Intestinal Metaplasia Subtype Research Articles

Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to transform to GC. By highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression, our results raise opportunities for GC precision prevention and interception.

Magnifying endoscopy with narrow-band imaging for diagnosis of subtype of gastric intestinal metaplasia.

Patients with incomplete gastric intestinal metaplasia (GIM) have a higher risk of gastric cancer (GC) than those with complete GIM. We aimed to clarify whether micromucosal patterns of GIM in magnifying endoscopy with narrow-band imaging (M-NBI) were useful for diagnosis of incomplete GIM. We enrolled patients with a history of endoscopic resection of GC or detailed inspection for suspicious or definite GC. The antrum greater curvature and corpus lesser curvature were regions of interest. Areas with endoscopic findings of light blue crest and/or white opaque substance (WOS) were defined as endoscopic GIM, and subsequent M-NBI was applied. Micromucosal patterns were classified into Foveola and Groove types, and targeted biopsies were performed on GIM with each pattern. GIM was classified into complete and incomplete types using mucin (MUC)2, MUC5AC, MUC6, and CD10 immunohistochemical staining. The primary endpoint was the association between micromucosal pattern and histological subtype. The secondary endpoint was endoscopic findings associated with incomplete GIM. We analyzed 98 patients with 156 GIMs. Univariate analysis (odds ratio [OR] 3.4, P=0.004), but not multivariate analysis (OR 0.87, P=0.822), demonstrated a significant association between micromucosal pattern and subtype. The antrum (OR 3.7, P=0.006) and WOS (OR 43, P=0.002) were independent predictors for incomplete GIM. The WOS had 69% sensitivity and 93% specificity. The M-NBI micromucosal pattern is not useful for diagnosis of GIM subtype. WOS is a promising endoscopic indicator for diagnosis of incomplete GIM. (UMIN-CTR000041119).

Improving the Endoscopic Detection and Management of Gastric Intestinal Metaplasia Through Training: A Practical Guide

Improving the Endoscopic Detection and Management of Gastric Intestinal Metaplasia Through Training: A Practical Guide

Multi-scale Multi-instance Multi-feature Joint Learning Broad Network (M3JLBN) for gastric intestinal metaplasia subtype classification

According to worldwide statistics, gastric intestinal metaplasia (GIM) is one of the most important characteristics for detecting the lesions in early gastric cancer. Currently, there are many detection methods employing multi-instance learning (MIL) on clinical medical images. For gastrointestinal endoscope (GE) images, there are very few existing works, which suffer from several issues: (i) only binary (i.e., healthy and GIM) cases are handled; (ii) the inter-instance correlation (i.e., the correlation between image patches or instances) cannot be captured; (iii) the multi-class label correlations among GIM subtype labels are neglected; (iv) multi-scale information is not considered. To address these issues, a novel Multi-scale Multi-instance Multi-feature Joint Learning Broad Network (M3JBLN) is proposed for practically required GIM subtype classification, which includes two new modules: (i) A multi-class MIL prediction module is designed based on probabilistic representation which can provide multi-class label correlations (pseudo label) through labeled multi-scaling training samples; (ii) A novel multiple features joint learning broad network (MFJLBN) based on broad learning system (BLS) is designed by integrating a new representation layer and multi-scaling module, which can jointly obtain inter-instance correlation in feature space under multiple scales. Under these two modules, the proposed M3JBLN jointly considers the multi-features of each instance at multiple scales to achieve more accurate subtype classification. The proposed M3JBLN is evaluated on a limited available GIM dataset acquired from patients who visited the Endoscopy Center of Kiang Wu Hospital (Macau, China) between January 2017 and April 25, 2021. Our method can respectively improve the performance with at least 7.5%, 7.6%, 7.6% and 6.6% under the four-evaluation metrics (accuracy, precision, recall and F1-score) compared to other classic methods.

Correction to: Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies.

Correction to: Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies.

Differences in Regression Patterns of Complete and Incomplete Intestinal Metaplasia at Ten Years after Helicobacter pylori Eradication.

This study was conducted to reveal the reversibility of subtype of intestinal metaplasia (IM) and Paneth cells after H. pylori eradication (HPE). Among 75 patients, we retrospectively examined the proportions of patients with complete type of IM (CIM), incomplete type of IM (IIM) and Paneth cells in their biopsy specimens obtained from the greater curvature of the antrum (A2) and the greater curvature of the middle corpus (B2) before and during a follow-up period of 10 years after HPE. Immunohistochemistry was used to determine IM type. Compared to before HPE, the proportion of patients with CIM did not decrease significantly during the 10-year follow-up after HPE both in A2 (32% vs. 21.3%, P = 0.13) and in B2 (6.7% vs. 2.7%, P = 0.60). IIM rates in A2 was significantly lower during this time (26.7% vs. 10.7%, P = 0.04), whereas no patients showed IIM in B2 before HPE. The proportion of patients with Paneth cells decreased significantly in A2 after 3, 8, and 9 years of HPE and in B2 after 4, 6 and 9 years of HPE (P < 0.05 for all). Thus, IIM and Paneth cells regressed during a period of 10 years after HPE.

Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies.

INTRODUCTION:Intestinal metaplasia (IM) is an independent risk factor for gastric cancer (GC). However, the subtypes of IM as a risk factor for GC remain controversial. We performed a systematic review and meta-analysis to evaluate the relationship between IM subtypes and GC risk.METHODS:Systematic searches were conducted in PubMed, EMBASE, and the Cochrane Library for published cohort studies of patients with complete IM (type I) or incomplete IM (type II or type III) from inception to May 15, 2021. We extracted relevant data and calculated pooled risk ratios (RRs) and 95% confidence intervals (CIs) comparing the GC risk with IM subtypes.RESULTS:Twelve cohort studies comprising 6,498 individuals were included in the study. Compared with complete IM, the pooled relative risk of GC risk of patients with incomplete IM was 5.16 (95% CI, 3.28–8.12), and the GC risk of type III IM was the highest, with a pooled relative risk of 2.88 (95% CI, 1.37–6.04) compared with that of type II. Compared with complete IM, the pooled relative risk of dysplasia risk in patients with incomplete IM was 3.72 (95% CI, 1.42–9.72), and the dysplasia risk of type III IM was 11.73 (95% CI, 2.08–66.08) compared with that of type I.DISCUSSION:Patients with incomplete IM, especially type III, were at a higher risk of GC and dysplasia than those with complete IM. The current evidence indicates a potential correlation between IM subtypes and GC risk, which may support the use of IM subtypes in GC surveillance.

High-risk individuals for gastric cancer would be missed for surveillance without subtyping of intestinal metaplasia.

The use of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Assessment based on Intestinal Metaplasia (OLGIM) staging system is recommended for identifying subjects at risk for developing gastric cancer; usually high-risk lesions are considered only as stages III and IV. Accumulating evidence suggests that incomplete intestinal metaplasia (IM) is important in the development of gastric cancer.Our aim has been to identify the prevalence of incomplete IM in patients with low-risk OLGA/OLGIM stages among a high-risk general population. Healthy adult volunteers aged 40-64years were invited to undergo upper endoscopy within a regional GISTAR pilot study in Kazakhstan (n = 166). Gastric lesions were staged according to OLGA/OLGIM staging system. High iron diamine-alcian blue (HID-AB) was used for subtyping IM. IM prevalence overall was 45.8%. Incomplete IM was present in 52.6% (type II in 30.3% and type III in 22.3%), whereas complete IM was found in 47.4% individuals. The prevalence of OLGIM I and II stage were 39.8 and 4.8%, respectively, whereas OLGIM III was observed in 1.2%. The prevalence of incomplete IM in patients stratified to OLGIM I was 54.5% (type II in 31.8% and type III in 22.7%). High prevalence of incomplete IM was detected not only in subjects with extensive IM, but in those stratified as at the OLGIM I stage. Without IM subtyping, patients with high risk of gastric cancer development would be missed for surveillance.

Gastric cancer screening in low incidence populations: Position statement of AEG, SEED and SEAP

This positioning document, sponsored by the Asociacion Espanola de Gastroenterologia, the Sociedad Espanola de Endoscopia Digestiva and the Sociedad Espanola de Anatomia Patologica, aims to establish recommendations for the screening of gastric cancer (GC) in low incidence populations, such as the Spanish. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates screening in the general population, individuals with relatives with GC and subjects with GC precursor lesions (GCPL). The goal of the interventions should be to reduce GC related mortality. We recommend the use of the OLGIM classification and determine the intestinal metaplasia (IM) subtype in the evaluation of GCPL. We do not recommend to establish endoscopic mass screening for GC or Helicobacter pylori. However, the document strongly recommends to treat H.pylori if the infection is detected, and the investigation and treatment in individuals with a family history of GC or with GCPL. Instead, we recommend against the use of serological tests to detect GCPL. Endoscopic screening is suggested only in individuals that meet familial GC criteria. As for individuals with GCPL, endoscopic surveillance is only suggested in extensive IM associated with additional risk factors (incomplete IM and/or a family history of GC), after resection of dysplastic lesions or in patients with dysplasia without visible lesion after a high quality gastroscopy with chromoendoscopy.

The Colombian Chemoprevention Trial: 20-Year Follow-Up of a Cohort of Patients With Gastric Precancerous Lesions

Helicobacter pylori eradication and endoscopic surveillance of gastric precancerous lesions are strategies to reduce gastric cancer (GC) risk. To our knowledge, this study is the longest prospective cohort of an H pylori eradication trial in a Hispanic population. A total of 800 adults with precancerous lesions were randomized to anti-H pylori treatment or placebo. Gastric biopsy samples taken at baseline and 3, 6, 12, 16, and 20 years were assessed by our Correa histopathology score. A generalized linear mixed model with a participant-level random intercept was used to estimate the effect of H pylori status on the score over time. Logistic regression models were used to estimate progression by baseline diagnosis and to estimate GC risk by intestinal metaplasia (IM) subtype and anatomic location. Overall, 356 individuals completed 20 years of follow-up. Anti-H pylori therapy (intention-to-treat) reduced progression of the Correa score (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.38-0.93). H pylori-negative status had a beneficial effect on the score over time (P= .036). Among individuals with IM (including indefinite for dysplasia) at baseline, incidence rates per 100 person-years were 1.09 (95% CI, 0.85-1.33) for low-grade/high-grade dysplasia and 0.14 (95% CI, 0.06-0.22) for GC. Incomplete-type (vs complete-type) IM at baseline presented higher GC risk (OR, 13.4; 95% CI, 1.8-103.8). Individuals with corpus (vs antrum-restricted) IM showed an OR of 2.1 (95% CI, 0.7-6.6) for GC. In a high-GC-risk Hispanic population, anti-H pylori therapy had a long-term beneficial effect against histologic progression. Incomplete IM is a strong predictor of GC risk.

A Summary of the 2020 Gastric Cancer Summit at Stanford University

There exists no coherent national strategy for the early detection or prevention of gastric cancer in the United States (US), even among identified high-risk groups such as Asian Americans, African Americans, Hispanic Americans, and Alaska Native/American Indian peoples. As a result, patients with gastric cancer in the US are diagnosed at later stages and demonstrate worse overall survival compared to nations of East Asia with established screening programs (Table 1). The under-recognition of gastric cancer risk within minority communities is a significant unaddressed healthcare disparity.

Prevalence of subtypes of gastric intestinal metaplasia and its relationship with Helicobacter pylori infection

Background: Gastric intestinal metaplasia is seen chronic gastritis associated with Helicobacter pylori. The objective of this study was to determine the prevalence of subtypes of intestinal metaplasia and presence of Helicobacter pylori infection.&#x0D; Materials and Methods: This was a cross sectional study done at Kathmandu Medical College teaching Hospital in Pathology department from December 2018 to August 2019. The endoscopic biopsies were evaluated for intestinal metaplasia and Helicobacter pylori with the help of Hematoxylin and Eosin stains as well as Giemsa stain. Subtypes of intestinal metaplasia were classified with the help of periodic acid- Schiff/Alcian Blue stain combination and High Iron Diamine- Alcian Blue stain at pH 2.5. The relationship between Helicobacter pylori and subtypes of intestinal metaplasia were compared. Fisher’s exact test was used for statistical evaluation. A p value of ˂0.05 was considered as statistically significant.&#x0D; Results: The prevalence of intestinal metaplasia was found in 57 (12.2%) biopsies. Type I intestinal metaplasia was found in 23 (40.4%) biopsies, type II in 10 (17.5%) biopsies and type III in 24 (42.1%) biopsies. Helicobacter pylori was positive in 28(49.1%) and it was negative in 29(50.9%) biopsies. No statistical significant correlation was seen in the subtypes of intestinal metaplasia with Helicobacter pylori status (p˃0.05).&#x0D; Conclusion: Intestinal metaplasia is frequently observed in endoscopic biopsies, most common being type III subtype.

Chronic gastritis and carcinogenesis issues

Risk factors contributing to the transformation of chronic atrophic gastritis into gastric cancer are analyzed. Detection and monitoring of patients with precancerous conditions/lesions (precancerous changes), proper screening of H. pylori make early diagnosis of gastric cancer real. Features of precancerous conditions are given in order of increasing risk of developing gastric cancer. Adenomatous polyps of the stomach take the first place. Subsequent precancerous conditions include: cancer of the operated stomach, Menetria disease (hypertrophic gastropathy), B12-deficient anemia, and gastric ulcer. A definition of intestinal metaplasia subtypes is proposed as a risk factor for gastric cancer, dividing into complete and incomplete one, taking into account reduction in the expression of gastric mucins MUC1, MUC5AC and MUC6. Currently, the development of gastric cancer (mainly of the “intestinal type”) is considered as a multistage process involving the sequence of mucosal change, such as chronic inflammation, atrophy, intestinal metaplasia, dysplasia and adenocarcinoma. Role of the organism’s genetic susceptibility to H. pylori infection, factors of pathogenicity contributing to epithelial metaplasia, are analyzed. Role of Toll-like type 4 receptors (TLR4) involved in the recognition of H. pylori is clarified. It is with this type of receptors that the development of an excessive immune response of the host is associated, resulting in damage to the mucous membrane in H. pylori-infected individuals. In particular, carriers of TLR4+896A&gt; G polymorphism have a more severe atrophy of the stomach and degree of inflammation, as well as an increased risk of non-cardiac gastric cancer.

Identifying high-risk individuals for gastric cancer surveillance from western and eastern perspectives: Lessons to learn and possibility to develop an integrated approach for daily practice.

Current evidence shows that individuals with gastric dysplasia, severe and extensive gastric atrophy, extensive gastric intestinal metaplasia and the incomplete subtype of intestinal metaplasia are at high risk for gastric cancer (GC) development. There are several approaches to identifying these subjects, including noninvasive methods, esophagogastroduodenoscopy and histology. The main approach in Western countries is histology-based while that in Eastern countries with a high prevalence of GC is endoscopy-based. Regarding asymptomatic individuals, the key issues in selecting applicable approaches are the ability to reduce GC mortality and the cost-effectiveness of the approach. At present, population-based screening programs have only been applied in a few Asian countries with a high risk of GC. Pre-endoscopic risk assessment based on demographic and clinical features, such as ethnicity, age, gender, smoking and Helicobacter pylori status, is helpful for identifying subjects with high pre-test probability for a possibly cost-effective approach, especially in intermediate- and low-risk countries. Regarding symptomatic patients with indications for esophagogastroduodenoscopy, the importance of opportunistic screening should be emphasized. The combination of endoscopic and histological approaches should always be considered as endoscopy provides a real-time assessment of the patient’s risk level. In addition, imaging enhanced endoscopy (IEE) has been shown to facilitate targeted biopsies resulting in better correlation between endoscopic and histological findings. Currently, the use of IEE is recommended for endoscopic examinations, and the Operative Link for Gastric Intestinal Metaplasia or Operative Link on Gastritis Assessment grading systems are recommended for histological examinations whenever available. However, resource limitations are an important barrier in many regions worldwide. Thus, for an approach to be applicable in real-life practice, it should be not only evidence-based but also resource-sensitive. In this review, we discuss the current understanding and approaches to identifying high-risk individuals from western and eastern perspectives, as well as the possibility of an integrated, resource-sensitive approach.

Nonlinear optical microscopy for label-freely detecting gastric intestinal metaplasia

Intestinal metaplasia has been widely considered as a precursor of gastric cancer. As a result, early detection and accurate diagnosis will have important clinical significance. Therefore, nonlinear optical microscopy using two-photon excited fluorescence combined with second harmonic generation was used for investigating gastric mucosal intestinal metaplasia in this work. The imaging results showed that this microscope has the ability to directly identify this lesion from normal tissues in the absence of labels, and to further differentiate the subtyping of intestinal metaplasia. Furthermore, nuclear areas from normal gastric mucosa and intestinal metaplasia subtypes were measured, respectively, to show the cell changes while gastric mucosa developed from normal to intestinal metaplasia. This study may provide an approach for further researching these diseases in the future, and highlights the potential of nonlinear optical microscopy as a diagnostic tool for label-free identification of gastric intestinal metaplasia.

Multiple White Flat Lesions of the Corpus: Subtype of Hyperplastic Polyps vs. Intestinal Metaplasia.

Multiple White Flat Lesions of the Corpus: Subtype of Hyperplastic Polyps vs. Intestinal Metaplasia.

Risk of gastric cancer among patients with gastric intestinal metaplasia

Plenty of studies have assessed the association between intestinal metaplasia (IM) and gastric cancer risk, while the results were inconsistent. We aimed to assess the risk of gastric cancer among patients with IM. Systematic literature searches were conducted in PubMed, Embase and Cochrane databases. Baseline characteristics and outcomes from the included studies were extracted independently by two investigators. Either a fixed-effects or a random-effects model was used to composite the pooled OR for gastric cancer risk. Finally, a total of 21 studies, which comprised 402,636 participants and 4,535 gastric cancer patients, were finally included in the current meta-analysis. Compared with those participants without IM, IM patients were at a higher risk of gastric cancer (pooled OR = 3.58, 95% CI 2.71-4.73). We observed that incomplete IM (pooled OR = 9.48, 95% CI 4.33-20.78) but not complete IM (pooled OR = 1.55, 95% CI 0.91-2.65) was significantly associated with a higher gastric cancer risk. Besides, it appeared that gastric cancer risk was higher among patients with IM in the corpus (pooled OR = 7.39, 95% CI 4.94-11.06) than those with IM in the antrum only (pooled OR = 4.06, 95% CI 2.79-5.91). And the pooled ORs for gastric noncardia cancer and gastric cardia cancer were 4.98 (95% CI 3.12-7.95) and 1.93 (95% CI 1.15-3.24), respectively. In conclusion, patients with IM were at a higher risk of gastric cancer, especially for incomplete IM and IM in the corpus. The current evidence supports the use of IM subtypes in the surveillance of gastric cancer.

Reversibility of Atrophic Gastritis and Intestinal Metaplasia by Eradication of Helicobacter pylori

Although there are many guidelines recommending Helicobacter pylori (H. pylori) eradication therapy for atrophic gastritis (AG) and intestinal metaplasia (IM), there have been contradictory reports regarding the reversibility of precancerous lesions such as AG and IM after eradication of H. pylori. There have been many reports that have shown AG seems to improve upon eradication of H. pylori to some extent. In contrast, IM has been regarded as 'the point of no return' according to previous reports. However, as recent studies have suggested the improvement of intestinal metaplasia as well, early eradication therapy for reversible histological status is important and necessary for the prevention of gastric cancer. In this review, we focused on the progress of gastritis resulting in AG and IM mainly by H. pylori, the relationship of AG and IM with gastric cancer, the subtype of IM, and the reversibility of AG and IM by eradication of H. pylori. Finally, we introduced the recent extension of indications for H. pylori eradication with coverage by medical insurance, which was published by the Korean Ministry of Health and Welfare in January 2018.

The Distribution of Incomplete Gastric Intestinal Metaplasia (GIM) Subtype among Biopsy Sites according to the Updated Sydney System and Its Association with GIM Extension.

Background Current guidelines recommend that extensive gastric intestinal metaplasia (GIM) be considered as a high-risk marker for the development of gastric cancer (GC). But there is emerging evidence that the incomplete GIM subtype is also a high-risk marker. Aims To evaluate the performance of biopsy sites according to the updated Sydney system on detecting the incomplete GIM subtype and to assess its association with GIM extension. Patients and methods A cross-sectional study was conducted on 280 Vietnamese patients with nonulcer dyspepsia. Biopsy specimens were taken from gastric sites according to the updated Sydney system, and sections were routinely stained with Giemsa and hematoxylin and eosin. Biopsy specimens with intestinalization were further evaluated for GIM subtypes with alcian blue 2.5 and periodic acid Schiff stainings. Two experienced pathologists jointly examined all the specimens and reached consensus. Results The rates of patients with GIM and the incomplete GIM subtype were 81 (28.9%) and 24 (8.4%), respectively. There was no GIM in specimens taken from the greater curvature of corpus. The proportions of the incomplete GIM subtype detected at the incisura angularis, lesser curvature of corpus, lesser curvature of antrum, and greater curvature of antrum were 34.3% (12/35), 34.5% (10/29), 40.5% (17/42), and 31.6 (6/19), respectively, which were not significantly different (p = 0.89). The presence of an incomplete GIM subtype was associated with multifocal GIM (i.e., ≥3 out of 5 biopsy sites with GIM) (OR = 4.02, CI 95%, 1.33–12.16, p = 0.022) and extensive GIM (i.e., GIM in specimens from both of corpus and antrum) (OR = 2.89, CI 95% 1.04–8.02, p = 0.045). Conclusions The proportions of an incomplete GIM subtype were not significantly different among gastric biopsy sites with intestinalization. The association between an incomplete GIM subtype and GIM extension, therefore, may be due to an sum accumulation effect.

Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial

ObjectiveTo evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions.Design795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori...