食管ESD术后狭窄防治

1、ESD术后食管狭窄防治中国人民解放军陆军军医大学新桥医院重庆市消化疾病临床医学研究中心赵晓晏-11-10第1页ESD适应症第2页Techniques in Gastrointestina lEndoscopy 19()159169第3页Risk of stricture formation in patients undergoing extensive ER/ESD. Study N. Diagnosis Extent of the circumference Stricture rate van Vilsteren FG4* 25 BE, AC or HGD 75% 88% Park JS

2、8* 5 SCC 75% 83% Ono S7* 10 SCC 75% 90% Katada C6* 19 SCC, HGD and AC 75% Wen J9* 7 SCC 75% 71% *No preventive strategy used. 第4页1.反抗炎药系统性用药；2.局部注射消炎或抗纤维原物质；3.单纯内镜方法（支架、扩张）；4.组织工程方法-细胞治疗；5.胃粘膜移植到食管；6.各种其它方法第5页post-ESD 食管狭窄防治方法预防性系列扩张腔内注射内固醇药品/局部类固醇凝胶全覆膜金属支架聚乙醇酸（PGA）片和纤维蛋白胶放射状切开/环状切除组织工程及再生医学自体粘膜移植Mi

3、nerva Chir ;73:394-409.第6页List of methods, which could be, at present, considered in clinical practice1、Oral steroids Partially effective, easy to do No RCT available Drawback: adverse events2、Local injection of steroids Easy to do RCT available Partially effective Drawback: a delayed perforation wa

4、s reported3、Stenting Only fully covered metallic stents appropriate Easy to do RCT available Limited efficacy Drawback: no clear data on stent removal, the need for fixation to decrease migration rateMinerva Chirurgica ;73(4):394-409第7页球囊扩张术/内固醇药品Characteristics of steroid refractory caseResected ci

5、rcumference: 9/10 or moreResected longitudinal diameter: 50 mmLocation of esophagus: cervical esophagusHistory of chemo-radio therapyGIE ;74(6):1389-1393第8页全身使用皮质类固醇长久使用造成感染、骨质疏松症、糖尿病、视力下降等不良反应第9页ActionAdministrationAdvantagesDisadvantages and limitationsClinical studyCorticosteroidsSteroidalOral in

6、takeStrongly inhibits the infiltration of inflammatory cells, the hyperplasia associated with granulation, and the fibrosis of the remaining submucosal layerGeneral side effects (severe infection, peptic ulcer, hyperglycemia, psychiatric symptoms, and osteoporosis)Delayed wound healingTriamcinolone

7、acetonideSteroidalLocal injectionInhibits the infiltration of inflammatory cells, the hyperplasia associated with granulation, and the fibrosis of the remaining submucosal layerRisk of ulcer formation due to accidental injection into the muscularisDelayed wound healingPre-clinical studyMMCInhibition

8、 of DNA synthesisLocal injectionInhibits the proliferation and activation of fibroblastsAn effect has not been shown for the prevention of esophageal strictures, although MMC improves recurrent dysphagia or restenosis after the dilatation of esophageal stricturesThe risks of perforation and secondar

9、y malignancyN-acetylcysteineAntioxidant moleculeOral intakeAntifibrotic effect without the inhibition of wound healingInsufficient effect in an animal model of severe esophageal stricture抗炎抗肉芽组织抗纤维化抗炎抗肉芽组织抗纤维化抑制纤维母细胞 活化与增生 抗纤维化重症感染消化性溃疡高血糖精神症状骨质疏松注射部位溃疡形成风险延缓伤口愈合第10页Ref.Resection sizeThe methodology

10、 of triamcinolone injectionTreatment outcomesCircumference1Length(mm)Injection needleConcentration (mg/mL)Single dose (mL)Number of punctures(/session)Total amounts (mg)SessionsThe rate of stricturesThe number of EBDObservation periodsHashimotoet al35 3/45425 G, 4 mm100.29-3118-62Three times219%1.7

11、(0-15)1 yr(28-60)(4/21)Hanaokaet al36 3/458 1125 G50.5-120-40100Single36.60%0 (0-2)2 mo(3/30)第11页局部使用皮质类固醇注射开始于其基部溃疡远端边缘，并在10毫米处向近端边缘均匀重复注射（0.5毫升/点，浓度10毫克/毫升）第12页其它含有消炎或抗纤维作用物质局部应用肉毒杆菌毒素小干扰RNA(CHST15)止血粉(TC.325, Hemospray)丝裂霉素CN-乙酰半胱氨酸氨甲酯（治疗支气管哮喘、瘢痕和肥厚疤痕抗过敏药品）第13页预防性扩张策略降低狭窄发生率（59% vs. 92%）减轻狭窄程度缩短治

12、疗时间9%穿孔率第14页食管支架自膨式全覆膜金属支架18.2% vs72.8%2-8w固定/移位（金属夹、锚定、缝合）组织生长次生梗阻生物降解支架（Walterova et al., presented at DDW ）质量问题多二恶英肉眼炎症降解颗粒和食物梗阻高塑组织反应其它材料或药品支架第15页移植人羊膜移植：羊膜由无血管间质和单层柱状细胞上皮组成，表示极少组织相容性抗原（免疫排斥不太可能）猪表皮脱细胞基质移植Xe-DermaWalterova et al., presented at DDW 药品洗脱支架第16页组织工程方法-细胞、组织疗法促进上皮愈合支持上皮重建抗炎抑制胶原形成第17页

13、组织细胞工程与再生医学Techniques in Gastrointestinal Endoscopy, ; 13(1):105-109Gastroenterolgy,;143:582588Annals of Translational Medicine, ;5(8):5-7第18页胶原蛋白玻璃胶（动物试验）2 cm第19页GIE ;85:1076-85第20页去细胞皮肤基质(动物试验)GIE ；86（6）:1160-1167第21页Dig Dis Sci. May 8. doi: 10.1007/s10620-018-5094-4. Autologous Flap Transfer for

14、Esophageal Stricture Prevention After Endoscopic Submucosal Dissection in a Porcine Model.Tang A1, Ma C1, Deng P1, Zhang H1, Xu Y1, Min M1, Liu Y2Control groupFlap groupWeight change (kg)3.0Dysphagia score0.6Clinical outcomes第22页Am J Gastroenterol. May 1:938. doi: 10.1038/s41395-01

15、8-0142-4.Autologous Skin-Grafting Surgery for the Prevention of Esophageal Stenosis After Complete Circular Endoscopic Submucosal Tunnel Dissection.Chai N1, Zhang W1, Linghu E2, Han Y3, Chai M1, Li Z1, Zou J1, Li L1, Xiong Y1Endoscopy. Oct;50(10):1017-1021. doi: 10.1055/a-0622-8019. Epub Jun 11.Endo

16、scopic mucosal autograft for treating esophageal caustic strictures: preliminary human experience.He K#1, Zhao L#1, Bu S2, Liu L1, Wang X1, Wang M1, Fan Z1第23页第24页Endoscopicmucosalautograftfortreatingesophagealcausticstrictures:preliminaryhumanexperience.He K#1,Zhao L#1,Bu S2,Liu L1,Wang X1,Wang M1,

17、Fan Z1.Author informationAbstractEsophagealcausticstricture is a stubborn disease and postoperative restenosis limits the clinical efficacy ofendoscopicdilation. Autologousmucosalgrafts have been successfully applied in the treatment of urethral stricture and in the prevention of stricture after ext

18、ensivemucosalresection. We aimed to usemucosalautografting performed endoscopically to treat refractoryesophagealstricture. METHODS: Three patients with intractable corrosiveesophagealstricture were treated endoscopically by combining dilation with autologousmucosaltransplantation. RESULTS: All proc

19、edures were successful with no severe complications.Mucosalregeneration was shown at the transplanted segments. One patient was able to maintain a normal diet with complete remission after 1year of follow-up.Intraluminal stenosis and dysphagia were significantly improved in another two patients. CON

20、CLUSIONS:Mucosalautografting can achieveesophagealre-epithelialization, inhibit undesired fibrosis, prevent restenosis, and promote functional regeneration.Endoscopy. Oct;50(10):1017-1021第25页其它胃粘膜移植到食管支架辅助粘膜切除术聚乙醇酸片和纤维蛋白胶World J Gastroenterol. Mar 7; 24(9): 10461055第26页 Current availabilityAdvantage

21、LimitationStepwise resectionGoodTechnically easy and safeLocal recurrenceDifficulty in additional endoscopic resectionPreemptive balloon dilationGoodWidely usedHigh failure rateInferior to steroid treatmentSelf-expandable metal stentsGoodWidely usedLimited efficacyLocal steroid injectionGoodSuperior

22、 to balloon dilation aloneSingle sessionNo concern of systemic adverse eventPotential risk of perforationOral steroid medicationGoodSuperior to balloon dilation aloneNoninvasiveSystemic adverse eventsLong administration periodLocal botulinum toxin injectionFairSuperior to balloon dilation aloneSingl

23、e sessionSmall number of literatureOral tranilastGoodNo concern of systemic adverse eventSmall number of literatureTissue shielding methodFairNoninvasiveNo adverse eventTime-consumingDifficult applicationCell sheet transplantationPoorNoninvasiveNo adverse eventTime-consumingExtremely high medical co

24、st第27页新桥医院临床实践第28页Gut and Liver（已接收）环状切除+气囊扩张第29页第30页BackgroundThe feasibility and safety of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms extending to the cervical esophagus currently remain unknown because of the limited number of cases. We aimed to clarify the clinic

25、al outcomes of these cases.MethodsThis was a case series study conducted at a single institution that enrolled 26 consecutive patients with superficial esophageal neoplasms extending to the cervical esophagus who underwent ESD between July and December .ResultsEn bloc and complete resection rates were both 100% and no major intraprocedural complications occurred. Thirteen patients were treated with prophylactic steroid therapy. The incidence of postoperative stricture in patients with a circumferential mucosal defect