Introduction

Endoscopic submucosal dissection (ESD) is widely accepted as the first-line treatment for early-stage EC, especially for endoscopic resection. However, stenosis is almost inevitable, when a circumferential mucosal defect involves over three-fourths of the esophageal circumference.¹ Multiple balloon dilation sessions are occasionally required, lowering patients’ quality of life.Local injection of corticosteroids, or oral corticosteroids administration are used to prevent strictures after ESD. Although these methods are effective, adverse events might occur. The application of polyglycolicacid (PGA) sheets combined with fibrin adhesive has also been reported to prevent stricture after esophageal ESD, but the effect of PGA alone is insufficient, steroids must be used in combination.² The administration of recombinant basic fibroblast growth factor (bFGF) to skin wounds can accelerate acute and chronic wound healing.³ However, its use in gastrointestinal tract treatment remains unreported, and its efficacy in preventing stricture after esophageal ESD is unknown.

Aims & Methods

This study aimed to evaluate the effectiveness of the combination of PGA sheets and bFGF through a comparative analysis. We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked polyglycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA+bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). sevaluated the mucosal constriction rate, and also performed several histological evaluations. We photographed five fields per section from each pig and measured the area stained with anti–α SMA antibody and anti–calponin-1 antibody per field of view (×200) with a digital image analyzer. To evaluate the state of tissue regeneration in the entire wound, we measured the thickness from the bottom edge of the area stained with Elastica–Masson staining to the surface layer of the wound.

Results

Esophageal stricture was significantly suppressed in the PGA+bFGF group compared with that in the control group (control: 63.6%, PGA: 42.2%, PGA+bFGF: 36.7%, p<0.05 for PGA+bFGF group vs control group). Moreover, areas stained with anti–α SMA antibody were significantly less in the PGA+bFGF and PGA groups compared with those in the control group (PGA+bFGF: 16.7%, PGA: 15.5%, control: 24.0%, p<0.01 for PGA+bFGF and PGA groups vs control group). Significant suppression in areas stained with anti–calponin-1 antibody was also observed in the PGA+bFGF and PGA groups compared with those in the control group (PGA+bFGF: 24.4%, PGA: 19.8%, control: 32.9%, p<0.001 for PGA+bFGF and PGA groups vs control group). Regarding the thickness of the fibrous layer in the wound, the difference between the thinnest and thickest areas was smallest in the PGA+bFGF group compared with the PGA and control groups (PGA+bFGF: 467.3, PGA: 934.9, control:726.2 μm, p<0.05 for PGA+bFGF group vs control group).

Conclusion

Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.

References

1. Miwata T, Oka S, Tanaka S, Kagemoto K, Sanomura Y, Urabe Y, et al. Risk factors for esophageal stenosis after entire circumferential endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma. Surg Endosc. 2016;30(9):4049-56.
2. Sakaguchi Y, Tsuji Y, Shinozaki T, Ohki D, Mizutani H, Minatsuki C, et al. Steroid injection and polyglycolic acid shielding to prevent stricture after esophageal endoscopic submucosal dissection: a retrospective comparative analysis (with video). Gastrointest Endosc. 2020;92(6):1176-86 e1.
3. Akita S, Akino K, Imaizumi T, Hirano A. Basic fibroblast growth factor accelerates and improves second-degree burn wound healing. Wound Repair Regen. 2008;16(5):635-41.

Clinical Case Summary

A 39-year-old woman with no previous significant medical history presented with a week-long history of diarrhea and black stools in the last 48 hours. Laboratory tests revealed mild anemia (Hb 11 mean corpuscular volume 78), and normal levels of inflammatory markers. Esophagogastroduodenoscopy (EGD) was performed, showing in the second portion of the duodenum atrophic mucosa with villous blunting, scalloped folds, and multiple superficial subcentimetric ulcers covered with fibrin, as shown in figures 1, 2, 3. Duodenal biopsies demonstrated marked villous atrophy, intraepithelial lymphocytosis, and absence of plasma cells. Given the villous atrophy, a differential diagnosis with celiac disease was considered, and anti-tissue transglutaminase IgA antibodies and anti-endomysial were requested, which came back negative. Further investigation revealed low levels of IgG and IgA, and after excluding secondary causes, diagnosis of common variable immunodeficiency and celiac disease-like enteropathy were established. Replacement treatment was initiated with intravenous immunoglobulins, resulting in clinical and endoscopic improvement of the patient.

References

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Malesza IJ, Malesza M, Krela-Kaźmierczak I, et al. Primary Humoral Immune Deficiencies: Overlooked Mimickers of Chronic Immune-Mediated Gastrointestinal Diseases in Adults. Int J Mol Sci 2020
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