Controlled release of basic fibroblast growth factor promotes healing of the pancreaticojejunal anastomosis: a novel approach toward zero pancreatic fistula.
BACKGROUND
Several reconstructive surgical techniques have been proposed for restoring pancreatico-jejunal continuity. Little has been done, however, to evaluate the efficacy of tissue engineering on anastomotic healing. We examined the effects of basic fibroblast growth factor (bFGF) incorporated in gelatin hydrogel (GH) microspheres on the anastomotic healing of pancreaticojejunostomy.


METHODS
As a preliminary experiment, 20 female Wistar rats received a jejunal subserosal injection of 1 microg of bFGF-GH (n = 10), 1 microg of Free-bFGF (n = 5), or gelatin alone (n = 5) to study the effects of bFGF on the histology of normal jejunum on day 7 after the injection. Next, 12 beagle dogs received a jejunal subserosal injection of 100-microg bFGF-GH (n = 7) or gelatin alone (n = 5) at the anastomotic site of pancreaticojejunostomy. Four types of assessment were performed to compare the 2 groups: pancreatography, breaking strength test, pathologic examination, and calculation of the microvessel density (MVD).


RESULTS
The bFGF-GH injection led to markedly increased levels of collagen and fibroblastic cellularity in the subserosal layer of the Wistar rats. In contrast, the rats treated by gelatin alone exhibited no such effects. No anastomotic failures were observed in the dogs treated by bFGF-GH. Histologic observations of this group revealed abundant granulation tissues. Treatment with bFGF-GH significantly increased the breaking strength and MVD over the levels measured in the control group (P < .01).


CONCLUSIONS
bFGF-GH accelerates healing of pancreaticojejunal anastomosis during the early postoperative period. Basic FGF-GH may show promise as a new technique for preventing anastomotic failure of pancreaticojejunostomy.
Aimoto
Takayuki
T
Nippon Veterinary and Animal Science University, and Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, Japan. aimoto@nms.ac.jp
Uchida
Eiji
E
Matsushita
Akira
A
Tabata
Yasuhiko
Y
Takano
Teruo
T
Miyamoto
Masaaki
M
Tajiri
Takashi
T
D000818:Animals; D003094:Collagen / Q000378:metabolism; D004285:Dogs; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology; D005780:Gelatin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007267:Injections; D007583:Jejunum / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D010185:Pancreatic Fistula / Q000517:prevention & control; D010193:Pancreaticojejunostomy; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin; D003094:Collagen