[Effect and mechanism of glucocorticoids in preventing stenosis after esophageal endoscopic submucosal dissection]

Zhonghua Yi Xue Za Zhi. 2022 May 31;102(20):1506-1511. doi: 10.3760/cma.j.cn112137-20210905-02024.
[Article in Chinese]

Abstract

Objective: To explore the role and specific mechanism of glucocorticoids in preventing stenosis after esophageal endoscopic submucosal dissection (ESD). Methods: Data of 81 patients [51 cases were male and 30 cases were female, aged (62.09±7.95) years] undergoing early esophageal cancer or precancerous lesions with a stripping range ≥3/4 circle hospitalized from January 2019 to February 2021 in Department of Gastroenterology, Zhongda Hospital, Southeast University. They were randomly divided into the control group (n=23), oral prednisone acetate group (n=28) and/or combined with local injection Triamcinolone acetonide group (n=30). Analysis the stenosis rates, endoscopic stent dilatation times, the scores of the Atkinson classification and QLQ-OES18 after 12 weeks. Also the expression of carbohydrate sulfotransferase15 (CHST15) mRNA, TGF-β1 and Collagen-Ⅰ protein were compared by real-time PCR or immunohistochemistry. Results: The stenosis rates of the control group, oral prednisone acetate group and/or combined with local injection Triamcinolone acetonide group were 82.6% (19/23), 46.4% (13/28) and 20.0% (6/30) (P<0.001); endoscopic stent dilatation times [M (Q1,Q3)] in these three groups were 2 (1, 3), 0 (0, 0) and 0 (0, 0) (P<0.001). After ESD, the scores of the Atkinson classification and QLQ-OES18 in the three groups were lower than before (P<0.001); and the expression of CHST15 mRNA in the three groups were 4.31±0.13, 3.44±0.07 and 2.84±0.21 respectively (P<0.001). Compared with the control group, the expression of CHST15 mRNA in oral prednisone acetate group was down-regulated (P<0.001), and was the lowest in oral prednisone acetate combined with local injection Triamcinolone acetonide group (P<0.001). As CHST15 mRNA was down-regulated, the expression of TGF-β1 and Collagen-I protein was also down-regulated (P<0.05). Conclusions: Oral prednisone alone or combined with local injection of triamcinolone acetonide both can prevent esophageal stenosis effectively. Oral combined with local injection of glucocorticoid is particularly more effective. Glucocorticoid can reduce the expression of CHST15 mRNA, thereby inhibiting the expression of TGF-β1 and Collagen-I protein.

目的: 探讨糖皮质激素预防食管内镜黏膜下剥离术(ESD)术后狭窄的效果及其具体机制。 方法: 前瞻性选取2019年1月至2021年2月因早期食管癌或癌前病变在东南大学附属中大医院消化科行ESD治疗、剥离范围≥3/4环周的81例患者,其中男51例,女30例;年龄(62.09±7.95)岁,随机数字表法将患者分为对照组(23例)、口服醋酸泼尼松组(28例)和口服醋酸泼尼松联合局部注射曲安奈德组(30例)。分析术后12周3组患者食管狭窄的发生率、内镜下探条扩张次数,比较手术前后Atkinson分级和食管癌患者补充量表(QLQ-OES18)评分。采用荧光定量PCR法和免疫组化法分别检测3组食管黏膜组织中碳水化合物磺基转移酶15(CHST15)mRNA以及转化生长因子β1(TGF-β1)和Ⅰ型胶原蛋白(collagen-Ⅰ)的表达。 结果: 对照组、口服醋酸泼尼松组和口服醋酸泼尼松联合局部注射曲安奈德组患者术后食管狭窄的发生率分别为82.6%(19/23)、46.4%(13/28)和20.0%(6/30),差异有统计学意义(P<0.001);术后探条的扩张次数[MQ1Q3)]分别为 2(1,3)、0(0,0)和0(0,0)次,差异有统计学意义(P<0.001);术前和术后Atkinson分级和QLQ-OES18评分的差异均有统计学意义(均P<0.001)。术后复查时,对照组、口服醋酸泼尼松组和口服醋酸泼尼松联合局部注射曲安奈德组患者食管组织中CHST15 mRNA的相对表达量分别为4.31±0.13、3.44±0.07、2.84±0.21,差异有统计学意义(P<0.001);口服醋酸泼尼松组与对照组比较,CHST15 mRNA的相对表达量下调(P<0.001),而口服醋酸泼尼松联合局部注射曲安奈德组与口服醋酸泼尼松组比较,CHST15 mRNA的表达进一步下调(P<0.001)。随着CHST15 mRNA表达的下调,口服醋酸泼尼松组和口服醋酸泼尼松联合局部注射曲安奈德组食管组织中TGF-β1和collagen-Ⅰ蛋白的表达亦下调(均P<0.05)。 结论: 单独口服或者口服联合局部注射糖皮质激素均可有效预防食管ESD术后狭窄,减少术后扩张次数,口服联合局部注射糖皮质激素效果更佳;糖皮质激素可降低食管黏膜组织中CHST15 mRNA的表达,抑制其所调控的TGF-β1和collagen-Ⅰ蛋白表达。.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetates
  • Aged
  • Constriction, Pathologic
  • Endoscopic Mucosal Resection* / adverse effects
  • Esophageal Neoplasms*
  • Esophageal Stenosis* / etiology
  • Esophageal Stenosis* / pathology
  • Esophageal Stenosis* / prevention & control
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • Prednisone
  • RNA, Messenger
  • Sulfotransferases
  • Transforming Growth Factor beta1
  • Triamcinolone Acetonide

Substances

  • Acetates
  • CHST15 protein, human
  • Glucocorticoids
  • Membrane Glycoproteins
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Sulfotransferases
  • Triamcinolone Acetonide
  • Prednisone