Distinguishing features of autoimmune gastritis depending on previous H. pylori infection or positivity to anti-parietal cell antibodies: results from the Autoimmune gastRitis Italian netwOrk Study grOup (ARIOSO).

OBJECTIVES: To describe the clinical features and the risk of developing gastric tumors in patients with autoimmune gastritis (AIG). METHODS: This was a retrospective, longitudinal, multicenter study conducted at eight Italian tertiary referral centers. We retrieved clinical data from all histologically proven AIG patients. Differences between H. pylori-exposed vs H. pylori-naïve, and anti-parietal cell antibody (PCA)-positive vs PCA-negative patients were investigated. The rate of gastric adenocarcinoma and type 1 gastric neuroendocrine neoplasm (gNEN) was assessed. A multivariable model for factors associated to gNEN was fitted. RESULTS: 1598 patients with AIG (median age 58 years, IQR 46-68; F:M ratio 2.7:1) were included. H. pylori-naïve patients were more likely to have a first-degree family history of AIG (14.7% vs 8.9%; p=0.012), type 1 diabetes mellitus (4.9% vs 2.3%; p=0.025), and pernicious anemia (30.9% vs 21.1%; p=0.003). PCA-positive patients had significantly more associated autoimmune diseases (59.0% vs 42.9%; p<0.001) and were more likely to have been diagnosed by a case-finding strategy (15.3% vs 2.6%; p<0.001). Overall, 15 cases (0.9%) of gastric adenocarcinoma and 153 cases (9.6%) of gNEN occurred, with a global rate of 0.12 (95% CI 0.07-0.20) and 1.22 (95% CI 1.03-1.42) per 100 person/year, respectively. Having a vitamin B12/iron deficiency manifestation at AIG diagnosis was associated with an 16.44 (95% CI 9.94-27.20 p<0.001) hazard ratio of gNEN. CONCLUSIONS: The "pure" AIG pattern has typical features of an autoimmune disease and seems to be unrelated to H. pylori. In a tertiary referral setting, the risk of developing overt gastric adenocarcinoma is low, while patients with vitamin B12 deficiency complications at onset may benefit from a more intense endoscopic follow-up for early gNEN detection.

Helicobacter Pylori infection in children with inflammatory bowel disease: a prospective multicenter study.

BACKGROUND: The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET). METHODS: IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively. RESULTS: 76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2-17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1-17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065). The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups. At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached. CONCLUSION: The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.

Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective.

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

Incidence and Predictors of Gastric Neoplastic Lesions in Corpus-Restricted Atrophic Gastritis: A Single-Center Cohort Study.

INTRODUCTION: Corpus-restricted atrophic gastritis is a chronic inflammatory disorder leading to possible development of type 1 neuroendocrine tumors (T1gNET), intraepithelial neoplasia (IEN), and gastric cancer (GC). We aimed to assess occurrence and predictors of gastric neoplastic lesions in patients with corpus-restricted atrophic gastritis at long-term follow-up. METHODS: A prospective single-center cohort of patients with corpus-restricted atrophic gastritis adhering to endoscopic-histological surveillance was considered. Follow-up gastroscopies were scheduled according to the management of epithelial precancerous conditions and lesions of the stomach guidelines. In case of new/worsening of known symptoms, gastroscopy was anticipated. Cox regression analyses and Kaplan-Meier survival curves were obtained. RESULTS: Two hundred seventy-five patients with corpus-restricted atrophic gastritis (72.0% female, median age 61 [23-84] years) were included. At a median follow-up of 5 (1-17) years, the annual incidence rate person-year was 0.5%, 0.6%, 2.8%, and 3.9% for GC/high-grade IEN, low-grade IEN, T1gNET, and all gastric neoplastic lesions, respectively. All patients showed at baseline operative link for gastritis assessment (OLGA)-2, except 2 low-grade (LG) IEN patients and 1 T1gNET patient with OLGA-1. Age older than 60 years (hazard ratio [HR] 4.7), intestinal metaplasia without pseudopyloric metaplasia (HR 4.3), and pernicious anemia (HR 4.3) were associated with higher risk for GC/HG-IEN or LG-IEN development and shorter mean survival time for progression (13.4, 13.2, and 11.1, respectively, vs 14.7 years, P = 0.01). Pernicious anemia was an independent risk factor for T1gNET (HR 2.2) and associated with a shorter mean survival time for progression (11.7 vs 13.6 years, P = 0.04) as well as severe corpus atrophy (12.8 vs 13.6 years, P = 0.03). DISCUSSION: Patients with corpus-restricted atrophic gastritis are at increased risk for GC and T1gNET despite low-risk OLGA scores, and those aged older than 60 years with corpus intestinal metaplasia or pernicious anemia seem to display a high-risk scenario.

Update on Serum Biomarkers in Autoimmune Atrophic Gastritis.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important. CONTENT: The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods. SUMMARY: Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.

Pseudopyloric Metaplasia Is Not Associated With the Development of Gastric Cancer.

INTRODUCTION: Corpus atrophic gastritis (CAG) is associated with intestinal metaplasia (IM) and pseudopyloric metaplasia (PPM). Prospective data on corpus mucosa PPM and its link to the development of gastric cancer (GC) are lacking. This study aimed to investigate the relationship between the presence of corpus mucosa PPM at baseline and the development of GC at follow-up in patients with CAG. METHODS: A longitudinal cohort study was conducted on patients with consecutive CAG adhering to endoscopic-histological surveillance. Patients were stratified for the presence/absence of corpus PPM without concomitant corpus IM at baseline, and the occurrence of gastric neoplastic lesions at the longest available follow-up was assessed. RESULTS: A total of 292 patients with CAG with a follow-up of 4.2 (3-17) years were included. At baseline, corpus PPM without corpus IM was diagnosed in 62 patients (21.2%). At the follow-up, GC was detected in 5 patients (1.7%) and gastric dysplasia (GD) in 4 patients (1.4%). In all these 9 patients with GC/GD at the follow-up, corpus IM was present at baseline and follow-up. Age <50 years (odds ratio [OR] 2.5), absence of pernicious anemia (OR 4.3), and absence of severe corpus atrophy (OR 2.3) were associated with corpus PPM without corpus IM. DISCUSSION: At the 4.2-year follow-up, in patients with CAG characterized at baseline with corpus PPM without corpus IM, GC or GD was not observed because these lesions were consistently associated with corpus IM. Corpus PPM without corpus IM was associated with younger age, absence of pernicious anemia, and severe corpus atrophy, suggesting a lower stage of disease progression. Corpus PPM alone seems not to be associated with GC, whose development seems to require the presence of corpus IM as a necessary step.

Current Perspectives in Atrophic Gastritis.

PURPOSE OF THE REVIEW: Atrophic gastritis is a complex syndrome with gastric atrophy as a common trait. Helicobacter pylori infection and autoimmunity are the two main contexts in which it develops. It is slightly symptomatic, affects various aspects of general health, and remains a predisposing factor for gastric cancer. This review will update current knowledge and progress on atrophic gastritis. RECENT FINDINGS: Atrophic gastritis affects mostly adults with persistent dyspepsia, deficient anemia, autoimmunity disease, long-term proton pump inhibitor use, and a family history of gastric cancer. Gastric biopsies, expressed as Sydney system grade and OLGA/OLGIM classifications, represent the gold standard for diagnosis and cancer risk stage, respectively. Recently, electronic chromoendoscopy has allowed "targeted biopsies" of intestinal metaplasia. The associated hypochlorhydria affects the gastric microbiota composition suggesting that non-Helicobacter pylori microbiota may participate in the development of gastric cancer. Physicians should be aware of multifaceted clinical presentation of atrophic gastritis. It should be endoscopically monitored by targeted gastric biopsies. Autoimmune and Helicobacter pylori-induced atrophic gastritis are associated with different gastric microbial profiles playing different roles in gastric tumorigenesis.

Endoscopic grading of gastric intestinal metaplasia (EGGIM): a multicenter validation study.

BACKGROUND: Random biopsies are recommended to identify individuals at risk of gastric adenocarcinoma. Cumulative evidence suggests that narrow-band imaging (NBI) can be used to grade gastric intestinal metaplasia (GIM). We aimed to externally validate a classification of endoscopic grading of gastric intestinal metaplasia (EGGIM). METHODS: Consecutive patients in two centers were submitted to high resolution white-light gastroscopy followed by NBI to estimate EGGIM - a score (0 - 10) resulting from the sum of endoscopic assessments of GIM, scored as 0, 1, or 2 for no GIM, ≤ 30 %, or > 30 % of the mucosa, respectively, in five areas (lesser and greater curvature of both antrum and corpus, and incisura). If GIM was endoscopically suspected, targeted biopsies were performed; if GIM was not noticeable, random biopsies were performed according to the Sydney system to estimate the operative link on gastric intestinal metaplasia (OLGIM; the gold standard). RESULTS: 250 patients (62 % female; median age 55 years) were included. GIM was staged as OLGIM 0, I, II, III, IV in 136 (54 %), 15 (6 %), 52 (21 %), 34 (14 %), and 13 (5 %) patients, respectively. All patients with GIM except three were identifiable with targeted biopsies. For the diagnosis of OLGIM III/IV, the area under the ROC curve was 0.96 (95 % confidence interval [CI] 0.93 - 0.98) and by using the cutoff > 4, sensitivity, specificity, and positive likelihood ratio were 89 %, 95 %, and 16.5, respectively; results were similar (91 %, 95 %, and 18.1) when excluding patients with foveolar hyperplasia. CONCLUSIONS: For the first time, an endoscopic approach was externally validated to determine the risk of gastric cancer without the need for biopsies. This can be used to simplify and individualize the management of patients with gastric precancerous conditions.

Gastroesophageal reflux symptoms and microscopic esophagitis in a cohort of consecutive patients affected by atrophic body gastritis: a pilot study.

AIM: In patients affected by atrophic body gastritis (ABG) gastro-oesophageal reflux (GER) related symptoms have been reported, despite the presence of hypochlorhydria. OBJECTIVE: Objectives of this single-centre study was to assess in ABG the occurrence of GER-related symptoms and their relationship with histopathologic oesophageal findings. MATERIALS AND METHODS: Fifty-four consecutive patients (20.4%male, 57.6 ± 14 years) undergoing to follow-up for ABG, underwent assessment of GER-related symptoms and gastroscopy with multiple gastric and oesophageal biopsies to investigate the presence of microscopic esophagitis (ME). RESULTS: At least one typical GER symptoms were reported in 24.1% with 9.2% of patients complaining of heartburn and 18.5% regurgitation. One or more atypical GERD symptoms were reported in 44.4% of patients. Two symptomatic ABG patients presented oesophageal lesions at endoscopy (one with erosive esophagitis (LA-C) and one with Barrett's oesophagus (C2M2)), 49% reported a mild ME and 24.5% a severe ME. No significant differences regarding GERD prevalence were found among patients with or without ME, but cough was the only symptom significantly more frequent in patients with ME (38.95% vs. 7.7%, p = .042). CONCLUSIONS: These data showed that GERD is present in a quarter of ABG patients, suggesting that hypochlorhydria not exclude per se arising of oesophageal symptoms. In ABG we found that ME is a frequent finding but its clinical relevance remains to be investigated with further studies.

Probiotics and Diverticular Disease: Evidence-based?

Diverticular disease (DD) is a common gastrointestinal condition. Clinical spectrum ranges from asymptomatic diverticulosis to symptomatic uncomplicated or complicated DD. Symptoms related to uncomplicated DD are not specific and may be indistinguishable from those of irritable bowel syndrome. Low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity, and abnormal colonic motility have been identified as factors potentially contributing to symptoms. Probiotics may modify the gut microbial balance leading to health benefits. Probiotics, due to their anti-inflammatory effects and ability to maintain an adequate bacterial colonization in the colon, are promising treatment options for DD. This review focuses on the available evidence on the efficacy of prebiotics in uncomplicated DD.

Gastric precancerous conditions and Helicobacter pylori infection in dyspeptic patients with or without endoscopic lesions.

OBJECTIVE: In dyspeptic patients, esophagogastroduodenoscopy is often negative for visible lesions. Biopsies of the normal-appearing mucosa for Helicobacter pylori detection are not routinely obtained. Diagnostic gain of routine biopsies is still debated. This study aimed to assess the occurrence of H. pylori infection and related gastric premalignant conditions in dyspeptic patients without visible lesions at esophagogastroduodenoscopy and whether the presence/absence of endoscopically visible lesions may address the endoscopist to obtain gastric biopsies. MATERIALS AND METHODS: Post hoc study on endoscopic-histological data from 589 patients with dyspepsia (median age 57 years) obtained during a prospective nationwide study. Patients with dyspepsia as indication for esophagogastroduodenoscopy, never treated for H. pylori, were included. All the patients underwent esophagogastroduodenoscopy with biopsies according to Sydney system. Clinical data were collected using a structured questionnaire. RESULTS: In 66.4% patients, the gastricduodenal mucosa appeared normal at esophagogastroduodenoscopy. In patients with or without visible lesions at esophagogastroduodenoscopy, H. pylori infection (51.5% vs. 50.1%, p = 0.82) and atrophic-metaplastic gastritis (33.3% vs. 27.6%, p = 0.18) were similar. Endoscopically visible lesions were poor predictors for H. pylori infection or gastric precancerous conditions showing positive and negative predictive values of 51.5% and 49.8% for H. pylori and 33.3% and 72.3% for atrophic-metaplastic gastritis. At logistic regression, the presence of H. pylori infection showed a negative association with ongoing antisecretory treatment (OR: 0.67), the presence of visible gastroduodenal lesions was not associated. CONCLUSIONS: Dyspeptic patients with or without visible endoscopic lesions had the same occurrence of H. pylori infection and related premalignant conditions, which might be missed without biopsies, in particular, in patients on anti-secretory treatment.

Occurrence of gastric cancer and carcinoids in atrophic gastritis during prospective long-term follow up.

OBJECTIVE: Atrophic gastritis (AG) is a risk condition for gastric cancer and type I gastric carcinoids. Recent studies assessing the overall risk of gastric cancer and carcinoids in AG at long-term follow up are lacking. This study aimed to investigate in a prospective cohort of AG patients the occurrence of gastric cancer and carcinoids at long-term follow up. METHODS: A total of 200 AG patients from a prospective cohort (67% female, median age 55 years) with a follow up of 7.5 (range: 4-23.4) years were included. Inclusion criteria were presence of AG and at least one follow-up gastroscopy with biopsies at ≥4 years after AG diagnosis. Follow-up gastroscopies at 4-year intervals were performed. RESULTS: Overall, 22 gastric neoplastic lesions were detected (crude incidence 11%). Gastric cancer was diagnosed in four patients at a median follow up of 7.2 years (crude incidence 2%). Eleven type I gastric carcinoids were detected at a median follow up of 5.1 years (crude incidence of 5.5%). In seven patients, six low-grade and one high-grade dysplasia were found. The annual incidence rate person-year were 0.25% (95% confidence interval [CI]: 0.067-0.63%), 0.43% (95% CI: 0.17-0.89%), and 0.68% (95% CI: 0.34-1.21%) for gastric cancer, dysplasia, and type I-gastric carcinoids, respectively. The incidence rates of gastric cancer and carcinoids were not different (p = 0.07). CONCLUSION: This study shows an annual incidence rate of 1.36% person-year for gastric neoplastic lesions in AG patients at long-term follow up. AG patients are similarly exposed to gastric cancer and type I gastric carcinoids.

Gastric cancer in patients with type I gastric carcinoids.

BACKGROUND: Atrophic body gastritis (ABG) is associated with both type I gastric carcinoids (T1-GCs) and intestinal-type gastric cancer. The occurrence of gastric cancer in ABG patients with type I gastric carcinoids has not yet been described. AIM: To describe the occurrence at follow-up of gastric cancer in ABG patients with type I gastric carcinoid in a retrospective case series in a single tertiary referral center. METHODS: Between 1994 and 2012, 17 new cases of T1-GCs were diagnosed among a cohort of ABG patients in a single tertiary referral center for ABG. The clinical charts of these 17 T1-GC patients were retrospectively evaluated for the occurrence of gastric cancer at follow-up (median 4.2 years, range 0.5-13). RESULTS: In 4 (23.5 %)/17 T1-GCs patients (3 females, age 40-78 years), gastric cancer occurred (median follow-up 5.9 years, range 5.1-13). Three cases were intestinal-type adenocarcinomas and one a signet-ring cell diffuse gastric cancer, localized in three cases in the antrum. In two patients, it was detected on random biopsies during follow-up gastroscopy; in the other two, gastroscopy was performed because of new symptoms. All patients with gastric cancer had associated autoimmune features (pernicious anemia, autoimmune thyroid disease and a spared antrum) compared to 77, 46 and 54 % of those without gastric cancer, although statistical significance was not reached. CONCLUSIONS: This case series shows that in patients with T1-GCs, gastric cancer may frequently occur at long-term follow-up. Thus, these patients should be monitored by a long-term surveillance program, including an accurate bioptic sampling of the antral mucosa.

Detection of gastric precancerous conditions in daily clinical practice: a nationwide survey.

BACKGROUND: The burden of gastric precancerous conditions and factors associated with their detection have not been fully investigated in community-based settings. Little is known about adherence to Sydney system for histopathology of gastric biopsies. OBJECTIVE: We aimed to investigate what really happens in clinical practice with regard to the detection of gastric atrophy and intestinal metaplasia in dyspeptic patients. METHODS: We performed a nationwide survey of 979 consecutive patients (50-65 years old) with dyspeptic symptoms, examined at 24 gastrointestinal endoscopy units throughout Italy. Clinical information was collected from questionnaires; a standard bioptic mapping was performed in each unit, biopsies from each patient were analyzed by histopathology performed according to daily clinical practice in each local histopathology center. RESULTS: Separate descriptions of antral and corporal biopsies were included in 679 pathology reports (69%), whereas Sydney system was applied in 324 reports (33%). Gastric atrophy without intestinal metaplasia (GA) and gastric atrophy with intestinal metaplasia (GIM) were detected in 322 (33%) patients. The full adherence to Sydney system significantly increased the probability of detecting GIM (OR 9.6, 95% CI 5.5-16.7), GA (OR 1.92, 95% CI 1.07-3.44), and either of the conditions (OR 6.67, 95% CI 4.36-10.19). CONCLUSIONS: This nationwide survey showed that in one-third of dyspeptic patients, gastric precancerous conditions are detected. In daily routine practice, only 1/3 of histology reports were worked out adhering to Sydney system showing that international guidelines are poorly observed in clinical practice. This may represent a critical element for surveillance strategies for gastric cancer.

Gastric carcinoid in the absence of atrophic body gastritis and with low Ki67 index: a clinical challenge.

BACKGROUND: Gastric carcinoids (GCs) represent 23% of all digestive neuroendocrine tumors (NETs). They can be distinguished into three types: type I (in the presence of atrophic body gastritis, ABG), type II (in the presence of Zollinger-Ellison/multiple endocrine neoplasia type I syndrome), type III (sporadic carcinoids, without any background pathology). AIM: To describe a case of undetermined type of GCs in an Italian referral center for NETs and its prevalence among GCs during a 6-year period. RESULTS: In a case series of 16 GCs seen at our unit between 2007 and 2012, 14 (83.3%) patients had type I carcinoid and 1 patient (6.2%) had type III carcinoid. One patient did not accomplish to the actual classification criteria. This patient had a well-differentiated carcinoid with low Ki67, but multiple gastric biopsies performed at 3-year follow-up gastroscopies excluded the presence of ABG. The patient had fundic cystic polyps, suggesting long-term use of proton pump inhibitors, possibly associated with GCs. CONCLUSIONS: This case shows that a GC may occur in the absence of ABG and with low Ki67 index, making classification according to actual criteria difficult. Further studies are needed to better understand the occurrence of this particular type of GCs.

Updated features associated with type 1 gastric carcinoids patients: a single-center study.

OBJECTIVE: Data on clinical presentation and associated features of patients with type 1 gastric carcinoids (T1-GCs) are scanty. This study aimed to provide detailed data on a series of patients with T1-GCs. MATERIAL AND METHODS: Clinical, laboratory, endoscopic, and histological data were assessed from 31 T1-GCs patients (cross-sectional design), consecutively diagnosed in a tertiary center according to a standardized diagnostic protocol. T1-GCs were diagnosed at baseline or follow-up gastroscopy for atrophic gastritis in 74.2% and 25.8% of patients, respectively. RESULTS: Seventy-one percent of T1-GC patients were female. Age ranged from 23 to 78 (median 58 years). T1-GCs were more frequently diagnosed between 40-49 years (35.5%) and 60-69 years (32.3%) (p = 0.0383). Thyroid disease was present in 54.8% (in 29% autoimmune). All 31 patients had either cobalamin or iron deficiency with or without anemia. Manifest pernicious anemia was present in 67.7% of patients and cobalamin deficiency without anemia in 9.7% patients. Iron deficiency anemia was present in 29% and iron deficiency without anemia in 12.9% of patients. In 48.4% of patients, T1-GCs appeared as polyps, which were single in all cases and had a median size of 4 mm (range 2-15 mm). In patients with polypoid T1-GCs, thyroid disease of autoimmune and nonautoimmune origin (p = 0.0181) was more frequently associated. CONCLUSION: This study shows that T1-GCs may be diagnosed at any age. Autoimmune features are frequently present as well as cobalamin and iron deficiency. The copresence of autoimmune diseases and micronutrient deficiencies should be accurately investigated, in particular in patients with polypoid T1-GCs.

Systematic review and meta-analysis: Risk of gastric cancer in patients with first-degree relatives with gastric cancer.

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

Saponin treatment for eukaryotic DNA depletion alters the microbial DNA profiles by reducing the abundance of Gram-negative bacteria in metagenomics analyses.

Background: Recent advances in microbiome sequencing techniques have provided new insights into the role of the microbiome on human health with potential diagnostic implications. However, these developments are often hampered by the presence of a large amount of human DNA interfering with the analysis of the bacterial content. Nowadays, extensive scientific literature focuses on eukaryotic DNA depletion methods, which successfully remove host DNA in microbiome studies, even if a precise assessment of the impact on bacterial DNA is often missing. Methods: Here, we have investigated a saponin-based DNA isolation protocol commonly applied to different biological matrices to deplete the released host DNA. Results: The bacterial DNA obtained was used to assess the relative abundance of bacterial and human DNA, revealing that the inclusion of 2.5% wt/vol saponin allowed the depletion of most of the host's DNA in favor of bacterial DNA enrichment. However, shotgun metagenomic sequencing showed inaccurate microbial profiles of the DNA samples, highlighting an erroneous increase in Gram-positive DNA. Even the application of 0.0125% wt/vol saponin altered the bacterial profile by depleting Gram-negative bacteria, resulting in an overall increase of Gram-positive bacterial DNA. Conclusion: The application of the saponin-based protocol drastically changes the detection of the microbial composition of human-related biological specimens. In this context, we revealed that saponin targets not only host cells but also specific bacterial cells, thus inducing a drastic reduction in the profiling of Gram-negative bacterial DNA.