Superficial Flat-type Early-stage Gastric Signet Ring Cell Carcinoma in the Atrophic Background Mucosa: Two Case Reports

Gastric signet ring cell carcinoma is a rare and highly malignant adenocarcinoma, which is characterized by early metastasis, rapid progression and poor prognosis. Several studies have shown that early-stage gastric signet ring cell carcinoma may have equal or better prognosis than other types of gastric cancer. However, most of the early-stage lesions are difficult to detect by endoscopy. Two female cases of early-stage gastric signet ring cell carcinoma with atrophic background mucosa occurring in the middle and lower part of the stomach were found in our endoscopy center. The diagnosis was confirmed by upper gastrointestinal white light endoscopy combined with narrow-band imaging and endoscopic biopsy, both lesions less than 2.0cm in diameter were surgically removed and identified as intramucosal adenocarcinoma. Through these two cases, we aim to illustrate the difficulty of early detection of gastric signet ring cell carcinoma with mucosal atrophy. We can roughly identify the demarcation of the lesion by combining white light endoscopy and narrow-band imaging, and slightly irregular microsurface and microvascular pattern of the lesion were found via magnifying endoscopic observation, but the demarcation can hardly be accurately identified.

Clonal transitions and phenotypic evolution in Barrett's oesophagus

Background & Aims: Barrett esophagus (BE) is a risk factor for the development of esophageal adenocarcinoma, however our understanding of how Barrett esophagus evolves is still poorly understood. We demonstrate that dynamic clonal phenotypic changes occur at the gland level, the mechanism by which these changes evolve, and how diversity may play a role in progression. Methods: We analyzed the distribution and diversity of gland phenotype between and within BE biopsies and the background mucosa of those that had progressed to dysplasia or developed BE post-esophagectomy, using immunohistochemistry and H&E analysis. Clonal relationships between distinct gland types were determined by laser capture microdissection sequencing of the mitochondrial genome. Results: Five different non-dysplastic gland phenotypes were identified in a cohort of 64 patients; most non-dysplastic patients showed a single gland phenotype per biopsy but some showed two or three gland types. We reveal a shared common ancestor between parietal cell-containing oxynto-cardiac glands and goblet cell-containing specialized Barrett glands through a shared somatic mtDNA mutation. We also reveal a similar relationship between specialized and cardiac-type glands, and specialized and Paneth cell-containing glands. Clonal-related distinct within gland phenotypes were also observed. The diversity of gland types was significantly increased adjacent to dysplasia compared to non-dysplastic BE and patients with post-esophagectomy BE, suggesting that gland diversity evolves in BE patients over time. Conclusions: We have shown that the range of BE phenotypes represent an evolutionary process and that changes in gland diversity may play a role in progression. Furthermore, we demonstrate common ancestry between gastric and intestinal glands in BE.

The Different Clinicopathological Features of Remnant Gastric Cancer Depending on Initial Disease of Partial Gastrectomy

Background: The incidence of gastric cancer increases in the remnant stomach after partial gastrectomy; however, its pathogenesis remains controversial. The clinicopathological features and immunohistochemical subtype were evaluated in patients with remnant gastric cancer considering the initial cause of partial gastrectomy. Methods: We categorized 59 cases of remnant gastric cancer who underwent curative surgery between 2001 and 2016 according to initial pathologies of benign (n = 24) or malignant (n = 35). Histological changes including pyloric metaplasia and intestinal metaplasia in the mucosa around the anastomosis site and the background mucosa of carcinomas were compared between the groups. Results: In the malignant group, the proportion of male patients was substantially lower, with a shorter interval. In background mucosa around the carcinomas, incidence of high-grade pyloric metaplasia was significantly higher in the benign group (13/20, 65.0% vs. 10/28, 35.7%), while high-grade intestinal metaplasia was only observed in the malignant group (0/20, 0% vs. 7/28, 25.0%). Conclusions: The cancers in the initial benign disease are mainly associated with pyloric metaplasia at the anastomosis site, reflecting reflux, but not with intestinal metaplasia. On the other hand, in the initial malignant disease group, intestinal metaplasia has an equally important role as reflux-associated pyloric metaplasia.

DNA Methylation Silencing of microRNA Gene Methylater in the Precancerous Background Mucosa with and without Gastric Cancer: Analysis of Effects of Helicobacter pylori Eradication and Long-Term Aspirin Use

The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs) such as miR-34c, miR-124a-3, miR-129-2, and miR-137 in the gastric mucosa with and without GC, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM). DNA was isolated from AM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in AM, but not in IM. miR-129-2 methylation in AM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either AM or IM irrespective of H. pylori infection. miR-129-2 methylation in AM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective in improving methylation in IM compared with AM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development.