Endoscopic balloon dilation with steroid injection versus radial incision and cutting with steroid injection for refractory esophageal anastomotic stricture: a randomized study

Abstract

Background

Esophageal stricture causes severe distress to patients; however, there are no established treatments for esophageal anastomotic strictures refractory to endoscopic balloon dilation (EBD). Steroid injection added to EBD and radial incision and cutting (RIC) are effective for such strictures, but it is unclear which is more effective. The objective of this study was to investigate the safety and efficacy of RIC plus steroid injection compared with EBD plus steroid injection for patients with refractory anastomotic strictures after esophagectomy.

Methods

This was a multicenter, randomized phase II/III trial. Patients with esophageal anastomotic strictures refractory to three or more dilations were eligible. The primary endpoint in phase II was the proportion of predefined grade 3/4 adverse events (AEs). The co-primary endpoints in phase III were restricture-free survival and number of EBDs in the 24 weeks after treatment.

Results

130 patients were enrolled, with a dysphagia score of grade 2 in 104 patients (80.0%). The median number of dilations before registration was five in each arm. Predefined grade 3/4 AEs occurred in two patients (3.1%) in each arm. Restricture-free survival was 10.6 weeks (95%CI 6.9–20.1 weeks) with EBD and 8.7 weeks (95%CI 7.1–10.9 weeks) with RIC (one-sided P=0.82). The median number of EBDs in the 24 weeks after initial treatment was one (interquartile range [IQR] 0–2) for EBD and two (IQR 0–3) for RIC (one-sided P=0.99).

Conclusions

EBD combined with steroid injection is the standard treatment for refractory anastomotic stricture after esophagectomy.

Publication History

Received: 21 September 2024

Accepted after revision: 07 April 2025

Accepted Manuscript online:
08 April 2025

Article published online:
16 May 2025

• References

• 1 van Workum F, van der Maas J, van den Wildenberg FJH. et al. Improved functional results after minimally invasive esophagectomy: intrathoracic versus cervical anastomosis. Ann Thorac Surg 2017; 103: 267-273
• 2 van Heijl M, Gooszen JA, Fockens P. et al. Risk factors for development of benign cervical strictures after esophagectomy. Ann Surg 2010; 251: 1064-1069
• 3 Ahmed Z, Elliott JA, King S. et al. Risk factors for anastomotic stricture post-esophagectomy with a standardized sutured anastomosis. World J Surg 2017; 41: 487-497
• 4 Hayata K, Nakamori M, Nakamura M. et al. Circular stapling versus triangulating stapling for the cervical esophagogastric anastomosis after esophagectomy in patients with thoracic esophageal cancer: A prospective, randomized, controlled trial. Surgery 2017; 162: 131-138
• 5 Mendelson AH, Small AJ, Agarwalla A. et al. Esophageal anastomotic strictures: outcomes of endoscopic dilation, risk of recurrence and refractory stenosis, and effect of foreign body removal. Clin Gastroenterol Hepatol 2015; 13: 263-271.e1
• 6 Kochhar R, Malik S, Reddy YR. et al. Outcomes of endoscopic dilation in patients with esophageal anastomotic strictures: comparison between different etiologies. Dysphagia 2020; 35: 73-83
• 7 Yoda Y, Yano T, Kaneko K. et al. Endoscopic balloon dilatation for benign fibrotic strictures after curative nonsurgical treatment for esophageal cancer. Surg Endosc 2012; 26: 2877-2883
• 8 Hanaoka N, Ishihara R, Motoori M. et al. Endoscopic balloon dilation followed by intralesional steroid injection for anastomotic strictures after esophagectomy: a randomized controlled trial. Am J Gastroenterol 2018; 113: 1468-1474
• 9 Dasari CS, Jegadeesan R, Patel HK. et al. Intralesional steroids and endoscopic dilation for anastomotic strictures after esophagectomy: systematic review and meta-analysis. Endoscopy 2020; 52: 721-726
• 10 Henskens N, Wauters L, Vanuytsel T. Intralesional steroid injections in addition to endoscopic dilation in benign refractory esophageal strictures : a systematic review. Acta Gastroenterol Belg 2020; 83: 432-440
• 11 Yano T, Yoda Y, Satake H. et al. Radial incision and cutting method for refractory stricture after nonsurgical treatment of esophageal cancer. Endoscopy 2013; 45: 316-319
• 12 Muto M, Ezoe Y, Yano T. et al. Usefulness of endoscopic radial incision and cutting method for refractory esophagogastric anastomotic stricture (with video). Gastrointest Endosc 2012; 75: 965-972
• 13 Zhu Y, Shrestha SM, Yu T. et al. Modified endoscopic radial incision and cutting method (M-RIC) for the treatment of refractory esophageal stricture. Surg Endosc 2022; 36: 1385-1393
• 14 Koseki M, Kikuchi D, Odagiri H. et al. Possibility of ultrathin endoscopy in radial incision and cutting for esophageal strictures. VideoGIE 2022; 7: 358-360
• 15 Xiang J, Linghu E, Li L. et al. Utility of radial incision and cutting with steroid injection for refractory stricture after endoscopic submucosal dissection for large superficial esophageal squamous cell carcinoma. Surg Endosc 2021; 35: 6930-6937
• 16 Yamada K, Tajika M, Tanaka T. et al. Radial incision and cutting under gel immersion as a useful method for refractory anastomotic stricture. Endoscopy 2022; 54: E832-E833
• 17 Schulz KF, Altman DG, Moher D. et al. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010; 340: c332
• 18 Kataoka K, Aoyama I, Mizusawa J. et al. A randomized controlled Phase II/III study comparing endoscopic balloon dilation combined with steroid injection versus radial incision and cutting combined with steroid injection for refractory anastomotic stricture after esophagectomy: Japan Clinical Oncology Group Study JCOG1207. Jpn J Clin Oncol 2015; 45: 385-389
• 19 Ogilvie AL, Dronfield MW, Ferguson R. et al. Palliative intubation of oesophagogastric neoplasms at fibreoptic endoscopy. Gut 1982; 23: 1060-1067
• 20 Schoenfeld DA, Richter JR. Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint. Biometrics 1982; 38: 163-170
• 21 Dakkak M, Hoare RC, Maslin SC. et al. Oesophagitis is as important as oesophageal stricture diameter in determining dysphagia. Gut 1993; 34: 152-155
• 22 Hordijk ML, van Hooft JE, Hansen BE. et al. A randomized comparison of electrocautery incision with Savary bougienage for relief of anastomotic gastroesophageal strictures. Gastrointest Endosc 2009; 70: 849-855
• 23 Kochman ML, McClave SA, Boyce HW. The refractory and the recurrent esophageal stricture: a definition. Gastrointest Endosc 2005; 62: 474-475