RESUMEN
BACKGROUND AND AIM: According to several guidelines, both invasive and non-invasive tests can be used to detect Helicobacter pylori (H. pylori). Invasive methods include H. pylori culture, histological staining, rapid urease tests (RUTs) and PCR. Non-invasive methods include urease breath test, stool antigen and serum IgG testing. The aim of our study was to compare all commercially available RUTs and histology in Germany. MATERIAL AND METHODS: One hundred fifty patients were enrolled in our study, irrespective of proton pump inhibitors (PPIs) or antibiotic use. If the results of RUTs and histology were diverging, real-time PCR to detect H. pylori DNA was undertaken. RESULTS: We detected no differences in the sensitivity or specificity between the different RUTs. In PPI and/or antibiotic-treated patients, RUTs seemed to be more sensitive for the detection of H. pylori infection compared to histology. In addition to the cheaper price of RUTs, they are also quicker to process. We show that histological staining in patients with signs of gastritis is expensive and not necessary, if there are no additional histological questions besides H. pylori status. CONCLUSIONS: In conclusion, we consider RUTs to be cheap and fast alternatives to histology in patients with endoscopic signs of gastritis, independently of whether PPIs or antibiotic are used. Histological evaluation is expensive, time consuming and may be unnecessary in some cases.
Asunto(s)
Pruebas Respiratorias/métodos , Gastritis/diagnóstico , Gastroscopía/estadística & datos numéricos , Ureasa/análisis , Anciano , Antibacterianos/uso terapéutico , Femenino , Gastritis/microbiología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Inhibidores de la Bomba de Protones/uso terapéutico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estómago/patologíaRESUMEN
Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment-naïve, intestinal type, gastroesophageal adenocarcinomas were assessed by the Illumina-HTv4.0 beadchip. Differential gene expression (limma), unsupervised subgroup assignment (mclust) and pathway analysis (gage) were undertaken in R statistical computing and results were related to demographic and clinical parameters. Unsupervised assignment of the gene expression profiles revealed three distinct molecular subgroups, which were not associated with anatomical location, tumor stage or grade (p > 0.05). Group 1 was enriched for pathways involved in cell turnover, Group 2 was enriched for metabolic processes and Group 3 for immune-response pathways. Patients in group 1 showed the worst overall survival (p = 0.019). Key genes for the three subtypes were confirmed by immunohistochemistry. The newly defined intrinsic subtypes were analyzed in four independent datasets of gastric and esophageal adenocarcinomas with transcriptomic data available (RNAseq data: OCCAMS cohort, n = 158; gene expression arrays: Belfast, n = 63; Singapore, n = 191; Asian Cancer Research Group, n = 300). The subgroups were represented in the independent cohorts and pooled analysis confirmed the prognostic effect of the new subtypes. In conclusion, adenocarcinomas at the GEJ comprise three distinct molecular phenotypes which do not reflect anatomical location but rather inform our understanding of the key pathways expressed.
Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/patología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Unión Esofagogástrica/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Transcriptoma/genética , Perfilación de la Expresión Génica/métodos , Humanos , Inmunohistoquímica/métodos , Fenotipo , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates. METHODS: Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 (61.6%) also underwent gastroscopy to correlate the results for serum pepsinogen I and II (sPG-I and sPG-II), sPG-I/II ratio, and anti-H. pylori antibodies with gastric histopathology findings (graded according to the updated Sydney classification and the Operative Link of Gastritis Assessment (OLGA) and the Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) systems). RESULTS: H. pylori was found in 85 patients (30.5%). Chronic atrophic gastritis was diagnosed in 89 (31.9%) patients. High-risk OLGA (IIIâ»IV) stages were present in 24 patients, and high-risk OLGIM stages were present in 14 patients. There was an inverse correlation of sPG-I with the degree of atrophy and intestinal metaplasia (IM), as well as with the respective OLGA (r = -0.425; p < 0.001) and OLGIM (r = -0.303; p < 0.001) stages. A pathological sPG-I result was associated with a relative risk (RR) of 12.2 (95% confidence interval: 6.29â»23.54; p < 0.001) for gastric preneoplastic changes. CONCLUSIONS: The assessment of serum pepsinogen allows the identification of patients at increased risk of gastric cancer. A prevention strategy of combining a screening colonoscopy with a serological screening for preneoplastic gastric changes should be considered in the general population.
Asunto(s)
Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Neoplasias Gástricas/diagnóstico , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/patología , Femenino , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/fisiología , Humanos , Masculino , Persona de Mediana Edad , Pepsinógeno A/sangre , Medición de Riesgo , Neoplasias Gástricas/sangre , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
Recent studies have suggested that Helicobacter pylori (H. pylori) constitutes a risk for the development of colonic neoplasia. Hypergastrinemia can be induced by H. pylori infection, and gastrin can act as putative promoter of colorectal carcinogenesis. Aim of our study was to assess whether H. pylori infection and/or increased serum gastrin levels are associated with the occurrence of colonic neoplasms. For this, we reviewed prospectively collected data of 377 patients with a minimum age of 50 years who underwent colonoscopy. H. pylori and CagA status were determined by serology. Serum gastrin levels were measured in fasting state by commercially available assay. In H. pylori infected patients (n = 138; 36.6%), the overall prevalence of colonic neoplasms was more frequent compared to H. pylori negative patients (n = 239; 63.4%) (OR = 2.73, 95% CI: 1.76-4.24). H. pylori infection occurred more frequently in patients with hyperplastic polyps (OR = 2.66, 95% CI: 1.23-5.74) and adenomas presenting with low grade intraepithelial neoplasia (IEN) (OR = 1.85, 95% CI: 1.14-2.99). Attributable risk for adenomas with high grade IEN and colorectal adenocarcinoma (n = 14) was not assessed due to the low number of cases. The expression of CagA was also associated with an increased risk for colonic neoplasms (OR = 2.25, 95% CI: 1.29-3.94). Hypergastrinemia did not increase the risk for any colonic neoplasms and there was no difference in basal serum gastrin levels between H. pylori positive and negative patients. In conclusion, H. pylori infection, including CagA expression is associated with an increased risk for the development of colonic neoplasm.
Asunto(s)
Antígenos Bacterianos/sangre , Proteínas Bacterianas/sangre , Neoplasias del Colon/microbiología , Gastrinas/sangre , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Anciano , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/biosíntesis , Proteínas Bacterianas/biosíntesis , Colon/microbiología , Neoplasias del Colon/complicaciones , Colonoscopía , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Helicobacter pylori/aislamiento & purificación , Humanos , Inflamación/inmunología , Inflamación/microbiología , Masculino , Pólipos/complicaciones , Pólipos/inmunología , Estudios Prospectivos , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: This review focuses on new treatment options for eradicating Helicobacter pylori that have emerged as a result of decreased efficacy of standard triple therapy due to increasing antibiotic resistance. We also report on new data regarding primary and secondary gastric cancer prevention strategies and the potential role of H. pylori as a risk factor for extragastric malignancies. RECENT FINDINGS: Treatment options have shifted from triple to various quadruple modifications. The length of therapy duration has, in general, been extended from 7 to 10 and 14 days. Nonbismuth-based quadruple therapies prescribed as sequential, concomitant, and hybrid have shown superiority as compared to standard triple therapy in the eradication of clarithromycin-resistant H. pylori. Bismuth-based quadruple therapy appears almost totally independent of antibiotic resistance and maintains high eradication rates. Levofloxacin is an adequate substitute for clarithromycin and is recommended in second-line regimens. However, it should be used prudently as H. pylori has developed resistance to levofloxacin in many regions of the world. Strategies for primary gastric cancer prevention by H. pylori eradication are effective, whereas H. pylori eradication for secondary gastric cancer prevention is uncertain. Very recent data implicate H. pylori as a risk factor for extragastric malignancies. SUMMARY: H. pylori therapy should be tailored according to local antibiotic resistance patterns. In many regions of the world, H. pylori is becoming increasingly resistant to clarithromycin, metronidazole, and levofloxacin. Gastric cancer prevention by H. pylori eradication is most effective, if implemented early in the course of infection. New data are provided which indicate H. pylori as risk factor for extragastric malignancies.
Asunto(s)
Antibacterianos/administración & dosificación , Farmacorresistencia Bacteriana/efectos de los fármacos , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/prevención & control , Bismuto/administración & dosificación , Claritromicina/administración & dosificación , Quimioterapia Combinada , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Humanos , Levofloxacino/administración & dosificación , Metronidazol/administración & dosificación , Inhibidores de la Bomba de Protones/administración & dosificaciónRESUMEN
Gastric cancer (GC) continues to be an important health threat as the third leading cause of cancer related death in both sexes worldwide. In a recent analysis, the mortality trends for the time period from 1980 till 2011 were significantly downward in all countries, but the declines in the USA, EU and several other major countries were of low magnitude when compared with the past. Furthermore, the relative contribution of cardia cancers compared with noncardia cancers increased among countries with higher GC rates. With respect to preneoplastic changes of the gastric mucosa, a large population-based study suggests that Helicobacter pylori infection and antigastric parietal cell antibodies-mediated autoimmune response might, for the most part, be independent and follow distinct pathways rather than causally related pathways leading to chronic atrophic gastritis. A large prospective, randomized, open-label Korean trial questioned the role of H. pylori eradication for the prevention of metachronous lesions after endoscopic resection of early GC. A review of 1258 Japanese cases undergoing curative endoscopic submucosa dissection for early GC showed that scheduled follow-up endoscopy is mandatory for detecting metachronous lesions at an early stage, where they can be treated by endoscopic resection. Ramucirumab, a vascular endothelial growth factor receptor-2 antagonist, is the first biological treatment that provides survival benefits to patients with advanced GC in progress after first-line chemotherapy. The target agent rilotumumab is currently being evaluated in patients with advanced GC overexpressing the HGF/c-MET signaling pathway. In the near future, ipilimumab and nivolumab, two immunostimulatory monoclonal antibodies with antineoplastic effects, might offer new therapeutic options for patients with advanced GC.
Asunto(s)
Infecciones por Helicobacter/microbiología , Neoplasias Gástricas/microbiología , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/fisiología , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/epidemiologíaRESUMEN
PURPOSE OF REVIEW: This review focuses on new aspects of recently published guidelines for the management of Helicobacter pylori infection as well as progress in diagnostic tests and treatment regimens. We also discuss new strategies for gastric cancer prevention. RECENT FINDINGS: The general recommendation to treat H. pylori infection whenever diagnosed still faces resistance for reasons that are pertinent to the diversity of related clinical outcomes and to the complexity of eradication regimens. Thus, new updated guidelines for the management of H. pylori infection have been released in several continents. Progress has been made in molecular diagnostic tests for the detection of antibiotic resistance and serological tests for the detection of advanced gastric atrophic changes. Effective quadruple therapies in various combinations of 'traditional drugs' have been introduced with sequential or concomitant order of administration. Moreover, traditional drugs in a new galenic formulation have been introduced to overcome increasing H. pylori antibiotic resistance. Effective strategies for gastric cancer prevention have been adopted in some countries with high gastric cancer incidence, and have successfully contributed to lower the gastric cancer incidence. A screen-and-treat strategy for individuals at increased risk for gastric cancer needs to be further explored also in areas with low/moderate incidence of gastric cancer. SUMMARY: New guidelines share many universal similarities across countries but respect and emphasize specific needs and requirements in individual communities. Various combinations of traditional drugs have been successfully introduced to overcome the increasing H. pylori antibiotic resistance. Gastric cancer prevention by a screen and treat strategy showed promising results.
Asunto(s)
Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnóstico , Humanos , Guías de Práctica Clínica como Asunto , Medición de Riesgo/métodos , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/prevención & controlRESUMEN
The best opportunity to reduce gastric cancer (GC)-related mortality remains prevention. Mass eradication of Helicobacter pylori infection in a Taiwanese population >30 years of age reduced GC incidence with an effectiveness of 25% (rate ratio 0.753, 95% CI 0.372-1.524). In the Shandong intervention trial conducted on a Chinese population aged 35-64 years, cancer incidence was reduced by 39% in subjects who received H. pylori treatment compared with the placebo group after 14.7 years of follow-up (absolute risk 3.0 vs 4.6%; odds ratio 0.61, 95% CI 0.38-0.96; p = .03). A high incidence of severe gastric atrophic changes and noninvasive gastric neoplasia has been reported in a Portuguese case-control study on first-degree relatives of patients with early-onset gastric carcinoma (i.e., diagnosed before 45 years), which emphasizes again the importance of GC screening in this population. For patients with advanced GC, new targeted therapies to improve survival are under scrutiny. Trastuzumab resistance may be present from early on, or develop during trastuzumab therapy in patients with GC, and an overexpression of the HER2/neu protein. New molecules to overcome trastuzumab resistance are also being evaluated. The association between H. pylori-induced gastritis and an increased risk of developing colonic neoplasms has been confirmed in a recent study, but the causality for this intriguing association has still to be clarified.
Asunto(s)
Infecciones por Helicobacter/microbiología , Helicobacter pylori/fisiología , Neoplasias Gástricas/microbiología , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Humanos , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
PURPOSE OF REVIEW: Progress continues in our understanding of the role of Helicobacter pylori infection in gastroduodenal as well as extragastric disorders. This review gives an overview on selected areas of the H. pylori infection and their clinical implications. RECENT FINDINGS: Indications for therapy have been extended and now include idiopathic thrombocytopenic purpura, iron deficiency anemia, and vitamin B12 deficiency. New data are presented on the role of H. pylori in neurodegenerative disorders and in the metabolic syndrome. H. pylori is associated with a (small) increase in the risk for colorectal adenoma and colon cancer. The biggest challenge is the selection of new therapies and treatment strategies because of the increasing failure of standard triple therapies. The best option in high clarithromycin resistance areas is bismuth-based quadruple therapy. Probiotic bacteria and yeasts reduce adverse effects of standard H. pylori eradication regimens. In gastric cancer prevention, screening programs based on the serological detection of preneoplastic conditions may prove useful. SUMMARY: New algorithms for preventing H. pylori-induced disease and eradicating the organism should be individualized.
Asunto(s)
Infecciones por Helicobacter/fisiopatología , Helicobacter pylori/patogenicidad , Neoplasias Gástricas , Antibacterianos/uso terapéutico , Neoplasias del Colon/microbiología , Farmacorresistencia Bacteriana , Fármacos Gastrointestinales/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Enfermedades Neurodegenerativas/microbiología , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica/microbiología , Probióticos/uso terapéutico , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/prevención & controlRESUMEN
The greatest challenge in Helicobacter pylori-related diseases continues to remain prevention of gastric cancer. New evidence supports the beneficial effect of H. pylori eradication not only on prevention of gastric cancer but also on the regression of preneoplastic conditions of the gastric mucosa. Concerning early detection of gastric cancer there are still no adequate means and there is urgent need to define appropriate markers, for example, by genome-wide research approaches. Currently, the best available method is the "serologic" biopsy based on pepsinogen I and the pepsinogen I/II ratio for identification of patients with severe gastric atrophy at increased risk for gastric cancer development. The treatment of early gastric cancer by endoscopic techniques can be performed safely and efficiently, but patients need meticulous follow-up for detection of metachronous lesions. In case of advanced disease, laparoscopically assisted surgical procedures are safe and favorable compared to open surgery. Two phase III trials support the role of adjuvant systemic treatment with different regimens. Unfortunately, there is still only slow progress in the development of palliative treatment regimens or modification of the existing therapy protocols. There is accumulating evidence for a role of H. pylori infection also in colorectal carcinogenesis. Seropositive individuals are at higher risk for the development of colorectal adenomas and consequently adenocarcinomas of this anatomical region. This phenomenon can partly be attributed to the increase of serum gastrin as response to atrophic changes of the gastric mucosa.
Asunto(s)
Infecciones por Helicobacter/patología , Helicobacter pylori/fisiología , Enfermedades Intestinales/patología , Neoplasias Gástricas/patología , Animales , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/terapia , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Humanos , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/microbiología , Enfermedades Intestinales/terapia , Intestinos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/terapiaRESUMEN
BACKGROUND: Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1), pepsinogen 2 (PG2) and gastrin 17 (G17) offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. METHODS: Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation), degree of mucosal abnormalities (intestinal metaplasia, atrophy) and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status). Association of the general factors to the different serological values have been statistically analyzed. RESULTS: Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003). The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058). The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p < 0.01). Laurén-specific analysis revealed that this is only true for intestinal type tumors. Univariate ANOVA revealed atrophy and CagA-status as the only independent factors for low PG1 and a low PG1/2-ratio. CONCLUSIONS: Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.
Asunto(s)
Adenocarcinoma/sangre , Adenocarcinoma/patología , Biomarcadores de Tumor/sangre , Mucosa Gástrica/patología , Neoplasias Gástricas/sangre , Neoplasias Gástricas/patología , Anciano , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/sangre , Atrofia , Proteínas Bacterianas/sangre , Femenino , Gastrinas/sangre , Infecciones por Helicobacter/sangre , Helicobacter pylori/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pepsinógeno A/sangre , Lesiones Precancerosas/sangre , Estudios RetrospectivosRESUMEN
Background: Antibiotic susceptibility of Helicobacter pylori to antibiotics may vary among different niches of the stomach. The progression of chronic H. pylori gastritis to atrophy changes intragastric physiology that may influence selection of resistant strains. Aim: To study the antibiotic resistance of H. pylori taking the severity of atrophic gastritis in antrum and corpus into account. Methods: Helicobacter pylori-positive patients (n = 110, m = 32, mean age 52.6 ± 13.9 years) without prior H. pylori eradication undergoing upper gastrointestinal (GI) endoscopy for dyspeptic symptoms were included in a prospective study. Patients were stratified into three groups depending on the grade of atrophy: no atrophy (OLGA Stage 0), mild atrophy (OLGA Stage I-II) and moderate/severe atrophy (OLGA Stage III-IV). Two biopsies each from the antrum and the corpus and one from the angulus were taken and assessed according to the updated Sydney system. H. pylori strains were isolated from antrum and corpus biopsies and tested for antibiotic susceptibility (AST) for amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin by the agar dilution methods. A Chi-square test of independence with a 95% confidence interval was used to detect differences in the proportion of patients with susceptible and resistant H. pylori strains. Results: Among 110 patients, primary clarithromycin resistance (R) was 30.0%, both in the antrum and corpus; metronidazole resistance accounted for 36.4 and 34.5% in the antrum and corpus; and levofloxacin was 19.1 and 22.7% in the antrum and corpus, respectively. Resistance rates to amoxicillin, tetracycline, and rifampicin were below 5%. Dual antibiotic resistance rate was 21.8%, and triple resistance rate was 9.1%. There was a significant difference in the resistance rate distribution in antrum (p < 0.0001) and corpus (p < 0.0001). With increasing severity of atrophy according to OLGA stages, there was a significant increase in clarithromycin-R and metronidazole-R. Conclusion: In treatment-naïve patients, antibiotic resistance and heteroresistance were related to the severity of atrophy. The high clarithromycin resistance in atrophic gastritis suggests that H. pylori antibiotic susceptibility testing should always be performed in this condition before selecting the eradication regimen.
RESUMEN
BACKGROUND: Several polymorphisms of genes involved in the immunological recognition of Helicobacter pylori and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL. METHODS: Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>A (rs5743336), TLR4 3725G>C (rs11536889), FAS 1377G>A (rs2234767), FAS 670A>G (rs1800682) and FASL 844T>C (rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis. RESULTS: Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for NOD1 796G/G genotype to be associated with increased risk of HRAG (62.4% vs. 54.5% in controls, p = 0.082). FAS 670G/G genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (p = 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. NOD1 796G>A and TLR4 3725G>C gene polymorphisms were also not associated with Helicobacter pylori infection. CONCLUSIONS: ACE, NOD1, TRL4 and FAS/FASL gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.
Asunto(s)
Gastritis Atrófica/genética , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Polimorfismo Genético , Lesiones Precancerosas/genética , Neoplasias Gástricas/genética , Población Blanca/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Proteína Ligando Fas/genética , Femenino , Gastritis Atrófica/microbiología , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Proteína Adaptadora de Señalización NOD1/genética , Peptidil-Dipeptidasa A/genética , Factores de Riesgo , Neoplasias Gástricas/etnología , Neoplasias Gástricas/microbiología , Receptor Toll-Like 4/genética , Receptor fas/genéticaRESUMEN
PURPOSE OF REVIEW: The article will give an overview on reasons for treatment failure and tries to show new concepts for Helicobacter pylori treatment. RECENT FINDINGS: Several new treatment options or modifications of already established regimens have been introduced to overcome treatment failure. Antibiotic resistance to H. pylori is the key factor for treatment failure. At the moment, standard triple therapy remains the primary choice in regions with proven low clarithromycin resistance rates. In areas with high clarithromycin resistance, four drug treatment regimens, including quadruple and sequential therapy, have proven the best results as first-line regimens. The options for second-line treatment regimens are manifold. Second-line treatment regimens need to be adapted accurately to local resistance rates. SUMMARY: Treatment of H. pylori infection is challenged by a dramatic fall in eradication rates all over the world. Newer regimens have been introduced including sequential, quadruple therapies and those regimens provide promising results, but the knowledge about local resistance rates remains the key to an effective therapy.
Asunto(s)
Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Farmacorresistencia Microbiana , Quimioterapia Combinada , Humanos , Insuficiencia del TratamientoRESUMEN
The validity and usefulness of the 7th edition of the UICC tumor node metastasis classification in the context of clinical management of gastric cancer are discussed. The most relevant new agent in gastric cancer therapy is trastuzumab for HER2-positive gastric carcinomas. This marks the success of continuous effort of translational research. Trastuzumab, initially applied in palliative settings, is currently being evaluated also in neoadjuvant treatment regimens. Several new meta-analyses support the carcinogenic effect of high salt intake and smoking in the context of Helicobacter pylori infection. Further data have become available on the efficacy of protective agents, acetyl salicylic acid/nonsteroidal anti-inflammatory drugs, and antioxidants. In search for a successful prevention strategy, the focus is on the identification of individuals at high risk who demand screening (testing) and surveillance. Serological assessment of gastric mucosal abnormalities with increased risk for gastric cancer development is extensively studied, and new data are presented from Asia as well as from Europe. New high-throughput techniques combined with bioinformatic vector analysis open the gate to the identification of new potential diagnostic and therapeutic targets. Furthermore, these approaches allow us to elucidate the interplay of bacterial virulence factors and the host's immune response as well as H. pylori-associated alterations of mucosal gene expression.
Asunto(s)
Infecciones por Helicobacter/genética , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/genética , Animales , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/terapia , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/fisiología , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/microbiologíaRESUMEN
PURPOSE OF REVIEW: The indication for Helicobacter pylori (H. pylori) eradication has been extended to few extragastroduodenal diseases. Scientific rigor needs to be applied as the list of clinical manifestations potentially related to H. pylori has disproportionally grown to its scientific evidence. Some potential beneficial aspects of H. pylori in allergic diseases and in the context of obesity are critically addressed in this review. The main challenge, however, continues to be the prevention of gastric cancer by H. pylori eradication. Strategies for identification of individuals and populations at risk are reported as well. A final aspect is dedicated to novel treatment regimens for overcoming the increasing treatment failures with proton pump inhibitor-based triple standards. RECENT FINDINGS: H. pylori infection is associated with some extragastric diseases such as idiopathic thrombocytic purpura and iron deficiency anemia that benefit from eradication therapy. The inverse relation of H. pylori prevalence and the increase in allergies and obesity, as reported from epidemiological studies, has prompted research for elucidating potential underlying pathophysiological mechanisms. Strategies for gastric cancer prevention include serological screening, which allow adopting eradication therapy in individuals at high risk. New treatments for H. pylori include sequential, bismuth-based quadruple and nonbismuth-based quadruple therapies. SUMMARY: The main clinical challenge remains prevention of H. pylori-related diseases by effective treatment and screening procedures.
Asunto(s)
Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Hipersensibilidad/microbiología , Neoplasias Gástricas/prevención & control , Anemia Ferropénica/microbiología , Antibacterianos/uso terapéutico , Asma/microbiología , Quimioterapia Combinada , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/efectos de los fármacos , Humanos , Tamizaje Masivo , Obesidad/microbiología , Púrpura Trombocitopénica Idiopática/microbiología , Pruebas Serológicas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiologíaRESUMEN
Gastric cancer still represents a global health care burden, and in the absence of strategies implemented for early detection, the disease continues to have a dismal prognosis. Patients presenting with clinical manifestations of gastric cancer have limited options for cure. Thus, early detection and prevention play a key role in the fight against gastric cancer. Serologic-based test methods have the potential to detect a subset of patients at high risk of gastric cancer that require a close clinical and endoscopic follow-up. More data have been produced to support Helicobacter pylori eradication as an efficient strategy to prevent gastric cancer. Treatment options for patients with an advanced disease are still limited, but the introduction of new agents opens a more optimistic perspective for the future.
Asunto(s)
Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Tamizaje Masivo/métodos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Neoplasias Gástricas/prevención & controlRESUMEN
The majority of gastric adenocarcinomas are related to chronic inflammation induced by Helicobacter pylori infection. For intestinal-type gastric cancer, a multistep process of mucosal alterations leading from gastritis via glandular atrophy, intestinal metaplasia and dysplasia to invasive carcinoma is well recognized. Ongoing clinical studies focus on a 'point of no return'. It is defined as a situation when certain alterations are no longer reversible by H. pylori eradication and progression to gastric cancer may continue. H. pylori affects the mucosal as well as the systemic immune response by secretion of cytokines and the recruitment of distinct inflammatory cells. The immune response is characterized by a balance between a Th1-dominated response and the recruitment of antigen-specific regulatory T cells that allow the bacteria to persist in human gastric mucosa. Besides immune-mediated effects, H. pylori induces cellular alterations as well as genetic alterations in genes that are essential for the epigenetic integrity and mucosal homeostasis. These genetic alterations during gastric cancer development are in focus of intensive research and should ultimately allow the identification of risk factors involved in gastric carcinogenesis. The detection of individuals at high risk for gastric cancer would help to design appropriate strategies for prevention and surveillance.
Asunto(s)
Inflamación/patología , Neoplasias Gástricas/patología , Estómago/patología , Predisposición Genética a la Enfermedad , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Humanos , Inflamación/complicaciones , Estómago/microbiología , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/microbiología , Factores de Virulencia/metabolismoRESUMEN
BACKGROUND: Despite evidence for the association of distal gastric cancer (GC) with the H. pylori infection, relevance of the infection for proximal GC is uncertain. AIMS: We analysed the prevalence of H.pylori in proximal and distal GC and its association with premalignant mucosal alterations in different gastric locations. METHODS: We performed a retrospective analysis on 152 patients with GC, stratified according to the location of the main tumor mass into proximal (n = 73) and distal (n = 79) GC. H.pylori prevalence and CagA-status were determined by serology. Intestinal metaplasia (IM), glandular atrophy and mucosal inflammation were diagnosed from histological specimens and graded according to the updated Sydney-classification. RESULTS: H.pylori prevalence (78.1 vs. 82.3%) and CagA-status (77.2 vs. 84.6%) were similar in proximal and distal GC as well as in intestinal and diffuse GC. IM (79.8 vs. 60.3%; P = 0.012) and atrophy (50.0 vs. 19.1%; P < 0.001) were more frequent in the mucosa surrounding intestinal tumors. There was a higher degree of surrounding IM in case of distally located compared to proximal tumors (P = 0.001). Overall, IM was more severe in the antrum than the corpus. In contrast, there was more severe active inflammation in the corpus than the antrum (P = 0.017). CONCLUSION: The prevalence of H.pylori is similar in proximal and distal GC if precise allocation of the primary tumor has been performed, especially at the esophagogastric junction. Distal tumors of the intestinal type are more often associated with local IM than proximal and diffuse type carcinomas. This suggests a distinct pathophysiological relevance of these mucosal alterations.
Asunto(s)
Infecciones por Helicobacter/epidemiología , Neoplasias Gástricas/epidemiología , Anciano , Atrofia/patología , Comorbilidad , Femenino , Mucosa Gástrica/patología , Helicobacter pylori , Humanos , Masculino , Metaplasia/patología , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: Multiple diagnostic methods and treatment strategies have been developed to detect and treat the Helicobacter pylori infection. Many of them have stood the test of time; others lost their value with the introduction of new test and treatment modalities. This review focuses on the current diagnostic methods and their clinical implications, as well as on established and novel treatment strategies. RECENT FINDINGS: The increasing antimicrobial resistance has resulted in a decline of the success rate of recommended eradication regimens. The current guidelines recommend as first-line treatment clarithromycin, amoxicillin or metronidazole, and proton pump inhibitor twice daily, but recent studies have demonstrated an increasing eradication failure with these regimens. Several treatment modifications have been adopted regarding duration and combination of substances. SUMMARY: The currently recommended first-line treatments are effective and well tolerated. In areas with high antimicrobial resistance rates, new antibiotic combinations and modifications in the sequence of drug administration are proposed as alternative treatment options to standard triple therapy. Future treatment strategies have to focus on regional antimicrobial resistance adopted treatment selection and the development of new antibiotics.