The effect of keratinocyte growth factor-2 on esophagogastric anastomotic wound healing in rats.
OBJECTIVE
Esophagogastric anastomotic leaks complicate 5-20% of esophagectomies for esophageal cancer, and they are responsible for approximately one-third of perioperative deaths. Growth factors enhance healing in several wound healing models. Keratinocyte growth factor-2 (KGF-2) is a newly identified growth factor that accelerates skin incisional healing. An animal experiment was done to test the hypothesis that KGF-2 would enhance esophagogastric anastomotic wound healing.


METHODS
Forty rats had single layer esophagogastric anastomoses constructed using interrupted 7-0 polypropylene sutures. In the experimental group (20 rats) 1 mg of KGF-2 was administered by intraperitoneal injection on the day of surgery, and for three consecutive days thereafter. Placebo (buffer solution only) was given to the control rats (20 rats). Rats were sacrificed on the fourth postoperative day and their anastomoses were excised, mounted in a tensiometer, and distracted at 10 mm/min to measure breaking strength. After that, anastomotic tissue was subjected to hydroxyproline analysis (an indicator of wound collagen). Skin and fascial wounds were also tested in a tensiometer.


RESULTS
There were two anastomotic leaks in the KGF-2 treated rats and none in the control rats (p = 0.26, not significant). Esophagogastric anastomotic breaking strength was 1.00 +/- 0.61 N in the KGF-2 treated rats and 1.58 +/- 0.62 N in the control rats (p = 0.017). Esophagogastric anastomotic tissue hydroxyproline concentration was 95.9 +/- 19.9 nmol/mg in the KGF-2 treated rats and 114.1 +/- 38.0 nmol/mg in the control rats (p = 0.10, not significant). Skin and fascia breaking strengths were also lower in the KGF-2 rats, but the difference was not significantly different (KGF-2 skin -0.97 +/- 0.48 N, Control skin -1.46 +/- 0.89 N, p = 0.064; KGF-2 fascia -3.60 +/- 2.06 N, Control fascia -4.67 +/- 1.88 N, p = 0.14).


CONCLUSIONS
Keratinocyte growth factor-2 did not enhance esophagogastric anastomotic wound healing in this model. However, the dosage and route of administration of KGF-2 may have been sub-optimal for promotion of anastomotic healing. Further studies with this new growth factor are needed.
Cui
Y
Y
Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA.
Urschel
J D
JD
Petrelli
N J
NJ
D000714:Anastomosis, Surgical; D000818:Animals; D004947:Esophagus / Q000601:surgery; D005260:Female; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013270:Stomach / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects*
C496465:Fgf10 protein, rat; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors