Process of healing of mucosal defects in the esophagus after endoscopic mucosal resection: histological evaluation in a dog model

Background and study aims: Resection of a large amount of the esophageal mucosa often causes esophageal ulcer and postoperative stricture. The aim of this study was to evaluate the process of healing of defects in the esophageal mucosa after endoscopic mucosal resection (EMR).

Materials and methods: Cap-assisted EMR was performed in the thoracic esophagus of six beagle dogs to prepare mucosal defects with a diameter ranging from 15 to 18 mm. The process of mucosal healing was assessed histologically immediately after EMR, and on postoperative day (POD) 2, 4, 7, 14, and 28.

Results: Immediately after EMR, a thin layer of the submucosa remained in the mucosal defect, and no damage to the muscularis propria was evident. Ulcer formation and inflammatory cell invasion were observed in the remaining submucosa on POD 2 and 4. Angiogenesis and collagen fiber hyperplasia were observed after POD 7. Complete epithelialization of the ulcer was observed on POD 28. In the muscularis propria, further destruction and atrophy were evident after POD 7. Fibrosis of the muscularis propria was observed on POD 28.

Conclusion: In the esophageal wall after epithelial loss resulting from EMR, atrophy and fibrosis of the muscularis propria remain even after epithelialization.

References

• 1 Ishihara R, Iishi H, Uedo N. et al . Comparison of EMR and endoscopic submucosal dissection for en bloc resection of early esophageal cancers in Japan.  Gastrointest Endosc. 2008;  68 1066-1072
• 2 Neuhaus H. Endoscopic submucosal dissection in the upper gastrointestinal tract: present and future view of Europe.  Dig Endosc. 2009;  21 Suppl 1 S4-S6
• 3 Ono S, Fujishiro M, Niimi K. et al . Predictors of postoperative stricture after esophageal endoscopic submucosal dissection for superficial squamous cell neoplasms.  Endoscopy. 2009;  41 661-665
• 4 Mizuta H, Nishimori I, Kuratani Y. et al . Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancer.  Dis Esophagus. 2009;  22 626-631
• 5 Maish M S, DeMeester S R. Endoscopic mucosal resection as a staging technique to determine the depth of invasion of esophageal adenocarcinoma.  Ann Thorac Surg. 2004;  78 1777-1782
• 6 Tanabe S, Koizumi W, Higuchi K. et al . Clinical outcomes of endoscopic oblique aspiration mucosectomy for superficial esophageal cancer.  Gastrointest Endosc. 2008;  67 814-820
• 7 Katada C, Muto M, Manabe T. et al . Esophageal stenosis after endoscopic mucosal resection of superficial esophageal lesions.  Gastrointest Endosc. 2003;  57 165-169
• 8 Nieponice A, McGrath K, Qureshi I. et al . An extracellular matrix scaffold for esophageal stricture prevention after circumferential EMR.  Gastrointest Endosc. 2009;  69 289-296
• 9 Sakurai T, Miyazaki S, Miyata G. et al . Autologous buccal keratinocyte implantation for the prevention of stenosis after EMR of the esophagus.  Gastrointest Endosc. 2007;  66 167-173
• 10 Radu A, Grosjean P, Fontolliet C, Monnier P. Endoscopic mucosal resection in the esophagus with a new rigid device: an animal study.  Endoscopy. 2004;  36 298-305
• 11 Corr D T, Gallant-Behm C L, Shrive N G, Hart D A. Biomechanical behavior of scar tissue and uninjured skin in a porcine model.  Wound Repair Regen. 2009;  17 250-259
• 12 Spanholtz T A, Theodorou P, Amini P. et al . Severe burn injuries: acute and long-term treatment.  Dtsch Arztebl Int. 2009;  106 607-613
• 13 Macri L, Clark R A. Tissue engineering for cutaneous wounds: selecting the proper time and space for growth factors, cells and the extracellular matrix.  Skin Pharmacol Physiol. 2009;  22 83-93
• 14 Badylak S F, Vorp D A, Spievack A R. et al . Esophageal reconstruction with ECM and muscle tissue in a dog model.  J Surg Res. 2005;  128 87-97
• 15 Siersema P D. Treatment options for esophageal strictures.  Nat Clin Pract Gastroenterol Hepatol. 2008;  5 142-152
• 16 Inoue H, Minami H, Sato Y. et al . Technical feasibility of circumferential ESD and preventive balloon dilation. [in Japanese].  Stomach and Intestine. 2009;  44 394-397
• 17 Ferguson D D. Evaluation and management of benign esophageal strictures.  Dis Esophagus. 2005;  18 359-364
• 18 Siersema P D. Stenting for benign esophageal strictures.  Endoscopy. 2009;  41 363-373
• 19 Saito Y, Tanaka T, Andoh A. et al . Novel biodegradable stents for benign esophageal strictures following endoscopic submucosal dissection.  Dig Dis Sci. 2008;  53 330-333
• 20 Nieponice A, Gilbert T W, Badylak S F. Reinforcement of esophageal anastomoses with an extracellular matrix scaffold in a canine model.  Ann Thorac Surg. 2006;  82 2050-2058
• 21 Ohki T, Yamato M, Murakami D. et al . Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model.  Gut. 2006;  55 1704-1710
• 22 De Luca M, Pellegrini G, Green H. Regeneration of squamous epithelia from stem cells of cultured grafts.  Regen Med. 2006;  1 45-57
• 23 Wood F M, Kolybaba M L, Allen P. The use of cultured epithelial autograft in the treatment of major burn injuries: a critical review of the literature.  Burns. 2006;  32 395-401