) stage I, II, III, IV로는각각 81.3%, 77.8%, 51.4%, 그리고 28.6% 로병기간유의한차이를보였다 (P<0.001, Fig. 4). 고찰분문부위암은다른부위의위암과달리예후가불량한데그이유로는조기에발견이어렵고진행된상태에서진단이되며, 생물학적으로공격적인특성이높아림프절침윤이많기때문이다. 따라서생존율과절제율이낮으며고유한생물학적, 해부학적특성을갖고있어정의와치료에대하여여러가지의견이제시되고있다.(1,2) 남녀유병률은보고에따라 1.46:1에서 5:1로남자에게높게나타나며,(5,6) 이러한경향은서양에서도마찬가지이다.(7,8) 현재통용되고있는 UICC/AJCC cancer staging은비록분문부가위에속하지만그에대한명확한해부학적정의가반영되어있지않기때문에분문부위암의진단에한계점을갖고있다. 과거 Nishi와 Aikou는위식도경계상하 1 cm 이내의암을경계부암, 2 cm 이내의암을분문부위암으로규정한바있다.(9) 이후 1996년 Siewert와 Stein이분류를다음과같이정의하고 1997년 2차국제위암회의 (Internatioanl Gastric Cancer Congress) 에서승인하였다. 즉, 위-식도경계부위에서상부 1 cm에서 5 cm까지를 type I, 하부 2 cm에서 5 cm까지를 type III 그리고중간부분을 type II로분류하였다.(1) 그중 type I 분문부위선암은 Barrett 선암으로간주되고동양보다는서양에서유병률이높은데이는위식도역류증이동양인에게는적다는것으로설명될수있다. 하지만 Siewert에의한분류가병리기전과위치에따른그들간의관계들을반영하는지는아직명확하게밝혀지지는않았다. 병리학적으로는분문부의점막은점액을분비하는선을
Ho Young Yoon, et al:cardia Cancer: Personal Experience 345 갖는원주세포를갖는다는점에서는전정부와비슷하지만반면펩신을분비하는주세포와산을분비하는벽세포가존재하지않거나있어도매우드물다는점에서는다르다.(10) 또한분문부위선암은조직학적으로 80% 가장형 (intestinal type) 을갖는데이는장화생화 (intestinal metaplasia) 로부터기원한것이라추측하고있다.(11) 위-식도경계부위를부검을하여분문부점막과산분비분문부점막 (oxyntic cardia mucosa) 이조직둘레의약 50% 정도에서만관찰되었고전체의 76% 에서그길이가 5 mm 미만이었는데위-식도역류존재여부에따라그길이는비례하여범위가증가한다고하였다. 이는위-식도역류가분문부점막의원인이된다는것을근거를제공하는것이라하였다.(12) 술식은암의병기, 암의위치, 환자의상태, 소장또는대장의간치여부등에따라결정되는데,(13) 수술방법에대해서는이견이있으나궁극적으로는종양학적인근치가되어야한다. Type I 분문부위선암은개흉이나경열공을통해식도를절제해야하고, type III 분문부위선암은위전절제술만으로충분하지만 type II 분문부위선암에대해서는여러가지의견이제시되고있으며논란이많다. 많은저자들은조기분문부위선암에서원위부식도절제와근위부위절제술이적절하다는의견을제시하고있고본연구에서도종양크기가크지않은 8예 (5.6%) 에서같은술식을사용하였지만술후산, 알칼리역류로인한가슴통증을 5예에서호소하였고그중 1예에서는수개월후위전절제술을시행하였기에이술식의선택에있어신중을기해야할것이다. 이러한후유증으로인해소장간치가 1955년처음으로소개되기시작하였고 (14) 후에는대장간치도이루어져수술후환자의삶의질은개선되었다. 분문부위암에서수술전증상의대부분이연하곤란이고따라서수술의목적중의하나가증상의개선인만큼국소재발이발생하면의의가없기때문에식도전절제술을시행하고목에서문합하자는보고도있다.(15) 개흉을통한식도절제후문합은경부문합보다음식물연하에유리하다는보고도있으나술후문합부누출이발생할경우치명적인합병증이될수있다는단점이있다.(16) 분문부위선암은점막하층으로전이되기때문에식도침윤이자주있으며수술시육안적으로침윤여부를평가하기어렵다. 따라서수술시근위절제연확보가충분하지않다면반드시동결절편조직검사가이루어져야한다. 림프군은크게세군으로생각할수있는데첫째, 식도주위, 종격동그리고하폐정맥주위에존재하는림프절둘째, 횡격막하및분문부주위림프절셋째, 좌위동맥과소만부, 총복강동맥림프절이해당되는데 Type I과 type II 분문부위선암에서하부종격동림프절제는일반적으로받아들여지고있으나, 실제적으로종격동림프절종창을수술대에서확인되는것이흔하지않다.(17) 아울러림프절전이는분문부주위, 위의소만부와대만 부, 좌위동맥을따라총복강동맥에걸친영역, 비장동맥을따르는췌장의상연에서비문 (splenic hillum) 에걸친영역, 하종격동, 좌부신과좌신동맥영역의빈도순으로양성을갖는다.(18-20) 비장절제에대해서는아직논란이되고있고본연구에서도이에대한어떠한결론을내릴수는없었지만저자의경우비문주위에다수의림프절종창이확인되었을때는비장절제를하였고통계적으로는 T3 이상군에서그빈도가많았지만의미를부여하기는어려웠다. 본연구에서 Type I의 5년생존율 (2예모두생존 ) 이가장좋고 type III가가장나빴지만통계학적으로는의의를갖지는못하였다. 이와같은결과는통계상미만형이빈번했고분화도가낮았으며림프절침윤이다른형에비해많았던것으로설명될수있다. 이는병리학적으로로렌분류상미만형이많고분화도가낮은빈도가많기때문이라는 Siewert의문헌과도일치되는결과이다.(21) 수술은대부분의경우개복을통한위전절제술및식도- 공장재건술이일반적이나 type II 분문부위선암인경우식도침윤이넓을때는열공을통한원위부식도절제술또는상황에따라식도절제술및재건술이필요하기도하다. 결 본연구의결과에비추어분문부선암의수술방법은종양의위치, 종양의형태, 숙련되고표준화된술식, 술후환자의관리와수술합병증의대처등과같은여러요인을고려하여선택하면충분한절제연을확보하면서근치적절제가가능하겠고비교적양호한치료성적을얻을수있다고사료되며, 원위부위암과는달리술전에항상식도침윤에따른개흉을염두하여야한다. 론 REFERENCES 1) Mittal R, Balaban D. The esophagogastric junction. N Engl J Med 1997;336:13924-32. 2) Steup WH, Leyn P, Lerut T. Tumors of the esophagogastric junction. J Thor Cardio Surg 1996;117:16-25. 3) Siewert JR, Stein HJ. Classification of carcinoma of the oesophagogastric junction. Br J Surg 1998;85:1457-9. 4) Sobin LH, Wittekind C. International Union Against Cancer. TNM Classification of Malignant Tumors. New York: John Wiley & Sons Inc.; 2002. 5) Kim JP, Yoo HY, Kim SC, Yang HK. Clinical analysis of gastric cardia cancer. J Kor Cancer Asso 1994;26:361-8. 6) Goo SG, Kwon SJ, Lee KS. Total gastrectomy for gastro-cardiac cancer-especially focused on prognostic factors-. J Korean Surg Soc 1992;43:167-75. 7) Brewster DH, Fraser LA, McKinney PA, Black RJ. Socioeconomic status and risk of adenocarcinoma of the oesophagus and cancer of the gastric cardia in scotland. Br J Cancer
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