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.

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.

Efficacy and Safety of Intravenous Ferric Carboxymaltose Treatment of Iron Deficiency Anaemia in Patients with Corpus Atrophic Gastritis: A Retrospective Study.

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.

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.

Gastric Microbiota Gender Differences in Subjects with Healthy Stomachs and Autoimmune Atrophic Gastritis.

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.

Comparison of Clinical, Biochemical and Histological Features between Adult Celiac Patients with High and Low Anti-Transglutaminase IgA Titer at Diagnosis and Follow-Up.

In adults, celiac disease (CD) diagnosis is based on specific serology (anti-transglutaminase IgA-anti-tTG) and duodenal histology. Evidence is raising the possibility of perform CD diagnosis based only on high anti-tTG titer in children. We aimed to evaluate clinical, histological and biochemical differences between adult patients with high tTG IgA titer (HT) and those with low titer (LT) at CD diagnosis and follow-up. This retrospective study included consecutive adult CD patients divided into two groups: HT (anti-tTG > 10 × ULN) and LT (anti-tTG < 10 × ULN). Clinical, biochemical and histological features were compared between groups at CD diagnosis and at follow-up. A total of 291 patients were included (HT: 47.1%; LT: 52.9%). At CD diagnosis, HT patients showed a non 'classical' presentation (p = 0.04), Marsh 3C (p = 0.005), hypoferritinaemia (p = 0.006) and osteopenia/osteoporosis (p = 0.04) more frequently than LT patients. A total of 216 patients (HT: 48.6%; LT: 51.4%) performed a follow-up after a median Gluten-free diet of 14 months; HT patients had persistent antibodies positivity (p = 0.001) more frequently and GI symptoms (p = 0.04) less frequently than LT patients. In conclusion, HT patients presented severe histological damage more frequently at diagnosis, recovering similarly to LT patients after the start of the Gluten-free diet. At follow-up, anti-tTG persisted positive in HT more frequently compared to LT patients, without differences regarding histological recovery and clinical improvement.

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.

Autoimmune atrophic gastritis and coeliac disease: A case-control study.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is rarely associated with coeliac disease (CD). AIMS: To assess the frequency of AAG-CD association and to compare clinical, biochemical, and histological features of adults affected by both diseases (cases) with AAG controls. METHODS: This case-control study included 9 cases (F55%, median age 47, range 23-59yrs) matched (1:3) by age (±4 yrs) and gender to 27 controls randomly selected from our AAG cohort (2009-2021). The AAG and CD diagnosis was based on internationally agreed criteria. RESULTS: Of 434 AAG patients (median age:62.5yrs, range18-92yrs, F:M ratio=2.2:1),9 had a concomitant diagnosis of CD. The occurrence of AAG-CD association was 2% and 1.65% among AAG/CD cohorts, respectively. Cases were significantly younger than AAG cohort (n = 425, p = 0.002). In 4/9cases, AAG was diagnosed by proactive screening for autoimmune disorders. Autoimmune thyroid disorders were present in 5/9 cases. Cases had a significant higher prevalence of normocytic anaemia than controls (p = 0.004). No significant differences were found between cases and controls concerning clinical and histological features. CONCLUSIONS: AAG-CD association is rare. Gastric and duodenal biopsies might be advisable in young people with normocytic anaemia and associated autoimmune disorders to timely diagnose clinically silent conditions.

The Impact of Proton Pump Inhibitors on the Development of Gastric Neoplastic Lesions in Patients With Autoimmune Atrophic Gastritis.

Introduction: Proton pump inhibitors (PPIs) have been widely prescribed as a primary treatment for acid-related disorders. A large body of literature reported several adverse outcomes due to PPI therapy, including an increased risk of gastric cancer (GC). Autoimmune atrophic gastritis (AAG) is a chronic inflammatory disorder affecting the oxyntic mucosa, leading to mucosal atrophy, intestinal metaplasia, and reduced gastric acid secretion, up to the possible development of dysplasia and intestinal-type GC. Whether PPI use may increase the GC risk in AAG patients has not yet been investigated. We conducted a case-control study in AAG patients to assess the association between the PPI use before AAG diagnosis and the development of GC at follow-up (FU). Materials and Methods: Patients were included from a prospective cohort of AAG patients (diagnosed 1992-2021) in a referral center for gastric autoimmunity; all patients adhered to an endoscopic-histological FU program according to Management of precancerous conditions and lesions in the stomach (MAPS) I/II (management of epithelial precancerous conditions) guidelines. At diagnosis, clinical/biochemical data and PPI use before AAG diagnosis (withdrawn at the time of diagnosis), for at least 12 months, were evaluated. Patients who developed gastric neoplastic lesions (GNLs) at FU were considered as cases; patients without a diagnosis of GNLs at FU were considered as controls. At a total FU of 2.3 years (1-13), 35 cases were identified, and controls were matched 2:1 by age ( ± 3 years), gender, and years of FU (n=70); therefore, a total of n=105 patients were included in the study. Results: The proportion of PPI users before AAG diagnosis was significantly higher in cases than in controls (54.3% vs. 18.6%, p<0.001). At logistic regression, considering as a dependent variable the development of GNLs at FU, a positive association was shown for PPI use before AAG diagnosis (OR 9.6, 95%CI 2.3-40.3), while other independent variables as the use of antiplatelets/anticoagulants (OR 2.8, 95%CI 0.7-12.0), age ≥ 50 years (OR 2.0, 95%CI 0.2-18.1), 1st-degree family history for GC (OR 2.4, 95%CI 0.4-15.2), and smoking habit (OR 0.4, 95%CI 0.1-2.1) were not associated. Conclusions: PPI use before the diagnosis of AAG appears to considerably increase the risk of subsequent GNL development. Considering the common misuse of PPIs, physicians should regularly reevaluate the appropriateness of ongoing PPI therapy, in particular in patients with a clinical suspicion of or already diagnosed AAG.

Sex-Gender Differences in Adult Coeliac Disease at Diagnosis and Gluten-Free-Diet Follow-Up.

Coeliac disease (CD) is an immune-mediated enteropathy triggered by gluten ingestion. At CD diagnosis, gender differences have been previously reported, but data regarding follow-up are scant. We investigated gender differences in CD adult patients both at the time of diagnosis and at follow-up after the start of the gluten-free diet (GFD). This is a longitudinal cohort study on adult CD patients diagnosed between 2008 and 2019. Clinical, biochemical, and histological data were assessed and compared between males and females. At diagnosis, female gender was significantly associated with signs of malabsorption (OR 3.39; 95% CI: 1.4-7.9), longer duration of symptoms and/or signs before the diagnosis (OR 3.39; 95% CI: 1.5-7.5), heartburn (OR 2.99; 95% CI: 1.1-8.0), dyspepsia (OR 2.70; 95% CI: 1.1-6.5), nausea/vomit (OR 3.53; 95% CI: 1.1-10.9), and constipation (OR 4.84; 95% CI: 1.2-19.6) and less frequently associated to higher body mass index (OR 0.88; 95% CI: 0.8-0.9) and osteopenia/osteoporosis (OR 0.30; 95% CI: 0.1-0.7) compared to male patients. After 12-30 months, females presented lower median BMI, performed less frequently histological control, and had more frequently anaemia and hypoferritinaemia compared to males. No significant differences concerning the presence of gastrointestinal symptoms, adherence to GFD, and Marsh score were found. Gender differences found at CD diagnosis mostly disappear at the follow-up, showing that these differences can be solved over time.

Mucosal Overexpression of Thymic Stromal Lymphopoietin and Proinflammatory Cytokines in Patients With Autoimmune Atrophic Gastritis.

INTRODUCTION: The immune mechanisms underlying human autoimmune atrophic gastritis (AAG) are poorly understood. We sought to assess immune mucosal alterations in patients with AAG. METHODS: In 2017-2021, we collected gastric corpus biopsies from 24 patients with AAG (median age 62 years, interquartile range 56-67, 14 women), 26 age-matched and sex-matched healthy controls (HCs), and 14 patients with Helicobacter pylori infection (HP). We investigated the lamina propria mononuclear cell (LPMC) populations and the mucosal expression of thymic stromal lymphopoietin (TSLP) and nicotinamide phosphoribosyltransferase (NAMPT). Ex vivo cytokine production by organ culture biopsies, under different stimuli (short TSLP and zinc-l-carnosine), and the gastric vascular barrier through plasmalemma vesicle-associated protein-1 (PV1) were also assessed. RESULTS: In the subset of CD19+ LPMC, CD38+ cells (plasma cells) were significantly higher in AAG compared with HC. Ex vivo production of tumor necrosis factor (TNF)-α, interleukin (IL)-15, and transforming growth factor ß1 was significantly higher in AAG compared with HC. At immunofluorescence, both IL-7R and TSLP were more expressed in AAG compared with HC and HP, and short TSLP transcripts were significantly increased in AAG compared with HC. In the supernatants of AAG corpus mucosa, short TSLP significantly reduced TNF-α, while zinc-l-carnosine significantly reduced interferon-γ, TNF-α, IL-21, IL-6, and IL-15. NAMPT transcripts were significantly increased in AAG compared with HC. PV1 was almost absent in AAG, mildly expressed in HC, and overexpressed in HP. DISCUSSION: Plasma cells, proinflammatory cytokines, and altered gastric vascular barrier may play a major role in AAG. TSLP and NAMPT may represent potential therapeutic targets, while zinc-l-carnosine may dampen mucosal inflammation.

No Danger for Medical Interest and Awareness towards Celiac Disease. Reply to Greenaway et al. Why Is There Medical Inertia and Nihilism to Celiac Disease? Comment on "Pivetta et al. In Elderly Anemic Patients without Endoscopic Signs of Bleeding Are Duodenal Biopsies Always Necessary to Rule Out Celiac Disease? Diagnostics 2022, 12, 678".

We would like to thank Greenaway et al. [...].

Endoscopic diagnosis of gastric intestinal metaplasia in patients with autoimmune gastritis using narrow-band imaging: does pseudopyloric metaplasia muddy the waters?

Background and study aims In autoimmune atrophic gastritis (AAG), associated with intestinal (IM) and/or pseudopyloric metaplasia (PPM), endoscopic surveillance is recommended for gastric cancer risk mainly linked to IM. Endoscopic Grading of Gastric Intestinal Metaplasia (EGGIM) reliably identifies IM, but has not been assessed in AAG. We aimed to assess the performance of EGGIM (index test) versus histology (reference test) of corpus IM in AAG. Patients and methods This was a cross-sectional study of 210 AAG patients undergoing surveillance gastroscopy with narrow-band imaging (NBI): corpus IM scored according to EGGIM, histology according to updated Sydney system, and morphological criteria. Results NBI identified corpus IM in 88.6 % of AAG patients: EGGIM were 0, 1, 2, 3, 4 in 11.4 %, 0.5 %, 33.3 %, 1.9 %, and 52.9 %, respectively. Histology identified corpus IM in 78.1 % and PPM in 79.5 % of patients. PPM was present with IM in 57.6 % and without IM in 21.9 % patients, 20.5 % had IM without PPM. EGGIM, compared to histology, correctly classified 76.2 % of patients, showing high sensitivity (91.5 %, 95 %CI 86.1-95.3). EGGIM correctly classified 93 % of patients with IM without PPM, 90.9 % with both metaplasias, and 21.7 % with PPM without IM yielding low specificity (21.7 %, 95 %CI 10.9-36.4). Conclusions In AAG, EGGIM showed high accuracy and sensitivity identifying > 90 % of patients with histological corpus IM. EGGIM overestimated IM when PPM without IM was present, yielding low specificity. These findings raise the question of whether in AAG, PPM and IM may display similar endoscopic features on NBI.

Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency.

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.

Gender-sex differences in autoimmune atrophic gastritis.

Gender-sex differences in autoimmune diseases are gaining increasing attention due to their effects on prevalence and clinical features. Data on gender-sex differences in autoimmune atrophic gastritis (AAG), a chronic not-self-limiting inflammatory condition characterized by corpus-oxyntic mucosa atrophy sparing the antrum, are lacking. This study aimed to assess possible gender-sex differences of clinical, serological, histological, and genetic features in AAG patients. Cross-sectional study on 435 patients with histological-AAG, stratified according to female-male gender. In subsets of patients, serum gastric-autoantibodies against intrinsic-factor (IFA) and parietal-cells (PCA) by luminescent-immunoprecipitation-system (LIPS) (n = 81) and of HLA-DRB1-genotyping (n = 89) were available and stratified according to sex. Female AAG-patients were preponderant: 69.2%vs30.8%, P < 0.0001(ratio 2.2:1). Females were more frequently PCA and/or IFA-positive than males (90.9%vs73.1%, P = 0.0361). HLA-DRB1*06-alleles were significantly more frequent in females [30%vs4%, P = 0.01, OR 10.1(95%CI 1.3-80.4); HLA-DRB1*04-alleles were more frequent and HLA-DRB1*03 and *05-alleles less frequent in females without reaching statistical significance. At logistic regression, iron-deficiency-anemia [OR 3.6(95%CI 1.9-7.0)], body-mass-index <25m2/kg [OR 3.1(95%CI 1.7-5.6)], autoimmune-thyroid-disease [OR 2.5(95%CI 1.4-4.5), and dyspepsia [OR 2.4(95%CI 1.4-4.3) were significantly associated to females. Body-mass-index>25m2/kg [OR 3.2(95%CI1.8-5.6)], absence of autoimmune-thyroid-disease [OR 2.3(95%CI 1.3-4.2)] and dyspepsia [OR 2.1(95%CI 1.2-3.7)], smoking habit [OR 1.8(95%CI 1.1-3.1)], and pernicious-anemia [OR 1.7(95%CI 1.0-3.0)], were significantly associated to males. AAG was preponderant in women who showed stronger autoimmune serological responsiveness and different HLA-DRB1 association. AAG showed differential clinical profiles in female and male patients occurring mainly in normal weight, dyspeptic women with iron-deficiency anemia and autoimmune thyroid disease, but in overweight male smokers with pernicious anemia. Stratification for sex and gender should be considered in future genetic, immunological, and clinical studies on autoimmune atrophic gastritis.

Usefulness of 68-Gallium PET in Type I Gastric Neuroendocrine Neoplasia: A Case Series.

Background: Type I gastric neuroendocrine neoplasia (gNEN) is a rare and low-grade tumor in which the therapeutic strategy is almost always endoscopic. For this reason, the use of radiology or nuclear medicine imaging is not recommended by guidelines. Conversely, in a small number of cases, locoregional or distant metastases may develop, thus suggesting a role for imaging techniques. This retrospective study was performed to explore the usefulness of [68Ga]Ga-DOTA-SST PET/CT in the management of patients with T1gNENs. Patients and Method: Single-center retrospective analysis, in an ENETS Center of Excellence, of patients with type I gNEN who underwent [68Ga]Ga-DOTA-SST PET/CT. The indication for performing [68Ga]Ga-DOTA-SST PET/CT was generally based on the presence of at least one of the following criteria: (1) polyps > 10 mm; (2) endoscopic positive (R1) margin after previous endoscopic resection; and (3) Ki-67 > 3%. Results: A total of 120 patients with T1gNEN were evaluated. Overall, 15 out of 120 (13%) patients had performed [68Ga]Ga-DOTA-SST PET/CT. The median Ki-67 value was 6% (IQR 1−9): 9 out of 15 (60%) were G1 tumors, and 6 out of 15 (40%) were G2 tumors. Ninety-three percent of patients were treated by tumor endoscopic resection, whereas surgery was performed in two patients (13%) after incomplete endoscopic resection; the remaining patients (6.6%) received somatostatin analogs due to the presence of multiple recurrent tumors. Overall, [68Ga]Ga-DOTA-SST PET/CT was positive in 8 out of 15 patients (53%). Following the [68Ga]Ga-DOTA-SST PET/CT findings, the clinical management was modified in 6 out of 15 (40%) patients. Conclusion: [68Ga]Ga-DOTA-SST PET/CT can be useful in a restricted and selected group of patients with gastric neuroendocrine neoplasia with relevant risk factors to establish the most appropriate therapeutic strategy.

In Elderly Anemic Patients without Endoscopic Signs of Bleeding Are Duodenal Biopsies Always Necessary to Rule Out Celiac Disease?

Iron-deficiency anemia in the elderly may be due to numerous gastrointestinal conditions. Anemia is frequent in celiac disease (CD); however, the use of routine duodenal biopsies, independently of age or serology, is debated. To determine the diagnostic yield of routine duodenal biopsies in adult and elderly patients with no bleeding anemia, a cross-sectional study analyzing 7968 gastroscopies (2017−2020) was performed; 744 were for anemia and 275 were excluded (GI bleeding or without duodenal biopsies). Of the 469 included patients, clinical, endoscopic, and histological features were analyzed in groups with or without histopathological changes in the duodenal mucosa (DM). Univariate/multivariate analyses were performed. Of the 469 patients, 41 (8.7%) had DM histopathological changes, 12 (2.6%) had CD, 26 (5.5%) had duodenal intraepithelial lymphocytosis (DIL), and 3 had (0.6%) other conditions. They were younger compared to patients with normal DM. DM histopathology was significantly inversely correlated with age group, with prevalences of 27%, 20%, 12.5%, 10%, and 2.5%, in the <40−50, 51−60, 61−70, 71−80, and >80-year age groups, respectively (p = 0.0010). Logistic-regression models showed that anemic patients aged >60, >70, or >80 years with endoscopically normal DM had a progressively three- to four-fold higher probability of having normal duodenal histology. In adults, anemic patients without bleeding, age and endoscopically normal DM are predictors of normal DM histology. In >70-year anemic patients, negligible DM pathology was found. The results suggest that routine duodenal biopsies are questionable in elderly anemic patients

Management of type-I gastric neuroendocrine neoplasms: A 10-years prospective single centre study.

BACKGROUND: This study aimed to evaluate the outcome of patients with type 1 gastric neuroendocrine neoplasia (T1gNENs) treated with different endoscopic approaches. METHODS: Patients were managed with endoscopic surveillance at regular intervals. Resection was performed by forceps or cold snare in tumours < 10 mm, otherwise mucosal resection (EMR) or submucosal dissection (ESD) were done. RESULTS: 127 T1gNENs, detected in 80 patients, were included. 87.4% of them were <5 mm, whereas 8.7% were 6-10 mm, 3.1% were 11-20 mm, and 0.8% was >20 mm. Ki67 <3%% was found in 85.8% tumours, whereas it was 3%-20% in the remaining 14.2% lesions. Noninterventional management (surveillance without radical resection) was performed in 15 patients (18.7%) with T1gNENs <5 mm. None of them underwent disease progression during follow-up. among the 65 patients treated by radical endoscopic resection, 37 patients (56.9%) had disease recurrence. 48.5% T1gNENs were removed by forceps, 16.8% by cold snare, 31.7% by EMR and 3% by ESD. The recurrence rate was similar among the different endoscopic techniques used. CONCLUSIONS: The management of T1gNENs may be planned based on tumour size. T1gNENs < 5 mm for which the initial removal is not radical could be followed up by noninterventional endoscopic surveillance.