含曲安奈德黏膜下注射液对预防大面积食管浅表肿瘤内镜黏膜下剥离术后食管狭窄的研究

Effects of triamcinolone acetonide‑saline submucosal injection for prevention of esophageal stricture after endoscopic submucosal dissection for extensive superficial esophageal neoplasms

摘要:

目的 评估使用含曲安奈德的黏膜下注射液对预防大面积食管浅表肿瘤内镜黏膜下剥离术（endoscopic submucosal dissection，ESD）后食管狭窄的有效性与安全性。方法 纳入2018年1月至2020年12月江苏省苏北人民医院消化内科收治的病灶范围>2/3食管环周的75例食管浅表肿瘤患者，按随机数字表法分为3组：A组（黏膜下注射液含有曲安奈德，n=25）、B组（ESD后立即予黏膜缺损处内镜下注射曲安奈德，n=25）、C组（仅行ESD，n=25）。ESD术后复查胃镜评估创面愈合情况、是否存在食管狭窄及食管狭窄程度。食管狭窄患者予内镜下球囊扩张术（endoscopic balloon dilatation，EBD）治疗。比较各组ESD完成情况、手术时间、曲安奈德使用量、食管狭窄发生率和进行EBD治疗的次数。结果 各组均顺利完成手术，无术中穿孔、大出血及术后迟发性穿孔发生。3组手术完成时间分别为A组（72.87±12.99）min、B组（94.15±14.22）min、C组（74.08±11.86）min，差异有统计学意义（F=20.925，P<0.001），其中A组、C组手术时间明显短于B组手术时间（LSD‑t=5.759，P<0.001；LSD‑t=5.432，P<0.001），A组、C组间比较差异无统计学意义（LSD‑t=0.327，P=0.745）。A组、B组所用曲安奈德量分别为（125±15）mg、（133±19）mg，差异无统计学意义（t=1.673，P=0.101）。A、B、C组术后1个月复查胃镜创面愈合率分别为76%（19/25）、84%（21/25）、76%（19/25），差异无统计学意义（χ2=0.636，P=0.728）。3组术后食管狭窄率分别为A组52%（13/25）、B组52%（13/25）、C组84%（21/25），差异有统计学意义（χ2=7.295，P=0.026），其中A组、B组术后食管狭窄率均低于C组（P=0.015；P=0.015）。A、B、C组术后狭窄患者接受EBD治疗的中位次数（范围）分别为4次（0~9次）、5次（0~13次）、9次（0~16次），差异有统计学意义（H=17.58，P<0.001），其中A组、B组的EBD次数均少于C组（H=23.96，P<0.001；H=19.00，P=0.002），而A组、B组间比较差异无统计学意义（H=4.96，P=0.407）。3组食管全周黏膜切除患者术后食管狭窄率均为100%，其中A组术后EBD治疗（6.90±1.10）次、B组（10.13±2.42）次、C组（15.29±0.76）次，差异有统计学意义（F=57.754，P<0.001），其中A组EBD次数少于B组（LSD‑t=4.294，P<0.001），B组少于C组（LSD‑t=6.294，P<0.001）。3组中非全周黏膜缺损患者术后EBD中位次数（范围）分别为A组0次（0~9次）、B组0次（0~6次）、C组8次（0~10次），差异有统计学意义（H=19.72，P<0.001），其中A组、B组的EBD中位次数均少于C组（H=17.93，P<0.001；H=16.62，P<0.001），而A组、B组间比较差异无统计学意义（H=1.31，P=0.779）。结论 含曲安奈德黏膜下注射液能安全有效预防大面积食管浅表肿瘤ESD后食管狭窄，与ESD后单次注射曲安奈德相比，能缩短手术时间，减少全周黏膜缺损患者食管浅表肿瘤ESD后食管狭窄的EBD次数。

Abstract:

Objective To evaluate the efficacy and safety of triamcinolone acetonide-saline submucosal injection for prevention of esophageal stricture after endoscopic submucosal dissection (ESD) for extensive superficial esophageal neoplasms. Methods A total of 75 patients who underwent ESD for superficial esophageal neoplasms involving larger than 2/3 of the esophageal circumference at the Department of Gastroenterology, Northern Jiangsu People''s Hospital from January 2018 to December 2020 were enrolled. Patients were randomly assigned to triamcinolone acetonide-saline submucosal injection group (group A, n=25), triamcinolone acetonide injections immediately after ESD group (group B, n=25) and the control group undergoing only ESD (group C, n=25). Serial gastroscopy was performed to assess wound healing and esophageal stricture. Endoscopic balloon dilatation (EBD) was performed when patients experienced esophageal stricture. The completion of ESD, time of operation, the amount of triamcinolone acetonide, the incidences of esophageal stricture and the time of EBD treatment of the three groups were compared. Results All ESD procedures were successfully performed without complications such as intraoperative perforation, massive bleeding or postoperative delayed perforation. The operation time of group A, B and C were 72.87±12.99 min, 94.15±14.22 min and 74.08±11.86 min, respectively, with significant difference (F=20.925, P<0.001). In pairwise comparison the above indicator in group A and group C was significantly shorter than that of group B (LSD-t=5.759, P<0.001; LSD-t=5.432, P<0.001), but there was no difference between group A and group C (LSD-t=0.327, P=0.745). There was no significant difference in the amount of triamcinolone acetonide between group A and group B (125±15 mg VS 133±19 mg, t=1.673, P=0.101). The rates of wound healing under endoscopy after 1 month of group A, B and C were 76% (19/25), 84% (21/25), and 76% (19/25), respectively, with no significant difference (χ2=0.636, P=0.728). The esophageal stricture rates were 52% (13/25) in both group A and B, and 84% (21/25) in group C, with significant difference among the three groups (χ2=7.295, P=0.026), and group A and B showed a significantly lower stricture rate than that of group C (P=0.015; P=0.015). The median time of EBD treatment of group A, B and C were 4 (range 0 to 9), 5 (range 0 to 13) and 9 (range 0 to 16), respectively, with significant difference (H=17.58, P<0.001). In pairwise comparison the above indicator in group A and B was significantly less than that of group C (H=23.96, P<0.001; H=19.00, P=0.002), but there was no significant difference between group A and group B (H=4.96, P=0.407). Esophageal stricture was observed in all patients with circumferential mucosa resected in the three groups. But the times of EBD treatment were 6.90±1.10 in group A, 10.13±2.42 in group B and 15.29±0.76 in group C with significant difference (F=57.754, P<0.001). In pairwise comparison the above indicator in group A was less than that in group B (LSD-t=4.294, P<0.001) and this indicator in group B was less than that in group C (LSD-t=6.294, P<0.001). Median EBD times in patients with non-circumferential mucosal defects in the three groups were 0 (range 0 to 9), 0 (range 0 to 6) and 8 (range 0 to10), respectively, with significant difference (H=19.72, P<0.001). In pairwise comparison, the EBD time in group A and B was less than that in group C (H=17.93, P<0.001; H=16.62, P<0.001), but there was no statistical difference between group A and B (H=1.31, P=0.779). Conclusion Triamcinolone acetonide-saline submucosal injection ESD can safely and effectively prevent esophageal stricture after ESD for large-area superficial esophageal neoplasms, reduce the operation time and time of EBD treatment in patients with circumferential mucosa defect compared with local injections of triamcinolone acetonide after ESD.