Features That Aid Identification of Autoimmune Gastritis in a Background of Active Helicobacter pylori Infection

Context.— Helicobacter pylori–associated and autoimmune gastritis may coexist in a subset of patients who require treatment for both disorders. Objective.— To delineate findings that identify autoimmune gastritis in the background of H pylori infection. Design.— We examined cases of (1) patients with H pylori–associated gastritis who had successful eradication therapy and subsequent biopsies diagnostic of autoimmune gastritis and (2) H pylori–associated gastritis wherein pathologists noted features of autoimmune gastritis during original interpretation. Control patients underwent H pylori eradication but lacked evidence of autoimmune gastritis or H pylori infection after 10 years of follow-up. Results.— Eight subjects had H pylori–associated gastritis followed by H pylori–negative sampling that showed autoimmune gastritis. Review of original samples showed full-thickness inflammation of oxyntic mucosa in 8 of 8 and oxyntic gland loss in 7 of 8 cases. Enterochromaffin-like (ECL) cell hyperplasia, pyloric metaplasia, and intestinal metaplasia were present in 4 of 8 (80% of 5 tested cases), 4 of 8, and 3 of 8 cases, respectively. Features of autoimmune gastritis were noted at the time of their original H pylori diagnosis in 11 study subjects. Ten of 11 samples displayed full-thickness inflammation of oxyntic mucosa and/or partial loss of oxyntic glands, 8 of 11 had ECL cell hyperplasia (all tested cases), 6 of 11 showed pyloric metaplasia, and 4 of 11 harbored intestinal metaplasia. Except for full-thickness oxyntic mucosa inflammation, these features were absent in control cases. Conclusions.— Full-thickness inflammation combined with oxyntic gland loss and ECL cell hyperplasia may help to identify autoimmune gastritis in patients with concomitant H pylori infection.

Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach

Micronutrient deficiencies are relatively common, in particular iron and cobalamin deficiency, and may potentially lead to life-threatening clinical consequences when not promptly recognized and treated, especially in elderly patients. The stomach plays an important role in the homeostasis of some important hematopoietic micronutrients like iron and cobalamin, and probably in others equally important such as ascorbic acid, calcium, and magnesium. A key role is played by the corpus oxyntic mucosa composed of parietal cells whose main function is gastric acid secretion and intrinsic factor production. Gastric acid secretion is necessary for the digestion and absorption of cobalamin and the absorption of iron, calcium, and probably magnesium, and is also essential for the absorption, secretion, and activation of ascorbic acid. Several pathological conditions such as Helicobacter pylori-related gastritis, corpus atrophic gastritis, as well as antisecretory drugs, and gastric surgery may interfere with the normal functioning of gastric oxyntic mucosa and micronutrients homeostasis. Investigation of the stomach by gastroscopy plus biopsies should always be considered in the management of patients with micronutrient deficiencies. The current review focuses on the physiological and pathophysiological aspects of gastric acid secretion and the role of the stomach in iron, cobalamin, calcium, and magnesium deficiency and ascorbate homeostasis.

Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management

Autoimmune gastritis (AIG) is a chronic immune-mediated, inflammatory condition that involves the destruction of the gastric oxyntic mucosa through the autoimmune-mediated loss of parietal cells, with replacement by atrophic and metaplastic tissue. Diagnosing AIG is important, given the need for ongoing clinical management and vigilance with respect to downstream complications, the most serious of which is gastric adenocarcinoma. Other clinical consequences include gastric neuroendocrine tumors, consequences related to decreased gastric acid and decreased intrinsic factor due to parietal cell destruction and antibodies against intrinsic factor (e.g. micronutrient deficiencies), as well as concomitant autoimmune disorders. Considering the prevalence of AIG and the potential for severe clinical outcomes, it is important to engage in efforts to reduce practice pattern variability related to diagnosis and management. Accordingly, herein, we review of the epidemiology, pathogenesis, clinical presentation of AIG, including both gastric and extragastric manifestations, and provide an overview of clinical management.

Autoimmune Gastritis and Gastric Microbiota

Autoimmune atrophic gastritis is an organ-specific immune-mediated condition characterized by atrophy of the oxyntic mucosa. Autoimmune atrophic gastritis (AIG) is characterized by a progressive loss of acid-secreting parietal cells leading to hypo-achlorhydria. Due to this peculiar intra-gastric environment, gastric microbiota composition in individuals with autoimmune atrophic gastritis was first supposed and then recently reported to be different from subjects with a normal acidic healthy stomach. Recent data confirm the prominent role of Helicobacter pylori as the main bacterium responsible for gastric disease and long-term complications. However, other bacteria than Helicobacter pylori, for example, Streptococci, were found in subjects who developed gastric cancer and in subjects at risk of this fearful complication, as well as those with autoimmune gastritis. Gastric microbiota composition is challenging to study due to the acidic gastric environment, the difficulty of obtaining representative samples of the entire gastric microbiota, and the possible contamination by oral or throat microorganisms, which can potentially lead to the distortion of the original gastric microbial composition, but innovative molecular approaches based on the analysis of the hyper-variable region of the 16S rRNA gene have been developed, permitting us to obtain an overall microbial composition view of the RNA gene that is present only in prokaryotic cells.

Ulcerative reflux esophagitis associated with Clostridium ventriculi following hiatoplasty – is antibiotic treatment necessary? A case report

Clostridium (C.) ventriculi (known as Sarcina ventriculi) is a ubiquitous gram-positive, anaerobic, acidophilic coccus found in patients with gastric motility disorders. The microorganisms can be identified histologically by their characteristic presentation in tetrads or packets of 8 in hematoxylin and eosin stains. Severe cases of emphysematous gastritis or gastric perforation have been described. Nevertheless, the significance of C. ventriculi in an upper gastrointestinal tract and its pathogenic character remain unclear. We present a 67-year-old woman who underwent hiatoplasty with gastropexy. After 3 months, she underwent a gastroscopy showing gastroesophageal reflux. Biopsies showed ulcerative reflux esophagitis with presence of C.ventriculi, subsequently confirmed by 16S ribosomal RNA gene amplicon sequencing. The barium swallow study revealed an atonic stomach with delayed gastric emptying. The patient was treated with PPI and domperidone. On follow up, 15 months post-operatively, a control gastroscopy showed a stomach with food residues and reflux-associated small erosions. The Clostridium organisms were detected only in oxyntic mucosa biopsies without erosions or ulcerations. We speculate that the recognition of the organisms in the biopsy material is important and suggests dysmotility disorder. However, in our opinion, the presence of C. ventriculi, even in combination with mucosal damage, does not necessarily prompt antibiotic treatment since no complications occurred and inflammation as well as gastric function improved under PPI and prokinetic therapy in our patient. Larger study groups with long-term follow-up are needed to understand whether these organisms could behave as pathogens or are only bystanders in the setting of delayed gastric emptying.

New evidence defining the pathology and pathogenesis of lower esophageal sphincter damage

Summary Background Present diagnosis and management of gastroesophageal reflux disease (GERD) has resulted in a dramatic increase in the incidence of esophageal adenocarcinoma. This is due to failure to identify pathologic changes of early GERD; at present, pathology is limited to management of Barrett esophagus (BE). Methods Convincing evidence have confirmed that cardiac mucosa distal to the squamocolumnar junction in the endoscopically normal person is a metaplastic GERD-induced esophageal epithelium, and not a normal proximal gastric epithelium. Results When cardiac mucosa is recognized as a metaplastic esophageal epithelium, it becomes self-evident that the present endoscopic definition of the gastro-esophageal junction is incorrect, and there exists a dilated distal esophagus (DDE) in what is incorrectly termed the “gastric cardia” presently mistaken for proximal stomach. It also becomes clear that the length of the DDE correlates with the presence and severity of GERD and represents the pathology of the entire spectrum of GERD. Further, it allows recognition that the DDE, measured as the gap between esophageal squamous epithelium and gastric oxyntic mucosa that is composed of cardiac mucosa, represents the pathologic anatomy of damage to the abdominal segment of the lower esophageal sphincter (LES). Conclusion The new understanding of the significance of cardiac mucosa provides a new and highly accurate histologic method of assessment of LES damage, the primary cause of GERD. This opens a new door to complete histologic assessment of GERD from its etiologic standpoint and to new research that permit early diagnosis of GERD at its outset. Ultimately, such early diagnosis has the potential to reverse the increasing trend of esophageal adenocarcinoma.

Autoimmune Gastritis

Context.— Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management. Objective.— To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG. Data Sources.— The sources of the study include a review of the pertinent literature for AG. Conclusions.— Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.

The Enterochromaffin-like [ECL] Cell—Central in Gastric Physiology and Pathology

Background: Studies on the regulation of gastric and pancreatic secretion began more than 100 years ago. Secretin was the first hormone postulated to exist, initiating the field of endocrinology. Gastrin produced in the antral mucosa was the second postulated hormone, and together with histamine and acetylcholine, represent the three major gastric acid secretagogues known since 1920. For a long time, the mast cell was the only recognized histamine-producing cell in the oxyntic mucosa and, in the mid-1980s, the ECL cell was recognized as the cell producing histamine, taking part in the regulation of gastric acid secretion. Methods: This review is based upon literature research and personal knowledge. Results: The ECL cell carries the gastrin receptor, and gastrin regulates its function (histamine release) as well as proliferation. Long-term hypergastrinemia results in gastric neoplasia of variable malignancies, implying that gastric hypoacidity resulting in increased gastrin release will induce gastric neoplasia, including gastric cancer. Conclusions: The trophic effect of gastrin on the ECL cell has implications to the treatment with inhibitors of acid secretion.