Intraoperative Submucosal Injection of Triamcinolone Acetonide Combined with Oral Prednisone for Prevention of Esophageal Stricture after ESD for Circumferential Superficial Tumors: A Retrospective Pilot Study

Technical Summary: Intraoperative Submucosal Injection of Triamcinolone Acetonide Combined with Oral Prednisone for Esophageal Stricture Prevention

Problem Statement
Endoscopic Submucosal Dissection (ESD) is the standard curative treatment for early esophageal neoplasms. However, when the resection involves a circumferential mucosal defect, the risk of post-ESD esophageal stricture is exceptionally high, historically ranging from 70% to 90% without prophylaxis. These strictures cause severe dysphagia, significantly impair quality of life, and necessitate repeated, invasive endoscopic balloon dilations (EBD), which carry their own risks of perforation and bleeding. Existing preventive strategies—such as postoperative local steroid injections, long-term systemic steroids, stent placement, or autologous mucosal transplantation—suffer from limitations including technical difficulty, high rates of adverse events (e.g., infection, osteoporosis, hyperglycemia), stent migration, or procedural complexity.

Methodology
This single-center, retrospective pilot study evaluated a novel combination prophylactic strategy in 11 patients (mean age 75.1 years) who underwent ESD for circumferential superficial esophageal neoplasms between January 2021 and December 2024. The intervention consisted of two coordinated components:

1. Intraoperative Full-Course Submucosal Injection: Unlike traditional methods that inject steroids only into the ulcer bed post-resection, this protocol utilized a solution containing Triamcinolone Acetonide (TA) diluted to 1 mg/mL in normal saline with indigo carmine. This solution was injected continuously and sequentially throughout the entire ESD procedure. It was used to create the initial submucosal cushion and, crucially, to maintain elevation and provide "carpet-like" coverage of the submucosal layer during the circumferential incision and gradual dissection. This ensured uniform drug distribution across the entire wound bed and the proximal/distal margins during the cutting process.
2. Sequential Short-Term Oral Prednisone: Following the procedure, patients received an 8-week tapering course of oral prednisone (starting at 30 mg/day and reducing to 5 mg/day by week 8). This was designed to sustain anti-inflammatory and anti-fibrotic effects while minimizing the systemic toxicity associated with long-term high-dose steroid therapy.

The primary endpoints were the incidence of clinically significant stricture (defined as Stooler dysphagia grade ≥1 requiring EBD) and the number of EBD sessions. Secondary endpoints included procedure time, total TA dosage, and mucosal healing rates.

Key Results

• Stricture Incidence: Only 1 out of 11 patients (9.1%) developed a clinically significant stricture requiring intervention. This patient (Case 4), who had the longest lesion (7.5 cm) and received the highest TA dose (80 mg), required two EBD sessions at 3 and 5 months post-ESD. The remaining 10 patients (90.9%) experienced no stricture requiring intervention; two reported mild dysphagia (Stooler grade 1) that resolved without endoscopic treatment.
• Safety Profile: The study reported no intraoperative perforations, delayed perforations, postoperative infections, or major bleeding. No severe systemic adverse events related to the 8-week prednisone course (e.g., severe infection, uncontrolled hyperglycemia, or osteoporotic fractures) were observed.
• Resection Efficacy: All procedures achieved 100% R0 resection.
• Dosage: The mean total TA dosage used was 47.3 mg.

Key Contributions
The study proposes a "local + short-term systemic" approach that addresses the specific challenges of circumferential ESD:

• Optimized Local Delivery: By integrating TA into the submucosal injection solution used throughout the dissection, the method ensures uniform coverage of the entire wound bed and, critically, the cut margins where scar contracture initiates. This avoids the technical difficulty and risks (perforation, uneven distribution) of injecting into a fragile, post-resection ulcer bed.
• Balanced Systemic Therapy: The 8-week tapering oral prednisone regimen replaces the need for multiple postoperative endoscopic re-injections (which increase cost and procedural risk) while avoiding the high adverse event rates associated with long-term (16+ weeks) systemic steroid use.
• Simplicity and Cost-Effectiveness: The strategy requires no specialized equipment (unlike stents) or complex surgical techniques (unlike mucosal transplantation) and does not add extra procedural steps to the standard ESD workflow.

Significance and Claims
The authors claim that this combination strategy offers a promising, simple, and cost-effective solution for preventing esophageal strictures after circumferential ESD. With a stricture rate of 9.1% compared to the historical 70–90% without prophylaxis, the study suggests that continuous intraoperative TA coverage combined with short-term oral steroids effectively inhibits fibrosis while maintaining a favorable safety profile. The authors emphasize that this approach minimizes the need for repeated invasive procedures and reduces the burden on both patients and healthcare systems.

However, the paper maintains a modest tone regarding its conclusions. It explicitly acknowledges the study's limitations, including its retrospective design, small sample size (n=11), and single-center nature. The authors state that while the preliminary results are encouraging, further validation through larger, multi-center, prospective randomized controlled trials is necessary to confirm the optimal TA concentration and precise steroid dosage adjustments.