Pylori-negative Chronic Gastritis Research Articles

Dyspepsia-Like Symptoms in Helicobacter pylori-Negative Chronic Gastritis are Associated with ASCA-, ANCA-, and Celiac Seropositivity but Not with Other Autoimmune Parameters: A Single-Centre, Retrospective Cross-Sectional Study.

IntroductionDyspeptic symptoms are frequent in the general population, with a high socioeconomic burden. Helicobacter pylori (H. pylori) might be a possible etiological factor; however, it is also common in H. pylori negative gastritis. Clarification of the underlying aetiology might be beneficial to set up the optimal treatment strategy for dyspepsia and chronic gastritis (CG) itself. We aimed to assess the prevalence of dyspeptic symptoms in patients with H. pylori negative CG and explore autoimmunity’s possible role.MethodsThis retrospective study included data from patients with H. pylori negative CG. Exclusion criteria were (1) acute gastritis; (2) reactive gastropathy; (3) subjects without any serology testing results; (4) H. pylori positivity; (5) presence of atrophy, intestinal metaplasia (IM), gastroesophageal reflux disease (GERD), ulcer, or cancer. The following endpoints were assessed (1) the rate of dyspepsia-like symptoms; (2) association between dyspepsia and autoimmune disease-related seromarker positivity (AISP); (3) frequency of other symptoms in CG and its association with AISP; (4) location of the inflammation and its association with AISP.ResultsFrom a total of 285 patients, 175 were included in this study. Among these patients, 95 experienced dyspeptic symptoms (54.29%) and were associated more with AISP (p = 0.012), especially with celiac seropositivity (p = 0.045), anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) positivity (p = 0.043). A significant association was not found with other tested autoimmune (AI)-related antibody positivity.ConclusionPositivity of seromarkers of autoimmune diseases in chronic gastritis may predispose to have dyspeptic symptoms and may be the causative factor behind some cases of uninvestigated dyspepsia. These data suggest that further prospective studies are needed to clarify whether screening for autoantibodies in patients with dyspepsia is cost-effective and helps the earlier diagnosis of autoimmune diseases.

Analysis of the relation between elevated neutrophil lymphocyte ratio, and erythrocyte sedimentation rate in Helicobacter pylori positive chronic gastritis patients

Background: Aim of the study was to analyse the relation between elevated neutrophil lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR) in Helicobacter pylori (H. pylori) positive chronic gastritis patients, as compared to the control group containing H. pylori negative chronic gastritis patients.Methods: Chronic gastritis patients were segregated in equal numbers based on H. pylori status. NLR was calculated, and ESR noted from the observations, comparison was done between the control and the study groups.Results: A total of 100 patients were included in the study. The 50 each from the control and study group. An observation of elevation in NLR and ESR in H. pylori positive chronic gastritis patients, as compared to the control group was seen. With an average NLR of 2.43 and 1.43, in the control and study group, respectively.Conclusions: Raise in NLR in H. pylori positive chronic gastritis patients with an associated raise in ESR suggests, the severity of the infection and the need for eradication and prevent complications.

Prevalence and Clinical Significance of Helicobacter Pylori-negative Chronic Gastritis in Children.

The clinical significance of Helicobacter pylori-negative chronic gastritis (HPNCG) in children is unclear. We examined this issue in patients who had undergone esophagogastroduodenoscopy with systematic gastric sampling. Data of 1178 consecutive children who underwent diagnostic esophagogastroduodenoscopy were collected. Baseline characteristics and long-term outcomes were compared between children with active and inactive HPNCG and those with normal gastric histology. Follow-up data were available for up to 13 years. Altogether 24 (2.0%) children had active and 235 (19.9%) inactive HPNCG, 27 (2.3%) were Hpylori-positive, 46 (3.9%) had other gastric pathology, and 846 (71.8%) normal histology. Diarrhea (31.3% vs 25.1%, P = 0.033), poor growth (23.6% vs 14.7%, P < 0.001), bloody stools (13.9% vs 7.2%, P < 0.001), anemia (46.5% vs 23.4%, P < 0.001), hypersedimentation (39.7% vs 21.4%, P < 0.001), hypoalbuminemia (40.4% vs 16.2%, P < 0.001), and elevated fecal calprotectin (62.4% vs 31.5%, P < 0.001) were more common and heartburn (13.9% vs 22.9%, P = 0.002) less common in the HPNCG group than in the controls. Both active (OR 3.64,95% CI 1.35-9.82) andinactive (2.98, 2.18-4.08) HPNCG predicted a diagnosis in the initial investigations. Crohn disease (41.7%) was the most common diagnosis in active HPNCG and celiac disease (37.4%) in inactive HPNCG. During follow-up, 7 (9.9%) of the 71 initially nondiagnosed HPNCG children received a diagnosis. HPNCG is a frequent finding in children undergoing EGD, the active form being associated especially with Crohn disease and the inactive with celiac disease. The long-term prognosis of patients with HPNCG who do not receive an initial diagnosis is good.

Helicobacter pylori-negative Chronic Gastritis in Children: A Systematic Review.

To systematically review the current evidence on Helicobacter pylori-negative chronic gastritis including natural history, available therapies and outcomes. Articles providing data on the prevalence, treatment or outcomes of Helicobacter pylori-negative gastritis were identified through a systematic search in the MEDLINE and EMBASE databases. All original research articles from human studies until October 31, 2021, were included. A total of 54 studies were included consisted of eosinophilic gastritis (n = 9), autoimmune gastritis (n = 11), collagenous gastritis (n = 16), focally enhanced gastritis (n = 6), lymphocytic gastritis (n = 5) and other causes including idiopathic gastritis and chronic renal failure related (n = 7). Most of the included studies were either cross-sectional or longitudinal cohorts except for collagenous gastritis, which mainly included case reports and case series. The prevalence of paediatric eosinophilic gastritis ranges between 5 and 7/100,000 and patients have generally favourable outcome with 50% to 70% clinical and histological response to either corticosteroids or elimination diets. Autoimmune gastritis and collagenous gastritis are extremely rare entities, commonly present with refractory iron deficiency anaemia, while lymphocytic gastritis is relatively common (10%-45%) in children with coeliac disease. Data on treatments and outcomes of autoimmune, collagenous, and focally enhanced gastritis are lacking with limited data implying poor response to therapy in the former 2 diagnoses. Helicobacter pylori-negative gastritis is uncommonly reported, mainly in small cohorts, mixed adult-paediatric cohorts or as sporadic case reports. As common symptoms are not specific, thus not always result in an endoscopic evaluation, the true prevalence of these distinct disorders may be underestimated, and thus under reported.

Diagnostic value of combined prealbumin-to-fibrinogen and albumin-to-fibrinogen ratios in Hp-negative gastric cancer.

This study aimed to investigate the diagnostic value of prealbumin-to-fibrinogen ratio (PFR) and albumin-to-fibrinogen ratio (AFR) alone or in combination in Helicobacter pylori-negative gastric cancer (Hp-NGC) patients. This study included 171 healthy controls, 180 Hp-NGC patients, and 215 Helicobacter pylori-negative chronic gastritis (HpN) patients. We compared the differences of various indicators and pathological characteristics between groups with Mann-Whitney U test and Chi-square test. The diagnostic value of PFR and AFR alone or in combination for Hp-NGC patients was assessed by the receiver operating characteristic (ROC) curve. PFR and AFR were related to the progression and clinicopathological characteristics of Hp-NGC. As the disease progressed, PFR and AFR values gradually decreased and were negatively related to the tumor size and depth of invasion. In addition, the area under the curves (AUCs) that resulted from combining PFR and AFR to distinguish Hp-NGC patients from healthy controls and HpN patients were 0.908 and 0.654, respectively. When combined with PFR and AFR in the differential diagnosis of tumors with a maximum diameter ≥ 5 cm and the T3 + T4 stage, the AUCs were 0.949 and 0.922; the sensitivity was 86.32% and 80.74%; and the specificity was 94.74% and 92.98%, respectively. PFR and AFR may be used as diagnostic biomarkers for Hp-NGC. The combination of PFR and AFR was more valuable than each indicator alone in the diagnosis of Hp-NGC.

Oral Microbiota and Salivary Levels of Oral Pathogens in Gastro-Intestinal Diseases: Current Knowledge and Exploratory Study.

Various bi-directional associations exist between oral health and gastro-intestinal diseases. The oral microbiome plays a role in the gastro-intestinal carcinogenesis and fusobacteria are the most investigated bacteria involved. This paper aims to review the current knowledge and report the preliminary data on salivary levels of Fusobacterium nucleatum, Porphyromonas gingivalis and Candida albicans in subjects with different gastro-intestinal conditions or pathologies, in order to determine any differences. The null hypothesis was “subjects with different gastro-intestinal diseases do not show significant differences in the composition of the oral microbiota”. Twenty-one subjects undergoing esophagastroduodenoscopy or colonscopy were recruited. For each subject, a salivary sample was collected before the endoscopy procedure, immediately stored at −20 °C and subsequently used for genomic bacterial DNA extraction by real-time PCR. Low levels of F. nucleatum and P. gingivalis were peculiar in the oral microbiota in subjects affected by Helicobater pylori-negative chronic gastritis without cancerization and future studies will elucidate this association. The level of C. albicans did not statistically differ among groups. This preliminary study could be used in the future, following further investigation, as a non-invasive method for the search of gastrointestinal diseases and associated markers.

CORRECTION OF NITRIC OXIDE SYSTEM IN PATIENTS WITH HELICOBACTER PYLORI-ASSOCIATED CHRONIC GASTRITIS AND CONCOMITANT TYPE 2 DIABETES MELLITUS

The current data suggest that Helicobacter pylori infection and type 2 diabetes mellitus may affect the state of nitric oxide system, which significantly influences stomach functioning. The aim of the research was to study the state of nitric oxide system in patients with Helicobacter pylori-associated chronic gastritis and concomitant type 2 diabetes mellitus, and to investigate the potential of eupatilin in its correction. 172 patients with confirmed chronic gastritis were enrolled into the study. They were divided into 4 groups: І (n=71) included individuals with Helicobacter pylori-positive chronic gastritis and type 2 diabetes mellitus; ІІ (n=21) included patients with Helicobacter pylori-negative chronic gastritis and type 2 diabetes mellitus; ІІІ (n=48) included patients with Helicobacter pylori-positive chronic gastritis without type 2 diabetes mellitus; IV (n=32) was made up with individuals having Helicobacter pylori-negative chronic gastritis without type 2 diabetes mellitus. According to prescribed therapeutic schemes the patients of groups І and ІІІ were additionally subdivided into the following subgroups: groups I-A (n=35) and III-A (n=24) underwent anti-Helicobacter therapy, groups I-В (n=36) and III-B (n=24) were prescribed to receive anti-Helicobacter therapy and eupatilin. Anti-Helicobacter therapy included pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg bid for 10 days. The patients received Eupatilin as an active agent of Stilen preparation, which contains 0.48 – 1.44 mg of eupatilin, tid for 28 days. Nitrites content and activity of inducible and constitutional nitric oxide synthases were analyzed in blood serum before the treatment and on the 28th day after the therapy completed. The patients of group I before the treatment were found to have an increase of nitrites level in 1.4 times, inducible nitric oxide synthase in 1.5 times higher in comparison to the patients of group II. An activity of constitutional nitric oxide synthase in patients with chronic gastritis and type 2 diabetes mellitus was found to be decreased regardless the Helicobacter pylori-status in 2.3 and 2.7 times in comparison to the patients of groups III and IV respectively. Eupatilin prescription promoted Helicobacter therapy eradication and treatment outcomes through nitrites decrease in 1.5 times, reduction of inducible nitric oxide synthase activity in 1.2 times, and growth of constitutional nitric oxide synthase in1.2 times in patients of I-B group in comparison to group I-A. Combined anti-Helicobacter therapy with eupatilin promotes successful Helicobacter pylori eradication, which was 6.2% higher in patients of I-B group than in I-A group. Conclusions: Helicobacter pylori-associated chronic gastritis in patients with type 2 diabetes mellitus is followed by rise of nitrites, inducible nitric oxide synthase activity and simultaneous decline of constitutional nitric oxide synthase in blood serum. Eupatilin prescription as a component of integrated anti-Helicobacter therapy increases the efficacy of Helicobacter pylori eradication and improves the state of nitric oxide-system due to its anti-inflammatory, antioxidant and cytoprotective properties.

Tissue transglutaminase activity in human gastric mucosa according to Helicobacter pylori infection.

Tissue transglutaminase (t-TG) is unique among TG enzymes because of its additional role in several physiological and pathological activities, including inflammation, fibrosis, and wound healing. The presence of t-TG has previously been described in the intestine of human and animal models, yet studies on t-TG activity in human gastric mucosa are missing. Helicobacter pylori infection is the major cause of gastritis and peptic ulcers. For the first time, our results show that t-TG activity was significantly higher in antral specimens of patients with chronic active gastritis associated with H. pylori infection compared to H. pylori negative chronic gastritis and normal antral mucosa. These findings suggest that t-TG has a role in the natural history of human gastritis, which requires further investigation but may be an avenue for new therapeutic options.

Gastritis – facts and doubts

IntroductionMany clinicians consider chronic gastritis to be equivalent to Helicobacter pylori infection. However, it is known that there are numerous other causes of the condition.AimDetermination of the incidence of gastritis in patients with dyspepsia referred for diagnostic endoscopy of the upper part of the digestive tract, identification of the parts of the stomach most frequently affected by the inflammation, as well as the impact of an insufficient number of collected samples on the correct diagnosis.Material and methodsUpper gastrointestinal endoscopy due to dyspepsia was performed in 110 patients. In the course of gastroscopy two biopsy specimens were collected for histopathological examination and towards H. pylori infection from the lesser and greater curvature in the antrum 3 cm from the pyloric sphincter, in the body – 4 cm proximally to the stomach angular incisure on the lesser curvature, and in the middle of the greater curvature, as well as in the subcardiac region on the side of the lesser and greater curvature.ResultsIn patients with dyspepsia H. pylori-negative chronic gastritis is more common than gastritis with accompanying H. pylori infection. Collection of too small a number of biopsy specimens results in failure to detect inflammatory changes and/or H. pylori infection, which may be limited to one part of the stomach. Biopsy specimens of gastric mucosa should be collected in compliance with the assumptions of the Sydney System. Helicobacter pylori infection in people with dyspepsia is now being reported more rarely than in the past (36%).ConclusionsIn patients with dyspepsia chronic H. pylori-negative gastritis is more common than gastritis with an accompanying H. pylori infection. Helicobacter pylori infection is not always equivalent to the presence of chronic gastritis.

Gastric pneumatosis: a radiological diagnosis with a wide clinical spectrum

We present the case of a 72-year-old woman with a history of type 2 diabetes, ischemic stroke, and fracture of the femur. She presented to the emergency department with a 3-day history of vomiting and epigastric pain. Her physical examination was remarkable only for a distended but nonpainful abdomen. She had a mild leucocytosis (11.3×109/L) and elevated C-reactive protein (113mg/L). Radiographs of her chest (● Fig.1) and abdomen (● Fig.2) showed intramural gas in the gastric wall, a pneumoperitoneum, and massive esophageal dilatation. These findings were also observed in a subsequent abdominal computed tomography (CT) scan (● Fig.3). Given the lack of systemic toxicity shewas admitted to the ward for conservative therapy and was kept nil by mouth with intravenous hydration and proton pump inhibitor (PPI) therapy. She did not start antibiotic therapy and blood cultures were negative. She underwent an upper gastrointestinal endoscopy, which showed erosions of the antral mucosa (● Fig.4) with Helicobacter pylori-negative chronic gastritis on histology. A significant reduction of the gastric gas with disappearance of the pneumoperitoneum was documented on a repeat CT scan on day 4.The patient recovered rapidly and was discharged after 1 week. She has been asymptomatic ever since. Gastric pneumatosis is a rare radiological sign that indicates a clinical disorder with a wide spectrum of severity, which ranges from the frequently fatal emphysematous gastritis to oligosymptomatic gastric emphysema. This case is interesting as it clearly illustrates the more benign end of the spectrum of gastric pneumatosis, which can range from this to a fulminating septic condition [1], with subacute presentations in between these extremes [2]. We feel that it is important to manage patients according to the whole clinical picture and not rely solely on imaging findings–even in the presence of traditionally ominous free intraperitoneal gas [3], which proved to be benign in our patient’s case.

Helicobacter pylori infection and administration of non-steroidal anti-inflammatory drugs down-regulate the expression of gastrokine-1 in gastric mucosa

Gastrokine-1 is a novel protein that plays an important role in the maintenance of the integrity of the gastric mucosa. However, whether Helicobacter pylori infection and non-steroidal anti-inflammatory drugs, which are known to cause gastric mucosal injuries, affect gastrokine-1 expression in the gastric mucosa is unknown. The aim of the present study was to determine gastric mucosal expression of gastrokine-1 in patients with Helicobacter pylori infection or long-term non-steroidal anti-inflammatory drug administration. A total of 40 patients with functional dyspepsia (20 with Helicobacter pylori-negative chronic gastritis, and 20 with Helicobacter pylori-positive chronic gastritis), and 37 Helicobacter pylori-negative long-term non-steroidal anti-inflammatory drug users (26 with aspirin, 11 with selective cyclooxygenase-2 inhibitors) were selected. In addition, 20 Helicobacter pylori-negative healthy volunteers were recruited as controls. All subjects underwent endoscopies with biopsies taken from the antrum and the sites with lesions. Gastric mucosal changes were detected endoscopically and histologically, and gastrokine-1 protein expression in the antral mucosa was analyzed by immunohistochemistry. Expression of gastrokine-1 protein was decreased in Helicobacter pylori-positive chronic gastritis compared with Helicobacter pylori-negative subjects and the healthy controls. Similarly, gastrokine-1 expression in non-steroidal anti-inflammatory drug users was also decreased, compared with the healthy controls, but there was no significant difference in gastrokine-1 expression between the aspirin group and selective cyclooxygenase-2 inhibitor group. Moreover, gastrokine-1 expression levels tended to be associated with the severity of chronic gastritis. Both Helicobacter pylori infection and long-term non-steroidal anti-inflammatory drug administration downregulate gastrokine-1 expression in the gastric mucosa, which may contribute to the gastric mucosal injuries induced by these two factors.

Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa

Gene silence of IRX1 tumor suppressor by promoter CpG methylation combined with loss of heterozygosity (LOH) has been identified in human gastric cancer. This study investigated the association between methylation of IRX1 and Helicobacter pylori infection in gastric mucosa tissues and cell line. IRX1 methylation was studied by methylation specific polymerase chain reaction (MSP) and bisulfate sequencing polymerase chain reaction (BSP) methods in gastric mucosa tissues from H. pylori-positive chronic gastritis patients or H. pylori-negative chronic gastritis patients. Promoter activity, methylation status and gene expressing level of IRX1 were evaluated by persistent infecting H. pylori on human gastric cells GES-1 in vitro. Electron microscopy was used to observe the effect of H. pylori infection on GES-1 gastric mucosa cells. The methylation level of IRX1 promoter in H. pylori positive chronic gastritis and H. pylori negative chronic gastritis was 55.30%±13.17 versus 5.20%±6.31, respectively (P<0.01). H. pylori infection stimulated increased microvillus, and mucous secretion on GES-1 cells. Infection of H. pylori induced IRX1 promoter methylation and downregulation of the promoter activity as well as gene expression significantly. This study firstly demonstrated that H. pylori infection contributes to IRX1 promoter methylation on gastric mucosa.

Helicobacter pylori-infection-associated CpG island hypermethylation in the stomach and its possible association with Polycomb repressive marks

Helicobacter pylori infection can induce CpG island (CGI) hypermethylation in gastric mucosa. Recently, genes occupied by Polycomb proteins in embryonic stem cells were shown to be vulnerable to aberrant DNA hypermethylation in cancers. To explore the relationship between H. pylori infection and DNA methylation changes in neoplastic and non-neoplastic stomach, we analyzed 25 CGIs and repetitive DNA elements from 82 chronic gastritis and 69 gastric carcinomas. Twenty-three CGIs showed significantly higher methylation levels in H. pylori-negative gastric carcinoma (n = 28) than in H. pylori-negative chronic gastritis (n = 39; P < 0.05), indicating cancer-associated methylation. Eight CGIs exhibited significantly higher methylation levels in H. pylori-positive chronic gastritis (n = 43) than in H. pylori-negative chronic gastritis (n = 39; P < 0.05). Six CGIs showed both cancer-associated and H. pylori-associated hypermethylation. Six (75%) of the eight H. pylori-associated hypermethylated genes contained at least one of three repressive marks (Suzl2 occupancy, Eed occupancy, histone H3 K27 trimethylation), whereas 31% of the remaining cancer-associated hypermethylated genes had at least one mark. The findings suggest that H. pylori infection strongly induces CGI hypermethylation in gastric epithelial cells and that susceptibility to H. pylori-induced DNA hypermethylation may be determined by Polycomb repressive marks in stem or progenitor cells.

Evaluation of the role of Helicobacter pylori as a promoter of gastric cancer from the viewpoint of structural chromosomal aberration

SummaryAimTo examine whether Helicobacter pylori induces structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI) in the infected gastric mucosa.MethodsSubjects were 13 patients with H. pylori‐positive and 9 with H. pylori‐negative gastric cancer and 20 patients with H. pylori‐positive and 4 patients with H. pylori‐negative chronic gastritis. Gastric mucosal tissues were endoscopically sampled from each subject. Each sample was checked for structural chromosomal aberrations (LOH and MSI) by PCR and microsatellite analysis, using a total of 31 primers corresponding to the regions containing the major genes of chromosomes 1q, 5q, 7q, 17p, 17q, 18q and 21q.ResultsAll tissue samples obtained from cancer‐affected regions of the stomach had structural chromosomal aberrations (LOH or MSI), irrespective of H. pylori infection. The degree of structural chromosomal aberration was greater in poorly differentiated than well‐differentiated adenocarcinoma. In addition, structural chromosomal aberrations were also found in a few samples obtained from the chronic atrophic gastritis group, irrespective of H. pylori infection.ConclusionsIt seems unlikely that H. pylori serves as a direct promoter of gastric cancer, and H. pylori‐positive chronic gastritis may not always be a precancerous state.

COLLAGENOUS GASTRITIS ASSOCIATED WITH GASTRIC PERFORATION

Purpose: Collagenous gastritis (CG) is an exceptionally rare clinicopatho-logic entity of unknown etiology characterized by thickening of the subep-ithelial collagen layer in the gastric mucosa. We report the first case of CG associated with gastric perforation. An 18-year-old male was referred following two perforated gastric ulcers. He had undergone patch repair following the first and partial gastrectomy with highly selective vagotomy following the second perforation. EGD revealed nodular erythema involving the proximal stomach. Biopsy revealed active chronic gastritis with no H. pylori. Evaluation for known etiologies of gastritis was unrevealing. Gastric acid analysis: 1 hour basal acid 0.91 m Eq/L, gastrin level, small bowel biopsy-normal, endomysial antibody-negative. EGD a year later showed persistent nodularity and biopsy revealed a thick layer of sub-epithelial collagen confirmed by trichrome staining (figure 1). Therapy with Bismuth subsalicylate resulted in no endoscopic or histologic improvement. Colonic biopsies were normal.FigureFirst described in 1989, less than 20 cases of CG have been reported. It is defined histologically by presence of a thickened subepithelial collagen band at least 10 μm in thickness with an inflammatory infiltrate of the lamiNaPropria. Some of the reported cases were associated with celiac disease, collagenous and lymphocytic colitis. The distribution of this band tends to be irregular, which may explain the delay in diagnosis in our patient. The pathogenesis remains obscure and no effective therapy has been described. Postulated pathogenetic theories include autoimmune injury and local abnormality of peri-cryptal collagen with leakage of plasma proteins and subsequent replacement with collagen. None of the reported cases were associated with perforation. Encasement of sub-epithelial blood vessels by collagen, as seen in our patient, could result in gastric mucosal ischemia making it more susceptible to acid related injury. Physicians should be aware of this entity during routine examination of gastric biopsies. CG should be considered in the differential diagnosis of unexplained H. pylori negative chronic gastritis. [figure 1]

The effect of Helicobacter pylori infection on levels of DNA damage in gastric epithelial cells.

Helicobacter pylori infection leads to an increased risk of developing gastric cancer. The mechanism through which this occurs is not known. We aimed to determine the effect of H. pylori and gastritis on levels of DNA damage in gastric epithelial cells. Epithelial cells were isolated from antral biopsies from 111 patients. DNA damage was determined using single cell gel electrophoresis and the proportion of cells with damage calculated before and 6 weeks after eradication of H. pylori. Cell suspensions generated by sequential digestions of the same biopsies were assayed to determine the effect of cell position within the gastric pit on DNA damage. DNA damage was significantly higher in normal gastric mucosa than in H. pylori gastritis [median (interquartile range) 65% (58.5-75.8), n = 18 and 21% (11.9-29.8), n = 65, respectively, p <.001]. Intermediate levels were found in reactive gastritis [55.5% (41.3-71.7), n = 13] and H. pylori negative chronic gastritis [50.5% (36.3-60.0), n = 15]. DNA damage rose 6 weeks after successful eradication of H. pylori[to 39.5% (26.3-51.0), p =.007] but was still lower than in normal mucosa. Chronic inflammation was the most important histological factor that determined DNA damage. DNA damage fell with increasing digestion times (r = -.92 and -.88 for normal mucosa and H. pylori gastritis, respectively). Lower levels of DNA damage in cells isolated from H. pylori infected gastric biopsies may be a reflection of increased cell turnover in H. pylori gastritis. The investigation of mature gastric epithelial cells for DNA damage is unlikely to elucidate the mechanisms underlying gastric carcinogenesis.

Antigenic Phenotyping of Lymphoid Cells and B Cell Gene Rearrangement in Type B Gastritis and in Gastritis Not Associated with Helicobacter pylori Colonization

Marginal-zone B cells of the mucosa-associated lymphoid tissue (MALT) are the normal counterpart of the neoplastic cells in MALT lymphoma. In both cases these lymphocytes express surface immunoglobulins, but are negative when stained for B cell associated antigens like CD10 and CD23. Furthermore, the B cell gene rearrangement has been found in Helicobacter pylori associated chronic gastritis and in extranodal type of marginal-zone lymphoma. The aim of this study was to quantify the number of IgM-, CD10-, and CD23-positive lymphocytes in patients with type B gastritis and to compare the results with the antigen profile of mononuclear cells in patients with gastritis not associated with H. pylori. Additionally, the immunoglobulin heavy-chain (IgH) gene rearrangement in H. pylori positive and H. pylori negative gastritis was studied. From 23 patients with a positive urease test and/or histologically proven H. pylori infection and chronic gastritis and from 22 patients with H. pylori negative chronic gastritis mucosa biopsy specimens were taken. Single-cell suspensions were obtained following enzymatic digestion. For immunocytochemistry, an alkaline phosphatase-antialkaline phosphatase method was applied. IgH gene rearrangement in formalin-fixed, paraffin-embedded specimens was determined by polymerase chain reaction in 11 patients with chronic gastritis. An increase in mu-positive plasma cells and B lymphocytes was detected in patients with H. pylori positive gastritis as compared with patients with H. pylori negative gastritis (10.0 vs. 3.9%, p < 0.001, and 4.3 vs. 1.6%, p < 0.01, respectively). In both groups, the proportion of CD10- and CD23-positive lymphocytes was <1%. IgH gene rearrangement was not restricted to type B gastritis; single bands were also present in 3 of 7 patients with H. pylori negative chronic gastritis. Our finding of IgH gene rearrangement in some of the patients with H. pylori negative chronic gastritis indicates that additional factors may be critical for these genotypical changes and for the pathogenesis of gastric MALT lymphoma.

Prevalence of Helicobacter pylori infection and gastric mucosal abnormalities in chronic pancreatitis

Objective: Chronic pancreatitis is often associated with abnormal gastric acid secretion. However, previous studies have taken into consideration neither the potential role of Helicobacter pylori ( H. pylori) infection nor histological features of the gastric mucosa in this context. The aim of this study was to analyze the prevalence of H. pylori infection as well as the pattern of gastritis in patients with chronic pancreatitis. Methods: Forty patients with chronic alcoholic pancreatitis were included in the study: 40 patients with alcoholic liver cirrhosis and normal exocrine pancreatic function and 40 asymptomatic nonalcoholic subjects matched for age and sex used as control subjects. Endoscopy was performed in all patients, and five biopsy specimens from the antrum (three from the gastric body and two from the cardia) were taken for histological grading of gastritis and H. pylori assessment. Results: Prevalence of H. pylori infection was similar in subjects with chronic pancreatitis (38%), asymptomatic subjects (28%) and liver cirrhosis (30%). Topography and expression of H. pylori-associated chronic gastritis was also not different among the three groups of subjects. In H. pylori-negative subjects, the presence of moderate to severe chronic antral gastritis was significantly more common in patients with chronic pancreatitis (40%) than in subjects with liver cirrhosis (18%) and in asymptomatic subjects (14%) ( p < 0.05). No difference was found among the three groups of patients with regard to gastritis activity, atrophy, and intestinal metaplasia in the various gastric regions. The chronicity grade of gastritis did not correlate with the severity of pancreatic insufficiency. Conclusion: Prevalence of H. pylori infection is not different in patients with chronic pancreatitis as compared with subjects alcoholic liver cirrhosis and asymptomatic subjects. A severe H. pylori-negative chronic gastritis is more common in patients with chronic pancreatitis. This chronic inflammation of the gastric mucosa could contribute to determining the changes in gastric physiology described in patients with chronic pancreatitis.

Gastric mucosal secretion of interleukin-10: relations to histopathology, Helicobacter pylori status, and tumour necrosis factor-alpha secretion.

Interleukin-10 (IL-10) is an 18 kDa peptide with a range of anti-inflammatory and immunosuppressive properties. To determine whether this cytokine is involved in gastric mucosal inflammation in Helicobacter pylori infection. The production of IL-10 by antral mucosal biopsy specimens during short term in vitro culture was determined by measuring IL-10 content of supernatants by enzyme linked immunosorbent assay (ELISA). H pylori status was determined by serology and histology, with gastritis scored using the Sydney system. Tumour necrosis factor-alpha (TNF-alpha) content of supernatants was also determined in a subgroup of patients. IL-10 secretion was significantly greater in patients with H pylori associated chronic gastritis than in patients who were H pylori negative with normal mucosa/reactive changes, and those with H pylori negative chronic gastritis (p < 0.01 and < 0.05 respectively). There was a significant correlation overall between IL-10 secretion and chronic inflammation score (r = 0.40). Secretion of TNF-alpha, which was significantly higher in H pylori infected patients than uninfected patients with a normal mucosa (p < 0.04), correlated with scores for chronic inflammation and activity (r = 0.39 and 0.38 respectively), but was only weakly correlated with IL-10 secretion (r = 0.22, NS). Gastric mucosal production of IL-10 and TNF-alpha are increased in chronic gastritis associated with H pylori infection, and mucosal cytokine secretion varies with important histopathological aspects of gastric inflammation. Whereas the secretion of IL-10 in H pylori infection may be protective, limiting tissue damage caused by inflammation, it may also contribute towards failure of the immune response to eliminate the organism.

High frequency of helicobacter negative gastritis in patients with Crohn's disease.

The frequency of gastric Crohn's disease has been considered low. This study was undertaken to determine the prevalence of chronic gastritis and Helicobacter pylori infection in patients with Crohn's disease. Oesophagogastroduodenoscopy was performed on 62 consecutive patients suffering from ileocolonic Crohn's disease. Biopsy specimens from the antrum and corpus were processed for both histological and bacteriological examinations. H pylori antibodies of IgG and IgA classes were measured in serum samples by enzyme immunoassay. Six patients (9.7%) were infected with H pylori, as shown by histology, and in five of them the infection was also verified by serology. Twenty one patients (32%) had chronic H pylori negative gastritis (negative by both histology and serology) and one of them also had atrophy in the antrum and corpus. Granulomas were found in four patients. The characteristic appearance of H pylori negative gastritis was focal and mostly mild inflammation resembling the inflammatory changes seen in the gut in Crohn's disease. Patients with H pylori negative chronic gastritis had a significantly more active disease in their gut than those with normal gastric mucosa (p < 0.01). It is concluded that H pylori positive gastritis is rare, while H pylori negative gastritis is relatively common in patients with Crohn's disease. H pylori negative 'Crohn's gastritis' seems to be associated with active Crohn's disease.