PubMed1999
BACKGROUND AND OBJECTIVES: 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.