Influence of neo-adjuvant chemotherapy with 5-fluorouracil on colonic anastomotic healing: experimental study in rats.
OBJECTIVE
We studied the effect of neo-adjuvant chemotherapy on the operative outcome and colonic anastomotic healing in a rat model.


METHODS
Firstly, we determined the maximum tolerated dose (MTD) of intraperitoneal 5-flurorouracil (5-FU) in Wistar rats. Secondly, animals were randomly divided into 3 groups: group CT-H received the MTD of 5-FU, group CT-L received 50% of the MTD and a control group received an equivalent volume of 0.9% saline, intraperitoneally. Colonic anastomosis was performed 4 days after chemotherapy. Animals were sacrificed 10 days after surgery. Evaluations were made of: weight evolution, surgical complications, anastomotic bursting pressure (BP) and histological analysis of the anastomotic site.


RESULTS
A dose of 20 mg/kg 5-FU, intraperitoneally, for 5 consecutive days was found to be the MTD. A significant weight loss occurred in group CT-H in comparison to the control group either during chemotherapy (p < 0.01) or after surgery (p = 0.01). Postoperative complications were seen only in group CT-H (30% versus 0% in CT-L and control groups). More intense adhesion formation was observed in group CT-H in comparison to the control group (p < 0.01). Intraperitoneal 5-FU induced more inflammation and fibrosis in the submucosa, either with the low or the high-dose, compared to the control animals (p < 0.05) and more pronounced vascular sclerosis was noticed with a dose of 20 mg/kg (p = 0.03). No significant differences in BP were found between the chemotherapy groups and the control group.


CONCLUSIONS
Neoadjuvant chemotherapy with 5-FU does not alter the strength of colon anastomosis in this rat model. A dose of 20 mg/kg induces significantly more intra-abdominal adhesions and histological alterations at the anastomotic site.
el-Malt
M
M
Department of Abdominal Surgery, Ghent University Hospital, Ghent University, Belgium. Mohamed.elmalt@rug.ac.be
Ceelen
W
W
Van den Broecke
C
C
Cuvelier
Cl
C
Van Belle
S
S
de Hemptinne
B
B
Pattyn
P
P
D000714:Anastomosis, Surgical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003106:Colon / Q000473:pathology / Q000601:surgery*; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil