A prospective randomized study comparing high- and low-dose leucovorin combined with same-dose 5-fluorouracil in advanced colorectal cancer.

Although the efficacy of 5-fluorouracil (5-FU) modulated by leucovorin is well established for advanced colorectal cancer, the question of the most effective regimen and optimal dose of leucovorin remains unanswered. This prospective randomized trial compares low-dose (group 1) and high-dose (group 2) leucovorin, combined with the same dose of 5-FU to determine whether high-dose leucovorin was more beneficial than low-dose on overall survival. Inclusion criteria were: unresectable metastatic colorectal carcinoma, with or without evaluable tumor response; a performance status of less than grade 3 (World Health Organization classification); and no previous chemotherapy for metastases. Forty-two patients were randomized in group 1 (leucovorin, 20 mg/m2/day, days 1 through 5) and 41 patients in group 2 (leucovorin, 200 mg/m2/day, days 1-5). All the patients in the two groups received a 1-hour infusion of 400 mg/m2/day 5-FU every 4 weeks. The two groups were matched with no statistically significant differences in gender ratio, site of primary tumor, performance status, and tumor extent. Toxicity in the two regimens was low and not significantly different between the two groups. Overall median survival was 346 days in group 1 and 323 days in group 2 and was not significantly different between the two groups. At 1 year, the test of equivalence was significant (p < 0.01), demonstrating an absence of more than 20% benefit in 1-year survival for the high-dose regimen. The use of high-dose leucovorin combined with 5-FU in the 5-day regimen does not significantly improve overall survival for patients who have metastatic colorectal cancer.

Ultrasonic and histopathological correlations of deep focal hepatic lesions induced by stereotaxic Nd-YAG laser applications.

Thirty six deep focal hepatic lesions were induced in eleven piglets by means of an Nd-YAG laser. Laser shots of 80 W power and 10 s duration were used, the beam being transmitted through an echoguided stereotaxic handpiece. From day 0 to day 120, the animals underwent ultrasonographic and morphological controls. At lasering time an hyperechoic image--12-18 mm in diameter--appeared due to boiling of tissue water. During the twenty postoperative days the lesion core was an echo-free area due to tissue vaporization, surrounded by an hyperechoic ring of increasing fibrosis, containing neovascularization and biliary ductules, while the hypoechoic outer area represented the peripheral halo of edema. In the long term, hyperechoic structures--swollen fibrotic septa of homogeneous fibrotic network--invaded the lesion site confirming good healing.