Introduction

Corpus atrophic gastritis (CAG) is associated with vitamin B12 deficiency. Untreated vitamin B12 deficiency can lead to megaloblastic anaemia (also known as Pernicious Anaemia) and other potential serious clinical manifestations such as acute cardiocerebral events and severe neurological consequences, thus timely B12 supplementation is relevant. To date, the dosage of intramuscular B12 supplementation in CAG patients with vitamin B12 deficiency is not standardized.

Aims & Methods

The aim was to assess the efficacy of cyanocobalamin treatment (Tx) at long term follow-up and predictors of increased cyanocobalamin requirement.
A monocentric retrospective longitudinal cohort study was conducted on 190 pts (62.1% F, age 63±1 yrs) consecutively diagnosed (2007-2021) with CAG and vitamin B12 deficiency. Inclusion criteria were age >18 years, histological diagnosis of CAG (updated Sydney System), serum B12 <250 pg/ml, intramuscular cyanocobalamin supplementation, and follow-up of at least 12 mos. Demographic, clinical, biochemical, and histological data were retrospectively collected. After the diagnosis of vitamin B12 deficiency pts were first treated with TxA schedule (5000μg intramuscular cyanocobalamin every 5 days for 3 times, followed by 5000μg intramuscular every 3 mos (20000μg/yr)), and revaluated at follow up. If TxA was not sufficient to restore B12 levels, TxB was prescribed (5000μg intramuscular cyanocobalamin every 5 days for 3 times, followed by 5000μg intramuscular cyanocobalamin every 2 mos (30000μg/yr)). Primary Tx endpoint was B12 normalization. Baseline and follow-up data of pts on TxA and TxB were compared by Student's t-test. Logistic regression was performed to find out predictors of increased B12 need.

Results

Macrocytic anaemia was mild, moderate and severe in 60, 17, 14 out of 190 pts, while 94 pts had vitamin B12 deficiency without anaemia. TxA efficaciously corrected vitamin B12 deficiency in 130 (68.4%) pts and was maintained until longest available follow-up (41±2.4 mos). The remaining 60 (31.6%) pts, due to persistent vitamin B12 deficiency observed at 12 (6-48) mos, were switched to TxB which was then maintained until longest available follow-up (49.9±4.1 mos). At longest available follow-up, a significant increase of Hb (TxA: 12±0.2 vs 13.1±0,2; TxB: 12.1±0.4 vs 13.8±0.2, p<0,0001) and B12 (TxA: 162.9±8.6 vs 400±22.2; TxB: 142.3±11.2 vs 323.4±22.3, p<0.001) was shown in both schedules. A significant decrease of MCV was shown in TxB only (96.4± 2.1 vs 88.1±0.9,p=<0.0001). At logistic regression, switch to TxB was associated with severe intestinal metaplasia (OR10.6, IC 95% 2.6-43.0, p=0.0009) and macrocytosis at diagnosis (OR2.8, IC95% 1.1-6.9, p=0.0231), and male gender (OR 2.5, IC95% 1.1-5.7, p=0,0213), while other features such as age, severity of vitamin B12 deficiency, previous vitamin B12 therapy, concomitant iron deficiency were not significantly associated with increased need of intramuscular cyanocobalamin.

Conclusion

At long term follow-up, about 70% of pts restore vitamin B12 deficiency with 5000μg intramuscular cyanocobalamin every 3 mos, while only 30% require an increased dosage of 5000μg intramuscular cyanocobalamin every 2 mos. In particular, male pts with severe intestinal metaplasia and macrocytosis at diagnosis require a higher dosage of cyanocobalamin to obtain B12 normalization. In CAG pts with vitamin B12 deficiency regular clinical-biochemical follow-up is important to monitor efficacy of B12 treatment to restore B12 levels and to treat and prevent clinical manifestations of vitamin B12 deficiency.

References

Lenti MV, Rugge M, Lahner E, Miceli E, Toh B-H, Genta RM, et al. Autoimmune gastritis. Nat Rev Dis Primers. (2020);
Green R, Allen L, Bjørke-Monsen A et al. Vitamin B 12 deficiency. Nature reviews | Disease primers (2017);
Devalia V, Hamilton MS et al. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. British Journal of Haematology (2014);

Introduction

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by corpus oxyntic mucosa atrophy and impaired gastric acid secretion(1,2). The increased gastric cancer (GC) risk in AAG is still debated. One mechanism favoring gastric carcinogenesis may be increased intragastric pH leading to intragastric microenvironment changes and facilitating bacterial dysbiosis(3-5). Oral microbiota and periodontal-dental disorders alterations have been linked to increased GC risk as well(6-8). In AAG, the increased intragastric pH may lead to survival of swallowed bacteria, possibly further contributing to the increased GC risk. The oral and gastric microbiota composition together have not been investigated so far in AAG patients.

Aims & Methods

The aim of the study was to investigate the oral and gastric microbiota composition in AAGpts in order to clarify the role of oral bacteria in gastric dysbiosis.
We conducted a case-control study: n=20 histologically diagnosed AAGpts(F75%,age 64 yrs) and n=20 ctrs with healthy stomach(HS)(F45%,age 56 yrs). From all pts and ctrs a sputum sample was obtained in the morning fasting without tooth brushing. Within 1 hour after sputum collection, pts and ctrs underwent gastroscopy with biopsies (updated Sydney system) for histopathological assessment and one further corpus biopsy for DNA extraction. Sputum(n=40) and biopsy(n=40) samples were collected in vials with DNA shield and frozen at -20°C since processing. DNA was extracted (QIAmp DNA kit) and prepared (Illumina Nextera XT DNA Library Preparation Kit). Paired-end sequencing was performed (Illumina MiSeq sequencer,MiSeq Reagent Kit v3). Fastq files were filtered to remove low-quality reads; filtered reads were taxonomically classified and subjected to Homo sapiens filtering (METAnnotatorX2 pipeline, up-to-date RefSeq database, NCBI).

Results

AAGpts and ctrs were similar with regard to clinical features, oral hygiene and paraodontal-dental disorders. Bacterial abundance in biopsies was higher in AAGpts than in ctrs (403 vs 223,p=0.06), but not different in sputum (27,728 vs 31,544,p=0.54). On biopsies, AAGpts showed a lower Shannon Index than ctrs (2.553 vs 2.617, p=0.001). On sputum, AAGpts showed a higher Shannon Index than ctrs (2.828 vs 2.738, p=0.0). Beta-diversity (Bray-Curtis dissimilarity) was not different between pts and ctrs, neither in sputum nor biopsies.
At the taxa level, in biopsies Streptococcus oralis, Fusobacterium pseudoperiodonticum, Veillonella rogosae, and Gemella sanguinis were significantly associated with pts(p<0.03); while in sputum the most significant associations were G.sanguinis, Prevotella multisaccharivorax, F.nucleatum, and F.peridonticum(p<0.03). The most abundantly shared taxa between sputum and biopsy were S.oralis and P.histicola, while G.sanguinis, F.pseudoperidonticum, and V.rogosae were shared in pts only.

Conclusion

This study confirmed gastric dysbiosis in AAG as shown by lower biodiversity and evenness. Gastric bacterial abundance was higher in AAG, probably due to non-acidic gastric pH permitting overgrowth of gastric bacteria. Oral bacterial abundance was similar in AAG and ctr with higher biodiversity-evenness in AAG pts, probably due to upstream passage of unactivated bacteria from stomach to mouth. Oral taxa related to increased GC risk were more commonly associated to AAG and shared between mouth and stomach. In AAG these findings show the role of oral microbiota in gastric dysbiosis, possibly contributing to increased GC risk.

References

1) Lenti MV,Rugge M,Lahner E,Miceli E,Toh BH,Genta RM,De Block C,Hershko C,Di Sabatino A. “Autoimmune gastritis” Nat Rev Dis Primers. 2020 Jul 9;6(1):56.
2) Rugge M,Genta RM,Malfertheiner P,Dinis-Ribeiro M,El-Serag H,Graham DY,Kuipers EJ,Leung WK,Park JY,Rokkas T,Schulz C,El-Omar EM;RE.GA.IN;the Real-world Gastritis Initiative-updating the updates. Gut. 2024 Feb 23;73(3):407-441. doi: 10.1136/gutjnl-2023-331164. PMID: 38383142.
3) Conti L, Annibale B, Lahner E. Autoimmune Gastritis and Gastric Microbiota. Microorganisms. 2020;8(11):1827. Published 2020 Nov 19. doi:10.3390/microorganisms8111827
4) Lin L, Li W, Yan L, et al. Comparison of gastric microbiota in patients with different gastric lesions in high and low risk areas of gastric cancer. BMC Microbiol. 2025;25(1):202. Published 2025 Apr 9. doi:10.1186/s12866-025-03926-4
5) Conti L, Borro M, Milani C, et al. Gastric microbiota composition in patients with corpus atrophic gastritis. Dig Liver Dis. 2021;53(12):1580-1587. doi:10.1016/j.dld.2021.05.005
6) Huang C, Li Y, He C. Oral microbes and gastrointestinal cancers: new strategies and insights. Clin Transl Oncol. Published online April 5, 2025. doi:10.1007/s12094-025-03891-4
7) Xia R, Jiang Z, Zhou Y, et al. Oral microbiota and gastric cancer: recent highlights and knowledge gaps. J Oral Microbiol. 2024;16(1):2391640. Published 2024 Aug 16. doi:10.1080/20002297.2024.2391640
8) Aguiar FJN, Menezes FDS, Fagundes MA, et al. Gastric adenocarcinoma and periodontal disease: A systematic review and meta-analysis. Clinics (Sao Paulo). 2024;79:100321. Published 2024 Jan 31. doi:10.1016/j.clinsp.2023.100321

Introduction

Corpus Atrophic Gastritis (CAG) is a precancerous inflammatory condition of the oxyntic mucosa. Up today, two types of CAG are distinguished: 1) autoimmune (corpus-restricted), defined for CAG sparing the antrum 2) Helicobacter pylori (Hp)-related (multifocal), which involves antrum too.
Antrum involvement/sparing is crucial for both CAG definition as autoimmune and gastric cancer risk level, which is increased in case of pan-atrophy/pan-metaplasia, according to OLGA and OLGIM scores. CAG natural history is still poorly known, especially regarding antrum evolution. In cases with previous antral involvement, possible antrum healing after cure of Hp infection was formerly described. So, given the importance of the criterium antrum-sparing, we aimed to assess antral mucosa changes at long-term follow-up(FU) beside baseline in a cohort of CAG patients.

Aims & Methods

Given the importance of the criterium antrum-spared, we aimed to assess antral mucosa changes at long-term follow-up(FU) beside baseline in a cohort of CAG patients.
We performed a retrospective study on 130 patients with CAG and antrum involvement according to updated Sydney System. Mean time of FU gastroscopy was 40.6(range 4-192) months. In 13 patients corpus atrophy was not confirmed at FU, so were excluded. At baseline, among the remaining 117 patients [mean age 63 (range 20-87) years; F 67.5%], 47 (40.2%) had antral non-atrophic and 70 (59.8%) had antral atrophic gastritis, metaplastic in 84.3%. Histologically diagnosed Hp infection was present in 27.3% of patients, all receiving eradication therapy, anti-parietal cells antibodies (APCA) were positive in 53.8%.

Results

At FU 29/117(24.8%) of patients with tout-court involved antrum showed a complete restitutio ad integrum of antral mucosa. In particular, on 70 cases with antral atrophy at baseline, atrophy regressed in 15 (21.4%). Hp infection at baseline was present in 38% of patients who reported complete antral healing at FU, cured in all but one. Both antral healing and atrophy regression were found to be similar in Hp-cured and not-cured/negatives (p>0.05). In 8 patients (6.8%) a worsening of antral histology at FU was reported: 5 developed antral atrophy, not present at baseline, and 3 antral atrophic patients developed intestinal metaplasia.

Conclusion

Nearly 25% of CAG patients with antral involvement showed complete antrum healing, with regression of baseline antral atrophy in 21.4%. Antral healing occurred also in patients without history of Hp infection and/or eradication. These data suggest that in CAG natural history, concomitant antral involvement may regress irrespective of Hp cure, implying cancer risk reduction and raising queries about histology as sole criteria diagnostic for autoimmune gastritis.

References

1. Lahner et al. Dig LIver Dis 2019
2. Sipponen P et al. Gastroenterology clinics of North America 2000
3. Annibale B Helicobacter 1997

Introduction

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by atrophy of the gastric corpus mucosa and preservation of the antrum. This condition is marked by the replacement of specialized oxyntic glands with pseudopyloric metaplasia (PPM) and/or intestinal metaplasia (IM) (1,2). Two main subtypes of gastric IM have been described: complete (cIM) which resembles the epithelium of the small intestine, containing Paneth cells (PanC), absorptive cells with a brush border (BB), and goblet cells (gobC), and incomplete (icIM) which exhibits histological features similar to the colonic epithelium, typically lacking PanC and/or absorptive cells (3,4). Gastric IM may progress to dysplasia (GD) and ultimately to cancer (GC), with the icIM subtype being more strongly associated with an elevated risk of neoplastic transformation (2,5).Surveillance of atrophic gastritis is particularly recommended in icIM (6,7). AAG has been reported to be associated to cIM rather than icIM(8) and also for this reason GC risk in AAG has been reported to be negligible (9).

Aims & Methods

To characterize the IM subtype in AAG patients who developed GC or GD in order to clarify the relationship between cIM or icIM and gastric neoplastic lesions in AAG.
We conducted a case-control study by performing histopathological assessment of gastric IM on formalin-fixed paraffin-embedded gastric corpus mucosa biopsies obtained from two groups:
1) cases (AAG GC+ or GD+): AAG pts (n=15, F 86%, median age 69) who developed GC (n=8) or GD (n=8) at AAG diagnosis or during long-term follow-up (FU) (median 7, range 0-13 yrs).
2) controls (AAG GC-GD-): AAG pts (n=38, F 60%, age 56 yrs) monitored for at least once 3 yrs after diagnosis who did not develop GC or GD over long-term FU (median 6 yrs, 3-17).
AAG was histologically diagnosed (1,2) and pts (cases or controls) with H.pylori (Hp) positivity at histology and/or serology and/or previous history of Hp were excluded.
Histopathological subtyping of gastric IM was performed on haematohylin-eosin-stained slides. cIM was defined by the presence intestinal metaplastic epithelium containing Paneth cells (PanC), goblet cells (gobC) and absorptive enterocytes with a brush border (BB)(9).

Results

AAG GC+GD+ (cases, n=15) and AAG GC-GD- (controls, n=37) were similar for sex, age, 1^st degree family history of GC, parietal cell autoantibodies positivity, presence of PPM and long-term FU.
The presence of PanC (13/15, 87% vs 31/37, 84%, p=0.80), gobC (15/15, 100% vs 37/37, 100%, p=1.00), and BB (14/15, 93% vs 35/37, 95%, p=0.86) was similar in AAG GC+GD+ and AAG GC-GD- pts. The presence of all 3 markers of cIM (PanC, gobC, BB) was found in 12/15 (80%) AAG GC+GD+ and 31/37 (81%) AAG GC-GD- pts (p=0.75). Also, the various combinations of these markers (PanC+gobC, PanC+BB, gobC+BB) were similar between groups: 87% vs 81%, 67% vs 81%, and 93% vs 95%, respectively (p>0.05). All pts had at least 2 of 3 markers.

Conclusion

Eighthy percent of AAG pts with GC or GD exhibited all defining histological features of cIM, including the presence of PanC, gobC, and absorptive cells with a BB, compared to 81% of AAG pts without neoplastic lesions.
In AAG with and without GC or GD, cIM is more common than icIM and gastric neoplastic lesions may occur in the absence of icIM. Therefore, icIM is not reliable as predictor for neoplastic risk and further studies are needed to identify new markers of neoplastic progression in AAG pts.

References

1) Lenti MV et al. Autoimmune gastritis. Nat Rev Dis Primers 2020
2) Rugge M et al. RE.GA.IN: the Real-world Gastritis Initiative-updating the updates. Gut 2024
3) El Zimaity HMT et al. Gastric intestinal metaplasia: subtypes and natural history. J Clin Pathol 2001
4) Sugano K et al. Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer? Gastroenterology 2023
5) Du S et al. Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies. Clinical and Translational Gastroenterology 2021
6) Shah SC et al. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021
7) Dinis-Ribeiro M et al. Management of epithelial precancerous conditions and early neoplasia of the stomach (MAPS III): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG) and European Society of Pathology (ESP) Guideline update 2025. Endoscopy 2025
8) Genta R et al. Incomplete Intestinal Metaplasia Is Rare in Autoimmune Gastritis. Dig Dis 2023
9) Rugge M et al. Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients. Gut 2023

Introduction

Autoimmune atrophic gastritis (AAG) leads to significant changes in the gastric mucosa, including hypo-achlorhydria and increased gastrin (G) levels, providing proliferative stimuli on the gastric mucosa (1-5).

Aims & Methods

The aim of our study is to evaluate the occurrence and characteristics of gastric polyps in AAG patients across six tertiary centers in Italy. We conducted a multicentric, cross-sectional study from January to June 2023, prospectively enrolling consecutive patients diagnosed with AAG, from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, serological data, and endoscopic and histopathological findings were collected.

Results

Among 612 AAG patients (73.9% female, median age 66) followed up for a median of 4 (IQR 2-7.5) years, 222 (36.3%) had at least one gastric polyp. Non-endocrine polyps (214) were found in 162 patients, including 151 (70.5%) inflammatory, 29 (13.6%) adenomatous, 18 (8.4%) fundic gland polyps, 13 (6.1%) adenocarcinomas, and one MALT lymphoma. Additionally, 108 patients (48.6% of the population with polyps and 17.6% of the overall AAG patients) presented with gastric neuroendocrine neoplasms (gNENs), 48 of whom also had non-endocrine polyps. The median polyp size was 4 (IQR 2-7) mm. Older age, smoking prevalence, and higher levels of G and chromogranin A (CgA) were associated with polyp presence. No significant differences in OLGA/OLGIM stages or H. pylori status were noted between patients with and without polyps.

Conclusion

This study represents the largest multicentric cohort of AAG patients, highlighting the significant presence of gastric polyps, including gNENs and various non-endocrine types including a not negligible proportion of patients who showed gastric adenocarcinoma. These results emphasize the importance of proactive endoscopic monitoring and comprehensive histopathological evaluation in patients with AAG, to effectively identify and manage these different gastric lesions.

References

1. Zhang H, Jin Z, Cui R, Ding S, Huang Y, Zhou L. Autoimmune metaplastic atrophic gastritis in chinese: a study of 320 patients at a large tertiary medical center. Scand J Gastroenterol. 2017;52(2):150-6.
2. Krasinskas AM, Abraham SC, Metz DC, Furth EE. Oxyntic mucosa pseudopolyps: a presentation of atrophic autoimmune gastritis. Am J Surg Pathol. 2003;27(2):236-41.
3. Kishino M, Nonaka K. Endoscopic Features of Autoimmune Gastritis: Focus on Typical Images and Early Images. J Clin Med. 2022;11(12).
4. Park JY, Cornish TC, Lam-Himlin D, Shi C, Montgomery E. Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting. Am J Surg Pathol. 2010;34(11):1591-8.
5. Massironi S, Elvevi A, Gallo C, Laffusa A, Tortorella A, Invernizzi P. Exploring the spectrum of incidental gastric polyps in autoimmune gastritis. Dig Liver Dis. 2023.

Introduction

Atrophic gastritis(AG) is mainly caused by Helicobacter pylori(Hp)infection or autoimmunity. Hp-related AG affects both corpus and antral mucosa resulting in multifocal AG(MF-AG), whereas AG driven by autoimmunity is corpus-restricted(CR-AG).
Corpus mucosa gastric atrophy carries an increased risk of gastric dysplasia(GD) and cancer(GC);the neoplastic risk in CR-AG is considered lower, but still debated. GD-GC lesions in AG may arise in the antrum, incisura angularis or, less frequently,the corpus.Data on characteristics and potential differences of GD-GC lesions between MF-AG and CR-AG are lacking.

Aims & Methods

This study aimed to assess clinical,endoscopic,and histological characteristics of GD-GC in MF-AG and CR-AG pts.
A multicenter,cross-sectional study was conducted across 14 Italian GI centers. Data on GD-GC in patients with MF-AG or CR-AG(2001-2023) were retrospectively collected based on clinical,endoscopic, and histological charts: site,dimension,endoscopic,and histologic features of GD-GC, perilesional gastric antral and corpus mucosa(updated Sydney system),and patients’ clinical data (age,sex,outcome after GD-GC diagnosis,Hp infection, parietal cell antibodies(PCA), family history for GC). Inclusion criteria were:patients with MF-AG or CR-AG and GD or GC diagnosis,aged>18 years, availability of endoscopic and histological description of GD-GC and perilesional gastric mucosa, completeness of clinical data.Data were stratified for MF-AG/CR-AG and the GD-GC, perilesional mucosa, and clinical characteristics were compared.

Results

A total of 84 pts[(F46[54.8%];age 70(33-90yrs)] were included. MF-AG and CR-AG were observed in 45(53.6%) and 39(46.4%) pts,respectively. High-grade(HG)-GD,low-grade(LG)-GD,and non-cardia GC were diagnosed in 6(7.1%),31(36.9%), and 47(56.0%)pts.
Age, GC family history,smoking habits, and PCA positivity were similar between MF-AG and CR-AG.Women(69.2% vs 42.2%,p=0.01) and pernicious anemia(29% vs 9.1%,p=0.04) were more frequent in CR-AG than in MF-AG.
The proportion of GD and GC in MF-AG and CR-AG pts was similar:HG-GD was present in 4(8.9%) vs 2(5.1%),LG-GD in 17(37.8%) vs 14(35.9%),GC in 24(53.5%) vs 23(59.0%)pts(p>0.05).
Compared to MF-AG,in CR-AG pts GD-GC were more frequently polypoid lesions (51.6% vs 27.3%,p=0.048) and more frequent in the corpus (55.3% vs 28.6%,p=0.02), but also occurred in the antrum(34.2%) and incisura(10.5%).The intestinal-type GC was the most prevalent and was more frequent in MF-AG than in CR-AG (87%vs60.9%,p>0.046), while diffuse GC was 2 times more frequent in CR-AG than in MF-AG, albeit not reaching statistical significance (26.1% vs 13%, p=0.27).
Concerning GC differentiation grade and staging, no significant differences were observed between MF-AG and CR-AG.Endoscopic treatment of GD-GC was similar in both groups. CR-AG patients underwent surgery more frequently than MF-AG(48.6% vs 23.1%,p=0.0207), but outcome was similar with 90.7% MF-AG and 92.1% CR-AG pts being alive.
Histopathological features of corpus mucosa (acute-chronic inflammation, severity of atrophy,pseudopyloric and intestinal metaplasia) were similar between MF-AG and CR-AG(p>0.05). The histological evidence of Hp in the antrum and corpus was low in both groups (2.3% vs 2.9%,p=0.87).

Conclusion

Non-cardia GC and GD may occur in both,MF-AG and CR-AG, displaying differences in topography and endoscopic presentation, but similarities in perilesional gastric corpus mucosa, differentiation, staging and outcome.
Endo-histological surveillance should be considered in pts with gastric corpus atrophy, irrespective of its etiology and extension.

References

Lahner E, et al. Dig Liver Dis. 2019 Dec;51(12):1621-1632.
Lenti MV, et al. Nat Rev Dis Primers. 2020 Jul 9;6(1):56.
Rugge M, et al. Gut. 2023 Jan;72(1):30-38.