Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Multiplex serology of Helicobacter pylori antigens in detection of current infection and atrophic gastritis - A simple and cost-efficient method.

INTRODUCTION: Helicobacter pylori express a large array of antigens, each of which is duly responsible for successful colonization and pathogenesis. Here, we have studied host serum antibody responses to four of its immunodominant antigens in association with the infection status and the resulting clinical outcomes. METHODS: For this purpose, four individual H. pylori proteins (UreB, CagA, Tip-α and HP0175) were produced in recombinant forms. Serum antibody responses of 246 (75 GC and 171 NUD) patients, against the above antigens, were evaluated by multiplex immunoblotting. The associations between the resulting data and the infection status, as well as clinical outcomes were evaluated using logistic regression models. RESULTS: Serum antibodies to all four recombinant antigens increased the chances of detecting screening ELISA-positive subjects, in an escalating dose-dependent manner, ranging from 2.6 (1.5-4.7) for HP0175 to 14.3 for UreB (4.3-50.7), exhibiting the lowest and highest odds ratios, respectively (PAdj ≤ 0.001), such that 98.2% of the subjects with antibodies to all four antigens, were also positive by the screening ELISA (P < 0.0001). Among the screening ELISA-positive subjects, the three antigens of CagA, Tip-α, and HP0175 were able to segregate current from past H. pylori infection (P < 0.05). Accordingly, subjects with antibodies to one or more antigen(s) were at 5.4 (95% CI: 1.8-16.4) folds increased chances of having current infection, as compared to triple negatives (PAdj = 0.003). In reference to the clinical outcomes, those with serum antibodies to CagA were more prevalent among gastric cancer, as compared to NUD patients (ORAdj: 5.4, 95% CI: 2.4-12.2, PAdj < 0.0001). When NUD patients were categorized according to their histopathologic status, multiple antigen analysis revealed that subjects with serum antibodies to one or more of the 3 current infection-positive antigens (CagA, Tip-α, and HP0175) were at 9.7 (95% CI: 2.1-44.9, P = 0.004) folds increased risk of atrophic gastritis, in reference to triple negatives. CONCLUSION: The non-invasive multiplex serology assay, presented here, was able to not only detect subjects with current H. pylori infection, it could also screen dyspeptic patients for the presence of gastric atrophy. This simple and cost-efficient method can supplement routine screening ELISAs, to increase the chances of detecting current infections as well as atrophic gastritis.

Narrow band imaging and serology in the assessment of premalignant gastric pathology.

BACKGROUND: Patient outcomes in gastric adenocarcinoma are poor due to late diagnosis. Detecting and treating at the premalignant stage has the potential to improve this. Helicobacter pylori is also a strong risk factor for this disease. AIMS: Primary aims were to assess the diagnostic accuracy of magnified narrow band imaging (NBI-Z) endoscopy and serology in detecting normal mucosa, H. pylori gastritis and gastric atrophy. Secondary aims were to compare the diagnostic accuracies of two classification systems using both NBI-Z and white light endoscopy with magnification (WLE-Z) and evaluate the inter-observer agreement. METHODS: Patients were prospectively recruited. Images of gastric mucosa were stored with histology and serum for IgG H. pylori and Pepsinogen (PG) I/II ELISAs. Blinded expert endoscopists agreed on mucosal pattern. Mucosal images and serological markers were compared with histology. Kappa statistics determined inter-observer variability for randomly allocated images among four experts and four non-experts. RESULTS: 116 patients were prospectively recruited. Diagnostic accuracy of NBI-Z for determining normal gastric mucosa was 0.87(95%CI 0.82-0.92), H. pylori gastritis 0.65(95%CI 0.55-0.75) and gastric atrophy 0.88(95%CI 0.81-0.94). NBI-Z was superior to serology at detecting gastric atrophy: NBI-Z gastric atrophy 0.88(95%CI 0.81-0.94) vs PGI/II ratio < 3 0.74(95%CI 0.62-0.85) p<.0001. Overall NBI-Z was superior to WLE-Z in detecting disease using two validated classifications. Inter-observer agreement was 0.63(95%CI 0.51-0.73). CONCLUSIONS: NBI-Z accurately detects changes in the GI mucosa which currently depend on histology. NBI-Z is useful in the detection of precancerous conditions, potentially improving patient outcomes with early intervention to prevent gastric cancer.

The potential value of serum pepsinogen for the diagnosis of atrophic gastritis among the health check-up populations in China: a diagnostic clinical research.

BACKGROUND: The aim of this study is to assess the validity of the measurement of pepsinogen as a screening test for chronic atrophic gastritis (AG) in health check-up populations in China. METHODS: Patients from consecutive regular health check-up were enrolled from January 2014 to June 2015. Endoscopy, combined with monitoring the Helicobacter pylori (Hp) infections, and measuring the serum pepsinogen (PG) were used to determine the diagnostic accuracy of PG for the screening of atrophic gastritis. Histopathology was assessed by the Operative Link on Gastritis Assessment (OLGA) system. Statistical analysis was performed using SPSS statistical software. RESULTS: The total Hp infection rate was 40%. Based on pathology, the 996 participants were divided into three groups: non-atrophic (NAG), mild-moderate atrophic (MAG): stage I and II of the OLGA classification, and severe atrophic (SAG): stage III and IV of the OLGA classification. Compared with NAG and MAG groups, PGR decreased significantly in SAG group (p < 0.05). PGI and PGII levels were significantly elevated in Hp-positive group, while the PGR was markedly decreased (p < 0.01). When MAG and SAG groups were combined and compared with NAG group, the best cutoff value for atrophy diagnosis was PGI ≤50.3 ng/ml; the cutoff value in Hp-negative group was absolutely higher than in Hp-positive group. When NAG and MAG groups were combined and compared with the SAG group, the best cutoff value for diagnosis of severe atrophy was at PGR ≤4.28. The cutoff values in Hp-negative and Hp-positive groups were calculated at PGR ≤6.28 and ≤4.28, respectively. CONCLUSIONS: Pepsinogens play an important role in the identification of patients with atrophic gastritis and severe AG. Use of different cutoff values of PG for Hp-negative and Hp-positive groups may offer greater efficacy in the diagnosis of AG.

Operative link on gastritis assessment stage is an appropriate predictor of early gastric cancer.

AIM: To assess the predictive value of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages in gastric cancer. METHODS: A prospective study was conducted with 71 patients with early gastric cancer (EGC) and 156 patients with non-EGC. All patients underwent endoscopic examination and systematic biopsy. Outcome measures were assessed and compared, including the Japanese endoscopic gastric atrophy (EGA) classification method and the modified OLGA method as well as the modified OLGIM method. Helicobacter pylori (H. pylori) status was determined for all study participants. Stepwise logistic regression modeling was performed to analyze correlations between EGC and the EGA, OLGA and OLGIM methods. RESULTS: For patients with EGC and patients with non-EGC, the proportions of moderate-to-severe EGA cases were 64.8% and 44.9%, respectively (P = 0.005), the proportions of OLGA stages III-IV cases were 52.1% and 22.4%, respectively (P < 0.001), and the proportions of OLGIM stages III-IV cases were 42.3% and 19.9%, respectively (P < 0.001). OLGA stage and OLGIM stage were significantly related to EGA classification; specifically, logistic regression modeling showed significant correlations between EGC and moderate-to-severe EGA (OR = 1.95, 95% CI: 1.06-3.58, P = 0.031) and OLGA stages III-IV (OR = 3.14, 95%CI: 1.71-5.81, P < 0.001), but no significant correlation between EGC and OLGIM stages III-IV (P = 0.781). H. pylori infection rate was significantly higher in patients with moderate-to-severe EGA (75.0% vs 54.1%, P = 0.001) or OLGA/OLGIM stages III-IV (OLGA: 83.6% vs 55.8%, P < 0.001; OLGIM: 83.6% vs 57.8%, P < 0.001). CONCLUSION: OLGA classification is optimal for EGC screening. A surveillance program including OLGA stage and H. pylori infection status may facilitate early detection of gastric cancer.

[Serological assessment of Helicobacter pylori-specific antibodies and their association with gastric lesions in a high-risk population].

OBJECTIVE: To determine the distributions of six Helicobacter pylori (Hp)-specific antibodies in a high-risk population of gastric cancer (GC) and explore the relationship between Hp virulence factors and precancerous gastric lesions. METHODS: Based on the two intervention trials conducted in Linqu County, the seropositivities for CagA, VacA, GroEL, UreA, HcpC and GGT were assessed by recombinant immunoassay (recomLine) in 623 participants with H. pylori infection determined by (13)C-urea breath test ((13)C-UBT) and/or enzyme linked immunosorbent assay (ELISA). RESULTS: In a total of 623 participants were detected by recomLine analysis, of which 594 were Hp-positive. The seropositivities rates of CagA, VacA, GroEL, UreA, HcpC and GGT were 84.0%, 38.2%, 66.7%, 17.7%, 58.8% and 42.8%, respectively. A total of 523 participants were determined as type I infection of Hp, accounting for 88.1%. Compared with superficial gastritis (SG), the infection rate of Hp type I was higher in the chronic atrophic gastritis (CAG) (P = 0.001). CONCLUSIONS: The results of this population-based study suggest that the virulence factors of Hp may be related to the development of GC in a Chinese high-risk population. The recomLine analysis may serve as a tool for identification of Hp strains and prediction of high-risk population of GC.

Operative Link for Gastritis Assessment gastritis staging incorporates intestinal metaplasia subtyping.

Both sulfomucin-type intestinal metaplasia (ie, types II and III intestinal metaplasia, colonic-type intestinal metaplasia) and gastritis in Operative Link for Gastritis Assessment stages III and IV are associated with an increased risk of intestinal-type gastric cancer. This study aimed to verify the hypothesis that gastritis in Operative Link for Gastritis Assessment stages III and IV (both consistently associated with an increased cancer risk) is associated per se with types II and III intestinal metaplasia. Two hundred consecutive cases of atrophic gastritis (Operative Link for Gastritis Assessment stages I, II, III, and IV) were considered (50 cases for each stage). All cases were stained with high iron diamine, and intestinal metaplasia was subtyped accordingly (type I [ie, small-intestinal type] and types II and III). Helicobacter pylori status was also considered, distinguishing H pylori-positive versus H pylori-negative versus H pylori-eradicated patients. A significant association was found between intestinal metaplasia subtype and the Operative Link for Gastritis Assessment stage of gastritis (the higher the stage, the more the colonic-type of intestinal metaplasia, and vice versa; Wilcoxon, P = .001). The strength of the association between Operative Link for Gastritis Assessment stages and the 3 intestinal metaplasia subtypes was confirmed by logistic regression analysis (P < .001; odds ratio, 4.84; 95% confidence interval, 2.97-7.88). Intestinal metaplasia subtyping also correlated with the patient's age (Kruskal-Wallis, P = .001) and H pylori status (Fisher exact, P < .001). Operative Link for Gastritis Assessment staging incorporates the prognostic message obtainable from histochemical gastric mucin subtyping.

Gastric plasma biomarkers and Operative Link for Gastritis Assessment gastritis stage.

INTRODUCTION: The Operative Link for Gastritis Assessment (OLGA) staging system has been proposed as a histopathological reporting system of gastric atrophy. Noninvasive methods for indirect evaluation of gastric mucosal atrophy by biomarkers are also being introduced. OBJECTIVES: To analyze gastric mucosal atrophy by biomarkers, pepsinogen I (PgI), pepsinogen II (PgII), PgI/PgII ratio, fasting gastrin-17 (G-17), stimulated gastrin-17 (sG-17), in relation to OLGA gastritis stage. PATIENTS AND METHODS: Gastric biopsies were taken from 269 prospective patients referred for upper endoscopy because of dyspeptic problems and evaluated by two expert pathologists (D.J. and P.S.). Atrophy was assessed according to the OLGA staging system. Pg I, PgII, Pg I/II, G-17, sG-17 were determined in a plasma sample. RESULTS: The mean levels of PgI and PgI/PgII decreased significantly from 90.8 µg/l and 7.6 in stage 0 gastritis to 64.3 µg/l and 4.3 in high-stage gastritis. The mean values of G-17 and sG-17 were significantly higher among patients with stage II gastritis compared with stage 0 and high-stage gastritis.The proportion of patients with normal mucosa and nonatrophic gastritis according to biomarkers decreased from 78% in stage 0 to 22% in high-stage (III-IV) gastritis. Among the latter no case with normal mucosa, according to biomarkers, was observed. CONCLUSIONS: A significant inverse correlation between the mean levels of PgI, PgI/II ratio and the OLGA stage was observed. Percentage of dyspeptic patients with normal mucosa, by blood biomarkers, decreased with increasing OLGA gastritis stages. OLGA staging system provides a good frame for scientific analysis of gastric mucosal atrophy.

Eradication of gastric cancer and more efficient gastric cancer surveillance in Japan: two peas in a pod.

We provide a historical review and update on current thinking regarding the possibility of elimination of gastric cancer from Japan. Because Helicobacter pylori infection is the cause gastric cancer, its elimination forms the cornerstone of eradication of gastric cancer. However, simply eradicating H. pylori from the entire population will not immediately solve the problem because many patients with H. pylori infections have already developed the precursor lesion, atrophic gastritis. Cure of H. pylori in these high risk patients will only reduce the risk of subsequent cancer. In contrast, treatment of low risk patients will prevent cancer. Thus, to eliminate gastric cancer it is necessary to identify and treat all infected individuals. In addition, those at increased risk for gastric cancer (i.e., atrophic gastritis irrespective of age) should be considered for endoscopic surveillance to identify those cancers that develop at an early stage. We propose that severity and extent of atrophy be used to separate those expected to benefit from endoscopy and annual surveillance from those with little or no potential benefit. We suggest an algorithm for eradicating gastric cancer that incorporates H. pylori and atrophic gastritis testing, H. pylori therapy, and surveillance to institute a program of surveillance restricted to those who could benefit most (i.e., those with moderate or severe atrophy). This will also allow a much closer matching of surveillance capacity and surveillance need making surveillance more clinically- and cost-effective.

[The assessment of nitric oxide metabolites in gastric juice in Helicobacter pylori infected subjects in compliance with grade of inflammatory lesions in gastric mucosa]. / Ocena stezenia metabolitów tlenku azotu w soku zoladkowym u zakazonych Helicobacter pylori z uwzglednieniem stopnia zmian zapalnych w blonie sluzowej zoladka.

UNLABELLED: The infection of H. pylori causes inflammatory lesions in gastric mucosa--until atrophic gastritis, intestinal metaplasia, dysplasia (precancerous states) and finally to gastric cancer or lymphoma. The mechanism of mentioned disturbances is complicated, no doubt that nitric oxide plays here very important role. It is proved, that H. pylori causes essential oxygen metabolism disturbances by activation of inflammatory infiltration's cells to oxide reactive forms as nitric oxide formation. Nitric oxide as oxide radical could react with other free radicals and contribute to oxidative lesions of gastric mucosa and alterations of its structure. The aim of the study was try to answer the question: 1. Is this the relationship between NO metabolites concentrations in gastric juice and morphological state of gastric mucosa? 2. Does H. pylori eradication influence on NO metabolites concentrations in gastric juice? 3. Does H. pylori eradication influence on grade of inflammatory lesions in gastric mucosa? MATERIAL AND METHODS: The study included 75 subjects between of 21 to 60 years, infected with H. pylori with diagnosed (according to the Sydney system) different stages of chronic gastritis progression. The type of inflammation, activity, the presence of atrophy, intestinal metaplasia and H. pylori infection were assessed. The study group was divided into 3 subgroups: group I--25 subjects with chronic active gastritis, group II--25 subjects with chronic atrophic gastritis without intestinal metaplasia, group III--25 subjects with chronic atrophic gastritis with intestinal metaplasia. Control group comprised 20 healthy subjects, without H. pylori infection. In each patient during gastroscopy 5 biopsy specimens for histopathologic examination and for urea test and 3 ml gastric juice were collected. The concentration of nitric oxide metabolites in gastric juice was determined with spectrophotometric method, based on Griess reaction. H. pylori infection was detected using fast urea test (CLO--test), confirmed by histopathological examination (stained Giemsa method) and non-invasive urea breath test (UBT-13C). In H. pylori--infected patients the above mentioned investigations were performed three times -before, in 8 weeks and in 12 months after antibacterial treatment's finish. In antibacterial therapy we use 7-days three-drugs therapy (omeprasole, amoksycillin and clarythromycin). RESULTS: The concentration of nitric oxide metabolites in gastric juice in healthy subjects was 6.81 +/- 2.23 micromol. In patients with chronic gastritis, H. pylori infected was significantly higher--in patients with chronic active gastritis was 9.29 +/- 2.19 micromol/l, in patients with chronic atrophic gastritis--10.25 +/- 2.31 micromol/l (p < 0.01), in patients with intestinal metaplasia--11.89 +/- 2.46 micromol/l (p < 0.01). 8 weeks after antibacterial treatment's finish the concentration of nitric oxide metabolites in gastric juice in each group decreased and were: in patients with chronic active gastritis was 8.18 +/- 1.63 micromol/l, in patients with chronic atrophic gastritis--10.02 +/- 2.28 micromol/l, in patients with intestinal metaplasia--10.83 +/- 2.32 micromol/l. The differences were not statistically significant. 12 months after antibacterial treatment's finish the concentration of nitric oxide metabolites in gastric juice in each group decreased and were: in patients with chronic active gastritis was 6.90 +/- 1.43 micromol/l, in patients with chronic atrophic gastritis--7.22 +/- 2.01 micromol/l, in patients with intestinal metaplasia--7.56 +/- 1.98 micromol/l. The differences were statistically significant--p < 0.05, p < 0.01. 8 weeks after antibacterial treatment's finish in each patient also the gastroscopy was performed and another biopsy specimen for histopathologic examination were collected. Only in group I in microscopic image the decreased of inflammation intensity was find (both in antrum and in corpus)--however the differences were not statistically significant. In the other groups the alterations in gastric mucosa do not improve significantly. The gastroscopy was performed again in 12 months after antibacterial treatment's finish. In group I the significant decrease or regression of inflammatory infiltration (in corpus and in antrum) was found. Also in group II the significant decrease of the grade of atrophy and similarly in III group the improvement of histopathological state were observed. CONCLUSIONS: 1. The increase of NO metabolites concentration demonstrates positive correlation with grade of inflammatory lesions in gastric mucosa. 2. The effective antibacterial therapy causes the decrease of NO metabolites concentration in gastric juice, especially in patients with chronic active gastritis. 3. Eradication influence on decrease of grade of lesions' progression in gastric mucosa just in 12 months after effective antibacterial therapy.

Assessment of atrophic gastritis using the OLGA system.

BACKGROUND: An international group of gastroenterologists and pathologists (Operative Link for Gastritis Assessment (OLGA)) proposed the staging system of atrophy. The aim of this study was to assess the severity of atrophic gastritis using the OLGA system. MATERIALS AND METHODS: The subjects comprised 163 H. pylori-positive patients: 18 with early gastric cancers of the intestinal type (GC), 55 with atrophic gastritis (AG), 49 with gastric ulcers or scars (GU), and 41 with duodenal ulcers or scars (DU). Biopsies were taken from the lesser and greater curvatures of the antrum and middle body. The OLGA gastritis stage (0-IV) (the severity and topography of atrophy) was obtained by combining antral with body atrophy scores. The gastritis grade (the severity and topography of inflammation) was obtained by combining antral and body inflammation scores. RESULTS: Most (84%) of patients with GC showed stage III or IV. Gastritis stages were significantly higher in patients with GC than in those with AG, GU, and DU. Gastritis stage became higher with age. Gastritis grades were slightly higher in patients with AG than in others. CONCLUSIONS: Our results indicate that higher stages are found in patients with GC using the OLGA staging system and that the high risk of GC can be recognized. It is simple to use and useful for the assessment of the severity of atrophic gastritis.

Rapid quantitative assessment of gastric corpus atrophy in tissue sections.

BACKGROUND/AIMS: Grading of Helicobacter pylori induced atrophic gastritis using the updated Sydney system is severely limited by high interobserver variability. The aim of this study was to set up a quantitative test of gastric corpus mucosal atrophy in tissue sections and test its reproducibility and correlation with the Sydney scores of atrophy. METHOD: Mucosal atrophy was assessed in 124 haematoxylin and eosin stained corpus biopsy specimens by two experienced gastrointestinal pathologists (EB, JL) according to the updated Sydney system as none (n = 33), mild (n = 33), moderate (n = 33), or pronounced (n = 25). In each specimen, the proportions of glands, stroma, infiltrate, and intestinal metaplasia in the glandular zone were measured as volume percentages using a point counting method. The optimal point sample size, intra-observer and interobserver reproducibility, discriminative power for degrees of atrophy, and correlations with H pylori status were evaluated. RESULTS: Counting 400 points in 200 fields of vision provided the smallest sample size that still had excellent intra-observer and interobserver reproducibility (r > or = 0.96). Overall, the volume percentage of glands (VPGL), infiltrate (VPI), and stroma (VPS) correlated well with the Sydney scores for atrophy (p < or = 0.003). However, no differences were found between non-atrophic mucosa and mild atrophy. No correlation was found between age and either the Sydney grade of atrophy or the VPGL or VPS. In non-atrophic mucosa and mild atrophy, H pylori positive cases showed a significantly higher VPI than did H pylori negative cases. A lower VPGL was seen in H pylori positive cases than in H pylori negative cases in the mild atrophy group. VPS did not correlate with H pylori status within each grade of atrophy. CONCLUSION: Point counting is a powerful and reproducible tool for the quantitative analysis of mucosal corpus atrophy in tissue sections. These data favour the combination of "none" and "mild" atrophy into one category, resulting in a three class grading system for corpus atrophy, when using the updated Sydney system.