Advertisement
Original communication| Volume 142, ISSUE 5, P734-740, November 2007

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 μg of bFGF-GH (n = 10), 1 μg 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-μg 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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Shrikhande S.V.
        • Qureshi S.S.
        • Rajneesh N.
        • Shukla P.J.
        Pancreatic anastomoses after pancreaticoduodenectomy: do we need further studies?.
        World J Surg. 2005; 29: 1642-1649
        • Muscari F.
        • Suc B.
        • Kirzin S.
        • Hay J.M.
        • Fourtanier G.
        • Fingerhut A.
        • et al.
        Risk factors for mortality and intra-abdominal complications after pancreatoduodenectomy: multivariate analysis in 300 patients.
        Surgery. 2005; 139: 591-598
        • Bassi C.
        • Falconi M.
        • Molinari E.
        • Salvia R.
        • Butturini G.
        • Sartori N.
        • et al.
        Reconstruction by pancreaticojejunostomy versus pancreaticogastrostomy following pancreatectomy.
        Ann Surg. 2005; 242: 767-773
        • Duffas J.P.
        • Suc B.
        • Msika S.
        • Fourtanier G.
        • Muscari F.
        • Hay J.M.
        • et al.
        A controlled randomized multicenter trial of pancreatogastrostomy or pancreatojejunostomy after pancreatoduodenectomy.
        Am J Surg. 2005; 189: 720-729
        • Li-Ling J.
        • Irving M.
        Somatostatin and octreotide in the prevention of postoperative pancreatic complications and the treatment of enterocutaneous pancreatic fistulas: a systematic review of randomized controlled trials.
        Br J Surg. 2001; 88: 190-199
        • Gouillat C.
        • Chpponi J.
        • Baulieux J.
        • Partensky C.
        • Saric J.
        • Gayet B.
        Randomized controlled multicentre trial of somatostatin infusion after pancreaticoduodenectomy.
        Br J Surg. 2001; 88: 1456-1462
        • Steenfos H.H.
        Growth factors and wound healing.
        Scand J Plast Reconst Surg Hand Surg. 1994; 2: 95-105
        • Nugent M.A.
        • Iozzo R.V.
        Fibroblast growth factor-2.
        Int J Biochem Cell Biol. 2000; 32: 115-120
        • Buntrock P.
        • Jentzsch K.D.
        • Heder G.
        Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity.
        Exp Pathol. 1982; 21: 46
        • McGee G.S.
        • Davidson J.M.
        • Buckley A.
        • Sommer A.
        • Woodward S.C.
        • Aquino A.M.
        • et al.
        Recombinant basic fibroblast growth factor accelerates wound healing.
        J Surg Res. 1988; 45: 145
        • Broadley K.N.
        • Aquino A.M.
        • Woodward S.C.
        • Buckley-Sturrock A.
        • Sato Y.
        • Rifkin D.B.
        • et al.
        Monospecific antibodies implicate basic fibroblast growth factor in normal wound repair.
        Lab Invest. 1989; 61: 571-575
        • Steenfos H.H.
        • Tarnow P.
        • Aram M.
        • Nakamura T.
        • Jansson J.
        Increased gene expression of scatter factor-hepatocyte growth factor and basic fibroblast growth factor in granulation tissue in the rat.
        Wound Repair Regen. 1993; 1: 231-235
        • Tabata Y.
        Significance of release technology in tissue engineering.
        Drug Discov Today. 2005; 10: 1639-1646
        • Tabata Y.
        • Hijikata M.
        • Ikeda Y.
        Enhanced vascularization and tissue granulation by basic fibroblast growth factor impregnated in gelatin hydrogels.
        J Control Release. 1994; 31: 189-199
        • Igai H.
        • Chang S.S.
        • Gotoh M.
        • Yamamoto Y.
        • Misaki N.
        • Okamoto T.
        • et al.
        Regeneration of canine tracheal cartilage by slow release of basic fibroblast growth factor from gelatin sponge.
        ASAIO J. 2006; 52: 86-91
        • Grikscheit T.C.
        • Siddique A.
        • Ochoa E.R.
        • Srinivasan A.
        • Alsberg E.
        • Hodin R.A.
        • et al.
        Tissue-engineered small intestine improves recovery after massive small bowel resection.
        Ann Surg. 2004; 240: 748-754
        • Ikeda Y.
        • Tabata Y.
        Protein release from gelatin matrices.
        Adv Drug Deliv Rev. 1998; 31: 287-301
        • Ehrlich H.P.
        • Traver H.
        • Hunt T.K.
        Effects of vitamin A and glucocorticoids upon inflammation and collagen synthesis.
        Ann Surg. 1973; 177: 222-227
        • Ogawa Y.
        • Chung Y.S.
        Microvessel quantitation in invasive breast cancer by staining for factor VII-related antigen.
        Br J Cancer. 1995; 71: 1297-1301
        • Yonekawa M.
        A study of the healing process of pancreatico-enterostomy (in Japanese).
        J Jpn Surg Soc. 1985; 86: 725-737
        • Takami H.
        Studies on the wound healing process of anastomosis of pancreaticojejunostomy using normal and duct ligated pancreas (in Japanese).
        J Keio Med Soc. 1985; 62: 629-652
        • Tabata Y.
        • Hijikata S.
        • Muniruzzaman M.
        • Ikada Y.
        Neovascularization effect of biodegradable gelatin microspheres incorporating basic fibroblast growth factor.
        J Biomater Sci Polym Ed. 1999; 10: 79-94
        • Kawai K.
        • Suzuki S.
        • Tabata Y.
        • Nishimura Y.
        Accelerated wound healing through the incorporation of basic fibroblast growth factor impregnated gelatin microspheres into artificial dermis using a pressure-induced decubitus ulcer model in genetically diabetic mice.
        Br J Plast Surg. 2005; 58: 1115-1123
        • Kawai K.
        • Suzuki S.
        • Tabata Y.
        • Ikada Y.
        • Nishimura Y.
        Accelerated tissue regeneration through incorporation of basic fibroblast growth factor-impregnated gelatin microspheres into artificial dermis.
        Biomaterials. 2000; 21: 489-499
        • Ono I.
        The effect of basic fibroblast growth factor (bFGF) on the breaking strength of acute incisional wounds.
        J Dermatol Sci. 2002; 29: 104-113