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ObjectiveOperative link on gastritis assessment (OLGA) staging for gastritis ranks the risk for gastric cancer (GC) in progressive stages (0–IV). This prospective study aimed at quantifying the cancer risk associated with each gastritis stage.DesignA cohort of 1755 consecutive patients with dyspepsia underwent initial (T-0) oesophagogastroduodenoscopy with mapped gastric biopsies, OLGA staging and assessment of Helicobacter pylori infection. Patients were followed for 55 months (median); patients with stages II III and IV underwent a second endoscopy/restaging (T-1), and those with stages 0 and I were followed clinically and through in-depth clinical and record checking. Endpoints were OLGA stage at T-1 and development of gastric epithelial neoplasia.ResultsAt T-0, 77.6% of patients had stage 0, 14.4% stage I, 5.1% stage II, 2.1% stage III and 0.85% stage IV. H. pylori infection was detected in 603 patients at T-0 and successfully eradicated in 602 of them; 220 had a documented history of H. pylori eradication; and 932 were H. pylori naïve-negative. Incident neoplastic lesions (prevalence=0.4%; low-grade intraepithelial neoplasia (IEN)=4; high-grade IEN=1; GC=2) developed exclusively in patients with stages III–IV. The risk for epithelial neoplasia was null in patients at stages 0, I and II (95% CI 0 to 0.4), 36.5 per 1000 person-years in patients at stage III (95% CI 13.7 to 97.4) and 63.1 per 1000 person-years in patients at stage IV (95% CI 20.3 to 195.6).ConclusionsThis prospective study confirms that OLGA staging reliably predicts the risk for development of gastric epithelial neoplasia. Although no neoplastic lesions arose in H. pylori-naïve patients, the H. pylori eradication in subjects with advanced stages (III–IV) did not abolish the risk for neoplastic progression.

The human immunodeficiency virus (HIV) pandemic heavily affects sub‐Saharan Africa. It is associated with persistently active Epstein‐Barr virus (EBV) infection. To determine if this translates into increased frequency of EBV‐associated gastric cancer (EBVaGC), we evaluated molecular profiles of gastric cancer (GC) in Zambia. Patients with GC or premalignant gastric lesions were enrolled in Lusaka, Zambia. We used patients without any of these lesions as a control group. Chromogenic in situ hybridization (CISH) on tumor tissue was used to identify EBVaGC. To identify the microsatellite unstable subtype, immunofluorescence staining for MutL homolog 1 (MLH1) was used. Exposure to EBV and HIV was assessed serologically. We enrolled 369 patients (median age 52 years [IQR 41‐65]; 198 (54%) female). Of these, 72 (20%) had GC and 35 (9%) had gastric premalignant lesions (PL). CISH identified EBVaGC in 5/44 (11%) of those with adequate tissue, while MLH1 loss was identified in 29/45 (64%). Both GC and PL were associated with the highest titers of antibodies to Early antigen‐diffuse (OR 2.5, 95% CI 1.0‐6.1, P = .048 and OR 3.9, 95% CI 1.1‐12.9, P = .03, respectively) at high concentrations. Human immunodeficiency virus infection was associated with a range of antibodies to EBV, but not with any cancer subtype. Despite the association of HIV with persistent EBV, the proportion of EBVaGC in Zambia is similar to populations with a low prevalence of HIV infection. The proportion of microsatellite unstable tumors may be higher than other populations. Human immunodeficiency virus infection is associated active Epstein‐Barr virus (EBV) infection. We found that this does not necessarily translate into an increased proportion of EBV‐associated gastric cancer. We also found a much higher proportion of microsatellite unstable tumors than that reported elsewhere. These findings provide good preliminary data that could be helpful in understanding not only gastric carcinogenesis but probably avenues for new therapies as well.

Concerning the first point on the classification of atrophic gastritis, the current literature is largely biased by the inconsistency of the histological criteria used to categorise atrophy. 1, 2 To amalgamate the different viewpoints and also test interobserver agreement in atrophy classification/scoring, an international group of pathologists recently published an extensive description of the different phenotypes of gastric atrophy. 3 By merging Western and Eastern experiences, the new proposal extensively describes the diagnostic categories that should be adopted to enable acceptable comparisons between clinicopathological studies involving gastric atrophy (both non-metaplastic and metaplastic). The NND (number needed to diagnose 6 ) values in detecting atrophy calculated for incisura, antrum, and corpus sampling were 2.17, 4.85, and 63.29, respectively. Because of different pricing policies in different countries, it is difficult to estimate the additional cost of processing and interpreting the extra biopsy sample taken from the incisura angularis.

Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

Background Gastric microbial dysbiosis were reported to be associated with gastric cancer (GC). This study aimed to explore the variation, diversity, and composition patterns of gastric bacteria in stages of gastric carcinogenesis based on the published datasets. Methods We conducted a gastric microbial analysis using 10 public datasets based on 16S rRNA sequencing, including 1270 gastric biopsies of 109 health control, 183 superficial gastritis (SG), 135 atrophic gastritis (AG), 124 intestinal metaplasia (IM), 94 intraepithelial neoplasia (IN), 344 GC, and 281 adjacent normal tissues. And QIIME2-pipeline, DESeq2, NetMoss2, vegan, igraph, and RandomForest were used for the data processing and analysis. Results We identified three gastric microbial communities among all the gastric tissues. The first community (designate as GT-H) was featured by the high abundance of Helicobacter . The other two microbial communities, namely GT-F, and GT-P, were featured by the enrichment of phylum Firmicutes and Proteobacteria, respectively. The distribution of GC-associated bacteria, such as Fusobacterium , Peptostreptococcus , Streptococcus , and Veillonella were enriched in tumor tissues, and mainly distributed in GT-F type microbial communities. Compared with SG, AG, and IM, the bacterial diversity in GC was significantly reduced. And the strength of microbial interaction networks was initially increased in IM but gradually decreased from IN to GC. In addition, Randomforest models constructed in in GT-H and GT-F microbial communities showed excellent performance in distinguishing GC from SG and precancerous stages, with varied donated bacteria. Conclusions This study identified three types of gastric microbiome with different patterns of composition which helps to clarify the potential key bacteria in the development of gastric carcinogenesis.

Confocal laser endomicroscopy (CLE) may increase the detection of gastric premalignant lesions, and facilitate targeted biopsies for histology. The study aim was to analyse premalignant lesions in Zambian adults using CLE. Using CLE and histology we analysed the antral mucosa for gastric premalignant lesions in asymptomatic adults living with HIV and in HIV seronegative adults. Fasting gastric pH and the presence of Helicobacter pylori (H. pylori) were also evaluated. We enrolled 84 HIV seropositive participants (median age 43 years; 55 (65%) female), of whom 32 (38%) were anti-retroviral therapy (ART)-naïve. Also enrolled were 22 HIV seronegative controls (median age 39 years, 12 (55%) females). Hypochlorhydria was found in 48 (57%) HIV positive and 8 (38%) HIV negative controls (P = 0.14). Detection of gastric intestinal metaplasia (GIM) was higher (P = 0.007) using CLE (49, 54%) than histology (9, 9%) and, using CLE, GIM was similar between HIV positive (41, 60%) and negative groups (8, 36%; P = 0.08). Gastric luminal fluorescein leakage was significantly associated with the presence of GIM [OR 8.2; 95% CI 2.5-31, P<0.001]. CLE is useful for the detection of GIM, and luminal fluorescein leakage may represent a novel CLE marker for GIM. GIM is common in Zambian adults, and is highly prevalent irrespective of HIV infection or use of ART.

Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger.

As CDX2 expression precedes the occurrence of gastric preneoplastic lesions in the intestinal differentiation pathway, study of these steps of gastric carcinogenesis may contribute toward understanding the early effects of gastric cancer determinants. Our aim was to quantify the association between Helicobacter pylori infection and other environmental factors and the gastric expression of CDX2. Dyspeptic patients undergoing an upper digestive endoscopy (Gastroenterology Department, Maputo Central Hospital) were consecutively invited to participate in this study and classified as having normal stomach/chronic nonatrophic gastritis (NS/CNAG), chronic atrophic gastritis (CAG), or intestinal metaplasia (IM). For all patients with CAG or IM and a subsample of NS/CNAG patients (sex-matched and age-matched, 1:2), H. pylori infection and CDX2 gene expression were assessed by histology and PCR and by immunohistochemistry, respectively. Age-adjusted, sex-adjusted, education-adjusted, and H. pylori infection-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were computed. CDX2 expression was observed in 56 NS/CNAG (49.1%), 39 CAG (86.7%), and all IM patients (n = 12). It was more frequent among the H. pylori-infected patients (OR = 2.26, 95% CI: 1.00–5.15). Infection with high-virulence strains was associated with CDX2 expression in patients with CAG (cagA⁺, OR = 3.20, 95% CI: 1.35–7.52) and IM (vacA m₁, OR = 5.86, 95% CI: 1.08–31.62). Patients with a lower frequency of vegetable consumption had a higher risk of marked CDX2 expression (OR = 3.64, 95 % CI: 1.02–12.95). The virulence of the infecting strains and vegetable consumption were associated with CDX2 expression and may play a role in the progression to more advanced lesions.

Background Esophageal squamous cell carcinoma (ESCC), head and neck SCC (HNSCC), and gastric adenocarcinoma (GA) are frequently detected at an early stage using endoscopic screening in Japanese alcohol‐dependent men. Methods We performed endoscopic screening with esophageal iodine staining and oropharyngolaryngeal inspection in 7582 Japanese alcohol‐dependent men (40‐79 years) during 1993‐2018, and retrospectively investigated their initial screening results. Results The 2008‐2018 screening showed lower detection rates for ESCC (2.6% vs 4.0%, P = .0009) and GA (0.5% vs 1.4%, P < .0001) for all age brackets, compared with the 1993‐2007 screening. The HNSCC detection rate did not change (1.0% vs 1.1%). Multiple logistic regression analyses showed that the 2008‐2018 screening had a reduced OR (95% CI) for ESCC (0.34 [0.25‐0.47]) and GA (0.19 [0.10‐0.35]), compared with the 1993–2007 screening. The reduction in H pylori infection is probably the main reason for the decrease in GA detection over time. Declining trends in pack‐years and gastric atrophy and increasing trends in age and body mass index (BMI) were found over time. The presence of advanced gastric atrophy increased the risk for ESCC as well as GA. The inactive heterozygous aldehyde dehydrogenase‐2*1/*2 genotype was a strong risk factor for ESCC, HNSCC, and GA. Fewer pack‐years and a larger BMI decreased the ESCC risk. However, these confounders cannot fully explain why the incidence of ESCC has decreased markedly over the recent decade. Conclusions The detection rates of ESCC and GA have markedly decreased during the past decade in the alcohol‐dependent population. The enigmatic declining trend of ESCC warrants research on this topic. Comparison of detection rates of esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma (GA) according to age groups and ALDH2 genotype between the 1993‐2007 screening period and the 2008‐2018 screening period in Japanese alcohol‐dependent men. The detection rates for ESCC and GA were consistently lower during the 2008‐2018 study period than during the 1993‐2007 study period regardless of age groups and ALDH2 genotype.

We evaluated associations between Epstein–Barr virus (EBV) antibody levels and precancerous gastric lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) in 183 subjects from Linqu, China. Immunoglobulin G antibody titers to EBV nuclear antigen (EBNA) and viral capsid antigen (VCA) were determined by two‐fold serial dilution using immunofluorescence assays. Histological progression and regression were assessed by gastroscopic examination at the time of phlebotomy and at follow up 2 years later. Antibody titers did not differ significantly among histological diagnoses determined at the time of phlebotomy. However, subjects with dysplasia at follow up had significantly higher geometric mean antibody titers for both anti‐VCA and anti‐EBNA. Subjects with greater than median antibody levels were more likely to progress between examinations, especially in the subgroup with intestinal metaplasia at the time of phlebotomy (odds ratios [95% confidence intervals]: 5.7 [1.6–20] for anti‐EBNA ≥1:320; 3.8 [1.0–15] for anti‐VCA ≥1:640). Our findings suggest a possible role for EBV reactivation at an early phase of gastric carcinogenesis. (Cancer Sci 2008; 99: 350–354)