The Effects of a Single Dose of 5-Fluorouracil on Keloid Scars: A Clinical Trial of Timed Wound Irrigation after Extralesional Excision

Abstract

The possibility of altering the pathophysiology of keloid scars was investigated in 11 patients, using a single application of 5-fluorouracil solution for 5 minutes after extralesional excision was performed. Similar excisional wounds treated with phosphate-buffered saline for 5 minutes served as synchronous controls. An objective scoring system and subjective assessment were made to assay the change in the quality of the wound-healing and scar tissue produced by this treatment. A keloid scar score was used at regular time intervals after treatment to assess the quality of scar produced, thereby enabling the treated and control scars to be clinically compared. Biopsies were taken of the control and treated scars 1 month after treatment; the biopsy specimens were then subjected to immunohistochemical analysis as well as a functional assessment of cultured keloid fibroblasts. The immunohistochemical antigens assayed were Ki-67 (also called MIB-1; a marker of cell proliferation); vascular cell adhesion molecule-1 (a marker of inflammation); transforming growth factor beta-1 (a factor involved in scarring) and CD-68 (a macrophage-specific marker). Fibroblast-populated collagen lattices provided a functional assessment of fibroblast contraction. All treated and control wounds healed without any dehiscence or infection. The keloid scar score revealed that there was a perceived improvement in condition for those treated with 5-fluorouracil, compared with the control specimens, during the 6-month follow-up period in the five patients who attended all their clinic appointments; data on later recurrence are not complete as yet. The wounds treated with 5-fluorouracil produced scars that had a significant (p < 0.01) reduction in all the markers assayed, apart from CD-68. Functionally, the keloid fibroblasts from three of five of the treated patients showed reduced contractile capacity. This pilot study demonstrates that a "single-touch" technique with 5-fluorouracil can produce a change in the characteristics of the healing keloid wound after extralesional excision. Long-term studies are required to elucidate the correct dosage and time of exposure to improve the efficacy of this potential treatment.

5-Fluorouracil Blocks Transforming Growth Factor-β–Induced α2 Type I Collagen Gene (COL1A2) Expression in Human Fibroblasts via c-Jun NH2-Terminal Kinase/Activator Protein-1 Activation

“…In the early 1980s, 5-FU was investigated as an adjunct to glaucoma filtering surgery, a procedure in which inhibition of wound healing is desirable to achieve surgical success (Gressel et al, 1984;Skuta et al, 1987). More recently, local 5-FU application has shown some success in the treatment and prevention of hypertrophic scars and keloids (Fitzpatrick 1999;Uppal et al, 2001).…”

V-Y Advancement Flap: Aesthetic Reconstruction for Auriculotemporal Keloid Excision

“…Curative treatment of keloids is difficult, and a plethora of treatment options has been studied. Treatment modalities include compression therapy, cryosurgery, injections (steroids, mitomycin C, 5-fluorouracil, interferon, or PRP), surgery, and postoperative radiotherapy, depending on the size and location of the keloid scar [3][4][5][6]. Studies have found that keloid treatment is most effective when using multiple modalities, but there is still much controversy as to what is the optimal treatment [7].…”

“…Abnormal scars may cause pain or pruritus, disturb the range of motion, diminish sensation, or cause aesthetic deformities that may lead to significant psychosocial distress. Treatment modalities include compression therapy, cryosurgery, injections (steroids, mitomycin C, 5-fluorouracil, interferon, or platelet-rich plasma [PRP]), surgery, and postoperative radiotherapy, depending on the size and location of the keloid scars [3][4][5][6].…”

A Comparative Clinical Study on Role of 5-Flurouracil Versus Triamcinolone in the Treatment of Keloids

“…The increased rate of proliferation seen in keloidal fibroblasts suggests that 5-FU may be effective in limiting keloid growth [14]. A major drawback of systemic 5-FU is its association with anemia, leucopenia, and thrombocytopenia.…”