Effect of rofecoxib on colon chemical carcinogenesis at colonic anastomotic area in the rat.

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.

Cyclooxygenase-2 inhibition in colon experimental carcinogenesis.

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.

Perianastomotic colonic tumors after inclusion of titanium or Lactomer in the anastomotic suture line. An experimental study in rats.

OBJECTIVE: The aim of the study was to find out if there are differences in the incidence of colonic tumors at the anastomosis after the inclusion of titanium or the absorbable material Lactomer in the anastomotic suture line. METHODS: Experimental study with 30 male Sprague-Dawley rats, assigned to 1 of 3 study groups: control (colonic anastomosis with interrupted suture); inclusion of titanium (8 mg) in the anastomotic suture line; and inclusion of Lactomer (8 mg) in the anastomotic line. After pharmacological carcinogenesis with 1-2 dimethylhydrazine, perianastomotic tumors were studied in the 20th postoperative week. RESULTS: The inclusion of titanium in the anastomotic line led to more tumors, a larger anastomotic tumoral area and a larger percentage of tumoral area than Lactomer (p < 0.05). The inclusion of Lactomer may have a protective effect against the induction of cancer in the anastomotic area. CONCLUSIONS: Titanium, a material used in mechanical instruments for digestive tract anastomoses, is not an innocuous material. Its presence in the anastomotic line can promote colonic carcinogenesis after induction. The use of mechanical staplers for colonic anastomoses should be relegated to difficult anastomoses that cannot be sewn manually.

Experimental model for the study of perianastomotic recurrence in colorectal cancer.

OBJECTIVE: To determine if an experimental model is valid for the study of perianastomotic recurrence in colorectal cancer, comparing it with previous experimental models. METHODS: Experimental study with 40 male Sprague-Dawley rats, assigned to one of the study groups: control group (n = 20), with manipulation of large descending bowel, and colonic anastomosis group (n = 20), with colonic section and colocolic anastomosis. After pharmacological carcinogenesis with 1-2 dimethylhydrazine at a weekly dose of 25 mg/kg for 18 weeks, colonic tumours were studied at the 20th postoperative week. RESULTS: Number of tumours, colic tumoral area and percentage of colic tumoral area were greater in the colonic anastomosis group. In this group with colonic anastomosis all determinations were higher at the perianastomotic large bowel. CONCLUSIONS: We think this experimental model may be the best model to study perianastomotic recurrence in large bowel cancer. The high incidence of induced colic tumours and their location at the perianastomotic area offer a good field to determine response to experimental manipulations on colorrectal cancer.

Influence of the surgical manipulation of the colon in colonic induced carcinogenesis in rats.

AIM: to investigate the influence of different experimental manipulations in a model of colonic experimental carcinogenesis with pharmacological induction in the rat. EXPERIMENTAL DESIGN: a total of 90 Sprague-Dawley male rats, divided into three groups, were used: non-surgical (n = 30); surgical with colonic trauma (n = 20), and surgical with colo-colonic anastomosis (n = 40). Carcinogenic induction was carried out with 1-2 dimethylhydrazine dihydrochloride. Colonic adenocarcinomas were identified and the number of tumors, as well as tumoral surface and percentage of tumoral surface was established. One-way ANOVA and Chi-square were employed for the statistical analysis. RESULTS: the number of tumors was greater in the surgical group than in the control group, and tumors preferentially developed around the manipulated colon. Surface and tumoral percentage were greater in the surgical group than in the control group, being also greater in the anastomosis group than in the group with colonic trauma. Within anastomosis groups, a greater tumor surface and percentage was found in the group with titanium than in the group with reabsorbable material. CONCLUSIONS: the experimental manipulation of the colon in rats enhances drug-induced colon carcingenesis. The creation of an anastomosis further increases the carcinogenic process compared with simulated anastomosis. This process is also enhanced by the quantity of suture material included in the anastomosis, and by the non-reabsorbable nature of the materials used in the anastomotic line.

Influence of rofecoxib on experimental colonic carcinogenesis in rats.

AIM: To investigate the effect of a selective cyclooxigenase-2 (COX-2) inhibitor, rofecoxib, in the prevalence of experimental colon tumors in rats. EXPERIMENTAL DESIGN: Experimental study with 35 male Sprague-Dawley rats, divided into four groups: a) control group without experimental manipulation (n = 5); b) pharmacological carcinogenesis with 1-2 dimethylhydrazine dihydrocloride (n = 10); c) pharmacological carcinogenesis and addition of acetylsalicylic acid (AAS) (n = 10); and d) carcinogenesis and addition of rofecoxib (n = 10). Carcinogenesis was induced with 1-2 dimethylhydrazine at a weekly dose of 25 mg/kg for 18 weeks. Colon tumors were isolated at 20 weeks. Antiinflammatory agents were given at a dose of AAS 30 mg/kg and rofecoxib at 3 mg/kg. RESULTS: The percentage of colonic tumors was significantly reduced in the rofecoxib group. This result was found for all tumors and for the malignant lesions, adenocarcinomas. CONCLUSIONS: Rofecoxib, a selective COX-2 inhibitor, reduced the percentage of drug-induced neoplastic glandular tissue in rats.