Abstract
The purpose of this experimental study was to research the effect of immediate postoperative intraperitoneal application of oxaliplatin and 5-fluorouracil on the cicatrization of anastomoses of the large intestine of rats. Material and Methods: Sixty male rats belonging to the Wistar race were randomly divided into 4 groups of 15 laboratory animals each and were subjected to excision of a part of the large intestine and anastomosis. To the rats of the 1st group (control group), 3 ml of saline solution were administered intraperitoneally intraoperatively, as well as on the first postoperative day. To the rats of the 2nd group (5-FU), 5-Fluorouracil (20 mg/Kg C) diluted into 3 ml of saline solution was administered intraperitoneally intraoperatively, as well as on the first postoperative day. To the rats of the 3rd group (oxaliplatin), oxaliplatin (2,4 mg/Kg C) diluted into 3 ml of saline solution was administered intraperitoneally intraoperatively. Finally, to the laboratory animals of ...
The purpose of this experimental study was to research the effect of immediate postoperative intraperitoneal application of oxaliplatin and 5-fluorouracil on the cicatrization of anastomoses of the large intestine of rats. Material and Methods: Sixty male rats belonging to the Wistar race were randomly divided into 4 groups of 15 laboratory animals each and were subjected to excision of a part of the large intestine and anastomosis. To the rats of the 1st group (control group), 3 ml of saline solution were administered intraperitoneally intraoperatively, as well as on the first postoperative day. To the rats of the 2nd group (5-FU), 5-Fluorouracil (20 mg/Kg C) diluted into 3 ml of saline solution was administered intraperitoneally intraoperatively, as well as on the first postoperative day. To the rats of the 3rd group (oxaliplatin), oxaliplatin (2,4 mg/Kg C) diluted into 3 ml of saline solution was administered intraperitoneally intraoperatively. Finally, to the laboratory animals of the 4th group (5-FU and oxaliplatin), 5-fluorouracil (20 mg/Kg C) and oxaliplatin (2,4 mg/Kg C) diluted into 3 ml of saline solution were administered intraperitoneally intraoperatively. On the first postoperative day, only 5-fluorouracil (20 mg/Kg C) diluted into 3 ml of saline solution was administered. The programmed sacrifice of the laboratory animals was performed during the 8th postoperative day. During the autopsy, inspection for findings of possible rupture of the anastomosis, as well as macroscopic control of the adhesions and measurement of the bursting pressure of the anastomosis were performed. Afterwards, a part of the large intestine including the anastomosis was sent for histopathological examination and evaluation of the inflammatory reaction (leucocytes count), of neoangiogenesis, of collagen synthesis, and of fibroblasts. Another part of the anastomosis was sent for count of hydroxyproline, an indirect marker of the deposition of collagen on the anastomosis. The comparison of the therapy groups was evaluated with the exact Fisher test and in the case of ordered data, with the x2 test with co-calculation of tension. For the total comparison of median and intermediate values of the therapy groups, the Kruskall- Wallis test was used. In case of presence of statistically significant difference (p<0,05) between the groups, comparison of all the therapy groups, two by two, in all the possible combinations followed, using the non-parametric Mann–Whitney test and the simple regulation according to Bonferroni, so a result is considered statistically significant if p<0,008 (0,005/6). In all the other statistical analyses, p<0,05 means statistically significant difference. The statistical analyses were performed with the statistic package SPSS10.0. Results: The reduction of the medium body weight in the 1st group was statistically significant lower, compared to the reduction of the medium body weight in the 2nd, 3rd and 4th groups (p<0,001, p<0,001 and p<0,001 respectively). The 2nd, 3rd and 4th groups, compared to one another did not present with statistically significant differences (p>0,2 for all the comparisons) in the medium body weight reduction. Rupture of the anastomosis was present in no rat of the 1st (control group) group, in 3 rats of the 2nd (5-FU) group, in 4 rats of the 3rd (oxaliplatin) group and in 7 rats of the 4th (5-FU and oxaliplatin) group. Between all the groups exists a statistically significant degree of dependence of the group to the rupture of the anastomosis (p=0,016). In the 2nd and the 3rd group, a statistically significant lower bursting pressure of the anastomosis was observed, compared to the 1st (control) group (p<0,001), without a statistically significant difference between the 2nd and the 3rd group (p=0,063). In the 4th group, statistically significant lower bursting pressure was observed, compared to the 1st group (p<0,001), as well as compared to the 2nd group (p<0,001) and the 3rd group (p<0,001). As well, the 2nd, 3rd and 4th groups presented with a statistically significant higher degree of adhesions compared to the 1st group (p<0,001), without a statistically significant difference between the 2nd, 3rd and 4th groups (p>0,008 for all the comparisons). The lowest degree of leukocytosis was observed in the 1st (control) group. The 2 (5-FU) group followed, then the 3rd (oxaliplatin) group and finally, the 4th (5-FU and oxaliplatin) group. The comparison of the median values of the groups, two by two, proves that statistically significant differences exist for all the comparisons (p<0,001), except for the comparisons between the 2nd and the 3rd group (p=0,054) and between the 3rd and the 4th group (p=0,024). The highest degree of neoangiogenesis was observed in the 1st (control) group. The 4th (5-FU and oxaliplatin) group followed, then the 3rd group (oxaliplatin), and finally, the 2nd (5-FU) group. The comparison of the medians of the groups of the laboratory animals two by two proves that statistically significant differences exist for the comparison between the 1st (control) group and the 2nd (5-FU) group, (p<0,001), between the 1st (control) group and the 3rd (oxaliplatin) group, (p=0,003), as well as for the comparison between the 2nd (5-FU) group and the 4th (5-FU and oxaliplatin) group, (p=0,006). Finally, the 2nd, 3rd and 4th groups presented with statistically significant lower values of hydroxyproline, as well as of the concentration of neocollagen and fibroblasts compared to the 1st (control) group, (p<0,001), without statistically significant differences between the 2nd, 3rd and 4th groups (p>0,200) concerning these three parameters for the evaluation of anastomosis cicatrization. Conclusion: The immediate postoperative, intraperitoneal application of 5-fluorouracil, oxaliplatin or combination of 5-fluorouracil and oxaliplatin perturbs the cicatrization of colonic anastomoses in rats. There must be mentioned that oxaliplatin has a negative effect on the cicatrization of anastomoses in a higher degree than 5-FU. The combination of 5-FU and oxaliplatin is even more detrimental to the process of cicatrization of the anastomoses of the large intestine.
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