Autoimmune atrophic gastritis: risk of gastric cancer

INTRODUCTION: Gastric cancer is the third leading cause of cancer mortality worldwide and the fifth for incidence. Atrophic gastritis and intestinal metaplasia are considered precancerous conditions on which dysplasia and gastric cancer could be developed. This transformation from normal gastric mucosa to gastric cancer is known as Correa’s cascade. Autoimmune gastritis is a chronic disease occurring in up to 8% of the general population. This condition is characterized by loss of the oxyntic glands with consequent hypochlorhydria, lack of intrinsic factor production, and, in a later stage, pernicious anemia. Cumulative evidence suggests that electronic chromoendoscopy with narrow band imaging (NBI) is highly accurate for the diagnosis of precancerous conditions. A new type of endoscopic classification has been proposed: the Endoscopic Grading of Gastric Intestinal Metaplasia (EGGIM) may be used to assess the risk of patients by the endoscopic assessment of IM in the antrum, in the incisura and in the corpus with the use of high resolution NBI scopes. AIMS: The aims of this project are: 1. To investigate the occurrence of and risk factors for gastric neoplastic lesions in patients with AIG and EAG 2. To investigate the role of electronic chromoendoscopy at follow-up in EAG and AIG in optimizing gastric preneoplastic and neoplastic lesions detection: comparison of the diagnostic yield with the use of NBI scopes of target oriented biopsies versus the updated Sydney system protocol with traditional white light (WL) scopes 3. To investigate specific endoscopic features at electronic chromoendoscopy of visible gastric polypoid lesions using HR-NBI compared to traditional WL gastroscopy in newly diagnosed and followed-up EAG and AIG patients. 4. To assess the cost-effectiveness of surveillance strategies based on independent risk factors in a low risk area to maximize the exploitation of the endoscopic resources in a longitudinal cohort study performed on patients with AIG and EAG. RESULTS: 1. MAG may be found in about one of three patients undergoing endoscopy for upper gastrointestinal symptoms. Clinical predictors are age older than 55 years, current smoking, active H. pylori infection, and postprandial fullness, especially for corpus-involving and corpus-restricted MAG. 2. More than half of AG patients complained of GI symptoms, in particular, dyspepsia, alone in 70% or associated to GERD in 17.7% of symptomatic patients, confirming the significant occurrence of symptoms in this population. In autoimmune gastritis patients, the demonstrated association between early satiety and postprandial fullness with younger age, no smoker and not anemic status should be kept in mind in the work-up of these patients. 3. GERD is not infrequent in atrophic body gastritis (ABG) being symptoms present in a quarter of patients, suggesting that ABG not exclude per se arising of oesophageal complaints. In ABG we found that microscopic esophagitis is a common finding but its clinical relevance remains to be investigated with further studies. 4. EGGIM classification showed a high diagnostic performance compared to OLGIM. This approach could be used to simplify the surveillance of these patients by avoiding biopsies. A possible confounding factor leading to overestimation of presence of intestinal metaplasia might be the presence of foveolar hyperplasia that should be taken into account before final staging is communicated to the patient. This endoscopic diagnostic tool could become a promising instrument for surveillance for gastric cancer. 5. When HR-endoscopy with NBI does not show suspicious areas of GIM, antrum and body biopsies can be sent in the same vial (when H. Pylori status is necessary) or do without biopsies when the purpose is only to detect patients with premalignant conditions deserving surveillance. 6. NBI analysis of the mucosal pattern seems to be effective to endoscopically discriminate between adenomas and HP, while the main characteristic of T1-GC seems to be the presence of a central erosion, sometimes with a clear demarcation line. The endoscopic NBI characterization of GPL may contribute to optimize the management of these lesions. 7. Our study provided a cost estimate of a 4-year endoscopic surveillance in Italy, and it showed how the restriction of an eventual program to subgroups of AG patients with pernicious anaemia may lead to a nearly 50% cost reduction still detecting 74% of gastric neoplastic lesions. CONCLUSIONS: Based on the studies conducted during this PhD project, the occurrence and risk factors for gastric neoplastic lesions in patients with AIG and EAG has been assessed; the role of electronic chromoendoscopy at follow-up in EAG and AIG in order to stage the presence of intestinal metaplasia and to distinguish between gastric polypoid lesions was demonstrated and the cost-effectiveness of surveillance strategies based on independent risk factors in a low risk area on patients with AIG and EAG was provided. In 2012 the first European guidelines on precancerous conditions (MAPS) where published and these studies were considered for the development of the update of this guideline in 2019 showing the importance of these evidences in the management of gastric precancerous conditions.