Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance.

INTRODUCTION: Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. METHODS: This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1-6 years. Patients were defined 'low risk' if they fulfilled requirements for discharge, and 'high risk' if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined 'low risk' with progression of disease during follow-up (FU) were considered 'misclassified' as low risk. RESULTS: 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were 'misclassified', showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were 'misclassified'. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were 'misclassified'. Seven patients developed gastric cancer (GC) or dysplasia, four patients were 'misclassified' based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4-83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. CONCLUSION: One-third of patients that would have been discharged from GC surveillance, appeared to be 'misclassified' as low risk. One additional endoscopy will reduce this risk by 70%.

Helicobacter pylori seroprevalence in six different ethnic groups living in Amsterdam: The HELIUS study.

BACKGROUND: Helicobacter pylori prevalence varies greatly worldwide. We explored the prevalence of H. pylori and CagA seropositivity among adults aged 18-44 years living in the Netherlands by ethnicity and migration status (first vs second generation). MATERIALS AND METHODS: Participants from six different ethnic groups were selected from the population-based multi-ethnic HELIUS study in Amsterdam, the Netherlands. Serum samples were tested for H. pylori antigens using a validated Luminex-based multiplex serology assay. Prevalence ratios were estimated using Poisson regression analysis. RESULTS: A total of 4683 participants aged 18-44 years were randomly selected based on sex, ethnicity, and age. H. pylori seroprevalence was highest in the Ghanaian group (84%), followed by Moroccan (81%), Turkish (66%), African Surinamese (51%), South-Asian Surinamese (48%), and Dutch (17%) participants. All ethnic minority groups had a significantly higher risk of being H. pylori seropositive compared to the Dutch group. This association was strongest among participants born outside the Netherlands (first generation), but was still significant and apparent among second-generation participants. Among first-generation participants, all groups, except the Moroccans, had a significantly higher proportion of individuals with a cagA + H. pylori strain compared to the Dutch participants. CONCLUSION: Helicobacter pylori seroprevalence among first-generation migrants is high in the Netherlands and remains elevated among second-generation migrants (ie, those born in the Netherlands). High exposure to H. pylori, and especially to the more virulent cagA+ strain, highlights the need for tailored prevention of gastric diseases (notably peptic ulcers and cancers) among migrants.

Surveillance of premalignant gastric lesions: a multicentre prospective cohort study from low incidence regions.

OBJECTIVE: International guidelines recommend endoscopic surveillance of premalignant gastric lesions. However, the diagnostic yield and preventive effect require further study. We therefore aimed to assess the incidence of neoplastic progression and to assess the ability of various tests to identify patients most at risk for progression. DESIGN: Patients from the Netherlands and Norway with a previous diagnosis of atrophic gastritis (AG), intestinal metaplasia (IM) or dysplasia were offered endoscopic surveillance. All histological specimens were assessed according to the updated Sydney classification and the operative link on gastric intestinal metaplasia (OLGIM) system. In addition, we measured serum pepsinogens (PG) and gastrin-17. RESULTS: 279 (mean age 57.9 years, SD 11.4, male/female 137/142) patients were included and underwent at least one surveillance endoscopy during follow-up. The mean follow-up time was 57 months (SD 36). Four subjects (1.4%) were diagnosed with high-grade adenoma/dysplasia or invasive neoplasia (ie, gastric cancer) during follow-up. Two of these patients were successfully treated with endoscopic submucosal dissection, while the other two underwent a total gastrectomy. Compared with patients with extended AG/IM (PGI/II≤3 and/or OGLIM stage III-IV), patients with limited AG/IM (PG I/II>3 and OLGIM stage 0-II) did not develop high-grade adenoma/dysplasia or invasive neoplasia during follow-up (p=0.02). CONCLUSION: In a low gastric cancer incidence area, a surveillance programme can detect gastric cancer at an early curable stage with an overall risk of neoplastic progression of 0.3% per year. Use of serological markers in endoscopic surveillance programmes may improve risk stratification.

Helicobacter pylori infection: a predictor of vomiting severity in pregnancy and adverse birth outcome.

BACKGROUND: Nausea and occasional vomiting in early pregnancy is common. Why some women experience severe nausea and occasional vomiting in early pregnancy is unknown. Causes are multifactorial and only symptomatic treatment options are available, although adverse birth outcomes have been described. Helicobacter pylori infection has been implicated in the cause of nausea and occasional vomiting in early pregnancy. OBJECTIVE: The purpose of this study was to investigate the association of H pylori with vomiting severity in pregnancy and its effect on birth outcome. STUDY DESIGN: We assembled a population-based prospective cohort of pregnant women in The Netherlands. Enrolment took place between 2002 and 2006. H pylori serology was determined in mid gestation. Women reported whether they experienced vomiting in early, mid, and late gestation. Maternal weight was measured in the same time periods. Birth outcomes were obtained from medical records. Main outcome measures were vomiting frequency (no, occasional, daily) and duration (early, mid, late gestation), maternal weight gain, birthweight, small for gestational age, and prematurity. Data were analyzed with the use of multivariate regression. RESULTS: We included 5549 Women, of whom 1932 (34.8%) reported occasional vomiting and 601 (10.8%) reported daily vomiting. Women who were H pylori-positive (n=2363) were more likely to report daily vomiting (adjusted odds ratio, 1.44; 95% confidence interval, 1.16-1.78). H pylori-positivity was associated with a reduction of total weight gain in women with daily vomiting (adjusted difference, -2.1 kg; 95% confidence interval, -2.7 to -1.5); infants born to women with H pylori and daily vomiting had slightly reduced birthweight (addjusted difference -60g; 95% confidence interval, -109 - -12) and an increased risk of being small for gestational age (adjusted odds ratio, 1.49; 95% confidence interval, 1.04-2.14). H pylori and daily vomiting did not significantly affect prematurity rate. CONCLUSION: This study suggests that H pylori is an independent risk factor for vomiting in pregnancy. In women with daily vomiting, H pylori is also associated with low maternal weight gain, reduced birth weight, and small for gestational age. Because effective treatments for severe nausea and occasional vomiting in early pregnancy are currently lacking, the effect of H pylori eradication therapy on nausea and occasional vomiting in early pregnancy symptom severity should be the target of future studies.

Helicobacter pylori colonization and pregnancies complicated by preeclampsia, spontaneous prematurity, and small for gestational age birth.

BACKGROUND: Preeclampsia (PE), small for gestational age (SGA), and spontaneous preterm birth (PTB) each may be complications of impaired placental function in pregnancy. Although their exact pathogenesis is still unknown, certain infectious agents seem to play a role. Helicobacter pylori (H. pylori) colonization has been associated with increased risk for PE. Our aim was to assess the association between H. pylori colonization and PE, SGA, and PTB. MATERIAL AND METHODS: We measured IgG anti-H. pylori and CagA antibodies in serum of pregnant women (median 20.5 weeks, range 16.5-29.4) who participated in a population-based prospective cohort study. Delivery and medical records were assessed. Information on demographics, education, and maternal risk factors was collected by questionnaire. We used multivariate logistic regression analyses to assess associations between H. pylori colonization and PE, SGA, and PTB. RESULTS: In total, 6348 pregnant women were assessed. H. pylori positivity was found in 2915 (46%) women, of whom 1023 (35%) also were CagA-positive. Pregnancy was complicated by PE, SGA, or PTB in 927 (15%) women. H. pylori colonization was associated with PE (aOR 1.51; 95%CI 1.03-2.25). Differentiation according to CagA status revealed the same risk. H. pylori was positively related with SGA, mainly explained by CagA-positive strains (aOR 1.34; 1.04-1.71). No association was observed between H. pylori and PTB. CONCLUSIONS: Our data suggest that H. pylori colonization may be a risk factor for PE and SGA. If these associations are confirmed by future studies and shown to be causal, H. pylori eradication may reduce related perinatal morbidity and mortality.

Intergenerational reduction in Helicobacter pylori prevalence is similar between different ethnic groups living in a Western city.

OBJECTIVE: Helicobacter pylori colonisation rates in childhood have declined in Western populations, but it is unknown whether this trend is similar in children of non-Western ethnic backgrounds, born in a Western country. We aimed to identify H. pylori status in children, and determine mother-to-child transmission and risk factors for colonisation. DESIGN: Antibodies against H. pylori and cytotoxin-associated gene A (CagA) were measured in children participating in a population-based prospective cohort study in Rotterdam, the Netherlands. Information on demographics and characteristics was collected using questionnaires. RESULTS: We analysed the serum of 4467 children (mean age 6.2 years±0.4 SD) and compared the results with the H. pylori status of their mothers (available for 3185 children). Overall, 438 (10%) children were H. pylori-positive, of whom 142 (32%) were CagA-positive. Independent risk factors for colonisation were: maternal H. pylori positivity (OR 2.12; 95% CI 1.62 to 2.77), non-Dutch ethnicity (OR 2.05; 95% CI 1.54 to 2.73), female gender (OR 1.47; 95% CI 1.20 to 1.80) and lower maternal education level (OR 1.38; 95% CI 1.06 to 1.79). Comparing mothers and children, we found an intergenerational decrease of 76% and 77% for Hp(+)CagA(-) and Hp(+)CagA(+)-strains, respectively, consistent across all nine ethnic groups studied. Male gender, higher maternal educational level and no older siblings, were independently associated with absence of H. pylori. CONCLUSIONS: Although the highest H. pylori and CagA prevalence was found in children of non-Dutch ethnicities, the decreased colonisation rates were uniform across all ethnic groups, implying the importance of environmental factors in H. pylori transmission in modern cities, independent of ethnicity.

Genes expressed in blood link osteoarthritis with apoptotic pathways.

OBJECTIVE: To identify novel gene expression networks in blood of osteoarthritis patients compared to controls. METHODS: A comprehensive exploration of gene expression in peripheral blood was performed by microarray analysis for a subset of osteoarthritis patients from the Genetics osteoARthritis and Progression (GARP) study in comparison with sex and age-matched healthy controls. To identify pathways, we performed gene enrichment analyses (database for annotation, visualisation and integrated discovery and search tool for the retrieval of interacting genes). Quantitative PCR analysis in overlapping and in additional osteoarthritis samples was performed for prioritised genes to validate and replicate findings. Classification of cases and controls was explored by applying statistical models. RESULTS: 741 probes representing 694 unique genes were differentially expressed between cases and controls, including 86 genes expressed with at least a 1.5-fold difference. ATF4, GPR18 and H3F3B were among the top genes identified (p<4.5 × 10(-8)). We found that in the blood of osteoarthritis patients the apoptosis pathway, including the well-known gene CASP3, was significantly enriched among the differentially expressed genes. Our findings were validated in independent samples and when using a small subset of the validated genes, we could accurately distinguish patients from controls (area under the curve 98%). CONCLUSIONS: In the current study, we have identified specific gene expression networks, in the easily accessible tissue blood, which associated consistently with osteoarthritis among GARP study cases. Our data further hint at the relevance of apoptosis as an aetiological factor in osteoarthritis onset, thereby qualifying expression profiling of blood as a useful tool to understand the underlying molecular mechanisms of osteoarthritis.

Helicobacter pylori and nonmalignant diseases.

Declining Helicobacter pylori prevalence rates have resulted in a decrease of peptic ulcer bleeding incidence. Moreover, eradication reduces peptic ulcer recurrence rate. Newer studies confirm that H. pylori eradication lowers the risk of recurrent peptic ulcer bleeding. Guidelines therefore advocate a test-and-treat strategy for patients with a history of ulcer bleeding and NSAIDs and/or aspirin use. There is mounting evidence that H. pylori status has no effect on symptoms and treatment efficacy in patients with gastroesophageal reflux disease (GERD). Some studies observed an improvement of GERD complaints after H. pylori eradication, which underlines that H. pylori treatment is not contra-indicated in GERD patients. The exact role of H. pylori in functional dyspepsia (FD) remains controversial. However, there is growing consensus that H. pylori-positive FD should be assessed as a separate entity. In these patients, eradication can be beneficial and appropriate. Finally, several studies suggest that H. pylori infection may also be associated with beneficial effects for the host. Epidemiologic studies showed an inverse relation between H. pylori infection and asthma and allergy, although data are conflicting and need to be expanded.

Ethnicity is a strong predictor for Helicobacter pylori infection in young women in a multi-ethnic European city.

BACKGROUND AND AIM: At the same time that Helicobacter pylori prevalence is declining in Western countries, immigrants from developing countries with high H. pylori prevalence have settled in Western urban areas. Actual epidemiological data on H. pylori in a migrant community may help in realizing a more selective approach to assess H. pylori-related diseases. We aimed to define H. pylori prevalence as well as risk groups for H. pylori in a cohort of young women living in a multi-ethnic European city. METHODS: We measured Immunoglobulin G (IgG) anti-H. pylori and CagA-antibodies in serum of pregnant women included in a population-based prospective cohort study, the Generation R study. Information on demographics and socioeconomic status was collected by questionnaires. Chi-square and logistic regression were used. RESULTS: In total, 3146 (46%) of the 6837 tested women (mean age 29.7 ± 5.3) were H. pylori-positive and 1110 (35%) of them were CagA-positive. The H. pylori prevalence in Dutch women was 24%, which was significantly lower than in non-Dutch women (64%; P < 0.001). In particular, H. pylori positivity was found in 92% of Moroccan (odds ratio 19.2; 95% confidence interval 11.8-32.0), 80% of Cape Verdean (7.6; 5.0-11.5), 81% of Turkish (9.0; 6.7-12.1), 60% of Dutch Antillean (3.3; 2.3-4.7), and 58% of Surinamese women (3.0; 2.3-3.8). Among H. pylori-positive Dutch subjects, 19% were CagA-positive compared with 40% of the non-Dutch subjects (P < 0.001). CONCLUSIONS: Despite a general trend of declining prevalence in Western countries, H. pylori remains highly prevalent in migrant communities, which may constitute target groups for screening and eradication to prevent H. pylori-related diseases.

Helicobacter pylori colonization and obesity - a Mendelian randomization study.

Obesity is associated with substantial morbidity, costs, and decreased life expectancy, and continues to rise worldwide. While etiological understanding is needed for prevention, epidemiological studies indicated that colonization with Helicobacter pylori (H. pylori) may affect body mass index (BMI), but with inconsistent results. Here, we examine the relationship between H. pylori colonization and BMI/obesity. Cross-sectional analyses were performed in two independent population-based cohorts of elderly from the Netherlands and Germany (n = 13,044). Genetic risk scores were conducted based on genetic loci associated with either H. pylori colonization or BMI/obesity. We performed a bi-directional Mendelian randomization. Meta-analysis of cross-sectional data revealed no association between anti-H. pylori IgG titer and BMI, nor of H. pylori positivity and BMI. Anti-H. pylori IgG titer was negatively associated with obesity (OR 0.99972; 95% CI 0.99946-0.99997, p = 0.03) and with obesity classes (Beta -6.91 •10-5; 95% CI -1.38•10-4, -5.49•10-7, p = 0.048), but the magnitude of these effects was limited. Mendelian randomization showed no causal relation between H. pylori genetic risk score and BMI/obesity, nor between BMI or obesity genetic risk scores and H. pylori positivity. This study provides no evidence for a clinically relevant association between H. pylori and BMI/obesity.

Current pharmacotherapy options for gastritis.

INTRODUCTION: Gastritis is a broad term, which is used for different conditions by clinicians, endoscopists and pathologists. Classification strategies have led to more congruence between specialists. The histological evaluation of the gastric mucosa is mandatory for diagnosing and classifying gastritis. Main aetiologic factor is infection with Helicobacter pylori. The clinical importance of gastritis lays in the fact that it predisposes to more pronounced damage to the gastric mucosa, in particular peptic ulcer disease, and eventually atrophic gastritis, intestinal metaplasia and gastric malignancy, both adenocarcinoma and MALT lymphoma. AREAS COVERED: This review covers the current pharmacotherapy options for different forms of gastritis. The main focus is on H. pylori-induced gastritis. Thereafter, other forms of gastritis like autoimmune gastritis and non-steroidal anti-inflammatory drug (NSAID)-related gastropathy are covered. EXPERT OPINION: The emerging problem of antibiotic resistance requires an accurate knowledge of local eradication rates. Standard triple therapy should be abandoned in regions with high clarithromycin resistance. In these areas, sequential or quadruple therapy is best initial treatment. Further research should focus on non-invasive and effective techniques of susceptibility testing, making a tailored and cost-effective approach. Primary prevention of NSAID-related gastropathy can be enhanced by better education for clinicians and patients, so that both right prescription of gastroprotective agents as therapy adherence will improve.