Influence of preoperative combined radiochemotherapy on surgical outcome and colonic anastomotic healing: experimental study in the rat.
OBJECTIVE
To study the influence of combined preoperative hyperfractionated irradiation with intraperitoneal 5-fluorouracil (5-FU) on surgical outcome and colonic anastomotic healing in a rat model.


METHODS
Male Wistar rats were given 41.6 Gy of preoperative radiotherapy (RT) or sham irradiation, with intraperitoneal 5-FU at low dose (10 mg/kg) or high dose (20 mg/kg). Animals were arranged in 6 groups: RT + low-dose 5-FU (RCT-L), RT + high-dose 5-FU (RCT-H), sham RT + low-dose 5-FU (CT-L), sham RT + high-dose 5-FU (CT-H), RT alone (R), and a control group (sham RT + intraperitoneal saline). Side-to-side colonic anastomoses were constructed from one irradiated and one nonirradiated limb 4 days after radiochemotherapy. Animals were sacrificed 10 days after surgery.


RESULTS
Compared to controls, more complications occurred in group RCT-H (50% versus 0%, p = 0.01). Adhesion formation was more intense in groups RCT-H and CT-H (p < 0.001 and p = 0.001, respectively). After therapy, white blood cell counts dropped significantly in all irradiated animals (p < 0.01), and platelet counts decreased significantly in group RCT-H (p = 0.01). No significant differences were noticed in anastomotic bursting pressure when the treated groups were compared to each other or to the control group.


CONCLUSIONS
Neoadjuvant radiochemotherapy has no adverse effect on the strength of colonic anastomosis in this rat model. However, the combined RT with high-dose 5-FU does increase operative morbidity and adhesion formation.
El-Malt
M
M
Department of Abdominal Surgery, Ghent University Hospital, Ghent University, Ghent, Belgium. Mohamed.elmalt@rug.ac.be
Ceelen
W
W
De Meerleer
G
G
Verstraete
A
A
Boterberg
T
T
Van Belle
S
S
de Hemptinne
B
B
De Neve
W
W
Pattyn
P
P
D000714:Anastomosis, Surgical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001772:Blood Cell Count; D003106:Colon / Q000187:drug effects* / Q000528:radiation effects* / Q000601:surgery; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005472:Fluorouracil / Q000627:therapeutic use*; D007263:Infusions, Parenteral; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis; D000267:Tissue Adhesions; D014945:Wound Healing
D000964:Antimetabolites, Antineoplastic; D012709:Serum Albumin; D005472:Fluorouracil