Department of Pediatric Surgery, Süleyman Demirel University Medical School, 32260, Isparta, Turkey.
J Pediatr Surg. 2011 Oct;46(10):1893-7. doi: 10.1016/j.jpedsurg.2011.03.001.
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.
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.
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).
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.
意外摄入腐蚀性物质可能会导致儿童出现严重问题。大约 20%的腐蚀性摄入会导致食管狭窄形成，这是由于成纤维细胞向细胞外基质过度合成胶原所致。最近的研究表明，单次应用 5-氟尿嘧啶（5-FU）是一种非常有效的成纤维细胞增殖和分化抑制剂，可以持续很长时间。我们使用实验模型研究了单次剂量 5-FU 对腐蚀性食管烧伤后狭窄形成的疗效。
将 40 只 Wistar-Albino 大鼠随机分为 4 组：第 1 组（假手术组），食管未受伤且未治疗；第 2 组（对照组），食管受伤且未治疗；第 3 组（腹腔内治疗组），食管受伤后立即用单次腹腔内剂量（20mg/kg）5-FU 治疗；第 4 组（局部治疗组），食管受伤后立即用浓度为 25mg/mL 的 5-FU 进行单次食管内应用。通过在远端食管内注入 10%NaOH 来产生腐蚀性食管烧伤。术后 28 天采集远端食管。通过测量狭窄指数（SI）和组织病理学损伤评分来评估组织学切片。通过生化方法测定组织中的羟脯氨酸（HP）水平。
与对照组相比，腹腔内治疗组的 SI（P<0.05）、组织病理学损伤评分（P<0.05）和 HP 水平（P<0.05）均显著降低。对照组和局部治疗组之间的 SI 和组织病理学损伤评分无显著差异（P>0.05），但两组之间的 HP 水平显著降低（P<0.05）。
单次腹腔内应用 5-FU 对腐蚀性食管烧伤后狭窄形成有预防作用。这一观察结果表明，5-FU 可能会在临床环境中预防这种不良并发症。现在需要进行临床研究来验证这种治疗形式。烧伤后立即局部应用 5-FU 于食管内无效。需要进一步研究以确定在局部损伤部位应用 5-FU 的适当时间。
