Preoperative UFT administration for patients with advanced colorectal cancer--increased uptake of 5-fluorouracil by tumor tissue is a prognostic factor.

The aim of this study was to clarify whether increased 5-fluorouracil (5-FU) uptake by tumor tissue following preoperative UFT administration is a prognostic factor after surgery in colorectal cancer patients. We examined the concentrations of 5-FU in tumor or normal tissue of 96 colorectal cancer patients who received UFT (400 mg/day) orally for 7 days prior to surgery. Patients were divided into two groups with high or low 5-FU concentrations in tumor tissue (defined as higher or lower than the cut-off value, respectively). The cut-off value of 5-FU was established based on the upper limit of the 95% confidence interval of the median of the concentration found in normal tissue (0.106 microg/g). Of the 96 patients, 62 (64.6%) were in the low-5-FU group and 34 (35.4%) in the high-5-FU group. The latter had a more favorable clinical outcome (p=0.0465). Cox regression analysis revealed that two independent variables, stage and 5-FU status in tumor tissue, were significant for prediction of survival. These findings suggest that increased uptake of 5-FU by tumor tissue following preoperative oral administration of UFT is an independent prognostic factor in colorectal cancer patients. This variable needs to be considered in the design of future therapeutic trials.

Multicenter randomized prospective study of adjuvant chemotherapy with UFT and mitomycin C in advanced colorectal cancer.

BACKGROUND: A randomized prospective trial was performed to determine the efficacy of preoperative and postoperative adjuvant oral UFT, administered with mitomycin C (MMC) after resection for advanced colorectal cancer. MATERIALS AND METHODS: A total of 126 patients were entered in the study. The patients received UFT (400 mg daily) administered orally for seven days prior to surgery and were randomly assigned to two groups immediately following surgery. Group A received MMC postoperatively; Group B received the same regimen as Group A, plus administration of UFT orally at a dose of 400 mg daily for one year. RESULTS: The survival results revealed no significant difference between groups A and B. In patients with nuclear DNA aneuploid tumors, the hematogenous recurrence rate after curative surgery was lower in Group B than in Group A (P = 0.0656). CONCLUSIONS: Preoperative and postoperative adjuvant oral UFT, administered with MMC after curative resection, may be effective in preventing hematogenous recurrence in colorectal cancer patients with nuclear DNA aneuploidy tumors.

Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer.

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

[A case of traumatic right diaphragmatic hernia].

A 65-year-old female was sent to our hospital by ambulance car after being struck by a car. Chest X-ray showed a elevation of the right diaphragm. Computed tomography and liver scintigram revealed herniation of the liver into the right thorax. As the blood gas analysis was in normal range and cerebral contusion coexisted, she was observed without operation. During 5 year after the injury, the hernia was gradually progressive and dyspnea appeared finally. She was readmitted to the hospital and operated upon through thoraco-abdominal approach. There are no report of spontaneous cure of the hernia. When traumatic diaphragmatic hernia is diagnosed, an operation consistent with the patient's general condition should be performed at that time.

[The usefulness of UFT administration in colorectal cancer with emphasis on postoperative administration (Part 3)].

To investigate the usefulness of the postoperative administration of UFT for colorectal cancer, 109 patients with a history of colorectal cancers from Nagasaki University First Department of Surgery and seven affiliated facilities were selected as subjects. After administering UFT 400 mg/day to both A and B groups one week prior to surgery, MMC 20 mg during surgery and 10 mg on the first day after surgery, the groups were divided into an A group, not administered UFT, and B group, administered UFT 400 mg/day. In addition, both groups were administered MMC 6 mg/m2 six times a month starting the first month after surgery. Although the A group consisted of 54 patients and the B group 55, 52 patients of the A group and 46 patient of the B group, for a total of 98, qualified as subjects for this investigation, and the following results were obtained. 1) Postoperative administration of UFT was useful in prolonging the survival period in non-curable resection cases, in Dukes C group cases, and in cases that exhibited a nuclear DNA aneuploid pattern. It was especially useful in improving the postoperative survival rate from the second year on. 2) When recurrent cases were examined, it was found to be effective in preventing remote metastasis in those cases administered UFT postoperatively. 3) There were no serious adverse effects and the majority of those that did occur were anorexia and diarrhea.

[Multihospital randomized study on pre- and post-operative adjuvant chemotherapy for colorectal cancer (Part 2)].

Prior to surgery, 400 mg/day of UFT was administered for seven days to 86 patients with colorectal cancer. After surgery, the survival rate and side effects of the MMC only group (group A) and the MMC + UFT group (group B) were investigated. The two year survival rate for all cases was 79.8% for group B as opposed to 67.1% for group A. The two year survival rate for cases of histological curative resection were 80.0% for group A and 91.4% for group B, but the difference was not significant. There were few side effects in either group, and a significant difference in the incidence was not observed. Based on the above, MMC combined with UFT, as adjunctive chemotherapy for colorectal cancer, is considered to be a safe and effective treatment.

[A review of colorectal cancer in atomic bomb survivors--treated cases at Nagasaki Genbaku Hospital from 1971-1984].

Clinical and pathological characteristics of patients with colorectal cancer amongst atomic bomb survivors, who had undergone operations from 1971-1984, have been reviewed and compared with that of a control group. The survival rate of the atomic bomb survivors over the age of 60 years was statistically better than that of the same age group in the controls. In this age bracket, the control group were in a more advanced stage of the disease than were the survivors, this accounting for the reason why the survivors had a better prognosis. Further, the fact that the survivors continually have received more medical attention than have the aged in the control group affects this statistic.

[Pre- and post-operative adjuvant chemotherapy of colorectal cancer. Part 1. Drug concentration in tissues following UFT administration].

The concentration of Tegafur, 5-FU and Uracil in tumor and normal tissue were measured in 47 colorectal cancer patients who had been administered UFT (400/mg) for seven days before operation. The concentration of Tegafur, 5-FU and Uracil in tumor was higher than in normal tissue (p less than 0.01), and the concentration of 5-FU was correlative to the concentration of Tegafur and Uracil in both tissues. The Dukes group and histological type were not related to the concentration of Tegafur, 5-FU and Uracil in either tissue. The uptake of each drug was good and high in tumor tissue.

Subcellular localization of intracellular forms of human chorionic gonadotropin in first trimester placenta.

To determine the subcellular sites for synthesis and processing of human chorionic gonadotropin subunits in cells, first trimester placental cells were fractionated subcellularly on sucrose density gradients. Analysis of the subcellular fractions by immunobinding techniques revealed that the rough endoplasmic reticulum-rich fraction contained only intermediates having high-mannose oligosaccharides, but the Golgi-rich fraction contained not only intermediates but also mature forms which were resistant to endoglycosidase H but sensitive to neuraminidase. These results show that human chorionic gonadotropin subunits are synthesized in the rough endoplasmic reticulum as forms containing high-mannose oligosaccharides, and their maturation occurs in the Golgi apparatus by trimming with endogenous glycosidases. They are then modified by addition of complex oligosaccharides and terminal sialic acid through glycosyltransferases.

[Lymphocyte subsets and response of breast cancer and benign mammary disease to PHA].

The lymphocyte counts, subsets and response to PHA in the peripheral blood of patients with breast cancer (stage I-III) and with a benign mammary disease have been evaluated. In the breast cancer cases, the lymphocyte counts and stimulation index of PHA increased gradually as the stages advanced but there was no statistical significance. The ratio and number of OKT 4 positive lymphocytes were significantly lower in patients with breast cancer (stage I) between 40 and 59 years old than in patients with benign mammary diseases between the same ages. This impairment of OKT 4 in breast cancer (stage I) cases was considered as either a cause of the carcinoma or as a reflection of the environment of steroid hormones.

[Two cases of papillary tumor of the pancreas].

Two patients with papillary tumors of the pancreas are reported. In both cases, the tumors occurred in women (62 and 60 years of age) who presented with upper abdominal mass and abdominal fullness. The resected tumors were 14 X 16 cm and 13 X 10.5 X 8.3 cm, respectively. Their histology resembled that of the papillary tumor of the pancreas reported by Frantz (1959). The ultrastructural details, including numerous mitochondria, basement membrane and no evidence of secretory or zymogen granules, suggest pancreatic duct cell origin. The first patient died of colon cancer six years and 10 months postoperatively. The second patient is without signs of recurrence five months after resection.