Published online May 16, 2018. doi: 10.4253/wjge.v10.i5.83
Peer-review started: January 31, 2018
First decision: February 27, 2018
Revised: March 4, 2018
Accepted: March 20, 2018
Article in press: March 20, 2018
Published online: May 16, 2018
The endoscopic submucosal dissection (ESD) for early-stage gastric cancer is first-line therapy in Japan, because of en bloc resection and a lower local recurrence rate of gastric cancer. However, bleeding from ESD-induced ulcer is a major complication of ESD treatment. When ESD is performed for gastric cancer, PPIs or vonoprazan are used to treat ESD-induced ulcers in Japan. It remains unclear whether vonoprazan with more potent and sustained acid inhibition than PPIs, H. pylori infection and characteristics of gastric mucosa (e.g., inflammation and atrophy) are associated with improved ulcer healing speed and prevention of post-ESD bleeding. Rapid healing of ESD-induced ulcers is key to the prevention of delayed bleeding.
Of many possible factors related to ESD-induced ulcer healing, such as location of the tumor, submucosal fibrosis, initial ulcer size, diabetes, coagulation abnormality, electrocoagulation during ESD, and method of gastric acid suppression, it is unclear whether above parameters actually affect the healing of ESD-induced ulcers and the incidence of gastrointestinal bleeding after ESD treatment. Especially, there was no report investigated with the healing speed of ulcer after ESD and characteristics of gastric mucosa (e.g., inflammation and atrophy).
The main objective was to clarify factors that might be associated with healing of post-ESD ulcers and bleeding, including H. pylori status, profile of the gastric tumor, kinds of acid inhibitory drugs, and severity of gastritis including of gastric atrophy and intestinal metaplasia.
We retrospectively enrolled 132 patients with gastric tumors scheduled for ESD, irrespective to H. pylori infection. Following ESD, patients were treated with daily lansoprazole 30 mg or vonoprazan 20 mg for 8 wk. Ulcer size was endoscopically measured on the day after ESD and at 4 and 8 wk. The gastric mucosa was endoscopically graded according to the Kyoto gastritis scoring system. We assessed the number of patients with and without a 90% reduction in ulcer area at 4 wk post-ESD and scar formation at 8 wk, and looked for risk factors for slower healing.
After ESD, mean healing rates of ESD-related ulcer were 90.4% ± 0.8% at 4 wk and 99.8% ± 0.1% at 8 wk. The reduction rate was associated with the Kyoto grade of gastric mucosal atrophy at 4 wk and ESD-induced ulcers with ≥ 90% healing at 4 wk were associated with absence of atrophy, depth of gastric tumor, and procedure time. In the univariate analysis to identify possible factors related to achievement of 90% healing at 4 wk, healing was associated with gastric atrophy, procedure time and initial ESD-induced ulcer size. In the multivariate analysis, the factor associated with 90% healing at 4 wk was gastric mucosal atrophy (OR = 5.678, 95%CI: 1.190-27.085, P = 0.029).
The healing speed of ESD-induced ulcers was affected by the severity of gastric atrophy, but not by H. pylori status, kinds of acid inhibitory drugs, or CYP2C19 genotype. Patients with severe gastric atrophy accompanied by intestinal metaplasia should be considered as likely candidates for ESD-related complication, due to delayed ulcer healing. Therefore, H. pylori eradication therapy is required to perform at younger age before progression of gastric mucosal atrophy to prevent development of H. pylori-related diseases and bleeding from ESD-induced ulcer.
Eradication of H. pylori can be carried out at any time in terms of ulcer healing and that PPI or vonoprazan treatment for ESD-induced ulcers can be administrated at the standard dose irrespective of CYP2C19 genotype. However, because this is a preliminary small study, further study is required to plan whether the healing speed of ESD-induced ulcers was affected by the severity of gastric atrophy in prospective multicenter study. In addition, we will clarify the potential mechanism about association with the healing of ESD-induced ulcer and severity of gastric atrophy as further study.