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We report the results of 5-fluorouracil (5-FU) combined with high-dose l-folinic acid (leucovorin) therapy for patients with advanced colorectal carcinoma. In each treatment course, the patients weekly received both 5-FU (600 mg/m2 by intravenous 15 min infusion) and l-folinic acid (250 mg/m2 by intravenous infusion over a period of 2 h). A total of six treatments were administered with a 14-day interval to the next course of six treatments. Forty-eight patients were evaluated for toxicity and 32 for response. The combined complete and partial response rate was 25% in 32 patients. Toxicity was within acceptable limits without grade 4 toxicity. Although the response rate was slightly lower than those reported in phase II trials in Japan, the result was satisfactory. This therapy can be the standard chemotherapy for colorectal cancer patients, even in Japan.

We have reviewed the cases of every patient presenting with bone metastasis after colorectal surgery and tried to establish the features of this clinical entity and generate basic strategies to the therapeutic management of this condition. Of 928 primary tumor resected colorectal cancer patients, 12 (1.3%) were identified with bone metastasis and included in this study. The majority of primary tumors were located at the rectosigmoid portion of the colon. All cases were highly advanced at the time of diagnosis, including 8 cases of stage IV by TNM classification. Sites of metastatic tumors were concentrated in lumber or pelvic bones. At the onset of bone metastasis, 9 of the 12 cases had other metastatic sites, i.e., only 3 patients had bone metastasis alone. Survival after onset of bone metastasis was very poor, with a median survival of approximately 5 months and a 20% survival rate at 1 year. With regard to cause of death, seven patients died of pulmonary failure, one of liver failure, and one of DIC. Only 2 cases of solitary osseous metastasis have survived more than 1 year. In order to significantly improve prognosis, the early detection of bone metastases is important.

The subject of this study was to examine the net effect of numerous changes in basic strategies, personnel and devices, upon the clinical courses and outcomes of rectal cancer patients. A total of 151 rectal cancer patients who underwent low anterior resection were divided into 4 groups (period 1 to 4) based upon the time period of the operation. They were compared among groups based upon the following parameters: blood loss, operation time, incidence of leakage and urinary dysfunction, incidence of ileus, duration of naso-gastric tube insertion, timing of initial oral feeding and survival. The blood loss during the operations, urinary dysfunction and duration of naso-gastric tube insertion tended to decrease in every period. Timing of initial oral feeding became faster. The operation times, incidence of leakage and ileus were nearly the same in each period. The 5-year survival rates on Dukes' C cases were 100% in period 4, 82.4% in period 3 and 50% in period 2. Survival rates became better. Our net outcome for rectal cancer treatment was satisfactory, because the survival rates became better under function preserving strategies.

Vascular endothelial growth factor expression before and after preoperative radiation therapy was examined in 16 stage III rectal carcinoma patients. The biopsied tissues before preoperative radiation therapy and the tissues at operation were immunohistochemically stained. Four cases were negative for VEGF expression before radiation, but the other 12 cases were positive, with 4 cases showing strong immunoreactivity. After radiation, all except 1 case showed VEGF positive patterns, in which 14 cases demonstrated strong staining. In 12 cases, VEGF expression became higher after radiation therapy than before, as compared to the only 1 case that showed lower expression than before.

The purpose of this study was to assess the usefulness of the Eppendorf 'Kistograph' as a device for measuring pO(2) in tumor and normal tissues of the laboratory mouse. To determine the appropriate calibration and electrode condition, nitrogen bubbling time was changed, and the current during calibration was recorded. Reproducibility of pO(2) measurements was tested in the series of human xenografts and murine isoplants at different time points or in the same tumor in successive determinations. pO(2) values obtained with the Eppendorf 'Histograph' were compared to those obtained with a manually controlled needle-type electrode manufactured by the Diamond-General Company. The pO(2) values after 9 min of nitrogen bubbling were closer to the expected values than those after 3 min bubbling. The current during nitrogen bubbling in calibration declined following the pO(2) measurement by an amount corresponding to 0.8 mm Hg. Good reproducibility of pO(2) measurement was shown in i) pO(2) values in the same cell line at different time points and ii) pO(2) values in two or three consecutive measurements in related regions within the same tumor. The Eppendorf 'Histograph' and the Diamond-General device showed no significant differences in pO(2) distribution in either subcutaneous tissue or MCaIV tumors. In conclusion, results of the Eppendorf 'Histograph' were consistent and reproducible and were similar to those obtained by the Diamond-General set-up.

The sequential administration of methotrexate (MTX) and 5-fluorouracil (5-FU) (MTX/5-FU therapy) on gastric cancers has shown higher response rates than standard chemotherapy. The response rate of these cancers, however, still showed from 18 to 48%. The purpose of this study was to determine the appropriate interval time and doses of MTX/5-FU therapy using a panel of 4 cell lines originated from the poorly-differentiated gastric cancers. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used as the chemosensitivity test. The sequential administration of MTX and 5-FU inhibited the growth of 2 cell lines more than 5-FU alone. In one cell line (GCIY), it inhibited the growth 6 times, and the longest interval time (6 h) was the most effective. In the other cell line (KATOIII), it inhibited growth 3 times, and the shortest interval time (O h) was the most effective. The growth inhibition in these cases did not depend on the dose of MTX (0.01 mu g/ml to 100 mu g/ml), but on the dose of 5-FU. In conclusion, 2 out of 4 cell lines showed a synergic effect between MTX and 5-FU. While the appropriate interval time between the two drugs varied between two cell lines, 5-FU dose was more critical than that of MTX. If 5-FU dose were to be increased in future trials with MTX, its efficacy might be higher. This model should also be good to screen other anti cancer drugs combined with MTX/5-FU therapy.