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Pittayanon R, Tiankanon K, Faknak N, Lerttanatum N, Sanpavat A, Klaikaew N, Rerknimitr R. Efficacy of Radiofrequency Ablation as a Treatment for High-Risk Gastric Intestinal Metaplasia: A Randomized, Self-Control Study. J Gastroenterol Hepatol 2025; 40:891-899. [PMID: 39762988 DOI: 10.1111/jgh.16875] [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: 07/27/2024] [Revised: 12/02/2024] [Accepted: 12/23/2024] [Indexed: 04/05/2025]
Abstract
BACKGROUND Guidelines recommend endoscopic surveillance for gastric cancer without therapeutic intervention every 3 years in patients with high-risk gastric intestinal metaplasia (GIM). This study aimed to evaluate the efficacy of radiofrequency ablation (RFA) in eradicating high-risk GIM. METHODS This randomized self-control trial was conducted between June 2020 and February 2023. Patients with histology-verified high-risk GIM were enrolled. The endoscopist performed a biopsy on both the left and right sides of the stomach (five each) by targeting the suspected GIM area where available; otherwise, a random biopsy was taken. Patients were randomized to receive a unilateral RFA on either the left or right side. A repeated RFA on the assigned side was performed every 2-3 months for a total of two to three times. The primary outcome was complete resolution of GIM at 1 year after RFA. RESULTS Forty-six patients with a mean age of 66 ± 8 years were analyzed. The complete resolution rate of overall GIM lesions after RFA was significantly higher (49/142; 34/5%) than that in the observation group (29/127; 22.8%, RR = 0.84, 0.73-0.98, p = 0.03). For the subgroup analysis, the complete resolution rate after RFA revealed a significantly higher value than observation only in the incomplete GIM group (24/87; 27.6% vs. 11/82; 13.4%, RR = 0.83, 0.71-0.97, p = 0.02). The percentage of patients with extensive GIM regression after RFA (15/25; 60%) was higher than in the observation group (9/25; 36%) but did not meet statistical significance (RR = 0.62, 0.35-1.09, p = 0.09). CONCLUSION In high-risk GIM, RFA can significantly eradicate incomplete GIM when compared with observation alone.
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Affiliation(s)
- Rapat Pittayanon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Chulalongkorn University, Bangkok, Thailand
| | - Kasenee Tiankanon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Chulalongkorn University, Bangkok, Thailand
| | - Natee Faknak
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross, Bangkok, Thailand
| | - Nathawadee Lerttanatum
- Department of Pathology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Anapat Sanpavat
- Department of Pathology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Naruemon Klaikaew
- Department of Pathology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Chulalongkorn University, Bangkok, Thailand
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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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Yan Z, Liu Y, Yuan Y. The plasticity of epithelial cells and its potential in the induced differentiation of gastric cancer. Cell Death Discov 2024; 10:512. [PMID: 39719478 DOI: 10.1038/s41420-024-02275-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 12/05/2024] [Accepted: 12/13/2024] [Indexed: 12/26/2024] Open
Abstract
Cell plasticity refers to the deviation of cells from normal terminal differentiation states when faced with environmental and genetic toxic stresses, resulting in the phenomenon of transforming into other cell or tissue phenotypes. Unlocking phenotype plasticity has been defined as a hallmark of malignant tumors. The stomach is one of the organs in the body with the highest degree of self-renewal and exhibits significant cell plasticity. In this paper, based on the review of the characteristics of normal differentiation of gastric epithelial cells and their markers, the four main phenotypes of gastric epithelial cell remodeling and their relationship with gastric cancer (GC) are drawn. Furthermore, we summarize the regulatory factors and mechanisms that affect gastric epithelial cell plasticity and outline the current status of research and future prospection for the treatment targeting gastric epithelial cell plasticity. This study has important theoretical reference value for the in-depth exploration of epithelial cell plasticity and the tumor heterogeneity caused by it, as well as for the precise treatment of GC.
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Affiliation(s)
- Ziwei Yan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Yingnan Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China.
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
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Hahn AI, Mülder DT, Huang RJ, Zhou MJ, Blake B, Omofuma O, Murphy JD, Gutiérrez-Torres DS, Zauber AG, O'Mahony JF, Camargo MC, Ladabaum U, Yeh JM, Hur C, Lansdorp-Vogelaar I, Meester R, Laszkowska M. Global Progression Rates of Precursor Lesions for Gastric Cancer: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00864-4. [PMID: 39362617 PMCID: PMC11958785 DOI: 10.1016/j.cgh.2024.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 08/27/2024] [Accepted: 09/04/2024] [Indexed: 10/05/2024]
Abstract
BACKGROUND & AIMS Whether gastric cancer (GC) precursor lesions progress to invasive cancer at similar rates globally remains unknown. We conducted a systematic review and meta-analysis to determine the progression of precursor lesions to GC in countries with low versus medium/high incidence. METHODS We searched relevant databases for studies reporting the progression of endoscopically confirmed precursor lesions to GC. Studies were stratified by low (<6 per 100,000) or medium/high (≥6 per 100,000) GC incidence countries. Random-effects models were used to estimate the progression rates of atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia to GC per 1000 person-years. RESULTS Among the 5829 studies identified, 44 met our inclusion criteria. The global pooled estimates of the progression rate per 1000 person-years were 2.09 (95% confidence interval, 1.46-2.99), 2.89 (2.03-4.11), and 10.09 (5.23-19.49) for AG, IM, and dysplasia, respectively. The estimated progression rates per 1000 person-years for low versus medium/high GC incidence countries, respectively, were 0.97 (0.86-1.10) versus 2.47 (1.70-2.99) for AG (P < .01), 2.37 (1.43-3.92) versus 3.47 (2.13-5.65) for IM (P = .29), and 5.51 (2.92-10.39) versus 14.80 (5.87-37.28) for dysplasia (P = .08). There were no differences for progression of AG between groups when high-quality studies were compared. CONCLUSIONS Similar progression rates of IM and dysplasia were observed among low and medium/high GC incidence countries. This suggests that the potential benefits of surveillance for these lesions in low-risk regions may be comparable with those of population-wide interventions in high-risk regions. Further prospective studies are needed to confirm these findings and inform global screening and surveillance guidelines.
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Affiliation(s)
- Anne I Hahn
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
| | - Duco T Mülder
- Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Robert J Huang
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Margaret J Zhou
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Benjamin Blake
- Weill Cornell Medical College of Cornell University, New York, New York
| | - Omonefe Omofuma
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - John D Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | | | - Ann G Zauber
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - James F O'Mahony
- Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands; School of Economics, University College Dublin, Dublin, Ireland
| | - M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Uri Ladabaum
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Jennifer M Yeh
- Department of Pediatrics, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts
| | - Chin Hur
- Division of General Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York
| | | | - Reinier Meester
- Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands; Health Economics & Outcomes Research, Freenome Holdings Inc, San Francisco, California
| | - Monika Laszkowska
- Gastroenterology, Hepatology, and Nutrition Service, Department of Subspecialty Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
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Becker EC, Salunke R, Saraceni C, Birk J. Biennial Endoscopic Surveillance of Gastrointestinal Metaplasia and Its Subtypes Reduces Gastric Cancer Mortality and Is Cost-Effective in a Markov State Transition Model. South Med J 2023; 116:951-956. [PMID: 38051169 DOI: 10.14423/smj.0000000000001632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023]
Abstract
OBJECTIVES Gastric cancer in the United States has a low survival rate mainly because of the late stage of diagnosis. Furthermore, there are no well-established guidelines concerning screening and surveillance even for higher risk patients such as those with nondysplastic noncardia gastrointestinal metaplasia (GIM), and thus they are not routinely performed. This study was designed to provide new evidence-based data that can be used to support the implementation of biennial surveillance guidelines in individuals with nondysplastic noncardia GIM. This practice can help detect early malignant lesions, thereby decreasing morbidity and mortality. We evaluated the cost-effectiveness of surveillance endoscopies for noncardia gastric cancer in populations with two different pathological diagnoses: mixed GIM and incomplete GIM (iGIM). METHODS Markov state transition models were developed using a cohort simulation of 1000 hypothetical patients. Analysis was conducted for both mixed and iGIM. Quality-adjusted life-years and transition probabilities were derived from the published medical literature. Costs associated with endoscopy, cancer care, and surgery were based on Medicare reimbursement. A willingness-to-pay threshold of $100,000 per quality-adjusted life-year was used to determine cost-effectiveness. RESULTS Our study determined that it is significantly cost-effective to perform biennial endoscopy surveillance in patients who have been incidentally found to have noncardia mixed GIM, with a cost savings of $5783.84 per person, and in those with iGIM, with a cost savings of $8093.08 per person. CONCLUSIONS Biennial endoscopy surveillance should be considered in all individuals found to have mixed or incomplete noncardia GIM on endoscopy. Furthermore, screening specifically for iGIM after differentiating between the two groups can lead to further cost savings. As such, we recommend that pathologists routinely differentiate between the two and recommend robust routine surveillance of iGIM.
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Affiliation(s)
| | | | - Corey Saraceni
- Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
| | - John Birk
- Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
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Kligman E, Ali H, Chen E, Peng F, Szafron D, Staggers K, Tan MC, Patel K, Othman MO. Ethnicity Is an Important Consideration in Screening for Gastric Intestinal Metaplasia. Dig Dis Sci 2022; 67:4509-4517. [PMID: 34981309 DOI: 10.1007/s10620-021-07326-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 11/03/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Gastric intestinal metaplasia (GIM) is a precursor to gastric adenocarcinoma, making it an attractive target for early detection by endoscopy. The aim of this study was to determine the prevalence, risk factors, and associated histologic findings of GIM among patients undergoing endoscopy in a diverse US population. METHODS We conducted a retrospective, cross-sectional study of patients undergoing elective endoscopy with gastric biopsies at 6 academic and community centers in Houston, Texas. GIM prevalence was estimated with a 95% confidence interval (CI), and patient demographic and clinical characteristics were summarized using mean with standard deviation, or frequency with percentage. Generalized estimating equations (GEE) were used to compare characteristics between those with and without GIM. RESULTS Our final cohort consisted of 2685 patients, including 216 cases with GIM and 2469 controls. The prevalence of GIM in our cohort was 8.04% (95% CI 7.07%, 9.14%). The mean age of GIM cases was higher than in the control group (59.8 vs 54.7 years, p < 0.0001). The prevalence of GIM in Asians, Hispanic, Black and Non-Hispanic Whites (NHW) was 14.7%, 11.7%, 9.8% and 5.8%, respectively. On multivariable analysis, factors associated with GIM include age (adj. OR 1.32 per 10 year increase, p < 0.0001), habitual smoking (adj. OR 1.68, p < 0.0001), and race (compared to NHW: Asian, adj. OR 2.34, p = 0.010; Hispanic, adj. OR 2.15, p < 0.001; Black, adj. OR 1.61, p < 0.001). CONCLUSION Asians, Hispanics, and African Americans have higher rates of GIM than NHW. Ethnicity should be an important consideration on determining who to screen for GIM in the US.
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Affiliation(s)
- Eugene Kligman
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, 7200 Cambridge Street. Suite 8A, Houston, TX, 77030, USA
| | - Hiba Ali
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Ellie Chen
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Frederick Peng
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - David Szafron
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Kristen Staggers
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
| | - Mimi C Tan
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, 7200 Cambridge Street. Suite 8A, Houston, TX, 77030, USA
| | - Kalpesh Patel
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, 7200 Cambridge Street. Suite 8A, Houston, TX, 77030, USA
| | - Mohamed O Othman
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, 7200 Cambridge Street. Suite 8A, Houston, TX, 77030, USA.
- Baylor St Luke's Medical Center, Houston, TX, USA.
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Abstract
Like most solid tumours, the microenvironment of epithelial-derived gastric adenocarcinoma (GAC) consists of a variety of stromal cell types, including fibroblasts, and neuronal, endothelial and immune cells. In this article, we review the role of the immune microenvironment in the progression of chronic inflammation to GAC, primarily the immune microenvironment driven by the gram-negative bacterial species Helicobacter pylori. The infection-driven nature of most GACs has renewed awareness of the immune microenvironment and its effect on tumour development and progression. About 75-90% of GACs are associated with prior H. pylori infection and 5-10% with Epstein-Barr virus infection. Although 50% of the world's population is infected with H. pylori, only 1-3% will progress to GAC, with progression the result of a combination of the H. pylori strain, host susceptibility and composition of the chronic inflammatory response. Other environmental risk factors include exposure to a high-salt diet and nitrates. Genetically, chromosome instability occurs in ~50% of GACs and 21% of GACs are microsatellite instability-high tumours. Here, we review the timeline and pathogenesis of the events triggered by H. pylori that can create an immunosuppressive microenvironment by modulating the host's innate and adaptive immune responses, and subsequently favour GAC development.
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Sun D, Lei L, Xia C, Li H, Cao M, He S, Zhang Z, Guo G, Song G, Peng J, Chen W. Sociodemographic disparities in gastric cancer and the gastric precancerous cascade: A population-based study. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2022; 23:100437. [PMID: 35355616 PMCID: PMC8958536 DOI: 10.1016/j.lanwpc.2022.100437] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
BACKGROUND Gastric carcinogenesis is a multistep process initiating with chronic gastritis and progressing through atrophy, intestinal metaplasia, and dysplasia to carcinoma. This study aims to comprehensively investigate sociodemographic disparities in each stage of gastric carcinogenesis and estimate to what extent the inequalities could be ascribed to risk factors of gastric cancer (GC). METHODS We used the baseline data from a community-based study in China's high-risk areas, totalling 27094 participants. Gastric mucosa status was ascertained by endoscopy and biopsies. An overall socioeconomic status (SES) variable was generated by latent class analysis. We calculated relative risks (RRs) and 95% confidence intervals (CIs) using modified Poisson regression to assess associations of sociodemographic factors with each cascade stage. We estimated the percentage of the excess risk for neoplastic lesions among vulnerable populations that can be explained by established risk factors. RESULTS Age and sex showed associations with all gastric lesions, whose RRs increased with lesion progressing. Compared with individuals without schooling, the RRs of neoplastic lesions for people with primary, secondary, and post-secondary education were 0·86 (95% CI 0·76-0·97), 1·00 (95% CI 0·88-1·13), and 0·70 (95% CI 0·47-1·03), respectively. Participants with medium SES had a lower risk of neoplastic lesions than people in the low SES group (RR 0·83, 95% CI 0·74-0·93). GC risk factors could explain 33·6% of the excess risk of neoplastic lesions among men and a small proportion of the disparities among SES groups. INTERPRETATION Age and sex were essential sociodemographic factors for GC and precursor diseases. Individuals with low educational levels or SES were more likely to have neoplastic lesions. About one-third of the sex difference and a slight fraction of the socioeconomic inequalities could be attributed to included risk factors. FUNDING Sanming Project of Medicine in Shenzhen, National Natural Science Foundation, and Special Project of Bejing-Tianjin-Hebei Basic Research Cooperation.
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Affiliation(s)
- Dianqin Sun
- Office of Cancer Screening, National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Pan-jia-yuan South Lane, Chaoyang District, Beijing 100021, China
| | - Lin Lei
- Department of Cancer Prevention and Control, Shenzhen Center for Chronic Disease Control, Shenzhen 518020, China
| | - Changfa Xia
- Office of Cancer Screening, National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Pan-jia-yuan South Lane, Chaoyang District, Beijing 100021, China
| | - He Li
- Office of Cancer Screening, National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Pan-jia-yuan South Lane, Chaoyang District, Beijing 100021, China
| | - Maomao Cao
- Office of Cancer Screening, National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Pan-jia-yuan South Lane, Chaoyang District, Beijing 100021, China
| | - Siyi He
- Office of Cancer Screening, National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Pan-jia-yuan South Lane, Chaoyang District, Beijing 100021, China
| | - Zhiyi Zhang
- Department of Gastroenterology, Gansu Wuwei Tumor Hospital, Wuwei, China
| | - Guizhou Guo
- Linzhou Cancer Hospital, Anyang 456500, China
| | - Guohui Song
- Cixian Cancer Institute, Handan 056500, China
| | - Ji Peng
- Department of Gastroenterology, Gansu Wuwei Tumor Hospital, Wuwei, China
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Pan-jia-yuan South Lane, Chaoyang District, Beijing 100021, China
- Corresponding author.
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9
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Lee JWJ, Zhu F, Srivastava S, Tsao SKK, Khor C, Ho KY, Fock KM, Lim WC, Ang TL, Chow WC, So JBY, Koh CJ, Chua SJ, Wong ASY, Rao J, Lim LG, Ling KL, Chia CK, Ooi CJ, Rajnakova A, Yap WM, Salto-Tellez M, Ho B, Soong R, Chia KS, Teo YY, Teh M, Yeoh KG. Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP). Gut 2022; 71:854-863. [PMID: 33975867 PMCID: PMC8995828 DOI: 10.1136/gutjnl-2021-324057] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 04/15/2021] [Accepted: 04/30/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. METHODS A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). RESULTS There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV. CONCLUSIONS We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.
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Affiliation(s)
- Jonathan W J Lee
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore,Department of Medicine, National University of Singapore, Singapore,Singapore Gastric Cancer Consortium, Singapore
| | - Feng Zhu
- Department of Medicine, National University of Singapore, Singapore,Singapore Gastric Cancer Consortium, Singapore
| | | | - Stephen KK Tsao
- Department of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore
| | - Christopher Khor
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - Khek Yu Ho
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore,Department of Medicine, National University of Singapore, Singapore
| | - Kwong Ming Fock
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore
| | - Wee Chian Lim
- Department of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore
| | - Tiing Leong Ang
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore
| | - Wan Cheng Chow
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - Jimmy Bok Yan So
- Singapore Gastric Cancer Consortium, Singapore,Department of Surgery, National University of Singapore, Singapore
| | - Calvin J Koh
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore,Department of Medicine, National University of Singapore, Singapore,Singapore Gastric Cancer Consortium, Singapore
| | - Shijia Joy Chua
- Department of Medicine, National University of Singapore, Singapore
| | | | - Jaideepraj Rao
- Department of Surgery, Tan Tock Seng Hospital, Singapore
| | | | | | | | | | - Andrea Rajnakova
- Andrea's Digestive, Colon, Liver and Gallbladder Clinic Pte Ltd, Singapore
| | - Wai Ming Yap
- Department of Pathology, Tan Tock Seng Hospital, Singapore
| | - Manuel Salto-Tellez
- Precision Medicine Centre of Excellence, Queen's University Belfast, Belfast, UK,Integrated Pathology Unit, Institute of Cancer Research, London, UK
| | - Bow Ho
- Department of Microbiology, National University of Singapore, Singapore
| | - Richie Soong
- Cancer Science Institute of Singapore, National University of Singapore, Singapore,Department of Pathology, National University of Singapore, Singapore,Pascific Laboratories, Singapore
| | - Kee Seng Chia
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Yik Ying Teo
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Ming Teh
- Singapore Gastric Cancer Consortium, Singapore,Department of Pathology, National University of Singapore, Singapore
| | - Khay-Guan Yeoh
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore .,Department of Medicine, National University of Singapore, Singapore.,Singapore Gastric Cancer Consortium, Singapore
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10
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Faknak N, Pittayanon R, Tiankanon K, Lerttanatum N, Sanpavat A, Klaikaew N, Rerknimitr R. Performance status of targeted biopsy alone versus Sydney protocol by non-NBI expert gastroenterologist in gastric intestinal metaplasia diagnosis. Endosc Int Open 2022; 10:E273-E279. [PMID: 35433197 PMCID: PMC9010080 DOI: 10.1055/a-1783-9081] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 11/29/2021] [Indexed: 12/24/2022] Open
Abstract
Background and study aims According to a recent guideline, patients with gastric intestinal metaplasia (GIM) should have at least five biopsies performed under the Sydney protocol to evaluate for risk of extensive GIM. However, only narrow-band imaging (NBI)-targeted biopsy may be adequate to diagnose extensive GIM. Patients and methods A cross-sectional study was conducted between November 2019 and October 2020. Patients with histology-proven GIM were enrolled. All patients underwent standard esophagogastroduodenoscopy performed by a gastroenterology trainee. The performing endoscopists took biopsies from either a suspected GIM area (NBI-targeted biopsy) or randomly (if negative for GIM read by NBI) to complete five areas of the stomach as per the Sydney protocol. The gold standard for GIM diagnosis was pathology read by two gastrointestinal pathologists with unanimous agreement. Results A total of 95 patients with GIM were enrolled and 50 (52.6%) were men with a mean age of 64 years. Extensive GIM was diagnosed in 43 patients (45.3%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of NBI-targeted biopsy vs. the Sydney protocol were 88.4% vs.100 %, 90.3% vs. 90.3%, 88.4% vs. 89.6%, 90.3% vs. 100%, and 89.5% vs. 94.7%, respectively. The number of specimens from NBI-targeted biopsy was significantly lower than that from Sydney protocol (311vs.475, P < 0.001). Conclusions Both NBI-targeted biopsy and Sydney protocol by a gastroenterologist who was not an expert in NBI and who has experience with diagnosis of at least 60 cases of GIM provided an NPV higher than 90%. Thus, targeted biopsy alone with NBI, which requires fewer specimens, is an alternative option for extensive GIM diagnosis.
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Affiliation(s)
- Natee Faknak
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai red Cross Society, Bangkok, Thailand
| | - Rapat Pittayanon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai red Cross Society, Bangkok, Thailand
| | - Kasenee Tiankanon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai red Cross Society, Bangkok, Thailand
| | - Nathawadee Lerttanatum
- Department of pathology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Anapat Sanpavat
- Department of pathology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Naruemon Klaikaew
- Department of pathology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai red Cross Society, Bangkok, Thailand
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11
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Chapelle N, Osmola M, Martin J, Blin J, Leroy M, Jirka I, Moussata D, Lamarque D, Olivier R, Tougeron D, Hay-Lombardie A, Bigot-Corbel E, Masson D, Mosnier JF, Matysiak-Budnik T. Serum Pepsinogens Combined with New Biomarkers Testing Using Chemiluminescent Enzyme Immunoassay for Non-Invasive Diagnosis of Atrophic Gastritis: A Prospective, Multicenter Study. Diagnostics (Basel) 2022; 12:695. [PMID: 35328248 PMCID: PMC8947400 DOI: 10.3390/diagnostics12030695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/05/2022] [Accepted: 03/05/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), a gastric precancerous lesion, is of growing interest for identification of patients at increased risk of gastric cancer. The aim was to analyze the diagnostic performance of serum pepsinogen testing using another method, chemiluminescent enzyme immunoassay (CLEIA), as well as of other new potential biomarkers. MATERIAL AND METHODS The sera of patients considered at increased risk of gastric cancer and undergoing upper endoscopy collected in our previous prospective, multicenter study were tested for pepsinogen I (PGI) and II (PGII), interleukin-6 (IL-6), human epididymal protein 4 (HE-4), adiponectin, ferritin and Krebs von den Lungen (KL-6) using the CLEIA. The diagnostic performance for the detection of AG was calculated by taking histology as the reference. RESULTS In total, 356 patients (162 men (46%); mean age 58.6 (±14.2) years), including 152 with AG, were included. For the detection of moderate to severe corpus AG, sensitivity and specificity of the pepsinogen I/II ratio were of 75.0% (95%CI 57.8-87.9) and 92.6% (88.2-95.8), respectively. For the detection of moderate to severe antrum AG, sensitivity of IL-6 was of 72.2% (95%CI 46.5-90.3). Combination of pepsinogen I/II ratio or HE-4 showed a sensitivity of 85.2% (95%CI 72.9-93.4) for the detection of moderate to severe AG at any location. CONCLUSION This study shows that PG testing by CLEIA represents an accurate assay for the detection of corpus AG. Additionally, IL-6 and HE-4 may be of interest for the detection of antrum AG. MINI-ABSTRACT Pepsinogens testing by chemiluminescent enzyme immunoassay is accurate for the detection of corpus atrophic gastritis. IL-6 and HE-4 maybe of interest for the detection of antrum atrophic gastritis.
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Affiliation(s)
- Nicolas Chapelle
- IMAD, Hepato-Gastroenterology & Digestive Oncology, University Hospital of Nantes, Hôtel Dieu, Place Alexis Ricordeau, CEDEX 1, 44093 Nantes, France; (N.C.); (I.J.)
- INSERM U1064 CRTI, 44093 Nantes, France;
- Faculty of Medicine, University of Nantes, 44300 Nantes, France; (J.B.); (E.B.-C.); (D.M.); (J.-F.M.)
| | - Malgorzata Osmola
- Department of Immunology, University Hospital of Nantes, 44093 Nantes, France;
- Department of Hematology, Transplantation and Internal Medicine, Medical University, 02-091 Warsaw, Poland
| | - Jérôme Martin
- INSERM U1064 CRTI, 44093 Nantes, France;
- Faculty of Medicine, University of Nantes, 44300 Nantes, France; (J.B.); (E.B.-C.); (D.M.); (J.-F.M.)
- Department of Immunology, University Hospital of Nantes, 44093 Nantes, France;
| | - Justine Blin
- Faculty of Medicine, University of Nantes, 44300 Nantes, France; (J.B.); (E.B.-C.); (D.M.); (J.-F.M.)
- Department of Biochemistry, University Hospital of Nantes, 44093 Nantes, France;
- INSERM U1235 TENS, 44300 Nantes, France
| | - Maxime Leroy
- Department of Biostatistics, CHU de Nantes, 44093 Nantes, France;
| | - Iva Jirka
- IMAD, Hepato-Gastroenterology & Digestive Oncology, University Hospital of Nantes, Hôtel Dieu, Place Alexis Ricordeau, CEDEX 1, 44093 Nantes, France; (N.C.); (I.J.)
| | - Driffa Moussata
- Department of Hepato-Gastroenterology, University Hospital of Tours, 37044 Tours, France;
| | - Dominique Lamarque
- Department of Hepato-Gastroenterology, Ambroise-Paré Hospital, AP-HP, Paris Saclay University, UVSQ, INSERM, Infection and Inflammation, 91190 Paris, France;
| | - Raphael Olivier
- Department of Hepato-Gastroenterology, Poitiers University Hospital, University of Poitiers, 86000 Poitiers, France; (R.O.); (D.T.)
| | - David Tougeron
- Department of Hepato-Gastroenterology, Poitiers University Hospital, University of Poitiers, 86000 Poitiers, France; (R.O.); (D.T.)
| | - Anne Hay-Lombardie
- Department of Biochemistry, University Hospital of Nantes, 44093 Nantes, France;
| | - Edith Bigot-Corbel
- Faculty of Medicine, University of Nantes, 44300 Nantes, France; (J.B.); (E.B.-C.); (D.M.); (J.-F.M.)
- Department of Biochemistry, University Hospital of Nantes, 44093 Nantes, France;
| | - Damien Masson
- Faculty of Medicine, University of Nantes, 44300 Nantes, France; (J.B.); (E.B.-C.); (D.M.); (J.-F.M.)
- Department of Biochemistry, University Hospital of Nantes, 44093 Nantes, France;
| | - Jean-François Mosnier
- Faculty of Medicine, University of Nantes, 44300 Nantes, France; (J.B.); (E.B.-C.); (D.M.); (J.-F.M.)
- Department of Pathology, University Hospital of Nantes, 44093 Nantes, France
| | - Tamara Matysiak-Budnik
- IMAD, Hepato-Gastroenterology & Digestive Oncology, University Hospital of Nantes, Hôtel Dieu, Place Alexis Ricordeau, CEDEX 1, 44093 Nantes, France; (N.C.); (I.J.)
- INSERM U1064 CRTI, 44093 Nantes, France;
- Faculty of Medicine, University of Nantes, 44300 Nantes, France; (J.B.); (E.B.-C.); (D.M.); (J.-F.M.)
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12
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Subtyping intestinal metaplasia in patients with chronic atrophic gastritis: an interobserver variability study. Pathology 2022; 54:262-268. [PMID: 35221041 DOI: 10.1016/j.pathol.2021.12.288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 11/18/2021] [Accepted: 12/01/2021] [Indexed: 12/25/2022]
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13
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Du S, Yang Y, Fang S, Guo S, Xu C, Zhang P, Wei W. Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies. Clin Transl Gastroenterol 2021; 12:e00402. [PMID: 34597278 PMCID: PMC8487777 DOI: 10.14309/ctg.0000000000000402] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 08/03/2021] [Indexed: 01/12/2023] Open
Abstract
INTRODUCTION Intestinal metaplasia (IM) is an independent risk factor for gastric cancer (GC). However, the subtypes of IM as a risk factor for GC remain controversial. We performed a systematic review and meta-analysis to evaluate the relationship between IM subtypes and GC risk. METHODS Systematic searches were conducted in PubMed, EMBASE, and the Cochrane Library for published cohort studies of patients with complete IM (type I) or incomplete IM (type II or type III) from inception to May 15, 2021. We extracted relevant data and calculated pooled risk ratios (RRs) and 95% confidence intervals (CIs) comparing the GC risk with IM subtypes. RESULTS Twelve cohort studies comprising 6,498 individuals were included in the study. Compared with complete IM, the pooled relative risk of GC risk of patients with incomplete IM was 5.16 (95% CI, 3.28-8.12), and the GC risk of type III IM was the highest, with a pooled relative risk of 2.88 (95% CI, 1.37-6.04) compared with that of type II. Compared with complete IM, the pooled relative risk of dysplasia risk in patients with incomplete IM was 3.72 (95% CI, 1.42-9.72), and the dysplasia risk of type III IM was 11.73 (95% CI, 2.08-66.08) compared with that of type I. DISCUSSION Patients with incomplete IM, especially type III, were at a higher risk of GC and dysplasia than those with complete IM. The current evidence indicates a potential correlation between IM subtypes and GC risk, which may support the use of IM subtypes in GC surveillance.
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Affiliation(s)
- Sijing Du
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing City, China;
| | - Yang Yang
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing City, China;
| | - Shuangshuang Fang
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing City, China;
- Graduate School of Beijing University of Chinese Medicine, Beijing City, China;
| | - Song Guo
- Department of Gastroenterology, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, China
| | - Chuchu Xu
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing City, China;
- Graduate School of Beijing University of Chinese Medicine, Beijing City, China;
| | - Ping Zhang
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing City, China;
| | - Wei Wei
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing City, China;
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14
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Businello G, Angerilli V, Parente P, Realdon S, Savarino E, Farinati F, Grillo F, Vanoli A, Galuppini F, Paccagnella S, Pennelli G, Mastracci L, Saragoni L, Fassan M. Molecular Landscapes of Gastric Pre-Neoplastic and Pre-Invasive Lesions. Int J Mol Sci 2021; 22:9950. [PMID: 34576114 PMCID: PMC8468646 DOI: 10.3390/ijms22189950] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/03/2021] [Accepted: 09/11/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric carcinoma (GC) represents one of the most common and most lethal malignancies worldwide. The histopathological characterization of GC precursor lesions has provided great knowledge about gastric carcinogenesis, with the consequent introduction of effective strategies of primary and secondary prevention. In recent years, a large amount of data about the molecular events in GC development is emerging, flanking the histomorphological descriptions. In this review, we describe the landscape of molecular alterations in gastric pre-invasive lesions with a glance at their potential use in the diagnostic and therapeutic decision-making process.
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Affiliation(s)
- Gianluca Businello
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy; (G.B.); (V.A.); (F.G.); (S.P.); (G.P.)
| | - Valentina Angerilli
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy; (G.B.); (V.A.); (F.G.); (S.P.); (G.P.)
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy;
| | - Stefano Realdon
- Veneto Institute of Oncology (IOV-IRCCS), 35128 Padua, Italy;
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (E.S.); (F.F.)
| | - Fabio Farinati
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (E.S.); (F.F.)
| | - Federica Grillo
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, 16132 Genova, Italy; (F.G.); (L.M.)
- Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, 16132 Genova, Italy
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, 27100 Pavia, Italy;
| | - Francesca Galuppini
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy; (G.B.); (V.A.); (F.G.); (S.P.); (G.P.)
| | - Silvia Paccagnella
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy; (G.B.); (V.A.); (F.G.); (S.P.); (G.P.)
| | - Gianmaria Pennelli
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy; (G.B.); (V.A.); (F.G.); (S.P.); (G.P.)
| | - Luca Mastracci
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, 16132 Genova, Italy; (F.G.); (L.M.)
- Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, 16132 Genova, Italy
| | - Luca Saragoni
- UO Anatomia Patologica, Ospedale G.B. Morgagni-L. Pierantoni, 47121 Forlì, Italy;
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy; (G.B.); (V.A.); (F.G.); (S.P.); (G.P.)
- Veneto Institute of Oncology (IOV-IRCCS), 35128 Padua, Italy;
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15
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Abstract
Data on the evolution of gastric precancerous lesions (GPL), especially in countries of a Low gastric cancer incidence area are limited. Our objective was to study a long-term evolution of GPL in France.
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16
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Zhang R, Rabinovitch PS, Mattis AN, Lauwers GY, Choi WT. Gastric Intestinal Metaplasia in Mucosa Adjacent to Gastric Cancers Is Rarely Associated With the Aneuploidy That Is Characteristic of Gastric Dysplasia or Cancer. Am J Surg Pathol 2021; 45:1374-1381. [PMID: 34091484 DOI: 10.1097/pas.0000000000001764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Most gastric cancers (GCs) are thought to develop via gastric intestinal metaplasia (GIM)-dysplasia-carcinoma pathway. Patients with extensive and/or incomplete GIM have been reported to have a higher risk of GC. GIM can also display dysplasia-like cytoarchitectural atypia limited to the bases of gastric pits without surface involvement. However, only a small proportion of GIM patients will develop gastric neoplasia, and it remains questionable if GIM is a direct precursor. A cohort of 82 GC patients with GIM who underwent gastrectomy were analyzed. DNA flow cytometry was performed on 109 GIM samples (including 88 predominantly complete GIM and 21 predominantly incomplete GIM subclassified based on morphology) obtained from adjacent mucosa of the 82 GCs. Only 2 (2%) of the 109 GIM samples demonstrated aneuploidy, both from 2 minority patients (Asian and Hispanic) with limited and complete GIM and no cytoarchitectural atypia. The remaining 107 GIM samples showed mild to focally moderate basal gland (metaplastic) atypia limited to the bases of gastric pits, but they all demonstrated normal DNA content regardless of anatomic location, histologic GIM subtype, or varying degrees of basal gland atypia. In conclusion, the vast majority of the GIM samples (98%) lack the aneuploidy that is characteristic of gastric dysplasia or cancer. This indicates that aneuploidy usually occurs after the development of gastric dysplasia rather than at the stage of GIM. The finding also suggests that the presence of GIM alone may not be sufficient to suggest an increased risk for GC and that the inclusion of other high-risk features (ie, extensive GIM, dysplasia, racial minorities, and/or family history of GC in a first-degree relative) and/or aneuploidy ought to play a role in the selection of GIM patients who may warrant endoscopic surveillance. Finally, GIM with mild to focally moderate basal gland atypia is likely to represent metaplastic atypia in most cases.
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Affiliation(s)
- Ruth Zhang
- Department of Pathology, University of California at San Francisco, San Francisco, CA Department of Pathology, University of Washington, Seattle, WA Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL
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17
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Wei N, Zhou M, Lei S, Zhong Z, Shi R. A meta-analysis and systematic review on subtypes of gastric intestinal metaplasia and neoplasia risk. Cancer Cell Int 2021; 21:173. [PMID: 33731114 PMCID: PMC7968216 DOI: 10.1186/s12935-021-01869-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 03/06/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Gastric intestinal metaplasia (GIM) is a significant risk factor for gastric cancer. Risk of gastric cancer/dysplasia between complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM) was controversial. Our study aimed to pool relative risk (RR) of cancer/dysplasia of IIM compared with CIM in GIM patients. METHODS PubMed, EMBASE, Cochrane Library and Web of Science were searched for studies concerning cancer/dysplasia in GIM patients. Random-effects or fixed-effects model was utilized for pooling RR. Sensitivity and publication bias analyses were conducted. Stability of results would be evaluated in case of publication bias. RESULTS 12 studies were included. Compared with CIM, pooled RR of cancer/dysplasia in IIM patients was 4.48 (95% CI 2.50-8.03), and the RR was 4.96 (95% CI 2.72-9.04) for cancer, and 4.82 (95% CI 1.45-16.0) for dysplasia. The pooled RR for cancer/dysplasia in type III IM was 6.27 (95% CI 1.89-20.77) compared with type II + I IM, while it was 5.55 (95% CI 2.07-14.92) compared with type II IM. Pooled RR between type II IM and type I IM was 1.62 (95% CI 1.16-2.27). Subgroup analyses showed that IIM was associated with a higher risk of gastric cancer/dysplasia in Western population (pooled RR = 4.65 95% CI 2.30-9.42), but not in East Asian population (pooled RR = 4.01 95% CI 0.82-19.61). CONCLUSIONS IIM was related to a higher risk of cancer/dysplasia compared with CIM. Risk of developing cancer/dysplasia from type I, II, and III intestinal metaplasia increased gradually.
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Affiliation(s)
- Ning Wei
- Medical School of Southeast University, Nanjing, 210009, China
- Department of Gastroenterology, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao, Nanjing, 210009, China
| | - Mengyue Zhou
- Medical School of Southeast University, Nanjing, 210009, China
- Department of Gastroenterology, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao, Nanjing, 210009, China
| | - Siyu Lei
- Medical School of Southeast University, Nanjing, 210009, China
- Department of Gastroenterology, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao, Nanjing, 210009, China
| | - Zhiheng Zhong
- Medical School of Southeast University, Nanjing, 210009, China
- Department of Gastroenterology, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao, Nanjing, 210009, China
| | - Ruihua Shi
- Medical School of Southeast University, Nanjing, 210009, China.
- Department of Gastroenterology, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao, Nanjing, 210009, China.
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18
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Liu X, Zhang M, Luo R, Mo K, He X. Significance of pepsinogen in screening for gastric intestinal metaplasia in Guangdong, China. J Int Med Res 2021; 49:300060521990495. [PMID: 33631996 PMCID: PMC7917884 DOI: 10.1177/0300060521990495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 01/05/2021] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE Diagnosis of gastric intestinal metaplasia (GIM) relies on gastroscopy and histopathologic biopsy, but their application in screening for GIM is limited. We aimed to identify serological biomarkers of GIM via screening in Guangdong, China. METHODS Cross-sectional field and questionnaire data, demographic information, past medical history, and other relevant data were collected. Blood samples were collected for pepsinogen (PG)I, PGII, gastrin-17, and Helicobacter pylori antibody testing, and gastroscopy and histopathologic biopsy were performed. Single factor and logistic regression analyses were used to evaluate the correlation between these indicators and GIM, and decision tree models were used to determine the cut-off points between indicators. RESULTS Of 443 participants enrolled, 87 (19.6%) were diagnosed with GIM. Single factor analysis showed that pepsin indicators (PGI, PGII, and PGI/PGII ratio) and the factors Mandarin as native language, urban residency, hyperlipidemia, and age were associated with GIM. Logistic regression analysis showed that PGI and age were associated with GIM. CONCLUSIONS Age is an important factor for predicting GIM progression; age >60 years increased its risk. Detection of GIM was higher in individuals with PGI levels >127.20 ng/mL, which could be used as a threshold indicating the need to perform gastroscopy and histopathologic biopsy.
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Affiliation(s)
- Xujuan Liu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
- Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Min Zhang
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Riyu Luo
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Keran Mo
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xingxiang He
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
- Xingxiang He, Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, No. 19, Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong Province 510080, China.
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19
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DE Miranda Neto AA, Marques SB, Baba ER, Yamazaki K, Ribeiro IB, DE Moura EGH. EXTENSIVE SQUAMOUS METAPLASIA OF THE STOMACH. ARQUIVOS DE GASTROENTEROLOGIA 2021; 57:335-336. [PMID: 32813817 DOI: 10.1590/s0004-2803.202000000-62] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 05/06/2020] [Indexed: 12/20/2022]
Affiliation(s)
- Antonio Afonso DE Miranda Neto
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Divisão de Endoscopia Gastrointestinal, São Paulo, SP, Brasil
| | - Sérgio Barbosa Marques
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Divisão de Endoscopia Gastrointestinal, São Paulo, SP, Brasil
| | - Elisa Ryoka Baba
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Divisão de Endoscopia Gastrointestinal, São Paulo, SP, Brasil
| | - Kendi Yamazaki
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Divisão de Endoscopia Gastrointestinal, São Paulo, SP, Brasil
| | - Igor Braga Ribeiro
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Divisão de Endoscopia Gastrointestinal, São Paulo, SP, Brasil
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20
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Wei N, Zhong Z, Shi R. A novel method of grading gastric intestinal metaplasia based on the combination of subtype and distribution. Cancer Cell Int 2021; 21:61. [PMID: 33472622 PMCID: PMC7816327 DOI: 10.1186/s12935-021-01758-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 01/04/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Studies have shown the value of subtypes and distribution of gastric intestinal metaplasia (GIM) for prediction of gastric cancer. We aim to combine GIM subtypes and distribution to form a new scoring system for GIM. METHODS This was a cross-sectional study. No GIM, type I, II, and III GIM of gastric antrum and corpus scored 0-3 points respectively. Then the severity of the whole stomach was calculated in two ways: 1. The gastric antrum and corpus scores were added together, with a score ranging from 0 to 6, which named "Subtype Distribution Score of Gastric Intestinal Metaplasia (SDSGIM)". 2. Direct classification according to a table corresponding to that of OLGIM. We compared the SDSGIM among benign lesions, dysplasia, and cancer and drew receiver operating characteristic (ROC) curve to determine the optimal cut-off value. According to the cut-off value and the classification from the table, the predictive ability of these two methods were calculated. RESULTS 227 patients were included. For SDSGIM, benign lesion group was significantly different from dysplasia or cancer group. Area under curve of ROC curve was 0.889 ± 0.023. The optimal cut-off value was 3. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SDSGIM for malignancy were 89.5%, 78.0%, 74.6%, 91.2% and 82.8%. And those for the second classification method were 84.2%, 82.6%, 77.7%, 87.9%, and 83.3% respectively. CONCLUSIONS This study firstly combined GIM subtypes with its distribution forming a novel scoring system, which showed high prediction accuracy for malignant lesions.
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Affiliation(s)
- Ning Wei
- Medical School of Southeast University, No. 87 Dingjiaqiao,, Nanjing, 210009 China
- Department of Gastroenterology, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao, Nanjing, 210009 China
| | - Zhiheng Zhong
- Medical School of Southeast University, No. 87 Dingjiaqiao,, Nanjing, 210009 China
- Department of Gastroenterology, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao, Nanjing, 210009 China
| | - Ruihua Shi
- Medical School of Southeast University, No. 87 Dingjiaqiao,, Nanjing, 210009 China
- Department of Gastroenterology, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao, Nanjing, 210009 China
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21
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Koulis A, Busuttil RA, Boussioutas A. Premalignant lesions of the stomach and management of early neoplastic lesions. RESEARCH AND CLINICAL APPLICATIONS OF TARGETING GASTRIC NEOPLASMS 2021:185-216. [DOI: 10.1016/b978-0-323-85563-1.00013-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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22
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Chapelle N, Petryszyn P, Blin J, Leroy M, Le Berre-Scoul C, Jirka I, Neunlist M, Moussata D, Lamarque D, Olivier R, Tougeron D, Mosnier JF, Matysiak-Budnik T. A panel of stomach-specific biomarkers (GastroPanel®) for the diagnosis of atrophic gastritis: A prospective, multicenter study in a low gastric cancer incidence area. Helicobacter 2020; 25:e12727. [PMID: 32700438 DOI: 10.1111/hel.12727] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/15/2020] [Accepted: 06/17/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. MATERIAL AND METHODS In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. RESULTS Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P = .015] and corpus AG [61.0% (95% CI 49.2; 72.0), P = .004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068). CONCLUSION Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.
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Affiliation(s)
- Nicolas Chapelle
- IMAD, Hepato-Gastroenterology & Digestive Oncology Unit, University Hospital of Nantes, Nantes, France
- University of Nantes, Nantes, France
- INSERM UMR1235, The Enteric Nervous System in Gut and Brain Disorders, Nantes, France
| | - Pawel Petryszyn
- Department of Clinical Pharmacology, Wroclaw Medical University, Wroclaw, Poland
| | - Justine Blin
- University of Nantes, Nantes, France
- INSERM UMR1235, The Enteric Nervous System in Gut and Brain Disorders, Nantes, France
- Department of Biochemistry, University Hospital of Nantes, Nantes, France
| | - Maxime Leroy
- Department of Biostatistics, University Hospital of Nantes, Nantes, France
| | - Catherine Le Berre-Scoul
- University of Nantes, Nantes, France
- INSERM UMR1235, The Enteric Nervous System in Gut and Brain Disorders, Nantes, France
| | - Iva Jirka
- IMAD, Hepato-Gastroenterology & Digestive Oncology Unit, University Hospital of Nantes, Nantes, France
| | - Michel Neunlist
- University of Nantes, Nantes, France
- INSERM UMR1235, The Enteric Nervous System in Gut and Brain Disorders, Nantes, France
| | - Driffa Moussata
- Department of Hepato-Gastroenterology, University Hospital of Tours, Tours, France
| | - Dominique Lamarque
- Department of Hepato-Gastroenterology, Ambroise-Paré Hospital, AP-HP, Paris Saclay University, UVSQ, INSERM, Infection and Inflammation, Paris, France
| | - Raphael Olivier
- IMAD, Hepato-Gastroenterology & Digestive Oncology Unit, University Hospital of Nantes, Nantes, France
- Department of Hepato-Gastroenterology, Poitiers University Hospital and University of Poitiers, Poitiers, France
| | - David Tougeron
- Department of Hepato-Gastroenterology, Poitiers University Hospital and University of Poitiers, Poitiers, France
| | - Jean-François Mosnier
- University of Nantes, Nantes, France
- Department of Pathology, University Hospital of Nantes, Nantes, France
| | - Tamara Matysiak-Budnik
- IMAD, Hepato-Gastroenterology & Digestive Oncology Unit, University Hospital of Nantes, Nantes, France
- University of Nantes, Nantes, France
- INSERM UMR1235, The Enteric Nervous System in Gut and Brain Disorders, Nantes, France
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Huang HL, Leung CY, Saito E, Katanoda K, Hur C, Kong CY, Nomura S, Shibuya K. Effect and cost-effectiveness of national gastric cancer screening in Japan: a microsimulation modeling study. BMC Med 2020; 18:257. [PMID: 32921305 PMCID: PMC7489209 DOI: 10.1186/s12916-020-01729-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 08/03/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A national endoscopic screening program for gastric cancer was rolled out in Japan in 2015. We used a microsimulation model to estimate the cost-effectiveness of current screening guidelines and alternative screening strategies in Japan. METHODS We developed a microsimulation model that simulated a virtual population corresponding to the Japanese population in risk factor profile and life expectancy. We evaluated 15 endoscopic screening scenarios with various starting ages, stopping ages, and screening intervals. The primary outcomes were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio. Cost-effective screening strategies were determined using a willingness-to-pay threshold of $50,000 per QALY gained. One-way sensitivity and probabilistic sensitivity analyses were done to explore model uncertainty. RESULTS Using the threshold of $50,000 per QALY, a triennial screening program for individuals aged 50 to 75 years was the cost-effective strategy, with an incremental cost-effectiveness ratio of $45,665. Compared with no endoscopic screening, this strategy is predicted to prevent 63% of gastric cancer mortality and confer 27.2 QALYs gained per 1000 individuals over a lifetime period. Current screening guidelines were not on the cost-effectiveness efficient frontier. The results were robust on one-way sensitivity analyses and probabilistic sensitivity analysis. CONCLUSIONS This modeling study suggests that the endoscopic screening program in Japan would be cost-effective when implemented between age 50 and 75 years, with the screening repeated every 3 years. These findings underscore the need for further evaluation of the current gastric cancer screening recommendations.
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Affiliation(s)
- Hsi-Lan Huang
- Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Division of Cancer Statistics Integration, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan
| | - Chi Yan Leung
- Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Division of Cancer Statistics Integration, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan.
| | - Eiko Saito
- Division of Cancer Statistics Integration, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan
| | - Kota Katanoda
- Division of Cancer Statistics Integration, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan
| | - Chin Hur
- Department of Medicine, Columbia University Irving Medical Center, New York City, USA
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA, USA
| | - Chung Yin Kong
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA, USA
- Department of Radiology, Harvard Medical School, Boston, MA, USA
| | - Shuhei Nomura
- Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Health Policy and Management, School of Medicine, Keio University, Tokyo, Japan
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Kenji Shibuya
- Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- University Institute for Population Health, King's College London, London, UK
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24
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Lam SK, Lau G. Novel treatment for gastric intestinal metaplasia, a precursor to cancer. JGH Open 2020; 4:569-573. [PMID: 32782940 PMCID: PMC7411557 DOI: 10.1002/jgh3.12318] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 02/19/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Gastric intestinal metaplasia (GIM) is precancerous with a worldwide prevalence of 25%. Eradicating Helicobacter pylori prevented about half of gastric cancers; failure to prevent the rest was attributed to GIM. GIM is irreversible and often extensive. There is no treatment. Existing endoscopic mucosal resection (EMR) is designed to treat early gastric cancer of usually <2 cm. We designed a two-endoscope technique of EMR for extensive lesions such as GIM. METHODS Forty patients with histologically confirmed moderate to severe GIM (operative link on GIM [OLGIM] classification) received the treatment in a daycare center. Chromoendoscopy with methylene blue was first performed to indicate the GIM. Submucosal saline injections were used to lift the stained mucosa to form multiple safety cushions, which were transformed into artificial polyps by suction and ligation, using a cap familiar to gastroenterologists for ligation of esophageal varices. EMRs were then achieved by snare polypectomy. By rotating two gastroscopes, one was designated to perform lift and snare and the other to perform suction and ligation; cycles of lift-ligate-snare were performed until all stained mucosa was removed. Assessment chromoendoscopy with ≥seven biopsies was performed at 6 months. RESULTS A total of 227 EMRs were performed, with a median of 3.5 per patient. Bleeding was uncommon and minimal. Gastric perforation ascribable to loss of a safety cushion occurred in one patient. Chromoendoscopy at 6 months in 36 willing patients showed no recurrence of GIM. CONCLUSION The two-endoscope technique of EMR for GIM was essentially safe and effective, with no recurrence at 6 months. It could be performed by endoscopists with standard skills.
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Affiliation(s)
- Shiu Kum Lam
- Humanity & Health GI & Liver Centre, Humanity & Health Medical GroupHong Kong SARChina
- Humanity & Health Clinical Trial CentreHumanity & Health Medical Group, Hong Kong SARChina
| | - George Lau
- Humanity & Health GI & Liver Centre, Humanity & Health Medical GroupHong Kong SARChina
- Humanity & Health Clinical Trial CentreHumanity & Health Medical Group, Hong Kong SARChina
- Liver Diseases & Transplant CentreThe Fifth Medical Centre of Chinese PLA General HospitalBeijingChina
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25
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Waldum HL. Clinical consequences of controversies in gastric physiology. Scand J Gastroenterol 2020; 55:752-758. [PMID: 32515242 DOI: 10.1080/00365521.2020.1771758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Studies on the regulation of gastric acid secretion started more than 100 years ago at an early phase of experimental physiology. In nearly the whole last century there were disputes about the interpretation of the findings: the interaction between the three principle gastric acid secretagogues acetylcholine, gastrin and histamine, the cell producing the relevant histamine which turned out to be the ECL cell, the ability of the ECL cell to divide and thus develop into tumours, the classification of gastric carcinomas and the mechanism for Helicobacter pylori carcinogenesis. The elucidation of the central role of the ECL cell and thus its main regulator, gastrin, solve all these controversies, and gives a solid base for handling upper gastrointestinal diseases.
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Affiliation(s)
- Helge L Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
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26
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Koulis A, Buckle A, Boussioutas A. Premalignant lesions and gastric cancer: Current understanding. World J Gastrointest Oncol 2019; 11:665-678. [PMID: 31558972 PMCID: PMC6755108 DOI: 10.4251/wjgo.v11.i9.665] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Revised: 05/29/2019] [Accepted: 08/21/2019] [Indexed: 02/05/2023] Open
Abstract
Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer (GC) and its premalignant states from gross histological models to increasingly precise molecular descriptions. In this review we reflect upon the historic approaches to describing premalignant lesions and GC, highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.
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Affiliation(s)
- Athanasios Koulis
- Upper Gastrointestinal Translational Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
- the Sir Peter MacCallum Department of Surgical Oncology, the University of Melbourne, Melbourne 3010, Australia
| | - Andrew Buckle
- Upper Gastrointestinal Translational Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
- the Sir Peter MacCallum Department of Surgical Oncology, the University of Melbourne, Melbourne 3010, Australia
| | - Alex Boussioutas
- Upper Gastrointestinal Translational Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
- the Sir Peter MacCallum Department of Surgical Oncology, the University of Melbourne, Melbourne 3010, Australia
- Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, 3050, Australia
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27
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Akbari M, Tabrizi R, Kardeh S, Lankarani KB. Gastric cancer in patients with gastric atrophy and intestinal metaplasia: A systematic review and meta-analysis. PLoS One 2019; 14:e0219865. [PMID: 31348819 PMCID: PMC6660080 DOI: 10.1371/journal.pone.0219865] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 07/02/2019] [Indexed: 02/07/2023] Open
Abstract
AIM Intestinal metaplasia (IM) and gastric atrophy (GA) are precancerous lesions in the stomach. There is a large debate on natural course of these lesions and surveillance strategy in these patients. This meta-analysis was aimed to find the most appropriate follow up and the rate of progression from IM and GA to GC. METHODS This meta-analysis is followed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases including EMBASE, PubMed, Web of Science databases, Scopus, and the Cochrane Library were searched until July 2018. Cochran's Q test and I-square (I2) test were used to examine heterogeneity across included studies. We pooled data using random-effect or fixed effect models indicated as incidence rate or proportion with 95% confidence intervals (CI). The variables of study included demographic data, endoscopy interval, follow up interval and time, GA and IM type and GC stage. Moreover, incidence rate of GC and progress rate, regress and persistence proportion in both GA and IM patients were assessed. RESULTS Overall, 68 original articles out of 32981 citations were included in our meta-analysis. The pooled GC incidence rate in patients with GA was 1.24 (95% CI, 0.80, 1.76; I2: 83.6%) cases per 1,000 person-years. The rates of later diagnosis of IM and gastric dysplasia in patients with GA were estimated as 41.42 (95% CI, 3.11, 64.45; I2: 95.6%) and 6.23 (95% CI, 2.34, 11.46; I2: 83.0%) cases per 1,000 person-years, respectively. The pooled regressed proportion was 32.23 (95% CI, 18.07-48.02; I2: 94.0%) and the persistence proportion was 38.83 (95% CI, 20.20-59.13; I2: 97.0%) per 100 observations in GA patients. In IM studies, the pooled incidence rate of GC was 3.38 (95% CI, 2.13, 4.85; I2: 93.4%) cases per 1,000 person-years. The progressed rate to dysplasia in IM patient was estimated to be 12.51 (95% CI, 5.45, 22.03; I2: 95.1%) cases per 1,000 person-years. The pooled regressed proportion was 31.83 (95% CI, 25.48-38.51; I2: 91.0%) and the persistence proportion was 43.46 (95% CI, 32.52-54.71; I2: 96.0%) per 100 observations in IM patients. CONCLUSION Overall, the incidence of GC in patients with IM and GA are low but there is heterogeneity in data with the highest rate in Asian, males with those with incomplete IM. There is probability of regression or persistence without progression in patients with IM and GA who receive appropriate management.
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Affiliation(s)
- Maryam Akbari
- Health Policy Research Center, Institute of Health, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Tabrizi
- Health Policy Research Center, Institute of Health, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sina Kardeh
- Cellular and Molecular Medicine Student Research Group, Shiraz School of Medicine, Shiraz, Iran
| | - Kamran B. Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
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Lu R, Shao Y, Tao X, Ye G, Xiao B, Guo J. Clinical significances of hsa_circ_0067582 and hsa_circ_0005758 in gastric cancer tissues. J Clin Lab Anal 2019; 33:e22984. [PMID: 31328820 PMCID: PMC6868420 DOI: 10.1002/jcla.22984] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 06/29/2019] [Accepted: 07/02/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) are a special class of endogenous noncoding RNAs that have numerous biological functions in normal situation and diseases including cancers. However, the clinical significance of circRNAs in gastric cancer (GC) remains largely unknown. Here, we chose two representative circRNAs, hsa_circ_0067582 and hsa_circ_0005758, to investigate their clinical significance in GC patients. METHODS Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we explored the expression levels of hsa_circ_0067582 and hsa_circ_0005758 in tissues with different stages of gastric tumorigenesis. Then, the relationships between their expression levels and GC patients' clinicopathological factors were further investigated. Receiver operating characteristic (ROC) curves were established for evaluating diagnostic values of hsa_circ_0067582 and hsa_circ_0005758. RESULTS Compared with healthy control tissues, both hsa_circ_0067582 and hsa_circ_0005758 were significantly decreased in GC tissues. Besides, hsa_circ_0067582 expression was associated with GC patients' tissue CEA level (P <.001) and stages (P = .037); and hsa_circ_0005758 expression was relevant to tissue CEA level (P < .001) and perineural invasion (P = .048). The area under the ROC curve (AUC) of hsa_circ_0067582 was up to 0.671. The cutoff value was set at 10.61, with which the sensitivity and specificity were 55.2% and 75.0%, respectively. Similar to hsa_circ_0005758, the AUC of hsa_circ_0005758 was 0.721. The cutoff value was set at 10.20, with which the sensitivity and specificity were 75.0% and 67.7%, respectively. CONCLUSION These results showed that both hsa_circ_0067582 and hsa_circ_0005758 may play an important role in gastric carcinogenesis; and they may be potential indicators for GC diagnosis.
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Affiliation(s)
- Rongdan Lu
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Yongfu Shao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Xueping Tao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Guoliang Ye
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
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Quach DT, Hiyama T, Gotoda T. Identifying high-risk individuals for gastric cancer surveillance from western and eastern perspectives: Lessons to learn and possibility to develop an integrated approach for daily practice. World J Gastroenterol 2019; 25:3546-3562. [PMID: 31367156 PMCID: PMC6658388 DOI: 10.3748/wjg.v25.i27.3546] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/28/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
Current evidence shows that individuals with gastric dysplasia, severe and extensive gastric atrophy, extensive gastric intestinal metaplasia and the incomplete subtype of intestinal metaplasia are at high risk for gastric cancer (GC) development. There are several approaches to identifying these subjects, including noninvasive methods, esophagogastroduodenoscopy and histology. The main approach in Western countries is histology-based while that in Eastern countries with a high prevalence of GC is endoscopy-based. Regarding asymptomatic individuals, the key issues in selecting applicable approaches are the ability to reduce GC mortality and the cost-effectiveness of the approach. At present, population-based screening programs have only been applied in a few Asian countries with a high risk of GC. Pre-endoscopic risk assessment based on demographic and clinical features, such as ethnicity, age, gender, smoking and Helicobacter pylori status, is helpful for identifying subjects with high pre-test probability for a possibly cost-effective approach, especially in intermediate- and low-risk countries. Regarding symptomatic patients with indications for esophagogastroduodenoscopy, the importance of opportunistic screening should be emphasized. The combination of endoscopic and histological approaches should always be considered as endoscopy provides a real-time assessment of the patient's risk level. In addition, imaging enhanced endoscopy (IEE) has been shown to facilitate targeted biopsies resulting in better correlation between endoscopic and histological findings. Currently, the use of IEE is recommended for endoscopic examinations, and the Operative Link for Gastric Intestinal Metaplasia or Operative Link on Gastritis Assessment grading systems are recommended for histological examinations whenever available. However, resource limitations are an important barrier in many regions worldwide. Thus, for an approach to be applicable in real-life practice, it should be not only evidence-based but also resource-sensitive. In this review, we discuss the current understanding and approaches to identifying high-risk individuals from western and eastern perspectives, as well as the possibility of an integrated, resource-sensitive approach.
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Affiliation(s)
- Duc Trong Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Hochiminh City, Ho Chi Minh 70000, Vietnam
| | - Toru Hiyama
- Health Service Center, Hiroshima University, Higashihiroshima 739-8514, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo 101-8309, Japan
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Oliveros R, Pinilla Morales RE, Facundo Navia H, Sánchez Pedraza R. Cáncer gástrico: una enfermedad prevenible. Estrategias para intervención en la historia natural. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2019; 34:177-189. [DOI: 10.22516/25007440.394] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
El cáncer gástrico es un problema de salud pública. Las cifras de mortalidad y supervivencia son impresentables en nuestro país. En Colombia no existe ningún programa ni estrategias de diagnóstico temprano, ni tampoco es priorizado como un problema de salud. Los trabajos existentes demuestran que la mayoría de los pacientes cuando son diagnosticados presentan estadios avanzados.
Un 90 % de los canceres gástricos se consideran consecuencia de un largo proceso inflamatorio sobre la mucosa gástrica. La infección por Helicobacter pylori es la principal etiología de la gastritis, la cual puede progresar a atrofia, metaplasia, displasia y cáncer. La atrofia gástrica establece un campo de cancerización más propenso a cambios moleculares y fenotípicos que terminan en un cáncer en crecimiento. Es claro que la historia natural proporciona un racional entendimiento clínico patológico para estrategias de prevención primaria y secundaria. Una evidencia bien establecida demuestra que la combinación de las estrategias primarias (erradicación del H. pylori) y secundarias (diagnóstico y seguimiento endoscópico de lesiones premalignas) pueden prevenir o limitar la progresión de la carcinogénesis gástrica. El riesgo de cáncer gástrico asociado con la gastritis por H. pylori puede ser estratificado de acuerdo con la gravedad y extensión de la atrofia de la mucosa gástrica. Esta aproximación está adaptada a diferentes países, de acuerdo con su incidencia específica de cáncer gástrico, condición socioeconómica y factores culturales, que requiere de la participación complementaria de los gastroenterólogos, los cirujanos, los oncólogos y patólogos.
Frente a este problema de salud pública no hay ninguna acción por parte de las autoridades de salud ni del gremio médico. Por tanto, se revisan las estrategias de manejo que permitan intervenir la historia natural de la enfermedad con el objetivo de disminuir la incidencia y mortalidad.
La implementación y estandarización de estas estrategias de manejo en nuestro medio podrán beneficiar a los pacientes con riesgo incrementado para cáncer gástrico y pueden implementarse (en países sin programas de tamizaje) de una forma racional, similar a como se está haciendo con el cáncer colorrectal, en todo el mundo.
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Duan X, Lian H, Li J, Wu B, Wang W, Wu T, Wang C, Dou Y, Zhou Z, Wang B, Xue L, Wang G. Expression of GCRG213p, LINE-1 endonuclease variant, significantly different in gastric complete and incomplete intestinal metaplasia. Diagn Pathol 2019; 14:61. [PMID: 31221180 PMCID: PMC6587291 DOI: 10.1186/s13000-019-0838-9] [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: 04/28/2019] [Accepted: 06/11/2019] [Indexed: 11/28/2022] Open
Abstract
Background Intestinal metaplasia (IM) of the gastric mucosa is classified as complete (Type I) and incomplete IM (Type II and III) subtypes, which showed significantly different risk for developing to gastric adenocarcinoma (GAC). GCRG213, a variant of L1-endonuclease (L1-EN), first identified in our lab, was upregulated in GAC tissue. However, the relationship between GCRG213 and IM subtypes is not clear. Our study explored the association of GCRG213 protein (GCRG213p) with IM subtypes. Methods Gastric cancer and/or para-tumor tissue samples were collected from 123 patients who underwent gastrectomy for intestinal type gastric adenocarcinoma. The subtypes of IM were characterized with Alcian blue-periodic acid-Schiff and High Iron Diamine-Alcian blue staining methods. Immunohistochemistry of GCRG213p was performed, and its expression in gastric adenocarcinoma and para-tumor tissue including dysplasia, IM, and normal mucosa were analyzed. Results GCRG213p was expressed in 48.94% IM, 57.14% dysplasia and 55.32% GAC, respectively. GCRG213p expression was higher in well and moderately differentiated adenocarcinoma (P = 0.037). In IM glands, GCRG213p expressed mainly in the cytoplasm of absorptive enterocytes with defined brush borders, but not in goblet cells. The expression of GCRG213p in type I IM (90.00%) was significantly higher than that in type II (36.36%) and type III (25.00%) (P < 0.001). In normal gastric mucosa, GCRG213p was exclusively positive in the cytoplasm of gastric chief cells. Conclusions The expression of GCRG213p in complete IM was significantly higher than in incomplete IM, which implies that GCRG213p may play a role on the developing of IM to adenocarcinoma. GCRG213p was exclusively expressed in chief cells, suggesting that it might be involved in cell differentiation from the chief cells to IM.
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Affiliation(s)
- Xiaojian Duan
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Hongwei Lian
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Jie Li
- Department of Pathology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
| | - Benyan Wu
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Weihua Wang
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Tao Wu
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Changzheng Wang
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Yan Dou
- Department of Gastroenterology, The First Medical Center, Chinese PLA General Hospital and National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Zhongren Zhou
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - Bingzhi Wang
- Department of Pathology and Resident Training Base, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Liyan Xue
- Department of Pathology and Resident Training Base, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
| | - Gangshi Wang
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China.
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Torbenson M. Common Types of Gastritis. SURGICAL PATHOLOGY OF NON-NEOPLASTIC GASTROINTESTINAL DISEASES 2019:121-135. [DOI: 10.1007/978-3-030-15573-5_6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Waldum HL, Fossmark R. Types of Gastric Carcinomas. Int J Mol Sci 2018; 19:ijms19124109. [PMID: 30567376 PMCID: PMC6321162 DOI: 10.3390/ijms19124109] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 12/15/2018] [Accepted: 12/15/2018] [Indexed: 12/16/2022] Open
Abstract
Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for Helicobacter pylori as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment. Therefore, it is essential to determine the role of the gastrin target cell, the ECL cell, in gastric carcinogenesis. Clinical trials with gastrin antagonists could improve prognoses in those with gastrin receptor positive tumours. However, further studies on gastric carcinomas applying relative available methods and with the highest sensitivity are warranted to improve our knowledge of gastric carcinogenesis.
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Affiliation(s)
- Helge L Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
- Department of Gastroenterology and Hepatology, St. Olav's University Hospital, 7006 Trondheim, Norway.
| | - Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
- Department of Gastroenterology and Hepatology, St. Olav's University Hospital, 7006 Trondheim, Norway.
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Gankyrin Drives Malignant Transformation of Gastric Cancer and Alleviates Oxidative Stress via mTORC1 Activation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:9480316. [PMID: 30420909 PMCID: PMC6215549 DOI: 10.1155/2018/9480316] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 08/13/2018] [Accepted: 08/23/2018] [Indexed: 12/11/2022]
Abstract
Gastric cancer, as a malignant epithelial tumor, is a major health threat leading to poor overall survival and death. It is usually diagnosed at an advanced stage due to asymptomatic or only nonspecific early symptoms. The present study demonstrated that gankyrin contributes to the early malignant transformation of gastric cancer and can be selected to predict the risk of gastric cancer in those patients harboring the precancerous lesions (dysplasia and intestinal metaplasia). In addition, a new insight into gastric cancer was provided, which stated that gankyrin alleviates oxidative stress via mTORC1 pathway activation. It can potentiate the mTORC1 by PGK1-AKT signaling that promotes the tumor process, and this phenomenon is not completely consistent with the previous report describing colorectal cancer.
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van der Poorten DK, McLeod D, Ahlenstiel G, Read S, Kwok A, Santhakumar C, Bassan M, Culican S, Campbell D, Wong SWJ, Evans L, Jideh B, Kane A, Katelaris CH, Keat K, Ko Y, Lee JA, Limaye S, Lin MW, Murad A, Rafferty M, Suan D, Swaminathan S, Riminton SD, Toong C, Berglund LJ. Gastric Cancer Screening in Common Variable Immunodeficiency. J Clin Immunol 2018; 38:768-777. [PMID: 30219982 DOI: 10.1007/s10875-018-0546-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 09/06/2018] [Indexed: 12/22/2022]
Abstract
Individuals with common variable immunodeficiency (CVID) have an increased risk of gastric cancer, and gastrointestinal lymphoma, yet screening for premalignant gastric lesions is rarely offered routinely to these patients. Proposed screening protocols are not widely accepted and are based on gastric cancer risk factors that are not applicable to all CVID patients. Fifty-two CVID patients were recruited for screening gastroscopy irrespective of symptoms or blood results and were compared to 40 controls presenting for gastroscopy for other clinical indications. Overall, 34% of CVID patients had intestinal metaplasia (IM), atrophic gastritis or moderate to severe non-atrophic gastritis, which can increase the risk of gastric cancer, compared to 7.5% of controls (p < 0.01). Focal nodular lymphoid hyperplasia, a precursor lesion for gastrointestinal lymphoma, was seen in eight CVID patients (16%), one of whom was diagnosed with gastrointestinal lymphoma on the same endoscopy. High-risk gastric pathology was associated with increased time since diagnosis of CVID, smoking, Helicobacter pylori, a low-serum pepsinogen I concentration, and diarrhea, but not pepsinogen I/II ratio, iron studies, vitamin B12 levels or upper gastrointestinal symptoms. There was a lower rate of detection of IM when fewer biopsies were taken, and IM and gastric atrophy were rarely predicted by the endoscopist macroscopically, highlighting the need for standardized biopsy protocols. The prevalence of premalignant gastric lesions in patients with CVID highlights the need for routine gastric screening. We propose a novel gastric screening protocol to detect early premalignant lesions and reduce the risk of gastric cancer and gastric lymphoma in these patients.
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Affiliation(s)
- David K van der Poorten
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, NSW, Australia.,Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia
| | - Duncan McLeod
- Department of Anatomical Pathology, Westmead Hospital, Sydney, NSW, Australia.,NSW Health Pathology, Sydney, NSW, Australia
| | - Golo Ahlenstiel
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Blacktown Clinical School, School of Medicine, Western Sydney University, Penrith, NSW, Australia.,Department of Gastroenterology and Hepatology, Blacktown Hospital, Blacktown, NSW, Australia.,Storr Liver Centre, Westmead Institute of Medical Research, Westmead, NSW, Australia
| | - Scott Read
- Storr Liver Centre, Westmead Institute of Medical Research, Westmead, NSW, Australia
| | - Avelyn Kwok
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Cositha Santhakumar
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Milan Bassan
- Department of Gastroenterology and Hepatology, Liverpool hospital, Sydney, NSW, Australia.,Faculty of Medicine, The University of New South Wales, Sydney, NSW, Australia
| | | | | | | | - Louise Evans
- Faculty of Medicine, The University of New South Wales, Sydney, NSW, Australia.,Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia
| | - Bilel Jideh
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, NSW, Australia
| | - Alisa Kane
- Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia
| | - Constance H Katelaris
- Department of Immunology, Campbelltown Hospital, Campbelltown, NSW, Australia.,Faculty of Medicine, Western Sydney University, Sydney, NSW, Australia
| | - Karuna Keat
- Department of Immunology, Campbelltown Hospital, Campbelltown, NSW, Australia.,Faculty of Medicine, Western Sydney University, Sydney, NSW, Australia
| | - Yanna Ko
- Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Jessie A Lee
- Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia
| | - Sandhya Limaye
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Ming Wei Lin
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Departments of Immunology and Immunopathology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Australia
| | - Ari Murad
- Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia
| | - Martina Rafferty
- Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Dan Suan
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Departments of Immunology and Immunopathology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Australia.,Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Sanjay Swaminathan
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Departments of Immunology and Immunopathology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Australia
| | - Sean D Riminton
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Catherine Toong
- NSW Health Pathology, Sydney, NSW, Australia.,Faculty of Medicine, The University of New South Wales, Sydney, NSW, Australia.,Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia.,Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Lucinda J Berglund
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia. .,NSW Health Pathology, Sydney, NSW, Australia. .,Departments of Immunology and Immunopathology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Australia.
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Wu S, Zhang Y, Zhang L, Ma JL, Zhou T, Li ZX, Liu WD, Li WQ, You WC, Pan KF. Methylation and Expression of Nonclustered Protocadherins Encoding Genes and Risk of Precancerous Gastric Lesions in a High-Risk Population. Cancer Prev Res (Phila) 2018; 11:717-726. [PMID: 30213786 DOI: 10.1158/1940-6207.capr-18-0119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 06/01/2018] [Accepted: 08/29/2018] [Indexed: 11/16/2022]
Abstract
Nonclustered protocadherins (PCDH) family is a group of cell-cell adhesion molecules. We have found differentially methylated genes in the nonclustered PCDHs family associated with Helicobacter pylori (H. pylori) infection in prior genome-wide methylation analysis. To further investigate the methylation and expression of nonclustered PCDHs encoding genes in H. pylori--related gastric carcinogenesis process, four candidate genes including PCDH7, PCDH10, PCDH17, and PCDH20 were selected, which were reported to be tumor suppressors for digestive cancers. A total of 747 participants with a spectrum of gastric lesions were enrolled from a high-risk population of gastric cancer. Promoter methylation levels of four genes were significantly higher in H. pylori-positive subjects than the negative group (all P < 0.001). Elevated methylation levels of PCDH10 and PCDH17 were observed with the increasing severity of gastric lesions (both P trend < 0.001). In the protein expression analysis, PCDH17 expression was inversely associated with gastric lesions; the OR [95% confidence interval (CI)] was 0.49 (0.26-0.95) for chronic atrophic gastritis (CAG), 0.31 (0.15-0.63) for intestinal metaplasia, and 0.38 (0.19-0.75) for indefinite dysplasia and dysplasia, compared with superficial gastritis. In addition, PCDH10 expression was significantly lower in CAG (OR, 0.40; 95% CI, 0.24-0.68). The inverse association between methylation and protein expression of PCDH10 and PCDH17 was further supported when we explored the methylation and mRNA expression in The Cancer Genome Atlas database (all P < 0.001). Our study found elevated promoter methylation and decreased expression of PCDH10 and PCDH17 in advanced gastric lesions, suggesting that elevated PCDH10 and PCDH17 methylation may be an early event in gastric carcinogenesis. Cancer Prev Res; 11(11); 717-26. ©2018 AACR.
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Affiliation(s)
- Si Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Yang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Lian Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Jun-Ling Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Tong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Zhe-Xuan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Wei-Dong Liu
- Linqu Public Health Bureau, Linqu, Shandong, People's Republic of China
| | - Wen-Qing Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Wei-Cheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
| | - Kai-Feng Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
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Venerito M, Vasapolli R, Rokkas T, Malfertheiner P. Gastric cancer: epidemiology, prevention, and therapy. Helicobacter 2018; 23 Suppl 1:e12518. [PMID: 30203589 DOI: 10.1111/hel.12518] [Citation(s) in RCA: 115] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastric cancer (GC) is still the third leading cause of cancer death in both sexes worldwide. Helicobacter pylori infection is the most important risk factor for GC and, in spite of the consistent trend of a decreasing incidence, in 2015 approximately 4.4 billion individuals-more than half the world's population-were infected with H. pylori. The birth cohort pattern of decreased H. pylori infection reported in a systematic review contributes to explain the declining GC mortality in Japan. Current trends in estimated annual percentage change of GC incidence foreshadow expected reversals in both falling incidence and male predominance among US non-Hispanic whites. Combining serum pepsinogen 1 and H. pylori serology was shown to be useful for GC risk stratification in a Finnish population. Gastritis staging by operative link on gastritis assessment was confirmed to be reliable in predicting GC risk in a large prospective study. In a randomized trial from South Korea, H. pylori eradication therapy significantly reduced the rates of metachronous GC in patients who received curative endoscopic resection for early GC. A study based on a territory-wide health care database of the Hong Kong Hospital Authority showed that aspirin use is associated with a reduced GC risk. Another study based on the same database showed that proton pump inhibitors increase GC risk, but methodological biases have most likely acted as confounders. Confirmatory data on the role of endoscopic submucosal dissection in patients with early GC have been published. The phase III FLOT4 trial has shown that the FLOT triplet regimen (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil) improves the outcome of patients with GC and locoregional disease as compared to the ECF triplet (epirubicin, cisplatin, and 5-fluorouracil). In the phase III ATTRACTION-2 trial, nivolumab was shown to be an effective treatment option with a relative safe profile for heavily pretreated patients with advanced GC.
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Affiliation(s)
- Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Riccardo Vasapolli
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | | | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
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Waddingham W, Graham D, Banks M, Jansen M. The evolving role of endoscopy in the diagnosis of premalignant gastric lesions. F1000Res 2018; 7. [PMID: 29946429 PMCID: PMC5998031 DOI: 10.12688/f1000research.12087.1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/01/2018] [Indexed: 12/18/2022] Open
Abstract
Gastric adenocarcinoma is a disease that is often detected late, at a stage when curative treatment is unachievable. This must be addressed through changes in our approach to the identification of patients at increased risk by improving the detection and risk assessment of premalignant changes in the stomach, including chronic atrophic gastritis and intestinal metaplasia. Current guidelines recommend utilising random biopsies in a pathology-led approach in order to stage the extent and severity of gastritis and intestinal metaplasia. This random method is poorly reproducible and prone to sampling error and fails to acknowledge recent advances in our understanding of the progression to gastric cancer as a non-linear, branching evolutionary model. Data suggest that recent advances in endoscopic imaging modalities, such as narrow band imaging, can achieve a high degree of accuracy in the stomach for the diagnosis of these premalignant changes. In this review, we outline recent data to support a paradigm shift towards an endoscopy-led approach to diagnosis and staging of premalignant changes in the stomach. High-quality endoscopic interrogation of the chronically inflamed stomach mucosa, supported by targeted biopsies, will lead to more accurate risk assessment, with reduced rates of under or missed diagnoses.
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Affiliation(s)
- William Waddingham
- Department of Endoscopy, University College London Hospital, London, UK.,UCL Cancer Institute, University College London, London, UK
| | - David Graham
- Department of Endoscopy, University College London Hospital, London, UK
| | - Matthew Banks
- Department of Endoscopy, University College London Hospital, London, UK
| | - Marnix Jansen
- UCL Cancer Institute, University College London, London, UK.,Department of Pathology, University College London, London, UK
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Quach DT, Le HM, Nguyen TS, Hiyama T. The Distribution of Incomplete Gastric Intestinal Metaplasia (GIM) Subtype among Biopsy Sites according to the Updated Sydney System and Its Association with GIM Extension. Gastroenterol Res Pract 2018; 2018:4938730. [PMID: 29853861 PMCID: PMC5964434 DOI: 10.1155/2018/4938730] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 04/01/2018] [Accepted: 04/18/2018] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Current guidelines recommend that extensive gastric intestinal metaplasia (GIM) be considered as a high-risk marker for the development of gastric cancer (GC). But there is emerging evidence that the incomplete GIM subtype is also a high-risk marker. AIMS To evaluate the performance of biopsy sites according to the updated Sydney system on detecting the incomplete GIM subtype and to assess its association with GIM extension. PATIENTS AND METHODS A cross-sectional study was conducted on 280 Vietnamese patients with nonulcer dyspepsia. Biopsy specimens were taken from gastric sites according to the updated Sydney system, and sections were routinely stained with Giemsa and hematoxylin and eosin. Biopsy specimens with intestinalization were further evaluated for GIM subtypes with alcian blue 2.5 and periodic acid Schiff stainings. Two experienced pathologists jointly examined all the specimens and reached consensus. RESULTS The rates of patients with GIM and the incomplete GIM subtype were 81 (28.9%) and 24 (8.4%), respectively. There was no GIM in specimens taken from the greater curvature of corpus. The proportions of the incomplete GIM subtype detected at the incisura angularis, lesser curvature of corpus, lesser curvature of antrum, and greater curvature of antrum were 34.3% (12/35), 34.5% (10/29), 40.5% (17/42), and 31.6 (6/19), respectively, which were not significantly different (p = 0.89). The presence of an incomplete GIM subtype was associated with multifocal GIM (i.e., ≥3 out of 5 biopsy sites with GIM) (OR = 4.02, CI 95%, 1.33-12.16, p = 0.022) and extensive GIM (i.e., GIM in specimens from both of corpus and antrum) (OR = 2.89, CI 95% 1.04-8.02, p = 0.045). CONCLUSIONS The proportions of an incomplete GIM subtype were not significantly different among gastric biopsy sites with intestinalization. The association between an incomplete GIM subtype and GIM extension, therefore, may be due to an sum accumulation effect.
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Affiliation(s)
- Duc Trong Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Department of Gastroenterology, Gia Dinh People's Hospital, Ho Chi Minh City, Vietnam
| | - Huy Minh Le
- Department of Surgical Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Trung Sao Nguyen
- Department of Surgical Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Toru Hiyama
- Health Service Center, Hiroshima University, Higashihiroshima, Japan
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40
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Quach DT, Hiyama T. Letter: extensive intestinal metaplasia is associated with the presence of incomplete intestinal metaplasia subtype and could be an easier marker for high risk of gastric cancer. Aliment Pharmacol Ther 2018; 47:1045-1046. [PMID: 29512911 DOI: 10.1111/apt.14553] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Linked ContentThis article is linked to Pittayanon et al and Pittayanon and Barkun papers. To view these articles visit https://doi.org/10.1111/apt.14082 and https://doi.org/10.1111/apt.14555.
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Affiliation(s)
- D T Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Hochiminh City, Hochiminh, Viet Nam
| | - T Hiyama
- Health Service Center, Hiroshima University, Higashihiroshima, Japan
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Pittayanon R, Barkun A. Letter: extensive intestinal metaplasia is associated with the presence of incomplete intestinal metaplasia subtype and could be an easier marker for high risk of gastric cancer Authors' reply. Aliment Pharmacol Ther 2018. [PMID: 29512908 DOI: 10.1111/apt.14555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- R Pittayanon
- Division of Gastroenterology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital the Thai Red Cross, Bangkok, Thailand.,Division of Gastroenterology, McGill University, the McGill University Health Centre, Montreal, Canada
| | - A Barkun
- Division of Gastroenterology, McGill University, the McGill University Health Centre, Montreal, Canada
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42
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Hwang YJ, Kim N, Lee HS, Lee JB, Choi YJ, Yoon H, Shin CM, Park YS, Lee DH. Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years. Aliment Pharmacol Ther 2018; 47:380-390. [PMID: 29193217 DOI: 10.1111/apt.14424] [Citation(s) in RCA: 117] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 07/31/2017] [Accepted: 10/27/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial. AIM To evaluate the reversibility of atrophic gastritis and intestinal metaplasia by H. pylori eradication with long-term follow-up. METHODS 598 subjects were prospectively enrolled and followed for up to 10 years. They were categorised as H. pylori-negative (n = 65), H. pylori non-eradicated (n = 91), and H. pylori-eradicated (n = 442). Histological assessment was performed for antrum and corpus by Sydney classification. RESULTS Histological follow-up was performed regularly at 1, 2, 3-4 and ≥5 years, with mean follow-up of 1.07 ± 0.21, 2.29 ± 0.83, 3.93 ± 1.02, and 6.45 ± 1.28 years, respectively. Atrophic gastritis in antrum and corpus gradually and significantly (both P < .05 for all timepoints) improved only in the H. pylori-eradicated group compared to that at baseline. Significant difference in atrophic gastritis between H. pylori-eradicated and H. pylori-negative groups disappeared from 1-year follow-up. Similarly, intestinal metaplasia in antrum and corpus improved significantly (both P < .05 for all timepoints) only in the H. pylori-eradicated group in comparison with that at baseline. Significant difference in intestinal metaplasia between H. pylori-eradicated and H. pylori-negative groups disappeared from ≥5 years of follow-up in the antrum and from 3 years of follow-up in the corpus. CONCLUSION H. pylori eradication may be a preventative strategy for intestinal-type gastric cancer by regression of atrophic gastritis and intestinal metaplasia.
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Affiliation(s)
- Y-J Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - N Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea.,Department of Internal Medicine and Institute of Liver Research, Seoul National University College of Medicine, Seoul, South Korea
| | - H S Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - J B Lee
- Division of Statistics in Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - Y J Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - H Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - C M Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - Y S Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - D H Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea.,Department of Internal Medicine and Institute of Liver Research, Seoul National University College of Medicine, Seoul, South Korea
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Ponzetto A, Figura N. Letter: the risk of cancer in patients with gastric intestinal metaplasia. Aliment Pharmacol Ther 2017; 46:1020-1021. [PMID: 29052860 DOI: 10.1111/apt.14329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- A Ponzetto
- Department of Medical Sciences, University of Turin, Torino, Italy
| | - N Figura
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
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Abstract
Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is triggered by environmental stimuli, which may act in concert with the deleterious effects of microorganisms and inflammation. The cell of origin for intestinal metaplasia in the oesophagus and stomach and for pancreatic acinar-ductal metaplasia has been posited through genetic mouse models and lineage tracing but has not been identified in other types of metaplasia, such as squamous metaplasia. A hallmark of metaplasia is a change in cellular identity, and this process can be regulated by transcription factors that initiate and/or maintain cellular identity, perhaps in concert with epigenetic reprogramming. Universally, metaplasia is a precursor to low-grade dysplasia, which can culminate in high-grade dysplasia and carcinoma. Improved clinical screening for and surveillance of metaplasia might lead to better prevention or early detection of dysplasia and cancer.
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Affiliation(s)
- Veronique Giroux
- University of Pennsylvania Perelman School of Medicine, 951 BRB, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
| | - Anil K Rustgi
- University of Pennsylvania Perelman School of Medicine, 951 BRB, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
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45
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Kinoshita H, Hayakawa Y, Koike K. Metaplasia in the Stomach-Precursor of Gastric Cancer? Int J Mol Sci 2017; 18:ijms18102063. [PMID: 28953255 PMCID: PMC5666745 DOI: 10.3390/ijms18102063] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 09/23/2017] [Accepted: 09/25/2017] [Indexed: 02/07/2023] Open
Abstract
Despite a significant decrease in the incidence of gastric cancer in Western countries over the past century, gastric cancer is still one of the leading causes of cancer-related deaths worldwide. Most human gastric cancers develop after long-term Helicobacter pylori infection via the Correa pathway: the progression is from gastritis, atrophy, intestinal metaplasia, dysplasia, to cancer. However, it remains unclear whether metaplasia is a direct precursor of gastric cancer or merely a marker of high cancer risk. Here, we review human studies on the relationship between metaplasia and cancer in the stomach, data from mouse models of metaplasia regarding the mechanism of metaplasia development, and the cellular responses induced by H. pylori infection.
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Affiliation(s)
- Hiroto Kinoshita
- Graduate School of Medicine, Department of Gastroenterology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
| | - Yoku Hayakawa
- Graduate School of Medicine, Department of Gastroenterology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
| | - Kazuhiko Koike
- Graduate School of Medicine, Department of Gastroenterology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
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46
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Pittayanon R, Barkun A. Editorial: the risk of cancer in patients with gastric intestinal metaplasia-Authors' reply. Aliment Pharmacol Ther 2017; 46:375-376. [PMID: 28677291 DOI: 10.1111/apt.14160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- R Pittayanon
- Division of Gastroenterology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital the Thai Red Cross, Bangkok, Thailand.,Division of Gastroenterology, McGill University and the McGill University Health Centre, Montreal, Quebec, Canada
| | - A Barkun
- Division of Gastroenterology, McGill University and the McGill University Health Centre, Montreal, Quebec, Canada
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47
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Kuipers EJ. Editorial: the risk of cancer in patients with gastric intestinal metaplasia. Aliment Pharmacol Ther 2017; 46:374-375. [PMID: 28677282 DOI: 10.1111/apt.14155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Ernst J Kuipers
- Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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