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N-乙酰半胱氨酸预防食管环周内镜黏膜下剥离术后狭窄:猪模型的随机试验

N-acetylcysteine for the prevention of stricture after circumferential endoscopic submucosal dissection of the esophagus: a randomized trial in a porcine model.

作者信息

Barret Maximilien, Batteux Frédéric, Beuvon Frédéric, Mangialavori Luigi, Chryssostalis Ariane, Pratico Carlos, Chaussade Stanislas, Prat Frédéric

机构信息

Department of Gastroenterology, Cochin Hospital, 27, rue du Faubourg St Jacques, Paris, 75014, France.

出版信息

Fibrogenesis Tissue Repair. 2012 May 28;5(1):8. doi: 10.1186/1755-1536-5-8.

Abstract

BACKGROUND

Circumferential endoscopic submucosal dissection (CESD) of the esophagus would allow for both the eradication of Barrett's esophagus and its related complications, such as advanced neoplasia. However, such procedures generally induce inflammatory repair resulting in a fibrotic stricture. N-acetylcysteine (NAC) is an antioxidant that has shown some efficacy against pulmonary and hepatic fibrosis. The aim of our study was to evaluate the benefit of NAC in the prevention of esophageal cicatricial stricture after CESD in a swine model.

ANIMALS AND METHODS

Two groups of six pigs each were subjected to general anesthesia and CESD: after randomization, a first group received an oral NAC treatment regimen of 100 mg/kg/day, initiated one week before the procedure, whereas a second group was followed without any prophylactic treatment. Follow-up endoscopies took place seven, fourteen, twenty-one, and twenty-eight days after CESD. Necropsy, histological assessment of esophageal inflammation, and fibrosis were performed on day 28.

RESULTS

The median esophageal lumen diameter on day 21 (main judgment criterion) was 4 mm (range 2 to 5) in group 1 and 3 mm (range 1 to 7) in group 2 (P = 0.95). No significant difference was observed between the two groups regarding clinical evaluation (time before onset of clinically significant esophageal obstruction), number of dilations, esophageal inflammation and fibrosis, or oxidative stress damage on immunohistochemistry.

CONCLUSIONS

Despite its antioxidant effect, systemic administration of NAC did not show significant benefit on esophageal fibrosis in our animal model of esophageal wound healing within the experimental conditions of this study. Since the administered doses were relatively high, it seems unlikely that NAC might be a valuable option for the prevention of post-endoscopic esophageal stricture.

摘要

背景

食管环形内镜黏膜下剥离术(CESD)可根除巴雷特食管及其相关并发症,如高级别瘤变。然而,此类手术通常会引发炎症修复,导致纤维化狭窄。N-乙酰半胱氨酸(NAC)是一种抗氧化剂,已显示出对肺和肝纤维化有一定疗效。本研究的目的是评估NAC在猪模型中预防CESD后食管瘢痕性狭窄的益处。

动物与方法

两组猪,每组6只,接受全身麻醉并进行CESD:随机分组后,第一组在手术前一周开始接受100mg/kg/天的口服NAC治疗方案,而第二组不进行任何预防性治疗。在CESD后第7、14、21和28天进行随访内镜检查。在第28天进行尸检、食管炎症的组织学评估和纤维化评估。

结果

第21天(主要判断标准)时,第一组食管腔中位直径为4mm(范围2至5mm),第二组为3mm(范围1至7mm)(P = 0.95)。两组在临床评估(出现具有临床意义的食管梗阻前的时间)、扩张次数、食管炎症和纤维化或免疫组织化学上的氧化应激损伤方面均未观察到显著差异。

结论

在本研究的实验条件下,尽管NAC具有抗氧化作用,但在我们的食管伤口愈合动物模型中,全身给予NAC对食管纤维化并未显示出显著益处。由于给药剂量相对较高,NAC似乎不太可能成为预防内镜后食管狭窄的有效选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c9/3482386/00cb5022a25c/1755-1536-5-8-1.jpg

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