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Surface Treatment with 5-Fluorouracil After Flexor Tendon Repair in a Canine in Vivo Model
Chunfeng Zhao, MD1; Mark E. Zobitz, MS1; Yu-Long Sun, PhD1; Kelly S. Predmore, BS1; Peter C. Amadio, MD1; Kai-Nan An, PhD1; Steven L. Moran, MD1
1 Department of Orthopedic Surgery, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905. E-mail address for S.L. Moran: moran.steven@mayo.edu
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Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR44391). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.
Investigation performed at the Biomechanics Laboratory, Division of Orthopedic Research, Mayo Clinic College of Medicine, Rochester, Minnesota

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2009 Nov 01;91(11):2673-2682. doi: 10.2106/JBJS.H.01695
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Background: Topical 5-fluorouracil has been reported to reduce adhesions in animal models of tenolysis. The purpose of this study was to investigate the effects of topical 5-fluorouracil on adhesion formation after tendon repairs were subjected to immediate postoperative rehabilitation in a canine model in vivo.

Methods: Sixty dogs were randomly assigned to either a 5-fluorouracil treatment (thirty dogs) or a control group (thirty dogs). Each treatment group was then divided into three survival time points: ten days, twenty-one days, and forty-two days. The second and fifth flexor digitorum profundus tendons from each dog were fully lacerated at the zone-II area and then were repaired. Passive motion therapy started at day 5 postoperatively and continued until the dogs were killed. The repaired tendons were evaluated for normalized work of flexion, gliding resistance, repair strength, gene expression for type-I and type-III collagen and transforming growth factor-ß1, and histological appearance.

Results: The normalized work of flexion of the repaired tendons treated with 5-fluorouracil was significantly lower than that of the repaired tendons without 5-fluorouracil treatment at ten days. However, there was no significant difference between treated and untreated tendons at twenty-one and forty-two days. There was also no significant difference in gliding resistance, repair failure strength, or stiffness between treated and untreated tendons at any time point, or in the gross or histological appearance of adhesions at the time of killing. The expression of types-I and III collagen and transforming growth factor-ß1 of the repaired tendon with 5-fluorouracil treatment was significantly lower than that of the tendons without treatment at ten days postoperatively, but not at twenty-one or forty-two days.

Conclusions: Although 5-fluorouracil treatment can reduce adhesions in in vivo models of tenolysis, this treatment had only a transient effect in an in vivo model of tendon repair that included passive motion.

Clinical Relevance: Topical 5-fluorouracil, at the dosing regimen tested in this study, does not appear to offer a major benefit over early postoperative motion protocols alone in the treatment of flexor tendon lacerations.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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