Keratinocyte Growth Factor-2 Does Not Enhance Esophagogastric Anastomotic Wound Healing in Rats

Esophagogastric anastomotic leaks complicate 5% to 20% of esophagectomies for esophageal cancer. 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. 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 3 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. There were 2 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). KGF-2 did not enhance esophagogastric anastomotic wound healing in this model. Similarly, intraperitoneal KGF-2 did not have a beneficial effect on skin or fascial wound healing.