Multifocal Atrophic Gastritis Research Articles

Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention.

New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.

Clinical and morphological characteristics of patients with chronic gastritis and high risk of gastric cancer

The purpose of this study is to conduct a clinical and morphological analysis of cases of chronic gastritis with a high risk of gastric cancer (GC). Materials and methods. The study included 26 cases of chronic atrophic gastritis of stages 3 and 4 with a high risk of developing GC according to the assessment using the OLGA system (Operative Link for Gastritis Assessment). The cases were diagnosed on material of gastric tissue biopsy in 2022. In total, 678 histological studies were performed during the year. Cases of chronic gastritis with a high risk of developing GC accounted for 3.8% of all chronic gastritis. Results. Cases of chronic gastritis with a high risk of developing GC were more often observed in older men (average age 67±12 years, ratio 2.25:1). Multifocal atrophic gastritis was in the first place in frequency of occurrence (61.5%), the connection with helicobacter infection was confirmed only in a third of cases (34.6%). Morphological changes were characterized by a predominant lesion of the antrum of the stomach and mixed complete and incomplete intestinal metaplasia. With the exception of one case in which pseudopancreatic metaplasia was detected in the antrum of the stomach, all cases of autoimmune gastritis (n=26) were assigned to stage 2 with a low risk of developing GC, which seems controversial to us. Conclusion. The results of our study showed a high percentage of pre-existing tumor lesions of the stomach in the group of chronic gastritis with a high risk of developing GC. Dysplasia was diagnosed in 5 out of 26 cases, GC with previously performed mucosectomy in 3 out of 26 cases. In addition, the patients had other tumor and precancerous lesions of the gastrointestinal tract. These data show the validity and practical value of using the OLGA system to identify high-risk groups for the development of tumors not only of the stomach, but also of gastrointestinal tumors of other localizations.

Autoimmune Atrophic Gastritis: The Role of miRNA in Relation to Helicobacter Pylori Infection.

IntroductionMicroRNAs (miRNAs) have been proposed as diagnostic markers, biomarkers of neoplastic progression, and possible therapeutic targets in several immune-mediated diseases. We aimed to analyze the expression profile of selected miRNAs (miR21, miR142, miR223, miR155) in patients with autoimmune atrophic gastritis (AAG), patients with non-autoimmune multifocal atrophic gastritis (MAG), and healthy control subjects (HC).Materials and methodsA total of 103 patients with AAG were consecutively recruited for this study among those attending our gastroenterology outpatient clinic. Participating patients were divided into two groups: primary, not Helicobacter pylori (HP)-associated related AAG (n=57, P-AAG) and HP-associated AAG (n=46, HP-AAG); this subgroup included HP-positive patients, patients with previously reported HP infection, and patients harboring antral atrophy, considered as a stigma of HP infection. We also included 20 sex-age-matched MAG patients and 10 HC. Upper endoscopy with gastric biopsies were performed on each AAG and MAG patient. Circulating levels of miR21-5p, miR142-3p, miR223-3p, and miR155-5p were measured by RT-PCR in all groups.ResultsMiR-21 was over-expressed in P-AAG (p=0.02), HP-AAG (p = 0.04), and MAG (p=0.03) compared with HC. By contrast, miR-142 was more expressed in HC than in HP-AAG (p=0.04) and MAG (p=0.03). MiR-155 showed no significant differences among the four subgroups, while, unexpectedly, miR-223 was overexpressed in HC compared to P-AAG (p=0.01), HP-AAG (p=0.003), and MAG (p<0.001), and was higher in P-AAG than in MAG (p=0.05).ConclusionsMiR-21 was over-expressed in patients with gastric precancerous conditions irrespective of etiology, while in the same subgroups miR-142 and miR-223 were under-expressed compared to healthy controls. Controlling miRNAs up- or downregulation could lead to a breakthrough in treating chronic autoimmune diseases and potentially interfere with the progression to cancer.

Immunotyping of lymphocytes in the gastric mucosa of patients infected by H. pylori in two regions with contrast in the risk of developing gastric cancer

To compare the immune response in gas tric mucosa of H. pylori infected patients in two regions comparing the risk of developing gastric can cer. 71 participants with symptoms of dyspepsia were included. The samples for biopsies were collected from different regions of the gastric mucosa; the identification of H. pylori was carried out by culture and polymerase chain reaction (PCR) of the ureA gene. For the characteri zation of the histopathological alterations and the immunophenotyping of lymphocytes, anti-human mouse monoclonal antibodies specific for each antigen were used: T lymphocytes: CD3 and CD8; B lymphocytes: CD20; Natural Killer Cells: CD56; Macrophages: CD68. The prevalence of H. pylori was 83.1%, the predominant types of gastritis were chronic gastritis and multifocal atrophic gastritis with intestinal metaplasia (63.4% and 22.5%, respectively). The cellular response was charac terized mainly by polymorphonuclear lymphocytes and positive anti-CD8 reactivity both in stroma and epithelium. Multifocal atrophic gastritis was more prevalent in the high-risk region for gastric cancer (GC) while non-atrophic gastritis and the expression of CD3 and CD8 antigens in the foveolar epithelium was higher in the low-risk region.

Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection.

Gastric cancer (GC) is the fifth most common cancer and the fourth most common cause of cancer-related death worldwide. The intestinal type of GC progresses from acute to chronic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and carcinoma. Infection of the stomach by Helicobacter pylori, a Gram-negative bacterium that infects approximately 50% of the world’s population, is the causal determinant that initiates the gastric inflammation and then disease progression. In this context, the induction of the innate immune response of gastric epithelial cells and myeloid cells by H. pylori effectors plays a critical role in the outcome of the infection. However, only 1% to 3% of infected patients develop gastric adenocarcinoma, emphasizing that other mechanisms regulate the localized non-specific response, including the gastric microbiota and genetic factors. This review summarizes studies describing the factors that induce and regulate the mucosal innate immune response during H. pylori infection.

Updated Kimura-Takemoto classification of atrophic gastritis.

BACKGROUNDThe Updated Sydney system for visual evaluation of gastric mucosal atrophy via endoscopic observation is subject to sampling error and interobserver variability. The Kimura-Takemoto classification system was developed to overcome these limitations. AIMTo compare the morphological classification of atrophic gastritis between the Kimura-Takemoto system and the Updated Sydney system.METHODSA total of 169 patients with atrophic gastritis were selected according to diagnosis by the visual endoscopic Kimura-Takemoto method. Following the Updated Kimura-Takemoto classification system, one antrum biopsy and five gastric corpus biopsies were taken according to the visual stages of the Kimura-Takemoto system. The Updated Kimura-Takemoto classification system was then applied to each and showed 165 to have histological mucosal atrophy; the remaining 4 patients had no histological evidence of atrophy in any biopsy. The Updated Kimura-Takemoto classification was verified as a reference morphological method and applied for the diagnosis of atrophic gastritis. Adding one more biopsy from the antrum to the six biopsies according to the Updated Kimura-Takemoto classification, constitutes the updated combined Kimura-Takemoto classification and Sydney system. RESULTSThe sensitivity for degree of mucosal atrophy assessed by the Updated Sydney system was 25% for mild, 36% for moderate, and 42% for severe, when compared with the Updated Kimura-Takemoto classification of atrophic gastritis for morphological diagnosis. Four types of multifocal atrophic gastritis were identified: sequential uniform (type 1; in 28%), sequential non-uniform (type 2; in 7%), diffuse uniform (type 3; in 23%), diffuse non-uniform (type 4; in 24%), and "alternating atrophic – non-atrophic" (type 5; in 18%). The pattern of the spread of atrophy, sequentially from the antrum to the cardiac segment of the stomach, which was described by the Updated Kimura-Takemoto system, was histologically confirmed in 82% of cases evaluated.CONCLUSIONThe Updated Sydney system is significantly inferior to the Updated Kimura-Takemoto classification for morphological verification of atrophic gastritis.

Endoscopic surveillance at 3 years after diagnosis, according to European guidelines, seems safe in patients with atrophic gastritis in a low-risk region

BackgroundAutoimmune and multifocal atrophic gastritis (AG) are at risk for gastric neoplastic lesions. European guidelines recommend surveillance with high-quality endoscopy every 3 years. AimTo prospectively investigate the occurrence of gastric neoplastic lesions at the 3-year follow-up in patients with autoimmune and multifocal AG. MethodsLongitudinal cohort study conducted between 2011 and 2019: consecutive patients with histological diagnosis of autoimmune or multifocal AG underwent follow-up gastroscopy 3 years after diagnosis with high-resolution-narrow-band-imaging endoscopes. ResultsOverall, 160 patients were included(F117(73.0%);median age 66(35–87)years). Autoimmune and multifocal AG were present in 122(76.3%) and 38(23.7%) patients, respectively. At the 3-year follow-up, 16(10.0%) patients presented 16 gastric neoplastic lesions: 3(18.7%) gastric cancers, 4(25.0%) low-grade dysplasia, 2(12.5%) low-grade dysplasia adenomas, 7(43.7%) type-1 neuroendocrine tumours. In these patients, OLGA and OLGIM III/IV stages were present in 4(25.0)% and 1(6.3%), respectively; 11(69.0%) presented autoimmune AG, and all but one(93.7%) had parietal cells antibodies positivity (p = 0.026 vs patients without lesions). All lesions were endoscopically(87.5%) or surgically(12.5%) treated with favourable outcome. Age>70 years was associated with a 9-fold higher probability of developing gastric epithelial neoplastic lesions (OR 9.6,95CI% 1.2–79.4,p = 0.0359). ConclusionsThe first endoscopic surveillance 3 years after diagnosis seems safe for autoimmune and multifocal AG patients and should be offered to elderly patients who are at higher risk for gastric neoplasia.

Abstract IA06: Understanding the molecular landscape of gastric premalignant lesions

Abstract Even though the incidence of gastric cancer has been declining over the years, it still has a very high mortality rate. The incidence and mortality of gastric cancer is, however, significantly higher in minority populations with African Americans and Hispanic individuals presenting 52% and 43%, respectively, more cases than Caucasians (data for male patients). Gastric adenocarcinoma has been strongly associated to infection with Helicobacter pylori (H. pylori). The infection triggers an inflammatory cascade, known as the Correa's cascade, that changes the normal gastric epithelium into nonatrophic gastritis (NAG), multifocal atrophic gastritis (MAG), intestinal metaplasia (IM), dysplasia, and cancer. It is known that these events involve immune infiltration and damage to the gastric mucosa; however, there is still too much to learn about the gastric premalignant stages and the evolution of them over time. Over the years we have identified single-nucleotide polymorphisms (SNPs) and differential expression of genes associated with premalignant stages and with evolution of the disease over time. We found that African Americans have increased incidence of advanced premalignant lesions and have more prevalence of infection with H. pylori than Whites. In addition, we found that SNPs and haplotypes in the interleukin 1 b gene (IL1B) are associated with advanced gastritis in African American individuals. Interestingly, the frequency of these inflammatory SNPs and haplotypes is different among African American and Caucasian individuals. In terms of gene expression, we have also found that the increased expression of the gene deleted in malignant brain tumors 1 (DMBT1) is associated with the development of advanced gastritis while the expression of CD44 is associated with progression of the disease over time. Given that CD44 is a molecule involved in the homing of inflammatory cells, its association with progression of premalignant stages over time highlights the role of the immune response in the outcome of these lesions. Interestingly, these immune responses seem to be also modulated by H. pylori itself. We have shown that H. pylori components are able to modulate acquired and innate immune responses. In addition, we have also found a microRNA pattern associated with advanced premalignant gastric lesions in both African Americans and Caucasians. Understanding the molecular landscape of the gastric lesions may help us devise strategies to intervene and limit their progression into more advanced lesions, including gastric cancer. Citation Format: Jone Garai, Maria B. Piazuelo, Maria C. Camargo, Pelayo Correa, Keith Wilson, Jovanny Zabaleta. Understanding the molecular landscape of gastric premalignant lesions [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA06.

Screening, Monitoring, and Treatment of Precancerous Atrophic Gastritis in the Prospective Study for Seven Years.

AIM:Develop a program to identify, treat, and prevent severe atrophic gastritis to reduce gastric cancer incidence and mortality. MAterials and Methods:In total, 2,847 people aged > 40 years old underwent serological noninvasive screening for atrophic gastritis by identifying postprandial gastrin-17 and pepsinogen-1 in the fasting state. Anti-H pylori IgG was found in 2,134 patients. Seven years later, 2,220 patientswho had undergone serological noninvasive screening were asked to fill out a questionnaire survey (were interviewed). We could not find any information on 627 of 2,847 patients. Next, 75 patients with multifocal atrophic gastritis who underwent gastroscopy and biopsies (the Updated Sydney System (USS)) were selected. To study gastrin-17 production, morpho-functional correlation was studies in 75 patients with multifocal atrophic gastritis. Results:During seven years, no reported case of gastric cancer was done among 2,220 persons who underwent serological screening and treatment. In the same population, 4.3 persons who did not receive screening during the same period, developed gastric cancer and died of it. In this study, we can say that 4.3 lives were saved out of 2,220 tested persons. The cost for screening this number of people amounted to €23,750. A comparison of the prevalence rate of the four stages of multifocal atrophic gastritis based on the data of the histopathology tests and noninvasive serologic screening in accordance with OLGA classification showed a strong correlation (the correlation coefficient is 0.812). This finding suggested that using this classification not only for histopathology tests for atrophic gastritis but also for serologic markers of antral mucosa and corpus ventriculi atrophy: gastrin-17 and pepsinogen-1. Conclusion:Complex pathogenetic treatment of atrophic gastritis significantly reduced gastric cancer risk and incidence for such patients.

Modern Possibilities of the Use of Non-Invasive Serological Biomarkers Severe in Population Studies

The ethnic and the gender factors materially affect the prevalence of gastric atrophy.? All the patients were divided into five ethnic groups: Russians, Karachays, Abazins, Circassians, Nogais. The decrease in serum gastrin-17 less than 10 pmol/l is a sensitive and specific biomarker for antral mucosal atrophy, pepsinogen-I less than 25 µg/l is a corpus mucosal atrophy biomarker (Se - 89% and 92%, Sp - 97% and 96%). Gastrin-17 and pepsinogen-I are also sensitive and specific biomarkers for mild, moderate, severe atrophy of the antrum and corpus (for severe antral mucosal atrophy Se - 96%, Sp - 92%, for severe corpus mucosal atrophy Se - 88%, Sp - 97%). A total of 75 patients with multifocal atrophic gastritis were examined histologically. 67 patients had gastrin-17 <10 pmol/l and pepsinogen-I <25 µg/l at the same time. 7 patients had gastrin-17 from 10 to 11.5 pmol/l, 1 patient had gastrin-17 = 19 pmol/l (Se - 89%). Therefore, the level of gastrin-17 and pepsinogen-I simultaneously decreases among patients with multifocal atrophic gastritis. The prevalence of atrophic gastritis is significantly different among some ethnic populations living in the same territory under the same environmental and living conditions. These differences prove the presence of genetic polymorphism in different ethnic groups of the population.

The Microbiota of Gastric Premalignant Lesions: 16S Sequencing Data in a Central American Population

Introduction: Gastric cancer develops through a cascade, from gastritis to atrophic gastritis and gastric intestinal metaplasia, to dysplasia and adenocarcinoma. Helicobacter pylori (Hp) plays a prominent role in this cascade, contributing to the high cancer incidence in regions such as Central America, but the role of other bacteria is less defined. We compared the gastric microbiota of patients with and without premalignant lesions (atrophic gastritis or intestinal metaplasia). Methods: We sequenced the V3—V4 region of the 16S ribosomal RNA gene extracted from gastric corpus biopsies obtained during routine clinical endoscopies at the national university hospital in Leon, Nicaragua. Using the Illumina MiSeq platform and QIIME processing pipeline, we obtained microbiota measures of alpha diversity, beta diversity, and individual taxa-both phyla and operational taxonomic units (OTUs). We compared these measures between groups using the Kruskal—Wallis test. Results: Of 81 subjects, 30 had premalignant lesions and 51 did not, with characteristics described in Table 1. Firmicutes was the dominant phylum in both groups, but only composed 43% of sequences in the premalignant group, compared to 68% of non—premalignant sequences (Figure 1). The difference was related to the Proteobacteria phylum (35% of OTUs in premalignant and 18% in non—premaligant), predominantly from Hp. No differences in alpha or beta diversity existed between groups however, whether calculated with Hp reads included or excluded (Figure 2). Alpha diversity was correlated with number of Hp counts (p<0.001). One OTU was found to be significantly less prevalent in premalignant than non—premalignant samples. The OTU belonged to the Bacillales order of the Firmicutes phylum (p=0.006).1216_A Figure 1 No Caption available.1216_B Figure 2. Summary of phyla detected in gastric biopsy specimens with gastric intestinal metaplasia (GIM), multifocal atrophic gastritis (MAG), non—atrophic gastritis (NAG), and “normal” histology, with H. pylori OTUs included.Conclusion: In this study of the gastric corpus microbiome, premalignant lesions were associated with increasing Hp density and a corresponding decrease in Firmicutes, but otherwise limited differences in microbiota compared to stomachs with minimal or non—atrophic gastritis on histology. Additional areas warranting study include the antrum microbiome and the microbiome in higher risk premalignant lesions (e.g., incomplete gastric intestinal metaplasia or dysplasia).1216_C Figure 3. Box plots of mean alpha diversity of corpus biopsies with and without premalignant lesions (gastric intestinal metaplasia or multifocal atrophic gastritis), according to A) Observed OTUs, B) chao1 index, C) phylogenetic diversity, D) Shannon index. Helicobacter pylori reads are excluded. No significant difference between—group difference was detected for any measure.

Atrophic Body Gastritis: Clinical Presentation, Diagnosis, and Outcome

Atrophic body gastritis is a chronic disorder characterised by atrophy of the oxyntic glands leading to reduced gastric acid and intrinsic factor secretion. Serological studies reported yearly prevalence and incidence rates between 3–9% and 0–11%, respectively. In atrophic body gastritis, the presence of parietal cells and/or intrinsic factor autoantibodies, and autoimmune diseases, such as autoimmune thyroid disease or Type 1 diabetes mellitus, are often observed. These cases are often diagnosed as autoimmune gastritis. This association has been included as part of the autoimmune polyendocrine syndrome. A frequent clinical presentation of atrophic body gastritis is pernicious anaemia, considered an autoimmune condition, arising from vitamin B12 malabsorption as a consequence of intrinsic factor deficiency. Another presentation may be an otherwise unexplained iron deficiency anaemia, as a result of iron malabsorption and consequence of reduced gastric acid secretion. To date, no universally accepted criteria are available to define autoimmune gastritis and to distinguish this clinical entity from chronic, Helicobacter pylori-driven, multifocal atrophic gastritis. In contrast with the classical perception of a silent condition, patients with atrophic body gastritis may complain of a spectrum of gastrointestinal symptoms, ranging from dyspepsia as early satiety, postprandial fullness, and epigastric pain, to gastro-oesophageal reflux symptoms such as regurgitation and heartburn. The timely diagnosis of atrophic body gastritis is important, as this condition puts patients at an increased risk of gastric cancer and other Type 1 carcinoids that may lead to micronutrient deficiencies crucial for erythropoiesis. The present review provides an update on epidemiological and clinical aspects as well as diagnosis and outcome of the disease.

Mo1181 Gastric Intestinal Metaplasia Outcomes: Results From a 17 Year Tertiary Centre Upper GI Surveillance Programme in Ireland

Adenocarcinoma of the stomach is the second leading cause of cancer related death in the world. Gastric intestinal metaplasia (GIM) is an important intermediate stage in the gastric cancer cascade through a series of well-defined precursor lesions including nonatrophic gastritis, multifocal atrophic gastritis, intestinal metaplasia, and dysplasia. The prevalence of GIM is unclear in many parts of the world and few studies have evaluated the rate of progression to gastric cancer in patients with GIM. There is a lack of clarity in published guidelines regarding appropriate surveillance of patients with GIM and there is wide disparity in the management of this premalignant condition.

Increased expression of deleted in malignant brain tumors (DMBT1) gene in precancerous gastric lesions: Findings from human and animal studies.

Helicobacter pylori infection triggers a cascade of inflammatory stages that may lead to the appearance of non-atrophic gastritis, multifocal atrophic, intestinal metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by binding to pathogens. Initial studies showed its deletion and loss of expression in a variety of tumors but the role of this gene in tumor development is not completely understood. Here, we examined the role of DMBT1 in gastric precancerous lesions in Caucasian, African American and Hispanic individuals as well as in the development of gastric pathology in a mouse model of H. pylori infection. We found that in 3 different populations, mucosal DMBT1 expression was significantly increased (2.5 fold) in individuals with dysplasia compared to multifocal atrophic gastritis without intestinal metaplasia; the increase was also observed in individuals with advanced gastritis and positive H. pylori infection. In our animal model, H. pylori infection of Dmbt1−/− mice resulted in significantly higher levels of gastritis, more extensive mucous metaplasia and reduced Il33 expression levels in the gastric mucosa compared to H. pylori-infected wild type mice. Our data in the animal model suggest that in response to H. pylori infection DMBT1 may mediate mucosal protection reducing the risk of developing gastric precancerous lesions. However, the increased expression in human gastric precancerous lesions points to a more complex role of DMBT1 in gastric carcinogenesis.

Is Gastric Xanthelasma an Alarming Endoscopic Marker for Advanced Atrophic Gastritis and Intestinal Metaplasia?

The clinical significance of gastric xanthelasmas is unknown. We conducted a case-control study in order to evaluate whether gastric xanthelasma is an indicator of advanced atrophic gastritis and intestinal metaplasia. The study was conducted among 1400 patients who underwent elective upper endoscopy. Patients with gastric xanthelasma and atrophy and/or intestinal metaplasia constituted the study group (n=55). The control group involved patients with only atrophic gastritis and/or intestinal metaplasia (n=50). Histopathologic findings of the groups including the distribution of atrophic gastritis and/or intestinal metaplasia, operative link on gastritis assessment score, operative link on gastritis intestinal metaplasia assessment (OLGIM) score, and presence of dysplasia and malignancy were compared. Subgroup analysis was performed in order to establish the relation between the characteristics (size, number, and localization) of xanthelasmas, atrophy, and intestinal metaplasia. Multifocal atrophic gastritis was significantly more common in patients with a gastric xanthelasma (41.8 vs. 26.0%, p=0.03). Patients with multiple xanthelasmas had a significantly higher rate of intestinal metaplasia (p=0.02) and a higher OLGIM score (p=0.02) compared to those with a single xanthelasma. Dysplasia was detected in 8 (14.5%) patients with a xanthelasma and 4 (8.0%) patients without a xanthelasma (p=0.2). Gastric xanthelasma(s) is a warning endoscopic sign for the presence of multifocal atrophic gastritis and advanced intestinal metaplasia.

The homing receptor CD44 is involved in the progression of precancerous gastric lesions in patients infected with Helicobacter pylori and in development of mucous metaplasia in mice

Infection with Helicobacter pylori (H. pylori) leads to inflammatory events that can promote gastric cancer development. Immune cells transition from the circulation into the infected mucosa through the interaction of their receptors and ligands in the endothelial compartment. CD44 expression is increased in advanced gastric lesions. However, the association of this molecule with the progression of these lesions over time has not been investigated. In addition, there is a lack of understanding of the CD44-dependent cellular processes that lead to gastritis, and possibly to gastric cancer. Here we studied H. pylori-positive subjects with gastric lesions that ranged from multifocal atrophic gastritis to dysplasia to determine gene expression changes associated with disease progression over a period of 6 years. We report that CD44 expression is significantly increased in individuals whose gastric lesions progressed along the gastric precancerous cascade. We also show that CD44−/− mice develop less severe and less extensive H. pylori-induced metaplasia, and show fewer infiltrating Gr1+ cells compared to wild type mice. We present data suggesting that CD44 is associated with disease progression. Mechanisms associated with these effects include induction of interferon gamma responses.

Genetic Variations and Gastric Cancer Risk

Gastric cancer used to be the leading cause of cancer deaths in the world until the 1980 when it was overtaken by lung cancer.1 Nowadays, stomach cancer is the second leading cause of cancer death in both sexes worldwide. In spite of worldwide global decrease, in 2020 (using computing models), the prevalence of gastric cancer is expected to rise in Portugal, for both sexes (Globocan). Most patients die during the first year after the diagnosis, even if submitted to costly and aggressive therapy.2 Intestinal type is more frequently observed in older patients and represents the end product of a cascade of events that begin with multifocal atrophic gastritis after exposure to environmental risk factors like Helicobacter pylori (H. pylori) infection. This is usually accompanied by intestinal metaplasia and leads to cancer via dysplasia.3 This lengthy process, commonly known as Correa Cascade, is dependent on continued chronic inflammation.4--6 Unlike intestinal gastric cancer, the diffuse type typically develops following chronic inflammation without passing through the intermediate steps of glandular atrophy and intestinal metaplasia. So far, H. pylori gastritis is the only universal precursor condition for this subtype of gastric cancer.7,8 Significant advances toward the understanding of gastric carcinogenesis have been achieved since the identification of H. pylori by Marshall and Warren in 1984,9 and its latter classification as a class I carcinogen by the International Agency for Research on Cancer. Colonization is usually asymptomatic and tumor progression only occurs in a subset

Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase.

Helicobacter pylori infection causes gastric cancer, the third leading cause of cancer death worldwide. More than half of the world's population is infected, making universal eradication impractical. Clinical trials suggest that antibiotic treatment only reduces gastric cancer risk in patients with non-atrophic gastritis (NAG), and is ineffective once preneoplastic lesions of multifocal atrophic gastritis (MAG) and intestinal metaplasia (IM) have occurred. Therefore, additional strategies for risk stratification and chemoprevention of gastric cancer are needed. We have implicated polyamines, generated by the rate-limiting enzyme ornithine decarboxylase (ODC), in gastric carcinogenesis. During H. pylori infection, the enzyme spermine oxidase (SMOX) is induced, which generates hydrogen peroxide from the catabolism of the polyamine spermine. Herein, we assessed the role of SMOX in the increased gastric cancer risk in Colombia associated with the Andean mountain region when compared with the low-risk region on the Pacific coast. When cocultured with gastric epithelial cells, clinical strains of H. pylori from the high-risk region induced more SMOX expression and oxidative DNA damage, and less apoptosis than low-risk strains. These findings were not attributable to differences in the cytotoxin-associated gene A oncoprotein. Gastric tissues from subjects from the high-risk region exhibited greater levels of SMOX and oxidative DNA damage by immunohistochemistry and flow cytometry, and this occurred in NAG, MAG and IM. In Mongolian gerbils, a prototype colonizing strain from the high-risk region induced more SMOX, DNA damage, dysplasia and adenocarcinoma than a colonizing strain from the low-risk region. Treatment of gerbils with either α-difluoromethylornithine, an inhibitor of ODC, or MDL 72527 (N(1),N(4)-Di(buta-2,3-dien-1-yl)butane-1,4-diamine dihydrochloride), an inhibitor of SMOX, reduced gastric dysplasia and carcinoma, as well as apoptosis-resistant cells with DNA damage. These data indicate that aberrant activation of polyamine-driven oxidative stress is a marker of gastric cancer risk and a target for chemoprevention.

Helicobacter pylori DNA methyltransferases and the epigenetic field effect in cancerization.

Helicobacter pylori, a Gram-negative, microaerophilic bacterium, has co-existed with humans beings as a prominent member of their gastric microbiota for approximately 105 years (Moodley et al., 2012). It infects approximately half the world's population, and most infected individuals are asymptomatic, but histologically exhibit superficial gastritis (The EUROGAST Study Group, 1993). Only a minority of infected individuals develop gastric or duodenal ulcers that necessitate treatment. Prolonged inflammation caused by chronic (often lifelong) infection predisposes a small fraction of infected individuals to develop gastric adenocarcinoma or lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) (Passaro et al., 2002). Unfortunately, the prognosis for cases of gastric cancer is very poor, with 5-year survival rates being lower than 15% (Peek and Blaser, 2002). A mechanism for carcinogenesis ensuing from H. pylori-triggered inflammation was first proposed by Pelayo Correa (Correa, 1992; Correa and Piazuelo, 2012). Briefly, chronic inflammation causes superficial gastritis that progresses over time to multifocal atrophic gastritis (MAG), characterized by the destruction of gastric glands. This is followed by intestinal metaplasia, wherein gastric epithelium undergoes an “epithelial-mesenchymal transition” and begins to exhibit an intestinal phenotype. The subsequent stage consists of dysplasia culminating in invasive carcinoma, which completes the “pre-cancerous cascade.” The final outcome is also dependent on host and pathogen genotypes, as well as environmental factors such as socioeconomic indicators, a high-salt diet, low fruit/vegetable intake and smoking (Khalifa et al., 2010). Most notably, H. pylori is the sole bacterium to be classified by the WHO as a class I carcinogen (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 1994).

Autoimmune gastritis: novel clues to histological diagnosis

To compare the histological features of a consecutive biopsy series of autoimmune gastritis (AIG) with other forms of chronic gastritis to identify morphological clues to the diagnosis. Morphological features in gastric biopsies were examined in 42 prospectively identified patients with AIG without concomitant neoplasia (n = 184 biopsies), 50 normal controls (NGB; n = 118 biopsies), 52 Helicobacter associated gastritis (HPG; n = 123 biopsies), 16 multifocal atrophic gastritis (MAG; n = 62 biopsies) and 50 chronic pangastritis without defined cause (CG; n = 117 biopsies). In AIG, inflammation was characterised by lymphocyte infiltration into the epithelium (98%), basal lymphoid aggregates (82.7%), basal predominance (59.6%), eosinophil infiltration [mean 34.5/high power field (HPF), >30 eosinophils/HPF in 46.1%] and neutrophil infiltration (44.2%). Architectural abnormality was characterised by muscularis mucosae thickening (92.9%) and gland irregularity (86.5%). Pancreatic metaplasia was identified in 21.2% of cases. Compared to NGB, HPG, MAG and CG, AIG displayed more eosinophil infiltration (p < 0.001) and more frequent lymphocyte infiltration of the epithelium, basal predominant inflammation and pancreatic acinar metaplasia (all p > 0.05). Basal predominance of inflammation, lymphocyte infiltration into gland epithelium, prominent eosinophils, architectural irregularity and muscularis mucosae thickening are common in AIG and are helpful when biopsy site and/or clinical history is uncertain.