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1.
N Engl J Med ; 382(5): 427-436, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-31995688

RESUMO

BACKGROUND: Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. METHODS: In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period. RESULTS: A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001). CONCLUSIONS: Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Inibidores da Bomba de Prótons/uso terapêutico , Neoplasias Gástricas/prevenção & controle , Adenoma/epidemiologia , Adenoma/etiologia , Adenoma/prevenção & controle , Adulto , Idoso , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/complicações , Humanos , Incidência , Estimativa de Kaplan-Meier , Lansoprazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , República da Coreia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/genética
2.
J Surg Oncol ; 121(3): 494-502, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31902137

RESUMO

BACKGROUND: Socioeconomic disparities in gastric cancer have been associated with differences in care and inferior outcomes. We evaluated the presentation, treatment, and survival for patients with gastric cancer (GC) in a metropolitan setting with a large African American population. METHODS: Retrospective cohort analysis of patients with GC (2003-2018) across a multi-hospital system was performed. Associations between socioeconomic and clinicopathologic data with the presentation, treatment, and survival were examined. RESULTS: Of 359 patients, 255 (71%) were African American and 104 (29%) Caucasian. African Americans were more likely to present at a younger age (64.0 vs 72.5, P < .001), have state-sponsored or no insurance (19.7% vs 6.9%, P = .02), reside within the lowest 2 quintiles for median income (67.4% vs 32.7%, P < .001), and have higher rates of Helicobacter pylori (14.9% vs 4.8%, P = .02). Receipt of multi-modality therapy was not impacted by race or insurance status. On multivariable analysis, only AJCC T class (HR 1.68) and node positivity (HR 2.43) remained significant predictors of disease-specific survival. CONCLUSION: Despite socioeconomic disparities, African Americans, and Caucasians with GC had similar treatment and outcomes. African Americans presented at a younger age with higher rates of H. pylori positivity, warranting further investigation into differences in risk factors and tumor biology.


Assuntos
Grupos de Populações Continentais/estatística & dados numéricos , Infecções por Helicobacter/complicações , Classe Social , Neoplasias Gástricas/mortalidade , Idoso , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Infecções por Helicobacter/virologia , Helicobacter pylori/isolamento & purificação , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/terapia , Taxa de Sobrevida , Estados Unidos
3.
Gene ; 726: 144173, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669639

RESUMO

A recent study published in GENE performed a meta-analysis on the relationship between genetic variant rs895819 in microRNA-27a and risk of stomach neoplasms, and the results indicated an association of rs895819 with increased risk of stomach neoplasms in heterogenous model among Chinese. However, the meta-analysis did not include one large sample size of study that met inclusion criteria. When including all related studies, our meta-analysis showed no significant association of rs895819 with stomach neoplasms risk in each different model in all population, Chinese and Europeans. Thus, pooling all related studies did not provide evidence on the association of rs895819 with increased risk of stomach neoplasms.


Assuntos
Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Genótipo , Humanos , MicroRNAs/genética , Fatores de Risco
4.
Int J Cancer ; 146(7): 1937-1949, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376289

RESUMO

Yes-associated protein (YAP) is a transcriptional coactivator that promotes cell proliferation, stem cell maintenance and tissue homeostasis. The YAP activity is primarily regulated through an inhibitory phosphorylation by the serine/threonine kinases of Hippo pathway. Here, we show that receptor tyrosine kinase (RTK) erythropoietin-producing hepatocellular receptor A2 (EphA2) interacts with and phosphorylates YAP protein, leading to stabilization, nuclear translocation and activation of YAP in gastric cancer (GC) cells. EphA2 induces chemotherapy-resistance by increasing YAP stability and nuclear YAP protein. Knockdown of YAP blocks EphA2-induced tumor growth in GC xenograft mouse models. Importantly, the coactivation of EphA2 and YAP is manifested in clinical human GC, and is related to GC recurrence. Thus, our results establish a novel EphA2-to-YAP pathway that drives GC growth, progression and therapy-resistance, targeting this pathway would be an efficient way for the treatment of GC, particularly chemotherapy-resistant GC.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Efrina-A2/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Camundongos , Modelos Biológicos , Fosforilação , Ligação Proteica , Transporte Proteico , Recidiva , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Medicine (Baltimore) ; 98(50): e18397, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852158

RESUMO

There are still many controversies about the characteristics and prognosis of gastric cardia cancer. We aimed to evaluate the clinical characteristics and outcome between cardia and noncardia cancer. Also, we evaluated the clinical outcome according to etiologic factors.We performed a retrospective cohort study of 92 patients with gastric cardia cancer from January 2003 to December 2013. The patients with noncardia cancer were selected as age- and sex-matched control.The frequencies of gastroesophageal reflux disease (GERD) and negative Helicobacter pylori infection without atrophy were significantly higher in gastric cardia cancers, but there was no difference in the frequency of obesity. The frequency of early gastric cancers was 40.0%, which was significantly lower than that of noncardia cancer. The rate of recurrence, disease-free survival, and overall survival duration were significantly lower in gastric cardia cancers (P < .01), even though there was no significant difference in the rate of curative resection (R0). In terms of the etiologic factors, there were no differences of disease prognosis, regardless of the presence of GERD, obesity, and H pylori infection with associated gastritis.Gastric cardia cancer showed distinct clinical characteristics and a negative prognostic impact compared with gastric noncardia cancer.


Assuntos
Adenocarcinoma/etiologia , Cárdia , Neoplasias Gástricas/etiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Estudos de Casos e Controles , Intervalo Livre de Doença , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/etiologia , Infecções por Helicobacter/epidemiologia , Humanos , Recidiva Local de Neoplasia/epidemiologia , Obesidade/epidemiologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia
6.
New Microbiol ; 42(4): 210-220, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31524946

RESUMO

Helicobacter pylori (H. pylori) is involved in the etiology of gastric cancer (GC). miRNAs are short RNAs that regulate gene expression by marking mRNAs for degradation. miRNAs are involved in tumorigenesis, metastasis, and cell proliferation. We aimed to investigate the miRNA expression profiles of tissues from H. pylori (+) and (-) GC patients. Forty GC patients, 20 H. pylori (+) and 20 H. pylori (-), and a healthy control group were included. The miRNA expression levels were investigated by microarrays and quantitative RT-PCR. We detected 9 upregulated and 4 downregulated miRNAs by microarray. We selected 5 upregulated and 5 downregulated miRNAs for the quantitative RT-PCR assay. The relative fold changes of miRNAs in the cancerous tissue and non-tumor mucosa specimens of H. pylori (+) GC patients for hsa-miR-194 were 4.24- and 3.83-fold higher, respectively, whereas the hsa-miR-145 expression levels were downregulated 0.33-fold and 0.43-fold, respectively, in the same group. The presence of H. pylori significantly upregulated hsa-miR-194 and downregulated hsa-miR-145 expression levels in H. pylori (+) GC cases, compared to H. pylori (-) GC cases. Regional differences in the virulence of H. pylori strains may also be involved in the up- or downregulation of miRNA expression levels.


Assuntos
Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter , Helicobacter pylori , MicroRNAs , Neoplasias Gástricas , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Humanos , MicroRNAs/metabolismo , Estudos Prospectivos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Turquia
7.
BMC Cancer ; 19(1): 920, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521128

RESUMO

BACKGROUND: Tumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear. This study aimed to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). METHODS: Using a prospective database containing 401 cases of GC, we evaluated TIL (cluster of differentiation 8 (CD8) expression) and TAM (cluster of differentiation 68 (CD68) expression) statuses via immunohistochemical staining. RESULTS: Compared with CD8+ TIL-negative cases (n = 196, 48.6%), CD8+ TIL-positive cases (n = 205, 51.1%) showed significantly better recurrence-free survival (RFS) [log-rank p<0.001; multivariate HR: 0.372; 95% confidence interval (CI): 0.239-0.579, p<0.001]. In contrast, compared with CD68+ TAM-negative cases (n = 217, 54.1%), CD68+ TAM-positive cases (n = 184, 45.9%) had significantly poor RFS [log-rank p<0.001; multivariate HR: 2.182; 95% CI: 1.435-3.318, p<0.001]. Thus, patients with a positive CD8+ TIL and negative CD68+ TAM status exhibited significantly increased RFS. Multivariate analysis demonstrated that CD8+ TILs and CD68+ TAMs may serve as independent prognostic markers for RFS. Incorporating CD8+ TIL and CD68+ TAM statuses into the AJCC TNM system generated a predictive model with better predictive accuracy for RFS. More importantly, patients with a positive TIL and negative TAM status showed a tendency of improved RFS after postoperative adjuvant chemotherapy (PAC). Similar results were obtained by overall survival (OS) analysis. CONCLUSIONS: CD8+ TIL and CD68+ TAM statuses were identified as independent prognostic factors that may be integrated into the current TNM staging system to refine risk stratification and to better predict the survival benefit from PAC in patients with GC. TRIAL REGISTRATION: The current controlled trial was registered at ClinicalTrials.gov (ID: NCT02327481 ) on December 30, 2014.


Assuntos
Antígeno B7-2/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Linfócitos T CD8-Positivos/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia
8.
Iran J Allergy Asthma Immunol ; 18(4): 393-401, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31522447

RESUMO

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.


Assuntos
Gastrite/etiologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Interleucina-8/genética , Polimorfismo Genético , Neoplasias Gástricas/etiologia , Alelos , Suscetibilidade a Doenças , Feminino , Gastrite/complicações , Gastrite/epidemiologia , Frequência do Gene , Genótipo , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Vigilância da População , Neoplasias Gástricas/epidemiologia , Tailândia/epidemiologia
9.
J Surg Oncol ; 120(7): 1137-1141, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31498442

RESUMO

BACKGROUND: Gastric cancer (GC) occasionally develops in the remnant stomach following pancreaticoduodenectomy (PD). In those who have undergone PD for adenocarcinoma, however, the interval and frequency of anastomotic GC are unknown. METHODS: We searched our institutional database for patients who had undergone PD for adenocarcinoma and subsequently developed GC between 1994 and 2018 and found six patients. We summarized the clinicopathologic features and prognosis of these patients with anastomotic GC. RESULTS: The median interval from PD to development of GC was 111.5 months. Four patients underwent curative resection of gastrojejunal anastomosis. Pathologic analysis showed signet ring cell carcinoma in four patients. The median overall survival after developing GC was 61 months. CONCLUSION: Our findings indicate that GC in the remnant stomach after PD is rare but can occur at gastrojejunostomy anastomosis after a prolonged period. Periodic and long-term follow-up +/- surveillance endoscopy to facilitate early detection of GC in the remnant stomach is recommended, particularly for symptomatic patients. Recognition of the anastomotic tumor as a second primary and not a pancreatic ductal adenocarcinoma recurrence/metastasis is crucial in the optimal treatment of these patients, as curative resection of early-stage GC may prolong survival.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Neoplasias Gástricas/etiologia , Adenocarcinoma/patologia , Idoso , Carcinoma Ductal Pancreático/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de Sobrevida
10.
Helicobacter ; 24 Suppl 1: e12642, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31486241

RESUMO

Gastric cancer is the third deadliest cancer in the world, and the absolute number of cases is increasing every year due to aging and growing of high-risk populations. This disease is a consequence of the complex interaction of microbial agents, with environmental and host factors, resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways. Despite the advances in our understanding of carcinogenesis, there are still reduced therapeutic options for patients with gastric cancer. In recent years, genomic analyses of gastric tumors have emphasized their molecular heterogeneity. The distinction of gastric cancer molecular subtypes may be a key to identify novel therapeutic targets, to predict patient outcome and response to therapy, and to guide early diagnosis strategies. In this review, we summarize the most recent updates on the relationship between microbial agents and gastric cancer, in particular, Helicobacter pylori, the non-H pylori microbiome, and Epstein-Barr virus. We also highlight the main advances made in the past year regarding the molecular characterization of gastric cancer, especially the signatures with potential clinical utility.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Helicobacter/complicações , Interações Hospedeiro-Patógeno , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Pesquisa Biomédica/tendências , Humanos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/fisiopatologia
11.
Anticancer Res ; 39(9): 4589-4596, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519555

RESUMO

Despite recent advances in the treatment of gastric cancer, mortality related to this disease is still substantial. Surgery and chemotherapy represent the cornerstones of patient management. Targeted treatments that include anti-angiogenic agents and the advent of immunotherapies can contribute to improved patient prognosis. Herein, we present an Austrian consensus on the systemic treatment of patients with gastric adenocarcinoma and lower gastroesophageal junction, including those with human epidermal growth factor receptor 2 (HER2)-positive disease. The consensus considers the curative setting, as well as first-line to late-line systemic treatment options in the palliative setting. For HER2-positive disease, first-line and second-line therapies are discussed, as well as HER2 testing. Potential future therapies are also listed, with a focus on anti-angiogenic treatments and checkpoint inhibition, that might provide a further step forward in the management of patients with gastric cancer.


Assuntos
Adenocarcinoma/terapia , Algoritmos , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Áustria , Terapia Combinada , Consenso , Gerenciamento Clínico , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologia
12.
Cancer Treat Rev ; 79: 101889, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31445415

RESUMO

The overall 5-year survival of gastric cancer (GC) has change only little in the last decades and it remains the fifth leading cause of cancer-related death worldwide. However, in the past few years a more effective combination chemotherapy has raised the bar of curability of about 10% in resectable disease. Morever, a deeper knowledge of GC biology have unveiled biomarkers to help personalize adjunctive treatments in patients candidate to surgery. Despite a plateau in efficacy of fist-line treatment, incremental survival advantages have been recorded in unresectable advanced disease. The growing number of effective drugs in second and later lines along with a more judicious delivery of cytotoxics and early supportive interventions have enabled more patients to proceed beyond first-line. The continuum of care has become a reality in a considerable proportion of patients that offer opportunities to improve outcomes. Finally, the advent of the immune checkpoint inhibitors has brought great expectations in molecularly-defined subset of patients. This Review summarizes the state-of-the art in the management of GC together with novel concepts that have entered clinical development with the potential of change practice in the foreseeable future.


Assuntos
Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Animais , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Quimioterapia Combinada , Humanos , Medicina de Precisão , Neoplasias Gástricas/etiologia , Pesquisa Médica Translacional , Resultado do Tratamento
13.
World J Gastroenterol ; 25(30): 4105-4124, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31435167

RESUMO

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.


Assuntos
Citocinas/genética , Mucosa Gástrica/patologia , Infecções por Helicobacter/epidemiologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Atrofia/epidemiologia , Atrofia/etiologia , Atrofia/patologia , Progressão da Doença , Mucosa Gástrica/microbiologia , Predisposição Genética para Doença , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Metaplasia/epidemiologia , Metaplasia/etiologia , Metaplasia/patologia , Polimorfismo de Nucleotídeo Único , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia
14.
Asian Pac J Cancer Prev ; 20(7): 2177-2180, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350982

RESUMO

Background: In the recent years, hepatitis B virus (HBV) infection has been considered as a risk factor for gastric cancer, but further studies are required to confirm these claim. The present study was aimed to evaluate the correlation between gastric pathology (precancerous and cancerous conditions) with HBV infection in Helicobacter pylori (H. pylori) positive or negative patients. Methods: In this cross-sectional study, 728 patients under endoscopy examination in Yazd Shaheed Sadoughi Hospital between 2017 and 2018 were participated. Histopathological analysis was performed on gastric specimens. Hepatitis B surface antigen (HBsAg) in sera was detected by the enzyme-linked immunosorbent assay (ELISA). The relationship between gastric pathology and HBV infection were explored by logistic regression analysis. Results: Of 728 patients, HBsAg and H. pylori infection were detected in 83 and 408 patients, respectively. Sixty nine patients were co-infected with H. pylori/HBV. H. pylori infection detected in patients with HbsAg positive significantly more than those were negative for HbsAg (p=0.029). None of HBV/H. pylori co-infected patients did not have normal gastric tissue. A significant difference was seen in histopathology of gastric tissue between HBsAg positive patients with and without H. pylori infection (p<0.0001). The HBsAg was associated with histopathology of gastric (OR=21.56, 95℅CI=7.070-65.741, p<0.001) and as a risk factor for gastritis (OR=12.457, 95℅CI= 3.007-51.614, P=0.001) but no cancer (OR=2.127, 95℅CI=0.242-18.704, P=0.496). Conclusion: The HBV infection alone is associated with some precancerous lesions but is not correlated with gastric cancer. It can increase development of premalignant conditions and carcinoma significantly in H. pylori positive patients.


Assuntos
Coinfecção/epidemiologia , Gastrite/patologia , Infecções por Helicobacter/complicações , Hepatite B/epidemiologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Estômago/patologia , Idoso , Coinfecção/virologia , Estudos Transversais , Feminino , Seguimentos , Gastrite/etiologia , Infecções por Helicobacter/virologia , Helicobacter pylori/isolamento & purificação , Hepatite B/virologia , Vírus da Hepatite B/isolamento & purificação , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/etiologia , Prognóstico , Fatores de Risco , Estômago/virologia , Neoplasias Gástricas/etiologia
15.
World J Gastroenterol ; 25(26): 3344-3358, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341360

RESUMO

Gastroduodenal disease (GDD) was initially thought to be uncommon in Africa. Amongst others, lack of access to optimal health infrastructure and suspicion of conventional medicine resulted in the reported prevalence of GDD being significantly lower than that in other areas of the world. Following the increasing availability of flexible upper gastro-intestinal endoscopy, it has now become apparent that GDD, especially peptic ulcer disease (PUD), is prevalent across the continent of Africa. Recognised risk factors for gastric cancer (GCA) include Helicobater pylori (H. pylori), diet, Epstein-Barr virus infection and industrial chemical exposure, while those for PUD are H. pylori, non-steroidal anti-inflammatory drug (NSAID)-use, smoking and alcohol consumption. Of these, H. pylori is generally accepted to be causally related to the development of atrophic gastritis (AG), intestinal metaplasia (IM), PUD and distal GCA. Here, we perform a systematic review of the patterns of GDD across Africa obtained with endoscopy, and complement the analysis with new data obtained on pre-malignant gastric his-topathological lesions in Accra, Ghana which was compared with previous data from Maputo, Mozambique. As there is a general lack of structured cohort studies in Africa, we also considered endoscopy-based hospital or tertiary centre studies of symptomatic individuals. In Africa, there is considerable heterogeneity in the prevalence of PUD with no clear geographical patterns. Furthermore, there are differences in PUD within-country despite universally endemic H. pylori infection. PUD is not uncommon in Africa. Most of the African tertiary-centre studies had higher prevalence of PUD when compared with similar studies in western countries. An additional intriguing observation is a recent, ongoing decline in PUD in some African countries where H. pylori infection is still high. One possible reason for the high, sustained prevalence of PUD may be the significant use of NSAIDs in local or over-the-counter preparations. The prevalence of AG and IM, were similar or modestly higher over rates in western countries but lower than those seen in Asia. . In our new data, sampling of 136 patients in Accra detected evidence of pre-malignant lesions (AG and/or IM) in 20 individuals (14.7%). Likewise, the prevalence of pre-malignant lesions, in a sample of 109 patients from Maputo, were 8.3% AG and 8.3% IM. While H. pylori is endemic in Africa, the observed prevalence for GCA is rather low. However, cancer data is drawn from country cancer registries that are not comprehensive due to considerable variation in the availability of efficient local cancer reporting systems, diagnostic health facilities and expertise. Validation of cases and their source as well as specificity of outcome definitions are not explicit in most studies further contributing to uncertainty about the precise incidence rates of GCA on the continent. We conclude that evidence is still lacking to support (or not) the African enigma theory due to inconsistencies in the data that indicate a particularly low incidence of GDD in African countries.


Assuntos
Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/epidemiologia , Úlcera Péptica/epidemiologia , Neoplasias Gástricas/epidemiologia , Endoscopia Gastrointestinal , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/etiologia , Gana/epidemiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/etiologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Metaplasia , Úlcera Péptica/diagnóstico , Úlcera Péptica/etiologia , Prevalência , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologia
16.
Ann Hematol ; 98(8): 1981-1987, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177299

RESUMO

Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45-1.33), 0.65 (0.30-1.39), 1.03 (0.38-2.79), and 0.84 (0.22-3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30-3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00-3.86), 1.92 (0.74-4.95), and 5.80 (1.12-30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/patogenicidade , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Carcinogênese/patologia , Estudos de Casos e Controles , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/complicações , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/fisiologia , Humanos , Japão , Modelos Logísticos , Linfoma de Zona Marginal Tipo Células B/etiologia , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/microbiologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/microbiologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pepsinogênio A/sangue , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
17.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(3): 451-458, 2019 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-31209416

RESUMO

OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION: EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , China , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Estudos Retrospectivos , Neoplasias Gástricas/etiologia
18.
Eur J Epidemiol ; 34(8): 753-763, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152367

RESUMO

Current experimental and epidemiological studies provide inconsistent evidence toward the association between tea consumption and cancer incidence. We investigated whether tea consumption was associated with the incidence of all cancers and six leading types of cancer (lung cancer, stomach cancer, colorectal cancer, liver cancer, female breast cancer and cervix uteri cancer) among 455,981 participants aged 30-79 years in the prospective cohort China Kadoorie Biobank. Tea consumption was assessed at baseline (2004-2008) with an interviewer-administered questionnaire. Cancer cases were identified by linkage to the national health insurance system. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the present population, daily tea consumers were more likely to be current smokers and daily alcohol consumers. 22,652 incident cancers occurred during 10.1 years follow-up (5.04 cases/1000 person-years). When we restricted analyses to non-smokers and non-excessive alcohol consumers to minimize confounding, tea consumption was not associated with all cancers (daily consumers who added tea leaves > 4.0 g/day vs. less-than-weekly consumers: HR, 1.03; 95%CI, 0.93-1.13), lung cancer (HR, 1.08; CI, 0.84-1.40), colorectal cancer (HR, 1.08; CI, 0.81-1.45) and liver cancer (HR, 1.08; CI, 0.75-1.55), yet might be associated with increased risk of stomach cancer (HR, 1.46; CI, 1.07-1.99). In both less-than-daily and daily tea consumers, all cancer risk increased with the amount of tobacco smoked or alcohol consumed. Our findings suggest tea consumption may not provide preventive effect against cancer incidence.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Cafeína/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/etiologia , Medição de Risco/métodos , Chá/efeitos adversos , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , População Rural , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Fumar Tabaco/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia
19.
BMC Cancer ; 19(1): 545, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174492

RESUMO

BACKGROUND: Geospatial technology has facilitated the discovery of disease distributions and etiology and helped target prevention programs. Globally, gastric cancer is the leading infection-associated cancer, and third leading cause of cancer mortality worldwide, with marked geographic variation. Central and South America have a significant burden, particularly in the mountainous regions. In the context of an ongoing population-based case-control study in Central America, our aim was to examine the spatial epidemiology of gastric cancer subtypes and H. pylori virulence factors. METHODS: Patients diagnosed with gastric cancer from 2002 to 2013 in western Honduras were identified in the prospective gastric cancer registry at the principal district hospital. Diagnosis was based on endoscopy and confirmatory histopathology. Geospatial methods were applied using the ArcGIS v10.3.1 and SaTScan v9.4.2 platforms to examine regional distributions of the gastric cancer histologic subtypes (Lauren classification), and the H. pylori CagA virulence factor. Getis-Ord-Gi hot spot and Discrete Poisson SaTScan statistics, respectively, were used to explore spatial clustering at the village level (30-50 rural households), with standardization by each village's population. H. pylori and CagA serologic status was determined using the novel H. pylori multiplex assay (DKFZ, Germany). RESULTS: Three hundred seventy-eight incident cases met the inclusion criteria (mean age 63.7, male 66.3%). Areas of higher gastric cancer incidence were identified. Significant spatial clustering of diffuse histology adenocarcinoma was revealed both by the Getis-Ord-GI* hot spot analysis (P-value < 0.0015; range 0.00003-0.0014; 99%CI), and by the SaTScan statistic (P-value < 0.006; range 0.0026-0.0054). The intestinal subtype was randomly distributed. H. pylori CagA had significant spatial clustering only in association with the diffuse histology cancer hot spot (Getis-Ord-Gi* P value ≤0.001; range 0.0001-0.0010; SaTScan statistic P value 0.0085). In the diffuse gastric cancer hot spot, the lowest age quartile range was 21-46 years, significantly lower than the intestinal cancers (P = 0.024). CONCLUSIONS: Geospatial methods have identified a significant cluster of incident diffuse type adenocarcinoma cases in rural Central America, suggest of a germline genetic association. Further genomic and geospatial analyses to identify potential spatial patterns of genetic, bacterial, and environmental risk factors may be informative.


Assuntos
Saúde da População Rural , Neoplasias Gástricas/epidemiologia , Idoso , Estudos de Casos e Controles , América Central/epidemiologia , Suscetibilidade a Doenças , Feminino , Geografia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Análise Espacial , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia
20.
Dis Esophagus ; 32(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31111880

RESUMO

Gastric conduit used for reconstruction after esophagectomy for cancer has the potential to develop a metachronous neoplasm known as gastric tube cancer (GTC). The aim of this study was to review literature and evaluate outcomes and possible treatment strategies for GTC. A comprehensive systematic literature search was conducted using PubMed, EMBASE, Scopus, and the Cochrane Library Central Register of Controlled Trials. No restriction was set for the type of publication, number, age, or sex of the patients. The search was limited to articles in English. Characteristics of esophageal cancer (EC) and its treatment and GTC and its treatment were analyzed. A total of 28 studies were analyzed, 12 retrospective analyses and 16 case reports, involving 229 patients with 250 GTCs in total. The majority of ECs (88.2%) were squamous cell carcinomas. In 120 patients (52.4%) a posterior mediastinal reconstructive route was used when esophagectomy was performed. The mean interval between esophagectomy and diagnosis of GTC was 55.8 months, with a median interval of 56.8 months (4-236 months). One hundred and twenty-four GTCs (49.6%) were located in the lower part of the gastric tube. One hundred and forty patients were endoscopically treated. Eighty-five patients underwent surgery. Thirty-six total gastrectomies with lymphadenectomy with colon or jejunal interposition were performed. Forty-three subtotal gastrectomies and 6 wedge resections were performed. The main reported postoperative complications were anastomotic leak, vocal cord palsy, and respiratory failure. Twenty-five patients were treated with palliative chemotherapy. Three-year survival rates were 69.3% for endoscopically treated patients, 58.8% for surgically resected patients, and 4% for patients who underwent palliative treatment. The feasibility of endoscopic resections in patients diagnosed with superficial GTC has been reported. Surgical treatment represented the preferred treatment method in operable patients with locally invasive tumor. Patients treated with conservative therapy have a scarce prognosis. The development of GTC should be taken into consideration during the extended follow-up of patients undergoing esophagectomy for cancer. Total gastrectomy plus lymphadenectomy should be considered the preferred treatment modality in operable patients with locally invasive tumor, when endoscopy is contraindicated. Long-term yearly endoscopic follow-up is recommended.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Intubação Gastrointestinal/efeitos adversos , Segunda Neoplasia Primária/etiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Gástricas/etiologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/patologia , Esofagectomia/instrumentação , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/cirurgia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
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