The efficacy of single-dose 5-fluorouracil therapy in experimental caustic esophageal burn.
BACKGROUND
Accidental ingestion of caustic substances may cause serious problems in children. Approximately 20% of caustic ingestions result in esophageal stricture formation, resulting from excessive collagen synthesis to the extracellular matrix by fibroblasts. Recent studies showed that a single application of 5-fluorouracil (5-FU) is a very effective inhibitor of fibroblast proliferation and differentiation for prolonged periods. Using an experimental model, we investigated the efficacy of single-dose 5-FU on stricture formation after caustic esophageal burn.


METHODS
Forty Wistar-Albino rats were divided randomly into 4 equal groups: group 1 (sham-operated group), the esophagus was uninjured and untreated; group 2 (control group), the esophagus was injured and left untreated; group 3 (intraperitoneal treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraperitoneal dose (20 mg/kg) of 5-FU; group 4 (local treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraesophageal application of 5-FU at a concentration of 25 mg/mL. Caustic esophageal burn was produced by instilling 10% NaOH in the distal esophagus. The distal esophagi were harvested at 28 days postoperatively. Histologic sections were assessed by measuring the stenosis index (SI) and histopathologic damage score. Hydroxyproline (HP) levels in the tissues were determined biochemically.


RESULTS
There were significant reductions in the SI (P < .05), histopathologic damage score (P < .05), and HP level (P < .05) in the intraperitoneal treatment group when compared with the control group. No significant differences in the SI and histopathologic damage score were detected between the control and local treatment groups (P > .05), whereas significant reduction in the HP level was determined between these groups (P < .05).


CONCLUSIONS
A single intraperitoneal dose of 5-FU had a preventive effect on stricture formation after caustic esophageal burn. This observation suggests that 5-FU may prevent this undesirable complication in the clinical setting. Clinical studies are now required to verify this form of treatment. Local intraesophageal application of 5-FU immediately after the burn injury was not effective. Further investigations are required to determine the appropriate timing of application of 5-FU at the local site of injury.
Department of Pediatric Surgery, Süleyman Demirel University Medical School, 32260, Isparta, Turkey. leduman@gmail.com
Levent
L
Duman
Behcet Ilker
BI
Büyükyavuz
Irfan
I
Altuntas
Alpaslan
A
Gökcimen
Levent
L
Ceyhan
Hakan
H
Darici
Firdevs
F
Aylak
Onder
O
Tomruk
D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy*; D002424:Caustics / Q000633:toxicity*; D002454:Cell Differentiation; D002455:Cell Division; D002921:Cicatrix / Q000209:etiology / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D004940:Esophageal Stenosis / Q000139:chemically induced / Q000188:drug therapy*; D004947:Esophagus / Q000737:chemistry / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000032:analysis; D007274:Injections, Intraperitoneal; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012972:Sodium Hydroxide / Q000633:toxicity*
D002424:Caustics; D012972:Sodium Hydroxide; D006909:Hydroxyproline; D005472:Fluorouracil