Autoimmune gastritis: histology phenotype and OLGA staging.

BACKGROUND: Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. AIMS: To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. METHODS: A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. RESULTS: Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H. pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant (P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. CONCLUSIONS: In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H. pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies.

Gastritis OLGA-staging and gastric cancer risk: a twelve-year clinico-pathological follow-up study.

BACKGROUND: Intestinal-type gastric cancer (GC) still ranks among the high-incidence, highly lethal malignancies. Atrophic gastritis is the cancerization field in which GC develops. The current histological reporting formats for gastritis do not include any (atrophy-based) ranking of GC risk. AIM: To test the gastritis OLGA-staging (Operative Link for Gastritis Assessment) in prognosticating neoplastic progression. METHODS: Ninety-three Italian patients were followed up for more than 12 years (range: 144-204 months). Clinical examinations, pepsinogen serology, endoscopy and histology (also assessing Helicobacter pylori status) were performed both at enrolment (T1) and at the end of the follow-up (T2). RESULTS: All invasive or intra-epithelial gastric neoplasia were consistently associated with high-risk (III/IV) OLGA stages. There was a significant inverse correlation between the mean pepsinogen ratio and the OLGA stage (test for trend; P < 0.001). OLGA-staging at T1 predicted both the OLGA stage (Kaplan-Maier log-rank test, P = 0.001) and the neoplasia at T2 (Kaplan-Maier log-rank test, P = 0.001). CONCLUSIONS: This long-term follow-up study provides the first evidence that gastritis OLGA-staging conveys relevant information on the clinico-pathological outcome of gastritis and therefore for patient management. According to OLGA-staging and H. pylori-status, gastritis patients could be confidently stratified and managed according to their different cancer risks.

Capsule endoscopy findings in patients with suspected Crohn's disease and biochemical markers of inflammation.

BACKGROUND: Because it provides a direct view of superficial lesions in the small bowel, capsule endoscopy is a promising diagnostic tool for studying patients with suspected Crohn's disease undetected by conventional modalities. AIM: To assess the role of capsule endoscopy in the diagnosis of patients with suspected Crohn's disease. PATIENTS AND METHODS: Thirty-eight patients (16 males, mean age 46.2 years) with suspected Crohn's disease but negative at conventional imaging were examined using capsule endoscopy. They were divided into 2 groups: 12 patients with ongoing symptoms (Group 1), and 26 with ongoing symptoms and biochemical markers of inflammation (Group 2). Capsule endoscopy findings were classified as diagnostic (multiple erosions/ulcerations), suspicious (

Capsule endoscopy for the diagnosis and follow-up of blue rubber bleb nevus syndrome.

Blue rubber bleb nevus syndrome is a rare disorder characterised by cutaneous and gastrointestinal vascular malformations. A 31-year-old man came under our observation with obscure gastrointestinal bleeding. Hemangiomas on his back and the multiple bluish vascular lesions in the distal ileum revealed by capsule endoscopy led to the diagnosis of blue rubber bleb nevus syndrome. The patient was treated with octreotide to prevent rebleeding. During the 12 months of treatment he had no gastrointestinal bleeding episodes or anaemia. Then repeat capsule endoscopy showed that the small bowel vascular lesions were unchanged. Capsule endoscopy may be a useful tool for diagnosing and monitoring the effects of therapy in patients with blue rubber bleb nevus syndrome.

Immunoglobulin heavy chain diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process.

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement. DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences. Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen. The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.

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.

Helicobacter pylori and pre-neoplastic and neoplastic gastric lesions.

The spiral bacterium Helicobacter pylori has gained increasing interest as an important gastroduodenal pathogen since its isolation from the gastric mucosa. The presence of Helicobacter pylori in the human stomach is closely associated with chronic gastric inflammatory disease and growing evidence suggests an aetiologic role of this organism in peptic disease. Moreover, epidemiological and histological studies suggest that Helicobacter pylori may be a risk factor for gastric carcinoma and primary gastric lymphoma. Evidence supporting the role of Helicobacter pylori in the pathogenesis of pre-cancerous lesions are reviewed here.

Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases.

The occasional finding within the gastric mucosa of unidentified epithelial cells with morphological features closely resembling those of pancreatic acinar cells has prompted us to investigate a retrospective series of 8,430 consecutive gastric biopsies and of 126 surgical specimens of gastric resection and total gastrectomy. The aims of the study were to morphologically and immunocytochemically characterize these cells, to define their actual prevalence in a large series of unselected cases, and to assess the clinicopathologic correlates of their occurrence. Pancreatic acinar-like cells characterized by abundant cytoplasm, which was acidophilic and finely granular in the apical and middle portions and basophilic in the basal compartment, have been identified in 101 cases (84 gastric biopsies and 17 gastrectomies). These cells, arranged in nests or in variably sized lobules among the gastric glands, were morphologically indistinguishable from pancreatic acinar cells, both by light and by electron microscopy. Furthermore, they were consistently immunoreactive for pancreatic lipase and trypsinogen and, in 75% of the cases, for pancreatic alpha-amylase. The appearance of these cells within the gastric mucosa was correlated significantly with chronic gastritis (p = 0.032) and with the simultaneous occurrence of intestinal and pyloric types of gastric metaplasia (p = 0.021). The findings indicate that this is a previously unrecognized pancreatic (acinar) metaplasia of the gastric mucosa, clinically and morphologically distinct from pancreatic heterotopia.

Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori.

Certain features of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) suggest the tumour is antigen-responsive. Given the close association between gastric MALT lymphoma and Helicobacter pylori, these organisms might be evoking the immunological response, and eradication of H pylori might inhibit the tumour. 6 patients in whom biopsies showed histological and molecular-genetic evidence of low-grade gastric B-cell MALT lymphoma with H pylori infection were treated with antibiotics. In all cases H pylori was eradicated and in 5, repeated biopsies showed no evidence of lymphoma. These results suggest that eradication of H pylori causes regression of low-grade B-cell gastric MALT lymphoma, and that anti-H-pylori treatment should be given for this lymphoma.

Preoperative cytodiagnosis of primitive carcinoid tumor of the Wirsung duct: a case report with immunocytochemical study.

A case of primitive carcinoid tumor of the Wirsung duct detected by fiberoptic guided brushing cytology is reported. The authors describe the main cytomorphologic characteristics and underline the role of immunocytochemistry in helping to reach a reliable preoperative diagnosis.

Gastric giardiasis.

AIMS: To assess the prevalence of gastric giardiasis in patients undergoing upper gastrointestinal endoscopy, and to define the clinicopathological correlates of gastric Giardia lamblia infection. METHODS: Consecutive gastric biopsy specimens (n = 15,023) from 11,085 patients, taken at Feltre City Hospital (north eastern Italy) from January 1986 to December 1991, were histologically and immunocytochemically examined for the occurrence of G lamblia trophozoites. Three gastric biopsy specimens from patients harbouring G lamblia infection, who repeated endoscopy before treatment, were also examined electron microscopically. RESULTS: Forty one patients (0.37% of the population study) harboured gastric giardiasis. All patients underwent upper gastrointestinal endoscopy because of dyspepsia, epigastric pain, or abdominal distension. Only two patients had diarrhoea at the time of investigation. Giardiasis was clinically unsuspected in all cases, although the nine patients who also had duodenal biopsies performed had concomitant intestinal giardiasis. Gastric giardiasis was invariably associated with chronic atrophic gastritis. Intestinal metaplasia of the gastric mucosa and Helicobacter pylori infection were found in 32 and 37 of the 41 patients with gastric giardiasis, respectively. CONCLUSIONS: The invariable association of gastric giardiasis with chronic atrophic gastritis, most often showing intestinal metaplasia and H pylori infection, indicates that a decreased gastric acidity is a prerequisite for localisation of G lamblia to the gastric mucosa. Though its possible role as a gastric pathogen remains to be elucidated, these findings suggest that trophozoites should be carefully searched for when examining gastric biopsy specimens showing chronic atrophic gastritis.

High incidence of primary gastric lymphoma in northeastern Italy.

We previously noted an extraordinarily high number of cases of primary gastric lymphoma (PGL) in northeastern Italy. We have now formally compared the incidence in Feltre, Italy, with that in three similar communities in the UK. Each community has a stable population served by a single endoscopy unit and histopathology laboratory. There were 13 times more cases of PGL in Feltre in 1986-91 than in the UK communities (66 vs 5 per 100,000 per 5 years). The incidence of gastric adenocarcinoma was also substantially higher in Feltre than in the UK (270 vs an average of 82 per 100,000 per 5 years), as was the prevalence of gastritis associated with Helicobacter pylori infection (87% of 1343 gastric biopsy samples in 1991).

Pepsinogen A/pepsinogen C or pepsinogen A multiplied by gastrin in the diagnosis of gastric cancer?

Being pepsinogen A (PGA) levels generally reduced and pepsinogen C (PGC) increased in gastric cancer patients, PGA/PGC ratio has been proposed as a useful marker of the tumour. We tested PGA, PGC and Gastrin (G) levels in patients with gastric cancer (39) and, as a control, in patients with epithelial dysplasia (21), chronic atrophic gastritis (57), gastric ulcer (11) or subjects lacking major or minor endoscopic and microscopic changes at gastroscopy (48). PGA and PGA/PGC levels were significantly reduced in gastric cancer patients (p less than 0.005 and p less than 0.0001 respectively with analysis of variance). Gastrin levels were also reduced in the same patients (p less than 0.005). We therefore adopted an index number (PGA x Gastrin) which was also dramatically reduced in gastric cancer (p less than 0.005); using an arbitrarily chosen cut-off, the "marker" showed very high sensitivity (76%), specificity (96%) and overall accuracy (74%, by Youden J test). We therefore suggest the use of the index number PGA x G in the diagnosis of gastric cancer, as the most useful gastrin presently available, to our knowledge.