Severity Of Gastric Mucosal Atrophy Research Articles

False Sero-Negative Results for Helicobacter Pylori Infection Indicate Increased Risk of Severe Atrophic Gastritis in Japanese Patients

Background/objective: H. pylori infection is commonly diagnosed using an anti-H. pylori IgG antibody test. However, a proportion of results are falsely sero-negative. We investigated characteristics of patients falsely seronegative for H. pylori in relation to gastric atrophy. Methods: H. pylori infection (Hp+ or Hp-) was determined based on culture test, rapid urease test (RUT), and polymerase chain reaction (PCR) test in 280 outpatients. Anti-H. pylori antibody titers ≥ 10 U/ml were diagnosed as sero-positive for H. pylori (IgG+), while those <10 U/ml were sero-negative (IgG-). Serum pepsinogen (PG) I/PG II ratios were calculated as a serological marker of gastric atrophy. Endoscopic gastric mucosal atrophy was also assessed according to the Kimura-Takemoto classification system. Results: The mean PG I/PG II ratio in each group was as follows: Hp-/IgG- (4.99 ± 1.04, n=10), Hp+/IgG+ (2.59 ± 1.51, n=240), Hp-/IgG+ (5.65 ± 2.72, n=4) and Hp+/IgG- (3.02 ± 2.61, n=26). The mean serum PG I/PG II ratio in the Hp+/IgG- group was lower than those of Hp-/IgG- and Hp-/IgG+ groups (P=0.028 and 0.072). Incidence of severe gastric mucosal atrophy in the Hp+/IgG- group was highest of the four groups. Conclusions: Individuals falsely sero-negative for H. pylori infection is at increased risk of severe atrophic gastritis, which is well known as precancerous lesion.

Sa1883 A Genetic Polymorphism of MAFK Gene Is Closely Associated With the Severity of Gastric Mucosal Atrophy

metronidazole (500 mg/12h)] or treatment (same four drugs taken concomitantly for ten days). Eradication was confirmed with 13C-urea breath test or histology 8 weeks after treatment. Adverse events (AEs) and treatment compliance were evaluated with questionnaires and residual medication count. Results: 342 consecutive patients were randomized. Mean age was 47 years, 60% were females, 23% were smokers, and 20% had peptic ulcer. Intention-to-treat eradication was 89.6% (95%CI=86-93%) for the concomitant, and 85.2% (81-89%) for the regimen (p=0.153). Respective perprotocol rates were 91.2% (88-95%) and 86.2% (82-90%) (p=0.131). Compliance was 89% for and 86% for sequential. AEs were reported in 65% of patients (no significant differences were found between treatments). AEs were mostly mild (60%) or moderate (35%) and had an average length of 6.5 days. Only 7 patients discontinuated treatment due to AEs. Multivariate analysis for sex, age, smoking habit, presence of ulcer and type of treatment found no association with effectiveness, although concomitant treatment showed an odds ratio of 1.5 towards better eradication rate in a borderline significance confidence interval (95%CI=0.8-2.9). Conclusion: Our results suggest that eradication rate differences between sequential and treatments are lower than 10%. However, a non-statistically significant trend towards an advantage (5%) of regimen was observed. The rate of adverse events was high but their intensity was mild and duration was short.

The appearance of the gastric submucosal microvessels and the degree of gastric mucosal atrophy may predict prognosis in gastric cancer patients

This study examined the morphological changes of the gastric mucosa around the stomach cancer in patients to correlate them with tumor progression. Twenty‐three patients (average age 61.6±2.68 years) with histologically confirmed gastric cancer were selected for study. Tissue samples, taken at least 3–5cm away from the edge of the tumor, were processed for histopathological examination. Sections were stained with Mayer's hematoxylineosin, and CD34 antibody. We found that the tumor size positively correlated with the severity of atrophic changes in the gastric mucosa (r=0.670, p=0.03) and negatively correlated with the completion of the eradication therapy prior to surgery (r=−0.540, p=0.022). For instance, the tumors were significantly larger in patients with the higher degree of gastric mucosal atrophy (5.53±1cm vs. 3.5±1.9cm, respectfully; p=0.016) and were significantly smaller in the patients with the history of eradication therapy (3.4±2.45cm vs. 5.2±1.74cm, respectfully; p=0.065). The presence of metastases in regional lymph nodes positively correlated with the presence of dilated capillaries in the gastric submucosa (r=0.863, p=0.001; in 85.7% of cases) and severe gastric mucosal atrophy (r=0.560, p=0.031; in 71.4% of cases). Therefore, we propose that the marked dilatation of submucosal microvessels and the high degree of gastric mucosal atrophy may be indicative of gastric cancer progression.

Association between common genetic variant of HRH2 and gastric cancer risk

Histamine plays important physiological roles in the upper gastrointestinal tract and acts via the H2 receptor. The -1018 G>A (rs2067474) in an enhancer element of the promoter and non-synonymous rs79385261 (Asn46Thr) were identified in HRH2. We attempted to clarify the associations of these polymorphisms with gastric carcinogenesis. The study was performed in 321 patients with gastric cancer and 599 subjects with no evidence of gastric malignancies on upper gastroduodenal endoscopy. The genotypes were determined using a one-tube multiplex PCR-SSCP method. The degree of gastritis was assessed in 496 subjects and serum pepsinogen (PG) I/II levels were measured in 124 subjects without gastric cancer. The minor allele of Asn46Thr could not be detected. The frequencies of the -1018 A allele in the non-GC and GC groups were 13.5% and 8.26%, respectively (p=0.00077). Overall, -1018 GG homozygotes had an increased risk for developing gastric cancer (OR 1.68; 95% CI 1.17-2.42; p=0.0052), especially intestinal type cancer (OR 1.94; 95% CI 1.23-3.08; p=0.0047). In subjects aged >60 years, the adjusted risk for gastric cancer among individuals who were -1018 GG homozygotes was 1.87 (range 1.19-2.93; p=0.0065) compared with A carriers. In the gastric cancer cases located in the antrum and at comparative advanced stage, -1018 GG homozygosity was a significantly increased risk factor. In subjects >60 years, the metaplasia score was significantly higher in -1018 GG homozygotes than A carriers. Both atrophy and metaplasia scores were significantly increased with age only in -1018 GG homozygotes. The PG I/II ratio was significantly decreased in H.pylori positive GG homozygotes than negative GG homozygotes and positive A carriers. Our results suggest that -1018 GG homozygosity of HRH2 may be associated with the severity of gastric mucosal atrophy. This genotype has an increased risk for the subsequent development of gastric cancer, especially intestinal type, at advanced age.

Etiological difference between ultrashort- and short-segment Barrett’s esophagus

Barrett's esophagus has been divided into three categories based on the extent of the metaplasia: long-segment (LSBE), short-segment (SSBE), and ultrashort-segment Barrett's esophagus (USBE). While both LSBE and SSBE are thought to be induced by gastroesophageal reflux, the etiology of USBE is still unclear. We conducted a case-control study to identify the differences in the pathogenesis between SSBE and USBE in a hospital-based population. The endoscopic findings and clinical factors of 199 patients with short-segment endoscopically suspected esophageal metaplasia (SS-ESEM) and 317 patients with ultrashort-segment ESEM (US-ESEM) were compared with those of 199 and 317 age- and gender-matched patients without ESEM. The severity of gastric mucosal atrophy was marginally associated with the presence of US-ESEM [odds ratio (OR) 1.20, 95% confidence interval (CI) 0.98-1.46, p = 0.08], but not with that of SS-ESEM. On the other hand, the presence of gallstones and that of severe reflux esophagitis were associated with the presence of SS-ESEM (OR 2.19, 95% CI 1.21-3.98; OR 1.72, 95% CI 1.08-2.75), but not with that of US-ESEM. Presence of gastric corpus atrophy without gallstones was associated with the presence of US-ESEM, but not with that of SS-ESEM. Presence of gastric corpus atrophy was associated with an increased likelihood of the presence of US-ESEM, whereas the presence of gallstones was associated with an increased likelihood of the presence of SS-ESEM, suggesting difference in etiology between US- and SS-ESEM.

Gallstones increase the prevalence of Barrett’s esophagus

Bile and acid exposures are thought to be major risk factors for Barrett's esophagus in Western countries. The association of gallstones with Barrett's esophagus has not been fully evaluated. The present study was designed as a case-control study for determining the possible factors associated with endoscopically suspected esophageal metaplasia (ESEM), defined as an endoscopic finding suggestive of Barrett's esophagus, in Japanese patients. A total of 528 patients with ESEM were allocated to the case group, while 528 age- and gender-matched patients without ESEM were allocated to the control group. Findings on esophagogastroduodenoscopy and clinical background factors were compared using a multivariate logistic regression model. The presence of gallstones and hiatus hernia and the severity of gastric mucosal atrophy were independently associated with the presence of ESEM [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.03-2.69; OR 2.75, 95% CI 1.75-4.33; OR 1.25, 95% CI 1.01-5.6, respectively]. Compared with subjects with neither gastric corpus atrophy nor gallstones, although subjects with gallstones alone were not associated with the presence of ESEM (OR 1.59, 95% CI 0.87-2.92), having both gastric corpus atrophy and gallstones was strongly associated with the presence of ESEM (OR 2.94, 95% CI 1.40-6.17). The presence of gallstones was independently associated with the presence of ESEM in the Japanese outpatient population, suggesting a causal association of distal esophageal bile exposure with the development of ESEM. Further studies are needed to confirm our findings in cases with histologically confirmed Barrett's esophagus.

Mannan-binding lectin B allele is associated with a risk of developing more severe gastric mucosal atrophy in Helicobacter pylori-infected Japanese patients

Mannan-binding lectin (MBL) is an important constituent of the innate immune system, and deficiency of MBL has been reported to increase the overall susceptibility of an individual to infectious disease. Codon 54 G/A variant of exon 1 (B allele) affects MBL2 gene and alters its activity. We investigated the influence of MBL2 variant on the risk of gastroduodenal diseases and on the severity of Helicobacter pylori-induced gastritis in a Japanese population. One hundred and two gastric ulcers, 48 duodenal ulcers, 275 nonulcer participants were included in this study. B allele of the MBL2 gene was detected by polymerase chain reaction based restriction fragment length polymorphism. The severity of the histological chronic gastritis in antral biopsy specimens were classified according to the updated Sydney system. MBL2 B allele was significantly associated with severity of gastric mucosal atrophy and intestinal metaplasia (atrophy, G/G vs. G/A vs. A/A; P=0.02, A/A vs. others; P=0.009, intestinal metaplasia; G/G vs. G/A vs. A/A; P=0.03, A/A vs. others; P=0.004). When participants were divided into the following three groups according to the severity of gastric atrophy: the nonatrophic gastritis (NA) group, the severe atrophic gastritis (SA) group, and mild atrophic gastritis (MA) group, the frequency of A/A was significantly higher in the SA group than in others (SA vs. MA; odds ratio=8.42, 95% confidence interval=1.05-67.45, SA vs. others; odds ratio=10.06, 95% confidence interval=1.26-80.45). Our data suggest that the MBL2 codon 54 B allele is associated with a risk of developing more severe gastric mucosal atrophy in H. pylori-infected Japanese patients.

Endoscopically Suspected Esophageal Metaplasia (Esem) Is Associated with the Complications of Hiatus Hernia, Reflux Esophagitis and Severe Gastric Mucosal Atrophy in Japanese Patients Who Underwent EGD

Endoscopically Suspected Esophageal Metaplasia (Esem) Is Associated with the Complications of Hiatus Hernia, Reflux Esophagitis and Severe Gastric Mucosal Atrophy in Japanese Patients Who Underwent EGD

Toll-like Receptor 2 (TLR) −196 to 174del Polymorphism in Gastro-duodenal Diseases in Japanese Population

Toll-like receptors (TLRs) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. -196 to -174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of TLR2 -196 to -174del polymorphism on the risk of gastro-duodenal diseases, on the severity of Helicobacter pylori-induced gastritis in a Japanese population. The study was performed on 309 patients with abdominal discomfort and 146 healthy controls. -196 to -174del polymorphism of TLR2 was investigated by allele-specific polymerase chain reaction method in all of the subjects. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system in H. pylori-positive subjects (n = 156). Patients with abdominal discomfort was consisted of 80 gastric ulcers (25.9%), 38 duodenal ulcers (12.3%), five gastric + duodenal ulcers (1.6%), 105 patients with gastritis (34.0%) and 81 normal healthy stomachs (26.2%). We did not find any association between TLR2 polymorphism and risk of gastric ulcer, duodenal ulcer, gastric and duodenal ulcer and gastritis compared to healthy controls. However, the TLR2-196 to -174ins allele was associated with severity of intestinal metaplasia in more than 60 years of ages (P = 0.02). The same allele also increased the risks of developing more severe gastric mucosal atrophy and intestinal metaplasia in female subjects (P < 0.05, P = 0.07 respectively). No association was observed between TLR2 polymorphism and severity of neutrophil and mononuclear cell infiltration. Our data suggest that the TLR2-196 to -174ins allele was associated with more severe intestinal metaplasia in patients older than was correlated with severity of gastric mucosal atrophy and intestinal metaplasia in female subjects.

Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and chronic gastritis

Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator, which plays a pivotal role in inflammatory and immune diseases. We attempted to clarify associations of the functional polymorphisms of the MIF gene promoter with the development of chronic gastritis. The study was performed with 290 stocked DNAs from subjects with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. Both the 7/7-CATT repeat at position -794 and the -173 C/C genotypes were significantly associated with a risk of developing severe gastric mucosal atrophy (OR, 9.69; 95% CI, 1.29-72.5; and OR, 4.60; 95% CI, 1.05-20.2, respectively). In subjects younger than 60 years old, the number of 7-CATT alleles was significantly correlated with both the activity and inflammation scores (p=0.0079 and 0.0080, respectively). Our results suggested that functional promoter polymorphisms of the MIF gene might be associated with the severity of gastric mucosal inflammation in younger subjects and with the subsequent development of mucosal atrophy.

Contribution Of Epidemiological Studies To Gastritis Immunology

Chronic gastritis, or chronic inflammation in gastric antral and/or corpus mucosa, is a common pathological condition affecting over half the general population. Progression of chronic gastritis from Helicobacter pylori infection to severe gastric mucosal atrophy usually takes decades and varies considerably from person to person. Therefore, studies of clinically selected material cannot provide a complete picture of natural evolution of the disease or its wide variability. An overview of immunological and morphological aspects of chronic gastritis in an epidemiological context, based on data from the literature and the author's studies, reveal dynamic interaction between H. pylori infection and host response to the organism's antigens, and to gastric autoantigens including gastric H+K+ ATPase. Further population and followup studies of antral and corpus gastritis at different stages of evolution are needed, in combination with new methods, to elucidate further the roles of infection, and gastric-antrum- and corpus-mucosa-related autoimmune responses, in the pathogenesis of chronic gastritis.