Ryunosuke Kumashiro

Late results of postoperative long term cancer chemotherapy for advanced carcinoma of the stomach

Postoperative long term cancer chemotherapy (PLCC) with the combination of Mitomycin-C, FT-207*, a furanyl analog of 5-fluorouracil, and PSK**, an immunopotentiator, was prescribed for patients with advanced gastric cancer. Five year survival rates for all stage III and stage IV patients were 52.8 and 19.3 per cent in the PLCC group. The rates were 26.7 and 2.2 per cent in the control groups (p<0.05). In curative cases of stage IV, the 5-year survival rate was 50.0% in the PLCC group while the rate was 11.1% in the controls. Mean survival time of patients with peritoneal dissemination or hepatic metastases was 12.8 and 10.9 months, respectively, for the PLCC group, in contrast to the lower 6.4 and 4.3 months for the controls. Thus, the 5-year survival rate of advanced gastric cancer patients in stage III and stage IV was markedly improved when these patients were treated with the protocol. Our findings clearly show that adjuvant chemotherapy should be administered for a long period postoperatively in order to achieve a significant improvement in patients with gastric cancer.

Gastric carcinoma with lymphoid stroma: Correlation to reactive hyperplasia in regional lymph nodes and prognosis

The pathological changes of regional lymph nodes in cases of gastric carcinomas with lymphoid stroma (LS group) and the prognostic significance of the findings were studied in comparison with those in cases of ordinary stroma (OS group). The purpose of this study was to elucidate the immune responses of regional lymph nodes, histologically, in patients with gastric carcinoma and lymphoid stroma. In the LS group, the incidence of paracortical hyperplasia (PH) was high, irrespective of lymph node metastasis, while that of germinal center hyperplasia (GH) was high in the absence of lymph node metastasis but tended to be low in the presence of metastasis. In the OS group, the incidences of PH and GH were low, particularly in the presence of lymph node metastasis. The five year survival rate in those with no lymph node metastasis was as favorable as that of patients with lymph node metastasis in the LS group, the latter being significantly higher than the rate in the OS group. These results indicate that gastric carcinomas with lymphoid stroma are closely related to reactive hyperplasias of the regional lymph nodes, particularly paracortical hyperplasia, and in such cases, there is a favorable prognosis, regardless of the lymph node metastasis.

Combined effect of prophylactic lymphadenectomy and long term combination chemotherapy for curatively resected carcinoma of the stomach

Effectiveness of prophylactic extensive lymph node dissection (PELD) plus postoperative long term combination chemotherapy (PLCC) for patients with curatively resected gastric carcinoma was assessed in terms of the degree of serosal invasion and lymph node metastasis. Either the Group 1 and Group 2 lymphnodes were eradicated by PELD. PLCC included intermittent intravenous administration of mitomycin C (0.4 mg/kg intraoperatively followed by 0.2 mg/kg every 3 months) and oral administration of Tegafur (600–800 mg/day) and PSK (3.0 g/day), an immunostimulator, for as long a period as possible. PELD alone resulted in a cure when the malignancy was confined to the mucosal and muscular layers of the stomach as well as to the Group 1 lymph nodes. In cases when the carcinoma involved the serosa and/or the Group 2 lymph nodes, the 5 year survival rate was about 55 per cent the PELD and PLCC groups, such being significantly higher than about 27 per cent in the PELD alone group. Therefore, PELD plus PLCC is highly effective for advanced gastric carcinoma, under a condition of curative resection.

Thrombolytic therapy of synthetic graftocclusions before vascular reconstructive procedures

The objective of this study was to evaluate the impact of thrombolysis of synthetic grafts before urgent vascular reconstruction. In 29 patients, 41 thrombosed synthetic grafts that underwent intraarterial thrombolysis were studied. The cases were divided into three groups: group I--complete thrombolysis followed by reconstruction; group II--complete thrombolysis alone; and group III--incomplete lysis requiring reconstruction or sympathectomy. Follow-up ranged from 1 to 556 days (mean: 149 days). Kaplan-Meier analysis was used to determine patency and limb salvage rates. One-year patency and limb salvage rates were 53% and 95%, 34% and 67%, and 38% and 48%, respectively, for groups I, II, and III. Eighteen complications occurred in 16 of the 41 (39%) episodes. One patient died of intracranial hemorrhage. The best results were achieved when complete lysis was followed by appropriate reconstruction. Patency was equally poor in complete thrombolysis alone and reconstructions required by incomplete thrombolysis. Limb salvage was better after complete thrombolysis, regardless of the appropriate reconstruction.

Late results of postoperative long-term cancer chemotherapy for the gastric cancer patients subjected to curative resection

Postoperative long-term cancer chemotherapy (PLCC) with a combination of Mitomycin-C (MMC), FT-207 and PSK (an immunostimulant) was prescribed for gastric cancer patients subjected to curative resection. The 5 year survival rates for patients with stage III and stage IV cancer were 58.3 per cent and 50.0 per cent in the PLCC groups, 48.0 per cent and 15.4 per cent in MMC groups, and 46.3 per cent and 13.3 per cent in no chemotherapy groups, respectively. In stage IV, the survival rate in PLCC group was significantly higher than that in MMC or no chemotherapy group (p<0.05). In the PLCC group, there was a tendency toward a dose-dependent effect in each group, and 5 year survival rate of stage III group administered over 60 mg of MMC, 60 g of FT-207 and 270 g of PSK was 70 per cent, such being remarkably higher than 46.3 per cent in those given no chemotherapy (p<0.07). There was no drug related death and only a slight leukopenia and hepatotoxicity occurred in some patients.

Postoperative long-term cancer chemotherapy (PLCC) extends life-span of non-curatively resected patients with stage IV gastric cancer

Postoperative long-term cancer chemotherapy (PLCC) with a combination of Mitomycin-C, Tegafur and PSK (an immunostimulant) was applied to non-curatively resected cases with stage IV gastric cancer (invading the adjacent organs and/or with metastasis to the liver, peritoneum, and/or distant lymph nodes). This approach has a significant life-prolongation effect. The two-year survival rate was 16.8 per cent in the PLCC group, such being higher than 6.7 per cent and 1.7 per cent in MMC and no chemotherapy groups (p<0.05). 50 per cent survival periods in those with liver metastasis were 8.3 months in the PLCC group, such being longer than 5.2 and 2.8 months in MMC and no chemotherapy groups (p<0.002) respectively. Combination therapy of PLCC and intra-arterial infusion of 5-FU through the proper hepatic artery prescribed for 8 patients with liver metastasis resulted in a 3-month prolongation of 50 per cent survival periods, compared with PLCC alone (p<0.05). In those with peritoneal dissemination the rate was 10.5 months in the PLCC group, that is longer than 6.5 months in the MMC group (p<0.02). In cases of invasion to other organs plus distant lymph node metastasis, the time was 11.0 in PLCC and 7.0 months in MMC groups (p<0.05). Thus, PLCC is a palliative approach for non-curatively resected carcinoma of the stomach.

Serial determinations of carcinoembryonic antigen for early detection of recurrent gastric cancer

In attempts to predict the recurrence of gastric cancer, postoperative changes in serum carcinoembryonic antigen (CEA) levels are monitored in our clinic by radioimmunoassay (Dainabot, Japan). Recurrences are suspected when serum CEA levels are 4 ng/ml, in the postoperative period. Out of 34 patients in whom there were increases in serum CEA, 18 were confirmed to have a recurrence and 15 of these 18 patients were assessed accurately by serial postoperative levels of CEA, two patients died of a recurrence after elevation of serum CEA levels. Thus, recurrence was predicted in 17 out of 34 patients (50 per cent) and in 12 out of 17 patients there was a metastasis to the liver. In 14 out of 34 patients there are no signs of recurrence 9 to 25 months after serum CEA elevations.

Hormone conditioned cancer chemotherapy for recurrent breast cancer prolongs survival

Left suprarenal-inferior mesenteric venous shunt (Inokuchi) was prescribed for 80 patients with recurrent breast cancer and the efficacy of hormone coditioned cancer chemotherapy was assessed. The patients were separated into 3 groups according to the historical regimen of combined chemotherapy: Group I; surgical hormone therapy alone, Group II; surgery plus short term chemotherapy, and Group III; surgery plus long term chemotherapy. The 5 year survival rate of the responsive patients to the surgical hormone therapy was as high as 84.6 per cent in Group III, as compared to that of Groups I and II, 41.7 per cent and 16.7, respectively. Survival was not prolonged in non-responsive patients, regardless of the group. These findings indicate that surgical hormone therapy combined with postoperative long term cancer chemotherapy is a valid and effective method for treating recurrence of breast cancer.

Bidirectional effects of splenectomy on the growth of syngeneic tumor in mice.

The effects of splenectomy on tumor growth following inoculation with a relatively large number of cells (1×107) and a smaller number of cells (5×105) of Meth I tumor were studied. When 1×107 tumor cells were inoculated, tumor growth in splenectomized mice was depressed, while tumor in sham-operated mice grew progressively. On the contrary, when 5×105 tumor cells were inoculated, the tumor take was lower in sham-operated than in splenectomized mice. The spleen cells from mice inoculated with either a large or small number of tumor cells, showed an equally potent cytotoxic activity, but no detectable suppressor cell activity. On the other hand, the activity of immunosuppressive factor was detected in sera from mice inoculated with 1×107 tumor cells, but not in those given 5×105 cells. The effect of splenectomy on tumor growth is, thus, bidirectional, depending on the dose of tumor cells inoculated.

Deficient superoxide-generating activity and its activation of blood monocytes in cancer patients

Superoxide (O2-)-generating activity of blood monocytes, the precursors of macrophages, from patients with advanced cancer and/or infection was studied. Monocytes from normal subjects generated 0.288 +/- 0.022 nmol O2-/min/10(5) cells (mean +/- S.E.M., n = 36) after sequential stimulation with cytochalasin E and wheat germ agglutinin. Monocytes from 69 non-infected adult patients with advanced malignancy of the stomach, esophagus and liver, and 7 pediatric patients with neoplastic disease released significantly less O2- than those from normal subjects (0.176 +/- 0.015, P less than 0.005). Infection increased the activity about 4-fold in patients with malignancy compared to non-infected cancer patients. These results suggest that monocytes of cancer patients are defective in secreting O2-, though the activity may be stimulated by infection.