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1.
Biosens Bioelectron ; 256: 116282, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626615

RESUMO

Helicobacter pylori (H. pylori) infection correlates closely with gastric diseases such as gastritis, ulcers, and cancer, influencing more than half of the world's population. Establishing a rapid, precise, and automated platform for H. pylori diagnosis is an urgent clinical need and would significantly benefit therapeutic intervention. Recombinase polymerase amplification (RPA)-CRISPR recently emerged as a promising molecular diagnostic assay due to its rapid detection capability, high specificity, and mild reaction conditions. In this work, we adapted the RPA-CRISPR assay on a digital microfluidics (DMF) system for automated H. pylori detection and genotyping. The system can achieve multi-target parallel detection of H. pylori nucleotide conservative genes (ureB) and virulence genes (cagA and vacA) across different samples within 30 min, exhibiting a detection limit of 10 copies/rxn and no false positives. We further conducted tests on 80 clinical saliva samples and compared the results with those derived from real-time quantitative polymerase chain reaction, demonstrating 100% diagnostic sensitivity and specificity for the RPA-CRISPR/DMF method. By automating the assay process on a single chip, the DMF system can significantly reduce the usage of reagents and samples, minimize the cross-contamination effect, and shorten the reaction time, with the additional benefit of losing the chance of experiment failure/inconsistency due to manual operations. The DMF system together with the RPA-CRISPR assay can be used for early detection and genotyping of H. pylori with high sensitivity and specificity, and has the potential to become a universal molecular diagnostic platform.


Assuntos
Técnicas Biossensoriais , Técnicas de Genotipagem , Infecções por Helicobacter , Helicobacter pylori , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Técnicas de Genotipagem/instrumentação , Técnicas de Genotipagem/métodos , Genótipo , Proteínas de Bactérias/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Microfluídica/métodos , Antígenos de Bactérias/genética , Antígenos de Bactérias/análise , DNA Bacteriano/genética , DNA Bacteriano/análise , DNA Bacteriano/isolamento & purificação , Recombinases/metabolismo
2.
World J Gastroenterol ; 30(13): 1851-1858, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38659477

RESUMO

Currently, the diagnostic strategy for chronic gastritis (CG) is aimed not just at fixing the presence of gastric mucosal inflammation, but also at gastric cancer (GC) risk stratification in a particular patient. Modern classification approach with the definition of the stage of gastritis determines the need, activities and frequency of dynamic monitoring of a patient. However, this attitude to the patient suffering from CG was far from always. The present publication is a literature review describing the key milestones in the history of CG research, from the description of the first observations of inflammation of the gastric mucosa, assessment of gastritis as a predominantly functional disease, to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy, assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy, intestinal metaplasia, dysplasia and GC.


Assuntos
Mucosa Gástrica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Humanos , Gastrite/diagnóstico , Gastrite/história , Gastrite/microbiologia , Gastrite/patologia , Doença Crônica , Mucosa Gástrica/patologia , Mucosa Gástrica/microbiologia , História do Século XX , Infecções por Helicobacter/história , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , História do Século XXI , Helicobacter pylori/isolamento & purificação , Biópsia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/história , Neoplasias Gástricas/diagnóstico , História do Século XIX , Progressão da Doença , Metaplasia , Valor Preditivo dos Testes
3.
BMC Gastroenterol ; 24(1): 139, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649806

RESUMO

BACKGROUND: Gastric hamartomatous inverted polyps (GHIPs) are not well characterized and remain diagnostically challenging due to rarity. Therefore, this study aims to investigate the clinicopathologic and endoscopic characteristics of patients with GHIP. METHODS: We retrospectively reviewed clinicopathologic and endoscopic features of ten patients with GHIP who were admitted to Beijing Friendship Hospital from March 2013 to July 2022. All patients were treated successfully by endoscopic resection. RESULTS: GHIPs were usually asymptomatic and found incidentally during gastroscopic examination. They may be sessile or pedunculated, with diffuse or local surface redness or erosion. On endoscopic ultrasonography, the sessile submucosal tumor-type GHIP demonstrated a heterogeneous lesion with cystic areas in the third layer of the gastric wall. Histologically, GHIPs were characterized by a submucosal inverted proliferation of cystically dilated hyperplastic gastric glands accompanied by a branching proliferation of smooth muscle bundles. Inflammatory cells infiltration was observed in the stroma, whereas only one patient was complicated with glandular low-grade dysplasia. Assessment of the surrounding mucosa demonstrated that six patients (60%) had atrophic gastritis or Helicobacter pylori-associated gastritis, and four patients (40%) had non-specific gastritis. Endoscopic resection was safe and effective. CONCLUSIONS: GHIPs often arise from the background of abnormal mucosa, such as atrophic or H.pylori-associated gastritis. We make the hypothesis that acquired inflammation might lead to the development of GHIPs. We recommend to make a full assessment of the background mucosa and H. pylori infection status for evaluation of underlying gastric mucosal abnormalities, which may be the preneoplastic condition of the stomach.


Assuntos
Pólipos Adenomatosos , Endossonografia , Mucosa Gástrica , Gastroscopia , Hamartoma , Pólipos , Neoplasias Gástricas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hamartoma/patologia , Hamartoma/diagnóstico por imagem , Hamartoma/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/diagnóstico por imagem , Mucosa Gástrica/patologia , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/cirurgia , Adulto , Idoso , Pólipos/patologia , Pólipos/cirurgia , Pólipos/diagnóstico por imagem , Gastropatias/patologia , Gastropatias/cirurgia , Gastropatias/diagnóstico por imagem , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Gastrite/patologia , Gastrite/complicações , Gastrite/diagnóstico por imagem , Gastrite Atrófica/patologia , Gastrite Atrófica/complicações , Ressecção Endoscópica de Mucosa
4.
Clin Gastroenterol Hepatol ; 21(1): 229-231.e1, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34793965

RESUMO

Helicobacter pylori is the most prevalent bacterial infection, affecting half of the world's population, with a high morbidity and mortality rate.1,2 Several invasive and noninvasive testing procedures are available, and their selective use serves the specific needs of diverse clinical scenarios. For gastric cancer prevention, mass screening is necessary and requires a noninvasive, rapid, accurate and cost-effective test. For this purpose H pylori serology currently seems to be the preferred noninvasive diagnostic method. Population-based testing and treatment for H pylori is cost effective in high-risk countries, but less effective in low- and medium-risk countries.3,4 Many serologic tests are available on the market, with inconsistent performance often being observed. Therefore, international guidelines recommend considering only serologic tests with high accuracy that have been validated in the respective local populations. To date, no rapid point-of-care test (POCT) has reached a sufficient degree of accuracy.


Assuntos
Anticorpos Antibacterianos , Antígenos de Bactérias , Proteínas de Bactérias , Infecções por Helicobacter , Helicobacter pylori , Testes de Diagnóstico Rápido , Humanos , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Sensibilidade e Especificidade , Testes Sorológicos/métodos
5.
Clin Chim Acta ; 540: 117201, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36572137

RESUMO

BACKGROUND: Helicobacter pylori lives in the human stomach and causes gastric cancer and other gastric diseases. The development of molecular technology has facilitated low-cost, rapid, and high-throughput detection of H. pylori. MATERIALS AND METHODS: The combination of isothermal recombinase polymerase amplification (RPA) and CRISPR-Cas12a was used for early diagnosis and monitoring of H. pylori in clinical settings. The UreB genes from 242 H. pylori strains were subjected to cluster analysis, and we designed corresponding RPA primers and screened 2 sets of CRISPR-derived RNAs (crRNAs) for accurate H. pylori recognition. We then performed specificity and sensitivity validation of seven strains using this RPA-CRISPR/Cas12a method. In addition, the cut-off values of this RPA-CRISPR/Cas12a method based on fluorescence values (i.e., RPA-CRISPR/Cas12a-FT) were determined by comparison with quantitative PCR (qPCR), and further experiments comparing different methods were performed using clinical samples. RESULTS: We developed a rapid detection system based on the combination of RPA and CRISPR-Cas12a, which was applied to the early diagnosis and monitoring of H. pylori in clinical settings. The RPA-CRISPR/Cas12a system was used to detect the UreB gene. We found that the limit of detection (LOD) for the CRISPR/Cas12a method based on the lateral flow dipstick result (i.e., CRISPR/Cas12a-LFD) was 100 copies, the cut-off value was 1.4; and for CRISPR/Cas12a-FT the LOD was 50 copies. This system was used to assess clinical samples and showed high reproducibility with proof-of-concept sensitivity, and the whole detection process was completed within 40 min. CONCLUSION: As a diagnostic method that can detect the UreB gene of H. pylori in gastric tissue samples rapidly, sensitively, visually, and in a high throughput manner, our method provides a new diagnostic option for clinicians. This system is ideal for hospitals or testing sites with limited medical resources.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Sistemas CRISPR-Cas/genética , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Nucleotidiltransferases , Recombinases , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Infecções por Helicobacter/diagnóstico
6.
Acta med. costarric ; 64(2)jun. 2022.
Artigo em Espanhol | SaludCR, LILACS | ID: biblio-1419884

RESUMO

Objetivo: Determinar la viabilidad del cultivo de la bacteria Helicobacter pylori en Costa Rica por medio de la documentación de toma de muestras, la comparación del diagnóstico histopatológico y la descripción de los diagnósticos asociados a los aislamientos obtenidos con los resultados de la ureasa rápida. Métodos: Investigación descriptiva que involucró a pacientes de entre los 35 y 70 años, de ambos sexos, que asistieron al Servicio de Endoscopia Digestiva del Hospital Clínica Bíblica entre febrero y junio del 2019 para estudio gastroscópico. Se obtuvieron biopsias gástricas para diagnóstico histopatológico, prueba de ureasa rápida y cultivo de Helicobacter pylori. Para este último, se transportaron las biopsias en un medio de transporte semisólido, se maceró el tejido y se cultivó enagar Skirrow y agar selectivo para Helicobacter; una placa de cada medio se incubó a 37 °C en microaerofilia entre 48 horas y 10 días. La positividad del cultivo se realizó por observación de la morfología colonial y la bacteria se identificó por análisis microscópico al fresco, tinción de Gram y pruebas bioquímicas (catalasa, ureasa y oxidasa). Resultados: Se incluyó a 44 pacientes (edad: 50.6 ± 10.0, 54.5% masculinos). Se recuperó Helicobacter pylori en biopsias de 27 pacientes (61.4% de éxito). La recuperación de la bacteria fue similar en el medio Skirrow y en el selectivo para Helicobacter. El porcentaje de éxito de recuperación semanal aumentó durante el estudio hasta alcanzar un éxito del 100% en la semana 11. Se comparó el cultivo con la ureasa rápida en 27 pacientes y la concordancia entre ambos métodos fue de un coeficiente kappa de Cohen de 0.48. El cultivo detectó la bacteria en un 56% de los pacientes, la ureasa rápida en un 37% y la combinación de ambas técnicas permitió la detección en un 60%. El diagnóstico endoscópico más frecuente en los pacientes con cultivo positivo fue la gastritis eritematosa y gastritis crónica superficial y el diagnóstico histopatológico predominante fue gastritis crónica con atrofia gástrica. El diagnóstico por cultivo coincidió con la detección por azul de toluidina en un 80.4% de los casos. Conclusiones: Se puede implementar el cultivo de Helicobacter pylori en Costa Rica. Este estudio tuvo un porcentaje de recuperación de la bacteria de 61.4%. La combinación del método de cultivo con la prueba de ureasa rápida y la detección histológica contribuye a un diagnóstico certero y oportuno. Recomendamos que, con base en protocolos descritos en esta investigación, cada laboratorio estandarice las condiciones que le permitan un buen porcentaje de recuperación y una implementación adaptada a sus actividades de rutina.


Aim: To document the recent experiences on the implementation of sampling and culturing Helicobacter pylori in Costa Rica, to compare it with other diagnostic methods: rapid urease test and histopathology and to describe the diagnoses associated with the obtained isolates. Methods: Descriptive research involving patients who visited the digestive endoscopy department of the Clínica Bíblica hospital in San José, Costa Rica between February and July of 2019 for gastroscopy. Gastric biopsies were obtained and histopathological analysis, rapid urease test, and bacteriological culture for Helicobacter pylori were performed. For culture techniques, the sample was transported in an in-house semi-solid medium. Biopsy fragments were macerated and plated on Skirrow agar and Helicobacterselective in-house agar, and incubated in microaerophilic atmosphere for 48 hours to 10 days. Culture positivity was determined by observation of the colonial morphology and microscopic observation; Gram staining and biochemical tests (urease, catalase, and oxidase) were used for bacterial identification. Results: 44 patients (mean aged 50.6 ± 10.0 years old, 54.5% male) were included in the study. Helicobacter pylori was recovered in biopsies from 27 patients (61.4% success rate). Bacterial growth was similar regardless the culture medium, but the physiological state of the bacteria was better in the Helicobacter-selective agar than in Skirrow. The weekly recovery rate increased to reach a 100% recovery plateau on week 11. Culture was compared with the rapid urease test in 27 patients, and the concordance between both methods using Cohen's kappa coefficient was 0.48. Whilst the culture detected Helicobacter pylori in 56% of the patients, and the rapid urease test in 37%, the combination of both allowed a 60% rate. The most frequent endoscopic diagnosis in patients with positive cultures were erythematous gastritis and chronic superficial gastritis, and the predominant histopathological diagnosis was chronic atrophic gastritis. Culture-based diagnosis was consistent with the histopathology detection of Helicobacter pylori in 80.4% of the cases. Conclusions: The implementation of H. pylori culture in Costa Rica is possible. This study had a 61.4% recovery rate. The combination of culture with rapid urease test and histopathology increases the probability of an accurate and timely diagnosis. We recommend that, based on previously described protocols such as ours, each laboratory adjusts the conditions to allow a good recovery rate and implement H. pylori diagnostic methods most suitable to their routine activities.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico , Bacteriologia , Helicobacter pylori/isolamento & purificação , Costa Rica
7.
Eur Rev Med Pharmacol Sci ; 26(9): 3100-3108, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35587060

RESUMO

OBJECTIVE: Gastric cancer (GC) is a heterogeneous disease with molecular diversity between and within tumors; therefore, searching for altered genes within this cancer is mandatory to reach the proper individualized targeted therapy. Expressions of Metallothionein (MT) and p21 are not uniform in various types of cancers and their predictive value in GC is controversial. This study aimed to assess the role of MT and p21 in intestinal-type GC and some of its precursor lesions. MATERIALS AND METHODS: Immunohistochemical staining for MT and p21 was applied on paraffin blocks belonging to 30 GCs and 51 benign gastric lesions/precancerous lesions [33 chronic gastritis and 18 chronic gastritis with gastric intestinal metaplasia (GIM)]; 27 of them were associated with H. pylori infection. RESULTS: MT expression was dramatically increased while p21 expression was dramatically decreased from chronic gastritis to GIM to GC. In precancerous lesions, H. pylori-positive cases had significantly higher MT expression and lower p21 expression compared to H. pylori-negative cases. In GCs, decreased expression of both MT and p21 was associated with high-grade and advanced-stage cancers. CONCLUSIONS: Both MT and p21 may have a role in the development and progression of GC, and both proteins may be useful for selecting targeted therapy for GC patients.


Assuntos
Metalotioneína , Lesões Pré-Cancerosas , Neoplasias Gástricas , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/genética , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/metabolismo , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Metalotioneína/biossíntese , Metalotioneína/genética , Metaplasia/metabolismo , Metaplasia/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
8.
BMC Gastroenterol ; 22(1): 101, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35255813

RESUMO

BACKGROUND: Protein-losing gastroenteropathy (PLGE) is a syndrome with a chief complaint of hypoalbuminemia, which occurs due to plasma protein leakage in the gastrointestinal tract, leading to general edema, ascites, and pleural effusions. CASE PRESENTATION: A 71-year-old woman visited another hospital for evaluation of hypoalbuminemia and systemic edema. She was hospitalized for a close inspection of hypoalbuminemia and was diagnosed with PLGE. Steroid and azathioprine therapy was prescribed; however, hypoalbuminemia did not improve, and the patient's condition worsened due to anasarca. As hospitalization was prolonged, the patient was transferred to our hospital. She was infected with Helicobacter pylori, and we performed H. pylori eradication. Following H. pylori eradication, her edema improved remarkably. CONCLUSION: We present the first case wherein H. pylori eradication successfully improved protein leakage in the lower gastrointestinal tract in a patient diagnosed with PLGE complicated with refractory to immunosuppressant treatment. H. pylori eradication should be considered in patients with PLGE complicated with H. pylori infection, without specific endoscopic finding or refractory to immunosuppressants.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Cirrose Hepática Biliar , Enteropatias Perdedoras de Proteínas , Idoso , Antibacterianos/uso terapêutico , Proteínas Sanguíneas/metabolismo , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Humanos , Imunossupressores/uso terapêutico , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/microbiologia , Enteropatias Perdedoras de Proteínas/sangue , Enteropatias Perdedoras de Proteínas/complicações , Enteropatias Perdedoras de Proteínas/tratamento farmacológico , Enteropatias Perdedoras de Proteínas/microbiologia
9.
Molecules ; 27(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35164000

RESUMO

Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, interfering with normal cellular signaling pathways. CagA plays an important role in the progression of GC by interacting with phosphatidylserine of the host cell membrane. Therefore, disrupting the CagA-phosphatidylserine connection using small molecules appears to be a promising therapeutic approach. In this report, we screened the natural compounds from ZINC database against the CagA protein using the bioinformatics tools. Hits were initially chosen based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, as well as other drug-like characteristics. To locate safe and effective hits, the PAINS filter, binding affinities estimation, and interaction analysis were used. Three compounds with high binding affinity and specificity for the CagA binding pocket were discovered. The final hits, ZINC153731, ZINC69482055, and ZINC164387, were found to bind strongly with CagA protein, with binding energies of -11.53, -10.67, and -9.21 kcal/mol, respectively, which were higher than that of the control compound (-7.25 kcal/mol). Further, based on binding affinity and interaction pattern, two leads (ZINC153731, ZINC69482055) were chosen for molecular dynamics (MD) simulation analysis. MD results showed that they displayed stability in their vicinity at 100 ns. This study suggested that these compounds could be used as possible inhibitors of CagA protein in the fight against GC. However, additional benchwork tests are required to validate them as CagA protein inhibitors.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Produtos Biológicos/farmacologia , Simulação por Computador , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Neoplasias Gástricas/tratamento farmacológico , Antígenos de Bactérias , Infecções por Helicobacter/microbiologia , Ensaios de Triagem em Larga Escala , Humanos , Simulação de Dinâmica Molecular , Estrutura Molecular , Neoplasias Gástricas/microbiologia
10.
J Microbiol Methods ; 192: 106393, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34919971

RESUMO

Due to the abuse of antibiotics, the prevalence of antibiotic resistant Helicobacter pylori strains continues to increase. Therefore, antibiotic resistance assessment is now essential in addition to general H. pylori diagnosis in medical institutions to fulfill clinicians administering effective antibiotic regimens. However, the conventional antibiotic resistance assessment methods, such as in vitro antibiotic susceptibility test and E-test, are skilled-staff dependent and time-consuming. The aim of this study was to establish an easy-operating TaqMan-MGB probe multiplex real-time PCR system for one-step detection of levofloxacin and clarithromycin resistance mutations with concurrent H. pylori infection diagnosis. Through the optimization of primers, probes and reaction buffers, this proposed system could accurately distinguish the recombinant plasmids with different mutation markers. More importantly, the diagnosis results of this detection system exhibited excellent consistence with the gold standard of gastric biopsy and Sanger sequencing on the detection of H. pylori infection and relevant antibiotic resistant strains, the Kappa values of which all exceeded 0.90. In addition, the results of this detection system could also be applied for the prevalence statistics of antibiotic resistance patterns for patients by age, gender and geographical location. This simple and rapid system should be beneficial for clinicians issuing personalized treatments according to the patient's H. pylori strains and avoid the abuse of antibiotics.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Helicobacter pylori/genética , Levofloxacino/farmacologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , DNA Girase/genética , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S/genética , RNA Ribossômico 23S/genética
11.
Int J Cancer ; 150(6): 928-940, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34664721

RESUMO

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.


Assuntos
Mucosa Gástrica/patologia , Microbioma Gastrointestinal/fisiologia , Mucosa Bucal/microbiologia , Lesões Pré-Cancerosas/etiologia , Neoplasias Gástricas/etiologia , Idoso , Estudos de Casos e Controles , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Metagenômica , Metaplasia , Pessoa de Meia-Idade
12.
Int J Cancer ; 150(1): 18-27, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449868

RESUMO

Helicobacter pylori (H. pylori) infection is considered the leading cause of gastric cancer. Gastric cancer is currently a common cancer with high incidence and mortality rates, but it is expected that the incidence rate will gradually decrease as the H. pylori infection prevalence decreases in the future. When evaluating the effectiveness of gastric cancer prevention strategies, it is essential to note the differences in long-term cumulative risks between H. pylori-infected and uninfected populations, but this has not yet been precisely evaluated. In our study, we aimed to estimate the cumulative incidence risks of developing gastric cancer from birth to 85 years among H. pylori-infected and uninfected populations by using population-based cancer registry data and birth year-specific H. pylori infection prevalence rates. Death from gastric cancer and other causes of death were considered in the estimations of the adjusted cumulative incidence risks stratified by sex and H. pylori infection status. After performing 5000 Monte Carlo simulations with repeated random sampling using observed cancer incidence in selected three prefectures (Fukui, Nagasaki, Yamagata) of prefectural population-based cancer registry in Japan, the mean adjusted cumulative incidence risk for gastric cancer in the H. pylori-infected population was 17.0% for males and 7.7% for females and 1.0% for males and 0.5% for females in the uninfected population. These results calculated with Japanese cancer registry data may be useful in considering and evaluating future prevention strategies for gastric cancer in Japan.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Método de Monte Carlo , Neoplasias Gástricas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Seguimentos , Infecções por Helicobacter/microbiologia , Humanos , Incidência , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/microbiologia , Adulto Jovem
13.
Dig Dis Sci ; 67(1): 208-215, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33559090

RESUMO

AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.


Assuntos
Amoxicilina/administração & dosagem , Esomeprazol/administração & dosagem , Gastrite , Infecções por Helicobacter , Levofloxacino/administração & dosagem , Ofloxacino/análogos & derivados , Adulto , Antibacterianos/administração & dosagem , Testes Respiratórios/métodos , China , Quimioterapia Combinada , Feminino , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Ofloxacino/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Resultado do Tratamento
14.
J Clin Pathol ; 75(2): 137-139, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33568425

RESUMO

To diagnose Helicobacter pylori (HP) infection and its related mucosal injuries requires the histopathological analysis of gastric biopsies. The move from glass slides interpretation towards digital pathology implies technical choices to maintain the performances of histopathological diagnosis. The intra-rater agreement in assessing gastritis diagnostic criteria between glass slides, low resolution and high resolution digital slides in the subject of the present study. One hundred gastric biopsies were re-assessed by a single digestive pathologist on glass slides and digitalised slides at low resolution (ie, x20 magnification and single focus without z-stack) and high resolution (ie, x40 magnification with seven focus levels and z-stack) about the criteria of the updated Sydney system and the detection of HP. Inter-analyses agreement were very good (Kappa values>0.81) for every criteria but slightly inferior (ie, Kappa values<0.9) comparing glass slides interpretations with low resolution digital slides-based ones. Indeed, some HP infections were misdiagnosed using x20 magnification histochemical stained digitalised slides (p<0.05). At the opposite, anti-HP immunohistochemistry slides and/or x40 magnification digitalisation permitted to maintain almost perfect concordance in diagnosis (Kappa value>0.9). As mentioned in current guidelines, a high resolution x40 magnification digitalisation must be favoured in order to avoid some misdetection of microorganisms as HP.


Assuntos
Gastrite/diagnóstico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Interpretação de Imagem Assistida por Computador , Microscopia , Estômago/microbiologia , Biópsia , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Imuno-Histoquímica , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Coloração e Rotulagem , Estômago/patologia
15.
J Investig Med ; 70(1): 73-78, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34341100

RESUMO

The clinical spectrum of autoimmune gastritis is silent in the early stages of the disease and no specific symptom is related to this entity. Although gastroscopic findings of this entity are well defined, data regarding colonoscopic findings are limited. The aims of this study were to determine the prevalence of colonoscopic findings and to explore factors that might affect these findings. This is a retrospective chart review of patients with autoimmune gastritis (n=240). Data regarding colonoscopic findings, serum gastrin and chromogranin A (CgA) levels and gastric histopathological results were extracted and compared with 550 patients positive for Helicobacter pylori and gastric atrophy. Control subjects had colonoscopy and gastroscopy with biopsies. Colorectal lesions were observed in 64 (26.6%) of patients with autoimmune gastritis and 36 (6.6%) patients had colorectal lesions in the control group (p<0.001). Serum gastrin (OR: 8.59, 95% CI 1.72 to 25.07, p<0.001) and CgA levels (OR: 6.79, 95% CI 0.41 to 27.26, p<0.001) were found as factors affecting the presence of colorectal carcinoma. Serum gastrin and CgA levels were also found as predictors for the presence of colorectal adenomas. There is a higher prevalence of colorectal neoplastic lesions in patients with autoimmune gastritis. Serum gastrin and CgA levels were found to be determinants of colorectal neoplastic lesions observed in patients. In the workup of these patients, serum gastrin and CgA levels may guide physicians for the demonstration of colorectal neoplastic lesions.


Assuntos
Cromogranina A/sangue , Colonoscopia , Neoplasias Colorretais/epidemiologia , Gastrinas/sangue , Gastrite/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Adulto , Idoso , Neoplasias Colorretais/diagnóstico por imagem , Feminino , Gastrite/epidemiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico por imagem , Prevalência , Estudos Retrospectivos
16.
Int J Cancer ; 150(2): 243-252, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34498732

RESUMO

Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population-based case-control study in Taixing, China (2010-2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47-2.63). Neither CagA-positive nor VacA-positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72-3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P-trend <.001). H. pylori showed nonsignificant effect modification (P-interaction = .385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy-related cancers and guide the prevention and control of AEGJ.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasias Esofágicas/epidemiologia , Junção Esofagogástrica/patologia , Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/microbiologia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/microbiologia , Feminino , Seguimentos , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
J Gastroenterol Hepatol ; 37(2): 291-300, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34569096

RESUMO

BACKGROUND: Two methods are used to evaluate gastritis: the updated Sydney system (USS) with pathology and Kyoto classification, a new endoscopy-based diagnostic criterion for which evidence is accumulating. However, the consistency of their results is unclear. This study investigated the consistency of their results. METHODS: Patients who underwent esophagogastroduodenoscopy and were evaluated for Helicobacter pylori infection for the first time were eligible. The association between corpus and antral USS scores (neutrophil activity, chronic inflammation, atrophy, and intestinal metaplasia) and Kyoto classification scores (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) was assessed. RESULTS: Seven-hundred-seventeen patients (mean age, 49.2 years; female sex, 57.9%; 450 H. pylori-positive and 267 H. pylori-negative patients) were enrolled. All endoscopic gastritis cases in the Kyoto classification were associated with high corpus and antral USS scores for neutrophil activity and chronic inflammation. A subanalysis was performed for H. pylori-positive patients. Regarding atrophy and intestinal metaplasia, endoscopic findings were associated with USS scores. Enlarged folds, nodularity, and diffuse redness were associated with high corpus USS scores for neutrophil activity and chronic inflammation, but with low antral USS scores for atrophy and intestinal metaplasia. The Kyoto classification scores were also associated with the pathological topographic distribution of neutrophil activity and intestinal metaplasia. CONCLUSIONS: Among H. pylori-positive individuals, endoscopic and pathological diagnoses were consistent with atrophy and intestinal metaplasia. Enlarged folds, nodularity, and diffuse redness were associated with pathological inflammation (neutrophil activity and chronic inflammation) of the corpus; however, they were inversely associated with pathological atrophy and intestinal metaplasia. The endoscopy-based Kyoto classification of gastritis partially reflects pathology.


Assuntos
Endoscopia Gastrointestinal , Gastrite , Estudos Transversais , Feminino , Gastrite/classificação , Gastrite/patologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
18.
Medicine (Baltimore) ; 100(49): e28062, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34889251

RESUMO

ABSTRACT: The study aimed to assess demographic, clinical, and endoscopic parameters in patients with predominant corporeal atrophic gastritis (CAG) and enterochromaffin-like cell hyperplasia suggestive for autoimmune etiology in comparison with patients presenting Helicobacter pylori atrophic gastritis limited to the gastric antrum (AAG).Demographical, clinical, and pathological data of consecutive patients who underwent an upper digestive endoscopy for bleeding screening risk, symptoms, or anemia in a single endoscopy unit were retrieved. The final study group included 63 patients with CAG and enterochromaffin-like cell hyperplasia on histology and a control group of 142 patients with AAG.Female patients were predominant in the group with CAG versus AAG (69.8% vs 46.4%, P = .002). Microcytic anemia (P < .001), but not macrocytic anemia (P = .14) was associated with CAG, the mean corpuscular volume of erythrocyte (MCV) (82.5 vs 86.5 fl, P = .01), the mean value of serum iron (11.8 vs 14.3 µmol/L, P = .02), and hemoglobin level (11.0 vs 12.7 g/dL P < .01) being significantly lower in patients with CAG versus AAG. Upper digestive endoscopies with no visible mucosal lesions (P = .01) were also more frequent in the patients with CAG, but there were not differences regarding digestive symptoms between groups. The linear regression models revealed that the low hemoglobin (P < .001) and low MCV (P = .03) are the independent variables that can predict CAG on histology, but not the serum iron level (P = .77)Consecutive patients investigated on endoscopy with CAG in comparison with those having AAG are more frequent female, they have microcytic anemia, and no mucosal lesions on endoscopy. The decreased hemoglobin level and low MCV, rather than the serum iron level are predictors for CAG versus AAG on histology in endoscopic population.


Assuntos
Mucosa Gástrica/patologia , Gastrite Atrófica/diagnóstico por imagem , Infecções por Helicobacter , Helicobacter pylori/isolamento & purificação , Hiperplasia/patologia , Endoscopia Gastrointestinal , Feminino , Gastrite Atrófica/sangue , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Hemoglobinas , Humanos , Revisões Sistemáticas como Assunto
19.
Medicine (Baltimore) ; 100(50): e27923, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34918639

RESUMO

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of bismuth pectin capsules and bismuth pectin granules in the first-line quadruple treatment of Helicobacter pylori (H. pylori). METHODS: This study was a multicenter, randomized, open-labelled controlled clinical trial. Patients with a H. pylori infection were randomized into 4 groups (1:1:1:1) and treated with a 14-day bismuth-containing quadruple therapy. The 4 groups received either bismuth potassium citrate capsules (220 mg), colloidal bismuth pectin capsules (200 mg), bismuth pectin granules (150 mg), or bismuth pectin granules (300 mg). The primary outcome was the eradication rate of H. pylori. The secondary outcomes included symptom improvement, patient compliance, and incidence of adverse events. This study was registered at ClinicalTrials.gov (NCT04209933). RESULTS: A total of 240 patients were included in this study, and 211 patients completed the follow-up. An intention-to-treat analysis showed that the H. pylori eradication rates of the 4 groups were 73.3%, 76.7%, 75.0%, and 71.7%, respectively. The per-protocol analysis showed that the H. pylori eradication rates of the 4 groups were 86.3%, 82.1%, 83.3%, and 86.0%. There was no significant difference among the 4 groups in the H. pylori eradication rate (P > .05). There were also no significant differences in the symptom improvement rate, overall adverse reaction rate, or patient compliance among the 4 groups. CONCLUSIONS: Bismuth pectin capsules and bismuth pectin granules had similar efficacy and safety for H. pylori eradication compared to bismuth potassium citrate. These data suggest that bismuth pectin can be an alternative to bismuth potassium citrate to eradicate H. pylori when using bismuth-containing quadruple therapy.


Assuntos
Antibacterianos/uso terapêutico , Bismuto/efeitos adversos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/uso terapêutico , Antibacterianos/efeitos adversos , Bismuto/uso terapêutico , Cápsulas/administração & dosagem , Quimioterapia Combinada , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Citrato de Potássio/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento
20.
Turk J Gastroenterol ; 32(12): 996-1002, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34876389

RESUMO

BACKGROUND: To determine the prevalence of Helicobacter pylori infection and the antibiotic susceptibility of H. pylori in patients after partial gastrectomy. METHODS: Patients who underwent gastroscopy from January 2009 to November 2017 and had a history of partial gastrectomy were retrospectively enrolled in the remnant stomach group. Contemporary non-gastrectomized patients with an endoscopic diagnosis of chronic gastritis were enrolled in the non-operated stomach group. The detection of H. pylori infection was performed by culture and histology. The in vitro antimicrobial susceptibility was examined by the agar dilution method on strains from gastric biopsies. RESULTS: In this study, a total of 728 gastrectomized and 5035 non-gastrectomized patients were included. There was a significantly lower prevalence of H. pylori infection in the gastric-remnant patients (8.65%) than in the non-gastrectomized patients (17.76%) (P < .001) with the diagnostic method of culture. In the gastric-remnant patients, the H. pylori strains had resistance rates to metronidazole, clarithromycin, levofloxacin, amoxicillin, and furazolidone of 100%, 20.63%, 22.22%, 0%, and 0%, respectively. In the nongastrectomized patients, H. pylori resistance to metronidazole, clarithromycin, levofloxacin, amoxicillin, and furazolidone was 90.49%, 24.61%, 21.70%, 0.22%, and 0.11%, respectively. Gastric-remnant patients had a significantly higher metronidazole resistance rate than non-gastrectomized patients (P = .005). Moreover, no significant changes in the resistance to 5 antibiotics were observed among the gastric-remnant patients from different age, gender, and surgical indication groups. CONCLUSION: Patients after partial gastrectomy showed a lower prevalence of H. pylori infection. Gastric-remnant patients were more likely to harbor metronidazole-resistant H. pylori strains.


Assuntos
Resistência Microbiana a Medicamentos , Gastrectomia/efeitos adversos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Feminino , Gastroscopia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prevalência , Estudos Retrospectivos , Adulto Jovem
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