Aspirin Use Is Not Associated with the Risk of Metachronous Gastric Cancer in Patients without Helicobacter pylori Infection

Introduction: Helicobacter pylori (H. pylori) eradication can prevent metachronous gastric cancer (MGC) after the performance of an endoscopic resection for early gastric cancer (EGC). However, 50% of infections persist after eradication, and the identification of MGC protective factors is important. The anti-tumor activity of aspirin has been demonstrated, but its efficacy in preventing MGC remains controversial. We evaluated the effect of aspirin on metachronous recurrence in H. pylori-negative patients. Methods: A total of 4351 patients were evaluated between January 2007 and December 2016, and 2151 patients who met the inclusion criteria were analyzed. The primary outcome was the cumulative incidence of MGC after an endoscopic resection for EGC. Results: During a 5-year median follow-up (interquartile range, 3.5–6.2), MGC developed in 176 (7.7%) patients, with a cumulative incidence of 89.4% in aspirin users and 92.7% in non-users; this difference was not statistically significant (p = 0.64). The duration of aspirin uses and the occurrence of MGC in both groups were not significantly different. There was no significant difference between groups when the duration of aspirin use was categorized into ≤1 year (hazard ratio (HR), 0.64; 0.20–2.01, p = 0.45), 1–4 years (HR, 1.35; 0.66–2.76, p = 0.41), and >4 years (HR, 1.17; 0.67–2.03, p = 0.58). Conclusions: Aspirin use was not associated with a lower risk of MGC in H. pylori-negative patients. Further prospective studies are needed.

Long-term Changes In Aberrant DNA Methylation And Gastritis After Helicobacter Pylori Eradication Focused On Metachronous Gastric Cancer

BackgroundA persistently high methylation level in gastric mucosa after Helicobacter pylori (H. pylori) eradication is presumed to be a risk for metachronous gastric cancer (MGC); however, long-term changes in aberrant DNA methylation and histological gastritis have been unclear. Our aim was to examine changes in DNA methylation and histological gastritis according to the occurrence of MGC.MethodsSubjects were classified into 3 groups: 25 patients in whom metachronous gastric cancers occurred after the initial endoscopic resection (ER) for early gastric cancer and H. pylori eradication (MGC group), 17 patients in whom MGC did not occur for more than 5 years after initial ER and H. pylori eradication (non-MGC group) and 29 patients without a history of gastric cancer who succeeded in eradication more than 5 years ago (HP group). Aberrance of DNA methylation in 3 genes (miR-124a-3, EMX1, NKX6-1) and histological score of atrophy and intestinal metaplasia (IM) were evaluated using biopsy samples before and more than a mean of 5 years after H. pylori eradication.ResultsThe methylation level of miR-124a-3 in the HP group and non-MGC group and that of EMX1 in the HP group significantly decreased in the long term after eradication. In the MGC group, H. pylori eradication did not improve aberrant methylation, and the Z-score significantly increased. There were significant positive correlations between methylation levels in miR-124a-3 and EMX1 and histological findings after eradication.ConclusionsA persistently high methylation level after H. pylori eradication reflected precancerous mucosal conditions and led to long-term MGC.

Gastric Xanthelasma, Microsatellite Instability and Methylation of Tumor Suppressor Genes in the Gastric Mucosa: Correlation and Comparison as a Predictive Marker for the Development of Synchronous/Metachronous Gastric Cancer

A predictive marker for the development of synchronous/metachronous gastric cancer (GC) would be highly desirable in order to establish an effective strategy for endoscopic surveillance. Herein, we examine the significance of gastric xanthelasma (GX) and molecular abnormalities for the prediction of synchronous/metachronous GC. Patients (n = 115) were followed up (range, 12–122; median, 55 months) in whom the presence of GX and molecular alterations, including microsatellite instability (MSI) and methylation of human mutL homolog 1 (hMLH1), cyclin-dependent kinase inhibitor 2A (CDKN2A) and adenomatous polyposis coli (APC) genes, had been confirmed in non-neoplastic gastric mucosa when undergoing endoscopic submucosal dissection (ESD) for early GC. At the start of surveillance, the numbers of positive subjects were as follows: GX, 59 (51.3%); MSI, 48 (41.7%); hMLH1, 37 (32.2%); CDKN2A, 7 (6.1%); APC, 18 (15.7%). After ESD treatment, synchronous/metachronous GCs occurred in patients with the following positive factors: GX, 16 (27.1%); MSI, 7 (14.6%); hMLH1, 6 (16.2%); CDKN2A, 3 (42.9%); APC, 3 (16.7%). The presence of GX had no significant relationship to positivity for MSI or methylation of hMLH1, CDKN2A or APC. GX was significantly (p = 0.0059) and independently (hazard ratio, 3.275; 95% confidence interval, 1.134–9.346) predictive for the development of synchronous/metachronous GC, whereas those genetic alterations were not predictive. GX is a simple and powerful marker for predicting the development of synchronous or metachronous GC.

Use of Antibiotics and Probiotics Reduces the Risk of Metachronous Gastric Cancer after Endoscopic Resection

Metachronous gastric cancer often occurs after endoscopic resection. Appropriate management, including chemoprevention, is required after the procedure. This study was performed to evaluate the association between medication use and the incidence of metachronous gastric cancer after endoscopic resection. This multicenter retrospective cohort study was conducted with data from nine hospital databases on patients who underwent endoscopic resection for gastric cancer between 2014 and 2019. The primary outcome was the incidence of metachronous gastric cancer. We evaluated the associations of metachronous gastric cancer occurrence with medication use and clinical factors. Hazard ratios were adjusted by age and Charlson comorbidity index scores, with and without consideration of sex, smoking status, and receipt of Helicobacter pylori eradication therapy during the study period. During a mean follow-up period of 2.55 years, 10.39% (140/1347) of all patients developed metachronous gastric cancer. The use of antibiotics other than those used for H. pylori eradication was associated with a lower incidence of metachronous gastric cancer than was non-use (adjusted hazard ratio (aHR) 0.56, 95% confidence interval (CI) 0.38–0.85, p = 0.006). Probiotic drug use was also associated with a lower incidence of metachronous gastric cancer compared with non-use (aHR 0.29, 95% CI 0.091–0.91, p = 0.034). In conclusion, the use of antibiotics and probiotic drugs was associated with a decreased risk of metachronous gastric cancer. These findings suggest that the gut microbiome is associated with metachronous gastric cancer development.

Gastric Adenoma: A High Incidence Rate of Developing Carcinoma and Risk of Metachronous Gastric Cancer according to Long-Term Follow-Up

<b><i>Introduction:</i></b> Gastric adenomas are histologically defined as benign epithelial tumors. While some of them remain adenomas for a long time, others progress to carcinomas. However, long-term outcomes of such cases are not entirely clear. Here, we explored the risk factors and incidence of developing carcinoma from gastric adenoma as well as metachronous gastric cancer. <b><i>Methods:</i></b> This study was conducted at a facility that adopted a follow-up strategy for gastric adenoma. Lesions histologically diagnosed as gastric intestinal-type adenomas between January 2004 and December 2016 were analyzed. Clinicopathological data were collected from patients’ medical records, and histological changes from adenoma to carcinoma during endoscopic follow-up and risk factors of cancer development were evaluated. <b><i>Results:</i></b> This study involved 409 lesions from 376 patients. The analysis of the development of gastric cancer from adenoma and metachronous gastric cancer was ultimately performed for 282 lesions from 258 patients and 269 lesions from 246 patients, respectively, due to different follow-up periods. The 5-year rate of carcinoma development was 34.0%. Risk factors for carcinoma development upon multivariate analysis were lesion size ≥15 mm and morphological depression. All cases with both factors developed gastric carcinoma, and 50.5% of those with either factor developed carcinoma within 5 years. Gastric adenoma was accompanied by metachronous gastric cancer in 1.5% of the patients annually. The only risk factor for metachronous gastric carcinoma was primary adenoma progressing to carcinoma during the follow-up period. <b><i>Discussion/Conclusion:</i></b> Given the high rate of carcinoma development in patients with risk factors, resection of gastric adenoma should be considered during the initial examination. Careful observation and follow-up should also be conducted to detect not only changes in the primary adenoma but also the occurrence of metachronous carcinoma, especially in cases of adenoma progressing to carcinoma.