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Clyne M, Ó Cróinín T. Pathogenicity and virulence of Helicobacter pylori: A paradigm of chronic infection. Virulence 2025; 16:2438735. [PMID: 39725863 DOI: 10.1080/21505594.2024.2438735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 11/18/2024] [Accepted: 12/02/2024] [Indexed: 12/28/2024] Open
Abstract
Infection with Helicobacter pylori is one of the most common infections of mankind. Infection typically occurs in childhood and persists for the lifetime of the host unless eradicated with antimicrobials. The organism colonizes the stomach and causes gastritis. Most infected individuals are asymptomatic, but infection also causes gastric and duodenal ulceration, and gastric cancer. H. pylori possesses an arsenal of virulence factors, including a potent urease enzyme for protection from acid, flagella that mediate motility, an abundance of outer membrane proteins that can mediate attachment, several immunomodulatory proteins, and an ability to adapt to specific conditions in individual human stomachs. The presence of a type 4 secretion system that injects effector molecules into gastric cells and subverts host cell signalling is associated with virulence. In this review we discuss the interplay of H. pylori colonization and virulence factors with host and environmental factors to determine disease outcome in infected individuals.
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Affiliation(s)
- Marguerite Clyne
- School of Medicine, University College Dublin, Dublin, Ireland
- The Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Tadhg Ó Cróinín
- The Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
- School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
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Li Z, Lu Y, Wang L, Shi L, Wang T. Reactive oxygen species-dependent nanomedicine therapeutic modalities for gastric cancer. NANOSCALE ADVANCES 2025; 7:3210-3227. [PMID: 40308560 PMCID: PMC12038724 DOI: 10.1039/d5na00321k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2025] [Accepted: 04/15/2025] [Indexed: 05/02/2025]
Abstract
Reactive oxygen species (ROS) play a double-edged role in gastric cancer (GC). Higher levels of ROS in tumor cells compared to normal cells facilitate tumor progression. Once ROS concentrations rise rapidly to toxic levels, they cause GC cell death, which is instead beneficial for GC treatment. Based on these functions, nano-delivery systems taking the therapeutic advantages of ROS have been widely employed in tumor therapy in recent years, overcoming the drawbacks of conventional drug delivery techniques, such as non-specific systemic effects. In this review, the precise impacts of ROS on GC have been detailed, along with ROS-based nanomedicine therapeutic schemes. These strategies mainly focused on the use of excess ROS in the tumor microenvironment for controlled drug release and a substantial enhancement of ROS concentrations for tumor killing. The challenges and opportunities for the advancement of these anticancer therapies are also emphasized.
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Affiliation(s)
- Zhiyan Li
- Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Nanjing 210008 China
| | - Yanjun Lu
- Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Nanjing 210008 China
| | - Lulu Wang
- Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Nanjing 210008 China
| | - Liuyi Shi
- Yangzhou University Medical College Yangzhou 225001 China
| | - Tao Wang
- Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Nanjing 210008 China
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Wu Z, Tang Y, Tang M, Wu Z, Xu Y. The relationship between the eradication of Helicobacter pylori and the occurrence of stomach cancer: an updated meta-analysis and systemic review. BMC Gastroenterol 2025; 25:278. [PMID: 40259215 PMCID: PMC12010618 DOI: 10.1186/s12876-025-03886-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Accepted: 04/11/2025] [Indexed: 04/23/2025] Open
Abstract
OBJECTIVE Helicobacter pylori (H. pylori) are classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC), highlighting its well-established role in gastric carcinogenesis. While previous studies and systematic reviews suggest that H. pylori eradication may lower the incidence and mortality of gastric cancer, the evolving body of evidence necessitates continual reassessment. In light of newly available data, we conducted a comprehensive meta-analysis to evaluate the association between H. pylori eradication therapy and gastric cancer risk, aiming to strengthen the evidence base and inform clinical decision-making. METHOD We systematically searched the Cochrane Library, PubMed, Web of Science, and Embase up to December 2024, including only randomized controlled trials (RCTs) while excluding non-RCT studies. The target population comprised adults diagnosed with H. pylori infection who were either healthy or had previously undergone gastrectomy for gastric tumors. Eradication therapy served as the intervention, while placebo was the control. Eligible studies had a treatment duration exceeding seven days and a follow-up period of more than three years. The Cochrane risk-of-bias tool was used to assess methodological quality, and effect estimates were expressed as relative risk (RR) and the number needed to treat (NNT). OUTCOMES A total of 11 RCTs encompassing 104,786 individuals were analyzed. The meta-analysis revealed that H. pylori eradication significantly reduced gastric cancer risk (RR: 0.61; 95% CI: 0.47-0.79; NNT = 332). Subgroup analysis indicated that among healthy adults, the relative risk (RR) for the occurrence of gastric cancer was 0.67 (95% CI: 0.48-0.93; NNT = 476). In individuals who had undergone endoscopic mucosal resection, the reduction was even more pronounced (RR: 0.51; 95% CI: 0.36-0.71; NNT = 21). Although stomach cancer-specific mortality showed a slight decline (RR: 0.84; 95% CI: 0.69-1.01), all-cause mortality remained statistically unchanged (RR: 1.00; 95% CI: 0.89-1.13). CONCLUSION Our findings support H. pylori eradication as an effective strategy for reducing gastric cancer incidence, particularly in East Asian populations. While the effect on overall mortality remains inconclusive, the observed reduction in gastric cancer-related mortality highlights the potential clinical significance of eradication therapy as a preventive measure. Further well-designed, long-term studies are warranted to reinforce the evidence base and optimize clinical recommendations.
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Affiliation(s)
- Zhouhan Wu
- Guangxi University of Chinese Medicine, Nanning, 530200, China
| | - Yi Tang
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), 54 Youdian Road, Hangzhou, 310006, Zhejiang, China
| | - Meiwen Tang
- Guangxi University of Chinese Medicine, Nanning, 530200, China
| | - Zhoutong Wu
- Guangxi University of Chinese Medicine, Nanning, 530200, China
| | - Yonghui Xu
- Guangxi University of Chinese Medicine, Nanning, 530200, China.
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Wu Y, Zhang K, Zheng Y, Jin H. A review of potential mechanisms and treatments of gastric intestinal metaplasia. Eur J Gastroenterol Hepatol 2025; 37:383-394. [PMID: 39975991 DOI: 10.1097/meg.0000000000002903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Gastric intestinal metaplasia (GIM) is a pathological process where gastric mucosal epithelial cells are replaced by intestinal-type cells, serving as a precursor lesion for gastric cancer. This transformation involves various genetic and environmental factors, affecting key genes and signaling pathways. Recent research has revealed complex mechanisms, including changes in gene expression, abnormal signaling pathway activation, and altered cell behavior. This review summarizes the latest research on GIM, discussing its pathogenesis, current treatment strategies, and potential efficacy of emerging approaches like gene editing, microbiome interventions, and integrative medicine. By exploring these strategies, we aim to provide more effective treatments for GIM and reduce gastric cancer incidence. The review also highlights the importance of interdisciplinary studies in understanding GIM mechanisms and improving treatment strategies.
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Affiliation(s)
- Yueyao Wu
- Department of Gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Wu Z, Wang X, Shi S, Kong D, Ren C, Bian L, Gu Y, An F, Zhan Q, Yan C, Hu C, Chen Y, Jiang R, Chen J. Heterogeneity of T cells regulates tumor immunity mediated by Helicobacter pylori infection in gastric cancer. BMC Cancer 2025; 25:567. [PMID: 40155861 PMCID: PMC11954285 DOI: 10.1186/s12885-025-13957-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 03/17/2025] [Indexed: 04/01/2025] Open
Abstract
The impact of Helicobacter pylori (H. pylori) status on gastric cancer survival remains unclear. In this study, we conducted a prognostic analysis of 488 gastric cancer patients and performed single-cell RNA sequencing (scRNA-seq) on 18,717 T cells from six tumor samples with varying H. pylori statuses. Our findings revealed that gastric cancer patients with H. pylori infection had significantly longer survival times compared to those with negative H. pylori status. After unsupervised re-clustering of T cells based on scRNA-seq data, we identified ten CD4+ and twelve CD8+ clusters. Among them, four CD8+ T cell clusters exhibited distinct distributions based on H. pylori infection status. One cluster, marked by CXCL13, showed high levels of IFNG and GZMB in H. pylori-infected patients, while another cluster, which expressed immune suppression related genes like AREG and PTGER2, was predominantly comprised of cells from non-infected patients. High PTGER2 expression was significantly associated with worse prognosis in patients with high CD8 expression. These insights advance our understanding of H. pylori's influence on T cell responses in gastric cancer, aiding in treatment and prognostic strategies.
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Affiliation(s)
- Zhisheng Wu
- School of Chemistry and Chemical Engineering, Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Medical School, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
| | - Xinya Wang
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China
| | - Shujing Shi
- Department of Rehabilitation, School of Sport and Health, Nanjing Sport Institute, Nanjing, China
| | - Deyuan Kong
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Chuanli Ren
- Department of Laboratory Medicine, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Lijun Bian
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yuanliang Gu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Fangmei An
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China
- Department of Gastroenterology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Qiang Zhan
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China
- Department of Gastroenterology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Caiwang Yan
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Chupeng Hu
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
| | - Yun Chen
- School of Chemistry and Chemical Engineering, Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Medical School, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China.
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
- Research center for clinical oncology, Jiangsu Cancer Hospital, the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
| | - Runqiu Jiang
- Jiangsu Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
| | - Jinfei Chen
- Department of Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
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Jia YP, Liu DC, Cao TL, Jiang HZ, Li T, Li Y, Ding X. Advances and global trends of precancerous lesions of gastric cancer: A bibliometric analysis. World J Gastrointest Oncol 2025; 17:102111. [PMID: 40092937 PMCID: PMC11866257 DOI: 10.4251/wjgo.v17.i3.102111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/22/2024] [Accepted: 12/30/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Precancerous lesions of gastric cancer (PLGC) represent a critical pathological stage in the development of intestinal gastric cancer. Early detection and diagnosis are key to reducing the incidence of gastric cancer. Substantial advancements have been made in PLGC research in recent years, making it necessary to provide updated reviews using bibliometric methods. We hypothesize that this review will identify emerging trends, key research areas, and gaps in PLGC research, providing insights that could guide future studies and enhance prevention strategies. AIM To comprehensively review the current state of research on PLGC, examining development trends and research hotspots. METHODS We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database. We employed Software, including VOSviewer, CiteSpace, R software, and SCImago Graphica, to map scientific networks and visualize knowledge trends in terms of publication volume, countries/regions, institutions, journals, authors, and keywords. RESULTS A total of 4097 articles were included, and overall publication volume showed an increasing trend. Over the past two decades, China published the most articles, followed by the United States, Japan, South Korea, and Italy. Among the top 10 contributors, the United States ranked highest in institutions, authors, and citations and demonstrated the strongest international collaboration. Research keywords in this field were clustered into three main categories: Risk factors, pathogenesis, and diagnosis and treatment. Pathogenesis and molecular biomarkers remain key areas of focus. Future research should explore the mechanisms of gut microbiota, immune microenvironment, metabolic reprogramming, and epigenetics. Advanced technologies, including single-cell sequencing, spatially resolved analysis, multi-omics approaches, artificial intelligence, and machine learning, will likely accelerate in-depth investigations of PLGC. CONCLUSION PLGC research has rapidly developed in recent years, gaining considerable attention. This bibliometric analysis reveals research state and emerging trends over the past 20 years, providing insights for future studies.
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Affiliation(s)
- Yuan-Ping Jia
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Dian-Chun Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Ting-Lan Cao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Hui-Zhong Jiang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Tao Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yuan Li
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xia Ding
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
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Fu Q, Yu H, Liu M, Chen L, Chen W, Wang Z, Li W. Effect of Helicobacter pylori eradication on gastric cancer risk in patients with intestinal metaplasia or dysplasia: a meta-analysis of randomized controlled trials. Front Microbiol 2025; 16:1530549. [PMID: 40143868 PMCID: PMC11938427 DOI: 10.3389/fmicb.2025.1530549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 02/18/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Observational studies suggest that Helicobacter pylori (H. pylori) is associated with an increased risk of gastric cancer, yet the effect of H. pylori eradication on gastric cancer risk in patients with intestinal metaplasia (IM) or dysplasia remains controversial. The purpose of this study was to summarize the evidence from randomized controlled trials (RCTs) investigating H. pylori eradication on gastric cancer risk in patients with IM or dysplasia to determine the evidence base. METHODS PubMed, Embase, Cochrane Library, Web of science and China National Knowledge Internet database were searched for RCTs published through May 2024 in adults with IM or dysplasia comparing the risk of gastric cancer following H. pylori eradication versus no eradication therapy. Relative risk (RR) with its 95% confidence interval (CI) using random-effects model were employed for the effect estimate. Sensitivity, meta-regression, and subgroup analyses were also calculated. RESULTS Sixteen RCTs involving 15,027 patients with IM or dysplasia met the inclusion criteria. In a pooled analysis, H. pylori eradication resulted in a 45% reduction in RR for gastric cancer risk relative to no eradication (RR: 0.55; 95% CI: 0.46-0.67; p < 0.001). H. pylori eradication significantly reduced the risk of gastric cancer in patients with dysplasia (RR: 0.51; 95% CI: 0.32-0.82; p = 0.005), and IM (RR: 0.61; 95% CI: 0.40-0.93; p = 0.022). Further, if the study conducted in countries other than those in Asia, sample size <500, percentage of male <50.0%, follow-up duration <5.0 years, and low study quality, then there was no significant association between H. pylori eradication and a decreased risk of gastric cancer. CONCLUSION H. pylori eradication is protective against gastric cancer in patients with IM or dysplasia. SYSTEMATIC REVIEW REGISTRATION INPLASY202530010, https://inplasy.com/.
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Affiliation(s)
- Qiang Fu
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Huidong Yu
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Ming Liu
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Liang Chen
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Weiyang Chen
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Ziyi Wang
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenya Li
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China
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Ford AC, Yuan Y, Park JY, Forman D, Moayyedi P. Eradication Therapy to Prevent Gastric Cancer in Helicobacterpylori-Positive Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies. Gastroenterology 2025:S0016-5085(25)00041-1. [PMID: 39824392 DOI: 10.1053/j.gastro.2024.12.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/12/2024] [Accepted: 12/24/2024] [Indexed: 01/20/2025]
Abstract
BACKGROUND AND AIMS Screening for, and treating, Helicobacter pylori in the general population or patients with early gastric neoplasia could reduce incidence of, and mortality from, gastric cancer. We updated a meta-analysis of randomized controlled trials (RCTs) examining this issue. METHODS We searched the literature through October 4, 2024, identifying studies examining effect of eradication therapy on incidence of gastric cancer in H pylori-positive adults without gastric neoplasia at baseline or H pylori-positive patients with gastric neoplasia undergoing endoscopic mucosal resection (EMR) in either RCTs or observational studies. The control arm received placebo or no eradication therapy in RCTs and no eradication therapy in observational studies. Follow-up was ≥2 years. We estimated relative risks (RR) of gastric cancer incidence and mortality. RESULTS Eleven RCTs and 13 observational studies were eligible. For RCTs, RR of gastric cancer was lower with eradication therapy in healthy H pylori-positive individuals (8 RCTs, 0.64; 95% confidence interval [CI], 0.48-0.84) and H pylori-positive patients with gastric neoplasia undergoing EMR (3 RCTs, 0.52; 95% CI, 0.38-0.71). RR of death from gastric cancer was lower with eradication therapy in healthy H pylori-positive individuals (5 RCTs, 0.78; 95% CI, 0.62-0.98). In observational studies, RR of future gastric cancer was lower with eradication therapy in H pylori-positive subjects without gastric neoplasia at baseline (11 studies, 0.56; 95% CI, 0.43-0.73) and H pylori-positive patients with gastric neoplasia undergoing EMR (2 studies, 0.19; 95% CI, 0.06-0.61). CONCLUSIONS This meta-analysis provides further evidence that administering eradication therapy prevents gastric cancer in H pylori-positive individuals, with consistency in results among studies of different design.
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Affiliation(s)
- Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.
| | - Yuhong Yuan
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, London Health Science Centre, London, Ontario, Canada
| | - Jin Young Park
- Early Detection, Prevention, and Infections Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - David Forman
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Paul Moayyedi
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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Heidary M, Akrami S, Madanipour T, Shakib NH, Mahdizade Ari M, Beig M, Khoshnood S, Ghanavati R, Bazdar M. Effect of Helicobacter pylori-induced gastric cancer on gastrointestinal microbiota: a narrative review. Front Oncol 2025; 14:1495596. [PMID: 39868371 PMCID: PMC11757270 DOI: 10.3389/fonc.2024.1495596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 12/12/2024] [Indexed: 01/28/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection is a typical microbial agent that interferes with the complex mechanisms of gastric homeostasis by disrupting the balance between the host gastric microbiota and mucosa-related factors, ultimately leading to inflammatory changes, dysbiosis, and gastric cancer (GC). We searched this field on the basis of PubMed, Google Scholar, Web of Science, and Scopus databases. Most studies show that H. pylori inhibits the colonization of other bacteria, resulting in a less variety of bacteria in the gastrointestinal (GI) tract. When comparing the patients with H. pylori-positive and H. pylori-negative GC, the composition of the gastric microbiome changes with increasing abundance of H. pylori (where present) in the gastritis stage, whereas, as the gastric carcinogenesis cascade progresses to GC, oral and intestinal-type pathogenic microbial strains predominate. H. pylori infection induces a premalignant milieu of atrophy and intestinal metaplasia, and the resulting change in gastric microbiota appears to play an important role in gastric carcinogenesis. The effect of H. pylori-induced GC on GI microbiota is discussed in this review.
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Affiliation(s)
- Mohsen Heidary
- Leishmaniasis Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Sousan Akrami
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Tohid Madanipour
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nafiseh Hosseinzadeh Shakib
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Marzie Mahdizade Ari
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Beig
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Roya Ghanavati
- School of Medicine, Behbahan Faculty of Medical Sciences, Behbahan, Iran
| | - Monireh Bazdar
- School of Medicine, Razi Hospital, Ilam University of Medical Sciences, Ilam, Iran
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10
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Liu Z, Xu H, You W, Pan K, Li W. Helicobacter pylori eradication for primary prevention of gastric cancer: progresses and challenges. JOURNAL OF THE NATIONAL CANCER CENTER 2024; 4:299-310. [PMID: 39735441 PMCID: PMC11674435 DOI: 10.1016/j.jncc.2024.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/20/2024] [Accepted: 06/27/2024] [Indexed: 12/31/2024] Open
Abstract
Gastric cancer remains a significant global health challenge, causing a substantial number of cancer-related deaths, particularly in China. While the exact causes of gastric cancer are still being investigated, Helicobacter pylori (H. pylori) infection has been identified as the primary risk factor, which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time. Since the 1990s, numerous efforts have focused on assessing the effectiveness of H. pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment. This body of work, including several community-based interventions and meta-analyses, has shown a reduction in both the incidence of and mortality from gastric cancer following H. pylori treatment, alongside a decreased risk of metachronous gastric cancer. In this review, we seek to consolidate current knowledge on the effects of H. pylori treatment on gastric cancer prevention, its systemic consequences, cost-effectiveness, and the influence of antibiotic resistance and host characteristics on treatment outcomes. We further discuss the potential for precision primary prevention of H. pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.
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Affiliation(s)
- Zongchao Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hengmin Xu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Weicheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Kaifeng Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wenqing Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
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Pan KF, Li WQ, Zhang L, Liu WD, Ma JL, Zhang Y, Ulm K, Wang JX, Zhang L, Bajbouj M, Zhang LF, Li M, Vieth M, Quante M, Wang LH, Suchanek S, Mejías-Luque R, Xu HM, Fan XH, Han X, Liu ZC, Zhou T, Guan WX, Schmid RM, Gerhard M, Classen M, You WC. Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial. Nat Med 2024; 30:3250-3260. [PMID: 39079993 DOI: 10.1038/s41591-024-03153-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 06/25/2024] [Indexed: 09/07/2024]
Abstract
Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .
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Affiliation(s)
- Kai-Feng Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
| | - Wen-Qing Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
| | - Lian Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | | | - Jun-Ling Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Kurt Ulm
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | | | - Lei Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Monther Bajbouj
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | | | - Ming Li
- Health Bureau of Linqu County, Weifang, China
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Michael Quante
- School of Medicine and Health, Technical University of Munich, Munich, Germany
- Freiburg: Klinik für Innere Medizin II, Universitätsklinikum Freiburg, Freiburg, Germany
| | - Le-Hua Wang
- Health Bureau of Linqu County, Weifang, China
| | - Stepan Suchanek
- Department of Medicine & Department of Gastrointestinal Oncology, 1st Faculty of Medicine, Charles University and Military University Hospital, Prague, Czech Republic
| | - Raquel Mejías-Luque
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Heng-Min Xu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiao-Han Fan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xuan Han
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zong-Chao Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Tong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei-Xiang Guan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Roland M Schmid
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Markus Gerhard
- School of Medicine and Health, Technical University of Munich, Munich, Germany.
| | - Meinhard Classen
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Wei-Cheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
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Zou PY, Zhu JR, Zhao Z, Mei H, Zhao JT, Sun WJ, Wang GH, Chen DF, Fan LL, Lan CH. Development and application of an artificial intelligence-assisted endoscopy system for diagnosis of Helicobacter pylori infection: a multicenter randomized controlled study. BMC Gastroenterol 2024; 24:335. [PMID: 39350033 PMCID: PMC11440712 DOI: 10.1186/s12876-024-03389-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 08/27/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND The early diagnosis and treatment of Heliobacter pylori (H.pylori) gastrointestinal infection provide significant benefits to patients. We constructed a convolutional neural network (CNN) model based on an endoscopic system to diagnose H. pylori infection, and then examined the potential benefit of this model to endoscopists in their diagnosis of H. pylori infection. MATERIALS AND METHODS A CNN neural network system for endoscopic diagnosis of H.pylori infection was established by collecting 7377 endoscopic images from 639 patients. The accuracy, sensitivity, and specificity were determined. Then, a randomized controlled study was used to compare the accuracy of diagnosis of H. pylori infection by endoscopists who were assisted or unassisted by this CNN model. RESULTS The deep CNN model for diagnosis of H. pylori infection had an accuracy of 89.6%, a sensitivity of 90.9%, and a specificity of 88.9%. Relative to the group of endoscopists unassisted by AI, the AI-assisted group had better accuracy (92.8% [194/209; 95%CI: 89.3%, 96.4%] vs. 75.6% [158/209; 95%CI: 69.7%, 81.5%]), sensitivity (91.8% [67/73; 95%CI: 85.3%, 98.2%] vs. 78.6% [44/56; 95%CI: 67.5%, 89.7%]), and specificity (93.4% [127/136; 95%CI: 89.2%, 97.6%] vs. 74.5% [114/153; 95%CI: 67.5%, 81.5%]). All of these differences were statistically significant (P < 0.05). CONCLUSION Our AI-assisted system for diagnosis of H. pylori infection has significant ability for diagnostic, and can improve the accuracy of endoscopists in gastroscopic diagnosis. TRIAL REGISTRATION This study was approved by the Ethics Committee of Daping Hospital (10/07/2020) (No.89,2020) and was registered with the Chinese Clinical Trial Registration Center (02/09/2020) ( www.chictr.org.cn ; registration number: ChiCTR2000037801).
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Affiliation(s)
- Pei-Ying Zou
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive, Malignancies, Daping Hospital, Army Medical University, Third Military Medical University), 10 Changjiang Branch Road, Chongqing, 400000, China
| | - Jian-Ru Zhu
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive, Malignancies, Daping Hospital, Army Medical University, Third Military Medical University), 10 Changjiang Branch Road, Chongqing, 400000, China
| | - Zhe Zhao
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive, Malignancies, Daping Hospital, Army Medical University, Third Military Medical University), 10 Changjiang Branch Road, Chongqing, 400000, China
| | - Hao Mei
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive, Malignancies, Daping Hospital, Army Medical University, Third Military Medical University), 10 Changjiang Branch Road, Chongqing, 400000, China
| | - Jing-Tao Zhao
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive, Malignancies, Daping Hospital, Army Medical University, Third Military Medical University), 10 Changjiang Branch Road, Chongqing, 400000, China
| | - Wen-Jing Sun
- Chongqing 13, People's Hospital, Chongqing, China
| | | | - Dong-Feng Chen
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive, Malignancies, Daping Hospital, Army Medical University, Third Military Medical University), 10 Changjiang Branch Road, Chongqing, 400000, China
| | - Li-Lin Fan
- Chongqing Jiulongpo District Second People's Hospital, Chongqing, China
| | - Chun-Hui Lan
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive, Malignancies, Daping Hospital, Army Medical University, Third Military Medical University), 10 Changjiang Branch Road, Chongqing, 400000, China.
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13
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Smith SM, Boyle B, Buckley M, Costigan C, Doyle M, Farrell R, Ismail MS, Kevans D, Nugent S, O’Connor A, O’Morain C, Parihar V, Ryan C, McNamara D. The second Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of Helicobacter pylori infection in adult patients in Ireland. Eur J Gastroenterol Hepatol 2024; 36:1000-1009. [PMID: 38829956 PMCID: PMC11198963 DOI: 10.1097/meg.0000000000002796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 05/08/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori ( H. pylori ) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies. OBJECTIVE The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting. METHODS The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12). CONCLUSION These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.
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Affiliation(s)
| | - Breida Boyle
- Department of Clinical Microbiology, St. James’s Hospital, Dublin
| | - Martin Buckley
- Department of Gastroenterology, Mercy University Hospital, Cork
| | - Conor Costigan
- School of Medicine, Trinity College Dublin
- Department of Gastroenterology, Tallaght University Hospital, Dublin
| | - Maeve Doyle
- Department of Microbiology, University Hospital Waterford, Waterford
| | - Richard Farrell
- Department of Gastroenterology, Connolly Hospital, RCSI, Dublin
| | | | - David Kevans
- School of Medicine, Trinity College Dublin
- Department of Gastroenterology, St. James’s Hospital, Dublin
| | - Sean Nugent
- Department of Gastroenterology, Whitfield Clinic, Waterford
| | - Anthony O’Connor
- School of Medicine, Trinity College Dublin
- Department of Gastroenterology, Tallaght University Hospital, Dublin
| | | | - Vikrant Parihar
- Department of Gastroenterology, Letterkenny University Hospital
| | - Cristín Ryan
- School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland
| | - Deirdre McNamara
- School of Medicine, Trinity College Dublin
- Department of Gastroenterology, Tallaght University Hospital, Dublin
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Moss SF, Shah SC, Tan MC, El-Serag HB. Evolving Concepts in Helicobacter pylori Management. Gastroenterology 2024; 166:267-283. [PMID: 37806461 PMCID: PMC10843279 DOI: 10.1053/j.gastro.2023.09.047] [Citation(s) in RCA: 44] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/10/2023] [Accepted: 09/18/2023] [Indexed: 10/10/2023]
Abstract
Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain clinically silent. Moreover, individuals with chronic H pylori infection are at risk for gastric preneoplastic lesions, which are also asymptomatic and only reliably diagnosed using endoscopy and biopsy. Thus, to make a significant impact in gastric cancer prevention, a systematic approach is needed to better identify individuals at highest risk of both H pylori infection and its complications, including gastric preneoplasia and cancer. The approach to H pylori eradication must also be optimized given sharply decreasing rates of successful eradication with commonly used therapies and increasing antimicrobial resistance. With growing acceptance that H pylori should be managed as an infectious disease and the increasing availability of susceptibility testing, we now have the momentum to abandon empirical therapies demonstrated to have inadequate eradication rates. Molecular-based susceptibility profiling facilitates selection of a personalized eradication regimen without necessitating an invasive procedure. An improved approach to H pylori eradication coupled with population-level programs for screening and treatment could be an effective and efficient strategy to prevent gastric cancer, especially in minority and potentially marginalized populations that bear the heaviest burden of H pylori infection and its complications.
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Affiliation(s)
- Steven F Moss
- Brown University, Providence, Rhode Island; Providence VA Medical Center, Providence, Rhode Island
| | - Shailja C Shah
- University of California at San Diego, San Diego, California; VA San Diego Healthcare System, San Diego, California
| | - Mimi C Tan
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
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15
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Garman KS, Brown H, Alagesan P, McCall SJ, Patierno S, Wang Q, Wang F, Hyslop T, Epplein M. Helicobacter pylori testing prior to or at gastric cancer diagnosis and survival in a diverse US patient population. Gastric Cancer 2024; 27:28-35. [PMID: 37985571 PMCID: PMC10842898 DOI: 10.1007/s10120-023-01448-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 10/25/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND Gastric cancer (GC) accounts for the greatest disparity in cancer mortality between Black and White Americans. Although clinical trials have shown that Helicobacter pylori (Hp) treatment reduces risk of GC, Hp testing and treatment is not consistently performed in the US, and may offer an opportunity to improve survival. METHODS In a diverse retrospective cohort of 99 GC cases diagnosed at Duke University from 2002-2020 (57% Black; 43% white), we examined the association of Hp testing and treatment prior to or at cancer diagnosis with overall survival using Cox regression analyses to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS Overall, 62% of patients were tested for Hp prior to or at GC diagnosis. Of those, 25% tested positive and were treated < 1 year prior to or at diagnosis, 15% tested positive and were treated ≥ 1 year prior to diagnosis, 6% tested positive without evidence of treatment, and 54% tested negative. Compared to never tested, Hp testing and treatment < 1 year prior to or at diagnosis was associated with a significantly reduced likelihood of death (HR 0.21, 95% CI 0.08-0.58). The benefit of any Hp test and treat prior to or at GC diagnosis was significant even among stage IV patients only (HR, 0.22; 95% CI 0.05-0.96). CONCLUSIONS These findings support Hp testing and treatment for patients at risk of or diagnosed with GC, and suggest Hp treatment may provide an opportunity to reduce GC mortality disparities in the US.
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Affiliation(s)
- Katherine S Garman
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, NC, USA
- Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, 2424 Erwin Road, Suite 602, Durham, NC, 27705, USA
| | | | | | | | - Steven Patierno
- Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, 2424 Erwin Road, Suite 602, Durham, NC, 27705, USA
- Departments of Medicine, Family Medicine and Community Health, and Pharmacology and Cancer Biology, Duke University, Durham, NC, USA
| | - Qichen Wang
- Department of Biostatistics & Bioinformatics, Duke University, Durham, NC, USA
| | - Frances Wang
- Department of Biostatistics & Bioinformatics, Duke University, Durham, NC, USA
| | - Terry Hyslop
- Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, 2424 Erwin Road, Suite 602, Durham, NC, 27705, USA
- Department of Biostatistics & Bioinformatics, Duke University, Durham, NC, USA
- Department of Biostatistics, Thomas Jefferson University, Philadelphia, PA, USA
| | - Meira Epplein
- Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, 2424 Erwin Road, Suite 602, Durham, NC, 27705, USA.
- Department of Population Health Sciences, Duke University, Durham, NC, USA.
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16
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Liang Y, Yang Y, Nong R, Huang H, Chen X, Deng Y, Huang Z, Huang J, Cheng C, Ji M, Chen Y, Hu F. Do atrophic gastritis and intestinal metaplasia reverse after Helicobacter pylori eradication? Helicobacter 2024; 29:e13042. [PMID: 38018403 DOI: 10.1111/hel.13042] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 11/15/2023] [Accepted: 11/17/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND It's still controversial whether Helicobacter pylori (H. pylori) eradication can reverse atrophic gastritis (AG) and intestinal metaplasia (IM). Therefore, we performed a meta-analysis to estimate the effect of H. pylori eradication on AG and IM. METHODS We searched the PubMed, Web of Science and EMBASE datasets through April 2023 for epidemiological studies, which provided mean glandular atrophy (GA) or IM score before and after H. pylori eradication, or provided ORs, RRs or HRs and 95% CIs for the association of AG or IM with H. pylori eradication. Weighted mean difference (WMD) and pooled ORs and 95%CIs were used to estimate the effect of H. pylori eradication on AG and IM. RESULTS Twenty articles with a total of 5242 participants were included in this meta-analysis. H. pylori eradication significantly decreased GA score in the antrum (WMD -0.36; 95% CI: -0.52, -0.19, p < 0.01), GA score in the corpus (WMD -0.35; 95% CI: -0.52, -0.19, p < 0.01), IM score in the antrum (WMD -0.16; 95% CI: -0.26, -0.07, p < 0.01) and IM score in the corpus (WMD -0.20; 95% CI: -0.37, -0.04, p = 0.01). H. pylori eradication significantly improved AG (pooled OR 2.96; 95% CI: 1.70, 5.14, p < 0.01) and IM (pooled OR 2.41; 95% CI: 1.24, 4.70, p < 0.01). The association remained significant in the subgroup analyses by study design, sites of lesions, regions and follow-up time. Although Publication bias was observed for AG, the association remained significant after trim-and-fill adjustment. CONCLUSIONS H. pylori eradication could significantly improve AG and IM at early stage.
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Affiliation(s)
- Yongqiang Liang
- Department of Gastroenterology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, People's Republic of China
- Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
- 2019 Preventive Medicine, School of Public Health, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
| | - Yuanhai Yang
- Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
- 2020 Preventive Medicine, School of Public Health, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
| | - Ruiheng Nong
- Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
- 2020 Preventive Medicine, School of Public Health, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
| | - Hao Huang
- Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
| | - Xiuyun Chen
- Department of Gastroenterology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, People's Republic of China
| | - Ying Deng
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China
| | - Zhicong Huang
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China
| | - Jingyao Huang
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China
| | - Chunsheng Cheng
- Department of Gastroenterology and Endoscopy Centre, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital) and The 6th Affiliated Hospital of Shenzhen University School of Medicine, Shenzhen, Guangdong, China
| | - Mingzhu Ji
- Department of Gastroenterology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, People's Republic of China
| | - Yinggang Chen
- National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Fulan Hu
- Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
- Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Centre, Shenzhen, Guangdong, People's Republic of China
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17
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Zhu F, Zhang X, Li P, Zhu Y. Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis. Helicobacter 2023; 28:e13013. [PMID: 37602719 DOI: 10.1111/hel.13013] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/21/2023] [Accepted: 07/23/2023] [Indexed: 08/22/2023]
Abstract
BACKGROUND The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions. MATERIALS AND METHODS PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses. RESULTS Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81-0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17-1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69-0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30-2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15-1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37-2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47-1.70), Hp eradication had no advantage compared to placebo or no treatment. CONCLUSIONS Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.
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Affiliation(s)
- Fangyuan Zhu
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Xiaoze Zhang
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Ping Li
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Yaodong Zhu
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
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Kang SJ, Kim JG, Moon HS, Kook MC, Lee JY, Bang CS, Tae CH, Gong EJ, Nam SY, Kim HJ. Clinical Practice Guideline for Gastritis in Korea. J Korean Med Sci 2023; 38:e115. [PMID: 37012690 PMCID: PMC10070048 DOI: 10.3346/jkms.2023.38.e115] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 03/09/2023] [Indexed: 04/05/2023] Open
Abstract
Gastritis is a disease characterized by inflammation of the gastric mucosa. It is very common and has various classification systems such as the updated Sydney system. As there is a lot of evidence that Helicobacter pylori infection is associated with the development of gastric cancer and that gastric cancer can be prevented by eradication, H. pylori gastritis has been emphasized recently. The incidence rate of gastric cancer in Korea is the highest in the world, and due to the spread of screening endoscopy, atrophic gastritis and intestinal metaplasia are commonly diagnosed in the general population. However, there have been no clinical guidelines developed in Korea for these lesions. Therefore, this clinical guideline has been developed by the Korean College of Helicobacter and Upper Gastrointestinal Research for important topics that are frequently encountered in clinical situations related to gastritis. Evidence-based guidelines were developed through systematic review and de novo processes, and eight recommendations were made for eight key questions. This guideline needs to be periodically revised according to the needs of clinical practice or as important evidence about this issue is published in the future.
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Affiliation(s)
- Seung Joo Kang
- Deparment of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | | | - Jong Yeul Lee
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Chung Hyun Tae
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Su Youn Nam
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Hyun Jung Kim
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
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19
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Niroomand E, Kumar SR, Goldberg D, Kumar S. Impact of Medicaid Expansion on Incidence and Mortality from Gastric and Esophageal Cancer. Dig Dis Sci 2023; 68:1178-1186. [PMID: 35972583 DOI: 10.1007/s10620-022-07659-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 08/02/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Individuals in Medicaid expanded states have increased access to treatment for medical conditions and other health care resources. Esophageal and gastric cancer are associated with several modifiable risk factors (e.g. smoking, drinking, Helicobacter pylori infection). The impact of Medicaid expansion on these cancers incidence and mortality remains uninvestigated. METHODS We evaluated the association between Medicaid expansion and gastric and esophageal cancer incidence and mortality in adults aged 25-64. We employed an observational design using a difference-in-differences method with state level data, from 2010 to 2017. Annual, age-adjusted gastric and esophageal cancer incidence and mortality rates, from the CDC Wonder Database, were analyzed. Rates were adjusted for by several socio-demographic factors. RESULTS Expansion and non-expansion states were similar in percent Hispanic ethnicity and female gender. The non-expansion states had significantly higher proportion of Black race, diabetics, obese persons, smokers, and those living below the federal poverty line. Adjusted analyses demonstrate that expansion states had significantly fewer new cases of gastric cancer: - 1.6 (95% CI 0.2-3.5; P = 0.08) per 1,000,000 persons per year. No significant association was seen between Medicaid expansion and gastric cancer mortality (0.46 [95% CI - 0.08 to 0.17; P = 0.46]) and esophageal cancer incidence (0.8 [95% CI - 0.08 to 0.24; P = 0.33]) and mortality (1.0 [95% CI - 0.06 to 0.26; P = 0.21]) in multivariable analyses. CONCLUSION States that adopted Medicaid expansion saw a decrease in gastric cancer incidence when compared to states that did not expand Medicaid. Though several factors may influence gastric cancer incidence, this association is important to consider during health policy negotiations.
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Affiliation(s)
- Elaheh Niroomand
- Department of Internal Medicine, University of Miami Miller School of Medicine/Jackson Memorial Hospital, 1611 NW 12th Ave, Miami, FL, 33136, USA
| | - Smriti Rajita Kumar
- Department of Internal Medicine, University of Miami Miller School of Medicine/Jackson Memorial Hospital, 1611 NW 12th Ave, Miami, FL, 33136, USA
| | - David Goldberg
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA
| | - Shria Kumar
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Miami, FL, USA.
- Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA.
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20
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Huang RJ, Laszkowska M, In H, Hwang JH, Epplein M. Controlling Gastric Cancer in a World of Heterogeneous Risk. Gastroenterology 2023; 164:736-751. [PMID: 36706842 PMCID: PMC10270664 DOI: 10.1053/j.gastro.2023.01.018] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 01/12/2023] [Accepted: 01/17/2023] [Indexed: 01/29/2023]
Abstract
Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review also highlights existing knowledge gaps in GC prevention as well as the role of emerging technologies for early detection and risk stratification.
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Affiliation(s)
- Robert J Huang
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.
| | - Monika Laszkowska
- Gastroenterology, Hepatology, and Nutrition Service, Department of Subspecialty Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Haejin In
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Joo Ha Hwang
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Meira Epplein
- Duke University, Department of Population Health Sciences, and Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, Durham, North Carolina
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21
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Mahmood R, Voisin A, Olof H, Khorasaniha R, Lawal SA, Armstrong HK. Host Microbiomes Influence the Effects of Diet on Inflammation and Cancer. Cancers (Basel) 2023; 15:521. [PMID: 36672469 PMCID: PMC9857231 DOI: 10.3390/cancers15020521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/12/2023] [Accepted: 01/13/2023] [Indexed: 01/19/2023] Open
Abstract
Cancer is the second leading cause of death globally, and there is a growing appreciation for the complex involvement of diet, microbiomes, and inflammatory processes culminating in tumorigenesis. Although research has significantly improved our understanding of the various factors involved in different cancers, the underlying mechanisms through which these factors influence tumor cells and their microenvironment remain to be completely understood. In particular, interactions between the different microbiomes, specific dietary factors, and host cells mediate both local and systemic immune responses, thereby influencing inflammation and tumorigenesis. Developing an improved understanding of how different microbiomes, beyond just the colonic microbiome, can interact with dietary factors to influence inflammatory processes and tumorigenesis will support our ability to better understand the potential for microbe-altering and dietary interventions for these patients in future.
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Affiliation(s)
- Ramsha Mahmood
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Athalia Voisin
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Hana Olof
- Department of Immunology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Reihane Khorasaniha
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Samuel A. Lawal
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Heather K. Armstrong
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
- Department of Immunology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
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22
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Kim N, Yoon H. Atrophic Gastritis and Intestinal Metaplasia. HELICOBACTER PYLORI 2023:641-659. [DOI: 10.1007/978-981-97-0013-4_55] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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23
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Backert S, Linz B, Tegtmeyer N. Helicobacter pylori-Induced Host Cell DNA Damage and Genetics of Gastric Cancer Development. Curr Top Microbiol Immunol 2023; 444:185-206. [PMID: 38231219 DOI: 10.1007/978-3-031-47331-9_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Gastric cancer is a very serious and deadly disease worldwide with about one million new cases every year. Most gastric cancer subtypes are associated with genetic and epigenetic aberrations caused by chromosome instability, microsatellite instability or Epstein-Barr virus infection. Another risk factor is an infection with Helicobacter pylori, which also triggers severe alterations in the host genome. This pathogen expresses an extraordinary repertoire of virulence determinants that take over control of important host cell signaling functions. In fact, H. pylori is a paradigm of persistent infection, chronic inflammation and cellular destruction. In particular, H. pylori profoundly induces chromosomal DNA damage by introducing double-strand breaks (DSBs) followed by genomic instability. DSBs appear in response to oxidative stress and pro-inflammatory transcription during the S-phase of the epithelial cell cycle, which mainly depends on the presence of the bacterial cag pathogenicity island (cagPAI)-encoded type IV secretion system (T4SS). This scenario is closely connected with the T4SS-mediated injection of ADP-glycero-β-D-manno-heptose (ADP-heptose) and oncoprotein CagA. While ADP-heptose links transcription factor NF-κB-induced innate immune signaling with RNA-loop-mediated DNA replication stress and introduction of DSBs, intracellular CagA targets the tumor suppressor BRCA1. The latter scenario promotes BRCAness, a disease characterized by the deficiency of effective DSB repair. In addition, genetic studies of patients demonstrated the presence of gastric cancer-associated single nucleotide polymorphisms (SNPs) in immune-regulatory and other genes as well as specific pathogenic germline variants in several crucial genes involved in homologous recombination and DNA repair, all of which are connected to H. pylori infection. Here we review the molecular mechanisms leading to chromosomal DNA damage and specific genetic aberrations in the presence or absence of H. pylori infection, and discuss their importance in gastric carcinogenesis.
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Affiliation(s)
- Steffen Backert
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
| | - Bodo Linz
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany
| | - Nicole Tegtmeyer
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
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24
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Kim N, Park YH. Atrophic Gastritis and Intestinal Metaplasia. HELICOBACTER PYLORI 2023:229-251. [DOI: 10.1007/978-981-97-0013-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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25
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Wang P, Li P, Chen Y, Li L, Lu Y, Zhou W, Bian L, Zhang B, Yin X, Li J, Chen J, Zhang S, Shi Y, Tang X. Chinese integrated guideline on the management of gastric precancerous conditions and lesions. Chin Med 2022; 17:138. [PMID: 36517854 PMCID: PMC9749368 DOI: 10.1186/s13020-022-00677-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 10/17/2022] [Indexed: 12/15/2022] Open
Abstract
The standardized diagnosis and management of gastric precancerous conditions and lesions are important to prevent gastric cancer. This guideline, created by 5 traditional Chinese medicine and Western medicine associations, based on the current morbidity and diagnosis and treatment of gastric precancerous conditions and lesions, provides specific key points and strategies for diagnosis and treatment in the following five aspects: definition and epidemiology, diagnosis and stage, surveillance, treatment and efficacy evaluation. It is hoped that these aspects, assessed by integrating Western medicine and traditional Chinese medicine and involving multidisciplinary participation, will play a guiding role in clinical diagnosis and treatment and achieve effective secondary prevention of gastric cancer.
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Affiliation(s)
- Ping Wang
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
| | - Peng Li
- Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
| | - Yingxuan Chen
- Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
| | - Li Li
- China Academy of Chinese Medical Sciences, Guanganmen Hospital, Beijing, China
| | - Yuanyuan Lu
- Air Force Medical University Xijing Hospital, Xi'an, China
| | - Weixun Zhou
- Peking Union Medical College Hospital, Beijing, China
| | - Liqun Bian
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
| | - Beihua Zhang
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
| | - Xiaolan Yin
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
| | - Junxiang Li
- Beijing University of Chinese Medicine School of Traditional Chinese Medicine, Beijing, China.
| | - Jie Chen
- Peking Union Medical College Hospital, Beijing, China.
| | - Shutian Zhang
- Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China.
| | - Yongquan Shi
- Air Force Medical University Xijing Hospital, Xi'an, China.
| | - Xudong Tang
- China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China.
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26
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Mohseni S, Tabatabaei-Malazy O, Ejtahed HS, Qorbani M, Azadbakht L, Khashayar P, Larijani B. Effect of vitamins C and E on cancer survival; a systematic review. Daru 2022; 30:427-441. [PMID: 36136247 PMCID: PMC9715902 DOI: 10.1007/s40199-022-00451-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 09/16/2022] [Indexed: 10/14/2022] Open
Abstract
PURPOSE Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer survival. METHODS Relevant English trials were retrieved from PubMed, Cochrane Library, Embase, Web of Science, Scopus databases, and Clinicaltrials.gov through 21/June/2022. Inclusion criteria were all trials which assessed sole/combinations intake of VC/VE on survival rate, mortality, or remission of any cancer. Exclusion criteria were observational and animal studies. RESULTS We reached 30 trials conducted on 38,936 patients with various cancers. Due to severe methodological heterogeneity, meta-analysis was impossible. High dose VC + chemotherapy or radiation was safe with an overall survival (OS) 182 days - 21.5 months. Sole oral or intravenous high dose VC was safe with non-significant change in OS (2.9-8.2 months). VE plus chemotherapy was safe, resulted in stabling diseases for 5 years in 70- 86.7% of patients and OS 109 months. It was found 60% and 16% non-significant reductions in adjusted hazard ratio (HR) deaths or recurrence by 200 mg/d tocotrienol + tamoxifen in breast cancer, respectively. Sole intake of 200-3200 mg/d tocotrienol before resectable pancreatic cancer was safe and significantly increased cancer cells' apoptosis. Combination VC and VE was non-significantly reduced 7% in rate of neoplastic gastric polyp. CONCLUSION Although our study is supported improvement of survival and progression rates of cancers by VC/VE, more high quality trials with large sample sizes are required to confirm. PROSPERO REGISTRATION NUMBER CRD42020152795.
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Affiliation(s)
- Shahrzad Mohseni
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ozra Tabatabaei-Malazy
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hanieh-Sadat Ejtahed
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Qorbani
- Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Leila Azadbakht
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Patricia Khashayar
- Center for microsystem technology, Imec and Ghent University, 9052 Gent, Zwijnaarde, Belgium
- Osteoporosis Research Center, Endocrinology & Metabolism Clinical Science Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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27
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Hamashima C. Forthcoming Step in Gastric Cancer Prevention: How Can Risk Stratification Be Combined with Endoscopic Screening for Gastric Cancer? Gut Liver 2022; 16:811-824. [PMID: 35314519 PMCID: PMC9668507 DOI: 10.5009/gnl210313] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 10/29/2021] [Accepted: 11/12/2021] [Indexed: 11/04/2022] Open
Abstract
Although the concern for gastric cancer prevention has increased, gastric cancer has remained a heavy burden worldwide and is not just a local issue in East Asian countries. However, as several screening programs (listed below) have shown some success, it is important to determine whether the situation is changing in some other countries and whether similar methods should be recommended. Endoscopic screening has been performed as a national program in South Korea and Japan, and the results have shown a reduction in gastric cancer mortality. Although the efficacy of Helicobacter pylori eradication has been established, the efficacy of the screen-and-treat strategy is presently being evaluated in randomized controlled trials. The serum pepsinogen test and endoscopic examination can divide high-risk subjects with severe gastric atrophy from average-risk subjects. Risk stratification is anticipated to contribute to an efficient method of prediction of gastric cancer development when combined with endoscopic screening. Countries with a high incidence rate should realize the immediate need to reduce gastric cancer death directly by endoscopic screening and should recognize screen-and-treat as a second option to reduce future risk. However, all forms of gastric cancer prevention programs have some harms and potential to increase unnecessary examinations. A balance of the benefits and harms should be always considered. Although further study is needed to obtain sufficient evidence for gastric cancer prevention, the best available method should be examined in the context of each country.
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Affiliation(s)
- Chisato Hamashima
- Health Policy Section, Department of Nursing, Faculty of Medical Technology, Teikyo University, Tokyo, Japan
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28
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Bordin DS, Livzan MA, Osipenko MF, Mozgovoy SI, Andreyev DN, Maev IV. The key statements of the Maastricht VI consensus. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:5-21. [DOI: 10.31146/1682-8658-ecg-205-9-5-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
An analysis of the most important changes and provisions of the Maastricht VI consensus published in August 2022 is presented. 41 experts from 29 countries took part in the creation of the consensus. Recommendations have been developed in five areas: (1) indications for treatment and clinical associations of Helicobacter pylori (H. pylori) infection, (2) diagnosis, (3) treatment, (4) prevention of gastric cancer, (5) H. pylori and gastric microbiota -intestinal tract (GIT), taking into account the level of evidence and the strength of recommendations. Emphasis is placed on molecular testing, which is becoming an increasingly accessible research method in the world to identify both H. pylori itself and its sensitivity to antibiotics. The growing resistance of H. pylori strains to previously effective antibacterial agents requires a treatment strategy that implies the ability to determine the sensitivity of H. pylori to antibacterial agents both in the population and in a particular individual. The use of modern diagnostic tests expands the possibilities of individualization of therapy, since it allows determining not only the presence of H. pylori in the gastric mucosa, but also the sensitivity of the infection to antibacterial drugs. Along with individual approaches to treatment, the most effective empirical therapy regimens are given in case of impossibility to determine individual resistance to antibiotics. New data on the effectiveness and results of the use of primary and secondary preventive strategies for gastric cancer are presented. Given the important role of the entire microbiome of the gastrointestinal tract in the functioning of the body, the question of the interaction of H. pylori with other microorganisms is discussed. The critical issues of the near future are related to the global prevention of gastric cancer; the need to control antibiotic resistance, and the development of new methods of therapy and prevention of Helicobacter pylori infection.
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Affiliation(s)
- D. S. Bordin
- State Budgetary Institution of Healthcare of the city of Moscow “A. S. Loginov Moscow Clinical Scientific and Practical Center of the Department of Healthcare of the City of Moscow”; Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation; Federal State Educational Establishment of Higher Education Tver State Medical University
| | - M. A. Livzan
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - M. F. Osipenko
- Federal State Educational Establishment of Higher Education Novosibirsk State Medical University of the Ministry of Health of the Russian Federation
| | - S. I. Mozgovoy
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - D. N. Andreyev
- Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
| | - I. V. Maev
- Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
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29
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Huang RJ, Epplein M, Hamashima C, Choi IJ, Lee E, Deapen D, Woo Y, Tran T, Shah SC, Inadomi JM, Greenwald DA, Hwang JH. An Approach to the Primary and Secondary Prevention of Gastric Cancer in the United States. Clin Gastroenterol Hepatol 2022; 20:2218-2228.e2. [PMID: 34624563 PMCID: PMC8983795 DOI: 10.1016/j.cgh.2021.09.039] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 09/02/2021] [Accepted: 09/10/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US. METHODS On March 5-6, 2020 a summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. After this summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This article represents a consensus statement prepared by the writing group. RESULTS The burden of GC is highly inequitably distributed in the US and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecologic studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention) and the majority of observational data (for secondary prevention) are derived from non-US sources. CONCLUSIONS There exist substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.
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Affiliation(s)
- Robert J Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California
| | - Meira Epplein
- Department of Population Health Sciences, Duke University, and Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, Durham, North Carolina
| | | | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang, South Korea
| | - Eunjung Lee
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Dennis Deapen
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Yanghee Woo
- Division of Surgical Oncology, Department of Surgery, City of Hope National Comprehensive Cancer Center, Duarte, California
| | - Thuy Tran
- Division of Surgical Oncology, Department of Surgery, City of Hope National Comprehensive Cancer Center, Duarte, California
| | - Shailja C Shah
- Gastroenterology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California; Division of Gastroenterology and Moores Cancer Center, University of California, San Diego, La Jolla, California
| | - John M Inadomi
- Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
| | - David A Greenwald
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Joo Ha Hwang
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California.
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30
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Chiang TH, Cheng HC, Chuang SL, Chen YR, Hsu YH, Hsu TH, Lin LJ, Lin YW, Chu CH, Wu MS, Lee YC. Mass screening and eradication of Helicobacter pylori as the policy recommendations for gastric cancer prevention. J Formos Med Assoc 2022; 121:2378-2392. [PMID: 36085264 DOI: 10.1016/j.jfma.2022.08.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 08/17/2022] [Accepted: 08/17/2022] [Indexed: 11/18/2022]
Abstract
Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a three-tier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening program to maximize the population benefits and cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.
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Affiliation(s)
- Tsung-Hsien Chiang
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Chi Cheng
- Department of Internal Medicine, Institute of Clinical Medicine, Institute of Molecular Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan
| | - Shu-Lin Chuang
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Yi-Ru Chen
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Hsin Hsu
- Health Promotion Administration, Ministry of Health and Welfare, Taiwan
| | - Tsui-Hsia Hsu
- Health Promotion Administration, Ministry of Health and Welfare, Taiwan
| | - Li-Ju Lin
- Health Promotion Administration, Ministry of Health and Welfare, Taiwan
| | - Yu-Wen Lin
- Public Health Bureau, Taitung County, Taiwan
| | | | - Ming-Shiang Wu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Chia Lee
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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31
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Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022; 71:gutjnl-2022-327745. [PMID: 35944925 DOI: 10.1136/gutjnl-2022-327745] [Citation(s) in RCA: 598] [Impact Index Per Article: 199.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/21/2022] [Indexed: 01/06/2023]
Abstract
Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.
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Affiliation(s)
- Peter Malfertheiner
- Medical Department 2, LMU, Munchen, Germany
- Department of Radiology, LMU, Munchen, Germany
| | - Francis Megraud
- INSERM U853 UMR BaRITOn, University of Bordeaux, Bordeaux, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
- Medical School, European University, Nicosia, Cyprus
| | - Javier P Gisbert
- Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Jyh-Ming Liou
- Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Christian Schulz
- Medical Department 2, LMU, Munchen, Germany
- Partner Site Munich, DZIF, Braunschweig, Germany
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy
| | - Richard H Hunt
- Medicine, McMaster University, Hamilton, Ontario, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Colm O'Morain
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy
- Veneto Tumor Registry (RTV), Padova, Italy
| | - Sebastian Suerbaum
- Partner Site Munich, DZIF, Braunschweig, Germany
- Max von Pettenkofer Institute, LMU, Munchen, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical School, Tochigi, Japan
| | - Emad M El-Omar
- Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
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Park SK, Chung Y, Oh CM, Ryoo JH, Jung JY. The influence of the dietary intake of vitamin C and vitamin E on the risk of gastric intestinal metaplasia in a cohort of Koreans. Epidemiol Health 2022; 44:e2022062. [PMID: 35914770 PMCID: PMC9754913 DOI: 10.4178/epih.e2022062] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 07/29/2022] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVES Studies have suggested that the dietary intake of antioxidant vitamins, such as vitamin C and vitamin E, has a potential role in inhibiting gastric carcinogenesis. The present study investigated the effect of antioxidant vitamins on the incidence of gastric intestinal metaplasia (GIM). METHODS This study included 67,657 Koreans free of GIM who periodically underwent health check-ups. Dietary intake was assessed by a semiquantitative food frequency questionnaire based on the Korean National Health and Nutrition Examination Survey. Participants were categorized into 4 groups by quartiles of dietary vitamin C and vitamin E intake. The Cox proportional hazard assumption was used to determine the multivariable hazard ratio (HR) and 95% confidence interval (95% CI) for GIM. RESULTS The third and fourth quartiles of vitamin C intake had a lower risk of GIM than the first quartile (multivariable-adjusted HR, 0.95; 95% CI, 0.88 to 1.03 in the second quartile, HR, 0.88; 95% CI, 0.81 to 0.97 in the third quartile, and HR, 0.85; 95% CI, 0.76 to 0.95 in the fourth quartile). Vitamin E intake greater than the second quartile level was significantly associated with a lower risk of GIM than the first quartile (multivariable-adjusted HR, 0.90; 95% CI, 0.82 to 0.97 in the second quartile, HR, 0.90; 95% CI, 0.82 to 0.99 in the third quartile, and HR, 0.83; 95% CI, 0.74 to 0.94 in the fourth quartile). This association was observed only in the subgroup analysis for men. CONCLUSIONS Higher dietary intake of vitamin C and vitamin E was associated with a lower risk of GIM.
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Affiliation(s)
- Sung Keun Park
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yeongu Chung
- Department of Neurosurgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chang-Mo Oh
- Departments of Preventive Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jae-Hong Ryoo
- Departments of Occupational and Environmental Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Ju Young Jung
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea,Correspondence: Ju Young Jung Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 67 Sejong-daero, Jung-gu, Seoul 04514, Korea E-mail:
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33
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Namasivayam V, Koh CJ, Tsao S, Lee J, Ling KL, Khor C, Lim T, Li JW, Oo AM, Yip BCH, Hussain I, Chua TS, Toh BC, Ong HS, Wang LM, So JBY, Teh M, Yeoh KG, Ang TL. Academy of Medicine, Singapore clinical guideline on endoscopic surveillance and management of gastric premalignant lesions. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2022; 51:417-435. [PMID: 35906941 DOI: 10.47102/annals-acadmedsg.2021433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions.
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Wang S, Kuang J, Zhang H, Chen W, Zheng X, Wang J, Huang F, Ge K, Li M, Zhao M, Rajani C, Zhu J, Zhao A, Jia W. Bile Acid-Microbiome Interaction Promotes Gastric Carcinogenesis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2200263. [PMID: 35285172 PMCID: PMC9165488 DOI: 10.1002/advs.202200263] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/21/2022] [Indexed: 05/11/2023]
Abstract
Bile reflux gastritis (BRG) is associated with the development of gastric cancer (GC), but the specific mechanism remains elusive. Here, a comprehensive study is conducted to explore the roles of refluxed bile acids (BAs) and microbiome in gastric carcinogenesis. The results show that conjugated BAs, interleukin 6 (IL-6), lipopolysaccharide (LPS), and the relative abundance of LPS-producing bacteria are increased significantly in the gastric juice of both BRG and GC patients. A secondary BA, taurodeoxycholic acid (TDCA), is significantly and positively correlated with the LPS-producing bacteria in the gastric juice of these patients. TDCA promotes the proliferation of normal gastric epithelial cells (GES-1) through activation of the IL-6/JAK1/STAT3 pathway. These results are further verified in two mouse models, one by gavage of TDCA, LPS, and LPS-producing bacteria (Prevotella melaninogenica), respectively, and the other by bile reflux (BR) surgery, mimicking clinical bile refluxing. Moreover, the bile reflux induced gastric precancerous lesions observed in the post BR surgery mice can be prevented by treatment with cryptotanshinone, a plant-derived STAT3 inhibitor. These results reveal an important underlying mechanism by which bile reflux promotes gastric carcinogenesis and provide an alternative strategy for the prevention of GC associated with BRG.
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Affiliation(s)
- Shouli Wang
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Junliang Kuang
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Hongwei Zhang
- Department of Metabolic and Bariatric SurgeryShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Wenlian Chen
- Cancer Institute, Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai200233China
| | - Xiaojiao Zheng
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Jieyi Wang
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Fengjie Huang
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Kun Ge
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Mengci Li
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Mingliang Zhao
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Cynthia Rajani
- Cancer Biology ProgramUniversity of Hawaii Cancer CenterHonoluluHI96813USA
| | - Jinshui Zhu
- Department of GastroenterologyShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Aihua Zhao
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
| | - Wei Jia
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200233China
- Cancer Biology ProgramUniversity of Hawaii Cancer CenterHonoluluHI96813USA
- School of Chinese MedicineHong Kong Baptist UniversityKowloon TongHong Kong999077China
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35
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Prasad SK, Bhat S, Shashank D, C R A, R S, Rachtanapun P, Devegowda D, Santhekadur PK, Sommano SR. Bacteria-Mediated Oncogenesis and the Underlying Molecular Intricacies: What We Know So Far. Front Oncol 2022; 12:836004. [PMID: 35480118 PMCID: PMC9036991 DOI: 10.3389/fonc.2022.836004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/22/2022] [Indexed: 01/10/2023] Open
Abstract
Cancers are known to have multifactorial etiology. Certain bacteria and viruses are proven carcinogens. Lately, there has been in-depth research investigating carcinogenic capabilities of some bacteria. Reports indicate that chronic inflammation and harmful bacterial metabolites to be strong promoters of neoplasticity. Helicobacter pylori-induced gastric adenocarcinoma is the best illustration of the chronic inflammation paradigm of oncogenesis. Chronic inflammation, which produces excessive reactive oxygen species (ROS) is hypothesized to cause cancerous cell proliferation. Other possible bacteria-dependent mechanisms and virulence factors have also been suspected of playing a vital role in the bacteria-induced-cancer(s). Numerous attempts have been made to explore and establish the possible relationship between the two. With the growing concerns on anti-microbial resistance and over-dependence of mankind on antibiotics to treat bacterial infections, it must be deemed critical to understand and identify carcinogenic bacteria, to establish their role in causing cancer.
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Affiliation(s)
- Shashanka K Prasad
- Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Smitha Bhat
- Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Dharini Shashank
- Department of General Surgery, Adichunchanagiri Institute of Medical Sciences, Mandya, India
| | - Akshatha C R
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sindhu R
- Department of Microbiology, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Pornchai Rachtanapun
- School of Agro-Industry, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai, Thailand
- Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University, Chiang Mai, Thailand
| | - Devananda Devegowda
- Centre of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Prasanna K Santhekadur
- Centre of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Sarana Rose Sommano
- Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University, Chiang Mai, Thailand
- Department of Plant and Soil Sciences, Faculty of Agriculture, Chiang Mai University, Chiang Mai, Thailand
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36
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Capparelli R, Iannelli D. Epigenetics and Helicobacter pylori. Int J Mol Sci 2022; 23:ijms23031759. [PMID: 35163679 PMCID: PMC8836069 DOI: 10.3390/ijms23031759] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/21/2022] [Accepted: 02/01/2022] [Indexed: 02/06/2023] Open
Abstract
Epigenetics regulates gene expression, cell type development during differentiation, and the cell response to environmental stimuli. To survive, bacteria need to evade the host immune response. Bacteria, including Helicobacter pylori (Hp), reach this target epigenetically, altering the chromatin of the host cells, in addition to several more approaches, such as DNA mutation and recombination. This review shows that Hp prevalently silences the genes of the human gastric mucosa by DNA methylation. Epigenetics includes different mechanisms. However, DNA methylation persists after DNA replication and therefore is frequently associated with the inheritance of repressed genes. Chromatin modification can be transmitted to daughter cells leading to heritable changes in gene expression. Aberrant epigenetic alteration of the gastric mucosa DNA remains the principal cause of gastric cancer. Numerous methylated genes have been found in cancer as well as in precancerous lesions of Hp-infected patients. These methylated genes inactivate tumor-suppressor genes. It is time for us to complain about our genetic and epigenetic makeups for our diseases.
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Grochowska M, Perlejewski K, Laskus T, Radkowski M. The Role of Gut Microbiota in Gastrointestinal Tract Cancers. Arch Immunol Ther Exp (Warsz) 2022; 70:7. [PMID: 35112169 PMCID: PMC8810472 DOI: 10.1007/s00005-021-00641-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 11/16/2021] [Indexed: 02/07/2023]
Abstract
Disturbances in gastrointestinal (GI) microbiota could play a significant role in the development of GI cancers, but the underlying mechanisms remain largely unclear. While some bacteria seem to facilitate carcinogenesis, others appear to be protective. So far only one bacterium (Helicobacter pylori) has been classified by the International Agency for Cancer Research as carcinogenic in humans but many other are the subject of intense research. Most studies on the role of microbiota in GI tract oncogenesis focus on pancreatic and colorectal cancers with the following three species: Helicobacter pylori, Escherichia coli, and Porphyromonas gingivalis as likely causative factors. This review summarizes the role of bacteria in GI tract oncogenesis.
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Affiliation(s)
- Marta Grochowska
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Karol Perlejewski
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Tomasz Laskus
- Department of Adult Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Marek Radkowski
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
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38
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Park CH. Helicobacter pylori Eradication and Gastric Cancer Prevention. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Since Warren and Marshall demonstrated Helicobacter pylori (H. pylori) as a cause of gastritis in the early 1980s, H. pylori has been associated with various gastric diseases, including gastric ulcer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, gastric adenoma, gastric adenocarcinoma, and hyperplastic gastric polyps. H. pylori eradication therapy can treat some associated diseases, including low-grade gastric MALT lymphoma, and significantly reduce the risk of peptic ulcer recurrence or progression of atrophic gastritis and intestinal metaplasia. In East Asia, where H. pylori and gastric cancer are prevalent, several studies have been conducted to prove whether the risk of gastric cancer development is reduced through H. pylori eradication therapy. Early studies failed to show the benefits of H. pylori eradication therapy in gastric cancer prevention. However, recent studies with extended follow-up periods have reported reduced risks of gastric cancer after treatment of H. pylori infection. H. pylori eradication therapy effectively prevents gastric cancer even in patients who were treated for early gastric cancer, and can be used in treating hyperplastic gastric polyps. Herein, we reviewed current evidence supporting the benefits of H. pylori eradication therapy to help clinicians understand its impact on gastric cancer prevention and hyperplastic polyp treatment.
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39
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Wu SR, Liu J, Zhang LF, Wang N, Zhang LY, Wu Q, Liu JY, Shi YQ. Lamb’s tripe extract and vitamin B 12 capsule plus celecoxib reverses intestinal metaplasia and atrophy: A retrospective cohort study. World J Clin Cases 2021; 9:10472-10483. [PMID: 35004979 PMCID: PMC8686147 DOI: 10.12998/wjcc.v9.i34.10472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 08/31/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic atrophic gastritis (AG) with intestinal metaplasia (IM) significantly increases the risk of gastric cancer. Some medicines have showed definite therapeutic effects in AG and IM regression.
AIM To validate the efficacy of Lamb’s tripe extract and vitamin B12 capsule (LTEVB12) initial therapy and celecoxib rescue therapy for IM and AG.
METHODS A total of 255 patients were included to receive LTEVB12 initial therapy (2 capsules each time, three times daily for 6 mo) in hospital in this study. The patients with failure of IM regression continued to receive celecoxib rescue therapy (200 mg, once daily for 6 mo). After each therapy finished, the patients underwent endoscopy and biopsy examination. The regression efficiency was assessed by the operative link on gastritis assessment (OLGA) and the operative link on the gastric intestinal metaplasia assessment (OLGIM) staging system. Logistic regression analysis was applied to identify factors associated with the curative effect.
RESULTS For LTEVB12 initial therapy, the reversal rates of IM and AG were 52.95% and 48.24%, respectively. Analogously, for celecoxib rescue therapy, the effective rates for IM and AG were 56.25% and 51.56%, respectively. The IM regression rate of complete therapy was up to 85.03%. In different OLGA and OLGIM stages of IM patients, therapeutic efficiency showed a significant difference in each group (P < 0.05). For both therapies, patients with high stages (III or IV) of both the OLGA and OLGIM evaluation systems showed a higher IM or AG regression rate than those with low stages (I or II). Among patients with high stages (OLGIM III and IV), the IM regression rate was above 70% for each therapy. Eating habits, fresh vegetable intake, and high-salt diet were identified as independent factors for the IM reversal effect of LTEVB12 therapy, especially high-salt diet (odds ratio = 1.852, P < 0.05).
CONCLUSION Monotherapy could reverse IM and AG. LTEVB12 initial therapy and celecoxib rescue therapy significantly increase the regression effect. IM may not be the point of no return among gastric precancerous lesions.
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Affiliation(s)
- Si-Ran Wu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Jie Liu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Li-Feng Zhang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Na Wang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Lu-Yao Zhang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Qiong Wu
- Department of Clinical Nutrition, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Jun-Ye Liu
- Department of Radiation Protective Medicine, Air Force Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Yong-Quan Shi
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, Shaanxi Province, China
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40
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Reyes DA, Sarría VMS, Salazar-Viedma M, D'Afonseca V. Histone Methyltransferases Useful in Gastric Cancer Research. Cancer Inform 2021; 20:11769351211039862. [PMID: 34413625 PMCID: PMC8369960 DOI: 10.1177/11769351211039862] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 07/26/2021] [Indexed: 11/29/2022] Open
Abstract
Gastric cancer (GC) is one of the most frequent tumors in the world. Stomach adenocarcinoma is a heterogeneous tumor, turning the prognosis prediction and patients’ clinical management difficult. Some diagnosis tests for GC are been development using knowledge based in polymorphisms, somatic copy number alteration (SCNA) and aberrant histone methylation. This last event, a posttranslational modification that occurs at the chromatin level, is an important epigenetic alteration seen in several tumors including stomach adenocarcinoma. Histone methyltransferases (HMT) are the proteins responsible for the methylation in specific amino acids residues of histones tails. Here, were presented several HMTs that could be relating to GC process. We use public data from 440 patients with stomach adenocarcinoma. We evaluated the alterations as SCNAs, mutations, and genes expression level of HMTs in these aforementioned samples. As results, it was identified the 10 HMTs most altered (up to 30%) in stomach adenocarcinoma samples, which are the PRDM14, PRDM9, SUV39H2, NSD2, SMYD5, SETDB1, PRDM12, SUV39H1, NSD3, and EHMT2 genes. The PRDM9 gene is among most mutated and amplified HMTs within the data set studied. PRDM14 is downregulated in 79% of the samples and the SUV39H2 gene is down expressed in patients with recurred/progressed disease. Several HMTs are altered in many cancers. It is important to generate a genetic atlas of alterations of cancer-related genes to improve the understanding of tumorigenesis events and to propose novel tools of diagnosis and prognosis for the cancer control.
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Affiliation(s)
- Dafne Alejandra Reyes
- Facultad de Ciencias Agrarias y Forestales, Universidad Católica del Maule, Talca, Chile
| | | | - Marcela Salazar-Viedma
- Laboratorio de Genética y Microevolución, Facultad de Ciencias Básicas, Universidad Católica del Maule, Talca, Chile
| | - Vívian D'Afonseca
- Centro de Investigación y Estudios Avanzados del Maule (CIEAM), Vicerrectoría de Investigación y Posgrado, Universidad Católica del Maule, Talca, Chile
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Weng CY, Xu JL, Sun SP, Wang KJ, Lv B. Helicobacter pylori eradication: Exploring its impacts on the gastric mucosa. World J Gastroenterol 2021; 27:5152-5170. [PMID: 34497441 PMCID: PMC8384747 DOI: 10.3748/wjg.v27.i31.5152] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 06/14/2021] [Accepted: 07/15/2021] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infects approximately 50% of all humans globally. Persistent H. pylori infection causes multiple gastric and extragastric diseases, indicating the importance of early diagnosis and timely treatment. H. pylori eradication produces dramatic changes in the gastric mucosa, resulting in restored function. Consequently, to better understand the importance of H. pylori eradication and clarify the subsequent recovery of gastric mucosal functions after eradication, we summarize histological, endoscopic, and gastric microbiota changes to assess the therapeutic effects on the gastric mucosa.
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Affiliation(s)
- Chun-Yan Weng
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Jing-Li Xu
- Department of Gastrointestinal Surgery, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Shao-Peng Sun
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Kai-Jie Wang
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Bin Lv
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
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Gu Z, Ling J, Cong J, Li D. A Review of Therapeutic Effects and the Pharmacological Molecular Mechanisms of Chinese Medicine Weifuchun in Treating Precancerous Gastric Conditions. Integr Cancer Ther 2021; 19:1534735420953215. [PMID: 32865036 PMCID: PMC7466872 DOI: 10.1177/1534735420953215] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Patients with precancerous gastric conditions are at a high risk for gastric carcinoma. The Chinese medicine Weifuchun (WFC) is used in treating chronic superficial gastritis and in postoperative adjuvant treatment of gastric cancer. Both monotherapy and combination therapy of WFC with other drugs can result in a favorable therapeutic outcome. WFC can dramatically improve clinical outcomes in patients with gastric precancerous lesions by targeting multiple pathways including pathways involved in the pharmacological action of Radix Ginseng Rubra (red ginseng), Rabdosia amethystoides, and fried Fructus Aurantii, including regulation of NF-κB, RUNX3/TGF-beta/Smad, Hedgehog (Hh) and Wnt signaling pathways, modulation of the expression of oncogenes and tumor suppressor genes, and indirect inhibition of Helicobacter pylori (Hp) by maintaining gastric microbial ecosystem. In this review, we will discuss the clinical efficacy and therapeutic regimen of WFC for gastric precancerous lesions and the molecular mechanisms involved. This review will highlight WFC-based therapeutic strategies in disrupting progress to gastric cancer and provide more information on the pharmacological mechanisms of WFC and its clinical application for the treatment of precancerous gastric lesions.
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Affiliation(s)
- Zhijian Gu
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jianghong Ling
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jun Cong
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Dan Li
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Alam W, Ullah H, Santarcangelo C, Di Minno A, Khan H, Daglia M, Arciola CR. Micronutrient Food Supplements in Patients with Gastro-Intestinal and Hepatic Cancers. Int J Mol Sci 2021; 22:8014. [PMID: 34360782 PMCID: PMC8347237 DOI: 10.3390/ijms22158014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/15/2021] [Accepted: 07/18/2021] [Indexed: 02/05/2023] Open
Abstract
Colorectal carcinogenesis is the second most common cause of mortality across all types of malignancies, followed by hepatic and stomach cancers. Chemotherapy and radiotherapy are key approaches to treating cancer patients, but these carry major concerns, such as a high risk of side effects, poor accessibility, and the non-selective nature of chemotherapeutics. A number of natural products have been identified as countering various forms of cancer with fewer side effects. The potential impact of vitamins and minerals on long-term health, cognition, healthy development, bone formation, and aging has been supported by experimental and epidemiological studies. Successful treatment may thus be highly influenced by the nutritional status of patients. An insufficient diet could lead to detrimental effects on immune status and tolerance to treatment, affecting the ability of chemotherapy to destroy cancerous cells. In recent decades, most cancer patients have been taking vitamins and minerals to improve standard therapy and/or to decrease the undesirable side effects of the treatment together with the underlying disease. On the other hand, taking dietary supplements during cancer therapy may affect the effectiveness of chemotherapy. Thus, micronutrients in complementary oncology must be selected appropriately and should be taken at the right time. Here, the potential impact of micronutrients on gastro-intestinal and hepatic cancers is explored and their molecular targets are laid down.
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Affiliation(s)
- Waqas Alam
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; (W.A.); (H.K.)
| | - Hammad Ullah
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
| | - Cristina Santarcangelo
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
| | - Alessandro Di Minno
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
- CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; (W.A.); (H.K.)
| | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
| | - Carla Renata Arciola
- Laboratorio di Patologia delle Infezioni Associate all’Impianto, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via San Giacomo 14, 40136 Bologna, Italy
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Abstract
Gastric cancer is the fifth most common cause of cancer and the third leading cause of cancer-related deaths globally. The number of gastric cancer-related deaths is only projected to increase, attributable primarily to the expanding aging population. Prevention is a mainstay of gastric cancer control programs, particularly in the absence of accurate, noninvasive modalities for screening and early detection, and the absence of an infrastructure for this purpose in the majority of countries worldwide. Herein, we discuss the evidence for several chemopreventive agents, along with putative mechanisms. There remains a clear, unmet need for primary chemoprevention trials for gastric cancer.
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Affiliation(s)
- Shailja C. Shah
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, 1030C MRB IV, 2215 Garland Avenue, Nashville, TN 37232-0252, USA;,Veterans Affairs Tennessee Valley Health System, Nashville Campus, Nashville, TN, USA,Corresponding author:
| | - Richard M. Peek
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, 1030C MRB IV, 2215 Garland Avenue, Nashville, TN 37232-0252, USA
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Acupuncture Regulates Serum Differentially Expressed Proteins in Patients with Chronic Atrophic Gastritis: A Quantitative iTRAQ Proteomics Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:9962224. [PMID: 34234838 PMCID: PMC8219412 DOI: 10.1155/2021/9962224] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/15/2021] [Accepted: 05/26/2021] [Indexed: 12/24/2022]
Abstract
Objective To identify differentially expressed proteins (DEPs) in sera of patients with chronic atrophic gastritis (CAG) using isobaric tags for relative and absolute quantitation (iTRAQ) and to explore acupuncture's mechanism in CAG. Methods Peripheral sera from 8 healthy volunteers (HC), 8 chronic nonatrophic gastritis (NAG) patients, 8 CAG patients, and 8 CAG patients who underwent acupuncture treatment (CAG + ACU) were collected followed by labeling with iTRAQ reagent for protein identification and quantification using two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS). Representative DEPs were selected through bioinformatics, and proteins were verified by enzyme-linked immunosorbent assay (ELISA). Results A total of 4,448 unique peptides were identified, corresponding to 816 nonredundant proteins. A 1.4-fold difference was used as the threshold. Compared with the HC group, 75 and 106 DEPs were identified from CAG and NAG groups, respectively. Compared with the CAG group, 110 and 66 DEPs were identified from the NAG and CAG + ACU groups, respectively. The DEPs were mainly involved in protein binding and the Notch signaling pathway-related proteins, and the upregulated proteins included actin-binding proteins (thymosin beta-4, tropomyosin-4, profilin-1, transgelin-2), while the downregulated proteins included Notch2 and Notch3. After acupuncture, the expression of these proteins in CAG patients was less differentiated from that in healthy people. The level of the above 6 proteins were verified by ELISA, and the results were similar to the results of iTRAQ analysis. Conclusions Actin-binding proteins and Notch signaling pathway-related proteins were correlated with the development and progression of CAG and thus are potential diagnostic markers for CAG. Acupuncture may play a role in regulating actin-binding proteins and Notch signaling pathway-related proteins to play a therapeutic role in CAG.
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Mughal MJ, Kwok HF. Multidimensional role of bacteria in cancer: Mechanisms insight, diagnostic, preventive and therapeutic potential. Semin Cancer Biol 2021; 86:1026-1044. [PMID: 34119644 DOI: 10.1016/j.semcancer.2021.06.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 05/28/2021] [Accepted: 06/08/2021] [Indexed: 02/08/2023]
Abstract
The active role of bacteria in oncogenesis has long been a topic of debate. Although, it was speculated to be a transmissible cause of cancer as early as the 16th-century, yet the idea about the direct involvement of bacteria in cancer development has only been explored in recent decades. More recently, several studies have uncovered the mechanisms behind the carcinogenic potential of bacteria which are inflammation, immune evasion, pro-carcinogenic metabolite production, DNA damage and genomic instability. On the other side, the recent development on the understanding of tumor microenvironment and technological advancements has turned this enemy into an ally. Studies using bacteria for cancer treatment and detection have shown noticeable effects. Therapeutic abilities of bioengineered live bacteria such as high specificity, selective cytotoxicity to cancer cells, responsiveness to external signals and control after ingestion have helped to overcome the challenges faced by conventional cancer therapies and highlighted the bacterial based therapy as an ideal approach for cancer treatment. In this review, we have made an effort to compile substantial evidence to support the multidimensional role of bacteria in cancer. We have discussed the multifaceted role of bacteria in cancer by highlighting the wide impact of bacteria on different cancer types, their mechanisms of actions in inducing carcinogenicity, followed by the diagnostic and therapeutic potential of bacteria in cancers. Moreover, we have also highlighted the existing gaps in the knowledge of the association between bacteria and cancer as well as the limitation and advantage of bacteria-based therapies in cancer. A better understanding of these multidimensional roles of bacteria in cancer can open up the new doorways to develop early detection strategies, prevent cancer, and develop therapeutic tactics to cure this devastating disease.
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Affiliation(s)
- Muhammad Jameel Mughal
- Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau
| | - Hang Fai Kwok
- Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau; MOE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau.
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Jiang Z, Li L, Chen J, Wei G, Ji Y, Chen X, Liu J, Huo J. Human gut-microbiome interplay: Analysis of clinical studies for the emerging roles of diagnostic microbiology in inflammation, oncogenesis and cancer management. INFECTION GENETICS AND EVOLUTION 2021; 93:104946. [PMID: 34052417 DOI: 10.1016/j.meegid.2021.104946] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 04/21/2021] [Accepted: 05/26/2021] [Indexed: 12/24/2022]
Abstract
Microorganisms have been known to coexist in various parts of human body including the gut. The interactions between microbes and the surrounding tissues of the host are critical for fine fettle of the gut. The incidence of such microorganisms tends to vary among specific type of cancer affected individuals. Such microbial communities of specific tumor sites in cancer affected individuals could plausibly be used as prognostic and/or diagnostic markers for tumors associated with that specific site. Microorganisms of intestinal and non-intestinal origins including Helicobacter pylori can target several organs, act as carcinogens and promote cancer. It is interesting to note that diets causing inflammation can also increase the cancer risk. Yet, dietary supplementation with prebiotics and probiotics can reduce the incidence of cancer. Therefore, both diet and microbial community of the gut have dual roles of prevention and oncogenesis. Hence, this review intends to summarize certain important details related to gut microbiome and cancer.
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Affiliation(s)
- Ziyu Jiang
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China
| | - Lingchang Li
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China
| | - Jianan Chen
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China
| | - Guoli Wei
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China
| | - Yi Ji
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China
| | - Xi Chen
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China
| | - Jingbing Liu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China.
| | - Jiege Huo
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China.
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Shaaban S, Zarrouk A, Vervandier-Fasseur D, S.Al-Faiyz Y, El-Sawy H, Althagafi I, Andreoletti P, Cherkaoui-Malki M. Cytoprotective organoselenium compounds for oligodendrocytes. ARAB J CHEM 2021. [DOI: 10.1016/j.arabjc.2021.103051] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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Jung HK, Kang SJ, Lee YC, Yang HJ, Park SY, Shin CM, Kim SE, Lim HC, Kim JH, Nam SY, Shin WG, Park JM, Choi IJ, Kim JG, Choi M. Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020. Gut Liver 2021; 15:168-195. [PMID: 33468712 PMCID: PMC7960974 DOI: 10.5009/gnl20288] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/14/2020] [Accepted: 10/20/2020] [Indexed: 01/10/2023] Open
Abstract
Helicobacter pylori infection is one of the most common infectious diseases worldwide. Although the prevalence of H. pylori is gradually decreasing, approximately half of the world's population still becomes infected with this disease. H. pylori is responsible for substantial gastrointestinal morbidity worldwide, with a high disease burden. It is the most common cause of gastric and duodenal ulcers and gastric cancer. Since the revision of the H. pylori clinical practice guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin-based triple therapy for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance, especially from clarithromycin. The clinical practice guidelines for the treatment of H. pylori were updated according to evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after an expert consensus on three recommendations regarding the indication for treatment and eight recommendations for the treatment itself. These guidelines were designed to provide clinical evidence for the treatment (including primary care treatment) of H. pylori infection to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards and will be revised if more evidence emerges in the future.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Gangnam Center, Seoul, Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Su Youn Nam
- Center for Gastric Cancer, Kyungpook National University Hospital Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea
| | - Jae Myung Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Miyoung Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
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Park JY, Herrero R. Recent progress in gastric cancer prevention. Best Pract Res Clin Gastroenterol 2021; 50-51:101733. [PMID: 33975687 DOI: 10.1016/j.bpg.2021.101733] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 02/10/2021] [Accepted: 02/15/2021] [Indexed: 01/31/2023]
Abstract
Gastric cancer remains a major challenge to public health on a global scale, causing the loss of 19 million disability-adjusted life years worldwide in 2017. The future burden will increase due to population growth and ageing. Considering its absolute burden and persisting disparities, in addition to the substantial prevalence of Helicobacter pylori infection worldwide that is treatable, gastric cancer is a logical target for urgent global action for prevention. In this review, we discuss recent progress in gastric cancer prevention and propose a concerted international effort to implement population-based H. pylori treatment programmes, as the best evidence-based strategy that is currently available for gastric cancer prevention, in the context of demonstration projects in selected populations, to be later scaled up. It is time for urgent action to reduce the important loss of life and productivity caused by this preventable malignancy.
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Affiliation(s)
- Jin Young Park
- International Agency for Research on Cancer, Lyon CEDEX 08, 69372, France.
| | - Rolando Herrero
- Agencia Costarricense de Investigaciones Biomédicas, Fundación INCIENSA, Costa Rica.
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