Prophylaxis Of Esophageal Strictures After Circumferential ESD By Endoscopic Deployment Of Carboxymethyl Cellulose Sheets

Objective: To investigate the efficacy and mechanism of carboxymethyl cellulose sheet in prevention of esophageal stenosis after endoscopic submucosal dissection(ESD).Methods: The experiment was divided into two parts.The first part is animal experiment.The 14 pigs were divided into two groups,group CMC(n=7)and control group(n=7).After the preoperative health observation,a circumferential artificial ulcer(5-cm long dissection in the lower esophagus between 40 cm and 45cm)was prepared by a standard ESD technique under the general anesthesia.In group CMC,the CMC sheet was placed immediately after the operation,and the control group was not treated.All experimental animals were sacrificed on the 14 day after operation.After the operation,two groups of animals were observed carefully.The change of body weight,dysphagia scores,endoscopic examination results and the mucosal stenosis data of the wound tissue were recorded.The second part is the basic experimental research.Histopathological examination was performed on specimen 14 days after operation.HE staining and Masson staining were used to compare the injury of the muscularis propria,the degree of fibrosis and the regeneration of epithelium in the two groups.Elisa method was used to detect the content of TGF-beta1,TNF-a,IL-1,IL-6 in the serum of animals before and on the 14 th day after operation.Real time quantitative PCR and Western blot were used to detect the expression of TGF-beta1,CTGF,a-sma in protein level and mRNA level respectively.Results: Part I.The two groups of body weight in 14 th day after operation were decreased,but the decreased weight of CMC group is lower than that of control group [(3.09±1.63%)vs.(4.97±3.40)%,p=0.220].On 7th day after operation,the dysphagia index of CMC group is lower than that of control group[(1.1+0.7)vs.(2.0+0.8),p=0.055];on 14 th day after operation,CMC group of dysphagia index is significantly lower than that of control group [(2.3+0.8)vs.(3.3+0.8),p=0.029].On 14 th day after operation,the esophagus of the two groups were all narrow,but the wound healing of CMC group was better than that of the control group.According to the gross specimen measurement,the esophageal mucosa stenosis rate of CMC group was significantly lower than that of the control group[(53+5.6)% vs.(72.1+4.0)%,p<0.05].Part II.According to the results detected by histopathology,the length of mucosal re-epithelium was(7.21+0.86)mm and(5.30 + 1.25)mm in CMC group and control group respectively,p=0.006;the thickness of esophageal submucosal fibrosis was significantly lower in CMC group than in control group [(1.01+0.24)mm vs.(1.54+0.21)mm,p=0.001].;the score of proper muscle layer injury was higher in CMC group than in the control group,p=0.016.The blood levels of TGF-beta1 is lower in the CMC group than in the control group [(3285.71 + 531.61)(4593.71+771.03),p=0.003];the difference of TGF-beta1 between preoperative and postoperative is also significant,p=0.021;but there was no statistically significance between the two groups in TNF-α,IL-1β and IL-6.The result of Real time PCR and Western blot showed that compared with the control group,the expression level of mRNA and protein of TGF-beta1,CTGF or α-sma was significantly lower in the CMC group respectively,p<0.05.Conclusion: Endoscopic deployment of CMC membrane after circumferential ESD of the esophagus can effectively reduce the process of esophageal stenosis in pigs,and therefore is a promising strategy for prevention of post-ESD esophageal stenosis.