Risk factors for lymph node metastasis from intramucosal gastric carcinoma

602

Risk Factors for Lymph Node Metastasis from lntramucosal Gastric Carcinoma Takekazu Yamao, M.D.' Kuniaki Shirao, M.o.' Hiroyuki Ono, M.D.' Hitoshi Kondo, M.D? Daizo Saito, M.D? Hajime Yamaguchi, M.D.* Mitsuru Sasako, M.D? Takeshi Sano, M . D . ~ Atsushi Ochiai, M.D.3 Shigeaki Yoshida, M.D?

' Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.

* Department of Surgery, National Cancer Center Hospital, Tokyo, Japan. Department of Pathology, National Cancer Center Hospital, Tokyo, Japan. Department of Internal Medicine, National Cancer Center Hospital East, Chiba. Japan.

BACKGROUND. Although regional lymph node metastasis from intramucosal early gastric carcinoma (EGC) is rare, it is very important to clarify the characteristics of patients having lyniph nodal metastases in order to determine appropriate therapy. METHODS. The authors investigated 1196 patients with solitary intramucosal EGC who underwent resection at the National Cancer Center Hospital in Tokyo, with special reference to lymph node metastases. Eight clinicopathologic factors (age, sex, tumor: size, location, macroscopic type, histologic type, histologic ulceration of the tumor, and lymphatic vessel invasion) were investigated by univariate and multivariate analyses for their possible relationship to lymph node metastasis. RESULTS. Lymph node metastases were found in 43 patients (3.5%). Univariate analysis revealed that younger age (< 5 7 years), macroscopic depressed type, larger tumor size ( 2 30 mm), undifferentiated histologic type, histologic ulceration of the carcinoma, and lymphatic vessel invasion had a significant association with regional lyniph node metastasis. Multivariate analysis revealed that lymphatic vessel invasion, histologic ulceration of the tumor, and larger size ( 2 3 0 mm) were independent risk factors for regional lymph node metastasis. The incidence of lymph node metastasis from intramucosal EGC negative for these 3 risk factors was only 0.36% (1 in 277 patients). CONCLUSIONS. Lymphadenectomy is unnecessary for patients with small intramucosal EGC with neither histologic ulceration of the tumor nor lymphatic vessel invasion because the incidence of regional lymph node metastasis is extremely low in those patients. The therapeutic options for such patients would be local resection or endoscopic resection. Cancer 1996; 77502-6. 0 1996 American Cancer Society.

KEYWORDS: early gastric carcinoma, regional lymph node metastasis, multivariate analysis, risk factor, lymphadenectomy, endoscopic treatment.

E

The work was supported in part by a Grant-inAid for Cancer Research (5-18 and 7-34) from Ministry of Health and Welfare, Japan. Address for reprints: Takekazu Yamao, M.D., Department of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo 104, Japan. Received April 20, 1995; revision received June 27, 1995; accepted June 27, 1995.

0 1996 American Cancer Society

arly gastric carcinoma (EGC)is defined as that confined to the mucosa or submucosa regardless of the presence or absence of regional lymph node metastasis.' As a result of diagnostic development, including X-ray and endoscopy, the detection of EGC has been increasing in Japan. The prognosis of patients with EGC has improved with surgical treatment.' Gastrectomy with complete removal of primary and secondary lymph nodes has been the standard operation for EGC in Japan."' This surgical strategy provides an excellent therapeutic outcome; the 5-year survival rate after curative gastrectomy is more than 90% in Japan.',"' Although one of the most important factors for the prognosis of patients with EGC is the presence or absence of regional lymph node metastasis,"-" the incidence of metastasis of intramucosal EGC is approximately 3% and is 20% in submucosal EGC.l3-Ifi Thus, it should be possible to modify the therapeutic strategy for intramucosal EGC, taking into consideration the

Nodal Metastasis of Early Gastric CarcinomaNarnao et al.

risk of surgery and quality of life for the patients. The purpose of this study is to clarify independent risk factors for regional lymph node metastasis from intramucosal EGC that would be useful for therapeutic determination.

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TABLE I Relationship between Clinicopathologic Factors and Regional Lymph Node Metastasis from Intramucosal EGC, and Univariate Analysis Results Regional lymph node metastases

MATERIALS AND METHODS Patients and Specimens A total of 2265 patients with EGC underwent gastrectomy

at the National Cancer Center Hospital in Tokyo between 1963 and 1993. The resected stomachs were opened along the greater or lesser curvatures, pinned on a plate, and fixed in formalin. The specimens containing the tumors and the surrounding gastric wall were cut into multiple slices, principally parallel to the lesser curvature, at an interval of 5 mm. Dissected lymph nodes were also fixed in formalin, cut into two, and embedded in paraffin. Each slice embedded in paraffin was prepared for histologic examination. All microscopic sections were stained with hematoxylin and eosin. All histologic examinations were made by pathologists. Of the 1196 specimens proven to be solitary intramucosal cancer, 43 (3.5%) revealed regional lymph node metastasis histologically. The distribution of positive lymph nodes in all 43 specimens was to primary lymph nodes ( n l ) in 31 (72%), secondary lymph nodes (1121 in 7 (16%), and unknown in 5 (12%),according to the Japanese Classification of Gastric Cancer outlined by the Japanese Research Society for Gastric Cancer.” Eight clinicopathologic factors were investigated by means of univariate and multivariate analyses for their possible association with lymph node metastasis. Each factor was divided into 2 or 3 subgroups: age younger than 57 years or 57 years or older (the mean age of the patients was 57 years); sex; location of the primary lesion as either C (upper third of stomach), M (middle third of stomach), or A (lower third of stomach), according to the Japanese Classification; l 7 macroscopic type (protruded type or depressed type); tumor size smaller than 30 mm or 30 mm or larger in diameter (the mean diameter of the tumor was 30 mm in diarneter); histologic type (differentiated type or undifferentiated type); histologic ulceration of the tumor (negative 0 1 positive); and lymphatic vessel invasion (negative or positive). The primary lesions were classified macroscopically according to the Japanese Classification” as follows: Type I (protruded type), IIa (superficial elevated type), 1Ib (flat type), IIc (superficial depressed type), and Ill (excavated type). In the current analysis, we defined macroscopic protruded type as Type I, Type Ha, or combined type with Type I or Type Ha, such as Ha plus IIc type, and defined macroscopic depressed type as Type IIb, IIc, 111, or combined type with Type IIb, IIc, or 111, such as IIc plus 1Ib or IIc plus 111. As for the histologic classification, tubular adenocarcinoma and papillary adenocarcinoma were classified as differentiated type, and poorly differen-

Clinicopathologicfactor

Negative

Positive

Percentage “of positive”

P value

Age (yr) 4 7 257

Sex Male Female Location in stomach C (upper third) M (middle third] A (lower third) Macroscopic type Protruded Depressed

Unknown*

554 599

30 13

5.1% 2.1%

0.005

754 399

25 18

3.2% 3.3%

0.327

103 683 367

)

1.970 3.5%

0.536

25 16

4.201

7

0.8% 4.3%