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自组装肽基质在猪模型中环周内镜黏膜下剥离后预防食管狭窄的应用。

Application of a self-assembling peptide matrix prevents esophageal stricture after circumferential endoscopic submucosal dissection in a pig model.

机构信息

Department of Gastroenterology, Cochin Hospital, APHP, Paris, France.

INSERM Unit 1016, Paris, France.

出版信息

PLoS One. 2019 Mar 12;14(3):e0212362. doi: 10.1371/journal.pone.0212362. eCollection 2019.

Abstract

INTRODUCTION

Circumferential endoscopic submucosal dissection (ESD) allows to treat large esophageal superficial neoplasms, however with a high occurrence of severe esophageal strictures. In a previous work, we demonstrated that the application of a prototype of self-assembling peptide (SAP) matrix on esophageal wounds after a circumferential-ESD delayed the onset of esophageal stricture in a porcine model. The aim of this work was to consolidate these results using the commercialized version of this SAP matrix currently used as a hemostatic agent.

ANIMALS AND METHODS

Eleven pigs underwent a 5 cm-long circumferential esophageal ESD under general anesthesia. Five pigs were used as a control group and six were treated with the SAP. In the experimental group, 3.5 mL of the SAP matrix were immediately applied on the ESD wound. Stricture rates and esophageal diameter were assessed at day 14 by endoscopy and esophagram, followed by necropsy and histological measurements of inflammation and fibrosis in the esophageal wall.

RESULTS

At day 14, two animals in the treated group had an esophageal stricture without any symptom, while all animals in the control group had regurgitations and an esophageal stricture (33 vs. 100%, p = 0.045). In the treated group, the mean esophageal diameter at day 14 was 9.5 ± 1 mm vs. 4 ± 0.6 mm in the control group (p = 0.004). Histologically, the neoepithelium was longer in the SAP treated group vs. the control (3075 μm vs. 1155μm, p = 0.014). On immunohistochemistry, the expression of alpha smooth muscle actin was lower in the treated vs. control group.

CONCLUSION

Apposition of a self-assembling peptide matrix immediately after a circumferential esophageal ESD reduced by 67% the occurrence of a stricture at day 14, by promoting reepithelialization of the resected area.

摘要

介绍

环周内镜黏膜下剥离术(ESD)可用于治疗大型食管浅表肿瘤,但会导致严重食管狭窄的发生率较高。在之前的研究中,我们证明了在猪模型中,在环周 ESD 后应用自组装肽(SAP)基质可延迟食管狭窄的发生。本研究旨在使用目前作为止血剂的商业化 SAP 基质版本来巩固这些结果。

动物和方法

11 头猪在全身麻醉下接受 5cm 长的环周食管 ESD。5 头猪作为对照组,6 头猪接受 SAP 治疗。实验组中,在 ESD 伤口上立即应用 3.5ml SAP 基质。第 14 天通过内镜和食管造影评估狭窄率和食管直径,然后进行尸检和食管壁炎症和纤维化的组织学测量。

结果

在第 14 天,实验组中有 2 头猪出现无症状的食管狭窄,而对照组所有猪均出现反流和食管狭窄(33%比 100%,p=0.045)。实验组第 14 天的食管直径为 9.5±1mm,对照组为 4±0.6mm(p=0.004)。组织学上,SAP 治疗组的新生上皮较长(3075μm比 1155μm,p=0.014)。免疫组化染色显示,SAP 治疗组的α平滑肌肌动蛋白表达低于对照组。

结论

环周食管 ESD 后立即应用自组装肽基质可将第 14 天狭窄的发生率降低 67%,通过促进切除区域的再上皮化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc89/6413927/3695ea6456d0/pone.0212362.g001.jpg

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