Ryuichiro Tamada

Langerhans cells and prognosis in patients with gastric carcinoma

Infitration of Langerhans cells (LC) and macrophages into tumor tissues was investigated using immunohistochemical methods, anti‐S‐100 protein and anti‐lysozyme antibodies in 174 cases of gastric carcinoma. Varying population densities of S‐100‐positive LC were noted in tumor tissues; lysozyme‐positive macrophages, however, were found in almost equal quantities. LC were mainly interspersed among the tumor cells, whereas macrophages were present in the stroma and around the necrotic foci. Although the survival time of patients with Stage I, II or IV gastric carcinoma did not relate to the density of LC, survival time in Stage III patients correlated well with the density of LC. In patients with a marked infiltration of LC, survival time was longer than in cases of only a slight infiltration (P < 0.001). Therefore, LC in immunological defense mechanisms of the host against the tumor may be clinically effective in a certain phase of tumor development.

The ATP assay is more sensitive than the succinate dehydrogenase inhibition test for predicting cell viability

The succinate dehydrogenase inhibition (SDI) test and the adenosine triphosphate (ATP) assay, are both used for in vitro human tumor chemosensitivity testing. We exposed HeLa cells to various concentrations of mitomycin C for 1, 2 or 3 days and found that the decrease in number of viable cells correlated with that of succinate dehydrogenase (EC 1.3.99.1) activity and that of intracellular ATP level of the viable cells. In the dead cells, the ATP level was extensively decreased, but the succinate dehydrogenase activity remained at a level of 24% of that of mitomycin C-untreated viable cells, even on day 3. Thus, the ATP level better reflected the cell viability. In clinical situations, the succinate dehydrogenase activity and the ATP level are assayed in whole cells following exposure to anticancer drugs, therefore the activity remaining in the dead cells must be taken into consideration for the chemosensitive prediction with the SDI test, but not with the ATP assay. This higher sensitivity of the ATP assay will enable a more accurate prediction of cell viability.

Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years.

In order to evaluate the combination of immunochemotherapy with mitomycin C (MMC), futraful (FT) and PSK, as an adjuvant to surgery for curatively resected gastric cancer, a randomized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan. The MMC+FT+ PSK group showed a significant increase in 5 year survival from the other groups (p<0.05). Moreover the survival rate was significantly higher in the MMC+FT+PSK group than in the MMC+FT group (p<0.01). According to the analysis on stratification, the MMC+FT+PSK group showed the best survival rate in cases with positive lymph node metastases, positive serosal invasion and positive lymph node metastases plus serosal invasion, and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction (p<0.01 or p<0.05). Thus, the combination of MMC, FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer submitted to curative resection.

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.

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.

Lymphangioma of the esophagus presenting symptoms of achalasia —A case report

A case of lymphangioma of the esophagus with symptoms of achalasia was presented. Compressible and folded intramural tumors were found from the middle to the lower part of the esophagus and the Mecholyl test was positive. After incisional biopsy at lower esophagus through full thickness of the wall, the opening was repaired with Thal-Hatafuku’s fundic patch procedures to relieve achalasia. Postoperative course was uneventful and symptoms of achalasia completely disappeared.

Mitomycin C plus carmofur (HCFU) adjuvant chemotherapy for noncuratively resected cases of colorectal carcinoma (interim report).

In order to examine the efficacy of adjuvant chemotherapy employing Mitomycin C (MMC) and carmofur (HCFU) for patients with noncuratively resected colorectal carcinoma, a cooperative study was performed by 54 institutions in the Kyushu and Chugoku areas in Japan. The prospective randomized controlled study consisted of two groups, one receiving only MMC and the other receiving MMC as well as HCFU. Out of an original total of 200, 170 cases were evaluable. Concerning the 30-month survival rate, a better result was observed in the MMC+HCFU group than in the MMC only group (Z-test: p<0.05). Significantly better survival rates were obtained in those cases with disseminating peritoneal metastasis, hepatic metastasis and Stage V cancer in the MMC+HCFU group as when compared with the MMC only group (generalized Wilcoxon test: p<0.05). No significant side effects due to the combined administration of HCFU were recognized. The combined administration of MMC and HCFU were recognized. The combined administration of MMC and HCFU was suggested to be a safe and effective adjuvant chemotherapy in noncuratively resected cases of colorectal carcinoma.

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.

Improved results of surgery for esophageal carcinoma in 148 patients

Since the late 1970s, there has been a remarkable decrease in the mortality of patients with esophageal cancer. Factors such as progress in pre- and post-operative management, operative technique, and anesthesia all play a contributory role in this improvement. Among 251 Japanese patients with esophageal carcinoma who underwent esophageal resection and reconstruction in our department of surgery since 1965, those treated from 1965–74 and others treated from 1975–1984 were investigated in detail. It became clear that pulmonary complications and anastomotic leakage were the two major complications related to operative mortality. The former has decreased by intensive postoperative care with strong emphasis on cough dynamics, and the latter because of the long gastric tube we devised and which has a good blood supply. These positive events make feasible early postoperative irradiation and cancer chemotherapy.

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.