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A 67-year-old woman with debilitation and massive ascites was admitted to our hospital and diagnosed with stage IV scirrhous gastric cancer with peritoneal dissemination. After successful nasojejunal tube feeding because of oral intake disability, TS-1 combined with paclitaxel chemotherapy was selected. TS-1 at 80mg/m2 was given daily via nasojejunal tube for 2 weeks, followed by a 1-week rest, and paclitaxel at 50mg/m2 was administered intravenously on day 1 and 8. There were no serious side effects. After 4 cycles, a partial response was observed and percutaneous transesophageal gastro-tubing (PTEG) was placed. After the fifth cycle, she was transferred to her home and received chemotherapy in an outpatient clinic. After 7 cycles, the disease progressed, and TS-1 combined with low-dose cisplatin was administered for 3 cycles. However, the patient died 16 weeks after discharge. PTEG was useful not only for a route of TS-1 administration, but also for receiving chemotherapy at home to maintain her quality.

With the purpose to prevent the dissemination and consequent metastasis of cancer cells at the time of operation we gave 10 mg of Mitomycin C per day for four consecutive days prior to surgical operation of gastric cancer (total of 322 patients), and this so-called adjuvant chemotherapy proved to be effective on the cases with serosal involvement and infiltrating type of cancer, irrespective of histological types. It also gave five-year survival rate of 35 per cent. However, to lymph nodes already metastasized, the adjuvant chemotherapy proved to be not effective.

1. Mitochondria isolated from human liver, hepatoma and gastric cancer contain DNA. The DNA content per mitochondrial protein is about ten times as much in cancer as in normal liver. 2. Human liver, hepatoma and gastric cancer contain circular DNA molecules in their mitochondria. Circular DNAs from normal liver and cancer mitochondria are mostly about 5 μ long, and the frequency of circular DNAs of multiple or shorter length is higher in cancer mitochondrial DNA. The outline of the present paper was presented at the 26th Congress of Japanese Cancer Association (1967) (52, 53).

We studied the effects of a splenectomy in combination with immunotherapy on the survival of patients who had undergone a total gastrectomy. It was found that a splenectomy was not effective against advanced gastric cancer at stage III, and that the spleen should be retained for immunotherapy. Splenectomy for gastric cancer at terminal stage IV, particularly in combination with immunotherapy, produced not only augmentation of cellular immunity, but also increased survival.

Some cases of early gastric cancer are accompanied with complications of the upper gastro-intestinal tract. The characteristics of these complications were investigated, and the problems of diagnosis and treatment were discussed. Out of 297 cases of early gastric cancer, 18 cases were accompanied with complications of the upper gastro-intestinal tract, including 11 cases of bleeding, a case of perforation and 6 cases of pyloric stenosis. All 18 cases were of the macroscopically depressed type, and about 85 percent of the 297 early gastric cancer cases were of the depressed type. The depressed lesions were often accompanied by ulceration which was an important factor causing the complications, and the mechanism of which appeared to be the same as that of a benign ulcer. There are some cases of early gastric cancer which are discovered by their complications, and it would be more difficult to find an early gastric cancer lesion if there were a benign lesion at the same time. Therefore, it is necessary to take much care when diagnosing and treating cases which have such complications. An endoscopic examination before the operation is especially important, and a biopsy is indispensable.

Levamisole (LMS) was given to stage III gastric cancer patients starting three days before gastrectomy, at a does of 150 mg/day for three consecutive days every other week. Survival rates of these patients were compared with those of stage III gastric cancer patients previously operated in our Department who had not received levamisole. The background factors of both groups were matched as closely as possible. Both groups were concomitantly treated with mitomycin C and FT-207. The survival rate of the LMS group was significantly higher than that of the control group when the tumor had a diameter of 4.0-8.0 cm, cancer cells infiltrated to the gastric serosa, there were metastases within the regional lymph nodes, cancer cells slightly invaded the venous capillaren and there was moderate infiltration of the stroma.

1. An attempt has been made to find the diagnostic criteria for early gastric cancer. It is most important to detect the evidences or suspected features of the malignant growth in incipient stage in order to attain the radical cure by surgical operation. 2. Twelve patients with early gastric cancer (groups A and B) were selected out of 476 patients who had undergone gastrectomy during the past three years in the Okayama Saiseikai General Hospital. The other 6 patients in the "precancerous group" (group C) were also studied, who had abnormal epithelial proliferation in the resected stomach membrane during the same period. 3. The processes of discovery of early cancer have been described. Fairly precise diagnosis can be made in the mucosal carcinoma, but it is not in the ulcer-carcinoma. It was generally difficult to estimate the degree of the malignancy and the extension of the growth preoperatively. 4. The details of the diagnostic aids are as follows. i. Negative occult blood of stool does not always mean the definite diagnostic aid. ii. The malignant gastric change may occur even in non-anacidity. Further investigations should be followed up on gastric ulcer patients if malignant alteration is under the consideration. iii. Minor roentgenological findings, such as the absence or irregularity of mucosal folds, rigid and/or overlapped contour, localized absence or decrease of the peristaltic waves and absence or bow-shaped deformity of the angulus, are of important significance. Such changes should be minutely sought for by X-ray film examination. iv. On gastroscopy and gastrocamera photography, such changes as erosion or irregular granular thickening of the membrane with abnormal reddening and edematous appearance, irregularity of ulcer edge, uneven swelling on ulcer margin with reddening and unsharpness of the edge of adherent coat on ulcer floor, must be noted in the early gastric cancer. v. It is not safe to leave a patient having stomach ulceration under a mere conservative management because it is often quite difficult to dissolve the question of malignancy of the lesion with all sorts of examinations. vi. So far as clinical examinations have indicated malignancy, histological examination must be carried out immediately at the time of operation, even when malignant lesion is absent in inspection and palpation on the exposure of the stomach. vii. On the gross observation of the resected stomach, a particular attention must be paid to erosion, depression or atrophy, irregular granular thickening and abnormal reddening on the restricted areas of the mucosal surface.

Previous in vitro and animal experiments have shown that sulforaphane, which is abundant in broccoli, inhibits Helicobacter pylori (H. pylori) infection and blocks gastric tumor formation. This suggests that broccoli consumption prevents chronic atrophic gastritis (CAG) introduced by H. pylori infection and, therefore, gastric cancer. For an epidemiological investigation of the relationship between the broccoli consumption and CAG, a cross-sectional study of 438 male employees, aged 39 to 60 years, of a Japanese steel company was conducted. CAG was serologically determined with serum cut-off values set at pepsinogen I < or = 70 ng/ml and a ratio of serum pepsinogen I/pepsinogen II < or = 3.0. Broccoli consumption (weekly frequency) and diet were monitored by using a 31-item food frequency questionnaire. The prevalence of CAG among men who ate broccoli once or more weekly was twice as high as that among men who consumed a negligible amount (P < 0.05). Multiple logistic regression analysis indicated that broccoli consumption once or more weekly significantly increased the risk for CAG (odds ratio, 3.06; 95% confidence interval, 1.12-8.38; P < 0.05), after controlling for age, education, cigarette smoking, and alcohol consumption. The present study failed to show an expected association between frequent broccoli consumption and a low prevalence of CAG.

We report 2 cases of small cell carcinoma (SmCC) of the stomach with distant metastasis that were treated with the same chemotherapeutic regimens as used to treat small cell lung cancer. Although the mean survival of patients with SmCC of the stomach is reported to be only 7 months, our patients survived for 15 and 14 months, respectively. In our experience, these chemotherapeutic regimens might provide a survival benefit for patients with SmCC of the stomach, although they demonstrated no remarkable antitumor effects.

To determine whether a relationship exists between DNA ploidy and the prognosis of hepatocellular carcinoma (HCC), flow cytometric DNA analysis was performed in paraffin-embedded specimens obtained from 44 patients with HCC who underwent hepatectomy. There were 26 diploid (59%) and 18 aneuploid (41%) tumors. No correlation was shown between DNA ploidy pattern and patient age, sex, liver cirrhosis, hepatitis B virus antigen and serum alpha-fetoprotein level. The ploidy pattern had no significant correlation with the presence of vascular invasion or intrahepatic metastasis. Only Edmondson's grade was well correlated with the ploidy pattern. We noted a significant correlation between survival rates and the presence of vascular invasion or intrahepatic metastasis (p < 0.05). In contrast, no significant correlation was found between DNA ploidy pattern and the prognosis of HCC. The results of this study indicate that DNA ploidy pattern may not be a useful indicator for the prognosis of HCCs after hepatic resection, unlike the results of gastric and colon cancers.

A cell line (HGC-27) was established by culture of the metastatic lymph node from a gastric cancer patient diagnosed histologically as undifferentiated carcinoma. HGC-27 cells were polygonal or short spindle-shaped and adhered to glass surfaces as a monolayer. The cells were probably derived from gastric cancer cells, as their origin from mesenchymal tissues can be excluded morphologically and enzyme-histochemically. Enzyme activities were generally negative or low, except for adenosine triphosphatase, lactic dehydrogenase and leucine aminopeptidase. These scanty findings might reflect the undifferentiated character of the original tumor cells. The cloning efficiency was 5.3% in liquid medium and 1.0% in soft agar. The doubling time was about 17 hr. Chromosomal analysis revealed a mode of 109 and 110 chromosomes.

1. The properdin levels in sera from mice bearing Ehrlich ascitic carcinoma and from rabbits with Brown-Pearce carcinoma decrease inversely with the increase of the ascites or the tumors. In the incipient period of tumor transplantation, the level rather rises. When the tumor is proliferating or large, the level keeps falling or is low. On the contrary, when the tumor is regressing or disappears, the level elevates or reverts to that before transplantation. Strong A and R III mice with spontaneous mammary cancer have markedly low serum properdin levels as compared with those of healthy mice. 2. The properdin levels are less than 2 units per milliliter of the serum in 44.4 per cent of patients with gastric cancer, in 18.2 per cent of ones with non-malignant tumor and in 18.2 per cent of ones with gastric or duodenal ulcer. The abnormal low level has been found in 33.3 per cent of patients without recurrence, who had undergone extended radical gastrectomy combined with radical lymphadenectomy for gastric cancer. 3. Some correlation can be seen between the serum properdin levels and the degree of progress of gastric cancer. 4. The cancer patients with low total serum protein have lower serum properdin levels than those having nomal protein. 5. As for influence of surgical operation on the serum properdin levels, there is observed a tendency that a minor operation causes the levels to increase and a major operation causes the levels to fall. 6. It has been inferred that the properdin system could be one of the host natural resistance against cancer.

Helicobacter pylori (H. pylori) infection in the stomach is etiologically closely associated with chronic active gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. In this study, we examined the antibody responses and cytokine profiles of three strains of mice (BALB/c, C3H/He, and C57BL/6) infected with H. pylori. Following this, correlations between host-immune reactions and intensity of inflammation were analyzed. H. pylori (ATCC43504) was intragastrically administered once a week to the mice from 4 weeks of age, and they were sacrificed at the ages of 4 and 7 months. In these mice, we examined the histology of the stomach, antibody titers against H. pylori, and serum levels of cytokines (IL-4, IL-10, TNF-alpha, IL-2 and Interferon-gamma). In BALB/c mice, inflammation of the stomach was minimal. Inflammation was observed in 63.6% of C57BL/6 mice and 33.3% of C3h/He mice. In C57BL/6 and C3H/He mice, all the cytokines tended to increase. In contrast, BALB/c mice were inactive in cytokine production except for IL-2. Two C3H/He mice developed severe inflammation with lymph follicles; one showed a response largely typical of Th-1, and the other showed a response largely typical of Th-2. Although a definite correlation was not shown between Th-1/Th-2 response evaluated by cytokine production and intensity of inflammation, it appears that in H. pylori-induced inflammation both cell-mediated (Th-1) and humoral (Th-2) immunity play a role in pathogenesis.

Thomsen-Friedenreich antigen (T antigen) has been supposed to be a cancer-specific carbohydrate antigen. We have previously shown that one third of the Japanese population normally expressed T antigen in gastric surface epithelia and the other two thirds expressed fucosyl-T antigen. Their sialylation and blocked-synthesis were associated with diseased conditions. In the present study, we studied gastric surface epithelial expression of monosaccharide antigen Tn, i.e., a precursor of T antigen, and sialyl-Tn. Normal fundic and pyloric epithelia, respectively, expressed Tn supranucleally and cytoplasmically, but did not express sialyl-Tn. In the intestinal metaplasias and intestinal-type adenomas, goblet cells expressed sialyl-Tn in their vacuoles, and absorptive cells expressed Tn apically. In gastric-type adenomas, Tn, but not sialyl-Tn, was detected. Intestinal-type cancers expressed Tn and sialyl-Tn more often than the diffuse-type cancers. Five cancers did not express Tn, sialyl-Tn, or the T-related antigens. In these, four were diffuse-type cancers. We concluded that: a) normal gastric epithelial cells express Tn; b) metaplastic differentiation is associated with sialylation of Tn and c) expression of Tn and sialyl-Tn is depressed in the gastric cancers.

Cytotoxic lymphocytes, including natural killer cells, lymphokine-activated killer cells, and cytotoxic T lymphocytes, adhere to and lyse cancer cells by recognizing cell surface antigens. Among the cell surface antigens, intercellular adhesion molecule-1 (ICAM-1) and HLA class I antigen are important for the cytotoxic activity of lymphocytes. The ICAM-1 and HLA class I antigen were examined in gastric cancer cell lines MKN-28 and MKN-45 by flow cytometry to determine whether their expression on the cell surface is enhanced by interferon gamma (IFN-gamma). The cell expression rate [stained cells/10(4) cells x 100(%)] was only 10% in ICAM-1 and about 20% in HLA class I antigen without IFN-gamma, but reached 70% in ICAM-1 and up to 60% in HLA class I antigen after incubation with IFN-gamma for 24-96 h. This enhanced expression of cell surface ICAM-1 and HLA class I antigen by IFN-gamma might increase sensitivity for cytotoxic lymphocytes.

Ninety-nine gastric cancer patients initially received levamisole at a daily dose of 150 mg for three consecutive days before operation. This therapy was repeated fortnightly (3-day administration followed by 11-day withdrawal period) for more than one month as long as possible and the survival rate up to 18 months was compared with thas of control patients. The 18 month survival rate of advanced Stage IV patients was significantly higher in patients receiving levamisole than that of control patients. The effects of levamisole in cases of advanced cancer have been discussed in relation to the literature available.

In order to improve the postoperative prognosis of gastric cancer patients we have performed preoperative endoscopic intratumoral administration of various biological response modifiers. In the present study we have investigated the kinetics and the immune response augmenting effect of intratumorally injected PSK, a protein-bound polysaccharide preparation, by immunohistochemical methods using anti-PSK antibody and various other antibodies. PSK-containing cells were located in the tumor tissues and follicular marginal zones of regional lymph nodes. Intratumorally administered PSK appeared to be phagocytized by the histiocytes and to cause them to become antigen-presenting cells. These cells may play a major role in augmenting immune responses in gastric cancer patients.

The present study was conducted to investigate the usefulness of the direct leucocyte migration agarose method for studying cell-mediated immunity in vitro. Comparative studies of the purified protein derivative (PPD) skin test and the leucocyte migration inhibition test (LMIT) in which PPD was used as test antigen indicated a significant qualitative and a weak quantitative correlation between these two tests. Furthermore a positive correlation was found between the LMIT and the macrophage migration inhibition test (MIT) using ultrasonicated authochthonous tumor antigen. Comparative studies of the LMIT, MIT, PPD skin and DNCB tests on the same patients showed that cases responding positively to the the PPD skin and DNCB tests tended to respond positively to the LMIT and MIT. Patients with digestive organ cancers were examined by the LMIT. With the advance of cancer, decreased positive test test rates were found. After gastric cancer operations the LMIT findings were divided into two groups: one type changed from positive to negative, and the other type changed from negative to positive. The former response was suggestive of a successful operation, and the latter response was suggestive of a non-curative operation. These results indicated that the direct leucocyte migration inhibition agarose test was useful investigating cell-mediated immunity.