Aim: to analyze qualitative short-time results of a new program for multidisciplinary liver evaluation in complex cases of liver metastasis from colorectal cancer.Patients and methods: 40 clinical consecutive evaluations with liver metastasis assessed for major liver resection by a multidisplinary specialist committee. Complementary explorations performed included CT and ultrasounds, and MRI or PET for doubtful cases. Liver resection was made in a single operation or two-stage hepatectomy, or combined with other techniques.Results: postoperative mortality at 30 days was 4%. Complications occurred in 28%, with surgical wound infection being most frequent (20%); 16.6% of resections were transfused, with a mean volume of 1000 ml. Two patients needed reoperation -one for an intraperitoneal abscess and one for bile-duct stenosis. Percentage of global relapse was 36%, with 26% of relapses out of the liver. Actuarial survival at one year follow-up was 90%, and 82% at two years; 64% of patients remain free of disease two years after the operation.Conclusions: programs for liver resection for colorectal cancer metastasis may be implemented by multidisciplinary teams of recent setup. There is a need to evaluate own results and then compare them with a standard of quality previously reported.

Aim: to investigate the effect of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib on the incidence of perianastomotic colonic tumors in a model of chemical carcinogenesis in the rat. Experimental design: experimental study with 45 male Sprague-Dawley rats randomly assigned to one of three groups: control (n = 15) with colocolic anastomosis and chemical carcinogenesis with 1-2 dimethylhydrazine (1-2 DMH); rofecoxib 0.0027% (n = 15) with colonic anastomosis, chemical carcinogenesis and the addition of dietary rofecoxib at doses of 27 parts per million (ppm), and rofecoxib 0.0058% (n = 15) with colonic anastomosis, chemical carcinogenesis and the addition of dietary rofecoxib at doses of 58 ppm. Carcinogenic induction was performed with 1-2 DMH at a weekly dose of 25 mg/kg of weight for 18 weeks, and colonic tumors induced were analyzed in postoperative week 20. The main parameter evaluated was the percentage of colonic neoplastic tissue, which relates tumor surface area to the colon's surface area. Results: rofecoxib at doses of 2.5 mg/kg or 0.0058 ppm significantly reduced chemical colon carcinogenesis in rats, both in the perianastomotic area and the rest of the colon (p < 0.01). In the extra-anastomotic area, rofecoxib at doses of 2.5 mg/kg has significantly greater inhibitory effect than rofecoxib in doses of 1.2 mg/kg or 0.0027 ppm (p < 0.005). Conclusions: rofecoxib causes a reduction in chemical colon carcinogenesis in rats. This effect is sustained in the perianastomotic area, and the investigation of its role in operated colorectal cancer with risk of locoregional recurrence may therefore be of interest.

Background: an overexpression of cyclooxygenase-2 (COX-2) has been seen in colon tumors; therefore, COX-2 specific inhibitors may be used as preventive agents. The aim of this study was to investigate the effect of both selective and non-selective COX-2 inhibitors on the incidence of colonic tumors in a model of chemical carcinogenesis in the rat. Design: experimental study with 65 male Sprague-Dawley rats randomly assigned to one of four groups: (a) control (n = 20), with chemical carcinogenesis using 1-2 dimethylhydrazine (1-2 DMH); (b) acetylsalicylic acid (ASA) (n = 15), with chemical carcinogenesis and the addition of ASA at 30 mg/kg; (c) low-dose rofecoxib (n = 15), with chemical carcinogenesis and the addition of rofecoxib at a dose of 1.2 mg/kg; (d) high-dose rofecoxib (n = 15), with carcinogenesis and the addition of rofecoxib at 3 mg/kg. Carcinogenic induction was performed with 1-2 DMH at a weekly dose of 25 mg/kg for 18 weeks. The main parameter evaluated was percentage of neoplastic colonic tissue, which relates tumor surface area to colon surface area. Results: rofecoxib at a dose of 3 mg/kg significantly reduced chemical colon carcinogenesis in rats (p < 0.01). Rofecoxib in lower doses had the same effect on adenomas (p < 0.05) with no effect on adenocarcinomas. Rofecoxib reduced COX-2 expression in tumoral tissue from adenomas and adenocarcinomas (p < 0.01). Conclusions: rofecoxib prevents chemical colon carcinogenesis in the rat, with a reduction of tumoral colonic percentage in adenocarcinomas and tumoral COX-2 expression.

Dear Sir,We have read with interest the article of Becerra et al. 1 about the increased toxicity and lack of efficacy of rofecoxib in combination with chemotherapy in the treatment of metastatic colorectal cancer.The dose of rofecoxib employed in their clinical study was 50 mg/day, with a reduction to 25 mg/day in 3 patients with digestive bleeding. With these doses, the potential reduction of carcinogenesis was not reached. There was even a lack in the response to conventional chemotherapy.In our opinion, a dose of 50 mg/day of rofecoxib is insufficient. We have made experimental studies on OFA rats to look for the best dose of rofecoxib to prevent promotion and progression of colorectal cancer. Doses that we have found effective in the reduction and prevention of colic pharmacologically induced carcinogenesis were 1.25 mg/kg/day, 2.5 mg/kg/day and 3 mg/kg/day. The lowest effective dose in our studies was 1.25 mg/kg/day, and the best dose for carcinogenesis reduction was 2.5 and 3 mg/kg/day.The lowest dose we have found effective suppose an increment of 50% in the rofecoxib that has been given at clinical study. The higher doses of rofecoxib in our experimental studies represent 3 or 4 times the dose of rofecoxib in the study of Becerra et al. 1 Rofecoxib at a dose of 25 or 50 mg/day is useful for acute and chronic pain, but if we want to see an effect on promotion or prevention of colorectal cancer, doses must be higher, probably from 2-3 mg/kg/day. 2-4 These experimental results will need clinical studies to investigate these doses in colorectal cancer in humans.We think that more studies with more patients are needed, including studies with other chemotherapy combinations with participation of oxaliplatine and CPT-11 and with higher doses of rofecoxib, to clarify the role of rofecoxib in colorectal cancer.Yours