Effect of gastrectomy on the pharmacokinetics of 5-fluorouracil and gimeracil after oral administration of S-1.

The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated in a total of 12 cases - nine in which partial gastrectomy was performed and three in which total gastrectomy was performed. A single oral dose of S-1, 50 mg as tegafur, was administered, serial peripheral blood samples were collected, and the concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured. The pre-operative S-1 dose was administered about 7 days before surgery and the post-operative dose was administered around post-operative hospital day 14. In the partial gastrectomy cases the maximum post-operative blood concentration (Cmax) of 5-FU and CDHP tended to be lower than before surgery, and the difference in 5-FU concentrations was significant. The area under the blood concentration-time curve (AUC0-8 h) for CDHP was significantly smaller post- than pre-operatively, but no significant difference was observed with regard to 5-FU. In the total gastrectomy cases the post-operative tmax of both 5-FU and CDHP was shorter than the pre-operative tmax, and no significant differences were observed between the pre- and post-operative AUC0-8 h values. Thus, the results of the present study showed that around post-operative hospital day 14, when total oral feeding had become possible after surgery for gastric cancer, the AUC0-8 h values of 5-FU and CDHP after S-1 administration were almost the same as before surgery and that gastrectomy had hardly any effect on the pharmacokinetics of S-1.

Correlation between expression of orotate phosphoribosyl transferase and 5-fluorouracil sensitivity, as measured by apoptosis index in colorectal cancer tissue.

BACKGROUND: 5-Fluorouracil remains a key drug in the treatment of colorectal cancer, and the development of a simple and effective test for selecting patients likely to benefit from postoperative adjuvant chemotherapy is an important objective. AIM OF THE STUDY: This study aimed to clarify the feasibility of measuring apoptotic cell rate (AI%) in tumor after short-term oral 5-fluorouracil administration prior to surgery with the objective of establishing a simpler method to test for sensitivity. METHODS: Forty-five colorectal cancer patients were allocated to two groups, and 21 patients were given oral 5-FU for 3 d prior to surgery. The AI% in surgical specimen, detected by TUNEL staining, was compared in the 5-FU-loaded and control groups. The correlation of AI% with 5-FU metabolic enzyme mRNA levels in tumor was also evaluated. RESULTS: The AI% was significantly higher in the tumor tissue of patients receiving 5-FU than in the control group (p < 0.0005). Although insignificant, thymidylate synthase mRNA level and orotate phosphoribosyl transferase mRNA demonstrated a weak positive correlation with AI%. CONCLUSIONS: The AI% measurement in tumor tissue following a 5-FU oral load for 3 d prior to surgery was feasible. It remains to be elucidated if this measurement as a new 5-FU sensitivity test reflects the prognosis with 5-FU-based postoperative adjuvant chemotherapy.

Laparoscopic cholecystectomy after coronary artery bypass grafting using the right gastroepiploic artery: report of a case.

A laparoscopic cholecystectomy (LC) was successfully performed on a 61-year-old man who had undergone coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). He complained of right hypochondralgia 20 days after CABG. Gallstones were diagnosed and a cholecystectomy was performed 9 months after CABG. Under general anesthesia, the operation was performed using a pneumoperitonium. When a laparoscope was inserted, the RGEA pedicle could be clearly recognized. The pedicle obstructed the operating field and made the working space narrower than usual. No ST changes on the electrocardiogram were seen during LC, especially during the initiation of pneumoperitonium, the insertion of the ports, or when retracting the gallbladder. The postoperative course was uneventful. To avoid complications, care should be taken not to stretch the RGEA pedicle during LC, and careful monitoring of the electrocardiogram is also necessary. It is difficult to view the operating field and the RGEA pedicle together. It is therefore better to insert another laparoscope for concomitant monitoring of the RGEA pedicle.