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Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model.

ABSTRACT: BACKGROUND & AIMS:Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation. METHODS:Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support membrane and control group (n = 6) received 4 paper support membranes. ADSC were labelled with PKH-67 fluorophore to allow probe-based confocal laser endomicroscopie (pCLE) monitoring. After 28 days follow-up, animals were sacrificed. At days 3, 14 and 28, endoscopic evaluation with pCLE and esophagography were performed. RESULTS:One animal from the control group was excluded (anesthetic complication). Animals from ADSC group showed less frequent alimentary trouble (17% vs 80%; P = 0.08) and higher gain weight on day 28. pCLE demonstrated a compatible cell signal in 4 animals of the ADSC group at day 3. In ADSC group, endoscopy showed that 1 out of 6 (17%) animals developed a severe esophageal stricture comparatively to 100% (5/5) in the control group; P = 0.015. Esophagography demonstrated a decreased degree of stricture in the ADSC group on day 14 (44% vs 81%; P = 0.017) and day 28 (46% vs 90%; P = 0.035). Histological analysis showed a decreased fibrosis development in the ADSC group, in terms of surface (9.7 vs 26.1 mm²; P = 0.017) and maximal depth (1.6 vs 3.2 mm; P = 0.052). CONCLUSION:In this model, transplantation of allogenic ADSC organized in double cell sheets after extended esophegeal ESD is strongly associated with a lower esophageal stricture's rate.

SUBMITTER: Perrod G

PROVIDER: S-EPMC4773126 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model.

Perrod Guillaume G Rahmi Gabriel G Pidial Laetitia L Camilleri Sophie S Bellucci Alexandre A Casanova Amaury A Viel Thomas T Tavitian Bertrand B Cellier Christophe C Clement Olivier O

PloS one 20160301 3

<h4>Background & aims</h4>Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation.<h4>Methods</h4>Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support m ...[more]

PMID: 26930409

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Project description:BackgroundEsophageal stricture is a major complication of endoscopic submucosal dissection (ESD) in patients with superficial esophageal cancer (SEC). Oral steroids have been used to prevent esophageal stricture in patients with more than 75% of the esophageal circumference resected. However, there are no established guidelines regarding the optimal duration of steroid use. This retrospective observational study aimed to compare the incidence of esophageal stricture according to the period of prophylactic oral steroid use and to identify the risk factors for esophageal stricture.MethodsEighty-one patients who were prescribed prophylactic steroid after undergoing ESD for SEC with more than 75% of esophageal circumference resected were enrolled. Patients were classified into the four-week steroid group (n=72) or eight-week steroid group (n=9) to compare the incidence of esophageal stricture. In addition, the patients were subdivided into those who developed esophageal stricture (n=24) and those who did not (n=57) to identify the risk factors for esophageal stricture.ResultsTwenty patients (27.8%) in the four-week oral steroid group and four patients (44.4%) in the eight-week oral steroid group developed esophageal stricture (P=0.44). The univariable analysis identified tumor size, longitudinal length of semi-circumferential resection, and proportion of circumferential resection as risk factors of esophageal stricture. The multivariable analysis identified the proportion of circumferential resection as an independent risk factor. After adjusting for the proportion of circumferential resection, the incidence of stricture was marginally higher in the eight-week steroid group [P=0.05; odds ratio (OR): 5.69; 95% confidence interval (CI): 1.01-32.15].ConclusionsEight weeks of oral steroid prophylaxis does not reduce the risk of stricture after extensive ESD more than four weeks of oral steroid prophylaxis. The proportion of circumferential resection is the strongest risk factor for stricture in patients with SEC undergoing ESD.

Project description:Background: Widespread endoscopic submucosal dissection (ESD) in early esophageal cancer patients is closely associated with esophageal stricture, which dramatically reduces patients' quality of life and increases huge medical burdens. Endoscopic injection of steroid was proved as a protective method for post-ESD strictures. Other materials such as botulinum toxin type A (BTX-A) may be potential candidates. We conducted this prospective cohort study to compare the efficacy and feasibility of endoscopic injection of BTX-A and triamcinolone acetonide (TA) for the prevention of esophageal stricture. Methods: Seventy-eight patients with esophageal mucosal defects of more than two thirds of the circumference were successively enrolled and divided into 3 groups: BTX-A group (group A, n=26), TA group (group B, n=16) and control group (group C, n=36). Patients in group A were immediately injected with BTX-A after ESD, in group B were immediately injected with TA and in group C received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 6 and 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in all groups received bougie dilation. All patients were followed up for one year. Results: The proportion of patients developing stricture in BTX-A group was 30.00% (intention to treat analysis, 9/30) and 26.92% (per protocol analysis, 7/26), in TA group was 40.90% (intention to treat analysis, 9/22) and 43.75% (per protocol analysis, 7/16), and in control group was 84.21% (intention to treat analysis, 32/38) and 83.33% (per protocol analysis, 30/36) (p<0.001). When further comparing between each of the two groups, the incidence of esophageal stricture was lower in BTX-A group than that in control group (p<0.001), and lower in TA group than that in control group (p=0.004). Furthermore, in entire circumference mucosal defect subgroup, the esophageal stricture was significantly lower in BTX-A group than that in TA group (33.3% vs 100%, p=0.0454). Conclusions: Endoscopic injection of BTX-A and TA were effective in preventing post-ESD esophageal strictures and BTX-A injection was particularly effective in entire circumference mucosal defect patients. Multi-centered, randomized prospective study with larger sample size should be conducted. (Clinical trial registration number: ChiCTR2100042970, registered 1 February 2021, retrospectively registered, http://www.chictr.org.cn/listbycreater.aspx).

Dataset Information

Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model.

Publications

Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model.

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