Masakazu Sakita

Conservative surgery for regional lymphadenectomy in the treatment of early gastric carcinoma

The relationship between lymph node metastases and postoperative prognosis in 209 patients with early gastric cancer was studied. As to the postoperative prognosis in relation to the extent of lymph nodes dissection, no significant difference was observed among the age-corrected 5-year survival rates following three surgical procedures in patients with early gastric cancer. Age-corrected 5-year survival rates were 0.92±0.44 R1-resection, 0.95±0.44 in R2-resection, and 1.00±0.06 in R3-resection, respectively. In addition, in 71 patients including 33 with early gastric cancer and 38 patients with advanced but relative early gastric carcinoma, the relationship between the immunostatus and postoperative prognosis was investigated. Postoperative age-corrected 5-year survival rate (0.904±1.153) of the optimal responders with good immunostatus was significantly higher than that (0.582±1.153) of the suboptimal responders with impaired immunostatus (P<0.01). Thus, conservative surgery for regional lymphadenectomy may be an effective procedure for cure of early gastric carcinoma, particularly in cases of a carcinoma limited to the mucosal area of the stomach.

Immunosuppressive activity of sera from gastric cancer patients

Sera from 60 gastric cancer patients and 20 patients with benign gastric diseases and 8 healthy controls were tested for inhibitory effects on the humoral response to sheep erythrocytes (SRBC) by the plaque forming cell assay (PFC R.I.) using mouse spleen cells and on the phytohemagglutinin (PHA)-induced blastogenesis of normal mouse spleen cells (PHA S.R.). Gastric cancer patient sera showed a significantly lower PFC R.I. than did sera from benign gastric disease patients and from the healthy controls. However, there was no appreciable interstage difference in the degree of depression. The PHA-induced blastogenesis of normal spleen cells was also decreased in the presence of sera from cancer patients, as compared to that in the presence of sera from benign disease patients and from the healthy controls. The depression progressed with advancing stage of cancer. The PHA S.R. showed significant negative correlations with serum levels of IAP, IS, α1-acid glycoprotein and α1-antitrypsin, but there were no such correlations between PFC R.I. and these glycoproteins in serum. There was also no correlation between the values of the PHA S.R. and the PFC R.I. These results suggest that these two assays may depict immunosuppressive activities operating through entirely different mechanisms.

Immunomorphologic study of regional lymph nodes in cancer: Response of regional lymph node cells from gastric and colorectal cancer to PHA stimulation

To obtain information regarding the immunologic capacity of uninvolved regional lymph nodes (RLNs) draining tumor, the in vitro response of regional lymph node cells (RLNCs) to PHA was investigated in lymph nodes from 55 patients with gastric or colorectal cancer, and gastric ulcer. Evaluation of data relative to cancer progress demonstrated that, in gastric cancer patients, the response of stimulated RLNCs from patients with middle stage carcinoma was significantly higher compared with those of cells from patients with early or late stage carcinoma, such being similar to the response of RLNCs from control patients with gastric ulcer. The results from colorectal cancer patients were also similar to those from patients with gastric cancer. Our results suggest that RLNs without metastasis contain cells capable of responding to PHA despite the presence of growing tumors in these cancer patients. In the results of PHA stimulation in relation to the lymph node morphology, we observed in both groups of patients with gastric or colorectal cancer that, regardless of the extent of the cancer lymph nodes with lymphocyte predominance there was a high PHA response while lymph nodes with lymphocyte depletion and unstimulated nodes exhibited a low PHA response. These results show a close relationship between this lymph node morphology and immunologic status of nodes.

Monocyte count, monocyte chemotaxis and chemotactic factor inactivator in gastric cancer patients

The monocyte count in the peripheral blood, chemotactic responsiveness (MCR) and chemotactic factor inactivator (CFI) were measured in 66 patients with gastric cancer. Monocyte counts in advanced gastric cancer patients were significantly increased. MCR was significantly depressed in gastric cancer patients in the advanced stage of the disease, as compared with findings in the control groups. Sixty-seven percent of the patients with stage IV carcinoma had abnormally depressed responses. The CFIs were significantly higher in gastric cancer patients than in the control groups, and there was a positive correlation between the degree of inhibition and extent of cancer progress. These data support the hypothesis that qualitative and quantitative abnormalities of circulating monocytes, as macrophage precursors, may hinder immunological host defense mechanisms.

Comparative Studies between Liposomes Containing Muramyl Dipeptide and Various Immunomodulators on Activation of Mouse Peritoneal Macrophages and NK Cells

We compared the effects among muramyl dipeptide (MDP), liposome-encapsulated MDP (liposome MDP), bacillus Calmette-Guérin (BCG) and OK-432 on cytotoxic activity of mouse peritoneal macrophages (PM) and natural killer (NK) cells in vitro and in vivo, and their tumor-inhibitory effects against MH134 ascitic tumors in C3H/He mice. The cytotoxicity of PM induced by free MDP was lower than that induced by BCG, but a significantly higher cytotoxicity was induced by liposomes containing MDP and OK-432. The peritoneal NK cells were not activated by MDP, liposome MDP or BCG, but OK-432 profoundly augmented peritoneal NK activity. Growth inhibition of ascitic tumor was not observed in free MDP and BCG intraperitoneally treated mice, but moderate growth inhibition was noted in liposome-MDP-treated mice; and in OK-432-treated mice, marked tumor growth inhibition and prolongation of survival time were observed. These results suggested that OK-432 is more advantageous in controlling malignant tumor growth in vivo than free MDP, liposome MDP or BCG because of its ability to activate both macrophages and NK cells.

Eradication of microscopic metastases with intratumoral injection of Bacillus Calmette-Guerin

The studies reported here were designed to examine the effects of intratumoral preoperative administration of Bacillus Calmette-Guerin (BCG) on the cure rates of C3H mice transplanted with MH134 tumor cells and on the metastatic rates in the regional lymph nodes. Furthermore, the morphological findings occurring in the regional lymph nodes were monitored during tumor growth using H-E stain and non-specific esterase staining. The cure rate of the Group treated with BCG intratumoral injection and surgery was significantly higher than that of the Group treated with surgery alone, and in the BCG+ surgery group metastatic rates of regional lymph nodes decreased consistently after operation. Moreover, in this group, extensive sinus histiocytosis and marked swelling of the regional nodes were frequently observed. Quantitative studies of the cell kinds using the esterase staining indicated that intratumoral injection of BCG has an effect on the influx of lymphoid cells into the regional nodes, but does not aid specific cell lineage to flow into the regional nodes. In cytostatic assays, it was shown that the regional lymph node cells and spleen cells in the BCG + surgery group always have a greater per cent of inhibition than those in the surgery alone group.

Pathological study for the acute toxicity of cisplatin microcrystals suspended in oil by intraperitoneal administration in mice.

Pathological changes were compared between two dosage formulations of cisplatin microcrystals suspended in oil (CDDP-Oil), and cisplatin aqueous solution(CDDP-Sol), by intraperitoneal administration in mice. Main toxic findings such as decreasement of the organ weights and histopathological degenerations were seen in the kidney, liver, and hematologic tissues of the spleen, lymph nodes and bonemarrow. Those changes were more heavy in mice died by the toxicity than in mice surviving during the observation period. Thus, the toxic changes were principally similar in the two dosage formulations, and there were no aditional toxic effects in the CDDP-Oil.