Multifocal Atrophic Gastritis Research Articles

The Gastric Precancerous Cascade

Although most gastric cancers are first detected after the fifth decade of life, they represent the end product of a prolonged precancerous process initiated during childhood as a consequence of the infection of the mucosa with Helicobacter pylori. The initial phase of the process consists of active non-atrophic gastritis. The following stages are: multifocal atrophic gastritis, intestinal metaplasia (initially of complete type, then incomplete type), dysplasia and finally invasive carcinoma. The progression of the lesions is modulated by other factors such as the diet: excessive salt intake accelerates the process while fresh fruits and vegetables play a protective role. In addition, the geographic location influences the process. In Colombia, the high altitude Andes mountains dwellers display more advanced lesions than the residents of the Pacific coast. It appears that the ancestral origin of the infecting H. pylori strains have a determining influence on their capacity to induce precancerous lesions. The H. pylori strains infecting the mountain dwellers are of predominantly European phylogeographic origin. The H. pylori strains infecting the Pacific coast dwellers are predominantly of African origin, probably less virulent. Chemoprevention trials have been partially effective, when the precancerous lesions are not too advanced. Such trials may not eliminate the infection but have a tendency to eliminate preferentially the most virulent bacterial strains.

4. Eosinophils in autoimmune atrophic gastritis – typically numerous and a potentially helpful diagnostic feature

<h3>Background</h3> Autoimmune atrophic gastritis (AAG) is an autoimmune condition characterised by loss of gastric parietal cells and subsequent replacement by metaplastic intestinal, gastric or pancreatic acinar epithelium. A lymphocyte rich inflammatory infiltrate localised to the parietal cell bearing gastric body and fundic mucosa and sparing the gastric antrum is typical. We have noted eosinophils to be a prominent component of the inflammatory process, and recently experimental evidence has suggested activation of the Th17 effector cell mechanism to be responsible. <h3>Aims</h3> To investigate eosinophils in AAG and their usefulness as a diagnostic adjunct. <h3>Methods</h3> Gastric body/fundic biopsies were collected in a consecutive prospective manner of AAG (<i>n</i>=52; diagnosed on basis of body only inflammation and suggestive history and/or antiparietal cell/ anti intrinsic factor antibodies and <i>H. pylori</i> immunohistochemical stain negative); <i>H. pylori</i> gastritis (HPG; <i>n</i>=49; immunohistochem-ical stain ± urease positive); multifocal atrophic gastritis (MAG; <i>n</i>=16; <i>H. pylori</i> immunohistochemical stain negative and atrophy of gastric antrum) and normal controls (NC; <i>n</i>=50; endoscopy and biopsy normal). Eosinophils were countered as the maximum in 1 HPF (field diameter 0.4mm) and maximum total in any 3 HPF. <h3>Results</h3> Maximum mean eosinophil numbers counts were as follows: 1 HPF, AAG 44; HPG 9; MAG 19; normal controls 3; 3 HPF, AAG 104; HPG 23; MAG 43, NC 6. There was a significant difference between the counts in AAG and those in NC, HPG and MAG (all <i>p</i> < 0.05). In 7 AAG cases (13.5%) eosinophil counts were ≤11 (the maximum count in NC). Eosinophils were common in both evolving and established disease as evidenced by the extent of metaplasia in biopsies. <h3>Conclusions</h3> A prominent increase in eosinophils is frequently identified in AAG and is greater than other conditions that comprise the histological differential diagnosis. This may serve as an additional diagnostic marker in histologically equivocal gastric body biopsies or where supportive clinical history is not available.

Abstracts and Case Studies From the College of American Pathologists 2012 Annual Meeting (CAP '12)

Abstracts and Case Studies From the College of American Pathologists 2012 Annual Meeting (CAP '12)

Letter: gastric atrophy as a precursor of gastric cancer – authors’ reply

The clinico-pathological assessment (and natural history) of autoimmune gastritis (AG) is a matter of debate.1 In their appreciated letter,2 Barbosa and Botelho de Carvalho suggest starting with the histological evidence of corpus-restricted gastritis as a reliable marker of autoimmunity targeting the oxyntic cell population. However, if we do, we should be aware that these ‘putative-AG’ patients include cases whose corpus inflammation/atrophy is part of a multifocal atrophic gastritis due to Helicobacter pylori infection. In our trial,3 we ‘cleansed’ our study population by requiring serology-confirmed gastric autoimmunity. Consistent with this choice, our study sample included 52 patients with antiparietal/anti-intrinsic factor antibodies, with corpus-predominant gastritis, but no histological evidence of corpus-restricted gastric atrophy. Among the patients with positive serology, 116 were followed up for longer than 24 months. At the end of the follow-up, 2 of the 6 cases enrolled as having non-atrophic gastritis featured stage II gastritis, supporting the hypothesis that the natural history of AG includes two subsequent phenotypes: initial non-atrophic and advanced atrophic disease.3 As for the OLGA staging, here again – and also in the autoimmune setting – OLGA staging consistently stratified patients by their different cancer risk.4-7 In fact, the stage of gastritis expresses ‘how advanced’ the disease is, irrespective of its aetiology. In our AG series, all incidental cancers coexisted with high-risk stages, basically confirming both that gastric atrophy is the field in which gastric cancer develops, and the clinical usefulness of staging in gastric cancer secondary prevention strategies.5 As for carcinoids, the related risk coincides with the histological score for corpus atrophy (more than with the OLGA stage): 17 of 19 (89.5%) carcinoids coexisted with score 3 corpus atrophy.3 In conclusion, in the presence of a compatible clinical syndrome, serology does identify autoimmune gastric disease, with a histology that includes both non-atrophic and atrophic phenotypes. Irrespective of the aetiology of gastritis, OLGA staging can convey clinically important information on the gastritis-associated cancer risk. The authors’ declarations of personal and financial interests are unchanged from those in the original article.3

Clinical Usefulness of the Serological Gastric Biopsy for the Diagnosis of Chronic Autoimmune Gastritis

Aim. To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori (Hp) antibodies, and measurement of blood gastrin. Methods. We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency. Results. 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with “borderline” PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases. Conclusions. The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic “serological biopsy.”

The gastric precancerous cascade

Invasive gastric carcinoma is preceded by a cascade of precancerous lesions. The first recognized histologic change is active chronic inflammation, which may persist as such: non-atrophic chronic gastritis (no gland loss), or advance to multifocal atrophic gastritis (MAG), the first real step in the precancerous cascade. The following steps are: intestinal metaplasia (first "complete" and then "incomplete"); dysplasia, first low grade and then high grade (equivalent to "carcinoma in situ"). The following step is invasive carcinoma, which is thought to be associated with degradation of the intercellular matrix.

From Open-Type Atrophic Gastritis to Gastritis Staging

Dear Sir, We read with great interest the latest issue of Digestive Diseases and Sciences and, given our particular interests, we would like to briefly comment on three thoughtprovoking papers signed by Genta [1], Uedo [2] and, not last, by Ahn and coworkers [3]. Genta looks at the worldwide epidemiology of gastric cancer (GC) and correlates different socio-economic habits with GC risk. Addressing the etiological co-factors involved in gastric carcinogenesis, Genta notes that, ‘‘The relative influence of ... these factors on the rise and fall of GC is difficult to evaluate; since none is a sufficient cause of cancer, they must have acted synergistically’’ [1]. In this respect, without curbing the ‘‘leading’’ etiological role of H. pylori, we would like to mention that we recently documented a similar prevalence of both H. pylori and Cag-A status coexisting with impressive differences in the incidence of GC in different Siberian populations [4]. Our observation strongly supports the role of factors other than H. pylori in the etiology of ‘‘epidemic’’ GC. As Genta’s editorial suggests, such a constellation of non-Hp, environmental (?) factors should be further and more extensively addressed. Moving on to Uedo’s paper and its conclusive question, ‘‘... from the perspective of a practical endoscopist: do we need to take many biopsy specimens for assessing gastric cancer risk in... routine EGD?’’ [2], the answer is provided by the author a few lines further on: when both ‘‘gastric serology’’ (which is paid too little attention in non-Japanese clinical practice) and clinical examination consistently point to the need for an invasive diagnostic procedure (EGD), there can be no doubt that endoscopy and microscopy combined can identify patients warranting further diagnostic/therapeutic measures. Finally, Ahn and coworkers highlight the increased GC risk associated with the open phenotype of gastritis (i.e., multifocal atrophic gastritis, not restricted to the antrum) [3, 5]. The authors (who do not mention their biopsy sampling protocol) founded their conclusions on an elegant histological/immunohistochemical study, but it is worth noting that distinguishing between complete and incomplete intestinal metaplasia (IM) on the strength of H&E is only partially reliable (mucin histochemistry, i.e., high iron diamine [HID], is more appropriate). The clinical question, however, is whether we should perform (expensive and time-consuming) histochemistry and/or immunohistochemistry stains for a reliable assessment of the risk of GC. As in Ahn’s experience, when intestinalization of the gastric mucosa spreads from the antrum to the oxyntic M. Rugge (&) M. Fassan Department of Medical Diagnostic Sciences and Special Therapies, Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy e-mail: massimo.rugge@unipd.it

Helicobacter pylori cagA and vacA Genotypes as Predictors of Progression of Gastric Preneoplastic Lesions: A Long-Term Follow-Up in a High-Risk Area in Spain

There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions. This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression. The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR)=2.28, 95% confidence interval (CI) 1.13-4.58; OR=2.90, 95% CI 1.38-6.13; and OR=3.38, 95% CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95% CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains. H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.

Low Serum Levels of Pepsinogen and Gastrin 17 Are Predictive of Extensive Gastric Atrophy with High-Risk of Early Gastric Cancer

Atrophic gastritis (AG) is a well-recognized high-risk condition for developing gastric cancer (GC). Gastrin 17 (G17), a hormone secreted from antral G cells, regulates gastric acid secretion, and its serum level is a possible indicator of antral atrophy. Serum pepsinogen is well established as the indicator of AG involving the corpus. Here we investigated whether serum PG and G17 levels would be useful for determining the topographic pattern of AG and estimating the risk of GC. Enrolled were 122 Japanese patients with early GC (114 well- to moderate-differentiated cancers and 8 poorly-differentiated cancers). In addition, 178 subjects without GC were recruited as control from those undergoing endoscopic examination (non-GC group). All subjects were histologically assigned to the following four groups: non-AG, antrum-predominant AG, corpus-predominant AG, and multifocal AG, affecting the antrum and corpus. Serum concentrations of pepsinogen and G17 were determined using ELISA. Multifocal AG was more frequent in the GC group than in the adjusted non-GC group, and had the highest risk of GC (OR 25.1). Serum G17 was significantly decreased with the exacerbation of antral atrophy in the coexistence of corpus atrophy. Serum biomarker profiles showed that the low levels of pepsinogen and G17 could discriminate between multifocal AG and other types of AG, but not with pepsinogen level alone. Serologically defined multifocal AG had the highest cancer risk among other serologically defined AG groups (OR 26.9). In conclusion, the low serum levels of pepsinogen and G17 are predictive of extensive gastric atrophy with high-risk of early GC.

Prevalence of atrophic gastritis in dyspeptic patients in Piedmont. A survey using the GastroPanel test

Chronic atrophic gastritis (CAG) is a precursor of the intestinal type of gastric cancer, the second leading cause of cancer-related death worldwide. GastroPanel is a recently marketed serological kit for the non-invasive diagnosis of CAG, defined by some authors "even more reliable than biopsy histology". The goal of this study was 1) to evaluate the agreement between the serum gastric profile provided by GastroPanel (PGI, PGII, G-17, AbHp) and histology over CAG diagnosis, and 2) to evaluate the prevalence of CAG by means of GastroPanel in a Northern Italian dyspeptic population. Basal blood samples for GastroPanel parameters evaluation (Biohit Plc, Finland) were collected after an overnight fast from 1387 dyspeptic patients (age range: 18-80 years; F 704). Gastroscopy with two biopsies each of the antrum and corpus was offered to a group of the first 400 consecutive patients (age 18-80 years, F 214) to compare the results of histology and GastroPanel in CAG. Agreement between GastroPanel and histology for corpus-prevalent CAG was 94%, with a sensitivity and specificity of 80% and 96%, respectively. In our series of 1387 dyspeptic patients, the prevalence of corpus-prevalent CAG, of antral-prevalent CAG and of multifocal CAG (antrum+ corpus) was 10.7%, 3.6% and 2.4%, respectively. Out of the 34 patients with multifocal atrophic gastritis, 12% were under 30 years of age. GastroPanel is a reliable non-invasive test for diagnosis of CAG and deserves consideration for current use in clinical practice as a valuable diagnostic tool.

CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions

AbstractThe C-terminus of the Helicobacter pylori CagA protein is polymorphic, bearing different EPIYA sequences (EPIYA-A, B, C or D), and one or more CagA multimerization (CM) motifs. The number of EPIYA-C motifs is associated with precancerous lesions and gastric cancer (GC). The relationship between EPIYA, CM motifs and gastric lesions was examined in H. pylori-infected Colombian patients from areas of high and low risk for GC. Genomic DNA was extracted from H. pylori strains cultured from gastric biopsies from 80 adults with dyspeptic symptoms. Sixty-seven (83.8%) of 80 strains were cagA positive. The 3’ region of cagA was sequenced, and EPIYA and CM motifs were identified. CagA proteins contained one (64.2%), two (34.3%) or three EPIYA-C motifs (1.5%), all with Western type CagA-specific sequences. Strains with one EPIYA-C motif were associated with less severe gastric lesions (non-atrophic and multifocal atrophic gastritis), whereas strains with multiple EPIYA-C motifs were associated with more severe lesions (intestinal metaplasia and dysplasia) (p <0.001). In 54 strains, the CM motifs were identical to those common in Western strains. Thirteen strains from the low-risk area contained two different CM motifs: one of Western type located within the EPIYA-C segment and another following the EPIYA-C segment and resembling the CM motif found in East Asian strains. These strains induced significantly shorter projections in AGS cells and an attenuated reduction in levels of CagA upon immunodepletion of SHP-2 than strains possessing Western/Western motifs. This novel finding may partially explain the difference in GC incidence in these populations.

Gastric cancer occurrence in preneoplastic lesions: A long‐term follow‐up in a high‐risk area in Spain

There are no established criteria to classify patients into high or low risk of progressing to gastric cancer (GC). The aim of the study was to identify predictors of GC occurrence among patients with gastric preneoplastic lesions. A prospective and retrospective follow-up study was carried out in a province in Spain with one of the highest risk of GC. The study included 478 patients who underwent gastric biopsy in 1988-1994 with diagnoses of normal mucosa, nonatrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG) and complete or incomplete intestinal metaplasia (IM) and who accepted to undergo a new biopsy during 2005-2007 or had an event during follow up. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using Cox proportional hazards risk (HR) models. The mean age of the patients was 50 years, 47% were males and the mean follow-up time was 12.8 years. During follow-up, 23 GC (4.8%) were diagnosed (21 adenocarcinomas and 2 lymphomas) with an incidence of 3.77 per 1,000 person per year. The incidence rate of GC for those with incomplete IM was 16.5 per 1,000 person years. Out the 21 adenocarcinomas, 16 had an incomplete IM in the baseline diagnosis. Incomplete IM (HR 11.3; 95% CI 3.8-33.9) and a family history of GC (HR 6.1; 95% CI 1.7-22.4) were the strongest risk factors for gastric adenocarcinoma. Subtyping of IM and family history of GC may be useful for the identification of high-risk patients who need more intensive surveillance.

Short-segment Barrett’s esophagus and cardia intestinal metaplasia: A comparative analysis

to investigate the endoscopy and histology of short-segment Barrett's esophagus (SSBE) and cardia intestinal metaplasia (CIM), and their correlation with Helicobacter pylori (H. pylori) gastritis and gastroesophageal reflux disease (GERD). biopsy specimens were taken from 32 SSBE patients and 41 CIM patients with normal appearance of the esophagogastric junction. Eight biopsy specimens from the lower esophagus, cardia, and gastric antrum were stained with hematoxylin/eosin, Alcian blue/periodic acid-Schiff, Alcian blue/high iron diamine and Gimenez dye. Results were graded independently by one pathologist. the SSBE patients were younger than the CIM patients (P < 0.01). The incidence of dysplasia and incomplete intestinal metaplasia subtype was higher in SSBE patients than in CIM patients (P < 0.01). H. pylori infection was correlated with antral intestinal metaplasia (P < 0.05), but not with reflux symptomatic, endoscopic, or histological markers of GERD in CIM patients. SSBE was correlated with reflux symptomatic and endoscopic esophagitis (P < 0.01), but not with H. pylori infection and antral intestinal metaplasia. dysplasia risk is significantly greater in SSBE patients than in CIM patients. CIM is a manifestation of H. pylori-associated and multifocal atrophic gastritis, whereas SSBE may result from GERD.

Eosinophils and mast cells in chronic gastritis: possible implications in carcinogenesis

Eosinophils and mast cells participate in the immune response against Helicobacter pylori, but their involvement in the gastric precancerous process is unclear. This study aimed to estimate eosinophil and mast cell density in antral mucosa in subjects from 2 Colombian populations with contrasting gastric cancer risks. Gastric mucosa biopsies were collected from 117 adult males (72 from a high-risk area and 45 from a low-risk area). A histopathology score was used to quantify severity of the lesions. Quantitation of eosinophils in hematoxylin-eosin-stained sections and mast cells in immunostained sections for CD117/c-Kit was performed. Helicobacter pylori infection and genotyping were assessed in Steiner stain and polymerase chain reaction, respectively. Logistic regression models and semiparametric cubic smoothing splines were used for analysis of the results. Eosinophil density was significantly higher in subjects from the low-risk area as compared with subjects from the high-risk area. In both populations, eosinophil density increased with the histopathology score in the progression of lesions from normal morphology to multifocal atrophic gastritis. Intestinal metaplasia and dysplasia specimens showed further increase in eosinophil density in the high-risk area but an abrupt decrease in the low-risk area. Mast cell density increased in parallel to the histopathology score in both populations. Our results suggest that eosinophils play a dual role in chronic gastritis. In the low-risk area, elevated eosinophil density represents a T helper 2-biased response that may down-regulate the effects of proinflammatory cytokines preventing cancer development. In contrast, in the high-risk area, eosinophils might promote a T helper 1-type response leading to progression of precancerous lesions.

Source of variation in the diagnosis of Helicobacter pylori-associated multifocal atrophic gastritis.

Introduction: Multiple sampling from different sites of the stomach as well as the number of fragments of gastric mucosa available for histopathologic evaluation are important sources of variation when classifying and grading chronic gastritis. Objective: To estimate the sensitivity of the number of fragments of gastric mucosa necessary to establish the diagnosis of atrophic gastritis with intestinal metaplasia, gastric dysplasia and H. pylori infection. In addition, this study will attempt to assess the intra-observer variability in the classification of these premalignant gastric lesions. Methods: This is a 6 year-cohort study, wherein 1958 gastric endoscopic procedures performed by two gastroenterologists were reviewed. Five gastric biopsy samples were obtained from the antrum, body and lesser curvature during each procedure. One pathologist was in charge of reviewing the five histopathology samples for each subject and providing a definitive diagnosis which was used as the gold standard. Each gastric mucosa sample reviewed led to an individual diagnosis for that sample which was compared with the gold standard. Intra-observer variability was assessed in 127 individuals who correspond to a random sample of 20% of the total endoscopic procedures performed during the 72 month-follow-up. Results: The sensitivity of the diagnosis of intestinal metaplasia (IM) and gastric dysplasia increased proportionally with the number of gastric mucosa samples reviewed. The lesser curvature of the stomach had the highest sensitivity for the diagnosis of IM and dysplasia, among all the stomach regions studied. Just one sample of gastric mucosa attained a sensitivity of 95.9% for the detection of H. pylori infection. The intra-observer agreement for the diagnosis of multifocal atrophic gastritis was 86.1% and the kappa value was 0.79 (95% CI 0.76-0.85). Alcohol-fixed biopsy specimens were inadequate to diagnose H. pylori infection and to assess dysplasia. Conclusion: The number of mucosa gastric fragments reviewed, the fixation method used, and the biopsy site are all important factors in order to ensure a correct classification of chronic gastritis.

Chronic Active Gastritis in X-linked Lymphoproliferative Disease

Gastric lesions in primary constitutive immune deficiencies include multifocal atrophic gastritis, erosive pangastritis, and a pattern of gastric lesions reminiscent of graft-versus-host disease. We describe the genetic anomalies in 2 monozygotic twins with an X-linked lymphoproliferative disease (XLP; MIM 308240), a rare familial setting of high susceptibility to Epstein-Barr virus (EBV). Since early childhood, both twin brothers exhibited a severe chronic active atrophic pangastritis. A germline screening of the SH2D1A (MIM 300490) and BIRC4 (MIM 300079) genes was performed, and also a high-resolution whole-genome SNP profiling (Infinium Sentrix Human-1 Genotyping BeadChip, Illumina). A 3 Megabase deletion in the Xq25 region, encompassing the SH2D1A gene, was defined by SNP array genotyping. Histologic analysis of yearly or twice yearly gastric biopsies in both children showed a Helicobacter pylori-negative, Epstein-Barr virus-negative chronic active atrophic pangastritis, with superficial ulcer formation, foveolar hyperplasia, glandular dilatation and ultimately pseudopyloric and intestinal metaplasia. No such chronic active inflammatory gastric lesions have been reported to date in XLP. The similarities between XLP and common variable immunodeficiency (MIM 240500) underscore the need for early recognition and close monitoring of these gastric lesions, with special regard to their neoplastic potential. No infectious cause was determined. We favor a dysimmune mechanism in the development of this chronic atrophic gastritis, presenting a striking similarity to the recently described atrophic autoimmune pangastritis.

Características clinicopatológicas de la dispepsia no investigada en España

Most patients with uninvestigated dyspepsia are diagnosed with functional dyspepsia. Various types of Helicobacter pylori gastritis have been described, each of which is associated with a distinct natural history of the infection (i.e. a different risk of ulcer or gastric cancer). To determine the clinical and pathological characteristics of patients with uninvestigated dyspepsia in our area and the prevalence of the distinct types of H. pylori gastritis among patients with functional dyspepsia. Ninety-eight patients (47 men and 51 women, mean age 35.8+/-13 years) with uninvestigated dyspepsia were included in this study. All the patients completed the Dyspepsia-Related Health Scale and all patients underwent gastroscopy with biopsy and the C13-urea breath test. Fourteen patients had organic causes of dyspepsia and 78 had functional dyspepsia. Fifty-one patients with functional dyspepsia (65%) had H. pylori infection; of these, 27 had pangastritis, 21 had antrum-predominant gastritis, 2 had multifocal atrophic gastritis and 1 had normal gastric mucosa. Among uninfected patients, 2 had multifocal atrophic gastritis. The prevalence of functional dyspepsia in this series was 85%. Twenty-seven percent of patients with functional dyspepsia had a combination of H. pylori infection and antrum-predominant gastritis, the type of gastritis predisposing to duodenal ulcer. Only 5% of the patients had multifocal atrophic gastritis, which is associated with a high risk of gastric cancer.

The Serological Gastric Biopsy: A Non-endoscopical/Histopathologic Diagnostic Approach in Management of the Dyspeptic Patients

Objective: To asses the sensitivity, specificity and the predictive value of a 'gastropanel' blood test, including serum pepsinogen I (S-PGI) and amidated gastrin-17 (S-G-17) in the diagnosis of atrophic gastritis most probably due to helicobacter pylori (Hp) and to compare the results of serology with the endoscopic/histopathologic findings as a gold standard diagnostic tool. This study comprised 86 dyspeptic outpatients who underwent a diagnostic gastroscopy with multiple biopsies from the antrum and corpus for histopathologic examination. Histopathologically, the series of cases included 46 patients diagnosed as having atrophic gastritis. Twenty five had an antral atrophy, 6 had corpus atrophy and 15 patients had an atrophic gastritis in both the antrum and corpus (multifocal atrophic gastritis) MAG. The remaining 40 cases were considered as controls, 32 had a non-atrophic gastritis (NAG) and both the antrum and corpus were normal and healthy in 8 subjects. The fasting levels of S-PGI and antibodies to Hp IgG-antibodies (S-HpAb) and postprandial amidated S-G-17 (S-G-17prand) were measured 20 min after a protein-rich drink and were determined using enzyme immunoassay (EIA) methods. The serologic and morphologic results were compared with estimating the sensitivity, specificity, positive and negative predictive (PPV and NPV) and accuracy values of the tests (S-G-17 and S-PGI). Mean values of both S-G-17prand and S-PGI decreased with increasing grade of antral and corpus atrophy, respectively. A low S-PGI (<25 mg L-1) was found in 4 of 6 patients with corpus atrophy (66.70%) and in 5 of 32 (15.62%) patients with NAG in the biopsy specimens. A low S-G-17prand (<5 pmol L-1) was found in 13 patients with Hp-associated antral atrophy and in 5 of 32 (15.62%) patients with NAG. The diagnosis of gastritis obtained with the blood test panel is in good agreement with the endoscopic and biopsy findings: 92% of the patients went into same gastritis categories with both the panel and endoscopic/histopathologic findings. The sensitivity, specificity, PPV, NPV and accuracy values of the blood test panel (S-G-17prand and S-PGI) in delineation of patients with atrophic gastritis (either in the antrum or the corpus, or both) versus NAG and normal stomach were 87.5, 82.60, 81.40, 88.40 and 85% respectively. Low levels of S-G-17prand and S-PGI are conceivable biomarkers of atrophic gastritis. The serologic method gave a reasonable sensitivity, specificity, PPV, NPV and accuracy values in the diagnosis of atrophic gastritis. So, it may be offered as the screening tool for atrophic gastritis.

Association of Interleukin-1beta Gene Polymorphisms with Precancerous Gastric Lesions in African Americans and Caucasians

Interleukin-1beta plays an important role in inflammation and gastric physiology. Polymorphisms of the IL1B gene have been associated with gastric atrophy and increased cancer risk, especially in Helicobacter pylori-infected subjects. The aim of this study was to evaluate the relationship between IL1B and IL1 receptor antagonist gene polymorphisms and the risk of multifocal atrophic gastritis in African Americans and Caucasians. Genomic DNA was extracted from gastric biopsies of 269 adult outpatients (172 African Americans and 97 Caucasians) undergoing diagnostic upper gastrointestinal endoscopy. Histological diagnosis was evaluated according to the updated Sydney System and H. pylori status was assessed by Steiner silver stain. Polymorphisms of the IL1B gene (-511, -31, and +3954) and the IL1 receptor antagonist were investigated by PCR-RFLP. Logistic regression models were used to identify variables associated with multifocal atrophic gastritis in terms of odds ratios and 95% confidence intervals. Considering subjects with normal histology and nonatrophic gastritis as controls, a significant association was found between IL1B+3954T carrier and multiatrophic gastritis (OR 2.23, 95% CI 1.28, 3.88). Analyses stratified by ethnic group demonstrated similar associations in both African Americans (OR 2.23, 95% CI 1.14, 4.37) and Caucasians (OR 2.04, 95% CI 0.74, 5.65). A positive but not significant association was found between the allele 2 of the IL1RN and the presence of multifocal atrophic gastritis. The remaining proinflammatory polymorphisms were not associated with this precancerous lesion. Our results suggest that the presence of IL1B+3954T allele is a risk marker for multifocal atrophic gastritis in the population studied.

Ulcers and Gastritis

Significant advances continue to be made in the area of gastritis and ulcer disease. Studies to identify the most appropriate use of capsule endoscopy have now confirmed that it is superior to other methods for identifying small-bowel mucosal pathology and sites of obscure gastrointestinal bleeding. It has increasingly been recognized that the complications of ulcer disease are secondary to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to interactions between NSAIDs and Helicobacter pylori. Effective prophylaxis for NSAID in H. pylori-negative individuals continues to be a challenge, as it has become clear that conclusions from studies focusing on endoscopic ulcers in patients whose H. pylori status was unknown provided a false sense of security. The concept of multifocal atrophic gastritis has been challenged. The precursor lesion to gastric cancer now appears to be a sheet of pseudopyloric metaplasia advancing into the gastric body with islands of intestinal metaplasia embedded within it. Multifactorial models such as those proposed for understanding periodontal disease, including the organism, environmental factors, and host factors, appear particularly applicable to understanding the pathogenesis of H. pylori-associated gastric cancer.