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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endoscopic Mucosal Resection / methods*
  • Esophageal Mucosa / pathology
  • Esophageal Stenosis / pathology
  • Esophageal Stenosis / prevention & control*
  • Esophagoscopy / methods
  • Esophagus / pathology
  • Female
  • Fibrosis
  • Hemostatics
  • Male
  • Models, Animal
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Postoperative Complications / prevention & control
  • Re-Epithelialization / drug effects
  • Swine

Substances

  • Hemostatics
  • Peptides
  • RADA16-I

Grants and funding

The study was funded by 3-D Matrix Europe SAS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Imabiotech and Novotec provided support in the form of salaries for authors GH and APM respectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.