Accuracies of Endoscopic Diagnosis of Helicobacter pylori-Gastritis: Multicenter Prospective Study Using White Light Imaging and Linked Color Imaging.

INTRODUCTION: The diagnosis of Helicobacter pylori infection status with white light imaging (WLI) is difficult. We evaluated the accuracies of using WLI and linked color imaging (LCI) for diagnosing H. pylori-active gastritis in a multicenter prospective study setting. METHODS: Patients who underwent esophagogastroduodenoscopy were prospectively included. The image collection process was randomized and anonymous, and the image set included 4 images with WLI or 4 images with LCI in the corpus that 5 reviewers separately evaluated. Active gastritis was defined as positive when there was diffuse redness in WLI and crimson coloring in LCI. The H. pylori infection status was determined by the urea breath test and the serum antibody test. Cases in which both test results were negative but atrophy or intestinal metaplasia was histologically confirmed were defined as past infections. The primary endpoint was the diagnostic accuracies of WLI and LCI, and the secondary endpoint was inter-observer agreement. RESULTS: Data for 127 patients were analyzed. The endoscopic diagnostic accuracy for active gastritis was 79.5 (sensitivity of 84.4 and specificity of 74.6) with WLI and 86.6 (sensitivity of 84.4 and specificity of 88.9) with LCI (p = 0.029). LCI significantly improved the accuracy in patients with past infections over WLI (36.8 in WLI and 78.9 in LCI, p < 0.01). The κ values were 0.59 in WLI and 0.70 in LCI. CONCLUSIONS: LCI is useful for endoscopic diagnosis of H. pylori-active or inactive gastritis, and it is advantageous for patients with past infections of inactive gastritis.

Can neopterin be a useful immune biomarker for differentiating gastric intestinal metaplasia and gastric atrophy from non-atrophic non-metaplastic chronic gastritis?

INTRODUCTION: Helicobacter pylori (H. pylori) is closely related to pre-neoplastic lesions such as gastric atrophy (GA), gastric intestinal metaplasia (GIM) and eventually gastric cancer (GC). The diagnosis of GIM and GA is usually based on endoscopic and histopathological features. Nowadays, there are no recognized good serological markers of GIM and GA. Neopterin is an important marker of cellular inflammation. In this study, we aimed to comparatively evaluate C-reactive protein (CRP) and neopterin levels in patients with GIM, GA and chronic gastritis, and to show the increased serum neopterin levels in GIM and GA according to non-atrophic and non-metaplastic chronic gastritis. PATIENTS AND METHODS: 98 patients with GIM and 68 patients with GA and 70 patients with non-atrophic non-metaplastic gastritis were included in the study. CRP and neopterin levels were assessed in patients and controls. RESULTS: CRP and neopterin levels were significantly higher in patients with GIM and GA than in controls (p<0.05 and p<0.001, respectively). A multiple logistic regression analysis showed that high levels of serum neopterin were positively correlated with GIM and GA. According to the ROC curve analysis, the best cut-off value to differentiate between patients with GIM and/or GA from controls was ≥10.15nmol/l (p<0.001) for serum neopterin levels and ≥1.95mg/l (p<0.001) for serum CRP levels. DISCUSSION: CRP and neopterin levels are significantly increased in GIM and GA. Neopterin may be a useful biomarker and diagnostic test for detecting GIM and GA in clinical practice. CRP levels may be helpful for this observation.

Serum anti-Helicobacter pylori antibody titer and its association with gastric nodularity, atrophy, and age: A cross-sectional study.

AIM: To clarify the role of serum anti-Helicobacter pylori (H. pylori) antibody titers in gastric cancer. METHODS: In this cross-sectional study, the effect of patients' baseline characteristics and endoscopic findings on their serum antibody titers were assessed. We evaluated consecutive patients who underwent esophagogastroduodenoscopy and their first evaluation for H. pylori infection using a serum antibody test. We excluded patients with a history of eradication therapy. The participants were divided into four groups according to their E-plate serum antibody titer. Patients with serum antibody titers < 3, 3-9.9, 10-49.9, and ≥ 50 U/mL were classified into groups A, B, C, and D, respectively. RESULTS: In total, 874 participants were analyzed with 70%, 16%, 8.7%, and 5.1% of them in the groups A, B, C, and D, respectively. Patients in group C were older than patients in groups A and B. Gastric open-type atrophy, intestinal metaplasia, enlarged folds, diffuse redness, and duodenal ulcers were associated with a high titer. Regular arrangements of collecting venules, fundic gland polyps, superficial gastritis, and gastroesophageal reflux disease were related to a low titer. Multivariate analysis revealed that nodularity (P = 0.0094), atrophy (P = 0.0076), and age 40-59 years (vs age ≥ 60 years, P = 0.0090) were correlated with a high serum antibody titer in H. pylori-infected patients. Intestinal metaplasia and atrophy were related to age ≥ 60 years in group C and D. CONCLUSION: Serum antibody titer changes with age, reflects gastric mucosal inflammation, and is useful in predicting the risk of gastric cancer.

Circulating microRNA-22-3p Predicts the Malignant Progression of Precancerous Gastric Lesions from Intestinal Metaplasia to Early Adenocarcinoma.

BACKGROUND: Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. AIM: Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. METHODS: Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. RESULTS: Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values < 0.05). CONCLUSIONS: Circulating miRNA-22-3p could be a potential biomarker for gastric precancerous dysplasia and early cancer detection.

Gastric xanthelasma and metabolic disorders: A large retrospective study among Chinese population.

AIM: To gain knowledge of xanthelasma, a large population-based study was conducted. METHODS: Patients who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China during Jan 2009 to Nov 2016 were included. General characteristics as well as clinical data were collected, including blood routine, serum biochemical analysis, endoscopic findinds, histological evaluation and comorbiditie. Statistical analyses was performed using SPSS 20.0 software for Windows (IBM Inc., Chicago, IL, United States) using Student's t-test, Mann-Whitney U test, χ2 test, univariable and multivariable logistic analysis. 2-tailed P value less than 0.05 was considered to be statistically significant. RESULTS: A total of 176006 endoscopies were retrieved and we included 1370 xanthelasma participants (703 men, 667 women) in this study. Prevalence of xanthelasma was 0.78% with average age of 56.6 ± 11.2 years. Chief complaint of xanthelasma consisted abdominal pain (24.2%), up-abdominal discomfort (14.1%), abdominal distention (10.1%), dyspepsia (9.1%), et al. Most xanthelasma occurred as single lesion in gastric antrum. Xanthelasma patients witnessed higher Helicobacter pylori (H. pylori) infection rate, more of other gastric lesions including atrophy, intestinal metaplasia and dysplasia (P < 0.01). In xanthelasma patients, serum carcinoembryonic antigen, triglyceride, fasting glucose, neutrophil, neutrophil-to-lymphocyte ratio were significantly higher, and high density lipoprotein-cholesterol, lymphocyte was lower (P < 0.05). Xanthelasma accompanied with more fatty liver disease and hepatic cyst, but fewer gallbladder polyp (P < 0.05). In logistic regression, it revealed that fasting plasma glucose (OR = 3.347, 1.170-9.575, P < 0.05), neutrophil (OR = 1.617, 1.003-2.605, P < 0.05), and carcinoembryonic antigen (OR = 2.011, 1.236-3.271, P < 0.01) were all independent risk factors in xanthelasma. CONCLUSION: Current study described a large xanthelasma cohort in Chinese population, revealed its relationship with H. pylori infection, carcinogenesis, metabolic dysfunction and inflammation as well.

Plasma ghrelin level and plasma ghrelin/obestatin ratio are related to intestinal metaplasia in elderly patients with functional dyspepsia.

BACKGROUND: Whether plasma ghrelin/obestatin levels are associated with Helicobacter pylori (H. pylori) infection, subtypes of functional dyspepsia (FD), and gastric mucosal histology has not yet been established in elderly patients. OBJECTIVE: The aim of this study was to determine whether plasma ghrelin and obestatin levels are related to gastric mucosal histology, H. pylori infection, and FD subtypes in elderly patients with FD. METHODS: Ninety-two patients diagnosed with FD and older than 60 years (median age 69.4; range 60-88) were included. Clinical symptoms investigated included postprandial fullness, epigastric pain, epigastric soreness, nausea, and vomiting. According to the Rome III criteria, patients diagnosed with FD were divided into two subtypes: epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Plasma ghrelin and obestatin levels were measured using enzyme immunoassay, and histological examination of gastric mucosa was performed. H. pylori infection was determined by histopathological examination of gastric mucosal biopsy and/or Campylobacter-like organism test. RESULTS: In our study, plasma ghrelin levels and plasma ghrelin/obestatin (G/O) ratio were significantly lower in subjects with intestinal metaplasia compared with those without intestinal metaplasia (ghrelin, p = 0.010; G/O ratio, p = 0.012). On the other hand, there were no significant differences in plasma ghrelin and obestatin levels between H. pylori-positive and H. pylori-negative groups. (ghrelin, p = 0.130; obestatin, p = 0.888). Similarly, no significant differences were detected between the EPS and PDS groups (ghrelin, p = 0.238; obestatin, p = 0.710). CONCLUSIONS: Patients with intestinal metaplasia, a known precursor of gastric cancer, had significantly less plasma ghrelin levels and G/O ratio than those without intestinal metaplasia.

Pepsinogen-II 100 bp ins/del gene polymorphism and its elevated circulating levels are associated with gastric cancer, particularly with Helicobacter pylori infection and intestinal metaplasia.

BACKGROUND: Polymorphism in the gene of pepsinogen-II (PG-II) and its serum level are effective biomarkers for terminal differentiation of gastric mucosa into gastritis, intestinal metaplasia (IM), and gastric cancer (GC) in relationship to Helicobacter pylori infection. METHODS: Genotyping of the PG-II 100 bp insertion/deletion (ins/del) polymorphism was performed in patients with GC (n = 192) and age- and gender-matched H. pylori-associated dyspepsia (n = 180) and healthy subjects (HS, n = 240) by PCR. IgG anti-H. pylori (in all subjects) and serum PG-II levels were estimated in 145 patients each with GC and dyspepsia and in 65 healthy controls (HC) using ELISA (Biohit Oyj, Finland). RESULTS: Five alleles were amplified by PCR: allele 5 (510 bp), allele 4 (480 bp), allele 3 (450 bp), allele 2 (400 bp), and allele 1 (shorter allele, 310 bp). Allele 1 carriage was infrequent, and serum PG-II level was higher among patients with GC than in HC [OR 0.43 (95 % CI, 0.29-0.85), p < 0.001 and mean ± SD; 17.53 ± 12.60 vs. 12.77 ± 7.53 µg/l, p = 0.005, respectively], particularly in the presence of H. pylori [OR 0.42 (0.25-0.71), p = 0.001 and 18.78 ± 12.63 vs. 13.97 ± 8.14, p = 0.034]. However, allele 1 carriage and PG-II levels were comparable among patients with GC and dyspepsia. Patients with IM also carried allele 1 infrequently and had higher levels of PG-II than those without [OR 0.5 (0.29-0.85), p = 0.011 and 20.07 ± 14.22 vs. 16.61 ± 12.08, p = 0.048]. CONCLUSIONS: Carriage of the shorter allele of the PG-II 100 bp ins/del polymorphism and elevated levels of PG-II are associated with GC, particularly with H. pylori infection and IM.

Decrease of serum total ghrelin in extensive atrophic gastritis: comparison with pepsinogens in histological reference.

OBJECTIVE: Ghrelin is mainly secreted by the gastric oxyntic mucosa and its production is impaired in chronic atrophic gastritis. This study aimed at evaluating how serum total ghrelin correlates with the extent of atrophy, and to compare its performance as a serologic marker with that of pepsinogen (PG). MATERIAL AND METHODS: Data were collected from 154 patients with atrophic gastritis. The histological extent of atrophy was assessed by three paired biopsies from the antrum, corpus lesser curvature (CLC), and corpus greater curvature (CGC). Fasting serum concentrations of total ghrelin, pepsinogen I and II were measured. Regression analysis was performed to evaluate the factors associated with serum total ghrelin. The serologic performance was compared with that of pepsinogen using receiver-operating characteristic (ROC) curves. RESULTS: The Helicobacter pylori infection rate was 85%, and extensive atrophic gastritis involving CGC was found in 24%. Serum total ghrelin was significantly decreased in patients with extensive CGC atrophy (median: 170.4 pg/mL, vs 201.1 pg/mL in patients without atrophy; p < 0.001), and its levels correlated with those of pepsinogen I and I/II ratio. The decrease of serum total ghrelin was independent of age, gender, body mass index (BMI), and H. pylori infection status. The sensitivity and specificity of serum total ghrelin in predicting extensive atrophy were 57% and 79%, respectively. The discriminatory ability was similar to that of pepsinogen I/II ratio (p = 0.612), and lower than that of pepsinogen I (p = 0.040). CONCLUSIONS: Serum total ghrelin is decreased during extensive atrophy involving CGC. The serologic performance is lower than that of pepsinogen I.

Proteomic profiling of human plasma identifies apolipoprotein E as being associated with smoking and a marker for squamous metaplasia of the lung.

Biomarkers to identify subjects at high-risk for developing lung cancer will revolutionize the disease outlook. Most biomarker studies have focused on patients already diagnosed with lung cancer and in most cases the disease is often advanced and incurable. The objective of this study was to use proteomics to identify a plasma biomarker for early detection of lung lesions that may subsequently be the harbinger for cancer. Plasma samples were obtained from subjects without lung cancer grouped as never, current, or ex-smokers. An iTRAQ-based proteomic analysis was performed on these pooled plasma samples. We identified 31 proteins differentially abundant in current smokers or ex-smokers relative to never smokers. Western blot and ELISA analyses confirmed the iTRAQ results that demonstrated an increase of apolipoprotein E (APOE) in current smokers as compared to both never and ex-smokers. There was a strong and significant correlation of the plasma APOE levels with development of premalignant squamous metaplasia. Additionally, we also showed that higher tissue levels of APOE are seen with squamous metaplasia, supporting a direct relationship. Our analysis reveals that elevated plasma APOE is associated with smoking, and APOE is a novel predictive protein biomarker for early morphological changes of squamous metaplasia in the lung.

The optimal serum pepsinogen cut-off value for predicting histologically confirmed atrophic gastritis.

BACKGROUND: Although serum pepsinogen tests are useful for predicting the presence of atrophic gastritis, the optimal cut-off values have not been fully evaluated. AIM: To determine the optimal serum pepsinogen cut-off value for predicting atrophic gastritis. METHODS: Patients scheduled for upper endoscopy at Severance Hospital, Korea, between August 2012 and October 2013, were recruited prospectively. Endoscopic biopsies for atrophic gastritis were obtained and histologically graded, based on the updated Sydney system. RESULTS: Ninety-five patients were enrolled in the study. The mean age was 57.7±12.1 years, and 44.2% of the patients were male. Serum pepsinogen I/II ratios were lower in patients with atrophic gastritis than in those without it (antrum, 4.2±1.7 vs. 5.2±2.1, P=0.040; corpus, 3.3±1.9 vs. 5.4±1.9, P<0.001). Serum pepsinogen I/II ratios were significantly correlated with histologic atrophic gastritis (antrum, P=0.030; corpus, P<0.001). Using a cut-off value of 4.9, the sensitivity and specificity of the serum pepsinogen I/II ratio for predicting atrophic gastritis in the antrum were 68.2% and 60.3%, respectively. CONCLUSION: The optimal serum pepsinogen I/II ratio cut-off values for atrophic gastritis of the antrum and for the corpus were 4.9 and 3.5, respectively. Serum pepsinogen I/II ratios, with these cut-off values, are useful for screening patients for the presence of atrophic gastritis.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer.

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

Serum gastrin and the pepsinogen I/II ratio as markers for diagnosis of premalignant gastric lesions.

BACKGROUND: Iran is a country with very high incidences of stomach cancer, especially in Northern parts. Here we assessed prognostic value of serum screening biomarkers among people >50 years old for early detection of precancerous lesions in a hot spot for gastric carcinoma in Guilan Province, North Iran. METHODS: A cross- sectional population-based survey was conducted on 1,390 residents of Lashtenasha city with the mean age (SD) of 61.8 (9.02) years old (50.8% females) to assess the association of gastrin and the pepsinogen (PG) I/II ratio with premalignant gastric lesions. Blood samples were taken for CBC, blood group, and serologic exams (PGI, PGII, and gastrin 17) from each subject. Expert gastroenterologists performed upper GI endoscopy and ROC curves were generated to determine appropriate cutoff points. RESULTS: Mean values of PGI, PGII, PGI/PGII and gastrin were significantly different between patients with and without atrophy or metaplasia (P<0.05). To diagnose atrophy and intestinal metaplasia, a significantly higher AUC was observed for the PGI/PGII ratio (70 and 72%, respectively) compared to the PGI (56, 55%), PGII (63, 64%) and gastrin (59, 61%) (all p<0.001). CONCLUSIONS: Biomarker tests such as the PGI/II ratio can be used in the screening and diagnosis of subjects at high gastric cancer risk in our region.

The association between precancerous gastric lesions and serum pepsinogens, serum gastrin, vascular endothelial growth factor, serum interleukin-1 Beta, serum toll-like receptor-4 levels and Helicobacter pylori Cag A status.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the association between serum pepsinogens, serum gastrin, serum vascular endothelial growth factor, serum interleukin-1 Beta, serum toll-like receptor-4 levels and Helicobacter pylori Cag A status in patients with various gastric precancerous lesions. METHODS: One hundred and sixty two consecutive patients with various gastric lesions [38 (23.5%) H. pylori positive chronic non-atrophic gastritis, 45 (27.8%) autoimmune gastritis, 42 intestinal metaplasia and 37 dysplasia] were enrolled into the study. Serum pepsinogen I and II, gastrin 17, vascular endothelial growth factor, interleukin-1 Beta, toll-like receptor-4 levels, H. pylori Cag A status were evaluated. RESULTS: H. pylori was positive in 98 (60.5%) patients and 38 of these patients were Cag A positive. Serum pepsinogen level was significantly lower in patients with autoimmune atrophic gastritis compared to the patients with non-atrophic chronic gastritis (p<0.001), intestinal metaplasia (P<0.001) and dysplasia (P=0.002). Mean serum gastrin was 1209.6±268.48 pg/mL in patients with autoimmune atrophic gastritis and 234.95±184.018 pg/mL in patients with chronic non-atrophic gastritis. Mean toll-like receptor-4 level was 0.56±0.098 ng/mL in patient with dysplasia, and this value was higher compared to patients with chronic non-atrophic gastritis (P=0.007), autoimmune atrophic gastritis (P=0.003) and intestinal metaplasia (P=0.006). Interleukin-1 Beta level was significantly lower in patients with dysplasia compared to patients with chronic non-atrophic gastritis (P=0.034). CONCLUSIONS: Serum pepsinogens, serum gastrin and H. pylori Cag A status are important tests in detecting gastric precancerous lesions. However, toll-like receptor-4 may be a sensitive test to differentiate the patients with dysplasia from the other precancerous gastric lesions. Non-invasive tests are sensitive in the diagnosis of gastric precancerous lesions.

Monoclonal antibody MG7 as a screening tool for gastric cancer.

MG7 is a gastric cancer-specific MAb with high specificity and sensitivity. By using MG7 MAb, we found that MG7Ag was increasingly detected in superficial gastritis, atrophic gastritis, intestinal metaplasia, atypical hyperplasia, and gastric cancer, indicating that MG7Ag could be considered an important early warning molecule of gastric cancer and MG7 MAb could be used as a tool for screening gastric cancer. We have developed a new and sensitive system, immuno-realtime PCR, for detection of MG7Ag in the serum. The use of qIPCR assays enabled the detection of MG7Ag in complex biological samples that were poorly accessible by conventional immunoassays.

Relevance of Helicobacter pylori genotypes in gastric pathology and its association with plasma malondialdehyde and nitric oxide levels.

Persistent infection with Helicobacter pylori confers an increased risk of peptic ulceration and gastric adenocarcinoma. Reactive oxygen and nitrogen species play a crucial role in the progression from normal gastric mucosa to cancer. The aim of the present study was to investigate the plasma malondialdehyde and nitric oxide levels in H. pylori related gastroduodenal diseases and associate their levels with gastric pathology and genotypes of H. pylori. Malondialdehyde and nitric oxide levels in plasma samples of 250 subjects were spectrophotometrically determined. Subsequently, genotypic and histopathological assessment was performed in gastric biopsies obtained during endoscopy. The levels of MDA and NO exceeded in subjects infected with genotype-1 of Hp than those with other genotypes suggesting more precise interaction of highly virulent strains of Hp in eliciting severe tissue damage. In conclusion, the study demonstrates close relationship between the plasma malondialdehyde and nitric oxide levels, gastric histopathology and genotypes of H. pylori.

Histologic and serum risk markers for noncardia early gastric cancer.

Corpus dominant gastritis and intestinal metaplasia (IM) are considered markers of increased risk of gastric carcinoma. The aim of our study was to determine serum and histologic risk markers of gastric cancer. Antral and corpus histology, pepsinogen and gastrin 17 levels were compared among patients with history of endoscopic mucosal resection (EMR) for early gastric cancer and controls. Serum pepsinogen (PG) and gastrin 17 levels were measured by RIA. There were 53 gastric cancer patients and 75 controls. The scores for IM in each region and atrophy at the lesser curvature of the corpus were significantly higher in the cancer group than in the H. pylori-positive control group. IM at the greater curvature of the corpus and atrophy at the lesser curvature of the corpus were associated with multiple malignant lesions. Although corpus gastritis was associated with an increased risk of gastric cancer (odds ratio [OR] = 3.4; 95% confidence interval [CI] 1.6-7.0) (p = 0.001), the most important marker was the presence of IM at the lesser curvature of the corpus (OR = 15.1; 95% CI 4.3-52.6) (p < 0.001)). The best cut-off points of serum markers for gastric cancer were a PG I concentration of 45 ng/mL or less and a gastrin 17 >60 pg/mL (sensitivity = 83%; specificity = 68%). IM at the lesser curvature of the corpus and the combination of serum gastrin 17 and PG I identified a group at high risk for development of gastric cancer. Annual endoscopic follow-up is warranted for patients with IM found at the greater curvature of the corpus.

Serum pepsinogens as a predicator of the topography of intestinal metaplasia in patients with atrophic gastritis.

The importance of atrophic gastritis with intestinal metaplasia is related to the fact that it increases the risk of gastric cancer development. The aim of this study is to evaluate the diagnostic potential of serum pepsinogens in predicting the topography of intestinal metaplasia. Both dye endoscopy and 13C-urea breath test were carried out in 878 subjects. Serum pepsinogen I, pepsinogen II, and IgG antibody to Helicobacter pylori were measured. The overall prevalence of intestinal metaplasia was higher in subjects with lower PG I/II ratios and lower PG I values. Based on ROC curves, a cutoff value for pepsinogen I/II ratio of less than 3.0 would have identified intestinal metaplasia with a sensitivity of 71.7% and a specificity of 66.7% in Helicobacter pylori-positive subjects. It is possible that serum pepsinogens could be used as a screening test for high-risk subjects with intestinal metaplasia.

Prognostic significance of high expression of proliferating cell nuclear antigen in patients with intestinal metaplasia.

Although some types of intestinal metaplasia are considered to be potentially pre-malignant lesions leading to gastric carcinoma, their high frequency and variability limit their usefulness as early markers of malignant progression. The present study was carried out to search for parameters which could be used in conjunction with histological diagnosis to identify groups of patients with a high risk for developing gastric neoplasia. The expression of proliferating cell nuclear antigen (PCNA), as revealed by immunohistochemical staining of anti-PCNA monoclonal antibody (PC10) in 82 endoscopic biopsy specimens, was compared with the histological classification of intestinal metaplasia, the biochemical composition of gastric mucins and the expression of blood group Lewis antigens. Statistically significant (p 0.001) correlation between the PCNA labelling index (the percentage of positive cells in more than 700 tumor cells per sample) and the histological type of intestinal metaplasia, the presence of sulphomucins, and the presence of anomalous Lewis a antigen was found. We conclude that a high PCNA-labelling index in the gastric mucosa, with a histological diagnosis of incomplete intestinal metaplasia, could constitute a good prognostic marker of the severity of the histologic lesion. These parameters, together with others such as the presence of sulphomucins and of cells expressing anomalous Lewis a antigen, may be used to define patients with a high risk of developing a gastric neoplasia.

Relationship between Helicobacter pylori infection, atrophic gastritis and gastric carcinoma in a Japanese population.

AIM: To evaluate the possible relationship between Helicobacter pylori infection and gastric carcinoma, and its precursor lesion, intestinal metaplasia, in a Japanese population. SUBJECTS AND METHODS: H. pylori infection was identified by the presence of anti-H. pylori immunoglobulin (Ig)G. The frequency of H. pylori infection was compared in 109 patients with gastric carcinoma, the same number of patients with atrophic gastritis and asymptomatic controls matched for age, sex and place of birth. To study the relation between H. pylori and intestinal metaplasia, sera and gastric antral and corpus mucosal biopsies were obtained from 58 asymptomatic controls, 92 patients with chronic gastritis and 80 patients with peptic ulcer. RESULTS: The presence of IgG antibody to H. pylori was significantly more frequent in those with gastric carcinoma than in asymptomatic controls (87.2 versus 74.3%; odds ratio 2.4; 95% confidence interval 1.2-4.8). The positive rates of H. pylori IgG antibody were 80.7% in patients with atrophic gastritis. Mean serum gastrin and pepsinogen II levels in H. pylori-positive patients were higher than those in H. pylori-negative patients. Serum gastrin and pepsinogen I levels were significantly higher in controls than gastric carcinoma patients (P < 0.01 and P < 0.05, respectively). Serum pepsinogen I:II ratios were significantly lower in controls than in gastric carcinoma patients (P < 0.01). Intestinal metaplasia was strongly associated with H. pylori infection, and was only found in patients with IgG antibodies to H. pylori. CONCLUSIONS: These results suggest that H. pylori infection is associated with the development of gastric cancer by providing a suitable environment for carcinogenesis of the gastric mucosa, such as gastric atrophy and intestinal metaplasia.

Lewis blood group-related antigen expression in normal gastric epithelium, intestinal metaplasia, gastric adenoma, and gastric carcinoma.

The expression of blood group-related antigens of the Lewis system in normal gastric mucosa, intestinal metaplasia, gastric adenoma, and gastric carcinoma was examined. Ninety-five percent of normal foveolar epithelial samples stained positive for Lewis(b) antigen, whereas only 10.0% expressed Lewis(a) antigen. In contrast, intestinal metaplasia specimens had increased Lewis(a) antigen expression and slightly decreased Lewis(b) antigen expression. A similar pattern of Lewis(a) and Lewis(b) expression was observed in gastric adenomas and intestinal type adenocarcinomas. Lewis(x) and Lewis(y) were detected in all normal deep glands, but were not expressed in the majority of intestinal metaplasia specimens. In addition, only 20-40% of gastric adenomas and gastric carcinomas expressed Lewis(x) and Lewis(y) antigens. These changes in Lewis antigen expression in intestinal metaplasia, adenomas, and intestinal type adenocarcinomas suggest that altered expression of Lewis blood group-related antigens may correlate with cell transformation processes.