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Oje A, Galati J, Peek RM. Current Understanding of Optimal Prevention of Helicobacter pylori-Induced Cancer. Gastroenterol Clin North Am 2025; 54:397-413. [PMID: 40348495 DOI: 10.1016/j.gtc.2024.12.005] [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: 05/14/2025]
Abstract
Gastric cancer is the fifth most common cancer and the fifth most common cause of cancer-related death globally. The key to improving outcomes lies in effective prevention and early detection, which are critical for successful curative interventions. Helicobacter pylori is the strongest known risk factor for gastric cancer, and eradication of this pathogen is critical for reducing cancer risk. By synthesizing current evidence and exploring the advanced therapeutic approaches, this review provides a comprehensive overview of best practices for mitigating gastric cancer through targeted bacterial intervention.
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Affiliation(s)
- Adesola Oje
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Jonathan Galati
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Richard M Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
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Liu Y, Li T, Lou L, Yang X, Kang C, Ren G, Zhang L, Zheng R, Kang X, Luo H, Liang S, Nie Y, Lv Y, Pan Y. Association between gastrointestinal lesions in individuals undergoing gastroscopy and colonoscopy simultaneously: a retrospective, observational study. BMC Gastroenterol 2025; 25:403. [PMID: 40413402 DOI: 10.1186/s12876-025-04012-9] [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: 03/21/2024] [Accepted: 05/20/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Due to the common developmental origination and influences by similar unhealthy lifestyle, upper and lower gastrointestinal (GI) diseases may be closely associated. However, the evidence remains elusive. This study aims to determine the prevalence of GI endoscopic lesions and the correlations between endoscopic lesions in individuals undergoing gastroscopy and colonoscopy simultaneously. METHODS A retrospective study was conducted on 18,556 individuals who underwent simultaneous gastroscopy and colonoscopy at the Endoscopy Center of Xijing Hospital of Digestive Diseases from January 2020 to March 2023. Data on sex, age, pathological and endoscopic results were collected. The Pearson chi-square test was used to analyze the occurrence of various GI lesions among age groups and correlations between GI lesions, and logistic regression was used to determine risk factors for common upper and lower GI lesions. RESULTS The mean age was 50.35 ± 12.31 years, and 55.5% of participants were male. At least one endoscopic abnormality was observed in 16,530 cases (89.1%), with 8253 cases (44.5%) showing abnormalities in both the upper and lower GI tract. The most common upper GI endoscopic lesions were chronic atrophic gastritis (CAG, 47.7%), reflux esophagitis (RE, 24.7%), and other gastritis (18.1%). Colorectal polyps (CPs) were the most prevalent lower GI endoscopic condition, observed in 37.5% of cases. The detection of CAG, RE, CPs increased with age, and was higher in man. Moreover, the presence of CAG was associated with the occurrence of CPs (kappa value = 0.135, p < 0.001), which was independent of age and gender. CONCLUSION Most GI diseases are more prevalent in men and the elderly. Additionally, CAG is independently correlated with the occurrence of endoscopic CPs.
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Affiliation(s)
- Yaling Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Tongxin Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Lijun Lou
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Xintian Yang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Chenxi Kang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Gui Ren
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Linhui Zhang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Rong Zheng
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Xiaoyu Kang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Hui Luo
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Shuhui Liang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Yongzhan Nie
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Yong Lv
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
| | - Yanglin Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
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Dinis-Ribeiro M, Libânio D, Uchima H, Spaander MCW, Bornschein J, Matysiak-Budnik T, Tziatzios G, Santos-Antunes J, Areia M, Chapelle N, Esposito G, Fernandez-Esparrach G, Kunovsky L, Garrido M, Tacheci I, Link A, Marcos P, Marcos-Pinto R, Moreira L, Pereira AC, Pimentel-Nunes P, Romanczyk M, Fontes F, Hassan C, Bisschops R, Feakins R, Schulz C, Triantafyllou K, Carneiro F, Kuipers EJ. Management of epithelial precancerous conditions and early neoplasia of the stomach (MAPS III): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG) and European Society of Pathology (ESP) Guideline update 2025. Endoscopy 2025; 57:504-554. [PMID: 40112834 DOI: 10.1055/a-2529-5025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
At a population level, the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), and the European Society of Pathology (ESP) suggest endoscopic screening for gastric cancer (and precancerous conditions) in high-risk regions (age-standardized rate [ASR] > 20 per 100 000 person-years) every 2 to 3 years or, if cost-effectiveness has been proven, in intermediate risk regions (ASR 10-20 per 100 000 person-years) every 5 years, but not in low-risk regions (ASR < 10).ESGE/EHMSG/ESP recommend that irrespective of country of origin, individual gastric risk assessment and stratification of precancerous conditions is recommended for first-time gastroscopy. ESGE/EHMSG/ESP suggest that gastric cancer screening or surveillance in asymptomatic individuals over 80 should be discontinued or not started, and that patients' comorbidities should be considered when treatment of superficial lesions is planned.ESGE/EHMSG/ESP recommend that a high quality endoscopy including the use of virtual chromoendoscopy (VCE), after proper training, is performed for screening, diagnosis, and staging of precancerous conditions (atrophy and intestinal metaplasia) and lesions (dysplasia or cancer), as well as after endoscopic therapy. VCE should be used to guide the sampling site for biopsies in the case of suspected neoplastic lesions as well as to guide biopsies for diagnosis and staging of gastric precancerous conditions, with random biopsies to be taken in the absence of endoscopically suspected changes. When there is a suspected early gastric neoplastic lesion, it should be properly described (location, size, Paris classification, vascular and mucosal pattern), photodocumented, and two targeted biopsies taken.ESGE/EHMSG/ESP do not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection unless there are signs of deep submucosal invasion or if the lesion is not considered suitable for endoscopic resection.ESGE/EHMSG/ESP recommend endoscopic submucosal dissection (ESD) for differentiated gastric lesions clinically staged as dysplastic (low grade and high grade) or as intramucosal carcinoma (of any size if not ulcerated or ≤ 30 mm if ulcerated), with EMR being an alternative for Paris 0-IIa lesions of size ≤ 10 mm with low likelihood of malignancy.ESGE/EHMSG/ESP suggest that a decision about ESD can be considered for malignant lesions clinically staged as having minimal submucosal invasion if differentiated and ≤ 30 mm; or for malignant lesions clinically staged as intramucosal, undifferentiated and ≤ 20 mm; and in both cases with no ulcerative findings.ESGE/EHMSG/ESP recommends patient management based on the following histological risk after endoscopic resection: Curative/very low-risk resection (lymph node metastasis [LNM] risk < 0.5 %-1 %): en bloc R0 resection; dysplastic/pT1a, differentiated lesion, no lymphovascular invasion, independent of size if no ulceration and ≤ 30 mm if ulcerated. No further staging procedure or treatment is recommended.Curative/low-risk resection (LNM risk < 3 %): en bloc R0 resection; lesion with no lymphovascular invasion and: a) pT1b, invasion ≤ 500 µm, differentiated, size ≤ 30 mm; or b) pT1a, undifferentiated, size ≤ 20 mm and no ulceration. Staging should be completed, and further treatment is generally not necessary, but a multidisciplinary discussion is required. Local-risk resection (very low risk of LNM but increased risk of local persistence/recurrence): Piecemeal resection or tumor-positive horizontal margin of a lesion otherwise meeting curative/very low-risk criteria (or meeting low-risk criteria provided that there is no submucosal invasive tumor at the resection margin in the case of piecemeal resection or tumor-positive horizontal margin for pT1b lesions [invasion ≤ 500 µm; well-differentiated; size ≤ 30 mm, and VM0]). Endoscopic surveillance/re-treatment is recommended rather than other additional treatment. High-risk resection (noncurative): Any lesion with any of the following: (a) a positive vertical margin (if carcinoma) or lymphovascular invasion or deep submucosal invasion (> 500 µm from the muscularis mucosae); (b) poorly differentiated lesions if ulceration or size > 20 mm; (c) pT1b differentiated lesions with submucosal invasion ≤ 500 µm with size > 30 mm; or (d) intramucosal ulcerative lesion with size > 30 mm. Complete staging and strong consideration for additional treatments (surgery) in multidisciplinary discussion.ESGE/EHMSG/ESP suggest the use of validated endoscopic classifications of atrophy (e. g. Kimura-Takemoto) or intestinal metaplasia (e. g. endoscopic grading of gastric intestinal metaplasia [EGGIM]) to endoscopically stage precancerous conditions and stratify the risk for gastric cancer.ESGE/EHMSG/ESP recommend that biopsies should be taken from at least two topographic sites (2 biopsies from the antrum/incisura and 2 from the corpus, guided by VCE) in two separate, clearly labeled vials. Additional biopsy from the incisura is optional.ESGE/EHMSG/ESP recommend that patients with extensive endoscopic changes (Kimura C3 + or EGGIM 5 +) or advanced histological stages of atrophic gastritis (severe atrophic changes or intestinal metaplasia, or changes in both antrum and corpus, operative link on gastritis assessment/operative link on gastric intestinal metaplasia [OLGA/OLGIM] III/IV) should be followed up with high quality endoscopy every 3 years, irrespective of the individual's country of origin.ESGE/EHMSG/ESP recommend that no surveillance is proposed for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history, incomplete intestinal metaplasia, persistent H. pylori infection). This group constitutes most individuals found in clinical practice.ESGE/EHMSG/ESP recommend H. pylori eradication for patients with precancerous conditions and after endoscopic or surgical therapy.ESGE/EHMSG/ESP recommend that patients should be advised to stop smoking and low-dose daily aspirin use may be considered for the prevention of gastric cancer in selected individuals with high risk for cardiovascular events.
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Affiliation(s)
- Mário Dinis-Ribeiro
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Gastroenterology Department, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Diogo Libânio
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Gastroenterology Department, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Hugo Uchima
- Endoscopy Unit Gastroenterology Department Hospital Universitari Germans Trias i Pujol, Badalona, Spain
- Endoscopy Unit, Teknon Medical Center, Barcelona, Spain
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Jan Bornschein
- Medical Research Council Translational Immune Discovery Unit (MRC TIDU), Weatherall Institute of Molecular Medicine (WIMM), Radcliffe Department of Medicine, University of Oxford, Oxford, UK
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | - Tamara Matysiak-Budnik
- Department of Hepato-Gastroenterology & Digestive Oncology, Institut des Maladies de l'Appareil Digestif, Centre Hospitalier Universitaire de Nantes Nantes, France
- INSERM, Center for Research in Transplantation and Translational Immunology, University of Nantes, Nantes, France
| | - Georgios Tziatzios
- Agia Olga General Hospital of Nea Ionia Konstantopouleio, Athens, Greece
| | - João Santos-Antunes
- Gastroenterology Department, Centro Hospitalar S. João, Porto, Portugal
- Faculty of Medicine, University of Porto, Portugal
- University of Porto, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Instituto de Investigação e Inovação na Saúde (I3S), Porto, Portugal
| | - Miguel Areia
- Gastroenterology Department, Portuguese Oncology Institute of Coimbra (IPO Coimbra), Coimbra, Portugal
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), RISE@CI-IPO, (Health Research Network), Portuguese Institute of Oncology of Porto (IPO Porto), Porto, Portugal
| | - Nicolas Chapelle
- Department of Hepato-Gastroenterology & Digestive Oncology, Institut des Maladies de l'Appareil Digestif, Centre Hospitalier Universitaire de Nantes Nantes, France
- INSERM, Center for Research in Transplantation and Translational Immunology, University of Nantes, Nantes, France
| | - Gianluca Esposito
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Italy
| | - Gloria Fernandez-Esparrach
- Gastroenterology Department, ICMDM, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Lumir Kunovsky
- 2nd Department of Internal Medicine - Gastroenterology and Geriatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Mónica Garrido
- Gastroenterology Department, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Ilja Tacheci
- Gastroenterology, Second Department of Internal Medicine, University Hospital Hradec Kralove, Faculty of Medicine in Hradec Kralove, Charles University of Prague, Czech Republic
| | | | - Pedro Marcos
- Department of Gastroenterology, Pêro da Covilhã Hospital, Covilhã, Portugal
- Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal
| | - Ricardo Marcos-Pinto
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), RISE@CI-IPO, (Health Research Network), Portuguese Institute of Oncology of Porto (IPO Porto), Porto, Portugal
- Gastroenterology Department, Centro Hospitalar do Porto, Porto, Portugal
- Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Leticia Moreira
- Gastroenterology Department, ICMDM, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Ana Carina Pereira
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Pedro Pimentel-Nunes
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), RISE@CI-IPO, (Health Research Network), Portuguese Institute of Oncology of Porto (IPO Porto), Porto, Portugal
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto (FMUP), Portugal
- Gastroenterology and Clinical Research, Unilabs Portugal
| | - Marcin Romanczyk
- Department of Gastroenterology, Faculty of Medicine, Academy of Silesia, Katowice, Poland
- Endoterapia, H-T. Centrum Medyczne, Tychy, Poland
| | - Filipa Fontes
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Public Health and Forensic Sciences, and Medical Education Department, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Cesare Hassan
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Raf Bisschops
- Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
- Department of Translational Research in Gastrointestinal Diseases (TARGID), KU Leuven, Leuven, Belgium
| | - Roger Feakins
- Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, United Kingdom
- University College London, London, United Kingdom
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Germany
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece
| | - Fatima Carneiro
- Institute of Molecular Pathology and Immunology at the University of Porto (IPATIMUP), Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
- Pathology Department, Centro Hospitalar de São João and Faculty of Medicine, Porto, Portugal
| | - Ernst J Kuipers
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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Wizenty J, Sigal M. Helicobacter pylori, microbiota and gastric cancer - principles of microorganism-driven carcinogenesis. Nat Rev Gastroenterol Hepatol 2025; 22:296-313. [PMID: 40011753 DOI: 10.1038/s41575-025-01042-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/16/2025] [Indexed: 02/28/2025]
Abstract
The demonstration that Helicobacter pylori is a pathogenic bacterium with marked carcinogenic potential has paved the way for new preventive approaches for gastric cancer. Although decades of research have uncovered complex interactions of H. pylori with epithelial cells, current insights have refined our view on H. pylori-associated carcinogenesis. Specifically, the cell-type-specific effects on gastric stem and progenitor cells deep in gastric glands provide a new view on the ability of the bacteria to colonize long-term, manipulate host responses and promote gastric pathology. Furthermore, new, large-scale epidemiological data have shed light on factors that determine why only a subset of carriers progress to gastric cancer. Currently, technological advances have brought yet another revelation: H. pylori is far from the only microorganism able to colonize the stomach. Instead, the stomach is colonized by a diverse gastric microbiota, and there is emerging evidence for the occurrence and pathological effect of dysbiosis resulting from an aberrant interplay between H. pylori and the gastric mucosa. With the weight of this evidence mounting, here we consider how the lessons learned from H. pylori research inform and synergize with this emerging field to bring a more comprehensive understanding of the role of microbes in gastric carcinogenesis.
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Affiliation(s)
- Jonas Wizenty
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy and BIH Charité Clinician Scientist Program, Berlin, Germany
| | - Michael Sigal
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
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Yang XE, Zhang SJ, Liu Y, Yao SY, Zhang SX, Liu XM, Liang LX, Wang F. Amoxicillin high-dose dual therapy for Helicobacter pylori primary eradication: Proton pump inhibitor and potassium-competitive acid blocker, which's better? World J Gastroenterol 2025; 31:100863. [PMID: 40248055 PMCID: PMC12001176 DOI: 10.3748/wjg.v31.i13.100863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 02/22/2025] [Accepted: 03/18/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori (H. pylori). AIM To assess the efficacy and safety of high-dose dual therapy (HDDT) utilizing various highly potent antisecretory medications, thereby providing additional clinical guidance for H. pylori eradication. METHODS The study population comprised untreated H. pylori patients from three medical centers in central China. From February 10, 2024 to March 31, 2024, 439 subjects were randomly allocated to either the esomeprazole-amoxicillin (EA) or esomeprazole-amoxicillin-clarithromycin-bismuth (B-quadruple) group. Subsequently, from April 1, 2024 to May 10, 2024, 367 subjects were randomly assigned to either the vonoprazan-amoxicillin (VA) or vonoprazan-amoxicillin-clarithromycin (VAC) group. The study recorded treatment efficacy, adverse events, compliance, symptom alleviation, and associated costs. RESULTS EA-dual demonstrated non-inferiority to B-quadruple regimen in modified intention-to-treat (mITT) and per-protocol (PP) analyses (P < 0.025). However, the eradication rate of EA was lower than that of the B-quadruple group [70.59% vs 83.49%, 92.86% vs 98.38%, 93.94% vs 98.38%, intention-to-treat (ITT), mITT, PP respectively, P < 0.05]. In ITT, mITT, and PP analyses, VA-dual was non-inferior to VAC treatment (84.15% vs 83.15%, 96.25% vs 92.73%, 96.75% vs 93.75%, P < 0.025). No significant differences were observed in adverse events, compliance, and symptom relief between groups. VA exhibited the lowest cost. Antibiotic use within 2 years, poor compliance, and suburban residence were associated with reduced eradication efficacy (P < 0.05). CONCLUSION The HDDT based on vonoprazan demonstrated non-inferiority to the VAC triple regimen, suggesting its potential as a recommended first-line treatment for H. pylori eradication. While B-quadruple therapy showed better eradication rate than EA therapy, the latter proved non-inferior in mITT and PP analyses. Notably, antibiotic use within the preceding two years, adherence to treatment protocols, and patient residence emerged as critical factors influencing eradication success.
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Affiliation(s)
- Xue-Er Yang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Sheng-Jun Zhang
- Department of Gastroenterology, The Second People's Hospital of Huaihua, Huaihua 418000, Hunan Province, China
| | - Yuan Liu
- Department of Gastroenterology, Yueyang Hospital of Traditional Chinese Medicine, Yueyang 414100, Hunan Province, China
| | - Shuo-Yi Yao
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Su-Xin Zhang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Xiao-Ming Liu
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Lun-Xi Liang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Fen Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
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Morgan DR, Corral JE, Li D, Montgomery EA, Riquelme A, Kim JJ, Sauer B, Shah SC. ACG Clinical Guideline: Diagnosis and Management of Gastric Premalignant Conditions. Am J Gastroenterol 2025; 120:709-737. [PMID: 40072510 DOI: 10.14309/ajg.0000000000003350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 12/13/2024] [Indexed: 03/14/2025]
Abstract
Gastric premalignant conditions (GPMC) are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. GPMC have an increased risk of progression to gastric adenocarcinoma. Gastric cancer (GC) in the United States represents an important cancer disparity because incidence rates are 2- to 13-fold greater in non-White individuals, particularly early-generation immigrants from regions of high GC incidence. The US 5-year survival rate for GC is 36%, which falls short of global standards and is driven by the fact that only a small percentage of GC in the US is diagnosed in the early, curable stage. This document represents the first iteration of American College of Gastroenterology guidelines on this topic and encompasses endoscopic surveillance for high-risk patients with GPMC, the performance of high-quality endoscopy and image-enhanced endoscopy for diagnosis and surveillance, GPMC histology criteria and reporting, endoscopic treatment of dysplasia, the role of Helicobacter pylori eradication, general risk reduction measures, and the management of autoimmune gastritis and gastric epithelial polyps. There is insufficient evidence to make a recommendation on upper endoscopic screening for GC/GPMC detection in US populations deemed high-risk for GC. Surveillance endoscopy is recommended for individuals at high risk for GPMC progression, as defined by endoscopic, histologic, and demographic factors, typically every 3 years, but an individualized interval may be warranted. H. pylori testing, treatment, and eradication confirmation are recommended in all individuals with GPMC. Extensive high-quality data from US populations regarding GPMC management are lacking, but continue to accrue, and the quality of evidence for the recommendations presented herein should be interpreted with this dynamic context in mind. The GPMC research and education agendas are broad and include high-quality prospective studies evaluating opportunistic endoscopic screening for GC/GPMC, refined delineation of what constitutes "high-risk" populations, development of novel biomarkers, alignment of best practices, implementation of training programs for improved GPMC/GC detection, and evaluation of the impact of these interventions on GC incidence and mortality in the US.
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Affiliation(s)
- Douglas R Morgan
- Division of Gastroenterology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Juan E Corral
- Division of Gastroenterology, Prisma Health, Greenville, South Carolina, USA
| | - Dan Li
- Department of Gastroenterology, Kaiser Permanente Medical Center, Santa Clara, California, USA
- Kaiser Permanente Northern California Division of Research, Oakland, California, USA
| | - Elizabeth A Montgomery
- Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Arnoldo Riquelme
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Center for Control and Prevention of Cancer (CECAN), Santiago, Chile
| | - John J Kim
- Division of Gastroenterology, Los Angeles General Medical Center, Los Angeles, California, USA
| | - Bryan Sauer
- Division of Gastroenterology, University of Virginia, Charlottesville, Virginia, USA
| | - Shailja C Shah
- Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA
- Gastroenterology Section, Jennifer Moreno Veterans Affairs Medical Center, La Jolla, California, USA
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Li D, Morgan DR, Corral JE, Montgomery EA, Riquelme A, Shah SC. Gastric Cancer Screening in the United States: A Review of Current Evidence, Challenges, and Future Perspectives. Am J Gastroenterol 2025; 120:765-777. [PMID: 40072512 DOI: 10.14309/ajg.0000000000003301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 12/18/2024] [Indexed: 03/14/2025]
Abstract
Gastric cancer remains a leading cause of cancer-related mortality worldwide. In the United States, gastric cancer incidence and mortality are substantially higher among non-White racial and ethnic groups and new immigrants from high-incidence countries. This is in large part related to the higher prevalence of Helicobacter pylori -associated gastric premalignant changes in these populations. Apart from primary prevention, early detection of gastric cancer is the principal strategy to reduce gastric cancer mortality and improve survival. Extensive evidence in Asian countries has demonstrated the benefits of endoscopic screening in detecting early-stage gastric cancer and reducing gastric cancer-related mortality. By contrast, direct, high-quality US-based data, such as from large clinical trials or observational studies, on important outcomes of gastric cancer screening are still lacking. In this review, we evaluate and summarize the latest global evidence on the epidemiology and predisposing factors of gastric cancer as well as the efficacy, benefits vs. risks, and cost-effectiveness of gastric cancer screening. We further discuss the critical knowledge gaps and challenges in promoting gastric cancer screening in the United States. Dedicated research is urgently needed to enrich the US-based data on gastric cancer primary and secondary prevention to inform clinical practice and reduce gastric cancer-related morbidity and mortality in a cost and resource efficient manner.
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Affiliation(s)
- Dan Li
- Department of Gastroenterology, Kaiser Permanente Medical Center, Santa Clara, California, USA
- Kaiser Permanente Northern California Division of Research, Oakland, California, USA
| | - Douglas R Morgan
- Division of Gastroenterology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Juan E Corral
- Division of Gastroenterology, Prisma Health, Greenville, South Carolina, USA
| | - Elizabeth A Montgomery
- Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Arnoldo Riquelme
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Center for Control and Prevention of Cancer (CECAN), Santiago, Chile
| | - Shailja C Shah
- Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA
- Gastroenterology Section, Jennifer Moreno Department of Veterans Affairs Medical Center, La Jolla, California, USA
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8
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Xie J, Zhang ML, Guo M, Li JG, Liu Y, Chen HH, Wang F. Antibiotic resistance of Helicobacter pylori and related risk factors in Hunan Province: A multicenter study. World J Gastroenterol 2025; 31:104835. [PMID: 40182588 PMCID: PMC11962852 DOI: 10.3748/wjg.v31.i12.104835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/23/2025] [Accepted: 03/06/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Antibiotic resistance is a key factor influencing the treatment outcomes of Helicobacter pylori (H. pylori) infection. The antibiotic resistance spectrum of H. pylori varies in different regions. We investigated the current status of antibiotic resistance of H. pylori in Hunan Province and analyzed the factors related to such resistance to provide strategies for the accurate clinical treatment of H. pylori infection. AIM To understand the antibiotic resistance of H. pylori in Hunan Province and provide guidance for the clinical treatment of H. pylori infection. METHODS This study selected patients who underwent gastroscopy in five hospitals in Hunan Province from April 2022 to April 2023. The sensitivity of H. pylori to clarithromycin, levofloxacin, metronidazole, amoxicillin, furazolidone, and tetracycline was detected using the Agar dilution method. RESULTS H. pylori strains from a total of 566 patients were isolated and identified. The resistance rates of H. pylori strains to clarithromycin, levofloxacin, metronidazole, amoxicillin, furazolidone, and tetracycline were 49.2%, 37.8%, 76.1%, 2.3%, 1.4%, and 0.7%, respectively. The resistance rates to clarithromycin, levofloxacin, and metronidazole were high in the four regions of Hunan Province, and the overall resistance rates in central Hunan Province were higher than those in other regions. The resistance rates of H. pylori strains to clarithromycin and levofloxacin were significantly different among the different age groups (P < 0.05), with the elderly group having a higher resistance rate than the young group. The resistance rate of H. pylori strains to clarithromycin was greater in patients with atrophic gastritis, and the resistance rate to levofloxacin was the lowest in patients with peptic ulcers. CONCLUSION The resistance rate of H. pylori to amoxicillin, clarithromycin, and metronidazole is high in Hunan Province. Age, stomach disease, and H. pylori reinfection may affect the antibiotic resistance of H. pylori.
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Affiliation(s)
- Jie Xie
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Ming-Lin Zhang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Min Guo
- Department of Gastroenterology, The First People’s Hospital of Changde, Changde 415003, Hunan Province, China
| | - Jian-Guo Li
- Department of Gastroenterology, The Fourth Hospital of Changsha, Changsha 410000, Hunan Province, China
| | - Yuan Liu
- Department of Gastroenterology, Yueyang Hospital of Traditional Chinese Medicine, Yueyang 414100, Hunan Province, China
| | - Hong-Hui Chen
- Department of Gastroenterology, The Second Affiliated Hospital of South China University, Hengyang 421099, Hunan Province, China
| | - Fen Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
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Li T, Jiang H, Gong Y, Liao M, Jia Y, Chen J, Dai M, Yan Y, Lu X, Chen R, Li Y, Chen Y, Lin J, Li Y, Ding X. CHI3L1: a key driver in gastritis-to-cancer transformation. J Transl Med 2025; 23:349. [PMID: 40108688 PMCID: PMC11921547 DOI: 10.1186/s12967-025-06352-2] [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] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 03/05/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Gastric cancer, recognized as one of the most lethal malignancies globally, progresses through a complex, multi-stage development. Elucidating the pathogenic mechanisms behind gastric carcinogenesis and identifying early diagnostic biomarkers are pivotal for decreasing the prevalence of gastric cancer. METHODS Using datasets on gastric cancer and its transformation from gastritis, we employed machine learning to create an early diagnostic model, identifying key genes and evaluating accuracy. We prioritized genes in the gastritis-to-cancer progression, identifying a central driver gene. Pathway analysis revealed its transformation role. Tissue microarrays and rat models validated the driver genes and networks, confirmed in cell and organoid models. We also identified cell types secreting CHI3L1 using single-cell RNA sequencing and multiplex immunohistochemistry, exploring their prognostic significance. RESULTS We identified 12 driver genes potentially involved in the gastritis-to-cancer transformation, with CHI3L1, MMP12, CXCL6, IDO1, and CCL20 emerging as the top five genes via a early gastric cancer diagnostic model. CHI3L1 was pinpointed as the central driver across the gastritis-to-cancer spectrum, with its upregulation, along with CD44, β-catenin, and c-Myc, noted in gastric precancerous lesions. In vitro and organoid studies revealed CHI3L1's role in activating the CD44-β-catenin pathway to induce malignancy. Furthermore, our findings indicate that fibroblasts and dendritic cells are the principal sources of CHI3L1 secretion, a factor that is associated with poor prognosis in gastric cancer. CONCLUSIONS This study highlights CHI3L1 as a key gene driving the progression from gastritis to gastric cancer, primarily by activating the CD44-β-catenin pathway, which enhances malignant cell traits. CHI3L1 is mainly secreted by fibroblasts and dendritic cells, and its high levels are linked to poor gastric cancer prognosis.
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Affiliation(s)
- Tao Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Huizhong Jiang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Yucheng Gong
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Mengting Liao
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Yuanping Jia
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Jiena Chen
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Ming Dai
- MOE Key Laboratory of Membraneless Organelle and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230027, China
| | - Yinan Yan
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xinyu Lu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Runhua Chen
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China
| | - Yuan Li
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases, Beijing University of Chinese Medicine, Beijing, 100029, China
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yan Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Jie Lin
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases, Beijing University of Chinese Medicine, Beijing, 100029, China
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yicong Li
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China.
| | - Xia Ding
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
- Research Center for Spleen and Stomach Diseases of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
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Benites-Goñi H, Cabrera-Hinojosa D, Latorre G, Hernandez AV, Uchima H, Riquelme A. OLGA and OLGIM staging systems on the risk assessment of gastric cancer: a systematic review and meta‑analysis of prospective cohorts. Therap Adv Gastroenterol 2025; 18:17562848251325461. [PMID: 40104323 PMCID: PMC11915242 DOI: 10.1177/17562848251325461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 02/18/2025] [Indexed: 03/20/2025] Open
Abstract
Background The Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) are established classification systems used to evaluate atrophic gastritis and intestinal metaplasia, respectively. Objectives We evaluated the association of OLGA and OLGIM scores and the risk of gastric cancer (GC) in only prospective cohort studies. Design Systematic review and meta-analysis. Data sources and methods We systematically searched four databases for prospective cohorts that evaluated the use of OLGA and OLGIM staging systems in predicting the risk of GC. We primarily compared OLGA/OLGIM III-IV versus OLGA/OLGIM 0-II categories and GC events. Pooled risk ratios (RR) and absolute risk differences with their 95% confidence intervals (CIs) were calculated. Results Eight studies were included (n = 12,526). The mean age of the patients ranged from 48.2 to 64.9 years. OLGA III-IV and OLGIM III-IV were associated with the development of GC in comparison to their 0-II categories (RR 32.31, 95% CI 9.14-114.21 and RR 12.38, 95% CI 5.75-26.65, respectively). OLGA III-IV and OLGIM III-IV were associated with an increase in the absolute risk of GC of 4% and 5%, respectively. The risk remained significant if we only included countries with high incidence of GC, and was greater if we excluded one study that included mostly patients with autoimmune gastritis. OLGA II and OLGIM II were associated with higher risk of high-grade dysplasia (HGD) and GC in comparison with OLGA 0-I and OLGIM 0-I, respectively. Conclusion Higher stages in OLGA and OLGIM systems are associated with a significantly increased risk of developing HGD and GC, validating these scoring systems for the assessment of GC risk and the design of endoscopic surveillance programs. Trial PROSPERO registration CRD42024565771.
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Affiliation(s)
- Harold Benites-Goñi
- Unidad de Revisiones Sistemáticas y Meta-análisis, Universidad San Ignacio de Loyola, Avenida La Fontana 550, 15024, Lima, Peru
- Department of Gastroenterology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru
| | | | - Gonzalo Latorre
- Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Adrian V Hernandez
- Unidad de Revisiones Sistemáticas y Meta-análisis, Universidad San Ignacio de Loyola, Lima, Peru
- Health Outcomes, Policy and Evidence Synthesis Group, University of Connecticut School of Pharmacy, Storrs, CT, USA
| | - Hugo Uchima
- Endoscopy Unit, Teknon Medical Center, Barcelona, Spain
- Endoscopy Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Arnoldo Riquelme
- Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile
- Centro para la Prevención y el Control del Cáncer, Santiago, Chile
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Voutsadakis IA. The Status of SOX2 Expression in Gastric Cancers with Induction of CDX2 Defines Groups with Different Genomic Landscapes. Genes (Basel) 2025; 16:279. [PMID: 40149431 PMCID: PMC11942492 DOI: 10.3390/genes16030279] [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: 02/10/2025] [Revised: 02/23/2025] [Accepted: 02/24/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Gastric adenocarcinoma is a highly lethal neoplasm with a short survival especially when metastatic. Few effective treatments are available for the control of the disease and palliation of patients with metastatic gastric cancer. Although progress has been made in the elucidation of molecular pathways invoked in gastric carcinogenesis, this knowledge has not yet led to major breakthroughs, in contrast to several other types of cancer. The role of stem cell transcription factors SOX2 and CDX2 is of particular interest in the pathogenesis of gastric cancer. METHODS The cohort of gastric adenocarcinomas from The Cancer Genome Atlas (TCGA) was interrogated and two groups of gastric cancers, with CDX2 induction and SOX2 suppression on the one hand and with CDX2 induction and SOX2 maintained expression on the other hand were retained. The induction of expression of the two transcription factors was defined as a mRNA expression z score compared with normal samples above zero. The two groups were compared for clinical-pathologic and genomic differences. RESULTS Among gastric cancers with up-regulated CDX2 mRNA, cancers with suppressed SOX2 mRNA were slightly more numerous (55.9%) than those with a maintained SOX2 expression. The SOX2 suppressed group had a higher prevalence of MSI high cancers (30.9% versus 10%) and of cases with high tumor mutation burden (35% versus 12.4%) than cancers with a SOX2 maintained expression, which presented more frequently high Chromosomal Instability (CIN). The group with SOX2 suppression had higher rates of mutations in many gastric cancer-associated genes such as epigenetic modifiers ARID1A, KMT2D, KMT2C, and KMT2B, as well as higher rates of mutations in genes encoding for receptor tyrosine kinases ERBB4 and FGFR1. On the other hand, TP53 mutations and amplifications in MYC, ERBB2, and CCNE1 were more common in the group with a maintained expression of SOX2, approaching significance for MYC. CONCLUSIONS Notable differences are present in the genomic landscape of CDX2-induced gastric cancer depending on the level of expression of SOX2 mRNA. Despite this, SOX2 mRNA expression levels were not prognostic.
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Affiliation(s)
- Ioannis A. Voutsadakis
- Algoma District Cancer Program, Sault Area Hospital, 750 Great Northern Road, Sault Ste. Marie, ON P6B 0A8, Canada; or
- Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, Canada
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12
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Liao W, Wang J, Li Y. Natural products based on Correa's cascade for the treatment of gastric cancer trilogy: Current status and future perspective. J Pharm Anal 2025; 15:101075. [PMID: 39957902 PMCID: PMC11830317 DOI: 10.1016/j.jpha.2024.101075] [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: 04/02/2024] [Revised: 07/18/2024] [Accepted: 08/16/2024] [Indexed: 02/18/2025] Open
Abstract
Gastric carcinoma (GC) is a malignancy with multifactorial involvement, multicellular regulation, and multistage evolution. The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa, in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis (Phase I) to gastric precancerous lesions (Phase II) and finally to GC (Phase III). Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa. Intervening in early gastric mucosal lesions, i.e., Phase I and II, will be the key strategy to prevent and treat GC. Natural products (NPs) have been an important source for drug development due to abundant sources, tremendous safety, and multiple pharmacodynamic mechanisms. This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis. In phase I, NPs modulate Helicobacter pylori urease activity, motility, adhesion, virulence factors, and drug resistance, thereby inhibiting H. pylori-induced gastric mucosal inflammation and oxidative stress, and facilitating ulcer healing. In Phase II, NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle, apoptosis, autophagy, and angiogenesis to reverse gastric precancerous lesions. In Phase III, NPs suppress cell proliferation, migration, invasion, angiogenesis, and cancer stem cells, induce apoptosis and autophagy, and enhance chemotherapeutic drug sensitivity for the treatment of GC. In contrast to existing work, we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development, providing new ideas for gastric cancer prevention, treatment, and drug development.
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Affiliation(s)
- Wenhao Liao
- Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China
| | - Jing Wang
- Department of Obstetrics and Gynecology, Chongqing Bishan Hospital of Traditional Chinese Medicine, Chongqing, 402760, China
| | - Yuchen Li
- Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, 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: 2] [Impact Index Per Article: 2.0] [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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14
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Pei B, Sun Q, Zhang Y, Wen Z, Ding W, Wu K, Li T, Li X. A novel nomogram for predicting the morbidity of chronic atrophic gastritis based on serum CXCL5 levels. BMC Cancer 2025; 25:63. [PMID: 39794766 PMCID: PMC11720569 DOI: 10.1186/s12885-024-13394-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025] Open
Abstract
OBJECTIVE This study aimed to investigate the diagnostic potential of serum CXC chemokine ligand 5 (CXCL5) in patients with chronic atrophic gastritis (CAG) and to establish a prediction model for better diagnosis of CAG. METHODS A retrospective analysis was conducted, encompassing 570 cases of CAG patients admitted to the Department of Gastroenterology of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, who underwent gastroscopy and received pathologically confirmed diagnoses between June 2018 and June 2023. Additionally, 570 cases without CAG who underwent health checkups were included and classified into the control group. Single-factor and multi-factorial logistic regression analyses were employed to identify risk factors of CAG, and a prediction model for diagnosing CAG was developed using R software. The predictive performance of the constructed model was verified and evaluated through ROC analysis, decision curve analysis (DCA), and prediction efficacy curve. RESULTS Multi-factorial logistic regression analysis revealed that history of smoking, family history of tumurs, Pepsinogen I (PG I), Gastrin 17 (G-17), Helicobacter pylori infection, D-dimer, and CXCL5 were independent risk factors in CAG patients. A nomogram for the diagnosis of CAG was constructed using R software. The ROC curve demonstrated that CXCL5 showed the best predictive efficacy as a single indicator, with an AUC of 0.897, a sensitivity of 0.789, and a specificity of 0.999. Furthermore, the nomogram exhibited an AUC of 0.992, a sensitivity of 0.958, and a specificity of 0.970. Calibration and DCA curves indicated that the predicted values of the nomogram were highly concordant with the observed values, thus demonstrating a high predictive value. CONCLUSION In this study, we found a correlation between serum CXCL5 level and CAG, and developed a prediction model to assist the clinical diagnosis of CAG.
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Affiliation(s)
- Bei Pei
- The First Clinical Medical College, Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China
| | - Qin Sun
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China
| | - Yi Zhang
- The First Clinical Medical College, Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China
| | - Ziang Wen
- The First Clinical Medical College, Nanjing Medical University, Nanjing, 210000, Jiangsu, China
| | - Wenjing Ding
- The First Clinical Medical College, Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China
| | - Kairui Wu
- The First Clinical Medical College, Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China
| | - Tingting Li
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China
| | - Xuejun Li
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230000, Anhui, China.
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15
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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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16
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Hoft SG, Brennan M, Carrero JA, Jackson NM, Pretorius CA, Bigley TM, Sáenz JB, DiPaolo RJ. Unveiling Cancer-Related Metaplastic Cells in Both Helicobacter pylori Infection and Autoimmune Gastritis. Gastroenterology 2025; 168:53-67. [PMID: 39236896 PMCID: PMC11663102 DOI: 10.1053/j.gastro.2024.08.032] [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: 04/23/2024] [Revised: 08/21/2024] [Accepted: 08/28/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND & AIMS Gastric metaplasia may arise as a consequence of chronic inflammation and is associated with an increased risk of gastric cancer development. Although Helicobacter pylori (Hp) infection and autoimmune gastritis (AIG) both induce gastric metaplasia, possible distinctions in resulting metaplastic cells and their respective cancer risks requires further investigation. METHODS Using both mouse models and human participants, we scrutinized the metaplasia originating from Hp infection and AIG. Gastric pathology and metaplasia were examined through histopathologic assessment. Molecular features of metaplastic cells were defined using single-cell transcriptomics in murine models of Hp infection and AIG, as well as in human biopsy specimens from patients with Hp infection and AIG. Expression of a newly defined cancer-related metaplastic biomarker was confirmed through immunofluorescence. RESULTS Metaplasia in Hp infection and AIG displayed comparable histopathologic and transcriptional features. Diverse metaplastic subtypes were identified across both disease settings, with subtle differences in the prevalence of certain subtypes between inflammatory contexts. Notably, Hp infection did not drive a unique metaplastic cell phenotype. One metaplastic subtype, which resembled incomplete intestinal metaplasia and shared transcriptional features with gastric cancer, was identified in both diseases. This cancer-like metaplastic subtype was characterized by expression of the cancer-associated biomarker ANPEP/CD13. CONCLUSION Both Hp infection and AIG trigger a diverse array of metaplastic cell types. Identification of a cancer-related metaplastic cell uniquely expressing ANPEP/CD13, present in both Hp- and AIG-induced gastritis, indicates the carcinogenic capacity of both diseases. This discovery can guide early detection and risk stratification for patients with chronic gastritis.
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Affiliation(s)
- Stella G Hoft
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Michelle Brennan
- Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Javier A Carrero
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Nicholas M Jackson
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Challen A Pretorius
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Tarin M Bigley
- Department of Pediatrics, Division of Rheumatology/Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri
| | - José B Sáenz
- Division of Gastroenterology, Departments of Medicine and Molecular Cell Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri
| | - Richard J DiPaolo
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri.
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Kuang W, Xu J, Xu F, Huang W, Majid M, Shi H, Yuan X, Ruan Y, Hu X. Current study of pathogenetic mechanisms and therapeutics of chronic atrophic gastritis: a comprehensive review. Front Cell Dev Biol 2024; 12:1513426. [PMID: 39720008 PMCID: PMC11666564 DOI: 10.3389/fcell.2024.1513426] [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: 10/18/2024] [Accepted: 11/25/2024] [Indexed: 12/26/2024] Open
Abstract
Chronic atrophic gastritis (CAG) is a prevalent digestive system disease characterized by atrophy of the gastric mucosa and the disappearance of inherent gastric glands. According to the theory of Correa's cascade, CAG is an important pathological stage in the transformation from normal condition to gastric carcinoma. In recent years, the global incidence of CAG has been increasing due to pathogenic factors, including Helicobacter pylori infection, bile reflux, and the consumption of processed meats. In this review, we comprehensively described the etiology and clinical diagnosis of CAG. We focused on elucidating the regulatory mechanisms and promising therapeutic targets in CAG, with the expectation of providing insights and theoretical support for future research on CAG.
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Affiliation(s)
- Weihong Kuang
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
| | - Jialin Xu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Fenting Xu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Weizhen Huang
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Muhammad Majid
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Hui Shi
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Xia Yuan
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Yongdui Ruan
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Xianjing Hu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
- Department of Acupuncture, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
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18
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Zhu L, Cai Q, Li G, Zou X. Bromodomain containing 4 inhibition combats gastric precancerous lesions via modulating macrophage polarization. Tissue Cell 2024; 91:102580. [PMID: 39396437 DOI: 10.1016/j.tice.2024.102580] [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: 04/23/2024] [Revised: 09/22/2024] [Accepted: 10/01/2024] [Indexed: 10/15/2024]
Abstract
OBJECTIVE Gastric precancerous lesions (GPL), characterized by intestinal metaplasia and dysplasia, marks a pivotal juncture in the transformation from gastritis to gastric cancer. Research on GPL could offer fresh perspectives on preventing cancer occurrence. METHODS This study employed 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) to establish GPL rat models and knocked BRD4 down in vivo to assess its impact on the lesions and macrophage morphology. Following that, the impacts of BRD4 knockdown on the malignant phenotypes of human gastric epithelial GES-1 cells were determined. Moreover, conditioned medium from macrophage was gathered and used for GES-1 cell culture. The involvement of macrophage polarization in the BRD4 regulatory mechanism in GES-1 cells was assessed. RESULTS This study elucidated that MNNG induced an increase level of BRD4 in the rat models. BRD4 knockdown reduced lesions based on pathological sections and immunohistochemistry to detect proliferative antigens. Western blotting and immunofluorescence showed that BRD4 knockdown suppressed epithelial-mesenchymal transition and macrophage M2 polarization. In in vitro experiments, BRD4 knockdown inhibited the malignant phenotype of GES-1 cells and the differentiation of THP-1 cells into M2 macrophages, respectively. The conditioned medium from M2 macrophages with BRD4 knockdown was co-incubated with GES-1 cells, which attenuated the malignant phenotypes compared with the medium from M2 macrophages. CONCLUSION Through in vivo and in vitro experiments, BRD4 upregulation was found to already occur during GPL, affecting macrophage polarization and epithelial cell cancerization. This finding provides an experimental basis for strategies targeting BRD4 inhibition at this critical stage.
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Affiliation(s)
- Lei Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China
| | - Qingxin Cai
- Department of Pharmacy, The First Specialized Hospital of Harbin, Harbin, Heilongjiang 150001, China
| | - Gang Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China
| | - Xiaoming Zou
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
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Lu X, Zhang W, Yang X, Yan X, Hussain Z, Wu Q, Zhao J, Yuan B, Yao K, Dong Z, Liu K, Jiang Y. Dronedarone hydrochloride inhibits gastric cancer proliferation in vitro and in vivo by targeting SRC. Transl Oncol 2024; 50:102136. [PMID: 39369581 PMCID: PMC11491965 DOI: 10.1016/j.tranon.2024.102136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 09/11/2024] [Accepted: 09/19/2024] [Indexed: 10/08/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is a significant global concern, ranking as the fifth most prevalent cancer. Unfortunately, the five-year survival rate is less than 30 %. Additionally, approximately 50 % of patients experience a recurrence or metastasis. As a result, finding new drugs to prevent relapse is of utmost importance. METHODS The inhibitory effect of Dronedarone hydrochloride (DH) on gastric cancer cells was examined using proliferation assays and anchorage-dependent assays. The binding of DH with SRC was detected by molecular docking, pull-down assays, and cellular thermal shift assays (CETSA). DH's inhibition of Src kinase activity was confirmed through in vitro kinase assays. The SRC knockout cells, established using the CRISPR-Cas9 system, were used to verify Src's role in GC cell proliferation. Patient-derived xenograft (PDX) models were employed to elucidate that DH suppressed tumor growth in vivo. RESULTS Our research discovered DH inhibited GC cell proliferation in vitro and in vivo. DH bound to the SRC protein to inhibit the SRC/AKT1 signaling pathway in gastric cancer. Additionally, we observed a decrease in the sensitivity of gastric cancer cells to DH upon down-regulation of SRC. Notably, we demonstrated DH's anti-tumor effects were similar to those of Dasatinib, a well-known SRC inhibitor, in GC patient-derived xenograft models. CONCLUSION Our research has revealed that Dronedarone hydrochloride, an FDA-approved drug, is an SRC inhibitor that can suppress the growth of GC cells by blocking the SRC/AKT1 signaling pathway. It provides a scientific basis for use in the clinical treatment of GC.
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Affiliation(s)
- Xuebo Lu
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou 450000 Henan, China
| | - Weizhe Zhang
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou 450000 Henan, China
| | - Xiaoxiao Yang
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou 450000 Henan, China
| | - Xiao Yan
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China
| | - Zubair Hussain
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China
| | - Qiong Wu
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou 450000 Henan, China
| | - Jinmin Zhao
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China
| | - Baoyin Yuan
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China
| | - Ke Yao
- Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou 450000 Henan, China
| | - Zigang Dong
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, Zhengzhou 450000, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou 450000, Henan, China; Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou 450000, Henan, China
| | - Kangdong Liu
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, Zhengzhou 450000, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou 450000, Henan, China; Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University 450000, Zhengzhou, Henan, China; Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou 450000, Henan, China
| | - Yanan Jiang
- The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, Zhengzhou 450000, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou 450000, Henan, China; Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University 450000, Zhengzhou, Henan, China; Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou 450000, Henan, China.
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20
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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: 7] [Impact Index Per Article: 7.0] [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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21
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Shi C, Tao R, Wang W, Tang J, Dou Z, Yuan X, Xu G, Liu H, Chen X. Development and validation of a nomogram for obesity and related factors to detect gastric precancerous lesions in the Chinese population: a retrospective cohort study. Front Oncol 2024; 14:1419845. [PMID: 39634264 PMCID: PMC11614725 DOI: 10.3389/fonc.2024.1419845] [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: 05/04/2024] [Accepted: 10/30/2024] [Indexed: 12/07/2024] Open
Abstract
Objectives The purpose of this study was to construct a nomogram to identify patients at high risk of gastric precancerous lesions (GPLs). This identification will facilitate early diagnosis and treatment and ultimately reduce the incidence and mortality of gastric cancer. Methods In this single-center retrospective cohort study, 563 participants were divided into a gastric precancerous lesion (GPL) group (n=322) and a non-atrophic gastritis (NAG) group (n=241) based on gastroscopy and pathology results. Laboratory data and demographic data were collected. A derivation cohort (n=395) was used to identify the factors associated with GPLs to develop a predictive model. Then, internal validation was performed (n=168). We used the area under the receiver operating characteristic curve (AUC) to determine the discriminative ability of the predictive model; we constructed a calibration plot to evaluate the accuracy of the predictive model; and we performed decision curve analysis (DCA) to assess the clinical practicability predictive model. Results Four -predictors (i.e., age, body mass index, smoking status, and -triglycerides) were included in the predictive model. The AUC values of this predictive model were 0.715 (95% CI: 0.665-0.765) and 0.717 (95% CI: 0.640-0.795) in the derivation and internal validation cohorts, respectively. These values indicated that the predictive model had good discrimination ability. The calibration plots and DCA suggested that the predictive model had good accuracy and clinical net benefit. The Hosmer-Lemeshow test results in the derivation and validation cohorts for this predictive model were 0.774 and 0.468, respectively. Conclusion The nomogram constructed herein demonstrated good performance in terms of predicting the risk of GPLs. This nomogram can be beneficial for the early detection of patients at high risk of GPLs, thus facilitating early treatment and ultimately reducing the incidence and mortality of gastric cancer.
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Affiliation(s)
- Chang’e Shi
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Gastroenterology, Anhui Public Health Clinical Center, Hefei, China
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University North District, Hefei, China
| | - Rui Tao
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, China
- Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China
- Department of Psychiatry, Anhui Psychiatric Center, Hefei, China
| | - Wensheng Wang
- Department of Gastroenterology, Anhui Public Health Clinical Center, Hefei, China
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University North District, Hefei, China
| | - Jinzhi Tang
- Department of Gastroenterology, Anhui Public Health Clinical Center, Hefei, China
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University North District, Hefei, China
| | - Zhengli Dou
- Department of Gastroenterology, Chaohu Hospital of Anhui Medical University, Hefei, China
| | - Xiaoping Yuan
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, China
- Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China
- Department of Psychiatry, Anhui Psychiatric Center, Hefei, China
| | - Guodong Xu
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, China
- Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China
- Department of Psychiatry, Anhui Psychiatric Center, Hefei, China
| | - Huanzhong Liu
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, China
- Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China
- Department of Psychiatry, Anhui Psychiatric Center, Hefei, China
- Department of Psychiatry, Huizhou NO.2 Hospital, Huizhou, China
| | - Xi Chen
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Lee YC, Chiang TH, Chiu HM, Su WW, Chou KC, Chen SLS, Yen AMF, Fann JCY, Chiu SYH, Chuang SL, Chen YR, Chen SD, Hu TH, Fang YJ, Wu MS, Chen THH, Yeh YP. Screening for Helicobacter pylori to Prevent Gastric Cancer: A Pragmatic Randomized Clinical Trial. JAMA 2024; 332:1642-1651. [PMID: 39348147 PMCID: PMC11581485 DOI: 10.1001/jama.2024.14887] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 07/09/2024] [Indexed: 10/01/2024]
Abstract
Importance Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown. Objective To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality. Design, Setting, and Participants A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020. Intervention Invitation for testing for H pylori stool antigen. Main Outcomes and Measures The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized. Results Of 240 000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63 508 were invited for HPSA + FIT, and 88 995 were invited for FIT alone. Of the 240 000 randomized, 38 792 who were unreachable and 48 705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31 497/63 508) for HPSA + FIT and 35.7% (31 777/88 995) for FIT alone. Among 12 142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P = .23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P = .57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%). Conclusions and Relevance Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone. Trial Registration ClinicalTrials.gov Identifier: NCT01741363.
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Affiliation(s)
- Yi-Chia Lee
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei City, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
| | - Tsung-Hsien Chiang
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
- Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei City, Taiwan
| | - Han-Mo Chiu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
| | - Wei-Wen Su
- Changhua Christian Hospital, Changhua County, Taiwan
| | | | - Sam Li-Sheng Chen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan
| | - Amy Ming-Fang Yen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan
| | - Jean Ching-Yuan Fann
- Department of Health Services Administration, College of Public Health, China Medical University, Taichung City, Taiwan
| | - Sherry Yueh-Hsia Chiu
- Department of Health Care Management and Healthy Aging Research Center, Chang Gung University, Taoyuan County, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
| | - Shu-Lin Chuang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei City, Taiwan
| | - Yi-Ru Chen
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan
| | - Shih-Dian Chen
- Chiayi Hospital, Ministry of Health and Welfare, Chiayi City, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
- Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Yi-Jen Fang
- Digestive Disease Center, Show-Chwan Memorial Hospital, Changhua County, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung-Hsing University, Taichung City, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
| | - Tony Hsiu-Hsi Chen
- Institute of Health Analytics and Statistics, College of Public Health, National Taiwan University, Taipei City, Taiwan
| | - Yen-Po Yeh
- Changhua County Public Health Bureau, Changhua County, Taiwan
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23
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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: 12] [Impact Index Per Article: 12.0] [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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24
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Ishibashi F, Suzuki S, Kobayashi K, Tanaka R, Kawakami T, Mochida K, Nagai M, Ishibashi Y, Morishita T. Cost-effective endoscopic screening for gastric cancer in a cohort with low Helicobacter pylori prevalence. J Gastroenterol Hepatol 2024; 39:2424-2431. [PMID: 39126193 DOI: 10.1111/jgh.16715] [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: 06/15/2024] [Revised: 07/06/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024]
Abstract
BACKGROUND AND AIM Periodic endoscopic screening for gastric cancer (GC) is widely performed in East Asia; however, the optimal screening strategy remains unclear. This study aimed to determine the most cost-effective endoscopic screening strategy for the detection and treatment of GC in a cohort with a low Helicobacter pylori prevalence. METHODS The following data were retrospectively extracted from participants who received screening endoscopy between April 2019 and March 2023: age, H. pylori infection status, presence of intestinal metaplasia, pathological diagnosis of GC, and the interval between the most recent endoscopies. A Markov state transition model was constructed based on the cohort data. The cost-effectiveness of 15 strategies with different starting ages (40/50/60 years) and screening intervals (1/2/3/4/5 years) was compared. The net monetary benefit (NMB) and incremental cost-effectiveness ratio (ICER) of quality-adjusted life-years gained by treatment were used as outcomes. RESULTS A simulation model was constructed based on the cohort data of 94 137 participants (mean age 54.5 years, males 57.9%; 74.4% H. pylori-naïve, 94.2% intestinal metaplasia-negative). The results of the base-case analysis showed that the screening strategy of 4-year intervals starting at the age of 40 years had the highest NMB (97 401 578 yen). In both the Monte Carlo simulation and one-way sensitivity analysis with a varying probability of H. pylori infection status transition, the ICER was superior in the screening strategy every 4 years, starting at age 40 years. CONCLUSIONS Our simulation showed that endoscopic screening at 4-year intervals starting at the age of 40 years was the most cost-effective method.
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Affiliation(s)
- Fumiaki Ishibashi
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
- Endoscopy Center, Koganei Tsurukame Clinic, Tokyo, Japan
| | - Sho Suzuki
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | | | - Ryu Tanaka
- Digestive Disease Center, Shinjuku Tsurukame Clinic, Tokyo, Japan
| | | | - Kentaro Mochida
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
- Endoscopy Center, Koganei Tsurukame Clinic, Tokyo, Japan
| | - Mizuki Nagai
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Yuichi Ishibashi
- Research and Development Initiative, Chuo University, Tokyo, Japan
| | - Tetsuo Morishita
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
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25
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Farinati F, Pelizzaro F. Gastric cancer screening in Western countries: A call to action. Dig Liver Dis 2024; 56:1653-1662. [PMID: 38403513 DOI: 10.1016/j.dld.2024.02.008] [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: 01/25/2024] [Revised: 02/11/2024] [Accepted: 02/12/2024] [Indexed: 02/27/2024]
Abstract
Gastric cancer is a major cause of cancer-related death worldwide, despite the reduction in its incidence. The disease is still burdened with a poor prognosis, particularly in Western countries. The main risk factor is the infection by Helicobacter pylori, classified as a class I carcinogen by the IARC, and It is well-known that primary prevention of gastric cancer can be achieved with the eradication of the infection. Moreover, non-invasive measurement of pepsinogens (PGI and PGI/PGII ratio) allows the identification of patients that should undergo upper gastrointestinal (GI) endoscopy. Gastric non-cardia adenocarcinoma is indeed preceded by a well-defined precancerous process that involves consecutive stages, described for the first time by Correa et al. more than 40 years ago, and patients with advance stages of gastric atrophy/intestinal metaplasia and with dysplastic changes should be followed-up periodically with upper GI endoscopies. Despite these effective screening and surveillance methods, national-level screening campaigns have been adopted only in few countries in eastern Asia (Japan and South Korea). In this review, we describe primary and secondary preventive measures for gastric cancer, discussing the need to introduce screening also in Western countries. Moreover, we propose a simple algorithm for screening that could be easily applied in clinical practice.
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Affiliation(s)
- Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, Padova 35128, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, Via Giustiniani 2, Padova 35128, Italy.
| | - Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, Padova 35128, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, Via Giustiniani 2, Padova 35128, Italy
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26
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Wang N, Niu X, Li L, Tang J, Bi Y, Liu S, Han K, Cheng Y, Cai Z, Chai N, Linghu E. A new, simplified endoscopic scoring system for predicting clinical outcome in gastric low-grade intraepithelial neoplasia: the "e-cout system". Neoplasia 2024; 56:101030. [PMID: 39047660 PMCID: PMC11318536 DOI: 10.1016/j.neo.2024.101030] [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: 05/09/2024] [Revised: 07/08/2024] [Accepted: 07/08/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND AND OBJECTIVES The clinical outcomes of gastric low-grade intraepithelial neoplasia (LGIN) exhibit significant diversity, and the current reliance on endoscopic biopsy for diagnosis poses limitations in devising appropriate treatment strategies for this disease. This study aims to establish a prognostic prediction scoring system (e-Cout system) for gastric LGIN, offering a theoretical foundation for solving this clinical challenge. METHODS Retrospectively selecting 1013 cases meeting the inclusion and exclusion criteria from over 300,000 cases of upper gastrointestinal endoscopy performed at the Digestive Endoscopy Center of our hospital between 2000 and 2022, the cohort included 484 cases as development cohort and 529 cases for validation. Employing relevant statistical analysis, we used development cohort data to establish the e-Cout system for gastric LGIN, and further used validation cohort data to for internal validation. RESULTS In the developmental stage, based on accordant regression coefficients, we assigned point values to six risk factors for poor prognosis: 4 points for microvessel (MV) distortion, 3 points for MV thickening, 2 points for ulcer, and 1 point each for lesion size > 2cm, disease duration > 1 year, and hyperemia and redness on the lesion surface. Patients were then categorized into four risk levels: low risk (0-1 point), medium risk (2-3), high risk (4-6), and very high risk (≥7). During the validation stage, significant differences in the three different outcomes of gastric LGIN were observed across all risk levels. The probability of reversal and progression showed a significant decrease and increase, respectively, with escalating of risk levels, and these differences were statistically significant (P< 0.001). CONCLUSIONS The proposed e-Cout system holds promise in aiding clinicians to predict the probability and risk levels of different clinical outcomes in patients with gastric LGIN. This system is expected to provide an improved foundation and guidance for the selection of clinical strategies for this disease.
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Affiliation(s)
- Nanjun Wang
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Xiaotong Niu
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China; Medical School of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Longsong Li
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Jing Tang
- Department of Radiology, The Fourth Medical Center of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing 100048, China
| | - Yawei Bi
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Shengzhen Liu
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Ke Han
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China; Medical School of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Yaxuan Cheng
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China; Medical School of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Zhaobei Cai
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China; Medical School of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Ningli Chai
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
| | - Enqiang Linghu
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
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27
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Pourfarzi F, Rashidi MM, Yazdanbod A, Nemati A, Dogaheh HP, Faghfuri E, Gorgani F, Hosseini-Asl S, Zamani B, Pourfarzi S, Etemadi A, Shafighian F, Rezaei N, Poustchi H, Malekzadeh R, Sadjadi A. Effectiveness of long-term low-dose aspirin in the prevention of gastric cancer after Helicobacter pylori eradication: study design and rationale of Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT). Trials 2024; 25:617. [PMID: 39300505 PMCID: PMC11412050 DOI: 10.1186/s13063-024-08455-5] [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: 05/07/2024] [Accepted: 09/05/2024] [Indexed: 09/22/2024] Open
Abstract
BACKGROUND In addition to Helicobacter pylori (H. pylori) infection eradication, some medications, including aspirin, metformin, and statins, have been suggested to have protective effects against gastric cancer (GC) development in observational studies. We launched the Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT) to evaluate the effectiveness of long-term low-dose aspirin use for the prevention of development and mortality of GC after H. pylori eradication. METHODS/DESIGN AGCPT is a prospective population-based double-blind, randomized clinical trial. The study sample was targeted at 21,000 participants aged from 35 to 70 years old, both sexes, in Ardabil, a province in northwest Iran with relatively high rates of GC incidence and mortality. All eligible participants were initially tested for H. pylori infection using a H. pylori stool antigen test. Participants with positive tests undergo H. pylori eradication by standard treatment regimens. All participants with a negative test and those with a positive test with a subsequent confirmed H. pylori eradication test were entered into the intervention phase. In the intervention phase, participants were allocated randomly into either the treatment (daily oral consumption of 81 mg enteric-coated aspirin tablets) arm or the control (placebo) arm using permuted balanced blocks. Subjects will be followed for an average period of 10 years to evaluate the incidence and mortality rates of GC. DISCUSSION In addition to preventing other diseases like cardiovascular events, aspirin may prevent GC incidence and mortality. AGCPT will investigate the difference between the two study arms in the proportion of the cumulative incidence and mortality rates of GC. The study's results may help policymakers and researchers update the strategies for GC prevention. TRIAL REGISTRATION This trial with the registry name of "The effect of Low-dose Aspirin in the Prevention of Gastric Cancer" was registered in the Iranian Registry of Clinical Trials, IRCT.ir, under the identifier IRCT201105082032N3. Registered on April 21, 2017.
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Affiliation(s)
- Farhad Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad-Mahdi Rashidi
- Digestive Disease Research Center (DDRC), Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Yazdanbod
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Ali Nemati
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hadi Peeri Dogaheh
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elnaz Faghfuri
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Fateme Gorgani
- Digestive Disease Research Center (DDRC), Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Saied Hosseini-Asl
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Bijan Zamani
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Sanaz Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Arash Etemadi
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Fateme Shafighian
- Digestive Disease Research Center (DDRC), Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Negar Rezaei
- Digestive Disease Research Center (DDRC), Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Oncology Research Center (DORC), Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Sadjadi
- Digestive Oncology Research Center (DORC), Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
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28
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Latorre G, Silva F, Montero I, Bustamante M, Dukes E, Uribe J, Corsi Sotelo O, Reyes D, Fuentes-López E, Pizarro M, Medel P, Torres J, Roa JC, Pizarro S, Achurra P, Donoso A, Wichmann I, Corvalán AH, Chahuan J, Candia R, Agüero C, Gonzalez R, Vargas JI, Espino A, Camargo MC, Shah SC, Riquelme A. Comparison of OLGA and OLGIM as predictors of gastric cancer in a Latin American population: the ECHOS Study. Gut 2024; 73:e18. [PMID: 38148138 DOI: 10.1136/gutjnl-2023-331059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 12/15/2023] [Indexed: 12/28/2023]
Affiliation(s)
- Gonzalo Latorre
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Felipe Silva
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Isabella Montero
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Miguel Bustamante
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eitan Dukes
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Javier Uribe
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Oscar Corsi Sotelo
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Diego Reyes
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eduardo Fuentes-López
- Department of Health Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Margarita Pizarro
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Patricio Medel
- Pharmacology and Toxicology Program, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Javiera Torres
- Department of Pathology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Carlos Roa
- Department of Pathology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Centro para la Prevención y el Control del Cáncer (CECAN), Santiago, Chile
| | - Sebastián Pizarro
- Department of Pathology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Pablo Achurra
- Department of Digestive Surgery, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Andrés Donoso
- Department of Digestive Surgery, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Ignacio Wichmann
- Department of Obstetrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
- Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Alejandro H Corvalán
- Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile
- Department of Hematology & Oncology, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Javier Chahuan
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Roberto Candia
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Carlos Agüero
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Robinson Gonzalez
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jose Ignacio Vargas
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Alberto Espino
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Shailja C Shah
- Gastroenterology Section, Veterans Affairs, San Diego Healthcare System, San Diego, California, USA
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Arnoldo Riquelme
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Centro para la Prevención y el Control del Cáncer (CECAN), Santiago, Chile
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29
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Eskandarion MR, Eskandarieh S, Shakoori Farahani A, Mahmoodzadeh H, Shahi F, Oghabian MA, Shirkoohi R. Prediction of novel biomarkers for gastric intestinal metaplasia and gastric adenocarcinoma using bioinformatics analysis. Heliyon 2024; 10:e30253. [PMID: 38737262 PMCID: PMC11088262 DOI: 10.1016/j.heliyon.2024.e30253] [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: 07/15/2023] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/14/2024] Open
Abstract
Background & aim The histologic and molecular changes from intestinal metaplasia (IM) to gastric cancer (GC) have not been fully characterized. The present study sought to identify potential alterations in signaling pathways in IM and GC to predict disease progression; these alterations can be considered therapeutic targets. Materials & methods Seven gene expression profiles were selected from the GEO database. Discriminate differentially expressed genes (DEGs) were analyzed by EnrichR. The STRING database, Cytoscape, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, NetworkAnalyst, MirWalk database, OncomiR, and bipartite miRNA‒mRNA correlation network was used for downstream analyses of selected module genes. Results Analyses revealed that extracellular matrix-receptor interactions (ITGB1, COL1A1, COL1A2, COL4A1, FN1, COL6A3, and THBS2) in GC and PPAR signaling pathway interactions (FABP1, APOC3, APOA1, HMGCS2, and PPARA and PCK1) in IM may play key roles in both the carcinogenesis and progression of underlying GC from intestinal metaplasia. IM enrichment indicated that this is closely related to digestion and absorption. The TF-hub gene regulatory network revealed that AR, TCF4, SALL4, and ESR1 were more important for hub gene expression. It was revealed that the development and prediction of GC may be affected by hsa-miR-29. It was found that PTGR1, C1orf115, CRYL1, ALDOB, and SULT1B1 were downregulated in GC and upregulated in IM. Therefore, they might have tumor suppressor activity in GC progression. Conclusion New potential biomarkers and pathways involved in GC and IM were identified that are important for the transformation of GC from IM to adenocarcinoma and can be therapeutic targets for GC.
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Affiliation(s)
| | - Sharareh Eskandarieh
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Shakoori Farahani
- Medical Genetics Ward, IKHC Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Habibollah Mahmoodzadeh
- Department of Surgery, Cancer Research Center, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
| | - Farhad Shahi
- Department of Medical Oncology, Cancer Research Center, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Oghabian
- Medical Physics Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Shirkoohi
- Cancer Research Center, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
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Liao X, Lin R, Zhang Z, Tian D, Liu Z, Chen S, Xu G, Su M. Genome-wide DNA methylation and transcriptomic patterns of precancerous gastric cardia lesions. J Natl Cancer Inst 2024; 116:681-693. [PMID: 38258659 DOI: 10.1093/jnci/djad244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 10/25/2023] [Accepted: 11/15/2023] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Intestinal metaplasia (IM) and intraepithelial neoplasia (IEN) are considered precursors of gastric cardia cancer (GCC). Here, we investigated the histopathologic and molecular profiles of precancerous gastric cardia lesions (PGCLs) and biomarkers for risk stratification of gastric cardia IM. METHODS We conducted a hospital-based evaluation (n = 4578) for PGCL profiles in high-incidence and non-high-incidence regions for GCC in China. We next performed 850K methylation arrays (n = 42) and RNA-seq (n = 44) in tissues with PGCLs. We then examined the protein expression of candidate biomarker using immunohistochemistry. RESULTS Of the 4578 participants, 791 were diagnosed with PGCLs (600 IM, 62 IM with IEN, and 129 IEN). We found that individuals from high-incidence regions (26.7%) were more likely to develop PGCLs than those from non-high-incidence areas (13.5%). DNA methylation and gene expression alterations, indicated by differentially methylated probes (DMPs) and differentially expressed genes (DEGs), exhibited a progressive increase from type I IM (DMP = 210, DEG = 24), type II IM (DMP = 3402, DEG = 129), to type III IM (DMP = 3735, DEG = 328), peaking in IEN (DMP = 47 373, DEG = 2278). Three DEGs with aberrant promoter methylation were identified, shared exclusively by type III IM and IEN. Of these DEGs, we found that OLFM4 expression appears in IMs and increases remarkably in IENs (P < .001). CONCLUSIONS We highlight that type III IM and IEN share similar epigenetic and transcriptional features in gastric cardia and propose biomarkers with potential utility in risk prediction.
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Affiliation(s)
- Xiaoqi Liao
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
| | - Runhua Lin
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, People's Republic of China
| | - Zhihua Zhang
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
| | - Dongping Tian
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, People's Republic of China
| | - Zhaohui Liu
- Department of Gastroenterology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, People's Republic of China
| | - Songqin Chen
- Department of Pathology, Jieyang People's Hospital, Jieyang, People's Republic of China
| | - Guohua Xu
- Department of Gastroenterology, Huiyang Sanhe Hospital, Huizhou, People's Republic of China
| | - Min Su
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, People's Republic of China
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Guzmán J, Castillo D, González-Siccha AD, Bussalleu A, Trespalacios-Rangel AA, Lescano AG, Sauvain M. Helicobacter pylori cagA, vacA, iceA and babA Genotypes from Peruvian Patients with Gastric Intestinal Metaplasia. Cancers (Basel) 2024; 16:1476. [PMID: 38672558 PMCID: PMC11047899 DOI: 10.3390/cancers16081476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 03/10/2024] [Accepted: 03/13/2024] [Indexed: 04/28/2024] Open
Abstract
We explored the clinical-stage association of gastric intestinal metaplasia (IM) compared to cases of chronic non-atrophic gastritis (CNAG) and its relationship with virulence genotypes of Helicobacter pylori (H. pylori) clinical isolates from patients with dyspepsia in Peru. This study was cross-sectional and included 158 H. pylori clinical isolates; each isolate corresponded to a different Peruvian patient, genotyped by polymerase chain reaction to detect cagA gene and EPIYA motifs, the vacA gene (alleles s1, s2, i1, i2, d1, d2, m1, m2 and subtypes s1a, s1b and s1c), the iceA gene (alleles 1 and 2), and the babA gene (allele 2). We observed that 38.6% presented with IM and that all clinical isolates were CagA positive. The EPIYA-ABC motif was predominant (68.4%), and we observed a high frequency for the vacA gene alleles s1 (94.9%), m1 (81.7%), i1 (63.9%), and d1 (70.9%). Strains with both iceA alleles were also detected (69.6%) and 52.2% were babA2 positive. In addition, it was observed that the cagA+/vacAs1m1 (PR: 2.42, 1.14 to 5.13, p < 0.05) and cagA+/vacAs1am1 (PR: 1.67, 1.13 to 2.45, p < 0.01) genotypes were associated with IM. Our findings revealed the cagA and vacA risk genotypes predominance, and we provided clinically relevant associations between Peruvian patients with H. pylori infection and IM clinical stage.
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Affiliation(s)
- Jesús Guzmán
- Laboratorio Centinela de Helicobacter pylori, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15024, Peru; (D.C.); (A.B.); (M.S.)
- Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia, Lima 15102, Peru;
| | - Denis Castillo
- Laboratorio Centinela de Helicobacter pylori, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15024, Peru; (D.C.); (A.B.); (M.S.)
| | - Anabel D. González-Siccha
- Departamento de Bioquímica, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo 13011, Peru;
| | - Alejandro Bussalleu
- Laboratorio Centinela de Helicobacter pylori, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15024, Peru; (D.C.); (A.B.); (M.S.)
| | - Alba A. Trespalacios-Rangel
- Grupo de Investigación en Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá 110231, Colombia;
| | - Andres G. Lescano
- Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia, Lima 15102, Peru;
| | - Michel Sauvain
- Laboratorio Centinela de Helicobacter pylori, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15024, Peru; (D.C.); (A.B.); (M.S.)
- UMR 152 Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD), Université de Toulouse, CEDEX 9, 31062 Toulouse, France
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Fang S, Liu Z, Qiu Q, Tang Z, Yang Y, Kuang Z, Du X, Xiao S, Liu Y, Luo Y, Gu L, Tian L, Liang X, Fan G, Zhang Y, Zhang P, Zhou W, Liu X, Tian J, Wei W. Diagnosing and grading gastric atrophy and intestinal metaplasia using semi-supervised deep learning on pathological images: development and validation study. Gastric Cancer 2024; 27:343-354. [PMID: 38095766 PMCID: PMC10896941 DOI: 10.1007/s10120-023-01451-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 11/09/2023] [Indexed: 02/28/2024]
Abstract
OBJECTIVE Patients with gastric atrophy and intestinal metaplasia (IM) were at risk for gastric cancer, necessitating an accurate risk assessment. We aimed to establish and validate a diagnostic approach for gastric biopsy specimens using deep learning and OLGA/OLGIM for individual gastric cancer risk classification. METHODS In this study, we prospectively enrolled 545 patients suspected of atrophic gastritis during endoscopy from 13 tertiary hospitals between December 22, 2017, to September 25, 2020, with a total of 2725 whole-slide images (WSIs). Patients were randomly divided into a training set (n = 349), an internal validation set (n = 87), and an external validation set (n = 109). Sixty patients from the external validation set were randomly selected and divided into two groups for an observer study, one with the assistance of algorithm results and the other without. We proposed a semi-supervised deep learning algorithm to diagnose and grade IM and atrophy, and we compared it with the assessments of 10 pathologists. The model's performance was evaluated based on the area under the curve (AUC), sensitivity, specificity, and weighted kappa value. RESULTS The algorithm, named GasMIL, was established and demonstrated encouraging performance in diagnosing IM (AUC 0.884, 95% CI 0.862-0.902) and atrophy (AUC 0.877, 95% CI 0.855-0.897) in the external test set. In the observer study, GasMIL achieved an 80% sensitivity, 85% specificity, a weighted kappa value of 0.61, and an AUC of 0.953, surpassing the performance of all ten pathologists in diagnosing atrophy. Among the 10 pathologists, GasMIL's AUC ranked second in OLGA (0.729, 95% CI 0.625-0.833) and fifth in OLGIM (0.792, 95% CI 0.688-0.896). With the assistance of GasMIL, pathologists demonstrated improved AUC (p = 0.013), sensitivity (p = 0.014), and weighted kappa (p = 0.016) in diagnosing IM, and improved specificity (p = 0.007) in diagnosing atrophy compared to pathologists working alone. CONCLUSION GasMIL shows the best overall performance in diagnosing IM and atrophy when compared to pathologists, significantly enhancing their diagnostic capabilities.
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Affiliation(s)
- Shuangshuang Fang
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine; Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Wangjing, Beijing, 100102, China
| | - Zhenyu Liu
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
- School of Artificial Intelligence, University of Chinese Academy of Science, Beijing, 100190, China
| | - Qi Qiu
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
- School of Artificial Intelligence, University of Chinese Academy of Science, Beijing, 100190, China
| | - Zhenchao Tang
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
| | - Yang Yang
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine; Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Wangjing, Beijing, 100102, China
| | - Zhongsheng Kuang
- Department of Pathology, The First Affiliated Hospital of Guangdong University of Traditional Chinese Medicine, Guangzhou, 510405, China
| | - Xiaohua Du
- Department of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, 510120, China
| | - Shanshan Xiao
- Department of Pathology, The First Affiliated Hospital of Guangdong University of Traditional Chinese Medicine, Guangzhou, 510405, China
| | - Yanyan Liu
- Department of Pathology, The First Affiliated Hospital of Guangdong University of Traditional Chinese Medicine, Guangzhou, 510405, China
| | - Yuanbin Luo
- Department of Pathology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, 730050, China
| | - Liping Gu
- Department of Pathology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, 730050, China
| | - Li Tian
- Department of Pathology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, 730050, China
| | - Xiaoxia Liang
- Department of Pathology, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, 030012, China
| | - Guiling Fan
- Department of Pathology, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, 030012, China
| | - Yu Zhang
- Department of Pathology, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, 030012, China
| | - Ping Zhang
- Department of Pathology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, China
| | - Weixun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Beijing, 100730, China
| | - Xiuli Liu
- Department of Pathology and Immunology, Washington University, St. Louis, MO, 98195, USA
| | - Jie Tian
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
- School of Artificial Intelligence, University of Chinese Academy of Science, Beijing, 100190, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, 710126, Shaanxi, China
| | - Wei Wei
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine; Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6, Zhonghuan South Road, Wangjing, Beijing, 100102, China.
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Rugge M, Genta RM, Malfertheiner P, Dinis-Ribeiro M, El-Serag H, Graham DY, Kuipers EJ, Leung WK, Park JY, Rokkas T, Schulz C, El-Omar EM. RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates. Gut 2024; 73:407-441. [PMID: 38383142 DOI: 10.1136/gutjnl-2023-331164] [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: 09/18/2023] [Accepted: 12/18/2023] [Indexed: 02/23/2024]
Abstract
At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine-DIMED, University of Padova, Padua, Italy
- Azienda Zero, Veneto Tumour Registry, Padua, Italy
| | - Robert M Genta
- Gastrointestinal Pathology, Inform Diagnostics Research Institute, Dallas, Texas, USA
- Pathology, Baylor College of Medicine, Houston, Texas, USA
| | - Peter Malfertheiner
- Medizinische Klinik und Poliklinik II, Ludwig Maximilian Universität Klinikum München, Munich, Germany
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany
| | - Mario Dinis-Ribeiro
- Porto Comprehensive Cancer Center & RISE@CI-IPO, University of Porto, Porto, Portugal
- Gastroenterology Department, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Hashem El-Serag
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Houston VA Health Services Research & Development Center of Excellence, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - David Y Graham
- Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Ernst J Kuipers
- Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - Jin Young Park
- International Agency for Research on Cancer, Lyon, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
| | | | - Emad M El-Omar
- Microbiome Research Centre, University of New South Wales, Sydney, New South Wales, Australia
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Yoo HW, Hong SJ, Kim SH. Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology 2024; 166:313-322.e3. [PMID: 37863270 DOI: 10.1053/j.gastro.2023.10.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 09/21/2023] [Accepted: 10/08/2023] [Indexed: 10/22/2023]
Abstract
BACKGROUND & AIMS The study investigated the association between Helicobacter pylori treatment and the risk of gastric cancer after endoscopic resection of gastric dysplasia. METHODS Patients who received endoscopic resection for gastric dysplasia between 2010 and 2020 from Korean nationwide insurance data were included. We verified the occurrence of new-onset gastric cancer and metachronous gastric neoplasm, which encompasses both cancer and dysplasia, >1 year after the index endoscopic resection. Newly diagnosed gastric cancer ≥3 years and ≥5 years was regarded as late-onset gastric cancer. A multivariable Cox regression model with H pylori treatment status as a time-dependent covariate was used to determine the risk of gastric cancer and metachronous gastric neoplasms. RESULTS Gastric dysplasia in 69,722 patients was treated with endoscopy, and 49.5% were administered H pylori therapy. During the median 5.6 years of follow-up, gastric cancer developed in 2406 patients and metachronous gastric neoplasms developed in 3342 patients. Receiving H pylori therapy was closely related to lower gastric cancer risk (adjusted hazard ratio [aHR], 0.88; 95% confidence interval [CI], 0.80-0.96). H pylori treatment also significantly decreased metachronous gastric neoplasm development (aHR, 0.76; 95% CI, 0.70-0.82). Furthermore, H pylori therapy showed a prominent protective effect for late-onset gastric cancer development at ≥3 years (aHR, 0.84; 95% CI, 0.75-0.94) and ≥5 years (aHR, 0.80; 95% CI, 0.68-0.95). CONCLUSIONS In this nationwide cohort, H pylori therapy after endoscopic resection of gastric dysplasia was associated with a reduced risk of gastric cancer and metachronous gastric neoplasm occurrence.
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Affiliation(s)
- Hae Won Yoo
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University College of Medicine, Bucheon, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University College of Medicine, Bucheon, Korea.
| | - Shin Hee Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University College of Medicine, Bucheon, Korea
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Ford AC, Graham DY. Toward Quantification of H pylori-associated Gastric Cancer Risk: Further Evidence Supporting Development of Population-based Strategies for H pylori Eradication. Gastroenterology 2024; 166:248-249. [PMID: 37924852 DOI: 10.1053/j.gastro.2023.10.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 10/23/2023] [Indexed: 11/06/2023]
Affiliation(s)
- Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom.
| | - David Y Graham
- Department of Medicine, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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Chen H, Liu SY, Huang SH, Liu M, Chen GX. Applications of artificial intelligence in gastroscopy: a narrative review. J Int Med Res 2024; 52:3000605231223454. [PMID: 38235690 PMCID: PMC10798083 DOI: 10.1177/03000605231223454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 12/11/2023] [Indexed: 01/19/2024] Open
Abstract
Gastroscopy, a critical tool for the diagnosis of upper gastrointestinal diseases, has recently incorporated artificial intelligence (AI) technology to alleviate the challenges involved in endoscopic diagnosis of some lesions, thereby enhancing diagnostic accuracy. This narrative review covers the current status of research concerning various applications of AI technology to gastroscopy, then discusses future research directions. By providing this review, we hope to promote the integration of gastroscopy and AI technology, with long-term clinical applications that can assist patients.
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Affiliation(s)
- Hu Chen
- The First Clinical Medical School, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Shi-yu Liu
- Department of Gastroenterology, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Si-hui Huang
- Department of Gastroenterology, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Min Liu
- School of Chemical Engineering & Technology, China University of Mining and Technology, Xuzhou, Jiangsu, China
| | - Guang-xia Chen
- Department of Gastroenterology, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China
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Sun Z, Deng H, Liu Y, Zhang J, Xu C. A Systematic Review and Meta-Analysis of Xiangsha Liujunzi Decoction in the Treatment of Chronic Gastritis. Comb Chem High Throughput Screen 2024; 27:386-399. [PMID: 37861042 DOI: 10.2174/0113862073252121230925103843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 08/27/2023] [Accepted: 09/06/2023] [Indexed: 10/21/2023]
Abstract
BACKGROUND Chronic gastritis (CG) is characterized by inflammation of the gastric mucosa, which can progress to atrophic gastritis, intestinal metaplasia, and dysplasia. Xiangsha Liujunzi Decoction (XSLJZD), a classic traditional Chinese medicine prescription commonly used to treat digestive system diseases, is widely used to treat CG. Therefore, it is necessary to systematically evaluate the efficacy and safety of XSLJZD in the treatment of CG. METHODS Chinese and English databases were searched, and randomized controlled trials of XSLJZD for the treatment of CG were collected from the establishment of the databases to December 28, 2022. Studies were screened according to inclusion and exclusion criteria. The methodological quality of the included studies was assessed using the risk-of-bias assessment tool in the Cochrane Handbook. Data from the included studies were extracted, and a meta-analysis was performed using Review Manager 5.3 and Stata 15.1. Finally, funnel plots and Egger's tests were used to assess publication bias. RESULTS Fourteen studies with a sample size of 1434 cases. XSLJZD has more advantages than conventional treatment in the treatment of CG, as it can improve the clinical cure rate, clinical efficacy rate, efficacy rate of endoscopic examination, recurrence rate, and TCM symptom scores, and is relatively safe. Funnel plots and Egger's tests indicated publication bias in the included studies. CONCLUSION The results of the meta-analysis showed that XSLJZD has advantages in treating CG compared with conventional treatment and is relatively safe. However, owing to the limitations in the quality and quantity of the included studies, caution is recommended when generalizing and applying these results. Further high-quality studies are needed to confirm these findings.
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Affiliation(s)
- Zheyu Sun
- Changchun University of Traditional Chinese Medicine, Changchun City, Jilin Province, China
| | - Haiyan Deng
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China
| | - Yuna Liu
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China
| | - Jing Zhang
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China
| | - Chunfeng Xu
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China
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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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Thiruvengadam NR, Gupta S, Buller S, Awad I, Gandhi D, Ibarra A, Latorre G, Riquelme A, Kochman ML, Cote G, Shah SC, Saumoy M. The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis. Clin Gastroenterol Hepatol 2024; 22:51-61. [PMID: 37302442 DOI: 10.1016/j.cgh.2023.05.028] [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: 03/24/2023] [Revised: 05/23/2023] [Accepted: 05/30/2023] [Indexed: 06/13/2023]
Abstract
BACKGROUND & AIMS Gastric intestinal metaplasia (GIM) is associated with a higher risk of noncardia intestinal gastric adenocarcinoma (GA). The aim of this study was to estimate lifetime benefits, complications, and cost-effectiveness of GIM surveillance using esophagogastroduodenoscopy (EGD). METHODS We developed a semi-Markov microsimulation model of patients with incidentally detected GIM, to compare the effectiveness of EGD surveillance with no surveillance at 10-year, 5-year, 3-year, 2-year, and 1-year intervals. We modeled a simulated cohort of 1,000,000 US individuals aged 50 with incidental GIM. Outcome measures were lifetime GA incidence, mortality, number of EGDs, complications, undiscounted life-years gained, and incremental cost-effectiveness ratio with a willingness-to-pay threshold of $100,000/quality-adjusted life-year (QALY). RESULTS In the absence of surveillance, the model simulated 32.0 lifetime GA cases and 23.0 lifetime GA deaths per 1000 individuals with GIM, respectively. Among surveilled individuals, simulated lifetime GA incidence (per 1000) decreased with shorter surveillance intervals (10-year to 1-year, 11.2-6.1) as did GA mortality (7.4-3.6). Compared with no surveillance, all modeled surveillance intervals yielded greater life expectancy (87-190 undiscounted life-years gained per 1000); 5-year surveillance provided the greatest number of life-years gained per EGD performed and was the cost-effective strategy ($40,706/QALY). In individuals with risk factors of family history of GA or anatomically extensive, incomplete-type GIM intensified 3-year surveillance was cost-effective (incremental cost-effectiveness ratio $28,156/QALY and $87,020/QALY, respectively). CONCLUSIONS Using microsimulation modeling, surveillance of incidentally detected GIM every 5 years is associated with reduced GA incidence/mortality and is cost-effective from a health care sector perspective. Real-world studies evaluating the impact of GIM surveillance on GA incidence and mortality in the United States are needed.
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Affiliation(s)
- Nikhil R Thiruvengadam
- Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California.
| | - Shashank Gupta
- Department of Medicine, Loma Linda University Health, Loma Linda, California
| | - Seth Buller
- Loma Linda University School of Medicine, Loma Linda, California
| | - Imad Awad
- Department of Medicine, Loma Linda University Health, Loma Linda, California
| | - Devika Gandhi
- Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California
| | - Allison Ibarra
- Division of Gastroenterology, University of California San Diego, San Diego, California
| | - Gonzalo Latorre
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Arnoldo Riquelme
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Centro para la Prevención y el Control del Cáncer (CECAN), Santiago, Chile
| | - Michael L Kochman
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Gregory Cote
- Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, Oregon
| | - Shailja C Shah
- Division of Gastroenterology, University of California San Diego, San Diego, California; Gastroenterology Section, Veterans Affairs San Diego Healthcare System, San Diego, California
| | - Monica Saumoy
- Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, New Jersey
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Huang X, Xie X, Kang N, Qi R, Zhou X, Wang Y, Jiang H. SERPINB5 is a novel serum diagnostic biomarker for gastric high-grade intraepithelial neoplasia and plays a role in regulation of macrophage phenotypes. Transl Oncol 2023; 37:101757. [PMID: 37573714 PMCID: PMC10425712 DOI: 10.1016/j.tranon.2023.101757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 07/31/2023] [Accepted: 08/07/2023] [Indexed: 08/15/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) develops from gastric precancerous lesions (GPL), and early diagnosis and treatment at the premalignant stage may achieve a higher benefit‒cost ratio with a reduced necessity for surgery. However, reliable noninvasive screening biomarkers of GPL are currently lacking. METHODS The marker genes of GPL encoding extracellular proteins were identified by bioinformatics analysis and further verified by immunofluorescence and immunohistochemistry assays. Serum samples were collected to measure the levels of SERPINB5, the diagnostic efficacy of which was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Finally, the effect of SERPINB5 on the phenotypic conversion of macrophages was verified by public data and in vitro experiments. RESULTS SERPINB5 was identified as an extracellular biomarker of GPL that had good diagnostic efficacy. High expression of SERPINB5 was observed in the epithelial cells and adjacent extracellular matrix on sections of gastric high-grade intraepithelial neoplasia (HGIN). Importantly, SERPINB5 determined in serum was significantly increased in the HGIN group, and the AUC for discriminating between HGIN and chronic gastritis or low-grade intraepithelial neoplasia was 0.9936 and 0.9750, respectively. Moreover, SERPINB5 expression was positively correlated with macrophage infiltration, and M1 marker NOS2 expression, but negatively correlated with M2 marker CSF1R expression. In THP-1-derived macrophages, SERPINB5 upregulated expression of M1-related cytokines TNF-α and IL-12, and M1 marker CD86, but suppressed production of M2-related cytokines TGF-β and IL-10. CONCLUSIONS Our study provides evidence that SERPINB5 may serve as a promising noninvasive serum biomarker for gastric HGIN screening and regulate macrophage phenotype conversion.
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Affiliation(s)
- Xiuhong Huang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang 050000, China
| | - Xiaoli Xie
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang 050000, China
| | - Ning Kang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang 050000, China
| | - Ran Qi
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang 050000, China
| | - Xue Zhou
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang 050000, China
| | - Yijun Wang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang 050000, China
| | - Huiqing Jiang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang 050000, China.
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Salazar Giraldo BE, Gómez Villegas SI, Vélez Gómez DE, Ramírez Lopera V, Pérez Cala TL, Martínez A. Frecuencia de la infección por Helicobacter pylori en pacientes que requirieron endoscopia digestiva en siete unidades de tres subregiones de Antioquia. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:290-303. [DOI: 10.22516/25007440.983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Objetivo: determinar la frecuencia de Helicobacter pylori y la presencia de factores sociodemográficos, hábitos de vida y antecedentes personales y familiares de enfermedades gastroduodenales en pacientes que requirieron y fueron llevados a endoscopia digestiva (sintomáticos o por tamización) en siete unidades de endoscopia de tres subregiones de Antioquia.
Materiales y métodos: estudio transversal realizado entre 2016 y 2018 que incluyó a 272 participantes. Los factores sociodemográficos, hábitos de vida, antecedentes personales y familiares se relacionaron con la infección por H. pylori. Se realizó estadística descriptiva y análisis bivariado para establecer la asociación entre las variables y el análisis multivariado (regresión binomial) para ajustar las razones de prevalencia de los factores asociados. Un valor p ≤ 0,05 se consideró estadísticamente significativo.
Resultados: la frecuencia de infección por H. pylori fue de 55,9%, con diferencias por subregión (área metropolitana del Valle de Aburrá: 54,3%, oriente: 64% y Urabá: 79,2%). Los factores asociados a la infección por H. pylori fueron sexo masculino (razón de prevalencia ajustada [RPA] = 1,26; intervalo de confianza [IC] del 95% = 1,04-1,52), edad de 18-55 años (RPA = 1,62; IC 95% = 1,22-2,16), ausencia de agua potable (RPA = 1,40; IC 95%: 1,15-1,72) y nivel educativo inferior al universitario (RPA = 1,73; IC 95% = 1,26-2,38).
Conclusión: la frecuencia de H. pylori fue mayor que en otros estudios recientes porque se emplearon diferentes pruebas diagnósticas para su detección y se demostraron diferencias en la frecuencia de la infección por región, lo cual se explica por la heterogeneidad en las poblaciones analizadas. Este estudio sugiere la necesidad de mejorar las condiciones de vida de la población para reducir la infección por H. pylori y dirigir medidas de prevención primaria de la infección especialmente en los grupos familiares, en hombres, individuos entre 18 y 55 años, sin agua potable y con un nivel educativo inferior al universitario.
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Zheng Z, Lu Z, Song Y. Long-term proton pump inhibitors use and its association with premalignant gastric lesions: a systematic review and meta-analysis. Front Pharmacol 2023; 14:1244400. [PMID: 37693896 PMCID: PMC10492503 DOI: 10.3389/fphar.2023.1244400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/14/2023] [Indexed: 09/12/2023] Open
Abstract
Background: Long-term maintenance therapy with proton pump inhibitors (PPIs) is a common treatment strategy for acid-related gastrointestinal diseases. However, concerns have been raised about the potential increased risk of gastric cancer and related precancerous lesions with long-term PPI use. This systematic review and meta-analysis aimed to evaluate this potential risk. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before 1 March 2023, with no language restrictions. The primary endpoint was the occurrence and progression of gastric mucosal atrophy, intestinal metaplasia, Enterochromaffin-like (ECL) cell hyperplasia, gastric polyps, and gastric cancer during the trial and follow-up. Data were analysed using a random effects model. Results: Of the 4,868 identified studies, 10 met the inclusion criteria and were included in our analysis, comprising 27,283 participants. Compared with other treatments, PPI maintenance therapy for more than 6 months was associated with an increased risk of ECL cell hyperplasia (OR 3.01; 95% CI 1.29 to 7.04; p = 0.01). However, no significant increase was found in the risk of gastric mucosal atrophy (OR 1.01; 95% CI 0.55 to 1.85; p = 0.97), intestinal metaplasia (OR 1.14; 95% CI 0.49 to 2.68; p = 0.76), gastric polyps (OR 1.13; 95% CI 0.68 to 1.89; p = 0.64), or gastric cancer (OR 1.06; 95% CI 0.79 to 1.43; p = 0.71). Conclusion: This systematic review and meta-analysis does not support an increased risk of gastric cancer or related precancerous lesions with long-term PPI maintenance therapy. However, long-term PPI use should be monitored for potential complications such as ECL cell hyperplasia. Further studies are needed to confirm these findings and evaluate the safety of PPI maintenance therapy for acid-related gastrointestinal diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42022379692).
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Affiliation(s)
- Zeyi Zheng
- School of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
| | - Ziyu Lu
- School of Basic Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
| | - Yani Song
- School of Water Resources and Hydropower Engineering, Wuhan University, Wuhan, Hubei, China
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Wang T, Girgis S, Chang HJ, Assi A, Fagan-Garcia K, Cromarty T, Munday R, Goodman KJ, Veldhuyzen van Zanten S, the CAN Help Working Group. Changes in Gastric Pathology after H. pylori Treatment in Community-Driven Research Aimed at Gastric Cancer Prevention. Cancers (Basel) 2023; 15:3950. [PMID: 37568765 PMCID: PMC10417032 DOI: 10.3390/cancers15153950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/22/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
Community-driven projects have characterized Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns about the frequent diagnosis of Hp infection among community members and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Projects included breath-test screening for Hp infection, gastroscopy with gastric biopsies, and treatment to eliminate Hp infection. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This analysis describes changes in precancerous gastric pathologies in project participants who had gastroscopy before baseline treatment during 2008-2013 and again in 2017. Throughout the study period, the same pathologist graded Hp density, active gastritis, chronic gastritis, atrophic gastritis, and intestinal metaplasia using the updated Sydney System. Of 310 participants from three communities with baseline pathology data, 69 had follow-up pathology data. Relative to baseline, the prevalence of Hp infection and precancerous gastric pathology was substantially lower at follow-up; most participants who were Hp-positive at baseline and Hp-negative at follow-up had reduced severity of active, chronic, and/or atrophic gastritis at follow-up. Though follow-up numbers are small, these results yield evidence that successful Hp treatment has the potential to reduce the risk of gastric cancer in Arctic Indigenous communities.
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Affiliation(s)
- Ting Wang
- Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2X8, Canada (the CANHelp Working Group)
| | - Safwat Girgis
- Department of Lab Medicine & Pathology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2X8, Canada
| | - Hsiu-Ju Chang
- Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2X8, Canada (the CANHelp Working Group)
| | - Ali Assi
- Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2X8, Canada (the CANHelp Working Group)
| | - Katharine Fagan-Garcia
- Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2X8, Canada (the CANHelp Working Group)
| | - Taylor Cromarty
- Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2X8, Canada (the CANHelp Working Group)
| | - Rachel Munday
- Susie Husky Health Centre, Aklavik, NT X0E 0A0, Canada
| | - Karen J. Goodman
- Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2X8, Canada (the CANHelp Working Group)
| | - Sander Veldhuyzen van Zanten
- Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2X8, Canada (the CANHelp Working Group)
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Li D, Jiang SF, Lei NY, Shah SC, Corley DA. Effect of Helicobacter pylori Eradication Therapy on the Incidence of Noncardia Gastric Adenocarcinoma in a Large Diverse Population in the United States. Gastroenterology 2023; 165:391-401.e2. [PMID: 37142201 DOI: 10.1053/j.gastro.2023.04.026] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 03/24/2023] [Accepted: 04/11/2023] [Indexed: 05/06/2023]
Abstract
BACKGROUND & AIMS High-quality data regarding the effect of Helicobacter pylori eradication on the risk of noncardia gastric adenocarcinoma (NCGA) remain limited in the United States. We investigated the incidence of NCGA after H pylori eradication therapy in a large, community-based US population. METHODS We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent testing and/or treatment for H pylori between 1997 and 2015 and were followed through December 31, 2018. The risk of NCGA was evaluated using the Fine-Gray subdistribution hazard model and standardized incidence ratios. RESULTS Among 716,567 individuals with a history of H pylori testing and/or treatment, the adjusted subdistribution hazard ratios and 95% confidence intervals of NCGA for H pylori-positive/untreated and H pylori-positive/treated individuals were 6.07 (4.20-8.76) and 2.68 (1.86-3.86), respectively, compared with H pylori-negative individuals. When compared directly with H pylori-positive/untreated individuals, subdistribution hazard ratios for NCGA in H pylori-positive/treated were 0.95 (0.47-1.92) at <8 years and 0.37 (0.14-0.97) ≥8 years of follow-up. Compared with the Kaiser Permanente Northern California general population, standardized incidence ratios (95% confidence interval) of NCGA steadily decreased after H pylori treatment: 2.00 (1.79-2.24) ≥1 year, 1.01 (0.85-1.19) ≥4 years, 0.68 (0.54-0.85) ≥7 years, and 0.51 (0.38-0.68) ≥10 years. CONCLUSION In a large, diverse, community-based population, H pylori eradication therapy was associated with a significantly reduced incidence of NCGA after 8 years compared with no treatment. The risk among treated individuals became lower than the general population after 7 to 10 years of follow-up. The findings support the potential for substantial gastric cancer prevention in the United States through H pylori eradication.
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Affiliation(s)
- Dan Li
- Department of Gastroenterology, Kaiser Permanente Northern California, Santa Clara, California; Division of Research, Kaiser Permanente Northern California, Oakland, California.
| | - Sheng-Fang Jiang
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Nan Ye Lei
- Department of Internal Medicine, Kaiser Permanente Northern California, Santa Clara, California
| | - Shailja C Shah
- Division of Gastroenterology, University of California San Diego, San Diego, California; Gastroenterology Section, VA San Diego Healthcare System, San Diego, California
| | - Douglas A Corley
- Division of Research, Kaiser Permanente Northern California, Oakland, California; Department of Gastroenterology, Kaiser Permanente Northern California, San Francisco, California
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Chen S, Shen W, Liu Y, Dong Q, Shi Y. Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial. Chin Med J (Engl) 2023; 136:1690-1698. [PMID: 37469024 DOI: 10.1097/cm9.0000000000002696] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori. METHODS This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed. RESULTS A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05). CONCLUSIONS The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.
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Affiliation(s)
- Shasha Chen
- Postgraduate Department, Xi'an Medical University, Xi'an, Shaanxi 710021, China
| | - Weina Shen
- Postgraduate Department, Xi'an Medical University, Xi'an, Shaanxi 710021, China
| | - Yuhuan Liu
- Postgraduate Department, Xi'an Medical University, Xi'an, Shaanxi 710021, China
| | - Qiang Dong
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi 710032, China
| | - Yongquan Shi
- Postgraduate Department, Xi'an Medical University, Xi'an, Shaanxi 710021, China
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi 710032, China
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Wang Y, Li Y, Wang B, Ran D, Zhu C, Li P, Jiang B, Wang S. Early onset, development and histological features of gastric signet-ring cell carcinoma. Front Oncol 2023; 13:1166549. [PMID: 37483506 PMCID: PMC10361758 DOI: 10.3389/fonc.2023.1166549] [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: 02/15/2023] [Accepted: 05/23/2023] [Indexed: 07/25/2023] Open
Abstract
Objective To explore the early onset, development and histological features of gastric signet-ring cell carcinoma (SRCC). Methods Three hundred and sixty-two patients with differentiated adenocarcinoma with signet-ring cells were enrolled. Histomorphological and immunohistochemical features and patterns of the specimens were observed in detail. Results Infection of the gastric mucosa, especially by Helicobacter pylori, can cause massive cell proliferation and transformation in the deep gastric foveola, the isthmus of the gastric gland, and the proliferative zone of the upper neck of the gland. Signet-ring-like heterocysts monoclonally proliferated after the redifferentiation and reproliferation, extending horizontally along the gastric foveola. Gastric foveolar-type SRCC grew infiltratively into the lamina propria of the mucosa and the submucosa, signet-ring cells could differentiate into undifferentiated adenocarcinoma with signet-ring cell differentiation, mucinous adenocarcinoma with signet-ring cell differentiation, gastric adenocarcinoma with signet-ring cell differentiation, and fundus gland adenocarcinoma with signet-ring cell differentiation. Conclusion Early SRCC developed from the proliferative zones of the fundus of the gastric foveola and the neck of the gastric gland, growing horizontally along the gastric foveola. It developed into gastric adenocarcinoma with signet-ring cell differentiation after reproliferation and retransformation in the mucosa.
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Affiliation(s)
- Yangkun Wang
- Department of Pathology, Shenzhen Longgang District Fourth People’s Hospital, Shenzhen, China
| | | | - Bin Wang
- Department of Radiation Therapy, Cancer Center, Shanghai Jiahui International Hospital, Shanghai, China
| | - Dongmei Ran
- Department of Pathology, Southern University of Science and Technology Hospital, Shenzhen, China
| | - Chaoya Zhu
- Department of Pathology, Third Affiliated Hospital of Zhengzhou University, Shenzhen, China
| | - Ping Li
- Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Bo Jiang
- Department of Pathology, No. 990 Hospital of The People's Liberation Army (PLA) Joint Logistics Support Force, Zhumadian, China
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Bogdanova I, Polaka I, Aleksandraviča I, Dzērve Z, Anarkulova L, Novika V, Tolmanis I, Leja M. Role of pre-existing incomplete intestinal metaplasia in gastric adenocarcinoma: A retrospective case series analysis. World J Clin Cases 2023; 11:2708-2715. [PMID: 37214563 PMCID: PMC10198109 DOI: 10.12998/wjcc.v11.i12.2708] [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: 12/27/2022] [Revised: 01/19/2023] [Accepted: 03/29/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial. AIM To analysis of patients having developed gastric adenocarcinoma during the period of follow-up. METHODS We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed. RESULTS Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy; all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type III intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment (OLGIM) stages (I-II) at the baseline. CONCLUSION The presence of incomplete intestinal metaplasia, in particular, that of Type III is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.
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Affiliation(s)
- Inga Bogdanova
- Department of Pathology, Academic Histology Laboratory, Riga LV1073, Latvia
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
| | - Inese Polaka
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
| | - Ilona Aleksandraviča
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
- Department of Research, Riga East University Hospital, Riga LV1079, Latvia
| | - Zane Dzērve
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
- Department of Endoscopy, Digestive Diseases Centre GASTRO, Riga LV1079, Latvia
| | - Linda Anarkulova
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
| | - Vita Novika
- Department of Endoscopy, Digestive Diseases Centre GASTRO, Riga LV1079, Latvia
| | - Ivars Tolmanis
- Department of Endoscopy, Digestive Diseases Centre GASTRO, Riga LV1079, Latvia
| | - Marcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
- Department of Research, Riga East University Hospital, Riga LV1079, Latvia
- Department of Gastroenterology, Digestive Diseases Centre GASTRO, Riga LV1079, Latvia
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48
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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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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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50
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Thrift AP, Wenker TN, El-Serag HB. Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention. Nat Rev Clin Oncol 2023; 20:338-349. [PMID: 36959359 DOI: 10.1038/s41571-023-00747-0] [Citation(s) in RCA: 310] [Impact Index Per Article: 155.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2023] [Indexed: 03/25/2023]
Abstract
Gastric cancer remains a major cause of cancer-related mortality worldwide. The temporal trends for this malignancy, however, are dynamic, and reports from the past decade indicate important declines in some regions and demographic groups, as well as a few notable exceptions in which gastric cancer rates are either stable or increasing. Two main anatomical subtypes of gastric cancer exist, non-cardia and cardia, with different temporal trends and risk factors (such as obesity and reflux for cardia gastric cancer and Helicobacter pylori infection for non-cardia gastric cancer). Shifts in the distribution of anatomical locations have been detected in several high-incidence regions. H. pylori is an important aetiological factor for gastric cancer; importantly, the anticipated long-term findings from studies examining the effect of H. pylori eradication on the risk of (re)developing gastric cancer have emerged in the past few years. In this Review, we highlight the latest trends in incidence and mortality using an evidence-based approach. We make the best possible inferences, including clinical and public health inference, on the basis of the quality of the evidence available, and highlight burning questions as well as gaps in knowledge and public health practice that need to be addressed to reduce gastric cancer burden worldwide.
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Affiliation(s)
- Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Theresa Nguyen Wenker
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
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