| Background and aim:Endoscopic submucosal dissection (ESD) has been widely used as an alterative to surgical resection for patients with early-stage gastric mucosal lesions. However, large artificial ulcers are developed from ESD procedures, which results in a higher risk of perforation and delayed bleeding. Proton pump inhibitor (PPI) has been reported to be effective drugs for ESD-induced ulcers. There has been no consensus regarding the optimal treatment durations and drug regimens in the treatment for endoscopic submucosal dissection (ESD)-induced ulcers. In view of this, this study is performed to assess the efficacy of lansoprazole plus rebamipide combination therapy compared with lansoprazole monotherapy for ESD-induced ulcer healing, and the efficacy and safety of ESD for early-stage gastric mucosal lesions are also explored.Method:This study is a prospective, multicenter, randomized, double blind controlled clinical trial. Total 213 patients receiving ESD are recruited from 6 centers in the study, and all ESD procedures are performed by experienced experts in ESD. All subjects are randomized to two groups, and 107 patients received lansoprazole and rebamipide combination therapy (lansoprazole 30 mg/d orally,300 mg orally, three times a day) with 106 patients are randomly assigned to lansoprazole plus placebo group. The treatment durations are 8 weeks. At 4 and 8 week after ESD, to assess the ulcer outcomes, an esophagogastroduodenoscopy exam are performed for all patients. We evaluated change in size of ESD-induced ulcers between baseline and 4 weeks, to investigate possible relevant factors including location of ulcer, patient’s age(>60 years old, and<60 years), and initial size (≥40mm, and<40mm) associated with healing rate. The efficacy and safety of ESD for early-stage gastric mucosal lesions are also assessed by analyzing the overall en bloc resection rate, complication rate, and hospital stays.Result:Total 213 procedures of ESD are performed, and the overall en bloc resection rate, curable resection rate and complication rate are 97.65%(208/213),93.06% (134/144), and 5.63%(12/213) in all lesions. The average hospital stays are 6.5 days. At 4 week, the healing rate of ESD-induced ulcers, in the lansoprazole plus rebamipide-treated patients, and lansoprazole plus placebo group are 17.20% and 13.48% respectively, and the improvement rate are 95.70% and 89.89% respectively, and the decreasing rate of ulcer area are 96.28% and 93.35% respectively. At 8 week, all ESD-induced ulcers in two groups are improved to the stage of H or S stage, and the healing rates of ulcers are respectively 92.05% and 91.76% in combination and monotherapy group. No complications due to the drugs are observed in two groups. However, there are no significant differences in the ulcer-healing rate at both 4 and 8 week between two groups(P>0.05), yet the decreasing rate of ulcer area at 4 week in lansoprazole plus rebamipide-treated patients are significantly higher than that in lansoprazole-treated group (96.28% vs 93.35%,P<0.05). The healing rate of ulcers in the gastric angle is significantly lower than that of ulcers located in the corpus and antrum (0.00% vs 24.21%, P<0.05), and the healing rate in patient aged below 60 years group is higher than that in those aged over 60 years(22.55% vs 12.5%, P<0.05). The improvement rate of large ulcers with the initial size over 40mm is lower that of the small ulcers<40mm (87.67% vs 96.33%, P<0.05).Conclusion:ESD is an effective and safe method for en bloc resection of early-stage gastric mucosal lesions.4-week treatment with either lansoprazole and rebamipide combination or lansoprazole monotherapy are not sufficient for healing ESD-induced ulcers, While 8-week duration of combination or monotherapy could make above 90% ESD-induced ulcers reach Scar stage. Ulcers located in the gastric angle, age (over 60 years old) and initial size larger than 40mm might contribute to delayed healing of ESD-induced ulcers after post-ESD 4 weeks. Therapeutic use of lansoprazole plus rebapide combination therapy seemed similar to PPI monotherapy for ESD-induced ulcers, which doesn’t improve the healing degree of ulcers, yet the combination therapy including rebapide can improve the healing speed of ulcers. |
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