Helicobacter Pylori-associated Gastritis Research Articles

Cranberry juice for prophylaxis of urinary tract infections – Conclusions from clinical experience and research

Cranberry juice (Vaccinium macrocarpon) is a widely used and recommended North-American folk remedy for prophylaxis of urinary tract infections (UTI). Clinical trials have documented its efficacy in women with recurrent UTI, but so far not in other groups of patients. The composition of effective cranberry products and its dosage in UTI prophylaxis have not been defined. Intriguing experimental research has identified an anti-adhesive mechanism of cranberry juice that prevents docking of bacteria on host tissues. This efficacy mechanism can be traced in patients' urine following oral intake of cranberry products and appears to be due to proanthocyanidins with an A-type linkage of flavanols. The application of this anti-adhesion mechanism of cranberry-proanthocyandins is currently also investigated in other common diseases of bacterial pathogenesis, for example Helicobacter pylori-associated gastritis and dental caries/periodontal disease. The use of cranberry products appears to be safe and provide additional benefits by anti-oxidant and cholesterol-lowering activity.

OXYSTEROLS INFLUENCE HEPATIC CELLS HOMEOSTASIS

gastric mucosa due to H. pylori infection may result in decreased numbers of ghrelin producing cells and lower plasma ghrelin levels [7,9]. In contrast, there was not significant difference in plasma ghrelin levels between H. pylori infected patients and H. Pylori uninfected patients in our study; 32,56±21,97 and 34,04±20,59 respectively (p:0,75), similar with another Turkish study [8]. In conclusion, according to our results, there is not a relation between plasma ghrelin levels and H. pylori infection. These conflicting results may be related to different H. pylori strains, as in Turkey the prevalence of the strains, such as CagA, that cause atrophic gastritis is lower [11]. Moreover; differences in studied populations in terms of race, sample size, nutritional status and habits can also affect results. Decreasing plasma ghrelin levels in H. pylori infected subjects can be compensated by other extra gastric ghrelin producing tissues, convenient to our results. All together, further studies are needed to demonstrate the association between H. pylori infection and plasma ghrelin levels.

α‐Defensin Expression in the Gastric Tissue of Children with Helicobacter pylori–Associated Chronic Gastritis: An Immunohistochemical Study

In this study, we evaluated the expression of alpha-defensin and its correlation with histological criteria in children with and without Helicobacter pylori-associated gastritis. Forty-five children were included. Immunohistochemical staining was performed and the relationship between alpha-defensin immunoscoring and H. pylori status and histological criteria was evaluated. Expression of alpha-defensin was significantly higher in the H. pylori-positive group (P < 0.001) and it was significantly associated with higher grades of chronic inflammation and neutrophil density (P < 0.001 for both). Our data show that alpha-defensin expression is increased in H. pylori infection in childhood and is associated with inflammatory tissue damage.

T1851 Near-Infrared Raman Spectroscopy for Early Diagnosis of Helicobacter pylori-Associated Chronic Gastritis

T1851 Near-Infrared Raman Spectroscopy for Early Diagnosis of Helicobacter pylori-Associated Chronic Gastritis

M1668 Gastric and Circulating Leptin Levels Are Related to Degree of Helicobacter pylori-Associated Gastritis

M1668 Gastric and Circulating Leptin Levels Are Related to Degree of Helicobacter pylori-Associated Gastritis

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.

Effect of volatile oil of amomum on expressions of platelet activating factor and mastocarcinoma-related peptide in the gastric membrane of chronic gastritis patients with helicobacter-pylori infection

To observe the effect of volatile oil of amomum (VOA) on the expressions of mastocarcinoma-related peptide (PS2) and platelet activating factor (PAF) in helicobacter pyloriassociated gastritis (HPG) and to analyze its potential mechanism. Eighty patients with HPG were randomly assigned to two groups, 42 patients in the treated group treated with 0.5 mL VOA, thrice per day; and the 38 patients in the control group receiving Western tertiary medicinal treatment. Gastroscopic picture and helicobacter pylori (HP) infection (by quick urease and Warthin-Starry stain) of the gastro-membrane, expressions of PS2 and PAF (by immunohistochemical assay and Western blotting) as well as the contents of aminohexose and phospholipid (by Neuhaus method) in the gastric membrane of all patients were detected before treatment and 4 weeks after treatment. The clinical efficacy in the two groups was compared. The total effective rate in the treated group was 88.1%, which was significantly higher than that in the control group (78.9%, P<0.05). After treatment, in the treated group, gastric membranous contents of aminohexose and phospholipid was increased, expression of PS2 elevated but that of PAF lowered, all showing significant difference as compared with those in the control group (P<0.01). In the control group, the expressions of PS2 and PAF changed insignificantly. The radical eliminating rate of HP in the treated group and the control group was insignificantly different between them (76.1% vs. 65.8%, P>0.05). The mechanism of VOA for anti-gastritis might be related with its action in increasing the expression of PS2 and decreasing the expression of PAF, and thus regulating the hydrophobicity of the gastric membrane.

Hypoxia-associated markers in gastric carcinogenesis and HIF-2α in gastric and gastro-oesophageal cancer prognosis

The study investigated hypoxia-associated markers (HIF-2α, Epo, Epo-R, Glut-1 and VEGF) along with Ki-67 in a gastric carcinogenesis model, and the prognostic significance of hypoxia-inducible factor (HIF)-2α in surgically treated gastro-oesophageal cancer. Protein expression was examined using immunohistochemistry on formalin-fixed, paraffin-embedded biopsies of normal mucosa (n=20), Helicobacter pylori-associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. Relationships between HIF-2α expression and prognosis were assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Expression of all markers increased with progression along the gastric carcinogenesis sequence (P=0.0001). Hypoxia-inducible factor-2α was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2α-expressing tumours was 22 (95% CI 18−26) months, whereas those with HIF-2α-negative tumours had a median survival of 37 (95% CI 29−44) months (P=0.015). Hypoxia-inducible factor-2α had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2α has no role as a routine prognostic indicator. However, the high expression of HIF-2α suggests that it may be of value as a potential therapeutic target.

Chromosomal instability in gastric mucosa-associated lymphoid tissue lymphomas: a fluorescent in situ hybridization study using a tissue microarray approach

Extranodal marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue [MALT] lymphomas) of the gastrointestinal tract have been known to have characteristic chromosomal aberrations including trisomies of chromosomes 3, 12, and 18. However, knowledge of the clinical significance of cytogenetic changes in MALT lymphomas is still limited. In the present study, the frequency of the numeric and structural aberrations of the chromosomes 1, 3, 12, 18 and X and of the MALT1 gene as well as their potential clinical significance were analyzed by using fluorescent in situ hybridization on a tissue microarray containing 257 tissue samples from 203 cases of surgically resected primary gastric lymphomas including 115 cases of MALT lymphomas, 88 cases of diffuse large B-cell lymphomas (DLBCLs, 75 with an associated MALT lymphoma, so-called ex-MALT DLBCL, and 13 de novo), and 54 controls cases of Helicobacter pylori-associated chronic gastritis. Clinical follow-up information was available in 137 cases. Trisomies 1, 3, 12, and 18 were detected in 3.3%, 44.4%, 12.3%, and 19.2% of MALT lymphomas and in 11.1%, 42.2%, 26.5%, and 22.0% of ex-MALT DLBCLs, respectively. In addition, we found gains of the X chromosome in 36.4% of MALT lymphomas, in 34.5% of ex-MALT DLBCLs, and in 36.4% of de novo DLBCLs. Structural and/or numeric abnormalities of the MALT1 gene were observed in 37.0% of MALT lymphomas and in 22.2% of ex-MALT DLBCLs. In de novo DLBCL, trisomies for chromosomes 3, 12, 18, and X were found in 42.9%, 10.0%, 11.1%, and 36.4%, respectively, whereas alterations of MALT1 (namely, translocations) were found in 20.0% of the cases. An unexpected high and previously unreported gain of chromosome X in gastric MALT lymphomas was found. This tumor appears, therefore, to be a genetically unstable neoplasia. Our results point out that t(11;18) and aneuploidy may be both involved in lymphomagenesis and that at least a subset of MALT lymphomas may progress toward high-grade neoplasia.

Gastric gelatinase B/matrix metalloproteinase-9 is rapidly increased inHelicobacter felis-induced gastritis

It has previously been shown that matrix metalloproteinase-9 (MMP-9) levels, originating from macrophages, are considerably increased in human Helicobacter pylori-associated gastritis. Here, the early kinetics of the MMP-9 response resulting from Helicobacter infection in C57BL/6 and MMP-9 knock-out mice using the murine Helicobacter felis model were examined. H. felis infection induced severe gastritis in the murine stomach at just 2 weeks after infection. Before gastritis, an increase was observed in MMP-9-positive cells detected by immunohistochemistry in the basal lamina propria. This finding was corroborated by gelatin zymography of stomach samples. As the gastritis increased so did the concentration of MMP-9 and the incidence of gastric MMP-9-positive cells, their location corresponding to that of macrophages. In contrast, systemic levels of MMP-9 remained unchanged. When MMP-9-deficient mice were infected with H. felis, no significant difference in gastritis development was detected compared with disease development in wild-type animals. We conclude that MMP-9 production is an early event in the response to gastric Helicobacter infection, a feature that may favor the recruitment of immune cells early during infection. At later stages, however, the increased levels of MMP-9 may damage the integrity of the stomach mucosa.

Endoscopic Patterns and Histopathological Features after Eradication Therapy in Helicobacter pylori-Associated Nodular Gastritis

The endoscopic finding of nodular gastritis (NG) is highly associated with presence of Helicobacter pylori infection. How the endoscopic patterns and histopathology of NG change after eradication of H. pylori is unclear. Twenty-one adults (3 men and 18 women) with H. pylori-associated NG found on endoscopy were enrolled for this study. The histological findings included gastritis activity, bacterial colonization, and lymphoid follicles. Repeat endoscopy for the endoscopic as well as histopathological features of gastric biopsy specimens was performed 2 months later after eradication treatment. H. pylori was successfully eradicated in 19 patients. Endoscopic NG disappeared in 12, improved in 5, and was unchanged in 4. After treatment, there was significant improvement in scores for gastritis activity [P < 0.001, 95% confidence interval (CI) 1.31-1.91], bacterial colonization (P < 0.001, 95% CI 0.71-1.14) and follicular gastritis (P = 0.047, 95% CI 0.04-0.52), primarily among patients whose endoscopic pattern resolved completely. The disappearance of nodularity on endoscopy was accompanied by a decrease in follicular gastritis score.

Should patients with pH-documented laryngopharyngeal reflux routinely undergo oesophagogastroduodenoscopy? A retrospective analysis

Patients with laryngopharyngeal reflux uncommonly suffer from conditions associated with gastroesophageal reflux disease. However, in some laryngopharyngeal reflux patients, oesophagitis and Barrett's metaplasia can be diagnosed by oesophagogastroduodenoscopy. However, it is unclear which patients with laryngopharyngeal reflux would benefit from routine oesophagogastroduodenoscopy. Retrospective analysis. Analysis of the results of oesophagogastroduodenoscopy in 28 patients with pH-documented laryngopharyngeal reflux. Oesophagogastroduodenoscopy showed oesophagitis in five patients (four with grade A, one with grade B), hiatus hernia in 10 patients (36 per cent), Barrett's metaplasia in two patients, Helicobacter pylori-associated chronic gastritis in two patients and gastric mucosal erosions in seven patients (25 per cent). In 13 patients, no abnormalities were detected (46 per cent). Barrett's metaplasia or grade B oesophagitis was diagnosed only in patients with heartburn as their main presenting symptom. Oesophagogastroduodenoscopy is indicated in at least those laryngopharyngeal reflux patients reporting heartburn as their main complaint.

Altered expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) during gastric carcinogenesis and its clinical implications on gastric cancer

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a 465-kDa catalytic subunit of DNA-PK, a DNA repair apparatus. DNA-PKcs has been reported to be a tumor suppressor, but details of its expression in human cancer are controversial. To determine the protein expression and clinical implications of DNA-PKcs in gastric carcinogenesis and cancer progression, we evaluated its expression status by immunohistochemistry in 122 non-neoplastic gastric mucosa samples, and in 115 gastric adenomas and 564 consecutive gastric cancers. In addition, we evaluated the clinicopathologic characteristics of gastric cancers showing altered DNA-PKcs expression, and performed microsatellite instability (MSI) analysis at BAT-26 and frameshift mutation analysis of DNA-PKcs. DNA-PKcs expression was negative in foveolar epithelium of normal gastric mucosal tissues, but was positive in most Helicobacter pylori-associated gastritis, intestinal metaplasia and gastric adenoma tissues. In gastric cancers, negative expression of DNA-PKcs was found in 114 of the 564 (20.2%) cancers and was significantly associated with intratumoral neutrophils, MSI-high (H) phenotype, tumor progression, and poor patient survival (p<0.05). Frameshift mutations of (A)10 mononucleotide repeats in DNA-PKcs were found in 24.3% of MSI-H gastric cancers and these were associated with negative expression of DNA-PKcs. Although patients with MSI-H gastric cancers were found to have a lower risk of lymph node metastasis, gastric cancers harboring the (A)10 mutation of DNA-PKcs were found to have a higher risk of lymph node metastasis. In conclusion, the expression of DNA-PKcs was found to be altered during gastric carcinogenesis and negative DNA-PKcs expression was associated with gastric cancer progression. The (A)10 frameshift mutation of DNA-PKcs in gastric cancers was a target of defective mismatch repair, and was associated with lymph node metastasis.

Helicobacter pylori-Associated Gastritis Is Related to babA2 Expression without Heterogeneity of the 3′ Region of the cagA Genotype in Gastric Biopsy Specimens

Background: Cytotoxin-associated gene A (cagA) is the major virulence factor of Helicobacter pylori strains and affects the clinical outcome of patients. Blood group antigen binding adhesin (BabA) helps the strains adhere to the epithelial cell layer and is the most important adhesin of H. pylori.Objectives: We tried to study the association between the status of babA2 and cagA in H. pylori strains and histological gastritis. Methods: Thirty-six patients were included. RNA was extracted from two frozen biopsy samples of the antrum and corpus, respectively, and cagA/babA2 genotypes were analyzed with reverse transcription polymerase chain reaction and direct sequencing. Two gastric specimens of the antrum and corpus, respectively, were also stained with hematoxylin and eosin to analyze H. pylori-related gastritis. Results: In the antrum, 56% of the specimens were babA2 positive and in the corpus 53%. The gastritis scores of activity and inflammation were associated with the presence of babA2 in antrum specimens but not in corpus specimens. cagA gene encoding in the CagA EPIYA-D region was detected in all samples, and the sequence was completely identical between those from the gastric corpus and antrum. Conclusion:babA2 expression is heterogeneous and correlated with the extent of gastritis in the antrum, but not in the corpus, whereas cagA shows a monotonous genotype.

Multiplex PCR To Detect H. pylori in MALToma and Its Role in Treatment and Prognosis: A Case Series

TablePurpose: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma develops in Helicobacter pylori-associated chronic gastritis. Current diagnostic techniques for H. pylori associated MALToma include CLO rapid urease test, conventional PCR, histologic studies. However, these methods are not very sensitive and do not provide accurate treatment guidance or prognosis. To report a case series in which Multiplex PCR (MPCR) was applied to detect H. pylori related MALToma and its use to guide treatment and prognosis. Methods: We performed MPCR in patients with a diagnosis of MALToma. Patients were treated and followed till their MPCR reaction became negative. Results: Four patients with a diagnosis of MALToma demonstrated MPCR positive reactions with negative or positive CLO, culture and pathology for H. pylori. In 2 patients, a negative MPCR reaction was used to determine a treatment endpoint. In one patient, in spite of multiple treatment tissue was negative for MPCR but positive for MALToma and it was therefore determined that it might be due to evolved MALToma. In another patient, the MALToma recurred after 9 months in spite of persisted negative MPCR. These two patients with MALToma in spite of negative MPCR received radiation and the MALToma was cured. (Table) Conclusion: In all patients we noted that MPCR was very sensitive and specific for diagnosis of H. pylori related MALToma. In all patients, MPCR was utilized to determine treatment efficacy and prognosis.Table

Abnormalities in the upper gastrointestinal tract in inflammatory bowel disease

The predominant histopathologic feature of inflammatory bowel disease is the infiltration of acute and chronic inflammatory cells, including polymorphonuclear neutrophils, macrophages and lymphocytes, in the affected intestine. Helicobacter pylori is recognized as the most common cause of upper gastrointestinal lesions, and Helicobacter pylori-associated gastritis is characterized by increased numbers of acute and chronic inflammatory cells. The pathogenesis of inflammatory bowel disease or Helicobacter pylori-associated gastritis involves immunological abnormalities, including the deficient or excessive expression of cytokines. The chronic inflammatory process in patients with Crohn's disease may affect any part of the gastrointestinal tract, whereas ulcerative colitis affects mainly the colon and rectum. Here, we discuss abnormalities in the upper gastrointestinal tract in inflammatory bowel disease. Although the prevalence rate of Helicobacter pylori infection is low in Crohn's disease, these patients often have abnormalities in the upper gastrointestinal tract.

Helicobacter pylori-associated atrophic gastritis and carotid intima-media thickness: is there a link?

Chronic infections are associated with cardiovascular diseases. Helicobacter pylori-induced chronic active gastritis results in atrophic gastritis. In this study, we attempted to determine carotid intima-media thickness in patients with and individuals without H. pylori-induced atrophic gastritis. Oesophagogastroduodenoscopy was performed on 123 patients for various reasons. Helicobacter pylori were considered positive when histological examination and rapid urease test showed H. pylori. Helicobacter pylori-positive cases were divided into two groups, namely atrophic gastritis and non-atrophic gastritis. Of 123 patients, 92 patients had H. pylori-positive non-atrophic gastritis and 31 had H. pylori-positive atrophic gastritis. There was no significant difference in carotid intima-media thickness between the two groups. Carotid intima-media thickness is not associated with H. pylori-induced atrophic gastritis.

Helicobacter pylori‐negative gastric mucosa‐associated lymphoid tissue lymphoma

The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphoma develops in Helicobacter pylori-associated chronic gastritis. Little is still known regarding the clinicopathologic features of gastric MALT lymphoma not associated with H. pylori infection. One hundred thirty-seven patients with gastric MALT lymphoma, in whom H. pylori status was evaluated using at least both serology and histology, were enrolled. Clinical, histopathologic, and molecular findings were compared between H. pylori-negative group (n = 12; 9%) and H. pylori-positive group (n = 125; 91%). t(11;18)(q21;q21) was investigated by reverse-transcription polymerase chain reaction and interphase fluorescence in situ hybridization. In cases without diffuse large B-cell lymphoma (DLBCL) component, H. pylori-negative lymphomas located more frequently in the proximal stomach (70%), less frequently appeared as superficial type (40%), and frequently invaded the submucosa or beyond (70%). Histologically, lymphoepithelial lesions (57%), lymphoid follicles (43%), and background mucosal atrophy (50%) in the H. pylori-negative group were less frequent than in the H. pylori-positive group (91%, 93%, and 100%, respectively). The frequencies of t(11;18)(q21;q21) (100%) and BCL10 nuclear expression (100%) in the H. pylori-negative group were significantly higher than in the H. pylori-positive group (2% and 27%, respectively). Response to antibiotic treatment was observed not only in the H. pylori-positive group (75%), but also in the H. pylori-negative group (2 of 7 patients, 29%). In cases with a DLBCL component, such differences were not observed between the 2 groups. H. pylori-negative gastric MALT lymphoma is characterized by frequent t(11;18)(q21;q21). Antibiotic treatment should be considered also for this disease, although cases with t(11;18)(q21;q21) may need additional strategies.

Mucosal lymphocyte subsets and HLA-DR antigen expression in paediatric Helicobacter pylori-associated gastritis.

Paediatric studies may provide important insights into the immunopathology of Helicobacter pylori-associated gastritis, as mucosal changes reflect different stages of the immunoinflammatory response. We characterized, by quantitative immunohistochemistry, gastric mucosal lymphocyte phenotype and HLA-DR antigen expression and evaluated correlation with histopathology, in H. pylori-infected (Hp+ve) and uninfected children (Hp-ve). In the infected group, lamina propria CD3+ and IgA plasmocyte cell numbers were significantly higher and a trend for predominance of CD8+ over CD4+ was observed both in epithelium and lamina propria. A correlation of inflammation score with lamina propria CD3+ and CD4+ cell numbers and of CD45RO+ T lymphocytes with density of colonization was observed. The proportion of epithelial cells expressing HLA-DR antigen was significantly higher in the Hp+ve group and furthermore, glandular HLA-DR expression correlated with lamina propria CD3+ cell numbers, emphasizing the potential role of epithelial cells as antigen-presenting cells at this stage of infection.

High Resolution Magnification Endoscopy Can Identify the Normal Gastric Mucosa, Helicobacter Pylori-Associated Gastritis and Gastric Atrophy

High Resolution Magnification Endoscopy Can Identify the Normal Gastric Mucosa, Helicobacter Pylori-Associated Gastritis and Gastric Atrophy