A Prospective Randomised Clinical Trial of the Intra-Operative Use of 5-Fluorouracil on the Outcome of Dupuytren’s Disease

Abstract

5-Fluorouracil reduces proliferation rates of fibroblasts, myofibroblast differentiation and contractility of ocular fibroblasts in vitro. This double-blind randomized clinical trial assesses whether intra-operative topical treatment with 5-fluorouracil reduces the recurrence rate after limited excision of Dupuytren's tissue. Patients with two-digit disease were randomized to having 5-fluorouracil (25mg/ml) treatment for 5 minutes on one digit and placebo on the other. Fifteen patients were enrolled with 18 months follow-up. There were no peri-operative complications. Wound healing was not delayed and there was no deterioration in the flexion deformity of the 5-fluorouracil treated digits. Patients were subsequently assessed by joint angle measurement at 3, 6, 12 and 18 months. There was no significant difference between control and 5-fluorouracil treated digits.

Reversal of TGF-β1 stimulation of α-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren's - derived fibroblasts

“…Treatment of DC-derived fibroblasts with 5-FU inhibited their proliferation and their differentiation to myofibroblasts [38]. However, clinical use of 5-FU at the time of surgery resulted in no difference between treated and untreated digits as determined by joint angle measurements [39], leaving its clinical utility open to question.…”

5-Fluorouracil Selectively Inhibits Collagen Synthesis

“…Encouraged by these and previous in vitro findings, 28 5-fluorouracil has now made the transition from in vitro to in vivo treatment, currently in use in a prospective, randomized, clinical trial investigating the intraoperative use of 5-fluorouracil in the treatment of Dupuytren's disease of the hand. 42 Adriaan O. Grobbelaar …”

Metalloproteinase Gene Expression Correlates With Clinical Outcome in Dupuytren's Disease

“…2 Alternative methods of treatment have been reported as less successful and are often used as an adjunct to surgery rather than in its place. 3 Disease progression is seen as inevitable in the long term rather than as a complication or failure of surgery, but it is extremely variable and often unpredictable. 4 The primary cell thought to be responsible for the alteration in architecture of the palmar fascia is the myofibroblast, 5 although it remains unclear whether the fascial fibroblasts are activated in situ (intrinsic theory) or whether active myofibroblasts are recruited from more distant sites after the disease state is established (extrinsic theory).…”