Gastric Cancers Emerging after H. pylori Eradication Arise Exclusively from Non-Acid-Secreting Areas

Abstract

Although Helicobacter pylori (H. pylori) eradication has some inhibitory effects on the subsequent development of gastric cancer, there are sporadic cases of gastric cancer even after successful eradication. The pathogenesis of gastric cancer emerging after H. pylori eradication remains to be clarified. In this study, employing Congo-red chromoendoscopy, which is capable of visualizing the acid-secreting fundic mucosa, we investigated the topographic relationship of the acid secretion pattern to the occurrence site of gastric cancers emerging after eradication. Fourteen consecutive patients who suffered from new gastric cancer after eradication, defined as lesions that were discovered at least 2 years after the eradication, were prospectively enrolled. Whether the neoplasias arose from acid-secreting or nonacid-secreting areas was evaluated with Congo-red chromoendoscopy. Biopsy specimens taken from the two areas were subjected to histologic evaluation and immunohistochemistry for Ki-67 and p53. The mean period from the eradication to the subsequent occurrence of gastric cancer was 74 (44) months. There were two cancer lesions in 5 cases, and thus there was a total 19 lesions from 14 cases. Congo-red chromoendoscopy revealed that all 19 lesions arose exclusively from non-acid-secreting areas. Histological examination revealed sustained hyperproliferation and accumulation of p53 protein was frequently detectable in non-acid-secreting areas. Genetic alteration such as p53 mutation seems to be already present in the residual non-acid-secreting areas after eradication, areas that could be the origin of gastric carcinogenesis after eradication. Identification of such high-risk areas should be a promising approach for estimating the individual cancer risk after eradication.

Chronological Changes in the Gastric Cancer Subsite in Akita, Japan: The Trends from the Data of a Hospital-Based Registration System

“…Interestingly, a recent study from Taiwan showed that not only H. pylori-negative subjects without gastric atrophy (true H. pylori-negative) but also H. pylori-negative subjects with gastric atrophy and a history of infection were more likely to have gastric cancer in the proximal location than H. pylori-positive subjects (Tsai et al 2017), which is consistent with our previous observation (Iijima et al 2012). Thus, the recent widespread use of eradication therapy in Japan is also responsible for the compositional changes favorable to corpus cancer.…”

Cutoff Serum Pepsinogen Values for Predicting Gastric Acid Secretion Status

“…Finally, the PG cutoff values calculated in the present analysis could not be applied to those with a history of H. pylori eradication because the correlation between gastric acid secretion and serum PGs is considerably altered after the therapy (Iijima et al 2009b). Since we have recently reported that gastric acid secretory capacity is inversely associated with the risk for gastric carcinoma emerging after successful eradication (Iijima et al 2012), the serum PG values after eradication might be useful for estimation of the cancer risk among eradicated patients. Alternative cut-off values specific to eradicated patients need to be established.…”

Alterations of theTP53Gene in Gastric and Esophageal Carcinogenesis

“…The pathogenesis of GC emerging after H. pylori eradication remains to be clarified. Iijima et al [83] assessed the relationship of the acid secretion pattern to the occurrence site of GC emerging after bacterial eradication in order to estimate the individual cancer risk. The p53 protein frequently was accumulated in non-acid-secreting areas, suggesting that genetic alteration such as TP53 mutation seems to be already present in the residual non-acid-secreting areas that could be the origin site of gastric carcinogenesis even after eradication.…”