Journal of Surgical Oncology 51:221-225 (1992)
Noncurative Resection for Advanced Gastric Cancer YOSHlHlKO MAEHARA, MD, YOSHlHlRO KAKEJI, MD, IKUO TAKAHASHI, MD, TOSHIRO OKUYAMA, MD, HIDE0 BABA, MD, HlDEAKl ANAI, MD, AND KElZO SUGIMACHI, MD, FACS From the Department of Surgery /I, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Between 1965 and 1985, 489 patients with advanced gastric cancer who were treated with gastric resection and in whom tumor cells remained after the operation were defined as cases of a “noncurative resection.” The clinicopathological features and prognosis of these patients were examined and two groups were prepared: locally advanced cancer and cancer with a distant metastasis. In locally advanced cancer cases, tumor cells remained in the neighboring organs, lymph nodes, and/or resected margins; in those with distant metastasis, peritoneal dissemination and/or liver metastasis were present regardless of whether or not the metastasis was removed, with or without locally noncurative factors. Serosal invasion was prominent and high rates of lymph node metastasis and lymphatic inolvement were evident in both groups. The survival rate for patients with locally advanced gastric cancer was better than that of patients with distant metastasis ( P < 0.01). Survival time in patients with locally advanced cancer can be lengthened by resecting all of the primary tumor and as much of the metastatic lesions as possible, even if the surgical management is “noncurative.” Aggressive postoperative chemotherapy for patients with distant metastasis from a gastric cancer is to be recommended. 0 1992 Wiley-Liss, lnc.
KEYWORDS:metastasis, prognosis, postoperative chemotherapy
INTRODUCTION The prognosis for patients with far advanced gastric cancer is unsatisfactory, with the 5-year survival rates after gastric resection ranging from 10 to 20% [I]. Attempts at curative resection require an intraoperative assessment of tumor spread and a decision as to the amount of tissue to be resected. When curative resection is not feasible, the alternatives are palliative resection, gastrojeunostomy bypass, or abdominal closure [2,3]. Such decision making must weigh both risk and benefit factors such as operative mortality, need, and efficacy of symptom relief and survival time. The surgical resection of gastric cancer is defined as “noncurative” when gastric resection is performed and when peritoneal dissemination and/or liver metastasis is present, regardless of whether or not the metastatic sites are removed, and/or when residual tumor cells are present in the neighboring organsT lymph nodes, Or the resection margin [4951. These foreboding signs are present at a late stage of the disease 0 1992 Wiley-Liss, Inc.
and greatly influence the prognosis [ 6 ] .Reports of palliative gastric resection prolonging survival and alleviation of bleeding episodes and obstruction in patients with far advanced cancer suggest that an aggressive approach is needed when resecting primary and/or metastatic lesions [7-91. We describe here the clinicopathological features and prognosis of patients with advanced gastric cancer following noncurative resection with special reference to locally advanced cancer and cancer with distant metastasis.
PATIENTS AND METHODS This study was done using data on 489 consecutively treated Japanese patients who underwent noncurative gastric resection for primary advanced gastric cancer beAccepted for 257 1992. Address reprint requests to Yoshihiko Maehara, MD, Department of Surgery 11, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan.
222
Maehara et al.
tween 1965 and 1985, in the Department of Surgery 11, Kyushu University Hospital, Fukuoka, Japan. There were 18 patients who died within the first 30 postoperative days (operative mortality, 3.7%), thus, 47 1 patients were entered into the study. In the same period, 650 patients were curatively resected (operative morality rate, 0.8%) and for 231, resection was not done. A noncurative operation was designated based on the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan [ 5 ] , as a malignant lesion in association with peritoneal dissemination and/or hepatic metastasis. Regardless of whether or not the metastatic lesion was resected, there was incomplete removal of a lymph node metastasis, tumor cells remaining in adjacent organs: carcinoma extcnding beyond the serosa and infiltrating into neighboring organs, and/or microscopic evidence of tumor cells beyond the confines or surgical resection. Of patients undergoing noncurative resection, 235 with no evidence of a distant metastasis were included in the noncurative resection group because there was a locally advanced tumor invading neighboring organs, lymph node metastasis, and/or cancer infiltration at the resected margin that could not be completely resected, and 231 with evidence of distant metastases (165 with peritoneal dissemination, 87 with liver metastasis, and 20 with both), with or without local noncurative factors. Pathological diagnosis and classification were based on the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan [ S ] .
Statistical Analysis The Chi-square and Mann Whitney tests were used to compare data on locally advanced gastric cancer to data on cancer with distant metastasis. The Kaplan-Meier method was used to analyze the survival rates, and the generalized Wilcoxon test was used to test for equality of the survival curves. The level of significance was P < 0.05. RESULTS Clinicopathological factors The clinicopathological data from 253 patients with locally advanced gastric cancer and 2 18 patients with distant metastasis who underwent gastric resection were compared (Table I). In both groups, the stage of the disease was advanced. There was no difference in prognostic factors between the two groups, except for cancer infiltration at the resected margin, lymph node metastasis, and lymph node dissection. In patients with a distant metastasis, cancer infiltration at the resected margin was less frequent, lymph node metastasis was prominent, and lymph node dissection was less extensive. Survival Rates The postoperative survival rate for patients with advanced cancers treated following curative resection was
better than for those who underwent noncurative resection or nonresection, as shown in Figure 1 ( P < 0.01). The 5-year survival rate was 49.8% for the curatively resected group, 5.6% for the noncuratively resected patients, and 1 . 1 % for those nonsurgically treated. In patients who underwent noncurative resection, the survival rate for those with a locally advanced gastric cancer was better than for those with a distant metastasis ( P < 0.01). The 5-year survival rate was 7.3% for patients with a locally advanced cancer and 1.8% in those with a distant metastasis (Fig. 2).
DISCUSSION Despite recent advances in the diagnosis and surgical management of gastric cancer, the prognosis for advanced gastric cancer is poor [ 10,111. This unfavorable course will influence intraoperative decision making. Allocation to a curative resection or noncurative resection group was partly based on intraoperative assessments. Viste et al. [ 121 reported that the postoperative survival time was not influenced greatly by whether a resection was considered to be curative or palliative. However, this conclusion lacks strength as only a small number of cases were analyzed. Our findings show that curative resection significantly improves survival rate and is associated with a low mortality rate, as was noted in other reports [3,6,13]. Thus surgical resection is at present the only approach with a curative potential for gastric cancer patients. Associated lymph node metastasis, invasion into neighboring structures, peritoneal dissemination. and liver metastasis present great problems in decision making for the surgeon. Meijer et a]. [ 141 reported that palliative resection has therapeutic value even in cases of a far advanced gastric cancer. Our data show that the S-year survival rate for noncurative resection is 5.6%, a value consistent with the data on the 61 cases reported by Bozzetti et al. [ 151. As a larger number of patients has a greater statistical power, we analyzed data on 489 patients. After noncurative resection, the difference in survival time between patients with a locally advanced cancer and those with a distant metastasis should be related to the number of remaining tumor cells. In patients with a locally advanced gastric cancer, maximizing the resection of involved organs and/or lymph node metastasis may extend the survival time of these patients to approach that of patients undergoing curative resection. The survival rate is lower in patients with a distant metastasis. Koga et al. [7] reported that the mean survival time is increased in patients with liver metastasis and who underwent a palliative gastrectomy. Kaibara et al. [IS] reported that resection of the primary focus combined with lymph node dissection extends survival time for patients with peritoneal dissemination. The surgical dissection of lymph nodes was less extensive in our patients with distant metastases. A more aggressive lymph node dissec-
Gastric Cancer a n d Noncurative Resection TABLE 1. Clinicopathological Comparison Between Noncurative Surgery in Locally Advanced Gastric Cancer and Noncurative Surgery in Cancer With Distant Metastasis Variable Age
Sex Men Women Maximum tumor diameter (cm) Location of tumor Upper (C) Middle (M) Lower ( A ) Whole stomach Gross appearance Type 1 Type 2 Type 3 Type 4 Type 5 Histology Differentiated Undifferentiated Depth of penetration No serosal invasion With serosal invasion Invasion into neighboring structures Cancer infiltration at the resected margin Negative Positive Lymphatic involvement Negative Positive Unknown** Vascular involvement Negative Positive Unknown** Histological growth pattern Expansive Intermediate Infiltrative Unknown** Histological lymph node metastasis Negative Positive Peritoneal dissemination Negative Positive Liver metastasis Negative Positive Operative procedure Partial resection Total resection Lymph node dissection RI R2 R3
Locally advanced (n = 253)
Distant metastasis (n = 218)
P value
12.7"
57.3 2 12.4
NS
161 (63.6%) 92 (36.4%) 10.1 t 4.0*
143 (65.6%) 75 (34.4%) 9.5 -C 3.8
NS
62 (24.5%) 39 ( I5 -4%) 94 (37.2%) 58 (22.9%')
59 (27. I %) 27 (12.4%) 82 (37.6%) 50 (22.9%)
NS
4 ( I .6%) 55 (21.7%) 112 (44.3%) 63 (24.9%) 19 (7.5%)
3 (1.4%) 52 (23.9%) 92 (42.2%) 62 (28.4%) 9 (4.1%)
NS
107 (42.3%) 146 (57.7%)
87 (39.9%) 131 (60. I % )
NS
28 ( 1 1. I % ) I15 (45.5%) 110 (43.4%)
17 (7.8%) 100 (45.9%) 101 (46.3%)
NS
145 (57.3%) 108 (42.7%)
155 (71.1%) 63 (28.9%)
38 (24.2%) 119 (75.8%) 96
24 (15.8%) 128 (84.2%) 66
NS
103 (67.3%) 50 (32.7%) 100
90 (61.2%) 57 (38.8%) 71
NS
26 ( 1 I .0%) 51 (21.5%) 160 (67.5%) 16
18 (8.3%) 54 (24.9%) 145 (66.8%) I
NS
27 (10.7%) 226 (89.3%)
6 (2.8%) 212 (97.2%)
P
< 0.01
253 ( 100%) 0 (0%)
61 (28.0%) I57 (72.0%)
P
< 0.01
253 (100%) 0 (0%)
137 (62.8%) 81 (37.2%)
P
< 0.01
I 1 1 (43.9%) 142 (56. I%)
90 (41.3%) 128 (58.7%)
126 (49.8%) 75 (29.6%) 52 (20.6%)
151 (69.2%) 52 (23.9%) 15 (6.9%)
59.5
%
*mean ? standard deviation; ** unknown cases were excluded from statistical analysis. NS = no significant difference.
NS
P
< 0.01
NS P
< 0.01
223
224
Maehara et al.
therapy combined with intraperitoneal hyperthermic perfusion for peritoneal dissemination [22] and intraarterial chemotherapy for liver metastasis [21] should be planned.
1
0
-. 1
2
3
I
I
4
5
Fig. 1.
Survival curves for patients who underwent curative resection noncurative resection (-) or nonresection (---). The difference in these survival curves is statistically significant ( P < 0.01).
(-),
(Years) Fig. 2 . Suvival curves for patients with locally advanced gastric or gastric cancer with distant metastasis for noncurative cancer (-) resection (-). The difference in these survival curves is statistically significant (P < 0.01).
tion may have to be done because postoperative residual or occult tumor cells grow rapidly in patients subjected to a noncurative resection [16,17]. These tumor foci should be more sensitive to cell-cycle specific drugs [IS] and the removal of tumor bulk (noncurative resection) potentiates the effects of adjuvant therapies. Surgery combined with perioperative chemotherapy and/or hyperthermia was reported to be effective for patients with distant metastasis [ 19-22 J . Criteria of treatment we recommend for cases of advanced gastric cancer are: (1) in patients without a distant metastasis, the primary and metastatic lesions in the lymph nodes andlor adjacent organs are resected, as a curative resection [23], and in the postoperative period, anticancer drug therapy is recommended regardless of whether or not a curative resection has been done [24,25]; and (2) in patients with a distant metastasis, the primary and metastatic lesions are resected. Perioperative chemo-
CONCLUSION The clinicopathological features and prognosis were examined in 489 patients with advanced gastric cancer who were treated with noncurative gastric resection. Survival time in patients with locally advanced cancer can be lengthened by resecting all of the primary tumor and as much of the metastatic lesions as possible, even if the surgical management is “noncurative.” Aggressive postoperative chemotherapy for patients with distant metastasis is to be recommended. REFERENCES 1. Korenaga D, Tsujitani S , Haraguchi M, Okamura T, Tamada R , Sugimachi K, Akazawa K, Nose Y: Long-term survival in Japanese patients with far advanced carcinoma of the stomach. World J Surg, 12236-240, 1988. 2. Eckbom GA, Gleysteen JJ: Gastric malignancy: Resection for palliation. Surgery 88:47&481, 1980. 3. Boddie AW, McMurtrey MJ, Giacco GG, McBride CM: Palliative total gastrectomy and esophagogastrectomy. A reevaluation. Cancer 51:1l95-1200, 1983. 4. Lawrence W Jr, Mcneer G: The effectiveness of surgery for palliation of incurable gastric cancer. Cancer I1:28-32, 1958. 5 . Japanese Research Society for Gastric Cancer: The General Rules for the Gastric Cancer Study in Surgery and Pathology. Part I. Clinical Classification. Jpn J Surg I1:127-139, 1981. Part 11. Histological classification of gastric cancer. Jpn J Surg 1 I :1 4 G 145, 1981. 6 . Maruyama K: The most important prognostic factors for gastric cancer patients. Scand J Gastroenterol 22 (suppl 133):63-68, 1987. 7. Koga S , Kawaguchi H, Kishimoto H, Tanaka K, Miyano Y, Kiniura 0, Takeda R, Nishidoi H: Therapeutic significance of noncurative gastrectomy for gastric cancer with liver metastasis. Am J Surg 140:35&359, 1980. 8. Kaibara N, Okamoto T, Kimura 0, litsuka Y, Takebayashi M, Yurugi E, Nishidoi H, Tamura H, Koga S: Possible role of lymph node dissection in the surgical treatment of gastric cancer with disseminating peritoneal metastasis. Jpn J Surg 13:404408, 1983. 9. Furukawa H, Hiratsuka M, Iwanaga T: A rational technique for surgical operation on Borrman type 4 gastric carcinoma: Left upper abdominal evisceration plus Appleby’s method. Br J Surg 75:l 16-1 19, 1988. 10. Maehara Y, Morigiuchi S , Kakeji Y , Kohnoe S , Korenaga D, Haraguchi M, Sugimachi K: Pertinent risk factors and gastric carcinoma with synchronous peritoneal dissemination or liver metastasis. Surgery 110:820-823, 1991. 1 1 . Maehara Y, Moriguchi S , Orita H, Kakeji Y, Haraguchi M, Korenaga D, Sugimachi K: Lower survival rate for patients with gastric carcinoma of Borrman type IV following gastric resection. Surg Gynecol Obstet 175: 13-16, 1992. 12. Viste A, Lillestol J , Soreide 0: Cancer of the stomach: Are curative resections of’ any importance with respect to postoperative survival in patients with locoregional disease? Int Surg 69: 133135, 1984. 13. Yamada E, Miyaishi S , Nakazato H, Kato K, Kito T, Takagi H, Yasue M, Kato T, Moriomoto T, Yamaguchi M: The surgical treatment of cancer of the stomach. Int Surg 65:387-399, 1980. 14. Meijer S, De Bakker OJGB, Hoitsma HFW: Palliative resection in gastric cancer. J Surg Oncol23:77-80, 1983. 15. Bozzetti F, Bonfanti G, Audisio RA, Doci R, Dossena G, Gennari
Gastric Cancer and Noncurative Resection
16. 17. 18.
19.
20.
L, Andreola S: Prognosis of patients after palliative surgical procedures for carcinoma of the stomach. Surg Gynecol Obstet 164:151-154, 1987. Schabel FM: Concepts for systemic treatment of micrometastases. Cancer 35:15-24, 1975. Gunduz N , Fisher B, Saffer EA: Effect of surgical removal on the growth and kinetics of residual tumor. Cancer Res 39:3861-3865, 1979. Maehara Y , Kusumoto T, Kusumoto H, Anai H, Sakaguchi Y , Kido Y , Okamura T, Korenaga D, Sugimachi K: 5-Fluorouracil and UFT-sensitive gastric carcinoma has a high level of thymidylate synthase. Cancer 63: 1693-1696, 1989. Koga S , Hamazoe R, Maeta M , Shimizu N, Kanayama H, Osaki Y: Treatment of implanted peritoneal cancer in rats by continuous hyperthermic peritoneal perfusion in combination with an anticancer drug. Cancer Res 44:1840-1842, 1984. Kanematsu T, lnokuchi K, Sugimachi K, Furuta T, Sonoda T, Tamura S, Hasuo K: Selective effects of lipiodolized antitumor agents. J Surg Oncol25:218-226, 1984.
225
2 I . Okuyama K, lsono K, Juan IK, Onoda S , Ochiai T, Yamamoto Y , Koide Y , Sato H: Evaluation of treatment for gastric cancer with liver metastasis. Cancer 55:2498-2505, 1985. 22. Kokubun M, Fujimoto S, Shrestha RD, Kobdyashi K, Kiuchi S , Konno C, Takahashi M, Ohta M, Okui K: Intraperitoneal hyperthermic perfusion treatment for patients with gastric cancer and peritoneal implantation. Reg Cancer Treat 3:31&319, 1991. 23. Korenaga D, Okamura T, Baba H, Saito A, Sugimachi K: Results of resection of gastric cancer extending to adjacent organs. Br J Surg 75:12-15, 1988. 24. Maehara Y , Moriguchi S, Sakaguchi Y, Emi Y , Kohnoe S , Tsujitani S , Sugimachi K: Adjuvant chemotherapy enhances long-term survival of patients with advanced gastric cancer following curative resection. J Surg Oncol 45:169-172, 1990. 25. Maehara Y , Watanabe A , Kakeji Y, Baba H, Kohnoe S , Sugimachi K: Postogastrectomy prescription of mitomycin C and UFT for patients with stage IV gastric carcinoma. Am J Surg 160:242-244, 1990.
Noncurative Resection for Advanced Gastric Cancer YOSHlHlKO MAEHARA, MD, YOSHlHlRO KAKEJI, MD, IKUO TAKAHASHI, MD, TOSHIRO OKUYAMA, MD, HIDE0 BABA, MD, HlDEAKl ANAI, MD, AND KElZO SUGIMACHI, MD, FACS From the Department of Surgery /I, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Between 1965 and 1985, 489 patients with advanced gastric cancer who were treated with gastric resection and in whom tumor cells remained after the operation were defined as cases of a “noncurative resection.” The clinicopathological features and prognosis of these patients were examined and two groups were prepared: locally advanced cancer and cancer with a distant metastasis. In locally advanced cancer cases, tumor cells remained in the neighboring organs, lymph nodes, and/or resected margins; in those with distant metastasis, peritoneal dissemination and/or liver metastasis were present regardless of whether or not the metastasis was removed, with or without locally noncurative factors. Serosal invasion was prominent and high rates of lymph node metastasis and lymphatic inolvement were evident in both groups. The survival rate for patients with locally advanced gastric cancer was better than that of patients with distant metastasis ( P < 0.01). Survival time in patients with locally advanced cancer can be lengthened by resecting all of the primary tumor and as much of the metastatic lesions as possible, even if the surgical management is “noncurative.” Aggressive postoperative chemotherapy for patients with distant metastasis from a gastric cancer is to be recommended. 0 1992 Wiley-Liss, lnc.
KEYWORDS:metastasis, prognosis, postoperative chemotherapy
INTRODUCTION The prognosis for patients with far advanced gastric cancer is unsatisfactory, with the 5-year survival rates after gastric resection ranging from 10 to 20% [I]. Attempts at curative resection require an intraoperative assessment of tumor spread and a decision as to the amount of tissue to be resected. When curative resection is not feasible, the alternatives are palliative resection, gastrojeunostomy bypass, or abdominal closure [2,3]. Such decision making must weigh both risk and benefit factors such as operative mortality, need, and efficacy of symptom relief and survival time. The surgical resection of gastric cancer is defined as “noncurative” when gastric resection is performed and when peritoneal dissemination and/or liver metastasis is present, regardless of whether or not the metastatic sites are removed, and/or when residual tumor cells are present in the neighboring organsT lymph nodes, Or the resection margin [4951. These foreboding signs are present at a late stage of the disease 0 1992 Wiley-Liss, Inc.
and greatly influence the prognosis [ 6 ] .Reports of palliative gastric resection prolonging survival and alleviation of bleeding episodes and obstruction in patients with far advanced cancer suggest that an aggressive approach is needed when resecting primary and/or metastatic lesions [7-91. We describe here the clinicopathological features and prognosis of patients with advanced gastric cancer following noncurative resection with special reference to locally advanced cancer and cancer with distant metastasis.
PATIENTS AND METHODS This study was done using data on 489 consecutively treated Japanese patients who underwent noncurative gastric resection for primary advanced gastric cancer beAccepted for 257 1992. Address reprint requests to Yoshihiko Maehara, MD, Department of Surgery 11, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan.
222
Maehara et al.
tween 1965 and 1985, in the Department of Surgery 11, Kyushu University Hospital, Fukuoka, Japan. There were 18 patients who died within the first 30 postoperative days (operative mortality, 3.7%), thus, 47 1 patients were entered into the study. In the same period, 650 patients were curatively resected (operative morality rate, 0.8%) and for 231, resection was not done. A noncurative operation was designated based on the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan [ 5 ] , as a malignant lesion in association with peritoneal dissemination and/or hepatic metastasis. Regardless of whether or not the metastatic lesion was resected, there was incomplete removal of a lymph node metastasis, tumor cells remaining in adjacent organs: carcinoma extcnding beyond the serosa and infiltrating into neighboring organs, and/or microscopic evidence of tumor cells beyond the confines or surgical resection. Of patients undergoing noncurative resection, 235 with no evidence of a distant metastasis were included in the noncurative resection group because there was a locally advanced tumor invading neighboring organs, lymph node metastasis, and/or cancer infiltration at the resected margin that could not be completely resected, and 231 with evidence of distant metastases (165 with peritoneal dissemination, 87 with liver metastasis, and 20 with both), with or without local noncurative factors. Pathological diagnosis and classification were based on the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan [ S ] .
Statistical Analysis The Chi-square and Mann Whitney tests were used to compare data on locally advanced gastric cancer to data on cancer with distant metastasis. The Kaplan-Meier method was used to analyze the survival rates, and the generalized Wilcoxon test was used to test for equality of the survival curves. The level of significance was P < 0.05. RESULTS Clinicopathological factors The clinicopathological data from 253 patients with locally advanced gastric cancer and 2 18 patients with distant metastasis who underwent gastric resection were compared (Table I). In both groups, the stage of the disease was advanced. There was no difference in prognostic factors between the two groups, except for cancer infiltration at the resected margin, lymph node metastasis, and lymph node dissection. In patients with a distant metastasis, cancer infiltration at the resected margin was less frequent, lymph node metastasis was prominent, and lymph node dissection was less extensive. Survival Rates The postoperative survival rate for patients with advanced cancers treated following curative resection was
better than for those who underwent noncurative resection or nonresection, as shown in Figure 1 ( P < 0.01). The 5-year survival rate was 49.8% for the curatively resected group, 5.6% for the noncuratively resected patients, and 1 . 1 % for those nonsurgically treated. In patients who underwent noncurative resection, the survival rate for those with a locally advanced gastric cancer was better than for those with a distant metastasis ( P < 0.01). The 5-year survival rate was 7.3% for patients with a locally advanced cancer and 1.8% in those with a distant metastasis (Fig. 2).
DISCUSSION Despite recent advances in the diagnosis and surgical management of gastric cancer, the prognosis for advanced gastric cancer is poor [ 10,111. This unfavorable course will influence intraoperative decision making. Allocation to a curative resection or noncurative resection group was partly based on intraoperative assessments. Viste et al. [ 121 reported that the postoperative survival time was not influenced greatly by whether a resection was considered to be curative or palliative. However, this conclusion lacks strength as only a small number of cases were analyzed. Our findings show that curative resection significantly improves survival rate and is associated with a low mortality rate, as was noted in other reports [3,6,13]. Thus surgical resection is at present the only approach with a curative potential for gastric cancer patients. Associated lymph node metastasis, invasion into neighboring structures, peritoneal dissemination. and liver metastasis present great problems in decision making for the surgeon. Meijer et a]. [ 141 reported that palliative resection has therapeutic value even in cases of a far advanced gastric cancer. Our data show that the S-year survival rate for noncurative resection is 5.6%, a value consistent with the data on the 61 cases reported by Bozzetti et al. [ 151. As a larger number of patients has a greater statistical power, we analyzed data on 489 patients. After noncurative resection, the difference in survival time between patients with a locally advanced cancer and those with a distant metastasis should be related to the number of remaining tumor cells. In patients with a locally advanced gastric cancer, maximizing the resection of involved organs and/or lymph node metastasis may extend the survival time of these patients to approach that of patients undergoing curative resection. The survival rate is lower in patients with a distant metastasis. Koga et al. [7] reported that the mean survival time is increased in patients with liver metastasis and who underwent a palliative gastrectomy. Kaibara et al. [IS] reported that resection of the primary focus combined with lymph node dissection extends survival time for patients with peritoneal dissemination. The surgical dissection of lymph nodes was less extensive in our patients with distant metastases. A more aggressive lymph node dissec-
Gastric Cancer a n d Noncurative Resection TABLE 1. Clinicopathological Comparison Between Noncurative Surgery in Locally Advanced Gastric Cancer and Noncurative Surgery in Cancer With Distant Metastasis Variable Age
Sex Men Women Maximum tumor diameter (cm) Location of tumor Upper (C) Middle (M) Lower ( A ) Whole stomach Gross appearance Type 1 Type 2 Type 3 Type 4 Type 5 Histology Differentiated Undifferentiated Depth of penetration No serosal invasion With serosal invasion Invasion into neighboring structures Cancer infiltration at the resected margin Negative Positive Lymphatic involvement Negative Positive Unknown** Vascular involvement Negative Positive Unknown** Histological growth pattern Expansive Intermediate Infiltrative Unknown** Histological lymph node metastasis Negative Positive Peritoneal dissemination Negative Positive Liver metastasis Negative Positive Operative procedure Partial resection Total resection Lymph node dissection RI R2 R3
Locally advanced (n = 253)
Distant metastasis (n = 218)
P value
12.7"
57.3 2 12.4
NS
161 (63.6%) 92 (36.4%) 10.1 t 4.0*
143 (65.6%) 75 (34.4%) 9.5 -C 3.8
NS
62 (24.5%) 39 ( I5 -4%) 94 (37.2%) 58 (22.9%')
59 (27. I %) 27 (12.4%) 82 (37.6%) 50 (22.9%)
NS
4 ( I .6%) 55 (21.7%) 112 (44.3%) 63 (24.9%) 19 (7.5%)
3 (1.4%) 52 (23.9%) 92 (42.2%) 62 (28.4%) 9 (4.1%)
NS
107 (42.3%) 146 (57.7%)
87 (39.9%) 131 (60. I % )
NS
28 ( 1 1. I % ) I15 (45.5%) 110 (43.4%)
17 (7.8%) 100 (45.9%) 101 (46.3%)
NS
145 (57.3%) 108 (42.7%)
155 (71.1%) 63 (28.9%)
38 (24.2%) 119 (75.8%) 96
24 (15.8%) 128 (84.2%) 66
NS
103 (67.3%) 50 (32.7%) 100
90 (61.2%) 57 (38.8%) 71
NS
26 ( 1 I .0%) 51 (21.5%) 160 (67.5%) 16
18 (8.3%) 54 (24.9%) 145 (66.8%) I
NS
27 (10.7%) 226 (89.3%)
6 (2.8%) 212 (97.2%)
P
< 0.01
253 ( 100%) 0 (0%)
61 (28.0%) I57 (72.0%)
P
< 0.01
253 (100%) 0 (0%)
137 (62.8%) 81 (37.2%)
P
< 0.01
I 1 1 (43.9%) 142 (56. I%)
90 (41.3%) 128 (58.7%)
126 (49.8%) 75 (29.6%) 52 (20.6%)
151 (69.2%) 52 (23.9%) 15 (6.9%)
59.5
%
*mean ? standard deviation; ** unknown cases were excluded from statistical analysis. NS = no significant difference.
NS
P
< 0.01
NS P
< 0.01
223
224
Maehara et al.
therapy combined with intraperitoneal hyperthermic perfusion for peritoneal dissemination [22] and intraarterial chemotherapy for liver metastasis [21] should be planned.
1
0
-. 1
2
3
I
I
4
5
Fig. 1.
Survival curves for patients who underwent curative resection noncurative resection (-) or nonresection (---). The difference in these survival curves is statistically significant ( P < 0.01).
(-),
(Years) Fig. 2 . Suvival curves for patients with locally advanced gastric or gastric cancer with distant metastasis for noncurative cancer (-) resection (-). The difference in these survival curves is statistically significant (P < 0.01).
tion may have to be done because postoperative residual or occult tumor cells grow rapidly in patients subjected to a noncurative resection [16,17]. These tumor foci should be more sensitive to cell-cycle specific drugs [IS] and the removal of tumor bulk (noncurative resection) potentiates the effects of adjuvant therapies. Surgery combined with perioperative chemotherapy and/or hyperthermia was reported to be effective for patients with distant metastasis [ 19-22 J . Criteria of treatment we recommend for cases of advanced gastric cancer are: (1) in patients without a distant metastasis, the primary and metastatic lesions in the lymph nodes andlor adjacent organs are resected, as a curative resection [23], and in the postoperative period, anticancer drug therapy is recommended regardless of whether or not a curative resection has been done [24,25]; and (2) in patients with a distant metastasis, the primary and metastatic lesions are resected. Perioperative chemo-
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