Japanese Journal of Clinical Oncology 31:153-156 (2001)
© 2001 Foundation for Promotion of Cancer Research
Node-positive Mucosal Gastric Cancer: a Follow-up Study
Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: Lymph node metastasis from mucosal gastric carcinoma is rare and the prognosis of the patients has seldom been reported.
Methods: Forty-five patients with node-positive mucosal gastric cancer were studied. They accounted for 2.5% of 1770 patients with mucosal gastric cancer who underwent gastrectomy with lymphadenectomy at the National Cancer Center Hospital, Tokyo. The clinicopathological features were studied and the current clinical status was sought.
Results: The majority of patients (87%) were treated with D2 lymphadenectomy. The metastasis was confined to the perigastric nodes (pN1 by Japanese classification) in 30 patients (67%). The number of positive nodes was less than seven (pN1 by TNM) in 42 patients (93%). Two patients had para-aortic nodal metastasis. The median follow-up period was 11 years. Four patients died of definite or possible recurrent disease and the disease-specific 5- and 10-year survival rates were 95 and 89%, respectively.
Conclusions: Although nodal metastasis is an important prognostic factor for gastric cancer, the prognosis was excellent as long as the primary tumor was confined to the mucosa and was treated with gastrectomy and lymphadenectomy.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Early gastric cancer (EGC) is defined as adenocarcinoma confined to either the mucosa or submucosa regardless of lymph node status. Although the prognosis of patients with EGC is generally satisfactory (1), some patients develop recurrence and lymph node involvement is considered to be the most important risk factor (2,3).
Lymph node metastasis from mucosal gastric carcinoma is rare. The characteristic features of node-positive mucosal tumors have been studied to establish the indications for endoscopic mucosal resection (4–6). However, the clinical course of these patients has rarely been reported (7), probably because the number of patients is too small for significant analysis. We conducted a follow-up study of 45 such patients treated in a single institution with a median follow-up of 11 years.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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All patients with mucosal gastric cancer in association with lymph node metastases, diagnosed between 1963 and 1999, were sought from the National Cancer Center Hospital database. The operative records and pathological reports of these patients were studied retrospectively. The current condition of the patients was ascertained from hospital charts, by inquiry at the city registry system or by direct telephone interviews.
The clinicopathological description of tumors according to the Japanese Classification of Gastric Carcinoma (8) was obtained from the patients’ records. In addition, the UICC TNM classification (9) was employed to record the nodal status. Macroscopically, the tumors were classified as either of depressed type (IIc, IIc + III, etc.) or elevated type (IIa or IIa + IIc). Histologically, they were classified as either of differentiated type (well or moderately differentiated adenocarcinoma) or undifferentiated type (poorly differentiated adenocarcinoma or signet ring cell carcinoma). The survival rates were calculated using the Kaplan–Meier method.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The resected stomach and lymph nodes were handled according to standard methods (8) and were histologically examined on 5 mm stepwise sections of the primary lesion and bisected planes for lymph nodes.
Forty-five patients (2.5%) out of 1770 who underwent gastrectomy for mucosal gastric cancer had lymph node metastasis. Total and distal gastrectomies were performed in six and 39 patients, respectively. A D2 lymphadenectomy was performed in 39 cases (87%), while the dissection was limited to D1 in six (13%). The number of dissected nodes ranged from 11 to 111 per case, with a median of 35.
Clinicopathological features of the 45 patients are listed in Table 1, in which cases are grouped according to Japanese N classification from N3 to N1 and placed with numerically decreasing lymph node involvement. The mean age of the patients was 50.1 years (range 25–74 years) and the male to female ratio was 1.6:1. The depth of tumor invasion was predicted endoscopically to be T1 in 43 cases (mucosal layer in 28 and submucosal layer in 15) and T2 in two cases.
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All tumors except one (case No. 30) were of macroscopically depressed type (98%) and the majority were associated with intratumoral ulcer or ulcer scar (91%). Tumor infiltration of the intramucosal lymph capillaries was observed in four cases (9%). The tumor size ranged from 10 to 120 mm with a median of 35 mm. Histologically, 76% of the tumors were of undifferentiated type.
Four patients were given oral anti-cancer agents (5-fluorouracil syrup or FT207) as postoperative adjuvant chemotherapy for a period from 3 months to 2 years. The rest were observed without any adjuvant therapy.
According to the Japanese Classification, 30 patients (67%) had pN1 metastasis. All these cases were also classified as pN1 by the TNM system (less than seven positive nodes). In 13 patients (29%), metastasis was seen in Japanese N2 nodes (along the left gastric, common hepatic, splenic or celiac arteries). However, 12 of these had less than seven positive nodes and were therefore classified as pN1 by the TNM system.
Two cases (4%, cases 1 and 2 in Table 1) had metastasis in the para-aortic nodes (pN3 by the Japanese Classification and pM1 by the TNM system) and deserve special mention. Both patients were preoperatively diagnosed to have a T1 (submucosal) tumor and underwent D2 gastrectomy initially. In spite of the macroscopic diagnosis of N0, the histological examination revealed that a number of N2 nodes were metastatic whereas the primary tumor was confined to the mucosa. Reoperation was accepted by the patients and lymphadenectomy around the abdominal aorta was performed with curative intent. Case No. 1 was a 71-year-old woman with a large tumor (120 mm) and 38 of 92 dissected nodes were involved, including 13 para-aortic nodes. Additional stepwise sectioning of the primary tumor for further histological examination failed to show submucosal invasion of the tumor. She refused the suggestion of adjuvant chemotherapy and died of carcinomatous lymphangitis 21 months following surgery. Case No. 2 had 15 positive nodes including five para-aortic nodes. She did not undergo chemotherapy and is disease-free 36 months postoperatively. These two cases had no specific features to distinguish them from other node-positive patients.
The follow-up period ranged from 12 to 390 months with a median of 130 months. Among 10 patients who were deceased at the time of study, six had died without any sign of gastric cancer recurrence. Two patients died of recurrent disease: case No. 1 with carcinomatous lymphangitis 21 months postoperatively and case No.15 with ovarian metastasis and peritoneal disease 69 months postoperatively. In a further two patients, recurrent tumor could not be excluded: case No. 3 died of disseminated intravascular coagulation, raising the possibility of bone marrow infiltration, and case No. 23 died of acute renal failure of unknown cause. The time interval between surgery and death of (possible) recurrent disease ranged between 21 to 92 months and two of four died more than 5 years after surgery.
The overall 5- and 10-year survival rates were 93 and 82%, respectively. When the deaths from other causes were treated as censored cases, the 5- and 10-year survival rates were 95 and 89%, respectively.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The reported rates of lymph node metastasis from mucosal gastric carcinoma vary between 0 and 21% (10,11). In the Nationwide Registry of Gastric Carcinoma in Japan between 1984 and 1988, 323 (2.3%) of 13 628 patients with mucosal cancer had nodal metastasis (12). Our series includes the largest number of cases reported from a single institution and the rate was 2.5%. Lymph node involvement in mucosal gastric carcinoma may reflect special metastatic properties of the tumor. However, the prognosis of these patients has rarely been reported.
Risk factors for nodal metastasis from EGC have been extensively studied to identify tumors suitable for local treatments without lymphadenectomy such as endoscopic mucosal resection. Large tumor size, macroscopically depressed type, histologically undifferentiated type and intratumoral ulcer or ulcer scar are recognized as risk factors for nodal metastasis (4). One or more of these risk factors was present in each of our patients.
Nodal metastasis was confined to the perigastric area in 30 of the 45 patients, whereas in the other 15 patients the positive nodes were found outside this area (Japanese N2 and N3). Two cases (0.1%) had multiple para-aortic nodal metastases. These are exceptional cases and the prognosis has been reported to be poor (13–16). Using conventional pathological parameters, we were unable to identify any specific features characterizing the biological aggressiveness of these cases.
We previously reported a follow-up study of 1475 patients with EGC together with a review of the Japanese literature (2). Twenty patients (1.4%) had died of recurrent disease and lymph node metastasis was the most important prognostic factor. From this review of the Japanese literature, 10.7% of EGC patients with nodal metastasis had died of recurrence. In the current study, we focused on patients with node-positive mucosal gastric carcinoma and conducted a retrospective review after a median follow up of 11 years. Two patients had died from definite recurrent disease and two others had died with possible recurrence. When these four cases were regarded as recurrent death, the disease specific 5- and 10-year survival rates were 95 and 89%, respectively.
Adjuvant chemotherapy with oral anticancer agents was given in four patients, one of whom died of recurrent disease (case No.15). All other patients were treated with surgery alone. The role of adjuvant chemotherapy in this condition remains unknown.
This is a retrospective study of a rare disease condition collected over a period of 37 years, and even in a single institution a number of surgeons with various therapeutic strategies were involved. The diagnostic modalities and their accuracies have also varied considerably. From our results, therefore, we could not draw any evidence to suggest a therapeutic strategy for tumors predicted to be of mucosal invasion. It should be noted, however, that the majority (87%) of our cases were treated with D2 lymphadenectomy and the excellent clinical outcome might not have been achieved without this constant surgical policy.
In conclusion, lymph node metastasis was present in 2.5% of 1770 resected mucosal gastric carcinoma. Metastasis to the nodes outside the perigastric area was found in 15 patients (0.8%), of whom two had exceptionally extensive metastases. Although nodal involvement is the most important prognostic factor for EGC, the prognosis of patients with node-positive mucosal gastric carcinoma was excellent following gastrectomy and appropriate lymphadenectomy.
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FOOTNOTES |
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+ For reprints and all correspondence: Takeshi Sano, Gastric Surgery Division, National Cancer Center Hospital, 1–1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: tksano@ncc.go.jp
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REFERENCES |
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Received August 22, 2000; accepted January 11, 2001.
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