Original Communications| Volume 25, ISSUE 2, P242-251, March 2000

Download started.


Effects of 5-fluorouracil on flexor tendon repair


      This study was performed to assess the effects of a single 5-minute exposure of 5-fluorouracil (5-FU) applied topically at the time of flexor tendon repair in an attempt to reduce postoperative adhesions. The flexor digitorum profundus tendon to the long and fourth toe of Leghorn chickens was lacerated and primarily repaired using a 2-strand technique. The repair site was then exposed to a single 5-minute application of 5-FU in concentrations of 5, 25, or 50 mg/mL. Legs were casted for 3 weeks. After death the tendon was examined for the work of flexion using a tensile testing machine and examined with light microscopy, scanning electron microscopy, and transmission electron microscopy for morphologic and histologic differences in adhesion formation. Forty-seven chickens were examined. Average work of flexion values were 0.12 J for normal tendon, 0.31 J for operative controls, 0.34 J for the 5 mg/mL group, 0.15 J for the 25 mg/mL group, and 0.19 J for the 50 mg/mL group. The work of flexion was significantly reduced in the 25 and 50 mg/mL groups compared with the operative controls (p = .008 and p = .03, respectively). Histologic sections as graded by a blinded pathologist revealed decreased adhesion formation in all the 5-FU-treated animals (p < .008). Histologic examination showed that the highest concentration of 5-FU was not as effective at reducing adhesions as the 25 mg/mL dose. This appeared to be due to increasing inflammatory changes seen around and within the tendons of the 50 mg/mL group. Overall, a single intraoperative application of 5-FU at concentrations of 25 mg/mL appears to be an effective mechanism for reducing postoperative flexor tendon adhesions. (J Hand Surg 2000;25A:242–251. Copyright © 2000 by the American Society for Surgery of the Hand.)


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


        • Peacock Jr., EE
        Biological principles in healing of long tendons.
        Surg Clin North Am. 1965; 45: 461-476
        • Lundborg G.
        Experimental flexor tendon healing without adhesion formation—a new concept of tendon nutrition and intrinsic healing mechanisms: a preliminary report.
        Hand. 1976; 8: 235-238
        • Gelberman RH
        • Vande Berg JS
        • Lundborg GN
        • Akeson WH.
        Flexor tendon healing and restoration of the gliding surface: an ultrastructural study in dogs.
        J Bone Joint Surg. 1983; 65A: 70-80
        • Gelberman RH
        • Manske PR
        • Vande Berg JS
        • Lesker PA
        • Akeson WH.
        Flexor tendon healing in vitro: a comparative histologic study of the rabbit, chicken, dog, and monkey.
        J Orthop Res. 1984; 2: 39-48
        • Manske PR
        • Lesker PA.
        Histologic evidence of intrinsic flexor tendon repair in various experimental animals: an in vitro study.
        Clin Orthop. 1984; 182: 297-304
        • Matthews P.
        The fate of isolated segments of flexor tendons within the digital sheath—a study in synovial nutrition.
        Br J Plast Surg. 1976; 29: 216-224
        • Becker H
        • Graham MF
        • Cohen IK
        • Diegelmann RF.
        Intrinsic tendon cell proliferation in tissue culture.
        J Hand Surg. 1981; 6: 616-619
        • Graham MF
        • Becker H
        • Cohen IK
        • Merritt W
        • Diegelmann RF.
        Intrinsic tendon fibroplasia: documentation by in vitro studies.
        J Orthop Res. 1984; 1: 251-256
        • Strickland JW.
        Flexor tendon injuries: I. Foundations of treatment.
        J Am Acad Orthop Surg. 1995; 3: 44-54
        • Herzog M
        • Lindsay WK
        • McCain WG.
        Effects of beta-aminioproprionitrile on adhesions following digital flexor tendon repair in chickens.
        Surg Forum. 1970; 21: 509-511
        • Kapetanos G.
        The effect of the local corticosteriods on the healing and biomechanical properties of the partially injured tendon.
        Clin Orthop. 1982; 163: 170-179
        • Kulick MI
        • Smith S
        • Hadler K.
        Oral ibuprofen: evaluation of its effect on peritendinous adhesions and the breaking strength of a tenorrhaphy.
        J Hand Surg. 1986; 11A: 110-120
        • Szabo RM
        • Younger E.
        Effects of indomethacin on adhesion formation after repair of zone II tendon lacerations in the rabbit.
        J Hand Surg. 1990; 15A: 480-483
        • Blumenkranz MS
        • Claflin A
        • Hajek AS.
        Selection of therapeutic agents for intraocular proliferative disease: cell culture evaluation.
        Arch Ophthalmol. 1984; 102: 598-604
        • Blumenkranz MS
        • Ophir A
        • Claflin AJ
        • Hajek A.
        Fluorouracil for the treatment of massive periretinal proliferation.
        Am J Ophthalmol. 1982; 94: 458-467
        • Khaw PT
        • Ward S
        • Grierson I
        • Rice NSC.
        Effects of β radiation on proliferating human Tenon's capsule fibroblasts.
        Br J Ophthalmol. 1991; 75: 580-583
        • Khaw PT
        • Occleston NL
        • Schultz G
        • Grierson I
        • Sherwood MB
        • Larkin G.
        Activation and suppression of fibroblast function.
        Eye. 1994; 8: 188-195
        • Khaw PT
        • Sherwood MB
        • MacKay SLD
        • Rossi MJ
        • Schultz G.
        Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon's capsule fibroblasts.
        Arch Ophthalmol. 1992; 110: 1150-1154
        • Khaw PT
        • Doyle JW
        • Sherwood MB
        • Grierson I
        • Schultz G
        • McGorray S.
        Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C.
        Arch Ophthalmol. 1993; 111: 263-267
        • Khaw PT
        • Doyle JW
        • Sherwood MB
        • Smith MF
        • McGorray S.
        Effects of intraoperative 5-fluorouracil or mitomycin C on glaucoma filtration surgery in rabbits.
        Ophthalmology. 1993; 100: 367-372
        • Doyle JW
        • Sherwood MB
        • Khaw PT
        • McGrory S
        • Smith MF.
        Intraoperative 5-fluorouracil for filtration surgery in the rabbit.
        Invest Ophthalmol Vis Sci. 1993; 34: 3313-3319
        • Khan U
        • Occleston NL
        • Khaw PT
        • McGrouther DA.
        Single exposures to 5-fluorouracil: a possible mode of targeted therapy to reduce contractile scarring in the injured tendon.
        Plast Reconstr Surg. 1997; 99: 465-471
        • Lane JM
        • Black J
        • Bora FW.
        Gliding function following flexor-tendon injury: a biomechanical study of rat tendon function.
        J Bone Joint Surg. 1976; 58A: 985-990
        • Peterson WW
        • Manske PR
        • Kain CC
        • Lesker PA.
        Effect of flexor sheath integrity on tendon gliding: a biomechanical and histologic study.
        J Orthop Res. 1986; 4: 458-465
        • Farkas LG
        • Thomson HG
        • Martin R.
        Some practical notes on the anatomy of the chicken toe for surgeon investigators.
        Plast Reconstr Surg. 1974; 54: 452-458
        • Ketchum LD.
        Primary tendon healing: a review.
        J Hand Surg. 1977; 2: 428-435
        • Lanigan L
        • Stürmer J
        • Baez KA
        • Hitchings RA
        • Khaw PT.
        Single intraoperative application of 5-fluorouracil during filtration surgery: early results.
        Br J Ophthalmol. 1994; 78: 33-37
        • Tang J
        • Ishii S
        • Usui M
        • Aoki M.
        Dorsal and circumferential sheath reconstruction for flexor sheath defect with concomitant bony injury.
        J Hand Surg. 1994; 19A: 61-69
        • Tang JB
        • Shi D
        • Zhang QG.
        Biomechanical and histologic evaluation of tendon sheath management.
        J Hand Surg. 1996; 21A: 900-908
        • Manske PR.
        Flexor tendon healing.
        J Hand Surg. 1988; 13B: 237-245
        • Lindsay WK
        • Birch JR.
        The fibroblast in flexor tendon healing.
        Plast Reconstr Surg. 1964; 34: 223-232
        • Khan U
        • Occleston NL
        • Khaw PT
        • McGrouther DA.
        Differences in proliferative rate and collagen lattice contraction between endotenon and synovial fibroblasts.
        J Hand Surg. 1998; 23A: 266-273
        • Peterson WW
        • Manske PR
        • Dunlap J
        • Horwitz DS
        • Kahn B.
        Effects of various methods of restoring flexor sheath integrity on the formation of adhesions after tendon injury.
        J Hand Surg. 1990; 15A: 48-56
        • Matthews P
        • Richards H.
        Factors in the adherence of flexor tendon after repair: an experimental study in the rabbit.
        J Bone Joint Surg. 1976; 58B: 230-236
        • Manske PR
        • Gelberman RH
        • Vande Berg JS
        • Lesker PA.
        Intrinsic flexor-tendon repair: a morphological study in vitro.
        J Bone Joint Surg. 1984; 66A: 385-396
        • Seiler III, JG
        • Chu CR
        • Amiel D
        • Woo SLY
        • Gelberman RH.
        Autogenous flexor tendon grafts: biologic mechanisms for incorporation.
        Clin Orthop. 1997; 345: 239-247
        • Salmon SE
        • Sartorelli AC.
        Cancer chemothreapy.
        in: 6th ed. Basic and clinical pharmacology. : Appleton & Lange, East Norwalk, CT1995: 832-834
        • Yamamoto T
        • Varani J
        • Soong HK
        • Lichter PR.
        Effect of 5-fluorouracil and mitomycin C on cultered rabbit subconjunctival fibroblasts.
        Ophthalmology. 1990; 97: 1204-1210
        • Occleston NL
        • Daniels JT
        • Tarnuzzer RW
        • et al.
        Single exposures to antiproliferatives: long-term effects on ocular fibroblast wound-healing behavior.
        Invest Ophthalmol Vis Sci. 1997; 38: 1998-2007
        • Ghadially FN.
        Ultrastructural pathology of the cell and matrix: a text and atlas of physiological and pathological alterations in the fine structure of cellular and extracellular components.
        in: 3rd ed. : Butterworths, London1988: 1242-1246
        • Akali A
        • Khan U
        • Khaw PT
        • McGrouther AD.
        Decrease in adhesion formation by a single application of 5-fluorouracil after flexor tendon injury.
        Plast Reconstr Surg. 1999; 103: 151-158