Search Results (74)

At present, the gold standard for gastric cancer (GC) confirmation relies mostly on histopathology, an invasive procedure. Noninvasive detection methods using serum for large-scale screening may be useful for the early diagnosis of GC. Helicobacter pylori (HP) infection and chronic atrophic gastritis are major GC risk factors. We recently developed a noninvasive test called the DSC test-based on the patient’s age, sex, their serum PGI and PGII, anti-HP immunoglobulin (IgG), and gastrin G17 levels-predicting GC risk as low (score 0, S0) or high (score 2, S2). The comparative investigation at the serum protein level of the two different patient groups detected by our DCS test (S0 and S2) may undoubtedly help to identify gastric disease-dependent proteins, resulting from bacterial infection or gastric mucosa inflammation, as well as get better insight into the molecular scenario associated with pre-cancerous conditions. We used an untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based proteomic profiling approach, followed by univariate statistical analysis to compare the different DSC groups across two patient cohorts (exploratory and validation). Significantly differentially abundant proteins differing more than 1.5-fold between S0 and S2 groups were selected and validated, and their putative role(s) in gastritis and GC were discussed. In both the exploratory and the validation cohorts, four proteins (beta-2-microglobulin, EGF-containing fibulin-like extracellular matrix protein 1, complement factor D, and cystatin-C) were more abundant, while two (sex hormone-binding globulin and pregnancy zone protein) were less abundant in the sera of S2 individuals (|fold change| ≥ 0.6, p < 0.05, t-test). The higher presence of beta-2-microglobulin (B2M) and the lower content of pregnancy zone protein (PZP) in S2 sera were validated by immunoblotting. Replacing age and sex in our DSC model with two specific candidate biomarkers can lead to a refined, albeit modest, improvement in classification accuracy. This study identified a proteomic signature that was differentially associated with the sera of patients with a different risk to develop advanced atrophy/GC according to the DSC test. Moving from a demographic model to a proteomic-driven model can better reflect the personalized biology of pathological processes associated with DSC. Full article

A 27-year-old male presented with chronic diarrhea, bloating, and abdominal pain since age 13. Initially attributed to lactose intolerance, treated with dairy-free diet, symptoms persisted despite negative workup—normal celiac serology, stool studies, and abdominal ultrasound. Recent symptoms included severe diarrhea, fatigue, weakness, 8 kg weight loss, hair loss, elevated IgE and fecal calprotectin. Gastroscopy showed flattened, granular gastric mucosa with focal hyperemia in the antrum and greater curvature. Histology revealed severe chronic inactive H. pylori-negative gastritis with a prominent subepithelial collagen band (verified by Crossmon’s trichrome), confirming collagenous gastritis—a rare entity first described in 1989. The condition has a slight female predominance and bimodal age peaks (adolescence and >60 years). Symptoms are nonspecific, including abdominal pain, diarrhea, weight loss and anemia. Pediatric cases often feature nodular mucosa and anemia; adults more commonly present with watery diarrhea, sometimes linked to collagenous colitis. Diagnosis requires histological features including patchy subepithelial collagen band ≥ 10 μm thick, lymphocytic or eosinophilic infiltration of the lamina propria, epithelial changes and entrapped capillaries. Patterns include atrophic, lymphocytic-like, and eosinophil-rich. Crossmon’s or Masson’s trichrome, Congo red, and tenascin immunohistochemistry aid in proving collagen and excluding amyloidosis. Treatment is mainly symptomatic or with proton pump inhibitors; corticosteroids may be effective in refractory cases. Full article

Gastric neuroendocrine tumors (NETs) are increasingly diagnosed as incidental findings during upper gastrointestinal endoscopy. For the gastroenterologist, the crucial challenge is not only at the time of endoscopic recognition but also when the pathology report states “well-differentiated gastric NET”. At that moment, the key clinical question is how to manage it correctly. Gastric NETs are biologically heterogeneous, and their management depends primarily on the pathophysiological setting in which they arise. Type 1 tumors develop in chronic atrophic gastritis and are usually indolent; type 2 tumors arise in the context of gastrinoma and MEN1; type 3 tumors are sporadic and carry a substantially higher metastatic risk. Consequently, the same histological label may correspond to profoundly different clinical scenarios. This review addresses what the gastroenterologist should do after receiving an incidental histological diagnosis of gastric NET, how to reconstruct the gastric background, when to suspect a sporadic type 3 lesion, how to select patients for endoscopic treatment versus staging or surgery, and how to interpret incomplete endoscopic resection. Particular attention is devoted to the emerging concept of proton pump inhibitor-associated gastric NETs, which may represent a distinct gastrin-driven subgroup with lower malignant potential than truly sporadic type 3 tumors. A practical algorithm and a clinicopathological comparison of the classic three gastric NET types are provided to support decision-making in daily practice. Full article

Background: Hepatitis B virus (HBV) is an infection proven to increase the risk of gastric cancer, especially among hepatitis B virus surface antigen (HBsAg) seropositive patients. However, the route through which HBV injures gastric mucosa and its mechanism of gastric carcinogenesis are still under investigation. Aims: The present study aimed to observe and evaluate associations between HBV infection with Helicobacter pylori, atrophic gastritis, and some other high-risk events for gastric cancer development. Methods: A retrospective cross-sectional study recruited participants undergoing a health check-up between 2018 and 2020 in the West China Hospital of Sichuan University. Participants were stratified into three statuses, including Group A (non-HBV infection), Group B (resolved HBV infection), and Group C (chronic HBsAg carriers or active HBV infection). Additionally, Groups A and B were categorized as HBsAg-seronegative, whereas Group C was defined as HBsAg-seropositive. High-risk events of gastric cancer included a history of gastric ulcer, Helicobacter pylori infection, serological atrophic gastritis (serum pepsinogens), hypergastrinemia (serum gastrin-17), and endoscopic findings of atrophic gastritis, gastric polyps, and gastric ulcer. Associations of HBV infection status or HBsAg seropositivity with Helicobacter pylori infection, atrophic gastritis and other high-risk events of gastric cancer were analyzed. Results: A total of 21,505 eligible observations were included, with Group C accounting for 6.1%. In Group C, the prevalence of gastric ulcer (p = 0.002) and very-high serum gastrin-17 level (p = 0.002) was significantly greater than in Group A. In multivariate analysis, both Helicobacter pylori infection (aOR = 2.79, 95% CI 2.44–3.21) and HBsAg seropositivity (aOR = 1.28, 95% CI 1.02–1.59) were significant risk factors for hypergastrinemia. No interaction was found between Helicobacter pylori co-infection risks and Group B (aOR = 1.10, 95% CI 0.84–1.43) or Group C (aOR = 1.40, 95% CI 0.66–2.95). Helicobacter pylori infection was identified as an independent risk factor for atrophic gastritis (aOR = 1.85, 95% CI 1.44–2.39). However, HBsAg seropositivity did not show a similar association with atrophic gastritis (aOR = 1.15, 95% CI 0.75–1.74). Moreover, HBV co-infection did not exert a synergistic effect on the risk of atrophic gastritis in individuals with Helicobacter pylori (aOR = 1.09, 95% CI 0.54–2.22). Additionally, multivariate analyses did not identify significant associations between HBV infection statuses and gastric polyps or ulcers. Conclusions: HBsAg seropositivity was not associated with increased risk of atrophic gastritis, gastric polyps or ulcers, or Helicobacter pylori infection, with the exception of hypergastrinemia. Additionally, HBV co-infection did not exert a synergistic effect on increasing the risk of atrophic gastritis in patients with Helicobacter pylori. Collectively, these findings suggest that the mechanism underlying the increased risk of gastric cancer in individuals with HBV may not be predominantly mediated via Helicobacter pylori infection and atrophic gastritis. Theories regarding HBV-induced genotoxicity or confounding effects warrant further investigation. Full article

Background and Clinical Significance: Pediatric autoimmune gastritis (AIG) is a rare and frequently underdiagnosed disorder characterized by chronic immune-mediated inflammation and atrophy of the gastric mucosa. In children, AIG typically presents with iron-deficiency anemia (IDA) refractory to oral iron supplementation, in contrast to the pernicious anemia more commonly observed in adults. Diagnosis relies on a combination of serological markers, such as anti-parietal cell antibodies, and histopathological confirmation, with gastric biopsies demonstrating oxyntic mucosal atrophy and lymphocytic infiltration. Early recognition is essential, particularly in patients with personal or familial autoimmune backgrounds, to prevent long-term complications including nutritional deficiencies and increased gastric neoplasia risk. Case Presentation: An 11-year-old boy was referred for evaluation of severe microcytic anemia. He was clinically asymptomatic, with normal growth and physical examination except for mucocutaneous pallor. Celiac disease, thyroid dysfunction, hemoglobinopathies, and infectious or inflammatory gastrointestinal causes were excluded. Despite six months of high-dose oral iron therapy, anemia persisted. Upper gastrointestinal endoscopy showed macroscopically normal mucosa; however, histopathological analysis of gastric body biopsies revealed chronic atrophic gastritis. Serological testing confirmed autoimmune etiology, with positive anti-parietal cell antibodies and hypergastrinemia. Since diagnosis, the patient has required two courses of intravenous iron supplementation, and remains under close follow-up for associated autoimmune and hematologic conditions. Conclusions: Refractory IDA may represent the sole clinical manifestation of AIG in pediatric patients, even in the absence of gastrointestinal symptoms. Histological assessment is crucial, as endoscopic findings may be normal. Early diagnostic suspicion allows timely management focused on correction of nutritional deficiencies and long-term surveillance to mitigate neoplastic risk. AIG should therefore be considered in children with anemia unresponsive to conventional iron therapy. Full article

Chronic atrophic gastritis (CAG) is a key precursor in the Correa cascade leading to gastric cancer and is driven by long-standing Helicobacter pylori infection, autoimmune reactions, environmental exposures, and persistent inflammation. Emerging evidence indicates that mild to moderate atrophy and part of intestinal metaplasia exhibit a degree of reversibility when etiological eradication, microenvironmental optimization, and regenerative stimulation are achieved. This review summarizes recent advances in the pathological basis, evaluation systems, therapeutic mechanisms, and clinical management strategies of CAG. Reversibility is closely related to residual glandular reserve, stem-cell plasticity, and effective mitigation of chronic inflammation. Current assessment tools integrate OLGA/OLGIM histological staging, high-quality endoscopy with AI assistance, and serological biomarkers. Fundamental interventions include early H. pylori eradication, mucosal protective agents, micronutrients, and small-molecule drugs targeting inflammation, oxidative stress, and epithelial regeneration. Novel strategies such as mesenchymal stem cells, exosomes, and focal endoscopic therapies demonstrate regenerative potential in preclinical studies. Traditional Chinese medicine provides multi-target regulation of inflammation, apoptosis, microecology, and stem-cell-related pathways, contributing to histological improvement. Contemporary guidelines emphasize early eradication, risk-stratified surveillance, and comprehensive intervention. Future directions focus on unified evaluation criteria, long-term prospective studies, multimodal combination regimens, and integration of AI-based risk modeling to achieve precise, cancer-preventive CAG management. Full article

Background/Objectives: Type 1 gastric neuroendocrine tumors (gNET) arise in the setting of autoimmune chronic atrophic gastritis and secondary hypergastrinemia. Vitamin D deficiency (VDD) has been associated with bone impairment and adverse outcomes in patients with neuroendocrine tumor (NET); however, data specifically addressing gNET remain limited. This study aimed to evaluate vitamin D status, supplementation requirements, and bone involvement in patients with type 1 gNET compared with those with entero-pancreatic NET (EP-NET). Methods: This retrospective study included patients with type 1 gNET followed at a tertiary referral center between 2010 and 2025 and an age- and sex-matched EP-NET cohort. VDD prevalence, time and dose required for normalization, supplementation formulations, bone status, and dietary habits were analyzed. Results: Twenty-six patients were included (thirteen gNET and thirteen EP-NET). VDD was significantly more prevalent in the gNET group compared with the EP-NET group (92.3% vs. 46.2%, p = 0.03, OR: 14). gNET required significantly higher daily cholecalciferol doses (3198.9 ± 1629 vs. 1580 ± 1121 IU/day, p = 0.008) and more frequently required multiple supplementation formulations (38.5% vs. 0%, p = 0.04). Multivariable linear regression analysis restricted to VDD patients confirmed that gNET was independently associated with higher daily cholecalciferol dose requirements (p = 0.037). Bone impairment, defined as osteoporosis or osteopenia, was significantly more common in the gNET group (61.5% vs. 15.4%, p = 0.04, OR: 8.8). Dietary adherence did not differ between groups. Conclusions: Type 1 gNET show a higher burden of VDD, increased vitamin D supplementation requirements, and a higher prevalence of bone impairment compared with EP-NET, irrespective of dietary habits. These findings suggest disease-specific mechanisms and support the need for tailored management in these patients. Full article

Chronic atrophic gastritis (CAG) is a precancerous gastric condition with limited therapeutic interventions, and the mechanisms underlying the benefits of Coptis chinensis Franch. (CCF) remain insufficiently defined. This study employed an integrated computational strategy to clarify the molecular basis of CCF activity against CAG. Network pharmacology was used to identify potential targets of the major CCF constituents berberine, coptisine, and palmatine, followed by molecular docking, machine learning-based IC₅₀ prediction, and molecular dynamics simulations. Fifty-eight overlapping targets between CCF compounds and CAG-related genes were identified, highlighting SRC, STAT3, MAPK1, and NFKB1 as central nodes enriched in inflammatory and immune pathways, including TNF and MAPK signaling. Docking analyses revealed strong interactions between all three compounds and SRC kinase, and machine learning models predicted IC₅₀ values in the low micromolar range (1.38–1.82 μM). Molecular dynamics simulations further suggest that berberine may stabilize the crucial regulatory regions of SRC, specifically the activation loop. It is hypothesized that this stabilization maintains the inactive conformation of the kinase domain and potentially shields Tyr416 from phosphorylation, thus potentially influencing kinase activation. These findings suggest that CCF may modulate key inflammatory and immune pathways implicated in CAG progression, with SRC emerging as a central node for further investigation. Full article

Background/Objectives: Helicobacter pylori (H. pylori) is a well-established pathogen associated with chronic gastritis and gastric malignancies. Recent studies suggest that members of the Streptococcus anginosus group (SAG), particularly S. anginosus and S. constellatus, may also contribute to gastric mucosal damage, especially when co-infecting with H. pylori. This study aimed to evaluate the prevalence of these three bacterial species and their associations with gastric lesions in Vietnamese patients. Methods: A cross-sectional study was conducted on 200 adult patients with gastritis diagnosed by endoscopy and biopsy. PCR analysed gastric tissue samples from the antrum and corpus for H. pylori, S. anginosus, and S. constellatus. Gastric lesions were classified histologically, and associations with bacterial infections were assessed using odds ratios (OR) and 95% confidence intervals. Results: Infection rates were 62.5% for H. pylori, 62% for S. constellatus, and 48.5% for S. anginosus. Coinfections were frequent, with 25% of patients infected by all three bacteria. Atrophic gastritis was the most common lesion (80%) and was significantly associated with all three bacteria, particularly H. pylori (OR = 7.7), and in co-infections (e.g., H. pylori + S. constellatus, OR = 7.4, p < 0.0001). Triple infection was strongly linked to both atrophy (OR = 5.1) and intestinal metaplasia/dysplasia (OR = 3.4, p = 0.007). Conclusions: Polymicrobial infections involving H. pylori and SAG bacteria are common in Vietnamese patients with gastritis and are significantly associated with more severe gastric lesions. These findings highlight the need for broader microbial screening and integrated management strategies to improve gastritis treatment and gastric cancer prevention in high-prevalence settings. Full article

Background/Objectives: Autoimmune metaplastic atrophic gastritis (AMAG) is a chronic, autoimmune-mediated condition associated with increased risk of malignancy and nutritional deficiencies, yet diagnostic and follow-up processes remain inconsistent and unclear. This study investigates follow-up testing performance in patients with AMAG and neuroendocrine tumors (NET), as well as the correlation between endoscopic impressions and histologic findings. Methods: We retrospectively analyzed 65 gastric biopsies with final diagnoses or comments mentioning the possibility of AMAG, 12 of which included well-differentiated WHO grade 1 NET arising in AMAG. H&E slides were reviewed to assess atrophy severity, the presence or absence of enterochromaffin-like (ECL) cell hyperplasia, and Helicobacter organisms. The final diagnostic line or comments made were scored from 1 to 5, based on the strength of the language used to alert the treating clinician to the likelihood of AMAG. Corresponding endoscopy reports were scored from 1 to 5 based on the likelihood of the reports documenting AMAG features. Data regarding follow-up laboratory testing relevant to AMAG and biopsy performance were collected from the electronic medical records. Results: Endoscopy scores showed no significant associations with the histology comment score or atrophy grade. The histology comment score was positively associated with performing at least a total of three laboratory tests (p = 0.03). No association was found between the presence or absence of follow-up biopsy and histology comment score (p = 0.60). Follow-up biopsy was more common in patients with NET than those with AMAG without NET (p < 0.001). Conclusions: Poor endoscopic–histologic correlation with variable follow-up practices highlights the need for standardized protocols in AMAG management. Enhanced adherence to biopsy guidelines, standardized pathology reporting, and consistent surveillance, particularly for patients with AMAG without NET, are imperative to improve diagnosis and outcomes. Future research should focus on optimizing endoscopic techniques, standardizing serological tests, and establishing evidence-based surveillance protocols for AMAG patients. Full article

Chronic gastritis (CG) is a prevalent digestive disorder. It progresses through multiple stages, has an insidious onset, and can lead to severe complications if untreated. Modern treatments primarily aim to eradicate Helicobacter pylori and relieve symptoms. However, drug resistance and adverse effects often limit their effectiveness. As a primary traditional Chinese medicine (TCM) therapy, acupuncture treats CG through multi-target mechanisms. This review systematically outlines the classification and pathology of CG. It also comprehensively analyzes animal and clinical studies on acupuncture for CG from the past decade. The study summarizes the mechanisms of acupuncture and related therapies for CG, covering gastric mucosal function, metabolism, intestinal flora, gastrointestinal hormones, apoptosis, inflammation, and oxidative stress. It further explores the relationships among diseases, interventions, acupoints, and molecular pathways. Additionally, it compares the therapeutic profiles of different external therapies. The review also examines the current state of clinical research, including the selection of acupoints, treatment duration, and outcome assessment. The results demonstrate that external therapies effectively alleviate common CG symptoms such as abdominal distension, acid reflux, and stomach pain. These treatments also improve gastric mucosal health and modulate serum levels of inflammatory factors, oxidative stress markers, and gastrointestinal hormones. In vivo experiments using chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG) models confirm these benefits, showing changes in key biomarkers and elucidating potential mechanisms. Nevertheless, future high-quality, large-sample clinical trials are still needed to firmly establish efficacy. Further mechanistic studies are also needed to validate the interconnections among relevant signaling pathways. Full article

The risk of Helicobacter pylori (H. pylori)-related gastric tumorigenesis is closely associated with the degree of chronic gastritis, although other gastric mucosa microbes may be relevant in this process. The morphological identification of the gastric mucosa associated with the cancer-promoting microbiome may have important implications for gastric cancer prevention. This study characterized gastric mucosa microbiome communities in relation to their mucosal morphologies. A total of 94 biopsies from non-neoplastic gastric bodies underwent 16S rRNA sequencing. Microbiome structures were characterized in relation to their mucosal morphologies, which were obtained using narrow-band imaging with magnifying endoscopy. H. pylori infection- and inflammatory mucosa-associated gastric mucosal morphologies exhibited decreased bacterial alpha diversity measures and an increase in the abundance of the Helicobacter genus, while the mucosal morphology associated with severely atrophic mucosa exhibited increased bacterial alpha diversity measures and a decrease in the abundance of the Helicobacter genus. This type of mucosal morphology was also associated with increased levels of well-known gastric cancer-related bacteria, e.g., Streptococcus. The microbial dysbiosis associated with gastric mucosa morphology also correlated well with the occurrence of gastric cancer and the DNA methylation status. Our results suggest that gastric microbiome communities correlate well with their premalignant condition-associated mucosal morphologies. Full article

Chronic infection with Helicobacter pylori is the leading environmental cause of gastric carcinogenesis, yet the molecular pathways remain incompletely defined. This review links H. pylori-derived outer membrane vesicles (OMVs) and host epithelial exosomes through their shared cargo of heat shock protein 60 (GroEL/Hsp60). We proposed the concept of the “muco-microbiotic layer” as a fifth, functionally distinct layer of the gastric wall, where bacterial and host extracellular vesicles (EVs) interact within the mucus–microbiota interface. In this compartment, OMVs carrying bacterial GroEL and exosomes containing human Hsp60 engage in bidirectional communication that may promote chronic inflammation and epithelial transformation, with putative participation of molecular mimicry. The high structural homology between microbial and human Hsp60 enables repeated immune exposure to trigger cross-reactive responses—potentially leading to autoimmune-driven tissue damage, immune tolerance, and immune evasion in pre-neoplastic lesions. This vesicular crosstalk aligns with the evolution from non-atrophic gastritis to atrophy, from intestinal metaplasia to dysplasia, and lastly adenocarcinoma. Therapeutically, targeting EV-mediated Hsp60/GroEL signaling might offer promising strategies: EV-based biomarkers for early detection, monoclonal antibodies against extracellular Hsp60/GroEL, modulation of vesicle release, and probiotic-derived nanovesicles to restore mucosal balance. Hence, recognizing the muco-microbiotic layer and its vesicle-mediated signaling provides a new framework for understanding the infection–inflammation–cancer axis and for developing diagnostic and therapeutic approaches in H. pylori-associated gastric cancer. Full article

Background/Objectives: Age-related changes in the gastric mucosa remain incompletely understood. We aimed to assess and compare clinical, endoscopic and histologic changes in the gastric mucosa associated with aging, and to explore whether gastric aging is associated with a distinct histological pattern. Methods: Single-center observational study. Younger (18–45 years) and older (≥70 years) adults undergoing elective upper endoscopy were included and underwent gastric biopsies. The clinical, endoscopic and histologic features were analyzed and compared. Results: A total of 100 patients were included (45 men/55 women), 50 with 18–45 years and 50 with ≥70 years. Dyspepsia, gastro-esophageal reflux disease and peptic ulcer disease were the most common indications for upper endoscopy. Gastric lesions (erythema, erosions, ulceration and polyps) were more common in older patients (80% vs. 50%, p = 0.003), as well as histologic changes such as chronic gastritis (56% vs. 38%, p = 0.004), chronic atrophic gastritis (CAG; 28% vs. 4%, p < 0.001) and intestinal metaplasia (28% vs. 4%, p < 0.001). These findings persisted after adjusting for Helicobacter pylori (H. pylori) status and proton pump inhibitor intake on the multivariate analysis. Prevalence of H. pylori was similar between both groups (28% vs. 32%, p = 0.189). Conclusions: Aging is associated with clinical, endoscopic and histologic changes in the gastric mucosa including CAG and metaplasia, independent of the presence of H. pylori. These findings may result from several aging-related pathophysiological processes and decades of cumulative gastric injury and support the hypothesis of an aging stomach phenotype, underscoring the need for an age-adjusted interpretation of gastric biopsies. Full article

Helicobacter pylori (H. pylori) infection and autoimmune inflammation of the gastric mucosa are recognized as the leading etiological factors of chronic atrophic gastritis. The mechanisms of atrophy formation and progression with the risk of gastric cancer development are heterogeneous, which requires a deeper study of the molecular mechanisms of relationship, peculiarities of the course of autoimmune gastritis both in combination with H. pylori and after eradication, as well as without H. pylori infection (naïve AIG). This article presents the specific molecular and cellular patterns in the formation of these related conditions. Full article