Comparative antitumor activity of 5-fluorouracil and its prodrugs in combination with hyperthermia in vitro.

We investigated the antitumor activities of 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5'-DFUR), 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207) in combination with hyperthermia in vitro. The antitumor effect of 5-FU (10(-4) M) was slightly enhanced by combination with hyperthermia (42 degrees C) for 2h, and the effect was determined to be additive. Synergistic enhancement of antitumor activity was obtained by the concurrent use of hyperthermia (42 degrees C, 2h) and 5'-DFUR (10(-4) M) or HCFU (10(-5) M). However, the antitumor effect of FT-207 (10(-4) M) in combination with hyperthermia was comparable that of hyperthermia alone. The synergistic enhancement of antitumor activity was not obtained for all drugs when the cells were preheated at 42 degrees C for 2h. On the other hand, when cells were pretreated with drugs before heat exposure, weak interactions were obtained after 5-FU and 5'-DFUR treatment, and a synergistic interaction was obtained after HCFU treatment. It is speculated that the metabolites of 5'-DFUR and HCFU enhance the cytotoxicity of 5-FU, or might change the threshold concentration for a cytotoxic effect of 5-FU in cancer cells.</p

Efficacy of adjuvant portal vein chemotherapy for liver micrometastases

To establish an effective chemotherapy against liver metastases, we compared the anti-proliferative effects of portal vein drug administration with that of intravenous administration, using a rat hepatic micrometastasis model. The model was produced by inoculating 1,2-dimethyl hydrazine (DMH)-induced rat colonic carcinoma (RCN-9) cells into the portal vein. The drugs used were 5-fluorouracil (5-FU), mitomycin-C (MMC) and cisdiammine-dichloroplatinum (CDDP), at total doses of 150mg/kg, 6mg/kg and 8mg/kg, respectively. Animals were classified into three groups in terms of drug administration times ; one time administration 2 days after tumor cell inoculation (day 2), three times on days 2, 9 and 16, and daily for fifteen days between day 2 and day 16. On day 21 after inoculation of the tumor cells, all rats were sacrificed and metastatic nodules were calculated. Portal vein administration of anticancer drugs, 5-FU, MMC, CDDP, had a tendency to inhibit the proliferation of liver micrometastases and was accompanied by fewer side effects, in comparison with intravenous infusion. In addition, significant prolongation of survival was achieved in the portal vein infusion group. These results suggest that intraportal administration of drugs is an effective modality to inhibit micro or occult liver metastases

Four cases of villous adenoma of rectum in our department : Comparative study of 88 cases of villous adenoma in Japan

We reviewed the charts of 4 patients with villous adenoma of the rectum seen at the First Dept. of Surg., Okayama Univ. Med. School between 1971 and 1990. This study included 2 men and 2 women, ranging in age from 52 to 83 years. Polypectomy was performed on 3 patients with villous adenoma and low anterior resection was performed on 1 patient. Recurrent tumors developed in one of the 3 patients who had undergone polypectomy. In addition, a series of 88 patients with villous adenoma of the rectum reported in Japan were also reviewed. The average age of the patients with villous adenoma was 62.9. There were 47 men and 41 women. The presenting symptoms of the 69 patients with tumor were mainly bleeding and watery or mucinous diarrhea. The tumor size and invasiveness of malignancy were also examined. The likelihood of malignancy correlated with size of tumor, and none of the lesions smaller than 2cm contained a malignant tumor site. Surgeons should consider the size, location and malignant change of the villous tumor with as much precise examination before and during operation so that unnecessary over surgery is avoided

Lateral lymph node metastasis of rectal carcinoma

The records of 182 consecutive rectal carcinomas treated in this department between JAN 1978 and DEC 1990 were reviewed to assess the outcome of the patients presenting with lateral pelvic lymph node infiltration. Lateral lymph node dissection was carried out in 24 (42.1%) of the 57 Ra tumors and 63 (72.4%) of the 87 Rb tumors, but in none of the 38 cases of Rs tumors. Lymph node involvement was detected 0% and 15.9% of the Ra and Rb tumors, respectively. In this series, none of the cases in which the tumors were confined to m, sm and pm had positive lymph nodes. However, 23.3% of the 43 cases in which invasion was beyond pm showed positive lymph node invasion. The main lymph nodes involved were located in the roots of the middle rectal arteries. Half of the patients presented with distant metastases within one year, with poorer prognosis considering the mean survival rate of 1.8 years. In conclusion, we advocate that in Rb rectal tumors with circular invasion or invasion beyond the pm, careful lateral lymph nede dissection should be carried out. On the other hand, we suggest the use of preoperative radiation therapy which could improve the curability, the disease-free interval, and survival rates

A report of thirteen cases of familial polyposis coli

Familial polyposis coli (FPC) is an inherited nonsex linked mendelian dominant disease in which there exist at least 100 adenomatous polyps throughout the entire large bowel. Thirteen patients with FPC, of whom 7 were male and 6 female, visited our department between 1966 and 1990. The mean age of the patients was 33.5. Eight of the 13 patients (61.5%) had gastric and/or duodenal polyps, and eight of the 13 patients (61.5%) had colorectal carcinomas at admission. Colectomy with ileorectal anastomosis (IRA) was performed on 2 patients. The functional results were good bowel frequency, good sphincter control and lack of dietary restriction. Clinical experience tended to suggest that the risk of rectal cancer following IRA is extreme and unacceptable, although our two cases were still free of rectal cancer. Since 1980, the total colectomy with mucosal proctectomy and ileal pouch-anal anastomosis was the procedure of choice in our department. Good results were obtained on the six patients on whom this procedure was performed

Lymph node metastases of right colon cancer

The lymph node metastases of the right side colon were studied. Among 58 cases of right side colon, nodal involvements were found in 53.4%. Metastases to the epicolic and paracolic nodes were confined to an area within 10 cm from the tumor margin. Metastases to the intermediate nodes were found in 20.7% and metastases to the main nodes in 15.5%. Jumping metastases were recognized in 5 out of 31 cases of nodal involvement (16.1%). As the rate of jumping metastases is unexpectedly high, lymph node dissection for right colon cancer should be done as far as the main nodes