糖皮质激素序贯疗法预防环周食管浅表肿瘤内镜黏膜下剥离术后狭窄的研究

Efficacy and safety of sequential therapy with glucocorticoids in preventing esophageal stricture after endoscopic submucosal dissection for circumferential superficial esophageal neoplasms

目的评估糖皮质激素序贯疗法预防环周食管浅表肿瘤内镜黏膜下剥离术(ESD)后食管狭窄的有效性和安全性,并探讨糖皮质激素的适宜剂量及疗程。方法回顾分析2017年1月至2022年12月38例在苏北人民医院因全周食管浅表肿瘤行ESD的患者病例资料,其中口服强的松组(n=10)仅术后第三天口服强的松30 mg/d,每三周减量5 mg;序贯长疗程组(n=11)术后立即予黏膜缺损处注射曲安奈德,第三天起口服强的松30 mg/d并每三周减量5 mg,而序贯短疗程组(n=17)注射曲安奈德48 h后口服强的松的起始剂量30 mg/d并逐渐减量,疗程共8周。主要观察指标:术后食管狭窄率、难治性狭窄率、内镜下球囊扩张(EBD)次数、食管狭窄的总治疗时间、术后1月、3月的创面愈合率、ESD和EBD手术并发症及使用糖皮质激素相关不良时间。结果口服强的松组、序贯长疗程组、序贯短疗程组ESD后食管狭窄率及难治性狭窄率分别为80%(8/10)、27.3%(3/11)、29.4%(5/17)和60%(6/10)、18.2%(2/11)、17.6%(3/17),差异有统计学意义(χ^(2)=8.007,P=0.018、χ^(2)=6.364,P=0.042),口服强的松组明显高于序贯治疗组(P<0.05),而序贯长疗程组和序贯短疗程组间无差异(P>0.05)。序贯长疗程组及序贯短疗程组术后EBD次数分别为0(0,8)、0(0,8),明显少于口服强的松组7.5(0,12)(H=9.882,P=0.007),而序贯长疗程组和序贯短疗程组间无差异(P>0.05)。口服强的松组术后食管狭窄患者的总治疗时间为(133.75±38.61)d,明显长于序贯长疗程组(85.33±20.74)d和序贯短疗程组(84.8±27.23)d(F=4.38,P=0.035),而两序贯组间比较无差异(P>0.05)。术后一月3组创面愈合率分别为50%、72.7%和76.5%,术后三月的创面愈合率分别为80%,90.9%和94.1%,两时间点各组间比较均无差异(χ^(2)=3.225,P=0.199;χ^(2)=3.429,P=0.180)。口服强的松组出现糖皮质激素相关不良反应6人次,序贯长疗程组有7人次,而序贯短疗程组仅2人次。结论糖皮质激素序贯疗法能安全有效地预防环周食管ESD后狭窄,为减少糖皮质激素相关不良时间,可适当减少序贯疗法中强的松的总剂量。

Objective To evaluate the efficacy and safety of sequential therapy with glucocorticoids in preventing esophageal stricture after endoscopic submucosal dissection(ESD)for circumferential superficial esophageal neoplasms,and to investigate the appropriate dosage and course of glucocorticoids.Methods A retrospective analysis was performed on data of 38 patients who underwent endoscopic submucosal dissection for circumferential superficial esophageal neoplasms from January 2017 to December 2022 in Northern Jiangsu People's Hospital.The patients were divided into an oral prednisone group(n=10),a sequential long-course group(n=11),and a sequential short-course group(n=17).Prednisone 30 mg was administered orally for 3 weeks and then the dose was reduced in 5 mg decrements every 3 weeks since the third day after ESD in the oral prednisone group.Patients in the sequential long-course group received intralesional triamcinolone injection combined with oral prednisone 30 mg/day,and the dosage was reduced in 5 mg decrements every 3 weeks.Patients in the sequential short-course group received prednisone at 30 mg/day,and the dosage was tapered over 8 weeks after intralesional triamcinolone injection.The frequency of esophageal stenosis and refractory stenosis,the number of endoscopic balloon dilatation(EBD)treatments,treatment time for esophageal stenosis,the rate of wound healing at 1 and 3 months after ESD,and adverse events potentially associated with glucocorticoid administration were compared among the three groups.Results The frequency of esophageal stenosis and refractory stenosis in the oral prednisone group,sequential long-course group,and sequential short-course group were 80%(8/10),27.3%(3/11),and 29.4%(5/17),and 60%(6/10),18.2%(2/11),and 17.6%(3/17),respectively,and the difference was statistically significant among the three groups(χ^(2)=8.007,P=0.018 andχ2=6.364,P=0.042,respectively).In pairwise comparisons,the above indicators in the sequential long-course group and sequential short-course group were significantly lower than those of the oral prednisone group(P<0.05),but there were no statistical difference between the sequential long-course group and sequential short-course group(P>0.05).The number of EBD treatments and treatment time for esophageal stenosis of the three groups were 7.5(range,0 to 12),0(range,0 to 8),and 0(range,0 to 8),and(133.75±38.61)d,(85.33±20.74)d,and(84.8±27.23)d,respectively,and the difference was statistically significant among the three groups(H=9.882,P=0.007 and F=4.38,P=0.035).In pairwise comparisons,the above indicators in the sequential long-course group and sequential short-course group were significantly less than those of the oral prednisone group(P<0.05),but there were no statistical difference between the sequential long-course group and sequential short-course group(P>0.05).The rate of wound healing in the oral prednisone group,sequential long-course group,and sequential short-course group at 1 and 3 months after ESD were 50%,72.7%,and 76.5%,and 80%,90.9%,and 94.1%,respectively,with no significant difference among the three groups(χ^(2)=3.225,P=0.199 and χ^(2)=3.429,P=0.180,respectively).Oral herpes virus infection,mycotic esophagitis,and pneumonia were observed in 6 patients in the oral prednisone group and in 7 in the sequential long-course group.Two patients had mycotic esophagitis in the sequential short-course group.Conclusion Sequential therapy with glucocorticoids can effectively prevent esophageal stricture after ESD for circumferential superficial esophageal neoplasms.To reduce glucocorticoid-associated adverse events,the total dose of prednisone in sequential therapy can be appropriately reduced.