Mucosal loss as a critical factor in esophageal stricture formation after mucosal resection: a pilot experiment in a porcine model

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.


Background and aim

Esophageal stricture is a major complication of large areas endoscopic submucosal dissection (ESD). Until now, the critical mechanism of esophageal stricture remains unclear. We examined the role of mucosal loss versus submucosal damage in esophageal stricture formation after mucosal resection using a porcine model.

Materials and methods

Twelve swine were randomly divided into two groups, each of 6. In each group, two 5-cm-long submucosal tunnels were made to involve 1/3rd of the widths of the anterior and posterior esophageal circumference. The entire mucosal roofs of both tunnels were resected in group A. In group B, the tunnel roof mucosa was incised longitudinally along the length of the tunnel, but without excision of any mucosa. Stricture formation was evaluated by endoscopy after 1, 2, and 4 weeks, respectively. Anatomical and histological examinations were performed after euthanasia.


Healing observed on endoscopy in both groups after 1 week. Group A (mucosa resected) developed mild-to-severe esophageal stricture, dysphagia, and weight loss. In contrast, no esophageal stricture was evident in group B (mucosa incisions without resection) after 2 and 4 weeks, respectively. Macroscopic examination showed severe esophageal stricture and shortening of esophagus in only group A. Inflammation and fibrous hyperplasia of the submucosal layer was observed on histological examination in both groups.


The extent of loss of esophageal mucosa appears to be a critical factor for esophageal stricture. Inflammation followed by fibrosis may contribute to alteration in compliance of the esophagus but is not the main mechanism of postresection stricture.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Ferguson DD et al (2005) Evaluation and management of benign esophageal strictures. Dis Esophagus 18:359–364

    CAS  Article  Google Scholar 

  2. 2.

    Lanza FL, Graham DY et al (1978) Bougienage is effective therapy for most benign esophageal strictures. JAMA 240:844–847

    CAS  Article  Google Scholar 

  3. 3.

    Siersema PD, de Wijkerslooth LR et al (2009) Dilation of refractory benign esophageal strictures. Gastrointest Endosc 70:1000–1012

    Article  Google Scholar 

  4. 4.

    Honda M, Kobayashi H, Nakayama Y et al (2017) The mechanism of esophageal stricture after endoscopic resection: histological and biomechanical evaluation in a canine model. Ann Cancer Res Ther 25:30–37

    Article  Google Scholar 

  5. 5.

    Groth SS, Odell DD, Luketich JD et al (2015) Esophageal strictures refractory to endoscopic dilatation. In: Pawlik TM, Maithel SK, Merchant NB (eds) Gastrointestinal surgery: management of complex perioperative complications. Springer, New York, pp 13–22

    Google Scholar 

  6. 6.

    Arao M, Ishihara R, Tonai Y et al (2018) Comparison of endo cut mode and forced coag mode for the formation of stricture after esophageal endoscopic submucosal dissection in an in vivo porcine model. Surg Endosc 32:2902–2906

    Article  Google Scholar 

  7. 7.

    Committee Asge Technology, Kantsevoy SV, Adler DG et al (2008) Endoscopic mucosal resection and endoscopic submucosal dissection. Gastrointest Endosc 68:11–18

    Article  Google Scholar 

  8. 8.

    Maple JY et al (2015) Endoscopic submucosal dissection. Gastrointest Endosc 81:1311–1325

    Article  Google Scholar 

  9. 9.

    Liu BR, Song JT, Kong LJ et al (2013) Tunneling endoscopic muscularis dissection for subepithelial tumors originating from the muscularis propria of the esophagus and gastric cardia. Surg Endosc 27:4354–4359

    Article  Google Scholar 

  10. 10.

    Liu BR, Song JT, Omar Jan M et al (2015) Video of the month. Modified peroral endoscopic myotomy. Am J Gastroenterol 110:499

    Article  Google Scholar 

  11. 11.

    Mendelson AH, Small AJ, Agarwalla A et al (2015) Esophageal anastomotic strictures: outcomes of endoscopic dilation, risk of recurrence and refractory stenosis, and effect of foreign body removal. Clin Gastroenterol Hepatol 13:263–271

    Article  Google Scholar 

  12. 12.

    Larghi A, Lightdale CJ, Memeo L et al (2005) EUS followed by EMR for staging of high-grade dysplasia and early cancer in Barrett’s esophagus. Gastrointest Endosc 62:16–23

    Article  Google Scholar 

  13. 13.

    Guo HM, Zhang XQ, Chen M et al (2014) Endoscopic submucosal dissection vs endoscopic mucosal resection for superficial esophageal cancer. World J Gastroenterol 20:5540–5547

    Article  Google Scholar 

  14. 14.

    Park YM, Cho E, Kang HY, Kim JM et al (2011) The effectiveness and safety of endoscopic submucosal dissection compared with endoscopic mucosal resection for early gastric cancer: a systematic review and metaanalysis. Surg Endosc 25:2666–2677

    Article  Google Scholar 

  15. 15.

    Isomoto H, Yamaguchi N et al (2013) Management of complications associated with endoscopic submucosal dissection/endoscopic mucosal resection for esophageal cancer. Dig Endosc 25(Suppl 1):29–38

    Article  Google Scholar 

  16. 16.

    Barret M, Batteux F, Beuvon F et al (2012) N-Acetylcysteine for the prevention of stricture after circumferential endoscopic submucosal dissection of the esophagus: a randomized trial in a porcine model. Fibrogenesis Tissue Repair 5:8

    CAS  Article  Google Scholar 

  17. 17.

    Wang W, Ma Z (2015) Steroid administration is effective to prevent strictures after endoscopic esophageal submucosal dissection. Medicine 94:e1664

    CAS  Article  Google Scholar 

  18. 18.

    Yokota K, Uchida H, Tanano A et al (2016) Steroid pulse therapy prevents restenosis following balloon dilatation for esophageal stricture. Pediatr Surg Int 32:875–879

    Article  Google Scholar 

  19. 19.

    Ohki T, Yamamoto M et al (2011) Application of cell sheet technology for esophageal endoscopic submucosal dissection. Tech Gastrointest Endosc 13:105–109

    Article  Google Scholar 

  20. 20.

    Ohki T, Yamato M, Murakami D et al (2006) Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model. Gut 55:1704–1710

    CAS  Article  Google Scholar 

  21. 21.

    Ohki T, Yamato M, Ota M et al (2012) Prevention of esophageal stricture after endoscopic submucosal dissection using tissue-engineered cell sheets. Gastroenterology 143:582–588

    Article  Google Scholar 

  22. 22.

    Abercrombie M et al (1970) Contact inhibition in tissue culture. Vitro 6:128–142

    CAS  Article  Google Scholar 

  23. 23.

    Hochberger J, Koehler P, Wedi E et al (2014) Transplantation of mucosa from stomach to esophagus to prevent stricture after circumferential endoscopic submucosal dissection of early squamous cell. Gastroenterology 146:906–909

    Article  Google Scholar 

  24. 24.

    Liao ZL, Liao GB et al (2018) Transplantation of autologous esophageal mucosa to prevent stricture after circumferential endoscopic submucosal dissection of early esophageal cancer (with video). Gastrointest Endosc 88:543–546

    Article  Google Scholar 

  25. 25.

    Weston AP, Qamar MT, Schmitz RJ et al (2000) Incidence of stricture formation, ulcer bleeding, perforation and massive hematoma formation from sclerotherapy versus band ligation of esophageal varice. Gastrointest Endosc 51:AB298

    Article  Google Scholar 

  26. 26.

    Kanai N, Yamato M et al (2012) Fabricated autologous epidermal cell sheets for the prevention of esophageal stricture after circumferential ESD in a porcine model. Gastrointest Endosc 76:873–881

    Article  Google Scholar 

Download references


We gratefully acknowledge the critical review of this article by David Y. Graham, MD., Professor of Medicine, Molecular virology and Microbiology, Baylor College of Medicine; and Professor Starvos N. Stavrpoulos, MD., Winthrop University Hospital, Chief of Endoscopy, and Director, program in Advanced GI endoscopy.


Supported by Henan province innovation talents of science and technology plan (No: 184200510020).

Author information




Study concept and design: B-RL; Acquisition of Data: DL, SU; Manuscript writing: SU; Analysis and interpretation: SU, YZ, LZ, DL, DH; Administrative, technical, or material support: WY, YS, XZ, YC, ZC, DH, YY; Critical revision of the manuscript for important intellectual content: B-RL; Funding obtained: B-RL.

Corresponding author

Correspondence to Bing-Rong Liu.

Ethics declarations


Drs. Bing-Rong Liu, Dan Liu, Wenyi Yang, Saif Ullah, Zhen Cao, Dezhi He, Xuehui Zhang, Yang Shi, Yangyang Zhou, Yong Chen, Donghai He, Lixia Zhao, Yulian Yuan, and Deliang Li have no conflicts of interests or financial ties to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, B., Liu, D., Yang, W. et al. Mucosal loss as a critical factor in esophageal stricture formation after mucosal resection: a pilot experiment in a porcine model. Surg Endosc 34, 551–556 (2020).

Download citation


  • Esophagus
  • Stricture
  • Mechanism
  • ESD