High prevalence of clarithromycin resistance and effect on Helicobacter pylori eradication in a population from Santiago, Chile: cohort study and meta-analysis.

Helicobacter pylori (H. pylori) eradication using standard triple therapy (STT) with proton pump inhibitors (PPI), amoxicillin and clarithromycin (CLA) has been the standard in Latin America. However, CLA resistance is a rising problem affecting eradication rates. Genetic polymorphisms of CYP2C19, a PPI metabolizer may also affect eradication. The primary aims of this study were to evaluate the effect of clarithromycin resistance on H. pylori eradication in a population from Santiago, and to establish the pooled clarithromycin resistance in Santiago, Chile. Symptomatic adult patients attending a tertiary hospital in Santiago were recruited for this study. CLA resistance and the polymorphisms of CYP2C19 were determined on DNA extracted from gastric biopsies, using PCR. The STT was indicated for 14 days and eradication was determined by a urea breath test 4-6 weeks after therapy. A meta-analysis of CLA resistance studies among adult residents in Santiago was performed. Seventy-three out of 121 consecutive patients had positive rapid urease test (RUT) and received STT. Sixty-nine patients (95%) completed the study. The H. pylori eradication rate was 63% and the prevalence of CLA resistance was 26%. According to the CYP2C19 polymorphisms, 79.5% of the RUT-positive patients were extensive metabolizers. Multivariable analyses showed that only CLA resistance was significantly and inversely associated with failure of eradication (OR: 0.13; 95% confidence interval [95% CI], 0.04-0.49). A meta-analysis of two previous studies and our sample set (combined n = 194) yielded to a pooled prevalence of CLA resistance of 31.3% (95% CI 23.9-38.7). Our study shows that CLA resistance is associated with failure of H. pylori eradication. Given the high pooled prevalence of CLA resistance, consideration of CLA free therapies in Santiago is warranted. We could recommend bismuth quadruple therapy or high-dose dual therapy, according to bismuth availability. Further studies need to evaluate the best therapy.

The fourth Mexican consensus on Helicobacter pylori. / IV consenso mexicano sobre Helicobacter pylori.

Important advances have been made since the last Mexican consensus on the diagnosis and treatment of Helicobacter pylori (H. pylori) infection was published in 2007. Therefore, the Asociación Mexicana de Gastroenterología summoned 20 experts to produce "The Fourth Mexican Consensus on Helicobacter pylori". From February to June 2017, 4 working groups were organized, a literature review was performed, and 3 voting rounds were carried out, resulting in the formulation of 32 statements for discussion and consensus. From the ensuing recommendations, it was striking that Mexico is a country with an intermediate-to-low risk for gastric cancer, despite having a high prevalence of H. pylori infection. It was also corroborated that peptic ulcer disease, premalignant lesions, and histories of gastric cancer and mucosa-associated lymphoid tissue lymphoma should be considered clear indications for eradication. The relation of H. pylori to dyspeptic symptoms continues to be controversial. Eradication triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor should no longer be considered first-line treatment, with the following 2 options proposed to take its place: quadruple therapy with bismuth (proton pump inhibitor, bismuth subcitrate, tetracycline, and metronidazole) and quadruple therapy without bismuth (proton pump inhibitor, amoxicillin, clarithromycin, and metronidazole). The need for antimicrobial sensitivity testing when 2 eradication treatments have failed was also established. Finally, the promotion of educational campaigns on the diagnosis and treatment of H. pylori for both primary care physicians and the general population were proposed.

Serum pepsinogen 1 and anti-Helicobacter pylori IgG antibodies as predictors of gastric cancer risk in Finnish males.

BACKGROUND: Serum pepsinogen 1 (SPG1) and anti-Helicobacter pylori serology have been used for gastric risk stratification in Asia. AIM: To assess utility of these markers in a Western population. METHODS: SPG1 measurements were available for 21 895 Finnish male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We used Cox proportional hazards models adjusted for potential confounders to estimate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI) for low SPG1 (<25 µg/L). In a subset (n = 3555) with anti-H. pylori serology, these markers jointly defined the following: Group A (H. pylori[-], SPG1[normal]; reference group), Group B (H. pylori[+], SPG1[normal]), Group C (H. pylori[+], SPG1[low]) and Group D (H. pylori[-], SPG1[low]). Odds ratios (ORs) and 95% CI were calculated using multivariate logistic regression. RESULTS: There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Pre-diagnostic low SPG1 was significantly associated with increased gastric cancer risk (HR 2.68, 95% CI 1.99-3.61). Among subjects with both SPG1 and H. pylori serology, groups B, C and D had increased gastric cancer ORs (95% CI) of 1.79 (1.21-2.64), 3.85 (2.36-6.28) and 6.35 (2.20-18.34), respectively. CagA seropositives had significantly higher ORs than CagA seronegatives within group B (Pheterogeneity  = 0.01). For groups B and C, repeat SPG1 level at 3 years did not further stratify gastric cancer risk. CONCLUSIONS: Low SPG1 was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.

International cancer seminars: a focus on esophageal squamous cell carcinoma.

The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Association of 4p14 TLR locus with antibodies to Helicobacter pylori.

A genome-wide association study among Europeans related polymorphisms of the Toll-like receptor (TLR) locus at 4p14 and the Fcγ receptor 2a locus at 1q23.3 to Helicobacter pylori serologic status. We replicated associations of 4p14 but not 1q23.3 with anti-Helicobacter pylori antibodies in 1402 Finnish males. Importantly, our analysis clarified that the phenotype affected by 4p14 is quantitative level of these antibodies rather than association with seropositivity per se. In addition, we annotated variants at 4p14 as expression quantitative trait loci (eQTL) associated with TLR6/10 and FAM114A1. Our findings suggest that 4p14 polymorphisms are linked to host immune response to H. pylori infection but not to its acquisition.

Determinants of Epstein-Barr virus-positive gastric cancer: an international pooled analysis.

BACKGROUND: Meta-analyses of the published literature indicate that about 9% of gastric cancers contain Epstein-Barr virus (EBV), with consistent and significant differences by sex and anatomic subsite. This study aimed to identify additional determinants of EBV positivity and their joint effects. METHODS: From 15 international populations with consistent laboratory testing for EBV, we pooled individual-level data for 5081 gastric cancer cases including information on age, sex, subsite, histologic type, diagnostic stage, geographic region, and period of diagnosis. First, we combined population-specific EBV prevalence estimates using random effects meta-analysis. We then aggregated individual-level data to estimate odds ratios of EBV positivity in relation to all variables, accounting for within-population clustering. RESULTS: In unadjusted analyses, EBV positivity was significantly higher in males, young subjects, non-antral subsites, diffuse-type histology, and in studies from the Americas. Multivariable analyses confirmed significant associations with histology and region. Sex interacted with age (P=0.003) and subsite (P=0.002) such that male predominance decreased with age for both subsites. The positivity of EBV was not significantly associated with either stage or time period. CONCLUSION: Aggregating individual-level data provides additional information over meta-analyses. Distinguishing histologic and geographic features as well as interactions among age, sex, and subsite further support classification of EBV-associated gastric cancer as a distinct aetiologic entity.

Polycyclic aromatic hydrocarbons in Brazilian commercial soybean oils and dietary exposure.

In this study the 13 polycyclic aromatic hydrocarbons (PAHs) identified as being genotoxic and carcinogenic by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) were determined in different brands of soybean oils available on the Brazilian market, totalling 42 samples. A solid-phase extraction (SPE) method for sample clean-up with a C18 cartridge, followed by reversed-phase HPLC with fluorescence detection, was used for determination. The method showed good recoveries for most PAHs studied with values between 74% and 111%. Good intra- and inter-day precisions (0.5 < RSD < 11.9) and high correlation coefficients (r(2)> 0.999) were obtained. The presence of PAHs was detected in all 42 samples with mean summed PAH levels ranging from 10.4 to 112.0 µg kg(-1). The mean and maximum dietary exposures for total PAHs were estimated as 12.4 and 19.1 ng kg bw(-1) day(-1), respectively.

CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions.

The C-terminus of the Helicobacter pylori CagA protein is polymorphic, bearing different EPIYA sequences (EPIYA-A, B, C or D), and one or more CagA multimerization (CM) motifs. The number of EPIYA-C motifs is associated with precancerous lesions and gastric cancer (GC). The relationship between EPIYA, CM motifs and gastric lesions was examined in H. pylori-infected Colombian patients from areas of high and low risk for GC. Genomic DNA was extracted from H. pylori strains cultured from gastric biopsies from 80 adults with dyspeptic symptoms. Sixty-seven (83.8%) of 80 strains were cagA positive. The 3' region of cagA was sequenced, and EPIYA and CM motifs were identified. CagA proteins contained one (64.2%), two (34.3%) or three EPIYA-C motifs (1.5%), all with Western type CagA-specific sequences. Strains with one EPIYA-C motif were associated with less severe gastric lesions (non-atrophic and multifocal atrophic gastritis), whereas strains with multiple EPIYA-C motifs were associated with more severe lesions (intestinal metaplasia and dysplasia) (p <0.001). In 54 strains, the CM motifs were identical to those common in Western strains. Thirteen strains from the low-risk area contained two different CM motifs: one of Western type located within the EPIYA-C segment and another following the EPIYA-C segment and resembling the CM motif found in East Asian strains. These strains induced significantly shorter projections in AGS cells and an attenuated reduction in levels of CagA upon immunodepletion of SHP-2 than strains possessing Western/Western motifs. This novel finding may partially explain the difference in GC incidence in these populations.

Long term follow up of patients treated for Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori infection induces progressive inflammatory changes in the gastric mucosa that may lead to gastric cancer. Understanding long term effects resulting from the cure of this infection is needed to design cancer prevention strategies. METHODS: A cohort of 795 adults with preneoplastic gastric lesions was randomised to receive anti-H pylori treatment and/or antioxidants. At the end of six years of intervention, those who did not receive anti-H pylori treatment were offered it. Gastric biopsies were obtained at baseline, and at 3, 6, and 12 years. A histopathology score was utilised to document changes in gastric lesions. Non-linear mixed models were used to estimate the cumulative effect of H pylori clearance on histopathology scores adjusted for follow up time, interventions, and confounders. RESULTS: Ninety seven per cent of subjects were H pylori positive at baseline, and 53% were positive at 12 years. Subjects accumulated 1703 person years free of infection. A multivariate model showed a significant regression in histopathology score as a function of the square of H pylori negative time. Subjects who were H pylori negative had 14.8% more regression and 13.7% less progression than patients who were positive at 12 years (p = 0.001). The rate of healing of gastric lesions occurred more rapidly as years free of infection accumulated, and was more pronounced in less advanced lesions. CONCLUSIONS: Preneoplastic gastric lesions regress at a rate equal to the square of time in patients rendered free of H pylori infection. Our findings suggest that patients with preneoplastic gastric lesions should be treated and cured of their H pylori infection.

Seroprevalence of Neospora caninum and Toxoplasma gondii antibodies in the South American opossum (Didelphis marsupialis) from the city of São Paulo, Brazil.

Antibodies to Neospora caninum and Toxoplasma gondii were assayed in sera of 396 opossums (Didelphis marsupialis) from the city of São Paulo, Brazil. Antibodies to N. caninum were assayed using the indirect immunofluorescent antibody test (IFAT). Antibodies (IFAT, approximately 1:25) to N. caninum were found in 84 opossums (D. marsupialis) in titers of 1:25 in 46, 1:50 in 20, 1:100 in 17, and 1:400 in 1. Antibodies to T. gondii were assayed with the modified agglutination test (MAT) and the IFAT. Antibodies to T. gondii (MAT, approximately 1:25) were found in 82 (20.4%) of the 396 opossums, in titers of 1:25 in 24, 1:50 in 26, 1:100 in 18, 1:200 in 13, and 1:800 in 1. The IFAT antibodies to T. gondii were found in 148 of 396 opossums, in titers of 1:16 in 41, 1:32 in 23, 1:64 in 13, 1:128 in 6, 1:256 in 20, 1:512 in 17, 1:1,024 in 10, 1:2,048 in 10, 1:4,096 in 7, and 1:8,192 in 1. This is the first report of N. caninum and T. gondii infections in D. marsupialis.

Prevalence of antibodies to Neospora caninum and Sarcocystis neurona in sera of domestic cats from Brazil.

Parasite Biology, Epidemiology and Systematics Laboratory, Animal and Natural Resources Institute, Agricultural Research Service, United States Department of Agriculture, Building 1001, Beltsville, Maryland 20705-2350 Antibodies to Neospora caninum and Sarcocystis neurona were determined in serum samples of 502 domestic cats from Brazil using direct agglutination tests with the respective antigens. Antibodies to S. neurona were not found in 1:50 dilution of any serum in the S. neurona agglutination test. suggesting that domestic cats from São Paulo city were not exposed to S. neurona sporocysts from opossums. Antibodies to N. caninum were found in 60 (11.9%) of 502 cats with titers of 1:40 in 36 cats, 1:80 in 18 cats, 1:160 in 5 cats, and 1:800 in 1 cat using the Neospora agglutination test (NAT). Antibodies to N. caninum were confirmed by Western blotting in the sera of 10 cats with NAT titers of 1:80 to 1:800; this finding suggests that at least 10 cats had N. caninum-specific antibodies confirmed by 2 tests. This is the first documentation of natural exposure of cats to N. caninum.

[Occurrence of canine visceral leishmaniasis in an agricultural settlement in the State of Mato Grosso do Sul, Brazil]. / Ocorrência de leishmaniose visceral canina em assentamento agrícola no Estado de Mato Grosso do Sul, Brasil.

During previous research on phlebotomine fauna in a settlement of the Brazilian National Agrarian Reform Institute (INCRA) on the Bodoquena Range, Mato Grosso do Sul State, Brazil, dogs were observed with clinical aspects suggestive of visceral leishmaniasis. A serological survey to leishmaniasis in 97 dogs, by indirect immunofluorescence test, showed 23 (23.7%) serum positive dogs. Samples of the parasites were identified as Leishmania (Leishmania) chagasi.

Ocorrência de leishmaniose visceral canina em assentamento agrícola no Estado de Mato Grosso do Sul, Brasil / Occurrence of canine visceral leishmaniasis in an agricultural settlement in the State of Mato Grosso do Sul, Brazil

During previous research on phlebotomine fauna in a settlement of the Brazilian National Agrarian Reform Institute (INCRA) on the Bodoquena Range, Mato Grosso do Sul State, Brazil, dogs were observed with clinical aspects suggestive of visceral leishmaniasis. A serological survey to leishmaniasis in 97 dogs, by indirect immunofluorescence test, showed 23 (23.7%) serum positive dogs. Samples of the parasites were identified as Leishmania (Leishmania) chagasi.

Durante estudos sobre a fauna flebotomínea em assentamento do Instituto Nacional de Reforma Agrária (INCRA) na Serra da Bodoquena, Estado de Mato Grosso do Sul, Brasil, foram observados cães com manifestações clínicas sugestivas de leishmaniose visceral. Inquérito sorológico para leishmaniose em 97 cães, utilizando reação de imunofluorescência indireta, mostrou 23 (23,7%) soros reagentes. Amostras do parasita foram identificadas como Leishmania (Leishmania) chagasi.