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1 J Korean Surg Soc 2011;80:23-28 DOI: /jkss 원 저 위암에서새로운 TNM 병기체계에따른예후의평가 영남대학교의과대학외과학교실 배정민ㆍ김세원ㆍ김상운ㆍ송선교 Evaluation of Prognostic Values according to the New TNM Classification in Gastric Cancer Jung Min Bae, M.D., Se Won Kim, M.D., Sang Woon Kim, M.D., Sun Kyo Song, M.D. Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea Purpose: In 2010, the new UICC/AJCC TNM classification for gastric cancer was declared. The new classification for gastric cancer has several changes from the 6th classification. We evaluated the prognostic values and differences according to the new UICC/AJCC TNM classification. Methods: From 2000 to 2004, 1,196 patients who underwent curative resection with D1+β or more lymph node dissection and with 15 or more lymph nodes retrieved were studied retrospectively. We analyzed clinical characteristics and survival outcomes retrospectively from medical records. Results: According to UICC/AJCC 7th TNM classification, the 5-year survival rate (5YSR) of each group for depth of invasion and node metastasis were significantly different. The 5YSR of stage II in 6th classification was 82.4% and the 5YSR of stage IIa and IIb in 7th classification were 92.2% and 82.9%. The 5YSR of stage IIIa and IIIb in 6th classification were 56.3% and 33.0%. The 5YSR of stage IIIa, IIIb and IIIc in 7th classification were 72.7%, 48.4% and 26.1%. In our Cox regression multivariate analysis, N stage of the 6th UICC/AJCC TNM classification was the main independent prognostic factor. Conclusion: N stage of the 6th UICC/AJCC TNM classification is a more reliable prognostic factor than N stage of the 7th UICC/AJCC TNM classification. Further study should be performed to confirm the appropriateness of N stage TNM classification for gastric cancer. (J Korean Surg Soc 2011;80:23-28) Key Words: Gastric cancer, AJCC, Prognosis 중심단어 : 위암, AJCC, 예후 서 위암환자들에서병기설정은적절한치료를결정하고향후환자들의예후를예측하며임상의사와의료기관사 책임저자 : 김상운, 대구시남구대명동 , 영남대학교의과대학외과학교실 Tel: , Fax: swkim@med.yu.ac.kr 접수일 :2010 년 10 월 18 일, 게재승인일 :2010 년 12 월 6 일본논문의요지는 2010 년대한위암학회춘계학술대회에서발표되었음. 론 이의통합적인연구를가능하게하는중요한분류방법이다. 또한이들병기체계는진단방법과치료방법의발전에따라변화되어왔고병기체계가변화할때마다기존병기체계와새로운병기체계사이의차이점에대한연구는끊임없이지속되어왔으며이런연구들은차후개정될새로운병기체계를더욱발전시키는원동력이되어왔다. 2009년에발표된 UICC/AJCC 7판 (1) 의위암의병기체계는기존 6판 (2) 에비해위벽침윤도와림프절전이도를분류하는기준이변화되었다. 따라서그에따른병기설정도변화되었다. 대한위암학회에서는 2010년 4월 위암기재사항을위한설명서 를발간하여 UICC/AJCC 7판에서변화된 23

2 24 J Korean Surg Soc. Vol. 80, No. 1 내용을수록하였으며, 2010년대한위암학회, 춘계학술대회에서는 UICC/AJCC 6판과 7판의비교연구와위벽침윤와림프절전이도분류의적절성에대한많은논의가있었다. 이에저자들은기존 UICC/AJCC 6판과 7판에따른병기설정을비교하여그에따른예후의변화및림프절전이도분류의적절성을평가하고자하였다. 방법 2000년 1월부터 2004년 12월사이에본원외과에서위암으로진단받고병기가결정된환자는 1,270명이었다. 이중 74명은수술전원격전이가있거나, 복강내원격림프절전이가존재하였거나, 복막전이, 간전이등이존재하여연구에서제외하였고, R0 위절제술과 D1+β 이상의림프절곽청술을시행하였고, 수술후병리검사상림프절수가 15개이상인나머지 1,196명을대상으로연구를시행하였다. 추적방법은의무기록을중심으로하였고, 의무기록상 60개월미만의환자는유선상으로생사및사망원인등을조사하였다. 대상환자들의평균추적기간은 50.1개월 ( 범위 : 4 120) 이었고대상환자들중 9.4% 인 120명의환자가추적후 60개월이전에추적소실되어중도절단자료 (censored data) 로취급하였다. 대상환자들의의무기록을중심으로후향적으로임상병리학적특징을분석하였고 UICC/AJCC 6판과 7판에따른위벽침윤도, 림프절전이도, TNM stage에따른 5년생존률을비교하였다. 통계분석은 SPSS 13.0 (SPSS Inc. Chicago, Illinois, USA) 을이용하여빈도분석, 생존분석을시행하였다. 생존분석은 Kaplan-Meier method를이용하였고, 통계학적유의성은 log-rank test를이용하였다. 생존분석에서통계학적으로유의한변수들을대상으로 Cox s proportional hazards 모델을이용한다변량분석을시행하였다. 모든경우에서 P값이 0.05 미만인경우를통계학적으로유의하다고판정하였다. 점막하암이 312명이었다. 진행위암에서는장막하암이가장많았다 (Table 1). 위벽침윤도에따른 UICC/AJCC 6판과 7판의 5년생존율은각군마다통계학적으로유의한차이를보였으며, 5년생존률곡선은 Fig. 1, 2와같다. UICC/AJCC 6판과 7판의위벽침윤도와림프절전이도에따른 5년생존률은각군마다통계학적으로유의한차이를보였으며, 생존률곡선은 Table 1. Clinicopathologic characteristics of gastric cancer patients Patients characteristics No of patients % Sex Male Female Cancer type Early gastric cancer Borrmann type I Borrmann type II Borrmann type III Borrmann type IV Borrmann type V Depth of invasion pt1a pt1b pt pt pt4a pt4b Number of node metastasis < 결 과 전체환자는 1,196명으로남자는 839명, 여자는 431명으로남녀비는 1.94:1이었다. 연령은 22세부터 81세까지였으며, 중간연령은 60세였다. 조기위암이 652명이었으며, 진행위암중에서는 Borrmann III 형태가가장많았다. 조기위암에서는점막암이 340명, Fig. 1. Survival curves of patients according to T stage of UICC/ AJCC 6 th.

3 Jung Min Bae, et al:evaluation of Prognostic Values according to the New TNM Classification in Gastric Cancer 25 Fig. 2. Survival curves of patients according to T stage of UICC/ AJCC 7 th. Fig. 5. Survival curves of patients according to TNM stage of UICC/AJCC 6 th. Fig. 3. Survival curves of patients according to N stage of UICC/ AJCC 6 th. Fig. 6. Survival curves of patients according to TNM stage of UICC/AJCC 7 th. Fig. 4. Survival curves of patients according to N stage of UICC/ AJCC 7 th. Fig. 3, 4와같다. UICC/AJCC 6판과 7판의병기에따른 5년생존률에서 6 판의경우에는각병기마다통계학적으로유의한생존률의차이를보였으나, 7판에서는 Ia와 Ib, IIa와 IIb, IIb와 IIIa 병기간에생존율의차이는통계학적으로유의하지않았다. 6 판과 7판의병기에따른생존률곡선은 Fig. 5, 6과같다. UICC/AJCC 7판의병기에따른 5년생존률은 Ia가 99.2%, Ib는 98.6%, IIa는 92.2%, IIb는 82.9%, IIIa는 72.7%, IIIb는 48.4%, IIIc는 26.1% 이었다 (Table 2). 각환자들이속한 UICC/ AJCC 6판과 7판의병기를비교해보면 Ia군은 UICC/AJCC 6판과 7판이동일한집단이었고, UICC/AJCC 6판의 Ib는 7 판에서 Ib와 IIa로분리되었다. UICC/AJCC 6판의 II는 UICC/AJCC 7판에서 IIa, IIb, IIIa의 3가지병기로분리되었다 (Table 2).

4 26 J Korean Surg Soc. Vol. 80, No. 1 병기분류에관계없이위벽침윤도와림프절전이도에따른집단의 5년생존률은 Table 3과같다. pt3이면서림프절전이가없는경우는 78명으로이집단이속하는병기는 UICC/AJCC 6판에서는 Ib로 96.1%, 7판에서는 IIa로 92.2% 이지만, 이들환자의 5년생존율은 88.1% 이었다. pt4a이면서림프절전이가없는환자들의 5년생존율은 88.9% 이었으나, 이집단이속하는병기는 UICC/AJCC 7판에서 IIb 이므로 5년생존률이 82.9% 이었다. pt4a이면서 UICC/AJCC 7 판의 N2에속하는환자들은 UICC/AJCC 7판에서 IIIb이므로 48.4% 이지만, 이집단만의 5년생존율이 31.1% 이었다. Cox s proportional hazards 모델을이용한다변량분석결 Table 2. Comparison of 5 year survival rate of gastric cancer patients according to the AJCC stages UICC/AJCC 6th edition 5 year survival rate UICC/AJCC 7th edition 5 year survival rate Ia 99.2 Ia 99.2 Ib 96.1 Ib 98.6 IIa 92.2 과 UICC/AJCC 6판의림프절전이도분류가가장중요한예후인자이었다 (Table 4). 고찰 1977년에 AJCC 1판이출판된이래로 2010년에 7판이출판되었다.(1) 국제적인암병기분류체계는의사로하여금환자들을계층화하여더나은치료를제공하고국제적인임상시험수행에있어공통의언어와같다고하였고가장좋은병기체계를만드는과정은끝이없는과정이라고하였다.(1) 그러나, 위암 UICC/AJCC 7판의병기분류의실제적용에있어몇가지논란이제기되고있다. 이에저자들은위암환자에서 UICC/AJCC 6판과 7판의병기분류를적용하여차이점및예후의변화를평가해보고자하였다. UICC/AJCC 6판과 7판에서 pt1은변화가없으나, 6판의 pt2는변화가있었다. pt2는 UICC/AJCC 6판에서는고유근육층과장막하층을포함하였으나, 7판에서는 pt2의고유근육층과 pt3의장막하층으로분리되었다. 5년생존율에있어서도고유근육층은 92.6%, 장막하층은 78.4% 이며통계학적으로유의한차이를보였다. 여러저자들이 UICC/ II 82.4 IIb 82.9 IIIa 72.7 IIIa 56.3 IIIb 48.4 IIIb 33.0 IIIc 26.1 IV 24.1 Table 4. Multivariate analysis according to Cox proportional hazard model P-value Exp (B) Step 2 6 th N stage N N N Table 3. Distribution of patients according to the T and N stages: the number of patients and 5 year survival rate were specified Depth of invasion Metastatic node < pt1 No year survival rate pt2 No year survival rate pt3 No year survival rate pt4a No year survival rate pt4b No year survival rate year survival rate was calculated if number of gastric cancer patient were more than 10.

5 Jung Min Bae, et al:evaluation of Prognostic Values according to the New TNM Classification in Gastric Cancer 27 AJCC 6판의 pt2 위암에서고유근육층과장막하층위암에서통계학적으로유의한예후의차이가존재함을주장하였다.(3-5) 더나아가 Ishigami 등 (6) 은고유근육층을 3부분으로세분화하여생존율의차이를보고하기도하였다. UICC/ AJCC 6판 (2) 에서는고유근육층과장막하층을 pt2a, pt2b 로분류는하였으나병기결정에는포함하지않았는데, 이번 UICC/AJCC 7판에서는고유근육층과장막하층의생존률의차이를고려하여병기설정에적용한것으로생각되며따라서 UICC/AJCC 7판에서고유근육층과장막하층을 pt2와 pt3로분리한것은 6판보다는적절한것으로생각된다. UICC/AJCC 7판에서는 6판과달리림프절전이도의분류도변화되었다. 6판에서는 N1이전이된림프절의개수가 1 개에서 6개, N2는 7개에서 15개, N3는 16개이상으로정의하였다. 그러나, UICC/AJCC 7판에서는 N1이 1개에서 2개, N2가 3개에서 6개, N3는 7개이상인경우이며, 병기설정과는관계가없으나, N3a를 7개에서 15개, N3b는 16개이상인경우로정의하였다. UICC/AJCC 7판의림프절전이도분류는저자들의연구에서각군마다통계적으로유의한생존율의차이를보였고, Deng 등 (7) 과 Ha 등 (8) 도통계학적으로유의하다고하였다. 그러나, 림프절전이도의분류에있어전이림프절개수의기준에대해서는많은주장이있어왔다.(9-13) 또한 UICC/AJCC 7판 (1) 에서도림프절전이도를분류하는전이림프절개수에대한명확한근거는제시하지않고있다. Deng 등 (7) 은 UICC/AJCC 7판의림프절전이도분류가 6판보다예후를반영하는데더우월하다고주장하였다. 그근거로 Cox proportional hazard model 을이용한다변량분석결과를제시하였다. 그러나, 다변량분석의경우다변량분석을할때포함되는변수에따라그결과가달라질수있는데, Deng 등 (7) 의연구에따르면다변량분석을시행할때에위절제술종류가포함되었는데, 위절제술의종류는예후에영향을미치지않는것으로알려져있어통계방법이부적절한것으로생각된다. 저자들의 Cox proportional hazard model을이용한다변량분석에의하면 UICC/ AJCC 6판의림프절전이도가 7판에비해예후에더많은영향을주는것으로나타났다 (Table 4). 따라서 UICC/AJCC 6판과 7판의림프절전이도에서예후를반영하는데어느방법이더적절한지는추후더많은연구가필요할것으로생각된다. UICC/AJCC 6판의병기에따른 5년생존률은각병기마다통계학적으로유의한생존률의차이를보였으나, 저자들의연구결과에의하면 UICC/AJCC 7판에서는전체적인 병기간의 5년생존률은통계학적으로유의하였으나, 병기간의대응에따른생존률의차이는유의하지않았는데, Ia 와 Ib, IIa와 IIb, IIb와 IIIa 사이의인접병기간에통계학적으로유의한차이를보이지않았다. Ha 등 (8) 도 Ia와 Ib, Ib와 IIa, IIa와 IIb, IIb와 IIIa 사이에통계학적으로유의한생존률의차이가없다고하였다. 이런인접병기간의생존률의통계학적인문제는대규모연구가필요할것으로생각되며 UICC/AJCC 7판의문제점으로생각된다. UICC/AJCC 6판의 IV는 UICC/AJCC 7판에서원격전이가존재하는경우에만 IV로분류하였다. UICC/AJCC 6판의 IV 구성에대해여러저자들이문제점을제기했다.(14-17) 본연구에서제외된 74명의환자의경우 UICC/AJCC 6판과 7판에서 IV로분류되며이들환자들의 5년생존율은 11.3% 이었다. 이들환자들을고려하면 UICC/AJCC 6판의 IV의 5 년생존률은 20.4% 가되어본연구결과인 24.1% 보다생존률이불량해지게된다. 그러나, UICC/AJCC 7판에서는이들환자들을분리하였고, UICC/AJCC 7판의 IIIc와 IV 간의생존률의차이는통계학적으로유의하였다. 따라서 UICC/AJCC 7판의 IV 분류는 UICC/AJCC 6판의 IV 보다개선된것으로생각된다. 각병기를구성하는위벽침윤도와림프절전이도의교차표를살펴보면실제동일한위벽침윤도와림프절전이도로구성된환자들의 5년생존률과그환자들이분류되어있는병기의생존률과비교할수있다 (Table 3). pt3이면서림프절전이가없는경우는이집단이속하는병기는 7판에서는 IIa로 92.2% 이지만, 이들환자의 5년생존률은 88.1% 이었고, pt4a이면서 UICC/AJCC 7판의 N2에속하는환자들은 UICC/AJCC 7판에서 IIIb이므로 48.4% 이지만, 이집단만의 5년생존율이 31.1% 이었다. 따라서이런환자군에서는 UICC/AJCC 병기에의한생존율보다더불량한예후를가질수있음을주의해야할것으로생각된다. 또한, Table 3에서보면 pt3와 pt4a에서 N3a와 N3b의경우같은병기에속하지만, 실제 5년생존률은많은차이가있음을알수있다. 따라서 UICC/AJCC 7판에서 7개이상의전이림프절을가질때일률적으로 N3로분류한것이부적절할수도있으므로림프절전이도분류하기위한적절한전이림프절개수의기준에대해향후많은연구가필요하리라생각된다.

6 28 J Korean Surg Soc. Vol. 80, No. 1 결 UICC/AJCC 7판은 6판에비해고유근육층과장막하층을분리하고 IV의분류등에서위암환자들의예후를자세하게세분화한것은적절하다고생각된다. UICC/AJCC 6판과 7판의림프절전이도분류에서예후를반영하는데어느분류방법이더적절한지는더많은연구가필요할것으로생각된다. 또한림프절전이도분류하기위한적절한전이림프절개수의기준에대해향후많은연구가필요하리라생각된다. 론 REFERENCES 1) Edge SB, American Joint Committee on Cancer. AJCC cancer staging manual. 7th ed. New York: Springer; ) Greene FL, American Joint Committee on Cancer., American Cancer Society. AJCC cancer staging manual. 6th ed. New York: Springer; ) Lu Y, Liu C, Zhang R, Li H, Lu P, Jin F, et al. Prognostic significance of subclassification of pt2 gastric cancer: a retrospective study of 847 patients. Surg Oncol 2008;17: ) Choi BH, Kim JH, Kwak JH, Jang HJ, Han MS. The analysis of clinical characteristics of pt2a and pt2b gastric cancer. J Korean Surg Soc 2009;77: ) Park DJ, Kong SH, Lee HJ, Kim WH, Yang HK, Lee KU, et al. Subclassification of pt2 gastric adenocarcinoma according to depth of invasion (pt2a vs pt2b) and lymph node status (pn). Surgery 2007;141: ) Ishigami S, Natsugoe S, Miyazono F, Hata Y, Uenosono Y, Sumikura S, et al. Clinical merit of subdividing gastric cancer according to invasion of the muscularis propria. Hepatogastroenterology 2004;51: ) Deng J, Liang H, Sun D, Wang D, Pan Y. Suitability of 7th UICC N stage for predicting the overall survival of gastric cancer patients after curative resection in China. Ann Surg Oncol 2010;17: ) Ha TK, Kim HJ, Kwon SJ. Does the New UICC/AJCC TNM Staging System (7th Edition) Improve Assessing Prognosis in Gastric Cancer Compared to the Old System (6th Edition)? J Korean Gastric Cancer Assoc 2009;9: ) Huang B, Zheng X, Wang Z, Wang M, Dong Y, Zhao B, et al. Prognostic significance of the number of metastatic lymph nodes: is UICC/TNM node classification perfectly suitable for early gastric cancer? Ann Surg Oncol 2009;16: ) Roviello F, Rossi S, Marrelli D, Pedrazzani C, Corso G, Vindigni C, et al. Number of lymph node metastases and its prognostic significance in early gastric cancer: a multicenter Italian study. J Surg Oncol 2006;94:275-80; discussion 4. 11) Gunji Y, Suzuki T, Hori S, Hayashi H, Matsubara H, Shimada H, et al. Prognostic significance of the number of metastatic lymph nodes in early gastric cancer. Dig Surg 2003;20: ) Zhang X, Watson DI, Jamieson GG. Lymph node metastases of adenocarcinoma of the esophagus and esophagogastric junction. Chin Med J (Engl) 2007;120: ) Deng JY, Liang H, Sun D, Zhan HJ, Wang XN. The most appropriate category of metastatic lymph nodes to evaluate overall survival of gastric cancer following curative resection. J Surg Oncol 2008;98: ) Seo YJ, Bae JM, Kim SW, Kim SW, Song SK. Different clinical outcomes of stage IV gastric cancer according to the curability of surgery. J Korean Surg Soc 2009;77: ) Ha TK, Kwon SJ. Subclassification of stage IV gastric cancer according to the presence of distant metastasis (IVa and IVb). J Korean Gastric Cancer Assoc 2006;6: ) An JY, Ha TK, Noh JH, Sohn TS, Kim S. Proposal to subclassify stage IV gastric cancer into IVA, IVB, and IVM. Arch Surg 2009;144:38-45; discussion ) Li C, Yan M, Chen J, Xiang M, Zhu ZG, Lin YZ. Prognostic influence of sub-stages according to ptnm categories in patients with stage IV gastric cancer. J Surg Oncol 2009;99:

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