Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from autoimmune gastritis. Pernicious anemia occurs in a later stage of autoimmune atrophic gastritis when gastric intrinsic factor deficiency and consequent vitamin B₁₂ deficiency may occur. The multifaceted nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, may lead to several dysfunctions, and thus, the proteiform clinical presentations of pernicious anemia. Indeed, pernicious anemia may lead to potentially serious long-term complications related to micronutrient deficiencies and their consequences and the development of gastric cancer and type 1 gastric neuroendocrine tumors. When not recognized in a timely manner or when pernicious anemia is diagnosed with delay, these complications may be potentially life-threatening and sometimes irreversible. The current review aimed to focus on epidemiology, pathogenesis, and clinical presentations of pernicious anemia in an attempt to look beyond borders of medical specialties. It aimed to focus on micronutrient deficiencies besides the well-known vitamin B₁₂ deficiency, the diagnostic approach for pernicious anemia, its long-term complications and optimal clinical management, and endoscopic surveillance of patients with pernicious anemia.

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological–psychiatric up to gastrointestinal and less commonly to gynecological–obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.

Summary: Background: Gastric cancer ranks fourth in terms of global cancer‐related deaths. Timely identification of high‐risk populations is crucial to reduce mortality. Although a family history of gastric cancer increases risk, European and British guidelines report weak recommendations and low‐quality evidence about the management of these patients.Aim: To quantify the association in case–control studies of patients with gastric cancer with first‐degree relatives with gastric cancer compared to those who do not.Methods: We conducted a systematic review and meta‐analysis of case–control studies up to November 2023. Data extraction was performed independently by two reviewers. The heterogeneity of effects across studies was quantified by I². We calculated odds ratios (OR) with 95% confidence intervals (CI) using random effects models.Results: We included 30 studies in the systematic review. In all studies, a first‐degree family history of gastric cancer represented a risk factor for gastric cancer. We included 21 studies on the risk of gastric cancer. There was a significantly increased association between gastric cancer and having first‐degree relative(s) with gastric cancer, but with significant heterogeneity among studies (OR = 2.92; 95% CI 2.402–3.552; p < 0.001; I² = 81.85%; p < 0.001).Conclusion: This meta‐analysis highlights the relevance of patients' family history of gastric cancer and the importance of this risk factor for the early detection of neoplastic conditions.

Gender differences and microbiota are gaining increasing attention. This study aimed to assess gender differences in gastric bacterial microbiota between subjects with healthy stomachs and those with autoimmune atrophic gastritis. This was a post hoc analysis of 52 subjects undergoing gastroscopy for dyspepsia (57.7% healthy stomach, 42.3% autoimmune atrophic gastritis). Gastric biopsies were obtained for histopathology and genomic DNA extraction. Gastric microbiota were assessed by sequencing the hypervariable regions of the 16SrRNA gene. The bacterial profile at the phylum level was reported as being in relative abundance expressed as 16SrRNA OTUs (>0.5%) and biodiversity calculated as Shannon-diversity index-H. All data were stratified for the female and male gender. Results showed that women with healthy stomachs had a higher gastric bacterial abundance and less microbial diversity compared to men. Likely due to hypochlorhydria and the non-acid intragastric environment, autoimmune atrophic gastritis seems to reset gender differences in gastric bacterial abundance and reduce biodiversity in males, showing a greater extent of dysbiosis in terms of reduced biodiversity in men. Differences between gender on taxa frequency at the phylum and genus level in healthy subjects and autoimmune atrophic gastritis were observed. The impact of these findings on the gender-specific natural history of autoimmune atrophic gastritis remains to be elucidated; in any case, gender differences should deserve attention in gastric microbiota studies.

Corpus atrophic gastritis (CAG) is defined as autoimmune when the antrum is spared, representing this element a crucial diagnostic criterium of autoimmune gastritis. In contrast, CAG with concomitant antral gastritis (AG), atrophic or non-atrophic, is generally attributed to H. pylori infection. During the natural history of CAG, possible antrum healing has been supposed. The current study aimed to assess the antral mucosa histopathological changes at long-term follow-up (FU) with respect to baseline in patients with CAG and concomitant atrophic or non-atrophic gastritis AG. Retrospective study on 130 patients with histologically diagnosed CAG with atrophic or non-atrophic AG. Mean FU gastroscopy was at 40.6 (range 4-192) months. Patients with confirmed CAG (n = 117; median age 66, range 20-87 years; 67.5 % F) were finally included. At baseline, 47 (40.2 %) had non-atrophic and 70 (59.8 %) atrophic AG. Helicobacter pylori (Hp) infection was present at histology in 27.3 % of patients, all treated. At FU, 30/117(25.6 %) patients showed a complete antral healing; 11/29(37.9 %) were Hp positive at baseline, cured in all but one. Atrophic AG regressed in 16/70(22.8 %) patients. Both, antral healing and regression of antral AG, were found to be similar in Hp-cured and not-cured/ naïve-negatives patients (p > 0.05). In a subset of CAG patients, AG may regress at long-term FU irrespective of Hp cure, thus mimicking autoimmune atrophic gastritis and raising concerns about its current histopathological diagnostic criteria.

Aims Gastric cancer (GC) is the fourth cause of death for neoplasia. To reduce GC mortality, a strategy is to diagnose preneoplastic conditions (PNC) in patients with risk factors. Since in first degree relatives (FDR) was found an up to 2.5 times increased risk for GC, recent guidelines suggest only an esophagogastroduodenoscopy (EGDS) screening in patients who have a FDR for GC. If PNC are diagnosed, Euopean guidelines MAPS II, suggest repeating EGDS shortening the interval.The aim is to determine the prevalence of PNC and GC inpatients undergoing EGDS for FDR for GC. Methods In this cross-sectional study, patients who underwent an EGDS with biopsies according to the updated Sydney system protocol, with the indication for FDR for GC from January 2008 to September 2022, were included. The PNC were staged with OLGA and OLGIM systems. Exclusion criteria were patients with previous gastric surgery and patients with an incomplete biopsy sampling Results Overall, 310 patients were included [64%F; 56(20-87)years]. We identified 2 (0.6%) GC and 2 (0.6%) low-grade dysplasia (none of these patients had previous dysplasia). Regarding PNC, 11 % were OLGA I-II, 0.3% OLGA III-IV whilst 10% were OLGIMI-II and 0.3% were OLGIMIII-IV. Hp infection was found in 25.5% of patients. Furthermore, in 2.25% of cases, corpus-restricted atrophic gastritis was diagnosed. Conclusions Our study support the role of the EGDS with biopsies in patients with FDR for GC as 2 GC and 2 low-grade dysplasia were found in patients with low-stages of OLGA/OLGIM, and 10% of patients would be required to follow-up according to European guidelines. Article published online: 14 April 2023 © 2023. European Society of Gastrointestinal Endoscopy. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany