An Unexpected Mucosal Metaplasia at the Gastric Cardia in Longstanding Pernicious Anemia

Derakhshan, Mohammad H.; Crumley, Andrew; Forshaw, Matthew; Mitchell, David; Going, James J.

doi:10.1038/ajg.2015.288

Cited by 4 publications

(5 citation statements)

References 4 publications

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“…The finding that glandular epithelium was gradually replaced with squamous epithelium, which seemed to expand from the lesser curvature side of the squamocolumnar junction, supports the ‘competition’ model for establishing the boundary of squamous and glandular epithelium . In fact, there have been several reports of squamous metaplasia in the gastric cardia in the setting of chronic injury to glandular epithelium , which might be modeled by our Tff1 ‐Cre; Cdh1 flox/flox mice.…”

Section: Discussionsupporting

confidence: 77%

Three types of metaplasia model through Kras activation, Pten deletion, or Cdh1 deletion in the gastric epithelium

Kinoshita

Hayakawa

Konishi

et al. 2018

The Journal of Pathology

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Chronic inflammation and intestinal metaplasia are strongly associated with gastric carcinogenesis. Kras activation and Pten deletion are observed in intestinal-type gastric cancer, and Cdh1 mutation is associated with diffuse-type gastric cancer. Although various mouse models of gastric carcinogenesis have been reported, few mouse lines enable gene manipulation selectively in the stomach. Here we established a Tff1-Cre bacterial artificial chromosome transgenic mouse line in an attempt to induce gene modification specifically in the gastric pit lineage. In the stomach, Tff1-Cre-mediated recombination was most evident in the pit lineage in the corpus and in entire antral glands; recombination was also observed in a few gastric chief and parietal cells. Outside the stomach, recombination was patchy throughout the intestines, and particularly frequently in the duodenum (Brunner glands), cecum, and proximal colon. In the stomachs of Tff1-Cre;LSL-Kras mice, proliferating cell clusters expanded throughout the corpus glands, with foveolar cell expansion with ectopic Alcian blue-positive mucins, oxyntic atrophy, and pseudopyloric changes with spasmolytic polypeptide-expressing metaplasia; however, gastric cancer was not observed even at 12 months of age. Corpus-derived organoids from Tff1-Cre;LSL-Kras mice exhibited accelerated growth and abnormal differentiation with a loss of chief and parietal cell markers. Tff1-Cre;Pten mice displayed similar changes to those seen in Tff1-Cre;LSL-Kras mice, both with aberrant ERK activation within 3 months. In contrast, Tff1-Cre;Cdh1 mice initially showed signet ring-like cells that were rapidly lost with disruption of the mucosal surface, and later developed gastric epithelial shedding with hyperproliferation and loss of normal gastric lineages. Eventually, the glandular epithelium in Tff1-Cre;Cdh1 mice was completely replaced by squamous epithelium which expanded from the forestomach. Tff1-Cre mice offer an additional useful tool for studying gastric carcinogenesis both in vivo and in vitro. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussionsupporting

confidence: 77%

Three types of metaplasia model through Kras activation, Pten deletion, or Cdh1 deletion in the gastric epithelium

Kinoshita

Hayakawa

Konishi

et al. 2018

The Journal of Pathology

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Section: Resultsmentioning

confidence: 99%

“…Several landmarks have been used to define the GOJ such as the squamocolumnar junction (SCJ), the PEGF and the DEPV 38 (figure 1A, IB). As the SCJ shifts towards proximally when there is columnar metaplasia of the oesophagus 39 40 or in rare cases, the SCJ shifts distally into the stomach, 41 it cannot be used as an anatomical landmark of the GOJ. PEGF has been used by many Western gastroenterologists for defining the GOJ, since 1987, when McClave et al proposed PEGF as an optimal endoscopic landmark for diagnosing the columnar-lined oesophagus.…”

Section: Textural Explanationmentioning

confidence: 99%

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction

Sugano

Spechler

El-Omar

et al. 2022

Gut

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ObjectiveAn international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ.DesignClinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised.ResultsTwenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett’s oesophagus (BO).ConclusionsThis international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

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“…Progressive widening of the lower esophageal sphincter, due to slowly increasing abdominal pressure and increased reflux, might progressively erode the distal esophageal epithelium over many years. There is some (indirect) evidence for this from studies of patients 51 resection specimen clearly showed a collar of squamous epithelium, which occupied the anatomic cardia 53 . Given the atrophic gastritis, the most parsimonious explanation is that in this case, due to continuous erosion of the friable gastric mucosa, the squamous epithelium outcompeted native glands in the proximal stomach.…”

Section: Studies Of Bile Salt Solubility Found It To Be Greatest At Imentioning

confidence: 99%

Insights Into the Pathophysiology of Esophageal Adenocarcinoma

2018

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Although researchers have identified genetic alterations that contribute to development of esophageal adenocarcinoma, we know little about features of patients or environmental factors that mediate progression of chronic acid biliary reflux to Barrett's esophagus and cancer. Increasing our understanding of the mechanisms by which normal squamous epithelium progresses to early-stage invasive cancer will help formulate rational surveillance guidelines and allow us to divest resources away from patients at low risk of malignancy. We review the cellular and genetic alterations that occur during progression of Barrett's esophagus, based on findings from clinical studies and mouse models of disease. We review the features of the luminal and mucosal microenvironment of Barrett's esophagus that promote, in a small proportion of patients, development of esophageal adenocarcinoma. Markers of clonal evolution can be used to determine patient risk for cancer and set surveillance intervals.

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An Unexpected Mucosal Metaplasia at the Gastric Cardia in Longstanding Pernicious Anemia

Cited by 4 publications

References 4 publications

Three types of metaplasia model through Kras activation, Pten deletion, or Cdh1 deletion in the gastric epithelium

Three types of metaplasia model through Kras activation, Pten deletion, or Cdh1 deletion in the gastric epithelium

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction

Insights Into the Pathophysiology of Esophageal Adenocarcinoma

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