Screening endoscopy has advanced to facilitate improvements in the detection and prognosis of gastric cancer. However, most early gastric cancers (EGCs) have subtle morphological or color features that are difficult to detect by white-light imaging (WLI); thus, even well-trained endoscopists can miss EGC when using this conventional endoscopic approach. This review summarizes the current and future status of linked color imaging (LCI), a new image-enhancing endoscopy (IEE) method, for gastric screening. LCI has been shown to produce bright images even at a distant view and provide excellent visibility of gastric cancer due to high color contrast relative to the surrounding tissue. LCI delineates EGC as orange-red and intestinal metaplasia as purple, regardless of a history of Helicobacter pylori (Hp) eradication, and contributes to the detection of superficial EGC. Moreover, LCI assists in the determination of Hp infection status, which is closely related to the risk of developing gastric cancer. Transnasal endoscopy (ultra-thin) using LCI is also useful for identifying gastric neoplastic lesions. Recently, several prospective studies have demonstrated that LCI has a higher detection ratio for gastric cancer than WLI. We believe that LCI should be used in routine upper gastrointestinal endoscopies.

Helicobacter Pylori (H. pylori) infection is the most important factor affecting clinical outcome in patients with gastric mucosal lesions. This study aimed to investigate H. pylori infection in patients with gastric mucosal lesions and their virulence genotype in Guiyang, China.

Pathological examinations of 1,364 biopsies from patients with upper gastrointestinal symptoms and H. pylori infection were analyzed according to different pathological types. The bacterial genome DNA was extracted from H. pylori strains isolated from gastric biopsies, and the cagA, vacA, and iceA virulence genes were detected and typed to analyze the correlation of their genotypes between different pathological lesions.

The positive rate of H. pylori infection was approximately 19.9% (272/1,364), as determined by histopathological examination (HPE). It was more frequently detected in men than in women. A total of 85 H. pylori isolates were obtained from 280 clinical samples (positive rate 30.4%, 85/280). Of these 85 strains, cagA, vacA, and iceA genes were identified in 85.9%, 100%, and 83.5% of samples, respectively. Approximately 74.1% of strains were cagA East Asian type (cagA-ABD), and 11.8% of were cagA Western strains (cagA-AB, cagA-ABC), only present in patients with chronic non-atrophic gastritis. Gastric intraepithelial neoplasia and gastric cancer harbored both Asian strains. A total of 7 combinations of vacA genotypes were noted, among which s1c/m1b (30.6%) and s1c/m2 (41.2%) were the dominant genotypes. The predominant iceA genotype was iceA1 (64.7%).

We observed that the positive rate of H. pylori infection was related to the pathological type of patients' gastric mucosal lesions. Isolated H. pylori strains showed a unique genotype, mainly East Asian type cagA (ABD), vacA s1c/m2 genotype, and iceA1. These results provide an important reference for further studies of H. pylori in Guizhou province, China.

Linked color imaging (LCI) increases the visibility of early gastric cancers, which may be associated with characteristic findings including background purple mucosae. These lesions are found in areas of chronic gastritis and surrounding mucosa. The aim of this study is to objectively characterize these lesions by color differences and color component values using LCI.

Fifty-two patients with early gastric cancer were enrolled. Color differences were calculated prospectively in malignant lesions and adjacent mucosa and compared with histological findings in resected specimens. Color component values of L*, a*, and b* were compared between purple and non-purple mucosae in areas of chronic gastritis. Based on histological findings, the accuracy of identifying gastric intestinal metaplasia was calculated.

Cancers and surrounding mucosa in 74% of lesions had similar colors using white light imaging (WLI), whereas purple mucosa surrounded part or all of cancers appearing orange-red, orange or orange-white using LCI. Greater color differences were seen using LCI compared to WLI, including flat-type cancers, leading to higher contrast. The surrounding purple mucosa corresponded histologically to intestinal metaplasia, facilitating the identification of malignant lesions. Forty lesions (83%) with purple mucosa and eight lesions (17%) with non-purple mucosa in areas of chronic gastritis were diagnosed as intestinal metaplasia by biopsy (83% accuracy). Color component values of purple mucosa differ significantly from those of non-purple mucosae.

LCI images have higher color contrast between early gastric cancers and surrounding mucosa compared to WLI. A characteristic purple color around gastric cancers using LCI represents intestinal metaplasia.

White light imaging (WLI) may not reveal early upper gastrointestinal cancers. Linked color imaging (LCI) produces bright images in the distant view and is performed for the same screening indications as WLI. LCI and blue laser imaging (BLI) provide excellent visibility of gastric cancers in high color contrast with respect to the surrounding tissue. The characteristic purple and green color of metaplasias on LCI and BLI, respectively, serve to increase the contrast while visualizing gastric cancers regardless of a history of Helicobacter pylori eradication. LCI facilitates color-based recognition of early gastric cancers of all morphological types, including flat lesions or those in an H. pylori-negative normal background mucosa as well as the diagnosis of inflamed mucosae including erosions. LCI reveals changes in mucosal color before the appearance of morphological changes in various gastric lesions. BLI is superior to LCI in the detection of early esophageal cancers and abnormal findings of microstructure and microvasculature in close-up views of upper gastrointestinal cancers. Excellent images can also be obtained with transnasal endoscopy. Using a combination of these modalities allows one to obtain images useful for establishing a diagnosis. It is important to observe esophageal cancers (brown) using BLI and gastric cancers (orange) surrounded by intestinal metaplasia (purple) and duodenal cancers (orange) by LCI.

Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium-competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid-suppressing drug [lansoprazole 30 mg (LAC), rabeprazole 10 mg (RAC), esomeprazole 20 mg (EAC), or vonoprazan 20 mg (VAC)] twice daily for 1 week. Eradication was successful in 73% (419/573) of patients using intention-to-treat (ITT) analysis and 76% (419/549) of patients in per-protocol (PP) analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p < 0.01) and PP analysis (VAC 85%, LAC 69% and RAC 70%, p < 0.01), and had a similarly high eradication rate to the EAC group (83% in ITT and 87% in PP). Although the eradication rate in the VAC and EAC groups was not significantly higher than in the LAC and RAC groups in patients with mild gastric atrophy with both ITT and PP analyses, it was significantly higher in patients with severe gastric atrophy (p < 0.01). The VAC group had a significantly higher H. pylori eradication rate than the LAC and RAC groups, and a > 80% eradication rate regardless of the degree of atrophy.

Helicobacter pylori (HP) has been implicated as a risk factor for cardiovascular and atherosclerotic diseases. Arterial stiffness determined by pulse wave velocity (PWV) or the cardio-ankle vascular index (CAVI) has been shown to be higher in HP-positive subjects than in HP-negative subjects; however, this result has been observed only in young subjects. The aim of the study was to investigate the possible correlation between HP infection and PWV or CAVI in middle-aged subjects.

We measured brachial-ankle PWV (baPWV), CAVI, metabolism markers, pepsinogens (PGs) and IgG antibody to HP in 343 individuals aged either 60 or 65 year old. Atrophic gastritis (AG) was diagnosed based on the values of PGs.

baPWV and CAVI were significantly higher in the AG-positive group than in the AG-negative group even after adjusting for possible confounding factors (baPWVc; 16.63+/-3.50 vs. 15.59+/-3.47 p=0.010, CAVIc; 8.59+/-1.20 vs. 8.27+/-1.19 p=0.022). baPWV and CAVI values tended to be higher in the HP-positive group than in the HP-negative group. High-density lipoprotein (HDL) cholesterol level and the adiponectin level were lower in the AG-positive group than in the AG-negative group.

There may be an association between atrophic gastritis and atherosclerosis in middle-aged subjects.

Helicobacter bilis DNA has been detected in human tissue and is a candidate for etiologic investigations on the causes of hepatic and biliary tract diseases, but reliable serologic tests need to be developed in order to pursue such investigations. The scope of this study was to assess the specificity of two assays for H. bilis immune response allowing for H. pylori, and their cross-reactivity in a population in Thailand at high risk for cholangiocarcinoma. Plasma samples from 92 Thai volunteers were independently tested in two laboratories (Massachusetts Institute of Technology [MIT] and Lund). MIT performed three analyses of H. pylori and H. bilis based either on (i) outer membrane protein (OMP) with no preabsorption or on antigens derived from whole-cell sonicate before (ii) or after (iii) preabsorption with H. pylori sonicate protein. Lund used cell surface proteins from H. pylori and H. bilis as antigens. Testing for H. bilis was preabsorbed with a whole-cell lysate of H. pylori. More than 80% of the samples were positive for H. pylori in both laboratories. As tested by MIT, 58.7% (95% confidence interval, 47.9 to 68.9%) were positive for H. bilis by OMP and 44.5% (34.1 to 55.3%) were positive for H. bilis sonicate protein, but only 15.2% (8.6 to 24.2%) remained positive after preabsorption with H. pylori sonicate protein. Lund found 34.5% of the samples positive for H. bilis (22.0 to 41.0%), which was statistically compatible with all three MIT results. Serologic responses to OMPs of the two bacteria coincided in 66 and 45% of the samples in the MIT and Lund assays, respectively. We found high cross-reactivity between the immune responses to H. pylori and H. bilis antigens. More-specific H. bilis antigens need to be isolated to develop serologic tests suitable for epidemiological studies.

The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia may lead to early diagnosis of gastric cancer. However, to-date no cost-effective model has been proposed. Improved endoscopic examination using magnification chromoendoscopy together with non-invasive functional assessment with pepsinogen serum levels are accurate in the diagnosis of intestinal metaplasia (extension) and minute dysplastic lesions. The aim of this study was to assess the feasibility and cost-effectiveness of a follow-up model for patients with atrophic chronic gastritis and intestinal metaplasia based on gastric mucosal status using magnification chromoendoscopy and pepsinogen.

A cohort of patients with lesions as severe as atrophic chronic gastritis were followed-up according to a standardized protocol using magnification chromoendoscopy with methylene blue and measurement of serum pepsinogen I and II levels. A single node decision tree and Markov chain modeling were used to define cost-effectiveness of this follow-up model versus its absence. Transition rates were considered time-independent and calculated using primary data following cohort data analysis. Costs, quality of life and survival were estimated based on published data and extensive sensitivity analysis was performed.

A total of 100 patients were successfully followed-up over 3 years. Seven cases of dysplasia were diagnosed during follow-up, all among patients with incomplete intestinal metaplasia at baseline, six of whom had extensive (pepsinogen I to II ratio <3) incomplete intestinal metaplasia. For those individuals with atrophic chronic gastritis or complete intestinal metaplasia, a yearly measurement of pepsinogen levels or an endoscopic examination on a 3-yearly basis would cost 455 euros per quality-adjusted life year (QALY) gain. Endoscopic examination and pepsinogen serum level measurement on a yearly basis would cost 1868 euros per QALY for patients with extensive intestinal metaplasia.

The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia is both feasible and cost-effective if improved accurate endoscopic examination of gastric mucosa together with non-invasive assessment of gastric mucosal status are used to identify individuals at high-risk for development of gastric cancer.

Since the discovery of Campylobacter-like organisms Helicobacter pylori (H pylori) more than two decades ago the possibility of a relationship with gastric cancer has been postulated, tested and supposedly proven. There have been numerous human studies of various designs from many countries around the world. Several meta-analyses have been published and more recently a small number of experimental animal studies were reported looking at the association between H pylori infection and gastric cancer. Over the years, the human epidemiological studies have produced conflicting results; the meta-analyses have as one would expect produced similar pooled estimates; while the early experimental animal studies require replication. The exact mechanisms by which H pylori might cause gastric cancer are still under investigation and remain to be elucidated.

Gastric atrophy induced by Helicobacter pylori is thought to predispose patients to noncardiac gastric cancer development. However, the host genetic factors that influence the progression of gastric atrophy have not been elucidated. In this study, we examined the effects of cytokine polymorphisms on H. pylori-induced gastric atrophy.

Blood samples were taken from 454 Japanese subjects. The interleukin-2 (IL-2; T-330G), IL-4 (C-33T), and IL-13 (C-1111T) polymorphisms were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Anti-H. pylori IgG antibody and pepsinogen I and II were measured to diagnose H. pylori infection and atrophic gastritis.

The odds ratios (ORs) for the association between IL-2 polymorphism [OR = 2.78, 95% CI (confidence interval) = 1.26-6.17 (T/T to G/G)] or IL-4 polymorphism [OR = 2.22, 95% CI = 1.01-4.89 (T/C to C/C)] were increased significantly with gastric atrophy, whereas the corresponding OR of IL-13 polymorphism was decreased with gastric atrophy [OR = 0.61, 95% CI = 0.39-0.96 (C/T and T/T to C/C)]. There were no significant H. pylori seropositivity-related differences between these polymorphisms. We examined the relationship between these polymorphisms and gastric atrophy separately in H. pylori-seropositive and -seronegative groups. In the H. pylori-seropositive group, the IL-2 T/T (OR = 2.78, 95% CI = 1.12-6.93) had a significant association with gastric atrophy.

These results reveal that the IL-2 gene polymorphism is associated with an increased risk of gastric atrophy induced by H. pylori infection and might predispose to gastric cancer.

A cohort of individuals (n = 136) with lesions as severe as atrophic chronic gastritis (ACG) was cross-sectionally evaluated for the validity assessment of pepsinogen I (PGI) and pepsinogen II (PGII) serum levels for the diagnosis of intestinal metaplasia (IM) and gastric dysplasia. PGI/PGII ratio [median (range)] was 4 (0.5-7.5) in patients with ACG (n = 35); 4.6 (1.9-6.8) in type I IM (n = 18); 4.2 (1.4-5.9) in type II or type III IM limited to the antrum and incisura (n = 20); 2.4 (0.4-5.6) in extensive incomplete IM (n = 38); and 1.3 (0.4-6.4) in low-grade dysplasia (n = 23) (P = .002). Using histopathologic data as a reference test, the area under the receiver operating characteristic curves (CI 95%) was 0.73 (0.64-0.82) for extensive IM, 0.72 (0.58-0.85) for the diagnosis of dysplasia, and 0.81 (0.66-0.95) for the diagnosis of high-grade dysplasia. Using a PGI/PGII ratio of < or =3 as the cutoff for dysplasia diagnosis, the sensitivity was 70% (62-78%), the specificity was 65% (57-73%), and the negative predictive value estimates were over 90%. No differences in PG levels according to age or gender were observed. Helicobacter pylori did not significantly influence validity measurement estimates. PGI/PGII serum level ratio can be used even in the management of patients with a high a priori probability for a positive test. It may be useful for the exclusion of more advanced lesions (extensive IM and neoplastic lesions).

Incomplete intestinal metaplasia (IM) is a precursor of stomach cancer. To identify risk factors of incomplete IM, a 2-stage survey was carried out in 1995 among 1,485 residents in Matzu, an area with highest mortality from stomach cancer in Taiwan. There were 312 study subjects including 174 men and 138 women sampled for the gastroendoscopic examination of IM. Information on personal and familial history of stomach cancer, cigarette smoking, alcohol consumption and intake frequency of various salted food items were obtained by personal interview based on a structured questionnaire. Blood samples were collected from each participant. Four biopsies per subject were taken from all subjects at gastroendoscopic examination to diagnose the status of IM pathologically. The Helicobacter pylori in biopsies was detected by the histomorphological or immunochemistry method, and antibodies against H. pylori in serum by the enzyme-linked immunosorbent assay. Plasma level of selenium was determined by atomic absorption spectrometry, plasma level of retinol, alpha-tocopherol, alpha-carotene, and beta-carotene by high performance liquid chromatography, genotypes of glutathione S-transferase (GST) M1 and T1 and cytochrome P450 (CYP) 2E1 by polymerase chain reaction. The significant association between history of stomach cancer among first-degree relatives and incomplete IM was found (odds ratio [OR] = 2.50; 95% confidence interval [CI] = 1.15-5.43). There was no association between H. pylori infection and incomplete IM. Alcohol drinkers for >20 years had an elevated risk compared to non-drinkers (OR = 3.34; 95% CI = 1.19-9.39). No associations between incomplete IM and plasma levels of selenium, retinol, alpha-tocopherol, alpha-carotene and beta-carotene were found. Salted food including salted meat, dehydrated salted vegetables and raw salted seafood consumed at ages of </=15 and 16-30 years old was associated with an increased IM risk with OR ranging from 2-3. More striking associations between incomplete IM and salted food intake were observed among subjects with genotypes of GSTM1 null, GSTT1 non-null and CYP2E1 c1/c1. Our study suggests the importance of gene-environment interaction on the development of incomplete IM.

Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the PAI. We examined whether the prevalence of somatic p53 mutation in gastric adenocarcinoma differed between subjects with and without infection with CagA(+) (a marker for the PAI) H. pylori strains. DNA from 105 microdissected tumor specimens was analyzed for mutation in exons 5-8 of the p53 gene by polymerase chain reaction-based single-strand conformation polymorphism followed by direct DNA sequencing. Enzyme-linked immunosorbent assays for IgG antibodies against H. pylori and CagA were performed on sera collected 2-31 years prior to cancer diagnosis. Tumors from CagA(+) subjects were significantly more likely to have p53 mutations than tumors from CagA(-) subjects (including H. pylori- and H. pylori(+)/CagA(-)): odds ratio = 3.72; 95% confidence interval, 1.06-13.07 after adjustment for histologic type and anatomic subsite of tumor and age at diagnosis and sex of subjects. Mutations were predominantly insertions and deletions (43%) as well as transition mutations at CpG dinucleotides (33%). The data suggest that CagA(+) H. pylori infection, when compared with CagA(-) infection or the absence of H. pylori infection, is associated with a higher prevalence of p53 mutation in gastric adenocarcinoma.

genotypes of Helicobacter pylori are the focus of interest because they play a prominent role in mucosal injury. The purpose of this study was to determine cagA and vacA genotypes of H. pylori using real-time polymerase chain reaction (PCR) method with a double strain DNA binding SYBR Green I.dye, and to compare this with those of two immunohistochemical methods.

forty-three paraffin-embedded biopsy tissue samples were examined by histology, epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) immunohistochemistry and melting curve analysis of real-time PCR.

the presence of cagA gene was associated with a significantly higher frequency of gastritis (P=0.003) than that of vacA gene with intestinal metaplasia (P=0.045). Significant difference was found between the presence of cagA gene and EGFR expression in intestinal metaplasia cases in comparison with cagA negative samples (P=0.0418). Statistically significant difference was detected between increased cell proliferation and the presence of gastritis.

this method seems to be suitable for H. pylori genotype determination. Sensitivity, speed and simplicity are key areas in the development of PCR assays for H. pylori. Results supported the notion that infection with cagA positive H. pylori strain causes more augmentated cell proliferation in the stomach mucosa.

There are three main types of blood test available for the management of Helicobacter pylori infection: those that detect an antibody response; tests of the pathophysiological state of the stomach; and those that indicate an active infection. Enzyme linked immunosorbent assay (ELISA) based kits are the most numerous of the commercially available tests. Originally the kits used crude antigen preparations but many of the newer kits use a more purified antigen preparation giving increased specificity but a lower sensitivity. The sensitivity, specificity, and predictive values of the tests can also be affected by the population under test and coexistent disease in the patients. Near patient test kits are based on either latex agglutination or immunochromatography. Generally, they have low sensitivities compared with laboratory tests. Commercial western blotting kits have also been developed and are used to detect the presence of specific virulence markers. The exact role of serology in the management of Helicobacter infection has still to be defined, although there is evidence that, used as a screening procedure, it can reduce endoscopy cost and workload. Gastrin and pepsinogen blood concentrations may provide valuable information on the pathophysiological state of the stomach--for example, the presence of inflammation or gastric atrophy. A combination of serology and serum concentrations of gastrin and pepsinogen may be used effectively to detect serious gastroduodenal disease in patients.