308 Chapter 13 DISCUSSION In this experiment, 42 healthy rats underwent a laparotomy to create a sufficient colonic end-to-end anastomosis to investigate whether a single intraperitoneal administration of a (drug-loaded) hydrogel affects anastomotic healing compared to saline administration. Twenty-two animals who completed the follow-up period of the experiment were included in the analyses, investigating macroscopic and microscopic anastomotic healing. Adhesion scores were not significantly different between groups. A higher AL score was found in the animals treated with unloaded hydrogel as compared to saline-treated animals, which did not remain significant after correction for multiple testing. A wider range of bursting pressure values was found in the hydrogel-treated groups compared to the saline-treated group, but the differences were not significant. In addition, fibroblast activity, inflammation and neoangiogenesis scores were not different between groups. Unexpectedly, intraperitoneal administration of unloaded and MMC-loaded hydrogel after anastomotic surgery did not prove safe due to intestinal blood loss in nearly half of the hydrogel-treated animals under the current study conditions. Animals that received unloaded hydrogel administered had a higher, but not significant, median AL score compared to animals treated with saline. The observed difference was attributed to the occurrence of small abscesses in several of the unloaded hydrogel-treated animals. However, no large abscesses or complete dehiscence with peritonitis were found in these animals. The hydrogel-treated animals demonstrated a wide range of bursting pressure values compared to the saline-treated animals. Previous studies reported wide ranges of bursting pressure values on different PODs 26, 27. Bosmans et al. published a mean bursting pressure of 104.1 ± 40.8 mBar on POD 7 in their control group. In contrast, Kosmidis et al. reported a higher mean bursting pressure of 198.38 ± 12.80 mBar and de Castro Durães et al. even of 267.07 mBar in control animals on POD 7 27, 28. In our cohort, 18/22, 16/22 and 3/22 animals had a bursting pressure above 104, 198 and 267 mBar, respectively. Although our measured bursting pressures seem to be in line with previously reported absolute values, it is noteworthy that the range in both hydrogel-treated groups is wider compared to the saline-treated group. In a few animals, we measured rather low bursting pressures, which may indicate disturbed anastomotic healing. Still, no large abscesses or complete dehiscence with fecal peritonitis were found. Although using the bursting pressure is the most reliable method of mechanical power assessment of the anastomosis 29, the wide range of values in the literature and our study may suggest this method is not optimal for AL assessment. Importantly, as this study involves an anastomotic safety model (in which normal healing is expected), we did not have to sacrifice an animal before the end of the experiment due to defective anastomotic healing or AL, nor did we identify animals with large abscesses or peritonitis. Already back in 1991, Fumagilli et al. investigated the effects of intraperitoneal chemotherapy on jejunal anastomotic healing in rats 16. Although different types of rats,
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