Helicobacter pylori infection‐induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications

Background

Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori‐induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication.

Materials and Methods

Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low‐grade intraepithelial neoplasia, high‐grade intraepithelial neoplasia, and intestinal‐type gastric cancer groups. Helicobacter pylori infection was determined by either ¹³C‐urea breath test or immunohistochemistry staining.

Results

In Helicobacter pylori‐negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low‐grade intraepithelial neoplasia, and declined in high‐grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori‐infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori‐negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori‐negative control. Labeling index of Ki67 in Helicobacter pylori‐negative groups was higher in gastric cancer than chronic atrophic gastritis and low‐grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori‐positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress.

Conclusions

These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori‐induced gastric cancer.     

Helicobacter pylori CagA Status,Mucosal Oxidative Damage and Gastritis Phenotype: A Potential Pathway to Cancer?

Background. Oxidative DNA damage is associated with Helicobacter pylori infection, atrophy and intestinal metaplasia. H. pylori‐cagA‐positive strains are associated with the highest risk of gastric cancer. Aims. To ascertain whether cagA‐positive H. pylori infection correlates with higher concentrations of 8OHdG and the presence of precancerous changes. Patients and Methods. 118 patients were studied (65M/53F, age 61 ± 14 years). Twelve were H. pylori‐negative. Among the H. pylori‐positive patients, 34 were cagA‐positive and 40 were cagA negative. In 32 patients H. pylori had been eradicated at least 6 months before endoscopic sampling. The phenotype of the gastritis (atrophic compared with nonatrophic, with and without intestinal metaplasia) was scored in biopsy samples obtained from the antrum, corpus, and angularis incisura. In antral biopsy samples, 8‐hydroxydeoxyguanosine was assessed by HPLC (electrochemical detector). CagA status was determined by PCR. Results. The highest scores for both mononuclear inflammation and activity of gastritis were significantly associated with cagA status (p = 0.036 antrum and p = 0.02 corpus). cagA‐positive infection significantly correlated with a higher prevalence of atrophic‐metaplastic lesions (p = 0.04). cagA‐positive patients had higher 8‐hydroxydeoxyguanosine levels than both cagA‐negative and H. pylori‐negative cases (p = 0.01). The 8‐hydroxydeoxyguanosine levels were significantly higher in multifocal atrophic gastritis (p = 0.04). The odds ratio for cagA‐positive patients having 8OHdG levels above a cut‐off calculated on the basis of the ROC curves were 7.12, overall, reaching 11.25 when only patients younger than 50 were considered. Conclusions. cagA‐positive patients were characterized: first, for higher scores for gastritis, activity and atrophic and metaplastic lesions; and second for greater oxidative DNA damage overall, at younger age and in the presence of multifocal atrophy. This setting may represent a cancer‐prone biological context.     

Predictive factors for improvement of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication: a three-year follow-up study in Korea

Background and Aims: To date, data on the effects of anti‐Helicobacter therapy on the improvement of atrophic gastritis (AG) and intestinal metaplasia (IM) have been conflicting. This study was performed to investigate whether eradication of H. pylori could lead to the improvement of AG and IM, and the prognostic factors associated with the improvement of AG and IM. Methods: Four hundred patients consisting of H. pylori‐negative (n = 116) and H. pylori‐positive (n = 284) groups were followed up 1 and 3 years after initial H. pylori tests. Serum levels of pepsinogen (PG), bacteria, environmental factors, and genetic polymorphisms were determined. Results: The grade of corpus atrophy decreased at 1 and 3 years after successful eradication (p < .001 and p = .033, respectively). However, there was no significant change in the IM in the antrum and in the corpus. Prediction factors for the improvement of corpus AG by H. pylori eradication were baseline low PG I/II ratio (≤3), high salt intake, and corpus‐predominant gastritis. IM improvement was also associated with spicy food intake and high baseline grade of IM, in addition to these factors. In addition, IL‐1B‐511 C/T and IL‐6‐572 C/G alleles were found to inhibit IM improvement. However, H. pylori‐negative and noneradicated group did not show any significant change in AG or IM. Conclusion: Corpus AG was reversed by H. pylori eradication, and improvement of IM by H. pylori eradiation was more definite in patients with severe IM, low PG I/II ratio, and corpus‐predominant gastritis, suggesting that H. pylori eradication is valuable even in severe cases.     

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

Background. 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. Methods. 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. Results. 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). Conclusions. 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.     

Interactions Among Gastric Somatostatin, Interleukin-8 and Mucosal Inflammation in Helicobacter pylori-Positive Peptic Ulcer Patients

Background. To investigate whether Helicobacter pylori infection, but not drugs, affects gastric somatostatin, interleukin‐8 (IL‐8), histological inflammation through eradication therapy, and interactions among these parameters. Methods. Twenty‐eight H. pylori‐positive patients (21 males; mean age 47.0 years) with either gastric ulcer (GU: n = 11) or duodenal ulcer (n = 17) diagnosed endoscopically were treated with dual therapy. Eradication was defined as negative microbiologic tests and ¹³C‐urea breath test. Levels of antral and gastric juice somatostatin and mucosal IL‐8 were measured by radioimmunoassay and enzyme‐linked immunosorbent assay, respectively. Histology was assessed by the Sydney system. Results. H. pylori was eradicated in 15 patients (10 males, 6 GU) out of 28 (54%). The patients’ backgrounds did not affect the eradication of H. pylori. Successes in eradication significantly increased antral and juice somatostatin contents, and dramatically decreased IL‐8 levels and histological gastritis. In contrast, persistent H. pylori infection did not affect somatostatin and histological gastritis. An inverse correlation was present between changes in somatostatin levels and histological activity. No relationship was observed in changed values between antral somatostatin and IL‐8. Conclusions. These results indicate that eradication of H. pylori, but not the drugs used, induced an increase in somatostatin levels in the antrum and gastric juice, suggesting a close relationship between H. pylori and gastric somatostatin regulation. A close correlation between an increase in gastric somatostatin levels and the normalization of histological activity was present, suggesting that certain peptide‐immune interactions in the gastric mucosa exist in H. pylori infection.     

The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea

Background and Aim: This study was performed to determine whether serum pepsinogen (PG) and gastrin testing can be used to detect gastric cancer in Korea. Methods: Serum levels of PG I (sPGI) and sPGII, PG I/II ratios, and gastrin levels were measured in 1006 patients with gastroduodenal diseases including cancer. Follow‐up tests were performed 1 year after Helicobacter pylori eradication. Results: sPGI and sPGII levels increased and PG I/II ratios decreased in line with the severity of activity, chronic inflammation, and the presence of H. pylori (p < .01). In contrast, sPGI levels and PG I/II ratios decreased in proportion with the severity of atrophic gastritis (AG)/intestinal metaplasia (p < .01). Gastrin levels were found to be correlated with chronic inflammation negatively in the antrum but positively in the corpus. H. pylori eradication reduced sPGI, sPGII, and gastrin levels, and increased PG I/II ratios to the levels of H. pylori‐negative patients, and was found to be correlated with reductions in activity and chronic inflammation of gastritis. The sensitivity and specificity of a PG I/II ratio of ≤ 3.0 for the detection of dysplasia or cancer were 55.8–62.3% and 61%, respectively. In addition, sPGI and sPGII levels of intestinal‐type cancer were significantly lower than those of the diffuse type, respectively (p = .008 and p = .05, respectively). Gastric cancer risk was highest in the H. pylori‐positive, low PGI/II ratio (≤ 3.0) group with an odds ratio of 5.52 (confidence interval: 2.83–10.77). Conclusion: PG I/II ratio (≤ 3.0) was found to be a reliable marker for the detection of dysplasia or gastric cancer, especially of the intestinal type. This detection power of PG I/II ratio (≤ 3.0) significantly increased in the presence of H. pylori, and thus, provides a means of selecting those at high risk of developing gastric cancer in Korea.     

Previous Helicobacter pylori infection–induced atrophic gastritis: A distinct disease entity in an understudied population without a history of eradication

Individuals with chronic atrophic gastritis who are negative for active H. pylori infection with no history of eradication therapy have been identified in clinical practice. By excluding false‐negative and autoimmune gastritis cases, it can be surmised that most of these patients have experienced unintentional eradication of H. pylori after antibiotic treatment for other infectious disease, unreported successful eradication, or H. pylori that spontaneously disappeared. These patients are considered to have previous H. pylori infection–induced atrophic gastritis. In this work, we define these cases based on the following criteria: absence of previous H. pylori eradication; atrophic changes on endoscopy or histologic confirmation of glandular atrophy; negative for a current H. pylori infection diagnosed in the absence of proton‐pump inhibitors or antibiotics; and absence of localized corpus atrophy, positivity for autoantibodies, or characteristic histologic findings suggestive of autoimmune gastritis. The risk of developing gastric cancer depends on the atrophic grade. The reported rate of developing gastric cancer is 0.31%‐0.62% per year for successfully eradicated severely atrophic cases (pathophysiologically equal to unintentionally eradicated cases and unreported eradicated cases), and 0.53%‐0.87% per year for spontaneously resolved cases due to severe atrophy. Therefore, for previous H. pylori infection–induced atrophic gastritis cases, we recommend endoscopic surveillance every 3 years for high‐risk patients, including those with endoscopically severe atrophy or intestinal metaplasia. Because of the difficulty involved in the endoscopic diagnosis of gastric cancer in cases of previous infection, appropriate monitoring of the high‐risk subgroup of this understudied population is especially important.     

Histology of gastritis and Helicobacter pylori infection in Thailand: a nationwide study of 3776 cases

Background. Dyspepsia is a very common problem in Thailand. Etiology of gastritis, incidence of Helicobacter pylori and mode of transmission of Helicobacter pylori infection in the country was proposed. Methods. A nation‐wide study of gastric biopsy in 3776 dyspeptic patients from six different geographic regions for incidence of gastritis, type of gastritis, incidence of H. pylori infection, gastric atrophic change and intestinal metaplasia in three age‐groups of each region was done. Results. 58.7% of dyspeptic patients had histological gastritis. Pangastritis was the most common type (77.3%) with mostly mild active inflammation (60.6%) and was found most commonly in the age group 31–60 years. Incidence of gastritis was slightly lower in the coastal and peninsular community compared with the mountain, jungle, semiarid plateau and fertile plain communities. Geographic factor, socioeconomic status and dietary habit were proposed to be important factors in inducing gastritis. H. pylori infection was found in 48.2% of dyspeptic patients with high incidence in the age‐group 31–60 years (63.7%) and 98.2% of H. pylori infection was found to be associated with gastritis. Semi‐arid plateau, mountain, jungle and fertile plain communities had high incidences of H. pylori infection varying from 54.0 to 67.1% while the coastal and peninsular communities had low incidences of 32%. Oral to oral spread is proposed to be the mode of bacterial transmission. Incidences of gastric atrophic change and intestinal metaplasia were low in this country and were found in 11.6% and 8.2% of subjects, respectively, with no significantly different distribution in geographic regions. Type I or intestinal type was found to be the most common type of intestinal metaplasia.     

Correlation Between Helicobacter pylori Infection, Gastric Inflammation and Serum Homocysteine Concentration

Background. Epidemiological studies have suggested a link between chronic Helicobacter pylori infection and ischemic heart disease but the underlying mechanism remains elusive. We hypothesized that H. pylori‐associated chronic gastritis causes impairment of absorption of vitamin cofactors that are essential in the metabolism of homocysteine and results in hyperhomocysteinemia. Materials and Methods. Forty‐nine dyspeptic patients were studied. H. pylori infection was defined by rapid urease test and histology. Fasting serum homocysteine level, which was measured by a validated commercial fluorescence polarization immunoassay, was correlated with H. pylori infection statuses and gastric histology. H. pylori‐infected patients were followed up for 24 weeks post eradication for changes in serum homocysteine concentration. Results. Univariate analyses showed that serum homocysteine level correlated with increasing age (p < .001), male sex (p = .003) and smoking habit (p = .025). There was no significant difference in serum homocysteine levels between H. pylori infected and uninfected subjects (median 10.5 vs. 10.2 µmol/l). After successful eradication of the bacterium, there was no significant reduction in homocysteine level. Moreover, there was no correlation between homocysteine level and gastric histology including H. pylori density, activity and inflammation scores, presence of atrophy or intestinal metaplasia. Conclusions. The postulated link between H. pylori infection and ischemic heart disease, if it actually exists, is unlikely to be mediated through hyper‐homocysteinemia.     

Helicobacter pylori infection,mucosal atrophy and intestinal metaplasia in Asian populations: a comparative study in age-, gender- and endoscopic diagnosis-matched subjects

Background. It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races. Materials and Methods. Chinese, Thai, Vietnamese and Japanese patients were matched by age, gender and endoscopic diagnosis, in order to compare the differences in incidence of H. pylori‐related peptic ulcer disease and the prevalence of H. pylori infection among four Asian populations (n = 700). Glandular atrophy scores and intestinal metaplasia scores were also compared among four Asian populations divided into H. pylori‐positive cases (n = 120, 109, 145, 80, respectively) and H. pylori‐negative cases (n = 55, 66, 30, 95, respectively). Results. Among peptic ulcers, gastric ulcer was more frequently seen in Japanese subjects than in the other Asian populations examined. On the other hand, duodenal ulcer was more frequently seen in other Asian populations than in Japanese subjects. The prevalence of H. pylori infection was similar in the Japanese (Tokyo) and Chinese (Beijing and Fuzhou) populations. It was higher in Thai (Chiang Mai) subjects compared with Japanese subjects. On the other hand, Vietnamese (Ho Chi Minh) subjects had significantly lower rates of H. pylori infection than Japanese subjects. The glandular atrophy and intestinal metaplasia scores in the stomach were significantly higher in the H. pylori‐positive Japanese subjects than in H. pylori‐positive subjects belonging to other Asian populations, except for the higher glandular atrophy scores in Chinese rather than Japanese subjects. On the other hand, there were no significant differences in the glandular atrophy and intestinal metaplasia scores in the angulus of the stomach among H. pylori‐negative subjects belonging to the different Asian populations examined. Conclusions. Gastric ulcer was more common among Japanese subjects, while duodenal ulcer was more common among the other Asian populations examined. Japanese subjects with H. pylori infection showed more severe atrophic and metaplastic gastritis compared with that in other Asian subjects with H. pylori infection. These results may be related to the higher incidence of gastric cancer noted in Japanese subjects and the lower incidence of the cancer seen in Thai and Vietnamese patients.     

Statistical model of the interactions between Helicobacter pylori infection and gastric cancer development

Background. The bacterium Helicobacter pylori is associated with a number of gastrointestinal diseases, such as gastric ulcer, duodenal ulcer and gastric cancer. Several histological changes may be observed during the course of infection; some may influence the progression towards cancer. The aim of this study was to build a statistical model to discover direct interactions between H. pylori and different precancerous changes of the gastric mucosa, and in what order and to what degree those may influence the development of the intestinal type of gastric cancer. Methods. To find direct and indirect interactions between H. pylori and different histological variables, log‐linear analyses were used on a case–control study. To generate mathematically and biologically relevant statistical models, a designed algorithm and observed frequency tables were used. Results. The results show that patients with H. pylori infection need to present with proliferation and intestinal metaplasia to develop gastric cancer of the intestinal type. Proliferation and intestinal metaplasia interacted with the variables atrophy and foveolar hyperplasia. Intestinal metaplasia was the only variable with direct interaction with gastric cancer. Gender had no effect on the variables examined. Conclusion. The direct interactions observed in the final statistical model between H. pylori, changes of the mucosa and gastric cancer strengthens and supports previous theories about the progression towards gastric cancer. The results suggest that gastric cancer of the intestinal type may develop from H. pylori infection, proliferation and intestinal metaplasia, while atrophy and foveolar hyperplasia interplay with the other histological variables in the disease process.     

Different Expression of Helicobacter pylori Gastritis in Children: Evidence for a Specific Pediatric Disease?

Background Infection with Helicobacter pylori causes active chronic gastritis. Once the infection is acquired, gastritis will persist for almost the rest of one's life. To date, very few data are available on H. pylori gastritis in relation to age. Therefore, we attempted to inestigate whether H. pylori gastritis in children exhibits features different from H. pylori gastritis in adults of two different age groups. Materials and Methods. Fifty consecutive children with a median age of 11 years (range, 3–18 years) were compared with two groups of 50 adult patients, one group with a median age of 43 (range, 19–56 years) and another group with a median age of 70 years (range, 59–86 years). All patients had H. pylori gastritis unrelated to active peptic ulcer disease. Two biopsy specimens were taken from the antrum and two from the corpus, and the following gastritis parameters were evaluated: degree and activity of gastritis, H. pylori colonization, replacement of foveolar epithelium by regenerative epithelium, mucous depletion, presence of atrophic gastritis with intestinal metaplasia, and presence of lymphoid follicles. Results. Degree and activity of gastritis, extent of H. pylori colonization, degree of replacement by regenerative epithelium, extent of mucous depletion, degree of atrophic gastritis with intestinal metaplasia, and the presence of lymphoid follicles in the antrum, as well as the presence of lymphoid follicles in the corpus differed significantly (chi-square test: p < .05). All these differences—except the once frequent occurrence of atrophic gastritis with intestinal metaplasia in adults—were attributable to a higher expression of these gastritis parameters in children. Conclusions. We conclude that H. pylori gastritis, particularly in the antrum, is more severely expressed in childhood. One reason for this might be a child-specific immune response to an infection with H. pylori. Alternatively, infection may represent a pediatric disease characterized by a nonatrophic, highly expressed form of gastritis, which changes its appearance once the host becomes adapted over time.     

Helicobacter pylori infection up-regulates gland mucous cell-type mucins in gastric pyloric mucosa

Background. Two types of mucous cell are present in gastric mucosa: surface mucous cells (SMCs) and gland mucous cells (GMCs), which consist of cardiac gland cells, mucous neck cells, and pyloric gland cells. We have previously reported that the patterns of glycosylation of SMC mucins are reversibly altered by Helicobacter pylori infection. In this study, we evaluated the effects of H. pylori infection on the expression of GMC mucins in pyloric gland cells. Methods. Gastric biopsy specimens from the antrums of 30 H. pylori‐infected patients before and after eradication of H. pylori and 10 normal uninfected volunteers were examined by immunostaining for MUC6 (a core protein of GMC mucins), α1,4‐N‐acetyl‐glucosaminyl transferase (α4GnT) (the glycosyltransferase which forms GlcNAcα1‐4Galβ‐R), and GlcNAcα1‐4Galβ‐R (a GMC mucin‐specific glycan). Results. MUC6, α4GnT, and HIK1083‐reactive glycan were expressed in the cytoplasm, supranuclear region, and secretory granules in pyloric gland cells, respectively. The immunoreactivity of MUC6 and α4GnT, but not of GlcNAcα1‐4Galβ‐R, in the pyloric gland increased in H. pylori‐associated gastritis, and after the eradication of H. pylori, the increased expression of MUC6 and α4GnT in the gastric mucosa of H. pylori‐infected patients decreased to almost normal levels. This up‐regulation was correlated with the degree of inflammation. Conclusions. In addition to the synthesis of GMC mucins increasing reversibly, their metabolism or release may also increase reversibly in H. pylori‐associated gastritis. The up‐regulation of the expression of gastric GMC mucins may be involved in defense against H. pylori infection in the gastric surface mucous gel layer and on the gastric mucosa.     

Increased gastric osteopontin expression by Helicobacter pylori Infection can correlate with more severe gastric inflammation and intestinal metaplasia

Background: Osteopontin (OPN) is involved in the gastric cancer progression. The study validated whether OPN expressions correlate with Helicobacter pylori‐related chronic gastric inflammation and the precancerous change as intestinal metaplasia (IM). Methods: This study included 105 H. pylori‐infected patients (63 without and 42 with IM) and 29 H. pylori‐negative controls. In each subject, the gastric OPN expression intensity was evaluated by immunohistochemistry, and graded from 0 to 4 for the epithelium, lamina propria, and areas with IM, respectively. For the H. pylori‐infected subjects, the gastric inflammation was assessed by the Updated Sydney System. Forty‐nine patients received follow‐up endoscopy to assess OPN change on gastric mucosa after H. pylori eradication. The in vitro cell‐H. pylori coculture were performed to test the cell origin of OPN. Results: The H. pylori‐infected patients had higher gastric OPN expression than the noninfected controls (p < .001). For the H. pylori‐infected patients, an increased OPN expression correlated with more severe chronic gastric inflammation (p < .001) and the presence of IM (OR: 2.6, 95% CI: 1.15–5.94, p = .02). Within the same gastric bits, lamina propria expressed OPN stronger than epithelium (p < .001), suggesting OPN predominantly originates from inflammatory cells. The in vitro assay confirmed H. pylori stimulate OPN expression in the monocytes, but not in the gastric epithelial cells. After H. pylori eradication, the gastric OPN expression could be decreased only in areas without IM (p < .05). Conclusions: Increased gastric OPN expression by H. pylori infection can correlate with a more severe gastric inflammation and the presence of IM.     

Helicobacter pylori-negative gastric cancer in South Korea: incidence and clinicopathologic characteristics

Background and Aim: It is difficult to determine the exact incidence rate of Helicobacter pylori (H. pylori) infection‐negative gastric cancer (HPIN‐GC) because H. pylori detection rates decrease with the progression of gastric atrophy and intestinal metaplasia. The aim of this study was to evaluate the incidence and clinicopathologic characteristics of HPIN‐GC in South Korea. Methods: Helicobacter pylori infection status was evaluated by histology, a rapid urease test (CLO test), culturing, serology, and history of H. pylori eradication for 627 patients with gastric cancer. Current H. pylori infection was defined as positive results from histology, the CLO test, and culturing. Previous H. pylori infection was defined as negative in all three biopsy‐based tests and positive serology or history of H. pylori eradication. Patients were considered to be negative for H. pylori infection if all results from five methods were negative. However, patients who were found to have severe gastric atrophy by the serum pepsinogen test or metaplastic gastric atrophy by histology were assumed to have had a previous H. pylori infection even if results from other tests for H. pylori infection were all negative. Results: The number of patients with gastric cancer with current or previous H. pylori infection was 439 (70.0%) and 154 (24.6%), respectively. The rate of HPIN‐GC occurrence was 5.4% (n = 34). Sex, age, Lauren type, location of the tumor, and treatment modalities were not different according to H. pylori infection status. However, HPIN‐GC had a more advanced pT classification (T3/T4; 51.9 vs 31.1%, p = .025) and a more advanced stage (more than stage I; 63 vs 41.3%, p = .027) than H. pylori‐positive gastric cancer. Conclusion: At least 5.4% cases of gastric cancer were H. pylori negative among South Korean patients. HPIN‐GC looks like to have a poorer prognosis than H. pylori‐positive cases.     

Discrimination of normal gastric mucosa from Helicobacter pylori gastritis using standard endoscopes and a single observation site: studies in children and young adults

Background. In the Helicobacter pylori‐negative normal stomach, collecting venules are visible in the gastric corpus as numerous minute points. This finding has been termed ‘regular arrangement of collecting venules’ (RAC). The aim of the present study was to investigate the reliability of the presence of the RAC pattern for discrimination of normal gastric mucosa from H. pylori gastritis in pediatric patients. Methods. Fifty‐two consecutive children, adolescents and young adults (male:female 24 : 28; median age 15 years, range 8–29 years) referred for endoscopy and assessed for H. pylori infection were prospectively studied. The lower lesser curvature of the corpus near the incisura was evaluated for the RAC pattern using a standard endoscope with the tip close to, but not in contact with, the gastric surface. Gastric biopsies were taken after the endoscopic observation. Results. In all the 29 RAC‐positive patients, active H. pylori gastritis was absent, whereas H. pylori gastritis was found in 20 of 23 RAC‐negative patients (86.9%). Conclusions. Identification of the RAC pattern at the lower lesser curvature of the corpus using close observation with a standard endoscope proved to be an effective and practical marker to discriminate normal histology from H. pylori gastritis among both children and young adults. Absence of the RAC pattern should prompt gastric mucosal biopsies despite otherwise normal‐appearing gastric mucosa.