Autoimmune atrophic gastritis (AAG) is characterized by an immunologically-driven destruction of gastric glands leading to atrophy of corporal oxyntic mucosa with consequent reduced gastric acid secretion and increased gastrin levels. In AAG, gastric cancer (GC) risk is increased. The altered intra-gastric milieu may lead to an altered composition of gastric microbiota, possibly having a role in gastric carcinogenesis, but data are conflicting. Parietal cell autoantibodies (PCA) are used to screen patients with other autoimmune disorders for AAG, albeit data on reliability are lacking. Recent European guidelines include AAG as condition to be monitored for GC. In AAG with PA an association with extra-gastric tumours was described. To quantity the risk of AAG patients of developing gastric or extragastric malignancies and to find out risk factors would be important to optimize surveillance. Pseudopyloric metaplasia, in particular spasmolytic-polypeptide expressing metaplasia (SPEM) has been linked to gastric cancerogenesis, its role in AAG patients has not been addressed so far.
This project is composed of four parts:
1. To investigate in patients with AAG the role of dysbiosis of the gastric microbiota as possible risk factor for development of gastric neoplastic/preneoplastic lesions
2. To investigate in a cohort of AAG patients stratified according to risk groups the occurrence of gastric malignancies when monitored by gastroscopy/histology at 3 year-intervals and to assess the risk of extra-gastric malignancies.
3. To investigate the occurrence of gastric autoantibodies against parietal cells in patients with high clinical suspicion of AAG to assess diagnostic performance as serological markers
4.To investigate in a cohort of patients with AAG the occurrence of gastric SPEM and its role as possible predictor associated with potential development of neoplastic complications.
1. During the last 25 years, the research group has built a cohort of patients with Hp-atrophic gastritis, AAG, and PA whose demographical, clinical, serological and histological data are registered in a database.
2. The research group is composed of gastroenterologists, endoscopists and biochemists with specific clinical and laboratory expertise in the field of gastric pre- and neoplastic lesions as well as autoimmunity, and it is part of national and international research networks on this research topics.
3. The participants form together a solid research group with a specific scientific background in this specific research field of atrophic gastritis, AAG, PA and gastric pre- and neoplastic lesions, whose projects have been granted by University Sapienza in the last 15 years.
The realization of the single parts of this project may contribute to advance of knowledge in the specific topic of AAG as the following results may be expected:
1. To investigate in patients with AAG the role of dysbiosis of the gastric microbiota as a possible risk factor for the development of gastric neoplastic and preneoplastic lesions in order to provide new insights into the increased neoplastic risk of these patients and to possibly open the way for new developable strategies to prevent this long-term malignant complication
EXPECTED RESULTS: to understand the role of the gastric microbiota composition in the risk of developing gastric neoplasms in patients with AAG or PA, eventually opening new perspectives of prevention by treatments able to modulate the gastric microbiota.
2. To investigate in a cohort of AAG patients stratified according to risk groups (presence of pernicious or iron-deficiency anemia, family history of gastric cancer) the occurrence of gastric malignant complications when monitored by gastroscopy/histology at 3 year-intervals according to European guidelines (MAPS), and to assess in the same cohort the associated risk of extra-gastric malignant complications.
EXPECTED RESULTS: to validate the proposed time interval of three years for endoscopic/histologic surveillance in AAG patients; to quantify the risk of patients with AAG to develop malignancies in other parts of the body and to find out eventual risk factors for developing these extra-gastric malignancies; this would be important as the confirmed risk of extra-gastric malignancies in AAG patients might justify a surveillance also of some specific organ or body district, at least in high-risk subgroups.
3. To investigate the occurrence of gastric autoantibodies against parietal cells in patients with high clinical suspicion of AAG to assess their diagnostic performance (together with serum pepsinogen I) as serological preendoscopic markers of AAG for a potential application in a case-finding strategy in possible high-risk groups.
EXPECTED RESULTS: to understand the role of serological autoantibodies against the proton pump of parietal cell as screening tool for AAG and its reliability for diagnostic use. A reliable serological marker for the presence of gastric body atrophy, a condition at increased risk for gastric neoplasms, may be useful as it could be easily used in large settings and positive patients should undergo gastroscopy in order to rule out possible neoplasms associated with AAG.
4.To investigate in a cohort of patients with AAG the occurrence of gastric pseudopyloric metaplasia (SPEM) and its role as possible predictor associated with potential neoplastic complications in order to provide insights into progressive AAG unrelated to known and currently used staging systems (OLGA/OLGIM).
EXPECTED RESULTS: to understand the role of pseudopyloric metaplasia in AAG patients at risk for gastric malignancies, which may eventually explain neoplastic complications of AAG patients not linked to high-risk OLGA/OLGIM stages.
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