Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income, Helicobacter pylori (H. pylori) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy, H. pylori infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis. H. Pylori eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.

Gastric cancer (GC) is a leading cause of global mortality, but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review will also highlight existing knowledge gaps in GC prevention, as well as the role of emerging technologies for early detection and risk stratification.

There is limited research evaluating the diagnosis and treatment of patients with autoimmune gastritis (AIG) and pernicious anemia (PA). We used a 2-phase data collection process to examine the literature and individual patient accounts. Phase one comprised a systematically conducted literature review focusing on diagnosis and treatment, relationships with healthcare practitioners and health-related quality of life (HRQOL). Phase two involved analysis of individual accounts via posts in online patient forums. We identified 6 main themes: the diagnosis journey, seeking treatment, patient-provider relationships, HRQOL, patient disempowerment, and the "expert patient." Our findings confirm significant knowledge gaps concerning AIG/PA across the healthcare community. These have a cascading effect starting with delays in diagnosis and poor treatment protocols and often lead to complete withdrawal from care seeking. The establishment of standard consensus guidelines and improved clinical awareness should be urgently addressed. Interventions that better help patients understand their illness are also needed to improve psychological health. Without these changes disengagement from health systems, and poor health outcomes, will continue for this population group.

Although medical research has been performed predominantly on men both in preclinical and clinical studies, continuous efforts have been made to overcome this gender bias. Examining retrospectively 21 data sets containing sex as one of the descriptive variables, it was possible to verify how many times our AI protocol decided to keep gender information in the predictive model. The data sets pertained a vast array of diseases such as dyspeptic syndrome, atrophic gastritis, venous thrombosis, gastroesophageal reflux disease, irritable bowel syndrome, Alzheimer diseases and mild cognitive impairment, myocardial infarction, gastrointestinal bleeding, gastric cancer, hypercortisolism, AIDS, COVID diagnosis, extracorporeal membrane oxygenation in intensive therapy, among others. The sample size of these data sets ranged between 80 and 3147 (average 600). The number of variables ranged from 19 to 101 (average 41). Gender resulted to be part of the heuristic predictive model 19 out of 21 times. This means that also for highly adaptive and potent tools like Artificial Neural Networks, information on sex carries a specific value. In the field of rheumatology, there is a specific example in psoriatic arthritis that shows that the presence of gender information allows a significantly better accuracy of ANNs in predicting diagnosis from clinical data (from 87.7% to 94.47%). The results of this study confirm the importance of gender information in building high performance predictive model in the field of Artificial Intelligence (AI). Therefore, also for AI, sex counts.

Vitamin B12, or cobalamin, belongs to the group of water-soluble vitamins and is ingested through food of animal origin such as eggs, milk, red meat and poultry, fish, and shellfish. Its clinical indication is the treatment of hypovitaminosis B12 administered orally or intramuscularly in the form of hydroxocobalamin. Hypovitaminosis B12 is mainly caused by deficient dietary intake (individuals with malnutrition, vegetarians or vegans, older adults, pregnant people, individuals with alcohol use disorder); when intestinal absorption is reduced (atrophic gastritis, malabsorption syndrome, gastrointestinal surgery); and for causes associated with the intake of drugs (antacids, metformin). Hypervitaminosis B12 has been associated with renal failure; liver diseases such as cirrhosis and acute-phase hepatitis; alcohol use disorder with or without liver involvement; solid tumors of the lung, liver, esophagus, pancreas, and colorectum; and in hematological malignancies such as leukemia and bone marrow dysplasia.

Gastric cancer (GC) is one of the most serious health problems worldwide. Chronic atrophic gastritis (CAG) is a gastric precancerous lesion (GPL), most commonly caused by Helicobacter pylori (H. pylori) infection that may also lead to GC by the direct way such as the translocation of CagA. Presently, the diagnosis of early GC (EGC) and CAG mainly relies on endoscopy, which has always been a challenge for endoscopists. And the accuracy of endoscopic diagnosing H. pylori is mostly 70%. The development of artificial intelligence (AI) can assist clinical works in many aspects including detection, invasion depth prediction, boundary delineation and anatomical location of EGC, and has achievable diagnostic ability, even comparable to endoscopists. We try to review the current status of various AI applications in EGC, CAG and H. pylori infection, and point out probable directions for future research in this field to promote the better application of AI in clinical practice. This article is protected by copyright. All rights reserved.

An 87-year-old man with dysphagia presented to our hospital. He was diagnosed with autoimmune gastritis (AIG) with severe atrophy and hypergastrinemia. The patient was positive for parietal cell antibody (PCA) and anti-intrinsic factor antibody (IFA), without evidence of H. pylori infection. A flat elevated tumor was detected in the middle corpus, and therapeutic endoscopic submucosal dissection was performed. Histopathological examination revealed atypical cells mimicking the fundic glands, which were positive for pepsinogen-I and partially positive for MUC6 and H + /K + -ATPase, proliferating to the deep layer. The final diagnosis was gastric adenocarcinoma of the fundic gland type (GAFG). AIG is expected to be difficult to develop GAFG because the basal gastric glands are highly atrophic due to the production of PCA. However, some chief cells may remain and could have the potential to develop into malignancy during AIG progression. Therefore, careful observation is required in patients with AIG when considering the occurrence of GAFG.

It is estimated that hypothyroidism treatment may be either suboptimal or excessive in about 32-45% patients treated with L-thyroxine (LT4). There are multiple possible causes of poor control of hypothyroidism, including narrow LT4 therapeutic index, food and drug interactions, comorbidities, and patient non-adherence. Some of these obstacles could possibly be overcome with the novel liquid LT4 formulation. Liquid LT4 reaches maximum blood concentration about 30 minutes faster than the tablet form. Faster pharmacokinetics might lead to more efficient LT4 absorption, as suggested by a recent real-world study in patients with primary and central hypothyroidism. Liquid LT4 treatment led to increased free thyroxine (FT4) and sex hormone binding globulin (SHBG) with decreased low-density lipoprotein (LDL) cholesterol concentration and substantially improved quality of life for the patients. Herein we present a series of 31 patients with hypothyroidism of different aetiologies treated with the novel liquid LT4 formulation in standard clinical care in light of the latest scientific publications on liquid LT4 formula. We observed normalization of thyroid function tests shortly after introduction of liquid LT4, irrespective of concurrent diseases or concomitant medications that could diminish LT4 absorption. In more detail, the treatment with liquid LT4 managed to normalize thyroid-stimulating hormone (TSH) concentrations in patients without any known causes of LT4 absorption disturbances, as well as in those with malabsorption: with gastric bypass, partial small and large intestine resection, scleroderma, gluten intolerance, celiac disease, atrophic gastritis, and polytherapy. In conclusion, considering many factors disturbing LT4 absorption, hypothyroidism therapy with liquid LT4 seems to be a particularly effective option.

The stomach is a hostile environment for most microbes because strong gastric acid kills indigenous microorganisms. Thus, the mass of indigenous microbes detected by traditional culturing method in a highly acidic stomach is reported to be very small. However, in a stomach with less acidity due to atrophic changes of the gastric mucosa, the number of live gastric microbiota dramatically increases and their composition changes. A probiotic is defined as a live microorganism that, when administered in adequate amounts, confers a health benefit on the host. The administration of probiotics to the stomach has thus far been considered impractical, mainly due to the strong acidity in the stomach. The identification of candidate probiotic strains with sufficient resistance to acidity and the ability to achieve close proximity to the gastric mucosa could enable the application of probiotics to the stomach. The utilization of probiotics alone for Helicobacter pylori (H. pylori) infection significantly improves gastric mucosal inflammation and decreases the density of H. pylori on the mucosa, although complete eradication of H. pylori has not yet been demonstrated. The use of probiotics in combination with antimicrobial agents significantly increases the H. pylori eradication rate, especially when the H. pylori strains are resistant to antimicrobial agents. While H. pylori has been considered the most important pathogenic bacterium for the development of gastric cancer, bacteria other than H. pylori are also suggested to be causative pathogens that promote the development of gastric cancer, even after the eradication of H. pylori. Increased non-H. pylori Gram-negative bacteria in the stomach with weak acidity accompanying atrophic gastritis may perpetuate gastric mucosal inflammation and accelerate carcinogenic progression, even after H. pylori eradication. Probiotics restore the acidity in this stomach environment and may therefore prevent the development of gastric cancer by termination of Gram-negative bacteria-induced inflammation. Functional dyspepsia (FD) is defined as the presence of symptoms that are thought to originate in the gastroduodenal region in the absence of any organic, systematic or metabolic diseases. Accumulating evidence has pointed out the duodenum as a target region underlying the pathophysiology of FD. A randomized placebo-controlled clinical trial using a probiotic strain (LG21) demonstrated a significant improving effect on major FD symptoms. One of the possible mechanisms of this effect is protection of the duodenal mucosa from injurious intestinal bacteria through the resolution of small intestinal bacterial over growth.

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.

Pernicious anemia (PA) is an autoimmune disease secondary to chronic atrophic gastritis leading to vitamin B12 deficiency. Rarely, some patients may develop advanced hematological complications that mimic those of thrombotic thrombocytopenic purpura (TTP). Differentiating these conditions is crucial because they require different management. We present a case of a 68-year-old male who presented with generalized weakness, fatigue, and shortness of breath. This patient had anemia, thrombocytopenia, and a markedly deficient serum level of vitamin B12. The symptoms initially mimicked those associated with TTP, but the activity of ADAMTS 13 was normal. A diagnosis of pseudo-TTP has been made due to vitamin B12 deficiency resulting from PA with reactive thrombocytosis. Ultimately, vitamin B12 deficiency pseudo-TTP should be considered a differential diagnosis for therapy refractory TTP because of its different management strategies ranging from parenteral Vitamin B12 in PA patients with highly favorable outcomes to more advanced treatment with less favorable outcomes in TTP patients.

Gastric cancer is one of the most frequent causes of cancer-related deaths worldwide. Gastric atrophy (GA) and gastric intestinal metaplasia (IM) of the mucosa of the stomach have been found to increase the risk of gastric cancer and are considered precancerous lesions. Therefore, the early detection of GA and IM may have a valuable role in histopathological risk assessment. However, GA and IM are difficult to confirm endoscopically and, following the Sydney protocol, their diagnosis depends on the analysis of glandular morphology and on the identification of at least one well-defined goblet cell in a set of hematoxylin and eosin (H&E) -stained biopsy samples. To this end, the precise segmentation and classification of glands from the histological images plays an important role in the diagnostic confirmation of GA and IM. In this paper, we propose a digital pathology end-to-end workflow for gastric gland segmentation and classification for the analysis of gastric tissues. The proposed GAGL-VTNet, initially, extracts both global and local features combining multi-scale feature maps for the segmentation of glands and, subsequently, it adopts a vision transformer that exploits the visual dependences of the segmented glands towards their classification. For the analysis of gastric tissues, segmentation of mucosa is performed through an unsupervised model combining energy minimization and a U-Net model. Then, features of the segmented glands and mucosa are extracted and analyzed. To evaluate the efficiency of the proposed methodology we created the GAGL dataset consisting of 85 WSI, collected from 20 patients. The results demonstrate the existence of significant differences of the extracted features between normal, GA and IM cases. The proposed approach for gland and mucosa segmentation achieves an object dice score equal to 0.908 and 0.967 respectively, while for the classification of glands it achieves an F1 score equal to 0.94 showing great potential for the automated quantification and analysis of gastric biopsies.