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Overall results after operations for gastric cancer in Japan are far superior to results obtained in the US and Europe. We have reviewed the Japanese literature in an effort to determine what factors explain this difference. It appears that the survival differences are due mainly to a greater frequency of early gastric cancer in Japan; meticulous histopathologic evaluation of the surgical specimens, resulting in more accurate pathologic staging; and the presumed benefit of extended nodal dissection when it extends outside of the level of node-positive disease. Although patients with both apparent and confirmed direct adjacent organ invasion can be helped by resection of those organs, extended resections of uninvolved pancreas and spleen do not improve rate of survival beyond the benefit of improved nodal dissection. Overall, there would appear to be justification for reexamining extended nodal dissection for gastric cancer in the US. Opportunities for a meaningful national study are significant.

During a period beginning in 1946 and ending in October of 1978, 1000 cases of solitary early gastric carcinoma were operated on at the Cancer Institute Hospital, Tokyo, Japan. The clinical characteristics and the macroscopic and chronological changes were studied in these cases. Early gastric carcinoma comprised one third of all resected gastric carcinoma. If early gastric carcinoma was divided into two groups, the depressed and the elevated, the former was more common. By location, the depressed type lesions were more frequently seen in the middle third of the stomach and the elevated type lesions in the lower third. By age, distribution of the elevated type lesions showed a peak with a mode at the age of 60 to 69 years and of the depressed type, a plateau with a mode at the age of 50 to 59 years. The relative incidence of the elevated type of gastric carcinoma to the depressed type was one to four. In depth of invasion, the mucosa and the submucosa were equally involved. Lymph node metastases were encountered in 12.7% of early gastric carcinoma cases. The incidence of positive nodes in mucosal carcinoma was 3.4% and that of submucosal lesions was 21.7%. Of the elevated type carcinoma, 20.9% of the cases had positive nodes. The 5-year survival rate of the patients with surgery for cure was 93.8% in contrast to 56.5% of those with palliative resection.

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The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.

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D2 lymphadenectomy in patients with early GC had little survival benefit because (1) metastasis to level 2 nodes was rare, (2) most causes of death were not related to the tumor, and (3) more than half the recurrences were hematogenous. Use of radical lymphadenectomy for early GC should be limited.