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World Journal of Gastroenterology Nov 2015There has been a great discrepancy of pathological diagnosis for gastric non-invasive neoplasia/dysplasia between Japanese and western pathologists. In Japan, lesions... (Review)
Review
There has been a great discrepancy of pathological diagnosis for gastric non-invasive neoplasia/dysplasia between Japanese and western pathologists. In Japan, lesions that most western pathologists diagnose as dysplasia are often considered adenocarcinoma based on nuclear and structural atypia regardless of the presence of invasion. In the Vienna classification, gastric non-invasive intraepithelial neoplasia (NIN) were divided into low grade and high grade (including intra-mucosal cancer of Japanese criteria). The diagnosis by both endoscopy and pathology of biopsy specimen is difficult. Recent advances of diagnostic modality such as magnified endoscopy and imaged enhanced endoscopy is expected to improve the diagnostic yield for NIN. There are two treatment strategies for NIN, observation and diagnostic therapy by endoscopic resection (ER). ER is acceptable because of its less invasiveness and high local control rate, on the other hand, cancer-developing rate of low-grade NIN is reported to be low. Therefore there is controversy for the treatment of gastric NIN. Prospective study based on unified pathological definition is required in the future.
Topics: Adenoma; Biopsy; Carcinoma in Situ; Gastrectomy; Gastroscopy; Humans; Neoplasm Grading; Neoplasm Invasiveness; Predictive Value of Tests; Stomach Neoplasms; Treatment Outcome; Watchful Waiting
PubMed: 26640329
DOI: 10.3748/wjg.v21.i44.12513 -
Gut and Liver Jan 2021Gastric cancer remains one of the most common causes of cancer-related death worldwide, although the incidence is declining gradually. The primary risk factor for... (Review)
Review
Gastric cancer remains one of the most common causes of cancer-related death worldwide, although the incidence is declining gradually. The primary risk factor for gastric cancer is infection. The Kyoto global consensus report recommends eradication of in all infected patients. However, because it is difficult to stratify the risk of carcinogenesis among patients with a history of infection, annual endoscopic surveillance is performed for everyone after eradication. This review summarizes the current approaches used to screen for novel molecules that could assist in the diagnosis of gastric cancer and reduce mortality. Most well-studied molecules are tissue protein biomarkers expressed by the gastric epithelium and associated with metaplasia-dysplasia-carcinoma sequences. Other strategies focus on the origin of cancer stem cell-related markers, such as CD44, and immune reaction-related markers, such as matrix metallopeptidases. Noninvasive methods such as blood-based approaches are more attractive. Serum pepsinogen levels predict the severity of gastric mucosal atrophy before eradication, whereas plasma ghrelin levels are associated with atrophy even after eradication. Cell-free DNAs and RNAs are attractive tools for the early detection of cancer. These ideas could lead to the development of more personalized strategies for cancer prevention based on cutting-edge technologies.
Topics: Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Precision Medicine; Stomach Neoplasms
PubMed: 31893631
DOI: 10.5009/gnl19257 -
The Korean Journal of Gastroenterology... Sep 2017Gastric adenoma (dysplasia) is a precancerous lesion. Therefore, managements of gastric adenomas are important for preventing the development of gastric cancers and for... (Review)
Review
Gastric adenoma (dysplasia) is a precancerous lesion. Therefore, managements of gastric adenomas are important for preventing the development of gastric cancers and for detecting gastric cancers at earlier stages. The Vienna classification divides gastric adenomas into two categories: high-grade dysplasia and low-grade dysplasia. Generally, endoscopic resection is performed for adenoma with high-grade dysplasia due to the coexistence of carcinoma and the potential of progression to carcinomas. However, the treatments of adenoma with low-grade dysplasia remain controversial. Currently two treatment strategies for the low-grade type have been suggested; First is the 'wait and see' strategy; Second is endoscopic treatment (e.g., endoscopic mucosal resection, endoscopic submucosal dissection, or argon plasma coagulation). In this review, we discuss the current optimal strategies for endoscopic management of gastric adenoma.
Topics: Adenoma; Argon Plasma Coagulation; Endoscopic Mucosal Resection; Humans; Precancerous Conditions; Remission Induction; Stomach
PubMed: 28934826
DOI: 10.4166/kjg.2017.70.3.115 -
Gastroenterology Mar 2021Inflammation in the gastrointestinal tract may lead to the development of cancer. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid...
BACKGROUND & AIMS
Inflammation in the gastrointestinal tract may lead to the development of cancer. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation during the inflammatory response and form covalent adducts with amine-containing macromolecules. Thus, we sought to determine the role of dicarbonyl electrophiles in inflammation-associated carcinogenesis.
METHODS
The formation of isoLG adducts was analyzed in the gastric tissues of patients infected with Helicobacter pylori from gastritis to precancerous intestinal metaplasia, in human gastric organoids, and in patients with colitis and colitis-associated carcinoma (CAC). The effect on cancer development of a potent scavenger of dicarbonyl electrophiles, 5-ethyl-2-hydroxybenzylamine (EtHOBA), was determined in transgenic FVB/N insulin-gastrin (INS-GAS) mice and Mongolian gerbils as models of H pylori-induced carcinogenesis and in C57BL/6 mice treated with azoxymethane-dextran sulfate sodium as a model of CAC. The effect of EtHOBA on mutations in gastric epithelial cells of H pylori-infected INS-GAS mice was assessed by whole-exome sequencing.
RESULTS
We show increased isoLG adducts in gastric epithelial cell nuclei in patients with gastritis and intestinal metaplasia and in human gastric organoids infected with H pylori. EtHOBA inhibited gastric carcinoma in infected INS-GAS mice and gerbils and attenuated isoLG adducts, DNA damage, and somatic mutation frequency. Additionally, isoLG adducts were elevated in tissues from patients with colitis, colitis-associated dysplasia, and CAC as well as in dysplastic tumors of C57BL/6 mice treated with azoxymethane-dextran sulfate sodium. In this model, EtHOBA significantly reduced adduct formation, tumorigenesis, and dysplasia severity.
CONCLUSIONS
Dicarbonyl electrophiles represent a link between inflammation and somatic genomic alterations and are thus key targets for cancer chemoprevention.
Topics: Animals; Benzylamines; Cell Nucleus; Cell Transformation, Neoplastic; Colitis-Associated Neoplasms; Disease Models, Animal; Epithelial Cells; Gastric Mucosa; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Humans; Lipids; Metaplasia; Mice; Mice, Transgenic; Organoids; Precancerous Conditions; Stomach Neoplasms
PubMed: 33189701
DOI: 10.1053/j.gastro.2020.11.006 -
Journal of Clinical Laboratory Analysis Jan 2022Gastrointestinal endoscopy and biopsy-based pathological findings are needed to diagnose early gastric cancer. However, the information of biopsy specimen is limited...
BACKGROUND AND AIM
Gastrointestinal endoscopy and biopsy-based pathological findings are needed to diagnose early gastric cancer. However, the information of biopsy specimen is limited because of the topical procedure; therefore, pathology doctors sometimes diagnose as gastric indefinite for dysplasia (GIN).
METHODS
We compared the accuracy of physician-performed endoscopy (trainee, n = 3; specialists, n = 3), artificial intelligence (AI)-based endoscopy, and/or molecular markers (DNA methylation: BARHL2, MINT31, TET1, miR-148a, miR-124a-3, NKX6-1; mutations: TP53; and microsatellite instability) in diagnosing GIN lesions. We enrolled 24,388 patients who underwent endoscopy, and 71 patients were diagnosed with GIN lesions. Thirty-two cases of endoscopic submucosal dissection (ESD) in 71 GIN lesions and 32 endoscopically resected tissues were assessed by endoscopists, AI, and molecular markers to identify benign or malignant lesions.
RESULTS
The board-certified endoscopic physicians group showed the highest accuracy in the receiver operative characteristic curve (area under the curve [AUC]: 0.931), followed by a combination of AI and miR148a DNA methylation (AUC: 0.825), and finally trainee endoscopists (AUC: 0.588).
CONCLUSION
AI with miR148s DNA methylation-based diagnosis is a potential modality for diagnosing GIN.
Topics: Aged; Aged, 80 and over; Artificial Intelligence; Biomarkers, Tumor; DNA Methylation; Diagnosis, Computer-Assisted; Early Detection of Cancer; Endoscopic Mucosal Resection; Endoscopy, Gastrointestinal; Female; Humans; Male; MicroRNAs; Middle Aged; Stomach; Stomach Neoplasms
PubMed: 34811809
DOI: 10.1002/jcla.24122 -
Gut Nov 1999
Review
Topics: Gastric Mucosa; Humans; Observer Variation; Precancerous Conditions; Stomach Neoplasms
PubMed: 10517922
DOI: 10.1136/gut.45.5.784 -
International Journal of Molecular... Sep 2017Despite a significant decrease in the incidence of gastric cancer in Western countries over the past century, gastric cancer is still one of the leading causes of... (Review)
Review
Despite a significant decrease in the incidence of gastric cancer in Western countries over the past century, gastric cancer is still one of the leading causes of cancer-related deaths worldwide. Most human gastric cancers develop after long-term infection via the Correa pathway: the progression is from gastritis, atrophy, intestinal metaplasia, dysplasia, to cancer. However, it remains unclear whether metaplasia is a direct precursor of gastric cancer or merely a marker of high cancer risk. Here, we review human studies on the relationship between metaplasia and cancer in the stomach, data from mouse models of metaplasia regarding the mechanism of metaplasia development, and the cellular responses induced by infection.
Topics: Animals; Biomarkers; Disease Models, Animal; Epigenesis, Genetic; Gastric Mucosa; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Mice; Neoplasm Grading; Precancerous Conditions; Signal Transduction; Stomach; Stomach Neoplasms
PubMed: 28953255
DOI: 10.3390/ijms18102063 -
World Journal of Gastroenterology Jan 2016Gastric cancer (GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa's cancer cascade, non-cardia GC... (Review)
Review
Gastric cancer (GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa's cancer cascade, non-cardia GC is usually developed through a series of mucosal changes from non-atrophic gastritis to atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia and adenocarcinoma. Atrophic gastritis and IM are therefore generally considered to be pre-neoplastic gastric lesions. Helicobacter pylori (H. pylori) infection is an important initiating and promoting step of this gastric carcinogenesis cascade. Emerging long-term data showed that eradication of H. pylori reduced the risk of subsequent cancer development. It however remains confusing whether eradication of the bacterium in individuals with pre-neoplastic gastric lesions could regress these changes as well as in preventing cancer. Whilst H. pylori eradication could likely regress AG, the presence of IM may be a point of no return in this cascade. Hence, surveillance by endoscopy may be indicated in those with extensive IM or those with incomplete IM, particularly in populations with high GC risk. The optimal interval and the best tool of surveillance endoscopy remains to be determined in future studies.
Topics: Anti-Bacterial Agents; Biopsy; Cell Transformation, Neoplastic; Disease Progression; Gastric Mucosa; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Precancerous Conditions; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Stomach Neoplasms
PubMed: 26811668
DOI: 10.3748/wjg.v22.i3.1311 -
The Turkish Journal of Gastroenterology... Jun 2020Traditional serrated adenomas (TSAs), despite their low incidence in colorectum, may originate in other parts of the gastrointestinal (GI) tract, including stomach and...
BACKGROUND/AIMS
Traditional serrated adenomas (TSAs), despite their low incidence in colorectum, may originate in other parts of the gastrointestinal (GI) tract, including stomach and small intestine. Malignant transformation for upper GI TSAs has recently been reported in the literature. Here, we present a series of gastric and small intestinal TSAs with the aim to characterize their morphologic and immunophenotypic features as well as their neoplastic potential in a compartmental manner using digitalized images.
MATERIALS AND METHODS
The study comprised 12 GI polyps with TSA features-5 gastric and 7 small intestinal. The extent of the characteristic features of TSA, including eosinophilic cells, ectopic crypt foci (ECF), slit-like serration, foveolar epithelium, goblet cells, together with dysplastic-carcinomatous foci were assessed on digitalized H-E images and were used as reference for immunohistochemical analysis.
RESULTS
All polyps in the cohort contained eosinophilic cells as the most extensive morphologic feature followed by ECF and slit-like serration in decreasing order. Serrated dysplasia was more common in gastric polyps, which more frequently showed neoplastic progression compared with the intestinal ones. CK20 was the most widely expressed marker with a preference to eosinophilic cells while ECFs were mostly negative. Ki67 showed the opposite pattern of CK20. MUC6 and MUC2 were selectively expressed in the basal zone and goblet cells, respectively.
CONCLUSION
Our results showed that the presence of eosinophilic cells with pencillate nuclei commonly accompanied by ECF and slit-like serration are the defining features of gastric and small intestinal TSAs. They frequently harbor neoplastic foci, particularly in gastric location where serrated dysplasia seems to be more common.
Topics: Adenoma; Aged; Aged, 80 and over; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Intestinal Neoplasms; Intestine, Small; Male; Middle Aged; Polyps; Stomach; Stomach Neoplasms
PubMed: 32721915
DOI: 10.5152/tjg.2020.19931 -
Surgical Pathology Clinics Sep 2020This review provides an overview of different types of gastric epithelial polyps. The polyps are classified based on their cell or epithelial compartment of origin. Some... (Review)
Review
This review provides an overview of different types of gastric epithelial polyps. The polyps are classified based on their cell or epithelial compartment of origin. Some of these polyps can be considered reactive or nonneoplastic, whereas others are neoplastic in origin, are sometimes associated with a hereditary polyposis/cancer syndrome, and may have malignant potential. The aim of this review is to provide a pragmatic overview for the practicing pathologist about how to correctly diagnose and deal with gastric epithelial polyps and when (not) to ponder, and when (not) to panic.
Topics: Adenomatous Polyps; Biopsy; Diagnosis, Differential; Gastric Fundus; Humans; Prognosis; Stomach; Stomach Neoplasms
PubMed: 32773193
DOI: 10.1016/j.path.2020.05.004