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A 41-year-old man with multiple liver metastases from sigmoid colon cancer received a radical resection of the original tumor and 16 courses of weekly high-dose 5-FU(WHF)chemotherapy via hepatic arterial reservoir. The metastatic lesions showed stable disease(SD), and systemic chemotherapy by mFOLFOX6 was begun via CV port. After 14 courses of mFOLFOX4, abdominal CT revealed liver metastases were remarkably reduced in size. Hepatic resection of lateral segment and radio frequency ablation(RFA)for S6 were enforced, and the patient was uneventfully discharged. Pathological findings of lateral segment revealed no residual cancer cells, indicating that the histological effect of mFOLFOX6 was Grade 3.

We examined clinicopathological characteristics and prognoses of seventy advanced colorectal cancer cases by measuring pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in tumor and normal tissue. PyNPase activities in cancerous tissue obtained from resected were 82.7 +/- 41.9 U/mg protein, which were significantly higher than 37.2 +/- 24.0 U/mg protein in normal tissue (p < 0.001). On the other hand, DPD activities in cancerous tissue were significantly lower in normal tissue (p < 0.05). In cases with lymphnode metastases, PyNPase activities of cancerous tissue were significantly higher than that of no lymphnode metastases cases (p < 0.05). In cases with grade 2 side-effects or higher by oral adjuvant chemotherapy, DPD activities in normal tissue were significantly lower than that of other cases (p < 0.05). With regard to Dukes' B and C cases that were resected curatively, PyNPase activities of cancerous tissue of higher group's prognosis were worse than that of the lower group. In the group received 5'-DFUR as adjuvant chemotherapy, non-recurrent survival rate of the group exhibiting higher PyNPase activities was better than that of the lower group.

We performed radiofrequency ablation (RFA) therapy combined with intrahepatic arterial infusion chemotherapy for 7 patients with liver metastasis from colorectal cancer. Synchronous metastasis accounted for 5 cases and metachronous for 2 cases. Two cases were H1, 2 cases H2, and 3 cases H3. Following the resection of colorectal primary lesion, we performed RFA for liver metastasis, using a Cool-tip electrode purchased from Radionics (Burlington, MA, USA). The mean number of sessions per patient was 5.1 (1-10). Ablation time of each session was changed according to tumor size, as follows: less than 1 cm in diameter: 2 min, 2 cm: 5 min, 2.5 cm: 10 min. By using intra-operative catheterization, weekly intrahepatic arterial infusion chemotherapy was performed for liver metastasis. Excellent ablation was achieved in all cases by CT evaluation and no significant side-effect was observed. Average observation period was 15 months (maximal survival period was 31 months) and 6 patients are alive. RFA therapy combined with intrahepatic arterial infusion chemotherapy achieved excellent therapeutic effect, and maintained good quality of life in patients.

Cancer cells are tested for sensitivity to anticancer agents before the drugs are used for treatment in clinical settings, but the results of these tests have not always been reported fully. Since 1973, one of the authors (Hirono) has been performing sensitivity tests of anticancer drugs by using primary culture cells derived from human cancer tissue, taking into account in vivo status and taking great care to reduce the number of procedural errors. From 1991, flow cytometry has also been adopted for use in anticancer drug sensitivity tests. In the present study, the outcomes of cancer patients were compared by dividing them into a group treated only with anticancer agents to which cancer cells had responded in sensitivity tests, and a group treated with other drugs. The subjects consisted of 132 patients with endometrial cancer stage III (n = 26) and IV (n = 10), ovarian cancer stage III (n = 26) and IV (n = 7), peritonitis carcinomatosa (n = 18), and suspected advanced ovarian cancer (n = 45). There was a significant prolongation in median survival time and survival time among the non-survivors according to the results of a Kaplan-Meier analysis. These findings suggest that sensitivity testing of cancer cells to anticancer drugs should be performed before the start of cancer chemotherapy in the clinical setting.

By means of a newly developed in vitro chemosensitivity test based on the morphological changes in the nucleus (nuclear damage assay) as previously described, we were able to screen currently available anticancer drugs within 24 hr with a 100% success rate. The nuclear damage assay was used to determine the chemosensitivity in 50 patients (66 assays) with ovarian cancer. The response rate for the 13 patients with measurable tumors, 8 of whom showed resistance to CAP (cyclophosphamide, adriamycin, and cisplatin) therapy, was 46 percent when they were given various combination chemotherapy protocols consisting of more than one active agent selected from group A and B agents by the nuclear damage assay. The newly developed in vitro chemosensitivity test proved to be useful when selecting a second line combination for patients with CAP-resistant ovarian cancer.

We have studied biologically active substances, tumor angiogenesis factors (TAF), which are supposed to be associated with the proliferation and metastases of choriocarcinoma cells. Eight human choriocarcinoma cell lines were used in the present study. TAF activity was assayed by bioassays using BALB/c mice subcutaneous tissue, chicken chorioallantoic membrane (CAM) and rabbit cornea in vivo and by proliferation of endothelial cells in vitro. 1. We found a positive correlation between the size of tumors developed in xenotransplantation and the number of blood vessels in the tumor tissues. A correlation between the number of blood vessels and TAF activity was also found. 2. With a gel-filtration method, TAF activity was observed in the common fractions in every cell line. The molecular weight of TAF was more than 10,000 daltons. 3. There was a heterogeneity of TAF activity among the cell lines. From these results, it appears that TAF initiates the choriocarcinoma cell-proliferation.