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Simple Summary: Gastric cancer (GC) is a major cause of mortality worldwide. It is preceded by the progressive development of lesions of the gastric mucosa, namely atrophic gastritis, intestinal metaplasia, and dysplasia, collectively referred to preneoplasia. Periodic monitoring has been proposed for the surveillance of intestinal metaplasia and dysplasia. However, endoscopy, the current gold standard in GC diagnosis, has a limited ability to detect gastric preneoplasia, especially in early stages. In order to overcome the limitations of endoscopy screening, the potential of blood biomarkers has been investigated, and some biomarkers have been identified consistently across different studies. Nevertheless, validation studies in specific populations must be conducted before these results can allow the design of non-invasive tests to be translated into clinical practice for the early detection of patients at risk of developing GC. Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence of gastric preneoplasia lesions (GPNLs), namely atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS). GC is currently diagnosed by endoscopy, which is invasive and costly and has limited effectiveness for the detection of GPNLs. Therefore, the discovery of non-invasive biomarkers in liquid biopsies, such as blood samples, in order to identify the presence of gastric preneoplasia and/or cancer lesions at asymptomatic stages is of paramount interest. This comprehensive review provides an overview of recently identified plasma/serum proteins and their diagnostic performance for the prediction of GPNLs and early cancer lesions. Autoantibodies appear to be promising biomarkers for AG, IM and early gastric cancer detection, along with inflammation and immunity-related proteins and antibodies against H. pylori virulence factors. There is a lack of specific protein biomarkers with which to detect DYS. Despite the need for further investigation and validation, some emerging candidates could pave the way for the development of reliable, non-invasive diagnostic tests for the detection and prevention of GC. [ABSTRACT FROM AUTHOR]

Parietal cell autoantibodies (PCAs), which recognize the enzyme H+/K+-ATPase as a target, are considered to be a diagnostic marker of autoimmune gastritis and pernicious anemia; these conditions are characterized by the presence of corpus atrophic gastritis. Circulating PCAs can be detected using several analytical methods that are commonly available in the clinical laboratory. Traditionally, indirect immunofluorescence (IIF) on rodent or primate stomach tissue is used as a screening test for the detection of PCAs. However, IIF suffers from a high inter-observer variability and lacks standardization. In addition, like immunoblotting, results are expressed only in a qualitative or semi-quantitative manner. Based on the few available studies that are reviewed herein, quantitative enzyme-linked immunosorbent assays (ELISAs) and fluorescence enzyme immunoassays (FEIAs) using purified H+/K+-ATPase perform better than IIF in the detection of PCAs, displaying higher sensitivity and utility in monitoring the disease. In light of their higher diagnostic accuracy, these solid-phase methods should be preferred to IIF in the screening of autoimmune atrophic gastritis. The use of methods to detect antibodies versus a specific subunit of H+/K+-ATPase (α or β) is currently confined to the world of research. Further investigation is required to define the clinical utility of H+/K+-ATPase subunit detection. [ABSTRACT FROM AUTHOR]

Featured Application: The methodology and findings can be used as a basis for further research into other predictive models for various diseases, contributing to the advancement of predictive analytics in healthcare. Chronic atrophic gastritis is a serious health issue beyond the stomach health problems that affect normal life. This study aimed to explore the influencing factors related to chronic atrophic gastritis (CAG) using non-invasive indicators and establish an optimal prediction model to aid in the clinical diagnosis of CAG. Electronic medical record data from 20,615 patients with CAG were analyzed, including routine blood tests, liver function tests, and coagulation tests. The logistic regression algorithm revealed that age, hematocrit, and platelet distribution width were significant influences suggesting chronic atrophic gastritis in the Chongqing population (p < 0.05), with an area under the curve (AUC) of 0.879. The predictive model constructed based on the Random Forest algorithm exhibited an accuracy of 83.15%, precision of 97.38%, recall of 77.36%, and an F1-score of 70.86%, outperforming the models constructed using XGBoost, KNN, and SVC algorithms in a comprehensive comparison. The prediction model derived from this study serves as a valuable tool for future studies and can aid in the prediction and screening of chronic atrophic gastritis. [ABSTRACT FROM AUTHOR]

The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided into five groups: Helicobacter pylori (H. pylori)-associated gastritis with gastric intestinal metaplasia (GIM) (n = 12), chronic atrophic gastritis (CAG) with GIM (n = 13), H. pylori-associated gastritis without GIM (n = 19), GC (n = 6) and controls (n = 5). TRPV1 expression was determined with immunohistochemistry and was significantly higher in patients with H. pylori-associated gastritis compared with controls (p = 0.002). TRPV1 expression was even higher in the presence of GIM compared with patients without GIM and controls (p < 0.001). There was a complete loss of TRPV1 expression in patients with GC. TRPV1 expression seems to contribute to gastric-mucosal inflammation and precursors of GC, which significantly increases in cancer precursor lesions but is completely lost in GC. These findings suggest TRPV1 expression to be a potential marker for precancerous conditions and a target for individualized treatment. Longitudinal studies are necessary to further address the role of TRPV1 in gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Gastric cancer remains a disease with an ominous prognosis, while early gastric cancer has a good-to-excellent prognosis, with 5-year survival rates of up to 92.6% after successful endoscopic resection. In this context, the accurate identification of patients with established gastric precancerous lesions, namely chronic atrophic gastritis and intestinal metaplasia, is the first step in a stepwise approach to minimize cancer risk. Although current guidelines advocate for the execution of random biopsies to stage the extent and severity of gastritis/intestinal metaplasia, modern biopsy protocols are still imperfect as they have limited reproducibility and are susceptible to sampling error. The advent of novel imaging-enhancing modalities, i.e., high-definition with virtual chromoendoscopy (CE), has revolutionized the inspection of gastric mucosa, leading to an endoscopy-based staging strategy for the management of these premalignant changes in the stomach. Nowadays, the incorporation of CE-targeted biopsies in everyday clinical practice offers not only the robust detection of premalignant lesions but also an improvement in quality, by reducing missed diagnoses along with mean biopsies and, thus, the procedural costs and the environmental footprint. In this review, we summarize the recent evidence regarding the endoscopic grading and sampling of gastric precancerous lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals with atrophic gastritis and gastric intestinal metaplasia, considered gastric precancerous conditions (GPC), are at increased risk of developing gastric adenocarcinoma. The identification and surveillance of these patients are important for the diagnosis of early gastric neoplasia. Non-invasive markers of GPC with good diagnostic performance could allow the implementation of a stepwise screening approach and, with successful personalized endoscopic surveillance, possibly decrease gastric cancer morbidity and mortality. Pepsinogen I and II and their ratio are the most broadly investigated biomarkers with moderate diagnostic performance. Their combination with other markers like Helicobacter pylori antibodies and gastrin-17 (called GastroPanel®) allows for more precise identification of GPC but without significant improvement in overall performance. Other new serum biomarkers could possibly enhance the performance of pepsinogens. Some of them may be considered stand-alone biomarkers; however, until now, no high-quality data support the use of any of them. Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, is necessary. In this review article, we present a broad review and the current knowledge status on serum biomarkers, including pepsinogens, gastrin, Gastropanel®, autoantibodies, and novel biomarkers, allowing us to estimate the risk of gastric precancerous conditions (GPC)—atrophic gastritis and gastric intestinal metaplasia. The aim of the article is to emphasize the role of non-invasive testing in GC prevention. This comprehensive review describes the pathophysiological background of investigated biomarkers, their status and performance based on available data, as well as their clinical applicability. We point out future perspectives of non-invasive testing and possible new biomarkers opportunities. [ABSTRACT FROM AUTHOR]

Background: Vonoprazan-based triple therapy has recently been reported as being more effective than proton pump inhibitors for the eradication of Helicobacter pylori (H. pylori), but it is apparent that the eradication rate could be further improved. Methods: We investigated the effect of the concomitant use of polaprezinc, a therapeutic agent for gastric ulcers, and vonoprazan-based seven-day triple therapy in patients with gastric ulcers compared to standard vonoprazan-based seven-day triple therapy in patients with atrophic gastritis. The regimen for the treatment of atrophic gastritis contained vonoprazan 20 mg, amoxicillin 750 mg, and clarithromycin 200 mg b.d. (VAC group) for seven days; and that for gastric ulcers contained VAC and polaprezinc 75 mg b.d. (VACP group) for seven days. Results: Between October 2021 and January 2023, 201 subjects were examined (VAC group, n = 165; VACP group, n = 36). In per-protocol (PP) analysis, the eradication rate was significantly higher in the VACP group (100%) than in the VAC group (88.2%) (p = 0.025). In patients with severe atrophic gastritis, eradication rates were significantly higher in the VACP group (100%) than in the VAC group (84.4%) in PP analysis. (p = 0.024). Conclusions: The concomitant use of polaprezinc and standard vonoprazan-based first-line eradication therapy is effective for H. pylori. [ABSTRACT FROM AUTHOR]

The management of gastric Helicobacter pylori (H. pylori) infection represents a significant concern in primary healthcare. This survey evaluates the approaches, attitudes, and knowledge regarding gastric H. pylori infection among Italian general practitioners (GPs) and young doctors undergoing general practice training (ITGPs). The survey enrolled 466 GPs and 70 ITGPs. Among GPs, specialist recommendations and the Maastricht–Florence guidelines were frequently referenced sources, while ITGPs relied more on the Maastricht–Florence guidelines and internet resources. ITGPs demonstrated more proactive approaches than GPs in investigating and treating conditions such as gastric ulcers, atrophic gastritis, and iron-deficiency anemia. However, there was limited attention given to the role of H. pylori treatment in first-degree relatives of gastric cancer patients. The most used diagnostic methods were the urea breath test and fecal test. Triple therapy was the most frequently chosen initial treatment regimen, with quadruple bismuth therapy becoming the primary option after initial treatment failure, followed by quinolone therapy and concomitant therapy. This survey underscores a disparity between real-world practices and the recommendations outlined in current guidelines, indicating a need for improved understanding of H. pylori guidelines among both GPs and ITGPs. [ABSTRACT FROM AUTHOR]

Simple Summary: Autoimmune atrophic gastritis can lead to serious conditions, including malabsorption and vitamin deficiencies, that may cause anemia, neurological disorders, and gastric malignancies. This paper provides recent evidence on the pathogenesis, diagnosis, clinical presentation, risk of malignancies, endoscopic surveillance, and treatment of autoimmune atrophic gastritis. This review provides a valuable update for healthcare professionals and researchers, and the findings may help improve the diagnosis and management of patients with autoimmune atrophic gastritis, leading to improved outcomes and shaping future research directions. Autoimmune atrophic gastritis (AAG) is a chronic condition characterized by the presence of atrophy in the oxyntic mucosa due to anti-parietal cell antibodies. This review provides a comprehensive and up-to-date overview of autoimmune atrophic gastritis, reporting recent evidence on epidemiology, pathogenesis, diagnosis, clinical presentation, risk of malignancies, and management. The prevalence of AAG has been estimated at between 0.3% and 2.7% in the general population. The diagnosis of AAG is based on a combination of the serologic profile and the histological examination of gastric biopsies. Patients with AAG are often asymptomatic but can also have dyspeptic or reflux symptoms. The atrophy of the oxyntic mucosa leads to iron and vitamin B12 malabsorption, which may result in anemia and neurological affections. Autoimmune atrophic gastritis is associated with an increased risk of type I neuroendocrine tumors (NETs) and gastric cancer, with an incidence rate of 2.8% and 0.5% per person/year, respectively. Management is directed to reinstate vitamins and iron and to prevent malignancies with endoscopic surveillance. In conclusion, atrophic autoimmune gastritis is an infrequent condition, often asymptomatic and misdiagnosed, that requires an early diagnosis for appropriate vitamin supplementation and endoscopic follow-up for the early diagnosis of NETs and gastric cancer. [ABSTRACT FROM AUTHOR]

Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts—both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG. [ABSTRACT FROM AUTHOR]

Among the vinca-alkaloid class, vincristine is a potent chemotherapeutic agent with significant neurotoxic effects and is employed to address a wide spectrum of cancer types. Recently, the therapeutic potential of the cholecystokinin type 2 receptor (CCK2R) as a target for vincristine-induced peripheral neuropathy (VIPN) was demonstrated. In this study, the impact of preventive CCK2R blockade using netazepide (Trio Medicines Ltd., London, UK) was investigated in a mouse model of vincristine-induced peripheral neuropathy. Netazepide is a highly selective CCK2R antagonist under development for the treatment of patients with gastric neuroendocrine tumors caused by hypergastrinemia secondary to chronic autoimmune atrophic gastritis. Vincristine-induced peripheral neuropathy was induced by intraperitoneal injections of vincristine at 100 µg/kg/d for 7 days (D0 to D7). Netazepide (2 mg/kg/d or 5 mg/kg/d, per os) was administered one day before vincristine treatment until D7. Vincristine induced a high tactile allodynia from D1 to D7. VIPN was characterized by dorsal root ganglion neuron (DRG) and intraepidermal nerve fiber (IENF) loss, and enlargement and loss of myelinated axons in the sciatic nerve. Netazepide completely prevented the painful symptoms and nerve injuries induced by vincristine. In conclusion, the fact that netazepide protected against vincristine-induced peripheral neuropathy in a mouse model strongly supports the assessment of its therapeutic potential in patients receiving such chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer is one of the most prevalent and deadliest neoplasms worldwide. Although significant advances have been made in recent decades to improve its treatment, an incomplete understanding of its etiology and pathogenesis still limits our ability to effectively prevent and treat gastric cancer. It is well established that the most common subtype of gastric cancer (intestinal gastric cancer) develops through a multi-step process, wherein pathologic changes in gastric cells progressively occur, ultimately leading to the development of tumors. Recent evidence suggests that, aside from environmental factors, the immune system plays a key role in the sequela from gastritis to metaplasia, dysplasia and finally, gastric cancer, primarily through type 2 immune responses. In this review, we summarize the current literature and provide an overall interpretation regarding the impact of T helper 2 (Th2) immunity on the development and progression of gastric cancer. Gastric cancer is one of the leading causes of cancer deaths worldwide, with chronic gastritis representing the main predisposing factor initiating the cascade of events leading to metaplasia and eventually progressing to cancer. A widely accepted classification distinguishes between autoimmune and environmental atrophic gastritis, mediated, respectively, by T cells promoting the destruction of the oxyntic mucosa, and chronic H. pylori infection, which has also been identified as the major risk factor for gastric cancer. The original dogma posits Th1 immunity as a main causal factor for developing gastritis and metaplasia. Recently, however, it has become evident that Th2 immune responses play a major role in the events causing chronic inflammation leading to tumorigenesis, and in this context, many different cell types and cytokines are involved. In particular, the activity of cytokines, such as IL-33 and IL-13, and cell types, such as mast cells, M2 macrophages and eosinophils, are intertwined in the process, promoting chronic gastritis-dependent and more diffuse metaplasia. Herein, we provide an overview of the critical events driving the pathology of this disease, focusing on the most recent findings regarding the importance of Th2 immunity in gastritis and gastric metaplasia. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is responsible for causing chronic gastritis, which can cause peptic ulcer and premalignant lesions such as atrophic gastritis, intestinal metaplasia, and dysplasia, with the risk of developing gastric cancer. Recent data describe that H. pylori colonizes the gastric mucosa of more than 50% of the world's population; however, this bacterium has been described as infecting the human population since its prehistory. This review focuses on the populations and subpopulations of H. pylori, differentiated by the polymorphisms present in their constitutive and virulence genes. These genes have spread and associated with different human populations, showing variability depending on their geographical distribution, and have evolved together with the human being. The predominant genotypes worldwide, Latin America and Chile, are described to understand the genetic diversity and pathogenicity of H. pylori in different populations and geographic regions. The high similarity in the sequence of virulence genes between H. pylori strains present in Peruvian and Spanish natives in Latin America suggests a European influence. The presence of cagA-positive strains and vacA s1 m1 allelic variants is observed with greater prevalence in Chilean patients with more severe gastrointestinal diseases and is associated with its geographical distribution. These findings highlight the importance of understanding the genetic diversity of H. pylori in different regions of the world for a more accurate assessment of the risk of associated diseases and their potential impact on health. [ABSTRACT FROM AUTHOR]

Endoscopy is the gold standard for the diagnosis of cancers and cancer precursors in the oesophagus and stomach. Early detection of upper GI cancers requires high-quality endoscopy and awareness of the subtle features these lesions carry. Endoscopists performing surveillance of high-risk patients including those with Barrett's oesophagus, previous squamous neoplasia or chronic atrophic gastritis should be familiar with endoscopic features, classification systems and sampling techniques to maximise the detection of early cancer. In this article, we review the current approach to diagnosis of these conditions and the latest advanced imaging and diagnostic techniques. [ABSTRACT FROM AUTHOR]

Cytotoxin-associated gene A (CagA) is an oncoprotein that H. pylori injects into the host's gastric epithelial cells and that induces proinflammatory cytokines, such as interleukin (IL)-18 and IL-1β. As a result, it leads to atrophic gastritis (AG), a precancerous lesion of gastric cancer. On the other hand, host cells degrade CagA using autophagy systems. However, few studies exist about the single nucleotide polymorphisms (SNPs) in MAP1LC3A, MAP1LC3B, ATG4A, ATG4B, ATG4C, ATG7, and ATG13, which belong to the autophagy-related genes concerning AG. This study aimed to detect biomarkers associated with AG. Herein, H. pylori-positive subjects (n = 200) were divided into the AG (n = 94) and non-AG (n = 106) groups. Thirty tag SNPs were selected from the above seven candidate genes. The SNP frequency between the two groups was analyzed. The frequency of the C/T or T/T genotype at rs4683787 of ATG7 was significantly lower in the AG group than in the non-AG group (p = 0.034, odds ratio = 0.535). Based on multivariate analysis, the C/C genotype of rs4684787 and age were independently associated with gastric mucosal atrophy. This finding helps stratify the patients needing timely endoscopic screening or early eradication of H. pylori. [ABSTRACT FROM AUTHOR]

Background: gastritis is a common stomach disease with a high global incidence and can potentially develop into gastric cancer. The treatment of gastritis focuses on medication or diets based on national guidelines. However, the specific diet that can alleviate gastritis remains largely unknown. Methods: we propose a microbiota-directed dietary strategy that investigates potential food factors using microbial exogenous metabolites. Given the current lack of understanding of the repeatable characteristics of gastric microbiota, we conducted a meta-analysis to identify the features of gastric bacteria. Local samples were collected as validation cohorts. Furthermore, RevEcoR was employed to identify bacteria's exogenous metabolites, and FooDB was used to retrieve foods that can target specific bacteria. Results: Bacteroides, Weissella, Actinomyces, Atopobium, Oribacterium, Peptostreptococcus, and Rothia were biomarkers between superficial gastritis (SG) and atrophic gastritis (AG) (AG_N) without H. pylori infection, whereas Bacillus, Actinomyces, Cutibacterium, Helicobacter, Novosphingobium, Pseudomonas, and Streptococcus were signatures between SG and AG (AG_P) with H. pylori infection. According to the exogenous metabolites, adenosyloobalamin, soybean, common wheat, dates, and barley were regarded as potential candidates for AG_N treatment, while gallate was regarded as a candidate for AG_P treatment. Conclusions: this study firstly profiled the gastric microbiota of AG and SG with or without H. pylori and provided a recommended diet for global AG according to exogenous metabolites. [ABSTRACT FROM AUTHOR]

Corpus Atrophic Gastritis (CAG) is characterised by iron malabsorption leading to iron deficiency anaemia (IDA), which rarely responds to oral therapy. Ferric carboxymaltose (FCM), shown to be a safe and effective intravenous iron therapy in other diseases, has not been investigated yet in CAG. Thus, we aimed to assess the safety and efficacy of FCM in CAG-related IDA. A retrospective study on 91 patients identified CAG as the only cause of IDA treated with FCM. Twenty-three were excluded for incomplete follow-up. Sixty-eight were evaluated for safety and efficacy, while three were evaluated for safety only due to infusion interruption for side effects. Haemoglobin and iron storage were evaluated pre-infusion (T0), at 4 weeks (T4) and 12 weeks (T12) after infusion. An eventual IDA relapse was analysed. Two cases reported mild side effects. Haemoglobin significantly increased at T4, and T12, reaching +3.1 g/dL. Ferritin increased at T4, decreasing at T12, while transferrin saturation increased progressively until reaching a plateau. IDA relapsed in 55.4% of patients at a mean of 24.6 months. The only factor associated with relapse was female gender [OR (95% CI): 6.6 (1.5–28.6)]. FCM proved to be safe and effective in treating CAG-related IDA, ensuring quick and long-lasting recovery. [ABSTRACT FROM AUTHOR]

Background and Objectives: Gastric neuroendocrine neoplasms (gNENs) represent rare but increasingly recognized tumors. They are distinguished into three main clinical types (type-1, type-2, and type-3) according to gastrin level and at histological evaluation in well-differentiated G1, G2, or G3 lesions, as well as poorly-differentiated lesions. Small type-1 and type-2 neoplasms with low proliferation indices demonstrated excellent survival without progression during an extended follow-up period, and for these reasons, active endoscopic observation or endoscopic resection are feasible options. On the other hand, surgery is the treatment of choice for more aggressive type-3, G3, or infiltrating neoplasms. The present study aims to comprehensively review and compare the available therapeutic strategies for gNENs. Materials and Methods: A computerized literature search was performed using relevant keywords to identify all of the pertinent articles with particular attention to gNEN endoscopic treatment. Results: In recent years, different endoscopic resective techniques (such as endoscopic mucosal dissection, modified endoscopic mucosal resection, and endoscopic full-thickness resection) have been developed, showing a high rate of complete resection for advanced and more aggressive lesions. Conclusions: Overall, gNENs represent a heterogeneous group of lesions with varying behavior which require personalized management. The non-operative approach for small type-1 gNENs seems to be feasible and should be promoted. A step-up approach with minimally invasive endoscopic therapies might be proposed, particularly for type-1 gNEN. On the other hand, it is important to recognize the negative prognostic factors in order to identify those rare cases requiring more aggressive approaches. A possible therapeutic algorithm for localized gNEN management is provided. [ABSTRACT FROM AUTHOR]

There is a generally recognized need for a morphological assessment of the individual risk of developing gastric cancer in a patient with chronic gastritis, according to the OLGA system (Operative Link for Gastritis Assessment). At the same time, the role of assessing the biopsy from the incisura angularis remains controversial. The aim of our study was to assess the value of incisura angularis biopsy in staging gastritis according to the OLGA system by examining the atrophic and inflammatory changes in the antrum, incisura angularis, and body. Materials and Methods: A total of 718 patients (576 women and 142 men) aged 20 to 84 years were examined. Most of the patients were in the age group of 50 to 70 years (54.6%). Depending on the detection of H. pylori and autoimmune gastritis markers, all patients were divided into three groups. The first group included 380 patients with H. pylori gastritis without signs of autoimmune gastritis. The second group consisted of 209 patients with autoimmune gastritis, in whom no infection was detected during the examination, and there were no indications of H. pylori eradication. The third group consisted of 129 patients with chronic gastritis of combined etiology (autoimmune and H. pylori). Endoscopy biopsies were taken according to the updated Sydney System. Histological assessments of the grade and the stage of gastritis were carried out according to the standard OLGA-based protocol. Then, the same assessments were evaluated without taking into account histological changes in the incisura angularis. Results: When assessing the severity of inflammatory changes in the gastric mucosa according to the OLGA system, grade II (72.3%) was most often detected in all groups of patients. A severe degree of activity of chronic gastritis was most often observed in the group of patients with H. pylori gastritis (6.1%). These indicators practically did not change if the assessment did not take the angulus biopsy into account. When assessing the severity of atrophy of the glands in the gastric mucosa in patients of the first group, mild stages of atrophy prevailed. Without taking into account the angulus biopsy, a decrease in the stage of atrophy was observed in 27 cases (7.11%), and in only 4 cases did stage IV change to stage III, while in 23 cases, discrepancies were noted only within groups with a mild stage of atrophy. There were no transitions from stage III to stage II. In the group of patients with autoimmune gastritis, pronounced stages of atrophy prevailed—in more than 77%. Without taking into account the angulus biopsy, a decrease in the stage of atrophy was observed in eight cases (3.83%), and in three (1.4%) patients, stage III was changed to stage II. In the group of patients with combined etiology (autoimmune + H. pylori), severe stages of atrophy also prevailed (70.5%). A decrease in the stage of atrophy without taking into account the angulus biopsy was only observed in three patients (2.32%), of which two cases concerned patients with mild stages of atrophy. Thus, in general, severe stages of atrophy of the gastric mucosa (stages III and IV according to the OLGA staging system) were detected in 313 patients (43.59%). If the assessment of the atrophy stage did not take into account changes in the angulus biopsy, then severe stages of atrophy (III and IV according to OLGA) were detected in 310 patients (43.17%). In total, changes in the assessment of the atrophy stage occurred in 38 patients (5.29%), and this was more often observed in patients with stages I and II of atrophy. Conclusions: Accounting for histological changes in the incisura angularis does not significantly affect the assessment of the grade and stage of chronic gastritis according to the OLGA system, regardless of the etiology of atrophic gastritis. [ABSTRACT FROM AUTHOR]

CAG is a burdensome and progressive disease. Numerous studies have shown the effectiveness of RUT in digestive system diseases. The therapeutic effects of RUT on MNNG-induced CAG and the potential mechanisms were probed. MNNG administration was employed to establish a CAG model. The HE and ELISA methods were applied to detect the treatment effects. WB, qRT-PCR, immunohistochemistry, TUNEL, and GES-1 cell flow cytometry approaches were employed to probe the mechanisms. The CAG model was successfully established. The ELISA and HE staining data showed that the RUT treatment effects on CAG rats were reflected by the amelioration of histological damage. The qRT-PCR and WB analyses indicated that the protective effect of RUT is related to the upregulation of the SHH pathway and downregulation of the downstream of apoptosis to improve gastric cellular survival. Our data suggest that RUT induces a gastroprotective effect by upregulating the SHH signaling pathway and stimulating anti-apoptosis downstream. [ABSTRACT FROM AUTHOR]

Chronic inflammation is linked to carcinogenesis, particularly in the digestive organs, i.e., the stomach, colon, and liver. The mechanism of this effect has, however, only partly been focused on. In this review, we focus on different forms of chronic hepatitis, chronic inflammatory bowel disease, and chronic gastritis, conditions predisposing individuals to the development of malignancy. Chronic inflammation may cause malignancy because (1) the cause of the chronic inflammation is itself genotoxic, (2) substances released from the inflammatory cells may be genotoxic, (3) the cell death induced by the inflammation induces a compensatory increase in proliferation with an inherent risk of mutation, (4) changes in cell composition due to inflammation may modify function, resulting in hormonal disturbances affecting cellular proliferation. The present review focuses on chronic gastritis (Helicobacter pylori or autoimmune type) since all four mechanisms may be relevant to this condition. Genotoxicity due to the hepatitis B virus is an important factor in hepatocellular cancer and viral infection can similarly be central in the etiology and malignancy of inflammatory bowel diseases. Helicobacter pylori (H. pylori) is the dominating cause of chronic gastritis and has not been shown to be genotoxic, so its carcinogenic effect is most probably due to the induction of atrophic oxyntic gastritis leading to hypergastrinemia. [ABSTRACT FROM AUTHOR]

Background: Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance and is susceptible to inflammation. Objectives: The objective of this study was to clarify whether hepcidin is involved in abnormal iron metabolism and ferroptosis during CAG pathogenesis. Methods: Non-atrophic gastritis (NAG) and chronic atrophic gastritis (CAG) patient pathology slides were collected, and related protein expression was detected by immunohistochemical staining. The CAG rat model was established using MNNG combined with an irregular diet. Results: CAG patients and rats exhibited iron deposition in gastric tissue. CAG-induced ferroptosis in the stomach was characterized by decreased GPX4 and FTH levels and increased 4-HNE levels. Hepcidin, which is mainly located in parietal cells, was elevated in CAG gastric tissue. The high gastric level of hepcidin inhibited iron absorption in the duodenum by decreasing the protein expression of DMT1 and FPN1. In addition, the IL-6/STAT3 signaling pathway induced hepcidin production in gastric tissue. Conclusion: Our results showed that the high level of gastric hepcidin induced ferroptosis in the stomach but also inhibited iron absorption in the intestines. Inhibiting hepcidin might be a new strategy for the prevention of CAG in the future. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On the other hand, gastric epithelial cells degrade CagA using an autophagy system, which is strictly regulated by the autophagy-related (ATG) genes. This study aimed to identify SNPs in ATG5, ATG10, ATG12, and ATG16L1 associated with gastric mucosal atrophy (GMA). Here, two-hundred H. pylori-positive participants without gastric cancer were included. The degree of GMA was evaluated via the pepsinogen method. Twenty-five SNPs located in the four candidate genes were selected as tag SNPs. The frequency of each SNP between the GMA and the non-GMA group was evaluated. The rs6431655, rs6431659, and rs4663136 in ATG16L1 and rs26537 in ATG12 were independently associated with GMA. Of these four SNPs, the G/G genotype of rs6431659 in ATG16L1 has the highest odd ratio (Odds ratio = 3.835, 95% confidence intervals = 1.337–1.005, p = 0.008). Further functional analyses and prospective analyses with a larger sample size are required. [ABSTRACT FROM AUTHOR]

Introduction: Diet is one of the most important factors contributing to the multistep process of carcinogenesis. The clinical relevance of exogenous food-derived xeno-microRNAs (miRNAs) in human diseases is poorly understood. In this study, we aimed to evaluate the potential clinical relevance of the xeno-miRNA miR-168 in the gastric mucosa along the preneoplastic conditions and gastric carcinogenesis. Methods: For a systematic analysis, we included stomach tissues from patients with different pathologies, including normal mucosa (N), chronic non-atrophic (CNAG) and atrophic gastritis (CAG) and intestinal metaplasia (IM) (n = 72), matched non-tumorous (NT) and tumorous (T) gastric cancer (GC) tissues (n = 81), matched colorectal cancer (CRC) tissues (n = 40), and colon mucosa and faeces from controls and IBD patients. Results: miR-168 was reproducibly detectable in all samples studied, with the highest levels in the proximal upper GI and in non-tumorous compared to tumorous tissues in both GC and CRC. There was no difference related to H. pylori positivity or inflammation grade, while higher miR-168 levels were observed in patients with moderate or severe AG/IM or OLGIM3/4. Survival analysis showed only a small, non-significant trend towards worse overall survival for patients with the highest to lowest miR-168 levels, while no differences were related to Lauren's classification. Conclusions: Food-derived xeno miRNAs are reproducibly detectable in the gastric and colonic mucosa. Although the clinically relevant function remains to be elucidated, higher levels of miR-168 in patients with moderate and severe IM merit further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Community-driven projects have characterized health impacts of Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns expressed by community leaders about the frequent diagnosis of Hp infection and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This follow-up study investigated changes in precancerous stomach pathologies after treatment to eliminate Hp infection among 69 project participants with follow-up data. Most participants who had successful treatment to eliminate Hp at baseline remained infection-free at follow-up and the prevalence of precancerous stomach pathologies was lower at follow-up than baseline. The more frequent improvements in precancerous stomach pathologies observed in participants who were Hp-negative at follow-up relative to those who were Hp-positive at follow-up suggests that treatment to eliminate Hp infection has the potential to reduce stomach cancer risk in participating communities. Community-driven projects have characterized Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns about the frequent diagnosis of Hp infection among community members and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Projects included breath-test screening for Hp infection, gastroscopy with gastric biopsies, and treatment to eliminate Hp infection. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This analysis describes changes in precancerous gastric pathologies in project participants who had gastroscopy before baseline treatment during 2008–2013 and again in 2017. Throughout the study period, the same pathologist graded Hp density, active gastritis, chronic gastritis, atrophic gastritis, and intestinal metaplasia using the updated Sydney System. Of 310 participants from three communities with baseline pathology data, 69 had follow-up pathology data. Relative to baseline, the prevalence of Hp infection and precancerous gastric pathology was substantially lower at follow-up; most participants who were Hp-positive at baseline and Hp-negative at follow-up had reduced severity of active, chronic, and/or atrophic gastritis at follow-up. Though follow-up numbers are small, these results yield evidence that successful Hp treatment has the potential to reduce the risk of gastric cancer in Arctic Indigenous communities. [ABSTRACT FROM AUTHOR]

Patients suffering from chronic gastritis and developing gastric mucosa atrophy are at increased risk of the development of gastric cancer. The diagnosis of chronic atrophic gastritis (CAG) is a complex procedure involving a detailed history taking, a thorough physical examination and the use of laboratory and instrumental diagnostic methods among which the endoscopy of the upper digestive tract is the cornerstone because it allows the assessment of the topography of gastritis and identification of erosions and areas of intestinal metaplasia with the use of NBI endoscopy. However, the diagnosis of CAG requires morphological examination of the gastric mucosa. So, in addition to assessing macroscopic changes in the gastric mucosa, it is necessary to take biopsy specimens in accordance with the protocols for their morphological and immunohistochemical examination. In the absence of specific diagnostic stigmas of CAG, close cooperation between a clinician, endoscopist and pathologist is necessary. The article presents systematized data on the histopathological assessment of the gastric mucosa atrophy to predict the risk of gastric cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is one of the most common cause of human infections. Infected patients develop chronic active gastritis in all cases, which can lead to peptic ulcer, atrophic gastritis, gastric cancer and gastric MALT-lymphoma. The prevalence of H. pylori infection in the population has regional characteristics and can reach 80%. Constantly increasing antibiotic resistance of H. pylori is a major cause of treatment failure and a major problem. According to the VI Maastricht Consensus, two main strategies for choosing eradication therapy are recommended: individualized based on evaluating sensitivity to antibacterial drugs (phenotypic or molecular genetic method) prior to their appointment, and empirical, which takes into account data on local H. pylori resistance to clarithromycin and monitoring effectiveness schemes in the region. Therefore, the determination of H. pylori resistance to antibiotics, especially clarithromycin, prior to choosing therapeutic strategy is extremely important for the implementation of these treatment regimens. [ABSTRACT FROM AUTHOR]

Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this "new" type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning with chronic atrophic gastritis (CAG), precedes GC. To test the possible existence of autoimmunity in patients with CAG, we aimed to analyze the prevalence of several autoantibodies in patients with CAG as compared to control patients. Sera of 355 patients included in our previous prospective, multicenter study were tested for 19 autoantibodies (anti-nuclear antibodies, ANA, anti-parietal cell antibody, APCA, anti-intrinsic factor antibody, AIFA, and 16 myositis-associated antibodies). The results were compared between CAG patients (n = 154), including autoimmune gastritis patients (AIG, n = 45), non-autoimmune gastritis patients (NAIG, n = 109), and control patients (n = 201). ANA positivity was significantly higher in AIG than in NAIG or control patients (46.7%, 29%, and 27%, respectively, p = 0.04). Female gender was positively associated with ANA positivity (OR 0.51 (0.31–0.81), p = 0.005), while age and H. pylori infection status were not. Myositis-associated antibodies were found in 8.9% of AIG, 5.5% of NAIG, and 4.4% of control patients, without significant differences among the groups (p = 0.8). Higher APCA and AIFA positivity was confirmed in AIG, and was not associated with H. pylori infection, age, or gender in the multivariate analysis. ANA antibodies are significantly more prevalent in AIG than in control patients, but the clinical significance of this finding remains to be established. H. pylori infection does not affect autoantibody seropositivity (ANA, APCA, AIFA). The positivity of myositis-associated antibodies is not increased in patients with CAG as compared to control patients. Overall, our results do not support an overrepresentation of common autoantibodies in patients with CAG. [ABSTRACT FROM AUTHOR]

Type I gastric neuroendocrine neoplasms (gNENs) are associated with atrophic gastritis and have a high recurrence rate, which means frequent endoscopies are required. The objective of this study was to identify factors predicting the local recurrence of type I gNENs. The clinical course and the pathological and biochemical data of patients with type I gNENs treated at Bnai Zion Medical Center between 2006 and 2022 were analyzed retrospectively. Twenty-seven type I gNENs were evaluated. The follow-up period was 41 months (range: 11–288 months). Recurrence of the tumor occurred in 13/27 (48%) patients after 35 months (median (M), interquartile range (IQR): 21–67.5). Serum gastrin levels were significantly higher in patients with recurrent disease versus patients with non-recurrent disease (788 vs. 394 ng/L; p = 0.047), while the Ki-67 index was significantly lower in patients with recurrent disease versus patients with non-recurrent disease (1% vs. 3.5%; p = 0.035). Tumor size, mitotic count, and serum chromogranin A levels did not correlate with recurrence. The present study emphasizes the role of gastrin in the pathogenesis of gNEN recurrence and highlights the debate regarding the ability of the Ki-67 index to predict the clinical course of this disease. [ABSTRACT FROM AUTHOR]

In this study, we aimed to assess the accuracy of the proposed novel, noninvasive serum DSC test in predicting the risk of gastric cancer before the use of upper endoscopy. To validate the DSC test, we enrolled two series of individuals living in Veneto and Friuli-Venezia Giulia, Italy (n = 53 and n = 113, respectively), who were referred for an endoscopy. The classification used for the DSC test to predict gastric cancer risk combines the coefficient of the patient's age and sex and serum pepsinogen I and II, gastrin 17, and anti-Helicobacter pylori immunoglobulin G concentrations in two equations: Y1 and Y2. The coefficient of variables and the Y1 and Y2 cutoff points (>0.385 and >0.294, respectively) were extrapolated using regression analysis and an ROC curve analysis of two retrospective datasets (300 cases for the Y1 equation and 200 cases for the Y2 equation). The first dataset included individuals with autoimmune atrophic gastritis and first-degree relatives with gastric cancer; the second dataset included blood donors. Demographic data were collected; serum pepsinogen, gastrin G17, and anti-Helicobacter pylori IgG concentrations were assayed using an automatic Maglumi system. Gastroscopies were performed by gastroenterologists using an Olympus video endoscope with detailed photographic documentation during examinations. Biopsies were taken at five standardized mucosa sites and were assessed by a pathologist for diagnosis. The accuracy of the DSC test in predicting neoplastic gastric lesions was estimated to be 74.657% (65%CI; 67.333% to 81.079%). The DSC test was found to be a useful, noninvasive, and simple approach to predicting gastric cancer risk in a population with a medium risk of developing gastric cancer. [ABSTRACT FROM AUTHOR]

Autoimmune metaplastic atrophic gastritis (AMAG) is associated with an increased risk of gastric neoplasms. This study aimed to systematically analyze the incidence rate of gastric cancer (GC), low-grade dysplasia (LGD) and type-1 gastric neuroendocrine tumor (gNETs) development in AMAG adults. Studies on AMAG patients reporting the incidence of gastric neoplasms was identified through a systematic search in PUBMED and EMBASE. Study quality was assessed using the Joanna Briggs Institute quality assessment tool. Incidence rates of GC, LGD and type-1 gNETs were examined by meta-analysis. Thirteen studies met eligibility criteria. Incidence rate of gastric cancer calculated from the pooled data was 0.14% per person-year in both single-center studies and national registration studies. Meta-analysis showed a relative risk of 11.05 (95% CI: 6.39–19.11) for gastric cancer development in AMAG patients. The calculated pooled gastric LGD and type-1 gNETs incidence rates were 0.52% and 0.83% per person-year, respectively. As for experience from our center, we presented three distinctive cases of gastric neoplasm arising from the background of AMAG. This study underscores the potential for malignant transformation of precancerous lesions and reiterates the importance of careful esophagogastroduodenoscopy screening. [ABSTRACT FROM AUTHOR]

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy. [ABSTRACT FROM AUTHOR]

Atrophic gastritis (AG) is commonly caused by the infection of the Helicobacter pylori (H. pylori) bacteria. If untreated, AG may develop into a chronic condition leading to gastric cancer, which is deemed to be the third primary cause of cancer-related deaths worldwide. Precursory detection of AG is crucial to avoid such cases. This work focuses on H. pylori-associated infection located at the gastric antrum, where the classification is of binary classes of normal versus atrophic gastritis. Existing work developed the Deep Convolution Neural Network (DCNN) of GoogLeNet with 22 layers of the pre-trained model. Another study employed GoogLeNet based on the Inception Module, fast and robust fuzzy C-means (FRFCM), and simple linear iterative clustering (SLIC) superpixel algorithms to identify gastric disease. GoogLeNet with Caffe framework and ResNet-50 are machine learners that detect H. pylori infection. Nonetheless, the accuracy may become abundant as the network depth increases. An upgrade to the current standards method is highly anticipated to avoid untreated and inaccurate diagnoses that may lead to chronic AG. The proposed work incorporates improved techniques revolving within DCNN with pooling as pre-trained models and channel shuffle to assist streams of information across feature channels to ease the training of networks for deeper CNN. In addition, Canonical Correlation Analysis (CCA) feature fusion method and ReliefF feature selection approaches are intended to revamp the combined techniques. CCA models the relationship between the two data sets of significant features generated by pre-trained ShuffleNet. ReliefF reduces and selects essential features from CCA and is classified using the Generalized Additive Model (GAM). It is believed the extended work is justified with a 98.2% testing accuracy reading, thus providing an accurate diagnosis of normal versus atrophic gastritis. [ABSTRACT FROM AUTHOR]

The expression of CXC motif chemokine 17 (CXCL17) and its reported membrane receptor G-protein-coupled receptor 35 (GPR35) in different gastric pathological lesions and their clinical implications are largely unknown. In this study, a total of 860 pathological sections were immune-stained with either anti-CXCL17 or anti-GPR35 antibodies. Their expression was scored within the area of the normal gastric gland of non-atrophic gastritis (NAG-NOR), intestinal metaplasia of atrophic gastritis (AG-IM), IM adjacent to GC (GC-IM), and GC tissue. The clinical significance and potential function of CXCL17 and GPR35 were explored using multiple methods. Our results suggested that CXCL17 expression was gradually upregulated during the pathological progress of gastric diseases (NAG-NOR < AG-IM < GC-IM), but significantly downregulated when GC occurred. GPR35 had a similar expression pattern but its expression in GC remained abundant. High CXCL17 expression in GC was associated with less malignant behavior and was an independent biomarker of favorable prognosis. Overexpressing CXCL17 in HGC27 cells significantly upregulated CCL20 expression. TCGA analysis identified that CXCL17 was negatively correlated with some cancer-promoting pathways and involved in inflammatory activities. CTRP analysis revealed that gastric cell lines expressing less CXCL17 and were more sensitive to the CXCR2 inhibitor SB-225002. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infects about half of the world's population and can lead to premalignant lesions and gastric cancer. Updated data about the correlation of histopathological diagnostics with endoscopic diagnostics are scarce. The objective of this study was to identify the concordance between endoscopic and histopathologic findings, with a focus on premalignant lesions. We performed a cross sectional, retrospective study over a 4-year period (2017–2021) on adult patients with dyspeptic symptoms and positive RUT (rapid urease test) in a single hospital centre, with a total of 133 patients infected with H. pylori being included in the study. Statistical associations between endoscopic appearance and histopathological results were found for atrophic antral gastritis (p = 0.001), intestinal metaplasia of the antrum (p = 0.018), gastric polyps (p < 0.001) and gastric corpus cancer (p = 0.012). Females were more likely to be diagnosed through endoscopy with gastric atrophy or intestinal metaplasia (p = 0.031), while chronic atrophic gastritis in corpus was more prevalent in patients older than 65 (p = 0.024). Overall, our study reveals only 21% concordance between Giemsa stain and RUT, highlighting the importance of combining rapid testing with endoscopic and histopathological diagnostic methods for a more accurate early diagnosis and prevention of gastric cancer. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is gradually being utilized in various fields as its performance has been improving with the development of deep learning methods, availability of big data, and the progression of computer processing units. In the field of medicine, AI is mainly implemented in image recognition, such as in radiographic and pathologic diagnoses. In the realm of gastrointestinal endoscopy, although AI-based computer-assisted detection/diagnosis (CAD) systems have been applied in some areas, such as colorectal polyp detection and diagnosis, so far, their implementation in real-world clinical settings is limited. The accurate detection or diagnosis of gastric cancer (GC) is one of the challenges in which performance varies greatly depending on the endoscopist's skill. The diagnosis of early GC is especially challenging, partly because early GC mimics atrophic gastritis in the background mucosa. Therefore, several CAD systems for GC are being actively developed. The development of a CAD system for GC is considered challenging because it requires a large number of GC images. In particular, early stage GC images are rarely available, partly because it is difficult to diagnose gastric cancer during the early stages. Additionally, the training image data should be of a sufficiently high quality to conduct proper CAD training. Recently, several AI systems for GC that exhibit a robust performance, owing to being trained on a large number of high-quality images, have been reported. This review outlines the current status and prospects of AI use in esophagogastroduodenoscopy (EGDS), focusing on the diagnosis of GC. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection is an important risk factor for developing gastric cancer. However, only a few H. pylori-infected people develop gastric cancer. Thus, other risk factors aside from H. pylori infection may be involved in gastric cancer development. This study aimed to investigate whether the nitrate-reducing bacteria isolated from patients with atrophic gastritis caused by H. pylori infection are risk factors for developing atrophic gastritis and gastric neoplasia. Nitrate-reducing bacteria were isolated from patients with atrophic gastritis caused by H. pylori infection. Among the isolated bacteria, Actinomyces oris, Actinomyces odontolyticus, Rothia dentocariosa, and Rothia mucilaginosa were used in the subsequent experiments. Cytokine inducibility was evaluated in monocytic cells, and mitogen-activated protein kinase (MAPK) activity and cell cycle were assessed in the gastric epithelial cells. The cytotoxicities and neutrophil-inducing abilities of the Actinomyces and Rothia species were enhanced when cocultured with H. pylori. Th1/Th2-related cytokines were also expressed, but their expression levels differed depending on the bacterial species. Moreover, H. pylori and Actinomyces activated MAPK (ERK and p38) and affected cell cycle progression. Some nitrate-reducing bacteria cocultured with H. pylori may promote inflammation and atrophy by inducing cytokine production. In addition, the MAPK activation and cell cycle progression caused by these bacteria can contribute to gastric cancer development. [ABSTRACT FROM AUTHOR]

The incidence of gastric cancer in Okinawa Prefecture is the lowest in Japan, which is attributed to differences in strains of Helicobacter pylori in Okinawa and other prefectures in Japan. Our aim was to compare the endoscopic findings of H. pylori-infected gastric mucosa in Okinawa and Tokyo. Patients who underwent upper gastrointestinal endoscopy (UGI) at Northern Okinawa Medical Center (Okinawa group) and Juntendo University Hospital (Tokyo group) from April 2019 to March 2020 were included. Patients diagnosed with H. pylori-infected gastric mucosa were retrospectively compared between the Okinawa and Tokyo groups according to the Kyoto Classification of Gastritis. The numbers of subjects (Okinawa/Tokyo) were 435/352, male/female ratio was 247:188/181:171, and age was 53.3 ± 14.7/64.6 ± 14.3 (mean ± standard deviation) years. Regarding the Kyoto Classification of Gastritis, the prevalence (Okinawa/Tokyo) of the closed type of atrophic gastritis was 73%/37% (p < 0.001), diffuse redness 80%/84% (p = 0.145), mucosal swelling 46%/46% (p = 0.991), enlarged fold 26%/32% (p = 0.048), spotty redness 77%/68% (p = 0.002), sticky mucus 17%/36% (p < 0.001), and intestinal metaplasia 32%/42% (p < 0.001). Age analysis also revealed that closed-type atrophy and spotty redness were more frequent in the Okinawa group than in the Tokyo group. There may be regional differences in endoscopic findings of H. pylori-infected gastric mucosa between Okinawa and Tokyo. [ABSTRACT FROM AUTHOR]

Background and Objectives: The role of α-enolase (ENO1) in Helicobacter pylori-related gastric lesions might be a critical factor in the pathogenesis, but remains undefined. Materials and Methods: This study investigated the differential expression of α-enolase in clinical gastric specimens and cultured normal/cancer cells in response to H. pylori (cagA+) infection and cagA transfection using qPCR, Western blots and histochemical methods. Results: A total of 172 gastric specimens were collected from 142 patients, the former comprising chronic superficial gastritis (CSG), precancerous diseases (PCDs, including atrophic gastritis, intestinal metaplasia and dysplasia) and gastric cancer (GC) cases. Among the CSG and PCD cases, the H. pylori-infected group had significantly elevated ENO1 mRNA levels compared with the uninfected group. In the GC cases, differential ENO1 expressions were detected between the cancer tissues and the paracancerous tissues. Notably, significant difference was first detected between the GC cell (AGS) and the normal cell (GES-1) as a response of ENO1 to H. pylori infection and cagA transfection. Conclusions: This report reveals that ENO1 expression is associated with H. pylori infection, cagA transfection, co-culture duration, multiplicity of infection, gastric normal/cancerous cell lines and cellular differentiation. The findings may be crucial bases for further ascertaining H. pylori pathogenic mechanism and formulating novel therapeutic and diagnostic strategies. [ABSTRACT FROM AUTHOR]

Heat-shock proteins (HSPs) are a family of proteins that have received considerable attention over the last several years. They have been classified into six prominent families: high-molecular-mass HSP, 90, 70, 60, 40, and small heat shock proteins. HSPs participate in protein folding, stability, and maturation of several proteins during stress, such as in heat, oxidative stress, fever, and inflammation. Due to the immunogenic host's role in the combat against cancer cells and the role of the inflammation in the cancer control or progression, abnormal expression of these proteins has been associated with many types of cancer, including esophagogastric cancer. This study aims to review all the evidence concerning the role of HSPs in the pathogenesis and prognosis of esophagogastric cancer and their potential role in future treatment options. This narrative review gathers scientific evidence concerning HSPs in relation to esophagus and gastric cancer. All esophagogastric cancer subtypes are included. The role of HSPs in carcinogenesis, prognostication, and therapy for esophagogastric cancer are discussed. The main topics covered are premalignant conditions for gastric cancer atrophic gastritis, Barrett esophagus, and some viral infections such as human papillomavirus (HPV) and Epstein–Barr virus (EBV). HSPs represent new perspectives on the development, prognostication, and treatment of esophagogastric cancer. [ABSTRACT FROM AUTHOR]

Gastric cancer is the second leading cause of cancer incidence in Japan, although gastric cancer mortality has decreased over the past few decades. This decrease is attributed to a decline in the prevalence of H. pylori infection. Radiographic examination has long been performed as the only method of gastric screening with evidence of reduction in mortality in the past. The revised 2014 Japanese Guidelines for Gastric Cancer Screening approved gastric endoscopy for use in population-based screening, together with radiography. While endoscopic gastric cancer screening has begun, there are some problems associated with its implementation, including endoscopic capacity, equal access, and cost-effectiveness. As H. pylori infection and atrophic gastritis are well-known risk factors for gastric cancer, a different screening method might be considered, depending on its association with the individual's background and gastric cancer risk. In this review, we summarize the current status and problems of gastric cancer screening in Japan. We also introduce and discuss the results of gastric cancer screening using H. pylori infection status in Hoki-cho, Tottori prefecture. Further, we review risk stratification as a system for improving gastric cancer screening in the future. [ABSTRACT FROM AUTHOR]

Autoimmune gastritis (AIG) is chronic atrophic gastritis caused by an autoimmune mechanism of unknown etiology and presents with various pathological conditions by causing an achlorhydria state through parietal cell damage. The most characteristic endoscopic finding in AIG is advanced corpus-dominant mucosal atrophy. A recent study that examined several cases in Japan revealed the presence of endoscopic features other than corpus-dominant advanced atrophy. Remnants of oxyntic mucosa and sticky adherent dense mucus were found in ≥30% of cases, and hyperplastic polyps were found in ≥20% of cases. In image-enhanced endoscopy (IEE), white globe appearance (WGA) was observed in 32% of AIG cases. Additionally, some reports have stated that the findings in AIG cases using IEE showed cast-off skin appearance (CSA) and foveola type mucosa; however, a consensus is yet to be achieved. These endoscopic results were found in cases of advanced-stage AIG. There have been few reports concerning early-stage AIG cases. In these few reports, all of the cases were pathologically diagnosed as early AIG. In all of the cases, the pathological findings almost always showed neither parietal cell destruction nor atrophy. Endoscopic findings such as "mosaic pattern with slight swelling of the areae gastricae", "diffuse reddened and edematous gastric fundic gland mucosa", and "pseudopolyp-like nodules" may be common characteristics of early images. In such early cases, high antibody titers, no atrophic changes, and few clinical abnormal findings were shown. Endoscopists are expected to update their knowledge regarding AIG diagnosis with the evolution of imaging equipment. [ABSTRACT FROM AUTHOR]

Simple Summary: The standard treatment for well-differentiated thyroid cancer is thyroidectomy followed by radioactive iodine (RAI) treatment or active surveillance. Despite adequate documentation of acute gastrointestinal adverse effects after RAI treatment, whether the gastrointestinal exposure causes long-term comorbidity or not remained unclear. We conducted a nationwide, population-based retrospective cohort study using the data from the Taiwan National Health Insurance Research Database (NHIRD) to clarify the association between long-term gastrointestinal disorders (including ulcers, atrophic gastritis, and secondary stomach malignancy) and RAI treatment in thyroid cancer patients. We found that patients with RAI treatment were at a significantly higher risk of developing gastric and duodenal ulcers than those without. In addition, a higher cumulative dose is associated with higher risk. Therefore, follow-ups at gastrointestinal clinics might be of great importance for patients presenting with chronic gastrointestinal discomforts, after receiving a single RAI dose of more than 1.11 GBq, and undergoing repeated treatment due to recurrent or residual thyroid cancer. (1) Background: The study aimed to investigate the association between radioactive iodine (RAI) treatment and long-term gastrointestinal disorders including ulcers, atrophic gastritis, and secondary malignant neoplasm of the stomach in patients with thyroid cancer. (2) Methods: The data of the study were extracted from the National Health Insurance Database (NHIRD) of Taiwan between 2000 to 2015. Patients of ages older than 20 with thyroid cancer after thyroidectomy were included and divided into groups with RAI (study cohort) and without RAI (comparison cohort). Multivariate Cox proportional hazards regression analysis and the Kaplan–Meier method were used for statistical analysis. (3) Results: A total of 7250 (with RAI: 5800, without RAI: 1450) patients were included. The Kaplan-Meier analysis revealed a significantly higher cumulative risk for overall gastrointestinal disorders in the group with RAI (log-rank p = 0.034). The risk for gastrointestinal disorders was higher when receiving a cumulative RAI dose higher than 1.11 GBq in the Cox regression analysis. In the subgroup analysis, the risks of gastric and duodenal ulcers are significantly higher in the group with RAI treatment. (4) Conclusions: This study revealed that RAI was associated with an increased risk for long-term gastrointestinal disorders, specifically gastric and duodenal ulcers, in thyroid cancer, especially when the cumulative dose exceeds 1.11 GBq. [ABSTRACT FROM AUTHOR]

Gastric cancer is a global health problem. The pathogenesis of this disease remains unclear. This study included 198 H. pylori (+) men aged 45 to 60 years old. Group A included 63 practically healthy men, group B included 45 men with severe atrophic body gastritis, group C included 37 men with epithelial gastric cancer stages I–II according to TNM, and group D included 54 men with epithelial gastric cancer stages III–IV according to the TNM scale. The content of malondialdehyde (MDA), diene conjugates (DCs), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPO) was detected using an enzyme immunoassay (ELISA) or spectrophotometric methods in the blood plasma. The concentrations of MDA and DC were increased in the patients of group B compared with group A, and in patients of groups C and D compared with groups A and B. The ratio of MDA/SOD and MDA/CAT was decreased in the patients in group D compared with the patients in group C, and was significantly higher compared with group A. The ratios of MDA/GPO and MDA/GST increased linearly and were at a maximum in groups C and D. Our work determined that indicators of oxidative stress may be the biochemical substrate, which brings together the various stages of the Correa cascade, and may explain disease progression. The dynamics of changes in the content of SOD and CAT in the plasma in patients with gastric cancer may be a target of future investigations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The adult gastric mucosa is characterised by deep invaginations of the epithelium called glands. These tissue architectural elements are maintained with the contribution of morphogen signals. Morphogens are expressed in specific areas of the tissue, and their diffusion generates gradients in the microenvironment. Cells at different positions in the gland sense a specific combination of signals that instruct them to differentiate, proliferate, regenerate, or migrate. Differentiated cells perform specific functions involved in digestion, such as the production of protective mucus and the secretion of digestive enzymes or gastric acid. Biopsies from gastric precancerous conditions usually display tissue aberrations and change the shape of the glands. Alteration of the morphogen signalling microenvironment is likely to underlie those conditions. Furthermore, genes involved in morphogen signalling pathways are found to be frequently mutated in gastric cancer. We summarise the most recent findings regarding alterations of morphogen signalling during gastric carcinogenesis, and we highlight the new stem cell technologies that are improving our understanding of the regulation of human tissue shape. [ABSTRACT FROM AUTHOR]

Gastric cancer is a heterogenous group of tumours, and a better understanding of the carcinogenesis and cellular origin of the various sub-types could affect prevention and future treatment. Gastric neuroendocrine tumours (NETs) and adenocarcinomas that develop in the gastric corpus and fundus of patients with chronic atrophic gastritis have atrophic gastritis, hypoacidity, and hypergastrinemia as common risk factors and a shared cellular origin has been suggested. In particular, signet ring cell carcinomas have previously been suggested to be of neuroendocrine origin. We present a case of a combined gastric NET and signet ring cell carcinoma in a patient with hypergastrinemia due to autoimmune chronic atrophic gastritis. The occurrence of such a combined tumour strengthens the evidence that gastric NETs and signet ring cell carcinomas develop from a common origin. [ABSTRACT FROM AUTHOR]

Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), a gastric precancerous lesion, is of growing interest for identification of patients at increased risk of gastric cancer. The aim was to analyze the diagnostic performance of serum pepsinogen testing using another method, chemiluminescent enzyme immunoassay (CLEIA), as well as of other new potential biomarkers. Material and Methods: The sera of patients considered at increased risk of gastric cancer and undergoing upper endoscopy collected in our previous prospective, multicenter study were tested for pepsinogen I (PGI) and II (PGII), interleukin-6 (IL-6), human epididymal protein 4 (HE-4), adiponectin, ferritin and Krebs von den Lungen (KL-6) using the CLEIA. The diagnostic performance for the detection of AG was calculated by taking histology as the reference. Results: In total, 356 patients (162 men (46%); mean age 58.6 (±14.2) years), including 152 with AG, were included. For the detection of moderate to severe corpus AG, sensitivity and specificity of the pepsinogen I/II ratio were of 75.0% (95%CI 57.8–87.9) and 92.6% (88.2–95.8), respectively. For the detection of moderate to severe antrum AG, sensitivity of IL-6 was of 72.2% (95%CI 46.5–90.3). Combination of pepsinogen I/II ratio or HE-4 showed a sensitivity of 85.2% (95%CI 72.9–93.4) for the detection of moderate to severe AG at any location. Conclusion: This study shows that PG testing by CLEIA represents an accurate assay for the detection of corpus AG. Additionally, IL-6 and HE-4 may be of interest for the detection of antrum AG. Mini-abstract: Pepsinogens testing by chemiluminescent enzyme immunoassay is accurate for the detection of corpus atrophic gastritis. IL-6 and HE-4 maybe of interest for the detection of antrum atrophic gastritis. [ABSTRACT FROM AUTHOR]

Duodenogastric reflux (DGR) causes bile reflux gastritis (BRG) and may develop into gastric cancer. DGR is classified as primary in non-operated stomachs or secondary to surgical intervention. Primary DGR and Helicobacter pylori (H. pylori) infection are reportedly related. However, the mechanism is not fully understood. This study aimed to elucidate the relationship between H. pylori infection and pyloric incompetence in a non-operated stomach. A total of 502 non-operated participants who underwent an upper intestinal endoscopy were prospectively enrolled. Endoscopic findings (EAC, endoscopic atrophy classification; nodular gastritis; xanthoma; fundic gland polyp; and incompetence of pylorus), sex, age, gastrin, pepsinogen (PG) I and PG II levels were evaluated. PG I/PG II ratio, anti-H. pylori-Ab positivity, and atrophic gastritis status were significantly different between the normal and incompetent pylori (p = 0.043, <0.001, and 0.001, respectively). Open-type atrophic gastritis was significantly higher in the incompetent pylori. Incompetence of the pylorus and EAC were moderately correlated (Cramer's V = 0.25). Multivariate analysis revealed that the presence of anti-H. pylori-Ab was the only independent factor associated with the incompetence of the pylorus, with an adjusted odds ratio of 2.70 (95% CI: 1.47–4.94, p = 0.001). In conclusion, pyloric incompetence was associated with H. pylori infection and moderately correlated to the severity of atrophic gastritis in non-operated stomachs. [ABSTRACT FROM AUTHOR]