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1 J Gastric Cancer 2010;10(3): DOI: /jgc Original Article Prognostic Factors in Gastric Cancer Patients with Peritoneal Carcinomatosis Hyun Il Kim, Tae Kyung Ha, and Sung Joon Kwon Department of Surgery, College of Medicine, Hanyang University, Seoul, Korea Purpose: Peritoneal carcinomatosis (PC) has a dismal prognosis and is occasionally encountered during initial exploration in patients with gastric cancer. The clinicopathological characteristics and survival were analyzed in patients with gastric cancer and PC. Materials and Methods: Among 2,083 gastric cancer patients who received surgery at the department of surgery, Hanyang University Hospital from 1992 to 2009, 130 patients revealed PC. Ten patients who were lost during follow-up were excluded. The remaining 120 patients were divided into three groups according to the type of surgery. The degree of PC was classified into P1(to the adjacent peritoneum) and P2 (to the distant peritoneum). Various other clinicopathological factors were analyzed using univariate and multivariate survival analyses. Results: Systemic chemotherapy (SC), type of surgery, lymph node dissection, degree of PC, and presence of ascites were significant prognostic factors. However, age, gender, resection of PC, and Borrmann type were not significant prognostic factors. In a multivariate analysis, SC and the degree of PC were independent prognostic factors. The survival benefit of SC was significant without reference to the type of surgery or degree of PC. Conclusions: A gastrectomy should be considered feasible in patients with gastric cancer and PC. The independent favorable prognostic factors were SC and a low degree of PC. SC improved the prognosis regardless of operation type and degree of PC. Key Words: Gastric cancer, Peritoneal carcinomatosis, Prognostic factor Introduction 위암은우리나라에서가장흔한악성종양으로최근위내시경및상부위장관조영술등이흔히시행됨에따라조기위암의빈도가증가하고있다. 그러나아직도진단시에이미진행된경우가많으며특히복막파종이동반된경우에는원발병소를완전히절제한다해도대부분의경우수술후재발하여사망의원인이된다.(1-3) 이러한원격전이가동반된위암에대하여는근치적수술이불가능하여위공장문합술과같은우회로술이나단순개복술에그치는경우가지배적이었으나최근에는삶의질및생존율을향상시키기위하여비근치적위절제 Correspondence to: Sung Joon Kwon Department of Surgery, College of Medicine, Hanyang University, 17, Haengdang-dong, Seongdong-gu, Seoul , Korea Tel: , Fax: sjkwon@hanyang.ac.kr Received July 19, 2010 Accepted September 4, 2010 술이예전보다적극적으로시도되고있다. 복막전이가있는위암인경우에시행된위절제술은위절제후암조직이주위장기나림프절혹은절제연에남아있는지여부에관계없이그수술을비근치적위절제술이라정의하고있다.(4,5) 개복시복막파종이동반된위암은파종의정도나치료의방법에따라예후에차이가있을수있기때문에예후에영향을미치는인자들을분석하는노력이필요하다.(6-8) 이에저자들은복막파종을동반한위암환자에서어떠한인자들이예후에영향을미치는가를알아보고예후증진에도움이되는인자를찾고자이연구를하였다. Materials and Methods 1997년 7월부터 2009년 12월사이에한양대학교병원외과에서위암으로수술받은 2,083명의환자가운데개복시에복막파종이발견된경우는 130명이었으며, 추적관찰이불가능하 Copyrights 2010 by The Korean Gastric Cancer Association

2 127 Gastric Cancer and Peritoneal Carcinomatosis 였던 10명의환자를제외한 120명을본연구의대상으로하였다. 추적률은 92.3% 였으며추적기간은 2~141개월 ( 평균 : 15.8± 22.0개월, 중앙값 : 9개월 ) 이었다. 대상환자의연령, 성별, 전신항암화학치료여부, 수술방법, 림프절곽청술정도, 복막파종의정도, 복수의유무, 복막파종의절제여부, 육안형등여러임상병리학적인자들을대상으로단변량생존분석과다변량생존분석을시행하였다. 수술방법은위절제군과위절제술이불가능했던경우 ( 우회로술군및단순개복술군 ) 로나누었다. 복막파종정도에대하여일본위암규약집 (9) 에서는 3등급으로분류하여 P1은위주위의복막에국한된파종이존재하는경우, P2는원발복막에소수의파종이존재하는경우, P3는원발복막에다수의파종이존재하는경우로구분하고있으며본연구에서는복막파종정도에따라 P1군과 P2&3군으로양분하였다. 수술방법의선택에있어 P1의경우는주변장기로의침윤 (T4) 정도가심하지않으면가능한한위절제술을시행하였으며 P2&3에대하여는너무심한복막파종 (P3) 의경우가아니고 T4가아닌경우에대하여는위절제술을우선적으로고려하였고 T4가동반된경우에대하여는우회술을, 복막파종이너무심 한 P3에대하여는단순개복술을시행하였다. 물론환자의전신상태도함께고려하여수술의범위와방법을최종판단하였다. 전신항암화학제는대부분이 Cisplatin 또는 5-FU를포함한복합요법제 (5-FU+Cisplatin, Taxotere+Cisplatin, TS-1+cisplatin, 5-FU+Oxaliplatin+Leucovorin) 였으며 2 cycle 이상수행한경우를전신항암화학치료군으로분류하였다. Results 1. 예후인자들에대한단변량생존분석전신항암화학치료시행군은시행하지않은군에비하여유의하게좋은생존기간을보였다. 수술방법에따른분석결과위절제술, 우회로술및단순개복술에따라유의한차이를보였으며복막파종정도, 복수동반여부, 림프절곽청정도등에따른생존율차이도유의하였다. 연령분포 (P=0.060), 복막파종절제여부 (P=0.085), 육안형 (P=0.093) 등이중간유의도를보였으며성별의차이는유의하지않았다 (Table 1). Table 1. Univariate survival analysis in peritoneal metastases of gastric cancer No. 1 ysr (%) 2 ysr (%) 5 ysr (%) Mean±SD (month) P Age (yr) <65 (94) ± (26) ±3.2 Sex Male (79) ± Female (41) ±3.2 Chemotherapy Yes (67) ±5.5 < No (53) ±1.7 Type of Gastrectomy (77) ±4.4 < surgery Bypass (21) ±2.0 Celiotomy (22) ±1.9 Node D0 (44) ± dissection D1 (8) ±1.3 D2 (68) ±4.1 Degree of PC P1* (31) ±9.5 < P2&3 (89) ±1.8 Ascites No (97) ± Yes (23) ±1.4 Resection of No (100) ± PC Yes (20) ±8.6 Borrmann 2 or 3 (85) ± type 4 (35) ±3.7 1 ysr = 1-year survival rate; 2 ysr = 2-year survival rate; 5 ysr = 5-year survival rate; SD = standard deviation; PC = peritoneal carcinomatosis; *Metastases to the adjacent peritoneum but not the distant peritoneum; Metastases to the distant peritoneum.

3 128 Kim HI, et al. 2. 예후인자들에대한다변량생존분석 단변량생존분석에서의미있는차이를보였던임상병리학적인자들 ( 전신항암화학제치료여부, 수술방법, 림프절곽청정도, 복막파종정도, 복수동반여부 ) 을이용하여다변량생존분석을시행한결과전신항암화학제치료여부와복막파종의정도만생존율에의미있는차이를보이는독립적인인자였다 (Table 2). 3. 복막파종정도및전신항암화학제치료여부에따른생존율분석 P1군에서는전신항암화학제치료를시행한군에서평균생존기간이 57.6개월, 시행하지않은군에서 17.0개월, P2&3군에 Table 2. Multivariate survival analysis in peritoneal metastases of gastric cancer P-value Exp(B) 95% C.I. Degree of PC* ~0.937 Chemotherapy ~0.860 *P1 vs P2&3; Performed vs not performed. 서는각각 15.5개월및 9.0개월로 P1군및 P2&3군모두에서통계적으로유의한차이를나타냈다 (Table 3). 4. 수술방법및전신항암화학제치료여부에따른생존율분석위절제술이시행된경우엔전신항암화학제치료시행군이미시행군에비하여중간유의도수준 (P=0.071) 으로예후가좋았고, 위절제술이시행되지못한경우 ( 우회로술, 단순개복술 ) 에는통계적으로유의하게 (P=0.044) 예후가좋았다 (Table 4). 위절제술이시행되고전신항암화학치료가시행된군 (n=52), 위절제술이시행되고전신항암화학제치료가시행되지않은군 (n=25), 위절제술이시행되지않고전신항암화학제치료가시행된군 (n=15), 위절제술이시행되지않고전신항암화학제치료도시행되지않은군 (n=28) 에서의평균생존기간은각각 30.1개월, 14.8개월, 12.8개월, 7.3개월로통계적으로유의하게 (P<0.0001) 생존율의차이를보였다 (Fig. 1). 5. 연령및전신항암화학제치료유무에따른생존율비교 65세미만군에서는전신항암화학제치료를받은군 (N=59, 중앙연령치 : 51세, 평균생존기간 : 29.7개월 ) 과전신항암화학제치료를받지않은군 (N=35, 중앙연령치 : 51세, 평균생존기간 : 10.3개월 ) 사이의생존율차이는통계적인의미 (P=0.002) 를 Table 3. Survival rate in P1 and P2 group according to the chemotherapy No. (%) 1 ysr (%) 2 ysr (%) 5 ysr (%) Mean±SD (month) P P1* Chemotherapy (+) ± Chemotherapy ( ) ±6.0 P2&3 Chemotherapy (+) ± Chemotherapy ( ) ±1.3 1 ysr = 1-year survival rate; 2 ysr = 2-year survival rate; 5 ysr = 5-year survival rate; SD = standard deviation; *Metastases to the adjacent peritoneum but not the distant peritoneum; P2&3 = metastases to the distant peritoneum. Table 4. Survival rate according to the chemotherapy in patients who received gastrectomy and bypass surgery or celiotomy only No. (%) 1 ysr (%) 2 ysr (%) 5 ysr (%) Mean±SD (month) P In gastrectomy group Chemotherapy (+) ± Chemotherapy ( ) ±3.1 In bypass surgery or celiotomy only group Chemotherapy (+) ± Chemotherapy ( ) ±1.5 1 ysr = 1-year survival rate; 2 ysr = 2-year survival rate; 5 ysr = 5-year survival rate; SD = standard deviation.

4 129 Gastric Cancer and Peritoneal Carcinomatosis 보였다. 그러나 65세이상군에서는전신항암화학제치료를받은군 (N=8, 중앙연령치 : 68세, 평균생존기간 : 11.7개월 ) 과전신항암화학제치료를받지않은군 (N=18, 중앙연령치 : 71세, 평균생존기간 : 11.0개월 ) 사이의생존율차이는통계적인의미를보이지못하였다 (Table 5). 65세미만이면서전신항암화학제치료를받지않은군과, 65세이상이면서전신항암화학제치료를받은군사이의생존율의차이는통계적인의미를보이지않았다 (Table 6). 6. 전신항암화학제치료시행군과미시행군사이의임상병리학적특성전신항암화학제치료를수행한군은수행하지않은군에비하여통계적으로유의하게저연령층이많고, 여자가많고, 위절제술이많이시행되었으며, 확대림프절곽청이보다많이시행되었다. 그러나복막파종의정도, 간전이소의동반여부, 복수의동반여부, 위내원발소의육안형의차이는통계적인유의성을나타내지못하였다 (Table 7). Discussion Fig. 1. Cumulative survival curves according to resection and chemotherapy. R(+) = gastric resection; R( ) = gastric non-resection; C(+) = chemotherapy conducted group; C( ) = chemotherapy notconducted group. 최근위암에대한진단및수술적치료기술의진보에도불구하고진행성위암의예후는불량하며 (10-13) 특히복강내전이나타장기로전이가있을때에는치료방법의결정이쉽지않다. 복막전이가발생하는기전은암세포가위장막층을침윤한후복강내로탈락되어복막에착상되고증식하는과정을거치는것으로위장막층의암침윤과복막파종은밀접한관계가있다고볼수있다.(14,15) 진행성위암의중요한예후인자로는복막전이, 간전이, 원격림프절전이, 그리고주위장기로의침윤등을들수있는데 (16) 이들은근치적위절제를불가능하게하는주요한원인이된다.(17) 이가운데복막전이는위암의가장흔한전이및재발의형태로서외과의가흔히접하게되는문제이므로복막파종이있는경우의생존율향상을위해예후인자를비교분석하는것은중요하다하겠다. Table 5. Survival rate according to the chemotherapy in young aged (<65 year) and old aged ( 65 year) patients No. (%) Meadian age (yr) 1 ysr (%) 2 ysr (%) 5 ysr (%) Mean±SD (month) P <65 yr CTx (+)* ± CTx ( ) ± yr CTx (+) ± CTx ( ) ±3.7 1 ysr = 1-year survival rate; 2 ysr = 2-year survival rate; 5 ysr = 5-year survival rate; SD = standard deviation; *Chemotherapy conducted group; Chemotherapy not-conducted group. Table 6. Survival rate according to the chemotherapy and the age No. (%) 1 ysr (%) 2 ysr (%) 5 ysr (%) Mean±SD (month) P Young & CTx ( )* ± Old & CTx (+) ±2.0 1 ysr = 1-year survival rate; 2 ysr = 2-year survival rate; 5 ysr = 5-year survival rate; SD = standard deviation; *Young aged (<65 yr) patient who did not received chemotherapy; Old aged ( 65 yr) patient who received chemotherapy.

5 130 Kim HI, et al. Table 7. Clinicopathologic characteristics according to the chemotherapy CTx (+)* (%) CTx ( ) (%) p Age (yr) <65 59 (88) 35 (66) (12) 18 (34) Mean±SD 50.9± ± Median Range 26~73 25~78 Gender Male 39 (58) 40 (75) Female 28 (42) 13 (25) Type of surgery STG or TG 52 (78) 25 (48) Bypass 7 (10) 14 (26) Celiotomy 8 (12) 14 (26) Node dissection D0 16 (24) 28 (53) D1 5 (7) 3 (5) D2 46 (69) 22 (42) Degree of PC P1 20 (30) 11 (21) P2&3 47 (70) 42 (79) Liver metastasis Absent 64 (96) 50 (94) Present 3 (4) 3 (6) Ascites Absent 55 (82) 42 (79) Present 12 (18) 11 (21) Borrmann type 2 or 3 49 (73) 36 (68) (27) 17 (32) STG = subtotal gastrectomy; TG = total gastrectomy; D0 = no node dissection; D1 = 1st tier node dissection; D2 = 1st and 2nd tier node dissection; PC = peritoneal carcinomatosis; *Chemotherapy conducted group; Chemo therapy not-conducted group; Metastases to the adjacent peritoneum but not the distant peritoneum; Metastases to the distant peritoneum. 본연구에서시행한단변량생존분석에서유의한임상병리학적인자는전신항암화학제치료여부, 수술방법, 림프절곽청정도, 복막파종정도, 복수동반여부였으며, 나이, 복막파종절제여부, 육안형등이중간유의도값을나타냈다. 그러나다변량생존분석에서는전신항암화학제치료여부와복막파종의정도만생존율에의미있는차이를보이는독립된예후인자였다. 본교실에서는수술방법의선택에대하여일정한기준을가지고시행하였다. 즉 P1의경우는주변장기로의침윤 (T4) 이없거나정도가심하지않으면가능한한위절제술을시행하였다. 즉 P1 31예가운데위절제술은 25예, 우회술은 6예에서시행되었다. 반면 P2&3 89예에대하여는너무심한복막파종의경우가아니고 (P2) T4가아닌경우에대하여는위절제술을우선적으로고려하였고 T4가동반된경우에대하여는우회술을우선적으로고려하였다. 그러나복막파종이너무심한 P3에대하여는단순개복술을시행하였다. 물론환자의전신상태도함께고려하였다. 이러한기준하에본연구에서는 25% 인 22예에대하여단순개복술을시행하였고 52예는위절제술을, 15예는우회로술을시행하였다. 복막파종예에대하여이와같은기준을정하여시술한결과위절제술관련사망은없었으며수술관련합병증의의미있는증가도없었다. 본연구에서전신항암화학치료가시행된예에서전신항암화학제의투약여부는환자의수행도 (performance status), 동반질환여부및정도, 환자또는보호자의치료거부의사여부, 수술후기대생존기간등복합요인에의존하여결정하였다. 전체대상환자에대한단변량생존분석에서전신항암화학제치료를시행한예들의예후가미시행군에비하여유의하게양호하였다. 특히전신항암화학제치료는 65세미만의젊은연령에서생존율증진효과가두드러졌다. Lawrence와 McNeer(4) 는위절제술을시행한경우와위측로형성술을시행한 379예를대상으로비교연구하였을때위절제술을시행한경우가생존율이더좋고삶의질도향상된다는보고를하였다.(18) 복막전이가있는경우에는간전이와원격림프절전이가없으면절제수술후 5년생존율이 8.9% 이고, 이가운데대망등주위복막에만전이가있고육안적잔류암이없는수술이가능했을때에는 5년생존율이 29.4% 로비교적예후가좋으므로보다적극적인수술을하자는보고도있으며,(19) 원격복막이나복강전체에복막전이가있어도간전이만없다면위절제술을시행하여연명효과를얻을수있다는보고도있다.(20) 복막파종이동반된위암에서원발위암병소절제술은우회로수술이나조직검사만을시행한경우보다생존율이유의하게높으며이는위출구폐쇄와출혈, 천공, 조절불가능한복수의발생가능성을원발병소절제로낮출수있고원발병소의절제가전신항암화학제치료의반응도를높일수있고 (21) 진행성위암환자에서도고식적위절제술은환자의생존율을향상시킬수있다 (22) 는연구보고들이있다. 본연구에서도위절제술을시행한군이미시행군에비하여생존율의향상이있었다. 그러나많은연구에서진행성위암의경우수술적인치료만으로는생존율향상을기대할수없으며추가적인치료가필요한것으로보고하고있다.(23-25) 본연구에서위절제술후전신항암화학제치료를시행한경우의평균생존기간 (30.1개월) 이위절제술후전신항암

6 131 Gastric Cancer and Peritoneal Carcinomatosis 화학제치료를시행하지않은경우 (14.8개월) 보다유의하게길었다. 그리고위절제술을시행하지못하고위측로형성술이나단순개복술을한경우에도전신항암화학치료를시행한경우의평균생존기간 (12.8개월) 이전신항암화학제치료를시행하지않은경우 (7.3개월) 보다유의하게향상되었다. 또한본연구에서연령층에따른분석을시행한결과전신항암화학제치료의연명효과는 65세미만군 (n=94) 에서는유의하였으나 65세이상군 (n=26) 에서는유의하지않았다. 65세이상군에서는치료를받은군 (n=8) 과받지않은군 (n=18) 의대상예가너무적었고동반질환의정도나수행도등에차이가있으므로이에대하여는잘계획된전향적무작위임상연구가필요하겠다. 결국복막파종이동반된위암환자에서복막파종으로근치적위절제술이불가능한진행성위암이라도적극적인위절제술후전신항암화학제치료가생존율향상에도움이되므로, 치료의적응이되는경우적극적절제를위한외과의의판단과노력이필요하고수술방법에상관없이수술후전신항암화학제치료등의적극적인치료가생존율의향상에도움이된다고할수있다. 즉위절제수술및전신항암화학제치료의적응증이되는경우라면보다적극적인시도가필요하겠으며이의결정은치료의방법에따른합병증발생등을함께고려하면서수행하여야하겠다. 복막파종이동반된위암환자의예후를증진시키기위해환자의전신상태가허락한다면위절제술을시행하는것이바람직하며이때복막파종의정도와전신항암화학제치료여부가독립적으로예후에영향을미치는인자이다. 특히전신항암화학제치료는위절제술의시행여부나복막파종의정도에관계없이모두의미있게예후를향상시키므로가능하다면그시행을긍정적으로검토해야하겠다. References 1. Gunderson LL, Sosin H. Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 1982;8: Wisbeck WM, Becheer EM, Russell AH. Adenocarcinoma of the stomach: autopsy observations with therapeutic implications for the radiation oncologist. Radiother Oncol 1986;7: Landry J, Tepper JE, Wood WC, Moulton EO, Koerner F, Sullinger J. Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys 1990;19: Lawrence W Jr, McNeer G. The effectiveness of surgery for palliation of incurable gastric cancer. Cancer 1958;11: Kajitani T. The general rules for the gastric cancer study in surgery and pathology. Part I. Clinical classification. Jpn J Surg 1981;11: Kim YJ, Kim BS, Choi WY, Yuk JH, Oh ST, Park KC. Prognostic significance of group 2 lymph node metastasis in pt3pn1 gastric cancer patients. J Korean Gastric Cancer Assoc 2004;4: Jang SW, Kim CH, Kim SW, Song SK. Prognostic factors and survival rates of stage III gastric cancer patients after a gastrectomy. J Korean Gastric Cancer Assoc 2004;4: Hyung WJ, Noh SH, Yoo CH, Huh JH, Shin DW, Lah KH, et al. Prognostic significance of metastatic lymph node ratio in T3 gastric cancer. World J Surg 2002;26: Kenkyukai I, ed. Japanese Classification of Gastric Carcinoma. 1st ed. Tokyo: Kanehara & Co., Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 2000;88: Lee KK, Kwon SJ. Clinicopathological analysis of stage IV gastric cancer. J Korean Surg Soc 1999;56: Kwon SJ. Results of surgical treatment for advanced gastric cancer analysis of prognostic factors. J Korean Surg Soc 1999;56(suppl): Kim JP, Kwon OJ, Oh ST, Yang HK. Results of surgery on 6589 gastric cancer patients and immunochemosurgery as the best treatment of advanced gastric cancer. Ann Surg 1992;216: Sugarbaker PH, Cunliffe W, Belliveau J, De Bruijn EA, Graves T, Mullins R, et al. Rationale for perioperative intraperitoneal chemotherapy as a surgical adjuvant for gastrointestinal malignancy. Reg Cancer Treat 1988;1: Yun JH, Yang DH, Kang NP. Clinical significance of intraperitoneal free cancer cells in prognosis and treatment of gastric cancer. J Korean Surg Soc 1997;53: Maekawa S, Saku M, Maehara Y, Sadanaga N, Ikejiri K, Anai H, et al. Surgical treatment for advanced gastric cancer. Hepatogatroenterology 1996;43: Maehara Y, Morigiuchi S, Kakeji Y, Kohnoe S, Korenaga D, Haraguchi M, et al. Pertinent risk factors and gastric carcinoma with synchronous peritoneal dissemination or liver metastasis. Surgery 1991;110:

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( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy