Pietro Caruana

Atrophic Body Gastritis: Distinct Features Associated with Helicobacter pylori Infection

Usually, atrophic body gastritis has been considered an autoimmune disease characterized by the presence of parietal cell antibodies. Previous investigations into the role of Helicobacter pylori infection have obtained conflicting results. The aim of this study was to investigate the prevalence and role of H. pylori in a prospectively investigated population of patients with corpus‐predominant atrophic gastritis.

Two-thirds of Atrophic Body Gastritis Patients Have Evidence of Helicobacter pylori Infection

Helicobacter pylori is involved in the induction of atrophic body gastritis (ABG). During the progression of atrophic gastritis the disappearance of H. pylori has been documented and in time serology is the only sign that indicates a previous infection. It has been shown that a positive serology, in ABG patients without histological evidence of infection, indicates an active H. pylori infection.

Atrophic body gastritis patients with enterochromaffin-like cell dysplasia are at increased risk for the development of type I gastric carcinoid.

Background/Aims In the presence of atrophic body gastritis, gastric carcinoid develops from gastric-body mucosa enterochromaffin-like cells. Few data exist on the prevalence of enterochromaffin-like dysplastic lesions in atrophic body gastritis patients and their presumed risk of evolution to carcinoid has never been assessed prospectively in humans. The aim of the present study was to investigate the prevalence and incidence of dysplastic and neoplastic enterochromaffin-like cell lesions in a consecutive series of patients with atrophic body gastritis. Methods A total of 130 atrophic body gastritis patients at diagnosis and 96 atrophic body gastritis patients at follow-up (median 30 months) underwent gastroscopy with multiple biopsies and fasting gastrinaemia evaluation. In patients with enterochromaffin-like cell dysplasia, a more detailed bioptic sampling at follow-up was performed. Results Of the 130 atrophic body gastritis patients, only one (0.7%) had a gastric carcinoid polyp, whereas enterochromaffin-like cell dysplasia was found in five patients (3.8%). At follow-up only one out of the 96 atrophic body gastritis patients (1%) was diagnosed as having a carcinoid polyp at 41 months. Enterochromaffin-like cell dysplasia was present in four additional patients (4.2%). Two atrophic body gastritis pernicious anaemia patients with enterochromaffin-like cell dysplasia developed a gastric carcinoid in the follow-up. Among nine atrophic body gastritis patients with enterochromaffin-like cell dysplasia, the incidence of carcinoid tumour was 22% compared to 1.1% of atrophic body gastritis patients without dysplasia (odds ratio: 26.00; 95% confidence interval: 2.089–323.52). During the follow-up, fasting gastrin levels increased significantly only in atrophic body gastritis patients with enterochromaffin-like cell dysplasia (mean 677.4 ± 66.1 vs 1112.2 ± 185.6;P = 0.0287). Conclusion This study provides the first clinical evidence that, in hypergastrinaemic atrophic body gastritis patients, enterochromaffin-like cell dysplasia carries a markedly increased risk for development of type I gastric carcinoid. This suggests that a more detailed endoscopic/bioptic procedure in this subgroup of atrophic body gastritis patients is able to detect gastric carcinoid at an early stage.

The long-term effects of cure of Helicobacter pylori infection on patients with atrophic body gastritis

Background : Helicobacter pylori infection induces atrophic body gastritis, but the long‐term effect of its cure on body atrophy is unclear.

Involvement of the corporal mucosa and related changes in gastric acid secretion characterize patients with iron deficiency anaemia associated with Helicobacter pylori infection

Recent studies have reported an association between iron deficiency anaemia and Helicobacter pylori. Helicobacter pylori could cause iron deficiency anaemia by altering iron absorption. We observed that most patients with Helicobacter pylori infection and iron deficiency anaemia present a chronic superficial pangastritis.

Role of Helicobacter pylori infection in pernicious anaemia

BACKGROUND Pernicious anaemia is associated with atrophic body gastritis and considered an autoimmune disease. Whether Helicobacter pylori is involved in the induction of pernicious anaemia is uncertain. AIMS To investigate the prevalence of Helicobacter pylori infection in pernicious anaemia patients and to ascertain whether the Helicobacter pylori-positive patients had distinctive clinical and gastric morphofunctional characteristics. PATIENTS AND METHODS A series of 81 consecutive pernicious anaemia patients underwent serological, functional and endoscopic/histological investigations. RESULTS A total of 49 (60.5%) patients were Helicobacter pylori-positive (males 61.2% vs females 38.8%). No difference was observed in clinical and morphofunctional characteristics between Helicobacter pylori-positive and negative patients, whereas distinctive functional/histological features between histologically Helicobacter pylori-positive (n=8) and serologically Helicobacter pylori-positive (n=41) cases were detected. In the histologically Helicobacter pylori-positive group, Pepsinogen I was higher [13 (058) vs 5 (0-26) ng/ml; p=0.0025)] and positivity for anti-parietal cell antibodies was lower [42.9% vs 76.9, p=0.0867]. Antral histological variables of the gastritis score were significantly higher in the histologically Helicobacter pylori-positive than in the serologically Helicobacter pylori-positive patients, but this latter group had a higher score of body atrophy (2.63+/-0.12 vs 1.71+/-0.29; p=0.0051). Body inflammation was also significantly higher in the histologically Helicobacter pylori-positive group (chronic inflammation: 1.43+/-0.2 vs 1.05+/-0.06; p=0.0271; inflammation acitivity: 0. 57+/-0.3 vs 0.15+/-0.06, p=0.0220). Antral mucosa was normal in 24/41 (58.5%) of the serologically Helicobacter pylori-positive patients, but only in 1/8 (12.5%) of the histologically Helicobacter pylori-positive patients (p=0.0232). CONCLUSIONS Almost two thirds of pernicious anaemia patients have evidence of Helicobacter pylori, but only those with an active Helicobacter pylori infection have distinctive functional and histological features. These findings support the hypothesis that Helicobacter pylori infection could play a triggering role in a subgroup of pernicious anaemia patients.

Production of basic fibroblast growth factor by gastric carcinoid tumors and their putative cells of origin

Using immunohistochemical techniques a subpopulation of endocrine cells in the human oxyntic mucosa was found to react with antibodies against basic fibroblast growth factor (bFGF). These cells were identified as histamine-producing enterochromaffin-like (ECL) cells and, to a minor extent, serotonin-producing enterochromaffin cells. Basic fibroblast growth factor immunoreactive cells were most frequently found in hyperplastic lesions of ECL cells occurring in hypergastrinemic patients (20 of 27 cases) and in ECL cell carcinoid tumors (10 of 17 cases). In addition, bFGF mRNA was demonstrated by Northern blot analysis of homogenates from two gastric carcinoids cytologically characterized as pure ECL cell tumors. Although the function of bFGF in normal cells remains unknown, its production in neoplastic conditions may be responsible for the associated desmoplastic and angioblastic proliferations. Moreover, secretion of bFGF by hyperplastic or neoplastic ECL cells may contribute to the circulating levels of the bFGF-like mitogenic factor identified in patients affected by multiple endocrine neoplasia type 1 syndrome.

Involvement of BCL-2 oncoprotein in the development of enterochromaffin-like cell gastric carcinoids.

To evaluate the involvement of the apoptosis-suppressing protein BCL-2 in the gastrin-dependent mechanism of induction of gastric enterochromaffin-like (ECL) cell carcinoids, the endocrine cell of the oxyntic mucosa were immunohistochemically investigated in (a) 10 normogastrinemic subjects with histologically normal gastric mucosa; (b) 22 patients with endocrine cell hyperplasia and affected by hypergastrinemic conditions with different risk of gastric carcinoid development, such as sporadic Zollinger-Ellison syndrome (sZES; n = 9), ZES associated with multiple endocrine neoplasia-1 (MEN-1; n = 4), and atrophic fundal gastritis (AFG; n = 9); (c) 14 patients with ECL gastric carcinoids accounting for a total of 31 tumors investigated. In the normal oxyntic mucosa, BCL-2 was consistently expressed by a subset of endocrine cells accounting for 50.0% (median; range, 24.6-74.0%) of the total number of endocrine cells immunostained for chromogranin A (CgA) in consecutive sections. BCL-2 immunoreactive cells were located mostly in the middle mucosal layer, suggesting a role for the protein during downward migration of maturing endocrine cells. No BCL-2 immunoreactivity was found in other specialized gastric epithelial cells. Expression of BCL-2 by hyperplastic oxyntic endocrine cells (mostly ECL cells) varied in parallel with the risk of carcinoid development. In fact, the ratio of BCL-2- to CgA-immunoreactive cells was reduced (median, 4.6%; p less than 0.0001; range, 0.9-42.0%) in sZES, a condition showing virtually no risk, unchanged (median, 55.6%; range 29.4-83.8 %) in cases of MEN-1/ZES with intermediate risk, and increased (median 87.6%; p less than 0.014; range, 48.8-199.4%) in cases of AFG, a condition at the highest risk of carcinoid. In ECL cell carcinoids, BCL-2 expression varied markedly from one tumor to another even in the same patient and was low or absent in most cases. In both hyperplastic and neoplastic ECL cells, an inverse relation between BCL-2 expression and CgA immunoreactivity, that is, the cell granule content, was found. These results suggest that BCL-2 expression by hyperplastic ECL cells is independent of the influence of serum gastrin and may contribute to the development of ECL cell carcinoid tumors by extending cell exposure to oncogenic factors. Once a carcinoid tumor is established, BCL-2 expression becomes inconsistent.

Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium.

We sought to study the relationship between serum pepsinogens and different histopathologic features of Helicobacter pylori-related chronic gastritis. One hundred forty-nine consecutive dyspeptic patients underwent endoscopy with biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels of pepsinogens (sPG) were significantly correlated with H. pylori density both of the corpus (sPGI: r = 0.32, P < .001; sPGII: r = 0.56, P < .001) and antrum (sPGI: r = 0.41, P < .001; sPGII: r = 0.43, P < .001) as well as with chronic inflammation (sPGI: r = 0.26, P < .001; sPGII: r = 0.49, P < .001) and activity (sPGI: r = 0.38, P < .001; sPGII: r = 0.50, P < .001) in the antrum. Only sPGII was correlated with chronic inflammation (r = 0.44, P < .001) and activity (r = 0.40, P < .001) in the corpus. SPGI was inversely correlated with atrophy (r = –0.33, P < .001) and intestinal metaplasia (r = –0.37, P < .001) in the corpus. sPGII levels could be considered as markers of gastric inflammation all over in the stomach. sPGI levels are inversely related to atrophic body gastritis.

'Serological biopsy' in first-degree relatives of patients with gastric cancer affected by Helicobacter pylori infection.

Background: Relatives of patients with gastric cancer are at increased risk of developing this disease, especially if they are infected by Helicobacter pylori. Moreover, H. pylori‐related atrophic gastritis and hypochlorhydria are well‐documented risk factors for noncardia gastric cancer. Serum pepsinogen I (sPGI) and II (sPGII) levels are low in this condition. The aim of our study was to assess by means of a ‘Gastropanel’ blood test, including sPGI, sPGII, gastrin‐17 (G‐17) and antibodies anti‐H. pylori (IgG‐Hp), both functional and morphological features of gastric mucosa in Hp + ve subjects with a family history of gastric cancer. Materials and Methods: Twenty‐five Hp + ve subjects consecutively referred to our department for gastrointestinal complaints, selected as first‐degree relatives of patients suffering from gastric cancer, were enrolled in the study and then matched for sex and age with 25 dyspeptic and Hp + ve subjects with no family history of gastric neoplasia. Blood samples were taken for determination of gastropanel in all patients; in addition, antibodies against CagA were analysed. Results: No statistically significant differences were detected zbetween the two groups as regards alcohol consumption, coffee intake and smoking habits. Mean sPGI levels in Group A (83.4 ± 58.4 μg/L) were significantly lower than those in Group B (sPGI 159.5 ± 80.6 μg/L; P < 0.0001) as well as sPGII (12.5 μg/L ± 6.24 versus 20.6 ± 58 μg/L; P < 0.006). No statistical difference was found between the two groups in relation to G‐17 levels, IgG‐Hp titres and antibodies against CagA. Conclusion: First‐degree relatives of patients with noncardia gastric cancer affected by H. pylori infection present lower sPGI and sPGII levels, possibly due to the increased frequency of atrophic lesions in these patients.