|
1
|
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.
Collapse
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
| |
Collapse
|
|
2
|
Benites-Goñi H, Cabrera-Hinojosa D, Latorre G, Hernandez AV, Uchima H, Riquelme A. OLGA and OLGIM staging systems on the risk assessment of gastric cancer: a systematic review and meta‑analysis of prospective cohorts. Therap Adv Gastroenterol 2025; 18:17562848251325461. [PMID: 40104323 PMCID: PMC11915242 DOI: 10.1177/17562848251325461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 02/18/2025] [Indexed: 03/20/2025] Open
Abstract
Background The Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) are established classification systems used to evaluate atrophic gastritis and intestinal metaplasia, respectively. Objectives We evaluated the association of OLGA and OLGIM scores and the risk of gastric cancer (GC) in only prospective cohort studies. Design Systematic review and meta-analysis. Data sources and methods We systematically searched four databases for prospective cohorts that evaluated the use of OLGA and OLGIM staging systems in predicting the risk of GC. We primarily compared OLGA/OLGIM III-IV versus OLGA/OLGIM 0-II categories and GC events. Pooled risk ratios (RR) and absolute risk differences with their 95% confidence intervals (CIs) were calculated. Results Eight studies were included (n = 12,526). The mean age of the patients ranged from 48.2 to 64.9 years. OLGA III-IV and OLGIM III-IV were associated with the development of GC in comparison to their 0-II categories (RR 32.31, 95% CI 9.14-114.21 and RR 12.38, 95% CI 5.75-26.65, respectively). OLGA III-IV and OLGIM III-IV were associated with an increase in the absolute risk of GC of 4% and 5%, respectively. The risk remained significant if we only included countries with high incidence of GC, and was greater if we excluded one study that included mostly patients with autoimmune gastritis. OLGA II and OLGIM II were associated with higher risk of high-grade dysplasia (HGD) and GC in comparison with OLGA 0-I and OLGIM 0-I, respectively. Conclusion Higher stages in OLGA and OLGIM systems are associated with a significantly increased risk of developing HGD and GC, validating these scoring systems for the assessment of GC risk and the design of endoscopic surveillance programs. Trial PROSPERO registration CRD42024565771.
Collapse
Affiliation(s)
- Harold Benites-Goñi
- Unidad de Revisiones Sistemáticas y Meta-análisis, Universidad San Ignacio de Loyola, Avenida La Fontana 550, 15024, Lima, Peru
- Department of Gastroenterology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru
| | | | - Gonzalo Latorre
- Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Adrian V Hernandez
- Unidad de Revisiones Sistemáticas y Meta-análisis, Universidad San Ignacio de Loyola, Lima, Peru
- Health Outcomes, Policy and Evidence Synthesis Group, University of Connecticut School of Pharmacy, Storrs, CT, USA
| | - Hugo Uchima
- Endoscopy Unit, Teknon Medical Center, Barcelona, Spain
- Endoscopy Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Arnoldo Riquelme
- Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile
- Centro para la Prevención y el Control del Cáncer, Santiago, Chile
| |
Collapse
|
|
3
|
Fansiwala K, Lewis MS, Pisegna JR. Gastritis: Pathophysiology and Clinical Management. Am J Gastroenterol 2025; 120:5-8. [PMID: 39569875 PMCID: PMC11695143 DOI: 10.14309/ajg.0000000000003216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/25/2024] [Indexed: 11/22/2024]
Affiliation(s)
- Kush Fansiwala
- Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA
| | - Michael S. Lewis
- Departments of Medicine and Pathology, Cedars Sinai Medical Center, Los Angeles, CA, 90048, USA
- Department of Pathology, VA Greater Los Angeles Medical Center, Los Angeles, CA, 90073, USA
| | - Joseph R. Pisegna
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Dept of Medicine VA Greater Los Angeles Healthcare System, Los Angeles, CA, 90073, USA
- Department of Human Nutrition David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA
| |
Collapse
|
|
4
|
Delgado-Guillena P, Jimeno M, López-Nuñez A, Córdova H, Fernández-Esparrach G. The endoscopic model for gastric carcinogenesis and Helicobacter pylori infection: A potential visual mind-map during gastroscopy examination. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:502214. [PMID: 38844201 DOI: 10.1016/j.gastrohep.2024.502214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 05/04/2024] [Accepted: 05/24/2024] [Indexed: 06/29/2024]
Abstract
Helicobacter pylori (Hp) is the main trigger of chronic gastric atrophy and the main leading cause of gastric cancer. Hp infects the normal gastric mucosa and can lead to chronic inflammation, glandular atrophy, intestinal metaplasia, dysplasia and finally adenocarcinoma. Chronic inflammation and gastric atrophy associated with Hp infection appear initially in the distal part of the stomach (the antrum) before progressing to the proximal part (the corpus-fundus). In recent years, endoscopic developments have allowed for the characterization of various gastric conditions including the normal mucosa (pyloric/fundic gland pattern and regular arrangement of collecting venules), Hp-related gastritis (Kyoto classification), glandular atrophy (Kimura-Takemoto classification), intestinal metaplasia (Endoscopic Grading of Gastric Intestinal Metaplasia), and dysplasia/adenocarcinoma (Vessel plus Surface classification). Despite being independent classifications, all these scales can be integrated into a single model: the endoscopic model for gastric carcinogenesis. This model would assist endoscopists in comprehending the process of gastric carcinogenesis and conducting a systematic examination during gastroscopy. Having this model in mind would enable endoscopists to promptly recognize the implications of Hp infection and the potential patient's risk of developing gastric cancer.
Collapse
Affiliation(s)
| | - Mireya Jimeno
- Department of Pathology, Hospital of Germans Trias i Pujol, Badalona, Spain
| | | | - Henry Córdova
- Department of Gastroenterology, Hospital Clinic of Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Spain
| | - Gloria Fernández-Esparrach
- Department of Gastroenterology, Hospital Clinic of Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Spain
| |
Collapse
|
|
5
|
Andersen GT, Ianevski A, Resell M, Pojskic N, Rabben HL, Geithus S, Kodama Y, Hiroyuki T, Kainov D, Grønbech JE, Hayakawa Y, Wang TC, Zhao CM, Chen D. Multi-bioinformatics revealed potential biomarkers and repurposed drugs for gastric adenocarcinoma-related gastric intestinal metaplasia. NPJ Syst Biol Appl 2024; 10:127. [PMID: 39496635 PMCID: PMC11535201 DOI: 10.1038/s41540-024-00455-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 10/13/2024] [Indexed: 11/06/2024] Open
Abstract
Biomarkers associated with the progression from gastric intestinal metaplasia (GIM) to gastric adenocarcinoma (GA), i.e., GA-related GIM, could provide valuable insights into identifying patients with increased risk for GA. The aim of this study was to utilize multi-bioinformatics to reveal potential biomarkers for the GA-related GIM and predict potential drug repurposing for GA prevention in patients. The multi-bioinformatics included gene expression matrix (GEM) by microarray gene expression (MGE), ScType (a fully automated and ultra-fast cell-type identification based solely on a given scRNA-seq data), Ingenuity Pathway Analysis, PageRank centrality, GO and MSigDB enrichments, Cytoscape, Human Protein Atlas and molecular docking analysis in combination with immunohistochemistry. To identify GA-related GIM, paired surgical biopsies were collected from 16 GIM-GA patients who underwent gastrectomy, yielding 64 samples (4 biopsies per stomach x 16 patients) for MGE. Co-analysis was performed by including scRNAseq and immunohistochemistry datasets of endoscopic biopsies of 37 patients. The results of the present study showed potential biomarkers for GA-related GIM, including GEM of individual patients, individual genes (such as RBP2 and CD44), signaling pathways, network of molecules, and network of signaling pathways with key topological nodes. Accordingly, potential treatment targets with repurposed drugs were identified including epidermal growth factor receptor, proto-oncogene tyrosine-protein kinase Src, paxillin, transcription factor Jun, breast cancer type 1 susceptibility protein, cellular tumor antigen p53, mouse double minute 2, and CD44.
Collapse
Affiliation(s)
- Gøran Troseth Andersen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Surgery, St. Olav's Hospital, Trondheim, Norway
- Department of Surgery, Namsos Hospital, Namsos, Norway
| | - Aleksandr Ianevski
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Mathilde Resell
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Naris Pojskic
- Laboratory for Bioinformatics and Biostatistics, University of Sarajevo - Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina
| | - Hanne-Line Rabben
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Synne Geithus
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Yosuke Kodama
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Tomita Hiroyuki
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Denis Kainov
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Jon Erik Grønbech
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Surgery, St. Olav's Hospital, Trondheim, Norway
| | - Yoku Hayakawa
- Department of Gastroenterology, Tokyo University Hospital, Tokyo, Japan
| | - Timothy C Wang
- Department of Digestive and Liver Diseases and Herbert Iring Comprehensive Cancer Center, Columbia University Medical Center, New York, USA
| | - Chun-Mei Zhao
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Duan Chen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
| |
Collapse
|
|
6
|
Jin G, Liu K, Guo Z, Dong Z. Precision therapy for cancer prevention by targeting carcinogenesis. Mol Carcinog 2024; 63:2045-2062. [PMID: 39140807 DOI: 10.1002/mc.23798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/11/2024] [Accepted: 07/16/2024] [Indexed: 08/15/2024]
Abstract
Cancer represents a major global public health burden, with new cases estimated to increase from 14 million in 2012 to 24 million by 2035. Primary prevention is an effective strategy to reduce the costs associated with cancer burden. For example, measures to ban tobacco consumption have dramatically decreased lung cancer incidence and vaccination against human papillomavirus can prevent cervical cancer development. Unfortunately, the etiological factors of many cancer types are not completely clear or are difficult to actively control; therefore, the primary prevention of such cancers is not practical. In this review, we update the progress on precision therapy by targeting the whole carcinogenesis process, especially for three high-risk groups: (1) those with chronic inflammation, (2) those with inherited germline mutations, and (3) those with precancerous lesions like polyps, gastritis, actinic keratosis or dysplasia. We believe that attenuating chronic inflammation, treating precancerous lesions, and removing high-risk tissues harboring germline mutations are precision methods for cancer prevention.
Collapse
Affiliation(s)
- Guoguo Jin
- Henan Key Laboratory of Chronic Disease Management, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China
| | - Kangdong Liu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Zhiping Guo
- Henan Key Laboratory of Chronic Disease Management, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, China
| | - Zigang Dong
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| |
Collapse
|
|
7
|
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.
Collapse
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
| |
Collapse
|
|
8
|
Kővári B, Carneiro F, Lauwers GY. Epithelial tumours of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:227-286. [DOI: 10.1002/9781119423195.ch13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
9
|
Liao X, Lin R, Zhang Z, Tian D, Liu Z, Chen S, Xu G, Su M. Genome-wide DNA methylation and transcriptomic patterns of precancerous gastric cardia lesions. J Natl Cancer Inst 2024; 116:681-693. [PMID: 38258659 DOI: 10.1093/jnci/djad244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 10/25/2023] [Accepted: 11/15/2023] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Intestinal metaplasia (IM) and intraepithelial neoplasia (IEN) are considered precursors of gastric cardia cancer (GCC). Here, we investigated the histopathologic and molecular profiles of precancerous gastric cardia lesions (PGCLs) and biomarkers for risk stratification of gastric cardia IM. METHODS We conducted a hospital-based evaluation (n = 4578) for PGCL profiles in high-incidence and non-high-incidence regions for GCC in China. We next performed 850K methylation arrays (n = 42) and RNA-seq (n = 44) in tissues with PGCLs. We then examined the protein expression of candidate biomarker using immunohistochemistry. RESULTS Of the 4578 participants, 791 were diagnosed with PGCLs (600 IM, 62 IM with IEN, and 129 IEN). We found that individuals from high-incidence regions (26.7%) were more likely to develop PGCLs than those from non-high-incidence areas (13.5%). DNA methylation and gene expression alterations, indicated by differentially methylated probes (DMPs) and differentially expressed genes (DEGs), exhibited a progressive increase from type I IM (DMP = 210, DEG = 24), type II IM (DMP = 3402, DEG = 129), to type III IM (DMP = 3735, DEG = 328), peaking in IEN (DMP = 47 373, DEG = 2278). Three DEGs with aberrant promoter methylation were identified, shared exclusively by type III IM and IEN. Of these DEGs, we found that OLFM4 expression appears in IMs and increases remarkably in IENs (P < .001). CONCLUSIONS We highlight that type III IM and IEN share similar epigenetic and transcriptional features in gastric cardia and propose biomarkers with potential utility in risk prediction.
Collapse
Affiliation(s)
- Xiaoqi Liao
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
| | - Runhua Lin
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, People's Republic of China
| | - Zhihua Zhang
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
| | - Dongping Tian
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, People's Republic of China
| | - Zhaohui Liu
- Department of Gastroenterology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, People's Republic of China
| | - Songqin Chen
- Department of Pathology, Jieyang People's Hospital, Jieyang, People's Republic of China
| | - Guohua Xu
- Department of Gastroenterology, Huiyang Sanhe Hospital, Huizhou, People's Republic of China
| | - Min Su
- Department of Pathology, Shantou University Medical College, Shantou, People's Republic of China
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, People's Republic of China
| |
Collapse
|
|
10
|
Tong QY, Pang MJ, Hu XH, Huang XZ, Sun JX, Wang XY, Burclaff J, Mills JC, Wang ZN, Miao ZF. Gastric intestinal metaplasia: progress and remaining challenges. J Gastroenterol 2024; 59:285-301. [PMID: 38242996 DOI: 10.1007/s00535-023-02073-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 12/26/2023] [Indexed: 01/21/2024]
Abstract
Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.
Collapse
Affiliation(s)
- Qi-Yue Tong
- Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
| | - Min-Jiao Pang
- Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
| | - Xiao-Hai Hu
- Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
| | - Xuan-Zhang Huang
- Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
| | - Jing-Xu Sun
- Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
| | - Xin-Yu Wang
- Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China
| | - Joseph Burclaff
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA
| | - Jason C Mills
- Section of Gastroenterology and Hepatology, Department of Medicine, Departments of Pathology and Immunology, Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
| | - Zhen-Ning Wang
- Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China.
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China.
| | - Zhi-Feng Miao
- Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China.
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, 155 N. Nanjing Street, Shenyang, 110001, Liaoning, China.
| |
Collapse
|
|
11
|
Fansiwala K, Qian Y, Liang PS. Gastric Cancer Risk Factors in a Veteran Population. Mil Med 2024; 189:e802-e808. [PMID: 37610320 DOI: 10.1093/milmed/usad319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 07/10/2023] [Accepted: 08/01/2023] [Indexed: 08/24/2023] Open
Abstract
INTRODUCTION Risk factors for gastric cancer in the United States are not well understood, especially in populations with a low proportion of immigrants. We conducted a matched case-control study in a Veteran Affairs Medical Center to identify risk factors for gastric cancer. MATERIALS AND METHODS Gastric cancer patients and age- and sex-matched controls were identified in a 1:4 ratio from January 1, 1997 to October 31, 2018. Demographic, medical, endoscopic, and histologic data were extracted. We performed conditional logistic regression to estimate odds ratios and 95% CIs for associations between potential risk factors and gastric cancer. RESULTS Most gastric cancer cases were diagnosed on initial endoscopy (71.4%). Of these, the most common presenting stage was stage IV (40.8%). Risk factors for gastric cancer included Black and Asian race and never or current (compared to former) drinkers, although Helicobacter pylori eradication and pernicious anemia were associated with decreased risk. CONCLUSIONS The high proportion of late-stage gastric cancer diagnoses highlights the need for improved risk stratification as well as screening and surveillance protocols in the U.S. population. Racial disparities among veterans in an equal-access system necessitate further investigation into the etiology of these disparities.
Collapse
Affiliation(s)
- Kush Fansiwala
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - Yingzhi Qian
- Department of Population Health, NYU Langone Health, New York, NY 10016, USA
| | - Peter S Liang
- Department of Population Health, NYU Langone Health, New York, NY 10016, USA
- Department of Medicine, VA New York Harbor Health Care System, New York, NY 10010, USA
- Department of Medicine, NYU Langone Health, New York, NY 10016, USA
| |
Collapse
|
|
12
|
Contreras-Panta EW, Choi E, Goldenring JR. The Fibroblast Landscape in Stomach Carcinogenesis. Cell Mol Gastroenterol Hepatol 2024; 17:671-678. [PMID: 38342299 PMCID: PMC10957461 DOI: 10.1016/j.jcmgh.2024.02.001] [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: 11/13/2023] [Revised: 01/31/2024] [Accepted: 02/01/2024] [Indexed: 02/13/2024]
Abstract
Numerous recent studies using single cell RNA sequencing and spatial transcriptomics have shown the vast cell heterogeneity, including epithelial, immune, and stromal cells, present in the normal human stomach and at different stages of gastric carcinogenesis. Fibroblasts within the metaplastic and dysplastic mucosal stroma represent key contributors to the carcinogenic microenvironment in the stomach. The heterogeneity of fibroblast populations is present in the normal stomach, but plasticity within these populations underlies their alterations in association with both metaplasia and dysplasia. In this review, we summarize and discuss efforts over the past several years to study the fibroblast components in human stomach from normal to metaplasia, dysplasia, and cancer. In the stomach, myofibroblast populations increase during late phase carcinogenesis and are a source of matrix proteins. PDGFRA-expressing telocyte-like cells are present in normal stomach and expand during metaplasia and dysplasia in close proximity with epithelial lineages, likely providing support for both normal and metaplastic progenitor niches. The alterations in fibroblast transcriptional signatures across the stomach carcinogenesis process indicate that fibroblast populations are likely as plastic as epithelial populations during the evolution of carcinogenesis.
Collapse
Affiliation(s)
- Ela W Contreras-Panta
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Eunyoung Choi
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - James R Goldenring
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee; Nashville VA Medical Center, Nashville, Tennessee.
| |
Collapse
|
|
13
|
García JR, García AB, Arranz MM. Gastritis y gastropatías (II). Gastritis crónica atrófica y gastritis hipertrófica. MEDICINE - PROGRAMA DE FORMACIÓN MÉDICA CONTINUADA ACREDITADO 2024; 14:83-90. [DOI: 10.1016/j.med.2024.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
14
|
Bogdanova I, Polaka I, Aleksandraviča I, Dzērve Z, Anarkulova L, Novika V, Tolmanis I, Leja M. Role of pre-existing incomplete intestinal metaplasia in gastric adenocarcinoma: A retrospective case series analysis. World J Clin Cases 2023; 11:2708-2715. [PMID: 37214563 PMCID: PMC10198109 DOI: 10.12998/wjcc.v11.i12.2708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/19/2023] [Accepted: 03/29/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial. AIM To analysis of patients having developed gastric adenocarcinoma during the period of follow-up. METHODS We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed. RESULTS Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy; all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type III intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment (OLGIM) stages (I-II) at the baseline. CONCLUSION The presence of incomplete intestinal metaplasia, in particular, that of Type III is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.
Collapse
Affiliation(s)
- Inga Bogdanova
- Department of Pathology, Academic Histology Laboratory, Riga LV1073, Latvia
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
| | - Inese Polaka
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
| | - Ilona Aleksandraviča
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
- Department of Research, Riga East University Hospital, Riga LV1079, Latvia
| | - Zane Dzērve
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
- Department of Endoscopy, Digestive Diseases Centre GASTRO, Riga LV1079, Latvia
| | - Linda Anarkulova
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
| | - Vita Novika
- Department of Endoscopy, Digestive Diseases Centre GASTRO, Riga LV1079, Latvia
| | - Ivars Tolmanis
- Department of Endoscopy, Digestive Diseases Centre GASTRO, Riga LV1079, Latvia
| | - Marcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga LV1079, Latvia
- Department of Research, Riga East University Hospital, Riga LV1079, Latvia
- Department of Gastroenterology, Digestive Diseases Centre GASTRO, Riga LV1079, Latvia
| |
Collapse
|
|
15
|
Xi J, Li Y, Zhang H, Bai Z. Dynamic variations of the gastric microbiota: Key therapeutic points in the reversal of Correa's cascade. Int J Cancer 2023; 152:1069-1084. [PMID: 36029278 DOI: 10.1002/ijc.34264] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 08/10/2022] [Accepted: 08/15/2022] [Indexed: 01/21/2023]
Abstract
Correa's cascade is a dynamic process in the development of intestinal-type gastric cancer (GC), and its pathological features, gastric microbiota and interactions between microorganisms and their hosts vary at different developmental stages. The characteristics of cells, tissues and gastric microbiota before or after key therapeutic points are critical for monitoring malignant transformation and early tumour reversal. This review summarises the pathological features of gastric mucosa, characteristics of gastric microbiota, specific microbial markers, microbe-microbe interactions and microbe-host interactions at different stages in Correa's cascade. The markers related to each Correa's cascade point were analysed in detail. We attempted to identify key therapeutic points for early cancer reversal and provide a novel approach to reduce the incidence of GC and improve precise treatment.
Collapse
Affiliation(s)
- Jiahui Xi
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.,Key Laboratory of Biotherapy and Regenerative Medicine, Gansu Province, Lanzhou, China
| | - Yonghong Li
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumour, Gansu Provincial Hospital, Lanzhou, China
| | - Hui Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.,General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zhongtian Bai
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.,Key Laboratory of Biotherapy and Regenerative Medicine, Gansu Province, Lanzhou, China.,General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
| |
Collapse
|
|
16
|
Zeng Y, Li QK, Roy S, Mills JC, Jin RU. Shared features of metaplasia and the development of adenocarcinoma in the stomach and esophagus. Front Cell Dev Biol 2023; 11:1151790. [PMID: 36994101 PMCID: PMC10040611 DOI: 10.3389/fcell.2023.1151790] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 02/28/2023] [Indexed: 03/16/2023] Open
Abstract
Introduction: Plasticity is an inherent property of the normal gastrointestinal tract allowing for appropriate response to injury and healing. However, the aberrancy of adaptable responses is also beginning to be recognized as a driver during cancer development and progression. Gastric and esophageal malignancies remain leading causes of cancer-related death globally as there are limited early disease diagnostic tools and paucity of new effective treatments. Gastric and esophageal adenocarcinomas share intestinal metaplasia as a key precancerous precursor lesion.Methods: Here, we utilize an upper GI tract patient-derived tissue microarray that encompasses the sequential development of cancer from normal tissues to illustrate the expression of a set of metaplastic markers.Results: We report that in contrast to gastric intestinal metaplasia, which has traits of both incomplete and complete intestinal metaplasia, Barrett's esophagus (i.e., esophageal intestinal metaplasia) demonstrates hallmarks of incomplete intestinal metaplasia. Specifically, this prevalent incomplete intestinal metaplasia seen in Barrett's esophagus manifests as concurrent development and expression of both gastric and intestinal traits. Additionally, many gastric and esophageal cancers display a loss of or a decrease in these characteristic differentiated cell properties, demonstrating the plasticity of molecular pathways associated with the development of these cancers.Discussion: Further understanding of the commonalities and differences governing the development of upper GI tract intestinal metaplasias and their progression to cancer will lead to improved diagnostic and therapeutic avenues.
Collapse
Affiliation(s)
- Yongji Zeng
- Section of Gastroenterology, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
| | - Qing K. Li
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States
| | - Sujayita Roy
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States
| | - Jason C. Mills
- Section of Gastroenterology, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Departments of Medicine, Pathology and Immunology, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States
- *Correspondence: Jason C. Mills, ; Ramon U. Jin,
| | - Ramon U. Jin
- Section of Hematology/Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- *Correspondence: Jason C. Mills, ; Ramon U. Jin,
| |
Collapse
|
|
17
|
Vo D, Ghosh P, Sahoo D. Artificial intelligence-guided discovery of gastric cancer continuum. Gastric Cancer 2023; 26:286-297. [PMID: 36692601 PMCID: PMC9871434 DOI: 10.1007/s10120-022-01360-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 12/19/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND Detailed understanding of pre-, early and late neoplastic states in gastric cancer helps develop better models of risk of progression to gastric cancers (GCs) and medical treatment to intercept such progression. METHODS We built a Boolean implication network of gastric cancer and deployed machine learning algorithms to develop predictive models of known pre-neoplastic states, e.g., atrophic gastritis, intestinal metaplasia (IM) and low- to high-grade intestinal neoplasia (L/HGIN), and GC. Our approach exploits the presence of asymmetric Boolean implication relationships that are likely to be invariant across almost all gastric cancer datasets. Invariant asymmetric Boolean implication relationships can decipher fundamental time-series underlying the biological data. Pursuing this method, we developed a healthy mucosa → GC continuum model based on this approach. RESULTS Our model performed better against publicly available models for distinguishing healthy versus GC samples. Although not trained on IM and L/HGIN datasets, the model could identify the risk of progression to GC via the metaplasia → dysplasia → neoplasia cascade in patient samples. The model could rank all publicly available mouse models for their ability to best recapitulate the gene expression patterns during human GC initiation and progression. CONCLUSIONS A Boolean implication network enabled the identification of hitherto undefined continuum states during GC initiation. The developed model could now serve as a starting point for rationalizing candidate therapeutic targets to intercept GC progression.
Collapse
Affiliation(s)
- Daniella Vo
- Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, MC 0703, Leichtag Building 132, La Jolla, CA, 92093-0703, USA
| | - Pradipta Ghosh
- Moores Cancer Center, University of California San Diego, La Jolla, USA
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, USA
- Department of Medicine, University of California San Diego, La Jolla, USA
| | - Debashis Sahoo
- Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, MC 0703, Leichtag Building 132, La Jolla, CA, 92093-0703, USA.
- Moores Cancer Center, University of California San Diego, La Jolla, USA.
- Department of Computer Science and Engineering, Jacob's School of Engineering, University of California San Diego, La Jolla, USA.
| |
Collapse
|
|
18
|
Chen X, Shen K, Deng Y, Mo J, Ni J, Hendi M, Chen S, Wang L, Si J. A Randomized Double-blind Clinical Trial of Weierkang Pills for the Treatment of Chronic Atrophic Gastritis. J Clin Gastroenterol 2023; 57:165-171. [PMID: 35050943 DOI: 10.1097/mcg.0000000000001663] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 12/05/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND GOALS There are currently no standard treatments for chronic atrophic gastritis and traditional Chinese medicine may be effective. This study aims to investigate the efficacy and safety of Weierkang pills in treating chronic atrophic gastritis. MATERIALS AND METHODS There were 108 patients in our study. They were randomly assigned to 2 groups. In group A, patients received Weierkang pills and patients in group B received folic acid combined with teprenone. Symptoms, endoscopic scores, and biopsy specimens were compared at baseline and 3 months after treatment. Meanwhile, the expressions of vascular endothelial growth factor and trefoil factor 3 (TFF3) in biopsy specimens were also compared. RESULTS Our study showed that the total effective rates of atrophy/intestinal metaplasia in group A reached the same level as group B (51.7% vs. 40.0%, P =0.419). Weierkang significantly improved the total effective rate of atrophy/intestinal metaplasia in gastric angle compared with group B (64.7% vs. 33.3%, P =0.024). Weierkang can significantly lower the total Kyoto risk score (2.6±1.1 vs. 3.3±1.0, P =0.002) and atrophy score (1.4±0.6 vs. 1.8±0.5, P =0.001) after treatment. In addition, Weierkang improves symptoms (1.3±1.3 vs. 2.3±1.8, P =0.003) and epigastric pain (0.2±0.4 vs. 0.5±0.6, P =0.041). The expression of TFF3 in gastric mucosa decreased significantly after treatment with Weierkang ( P =0.002). CONCLUSIONS Weierkang can improve the endoscopic appearance and pathologic changes of chronic atrophic gastritis patients. Symptoms also improved. TFF3 may be involved the pathophysiology mechanism.
Collapse
Affiliation(s)
- Xueqin Chen
- Departments of Gastroenterology
- Institute of Gastroenterology
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Kai Shen
- Departments of Gastroenterology
- Institute of Gastroenterology
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Yanyong Deng
- Departments of Gastroenterology
- Institute of Gastroenterology
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang Province, China
| | | | | | - Maher Hendi
- General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
| | - Shujie Chen
- Departments of Gastroenterology
- Institute of Gastroenterology
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Lan Wang
- Departments of Gastroenterology
- Institute of Gastroenterology
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jianmin Si
- Departments of Gastroenterology
- Institute of Gastroenterology
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang Province, China
| |
Collapse
|
|
19
|
Kanemitsu T, Uedo N, Ono T, Nimura S, Hasegawa R, Imamura K, Ohtsu K, Ono Y, Miyaoka M, Ueki T, Tanabe H, Ohta A, Iwashita A, Yao K. Magnifying endoscopy with narrow-band imaging for diagnosis of subtype of gastric intestinal metaplasia. J Gastroenterol Hepatol 2023; 38:94-102. [PMID: 36268636 DOI: 10.1111/jgh.16034] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 10/14/2022] [Accepted: 10/16/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND AND AIM Patients with incomplete gastric intestinal metaplasia (GIM) have a higher risk of gastric cancer (GC) than those with complete GIM. We aimed to clarify whether micromucosal patterns of GIM in magnifying endoscopy with narrow-band imaging (M-NBI) were useful for diagnosis of incomplete GIM. METHODS We enrolled patients with a history of endoscopic resection of GC or detailed inspection for suspicious or definite GC. The antrum greater curvature and corpus lesser curvature were regions of interest. Areas with endoscopic findings of light blue crest and/or white opaque substance (WOS) were defined as endoscopic GIM, and subsequent M-NBI was applied. Micromucosal patterns were classified into Foveola and Groove types, and targeted biopsies were performed on GIM with each pattern. GIM was classified into complete and incomplete types using mucin (MUC)2, MUC5AC, MUC6, and CD10 immunohistochemical staining. The primary endpoint was the association between micromucosal pattern and histological subtype. The secondary endpoint was endoscopic findings associated with incomplete GIM. RESULTS We analyzed 98 patients with 156 GIMs. Univariate analysis (odds ratio [OR] 3.4, P = 0.004), but not multivariate analysis (OR 0.87, P = 0.822), demonstrated a significant association between micromucosal pattern and subtype. The antrum (OR 3.7, P = 0.006) and WOS (OR 43, P = 0.002) were independent predictors for incomplete GIM. The WOS had 69% sensitivity and 93% specificity. CONCLUSIONS The M-NBI micromucosal pattern is not useful for diagnosis of GIM subtype. WOS is a promising endoscopic indicator for diagnosis of incomplete GIM. (UMIN-CTR000041119).
Collapse
Affiliation(s)
- Takao Kanemitsu
- Department of Endoscopy, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Noriya Uedo
- Department of Endoscopy, Fukuoka University Chikushi Hospital, Chikushino, Japan.,Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Takahiro Ono
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Satoshi Nimura
- Department of Pathology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Rino Hasegawa
- Department of Endoscopy, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Kentaro Imamura
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Kensei Ohtsu
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Yoichiro Ono
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Masaki Miyaoka
- Department of Endoscopy, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Toshiharu Ueki
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Hiroshi Tanabe
- Department of Pathology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Atsuko Ohta
- Department of Pathology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Akinori Iwashita
- Department of Pathology, Fukuoka University Chikushi Hospital, Chikushino, Japan
| | - Kenshi Yao
- Department of Endoscopy, Fukuoka University Chikushi Hospital, Chikushino, Japan
| |
Collapse
|
|
20
|
Libânio D, Ortigão R, Pimentel-Nunes P, Dinis-Ribeiro M. Improving the Diagnosis and Treatment of Early Gastric Cancer in the West. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2022; 29:299-310. [PMID: 36159192 PMCID: PMC9485920 DOI: 10.1159/000520529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 10/02/2021] [Indexed: 11/19/2022]
Abstract
Gastric cancer is the third leading cause of cancer-related death. In Western countries, its lower prevalence and the absence of mass screening programmes contribute to late diagnosis and a slower implementation of minimally invasive treatments. A secondary prevention strategy through endoscopic surveillance of patients at high risk of intestinal-type gastric adenocarcinoma or by screening gastric cancer within colorectal screening programmes is cost-effective in intermediate-risk countries, though the identification of these patients remains challenging. Virtual chromoendoscopy with narrow-band imaging improves the accuracy of endoscopic diagnosis, significantly increasing the sensitivity for intestinal metaplasia while preserving specificity. Endoscopic grading of gastric intestinal metaplasia is feasible, correlates well with histological staging systems and also with gastric neoplasia risk and can be used to stratify risk. Endoscopic submucosal dissection (ESD) in the West achieves efficacy and safety outcomes similar to those reported for Eastern countries, and the long-term disease-specific survival is higher than 95%. A prospective comparative study with gastrectomy confirms its higher safety and its benefits concerning health-related quality of life. However, ESD is associated with a 5% risk of postprocedural bleeding and a 20% risk of non-curative resection. The knowledge of risk factors for adverse events and non-curative resection can improve patient selection. The risk of metachronous lesions after ESD is high (3-5% per year), and endoscopic surveillance is needed. The management of patients with non-curative resection can be optimized using risk scoring systems for lymph node metastasis.
Collapse
Affiliation(s)
- Diogo Libânio
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision of the Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Raquel Ortigão
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Pedro Pimentel-Nunes
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision of the Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Mário Dinis-Ribeiro
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision of the Faculty of Medicine of the University of Porto, Porto, Portugal
| |
Collapse
|
|
21
|
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.
Collapse
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
| |
Collapse
|
|
22
|
Koulis A, Di Costanzo N, Mitchell C, Lade S, Goode D, Busuttil RA, Boussioutas A. CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia. BMC Gastroenterol 2022; 22:197. [PMID: 35448971 PMCID: PMC9026694 DOI: 10.1186/s12876-022-02268-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 03/30/2022] [Indexed: 12/24/2022] Open
Abstract
Background Intestinal metaplasia (IM) is considered a key pivot point in the Correa model of gastric cancer (GC). It is histologically subtyped into the complete and incomplete subtypes, the latter being associated with a greater risk of progression. However, the clinical utility of IM subtyping remains unclear, partially due to the absence of reliable defining biomarkers. Methods Based on gene expression data and existing literature, we selected CD10 and Das1 as candidate biomarkers to distinguish complete and incomplete IM glands in tissues from patients without GC (IM-GC) and patients with GC (IM + GC). Immunohistochemical staining of individually subtyped IM glands was scored after blinding by two researchers using tissue belonging to both IM-GC and IM + GC patients. Whole tissue Das1 staining was further assessed using digital image quantification (cellSens Dimension, Olympus). Results Across both cohorts CD10 stained the IM brush border and was shown to have a high sensitivity (87.5% and 94.9% in IM-GC and IM + GC patients respectively) and specificity (100.0% and 96.7% respectively) with an overall AUROC of 0.944 for complete IM glands. By contrast Das1 stained mainly goblet cells and the apical membrane of epithelial cells, mostly of incomplete IM glands with a low sensitivity (28.6% and 29.3% in IM-GC and IM + GC patients respectively) but high specificity (98.3% and 85.1% respectively) and an overall AUROC of 0.603 for incomplete IM glands. A combined logistic regression model showed a significant increase in AUROC for detecting complete IM glands (0.955 vs 0.970). Whole tissue digital quantification of Das1 staining showed a significant association with incomplete IM compared to complete IM, both in IM-GC and in IM + GC patients (p = 0.016 and p = 0.009 respectively, Mann–Whitney test and unpaired t test used). Additionally, complete IM in IM + GC patients exhibited significantly more Das1 staining than in IM-GC patients (p = 0.019, Mann–Whitney test). Conclusions These findings suggest that CD10 is an outstanding biomarker for complete IM and Das1 may be useful as a secondary biomarker for IM glands at greater risk of progression irrespective of IM subtype. Overall, the clinical use of these biomarkers could lead to improved patient stratification and targeted surveillance. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02268-z.
Collapse
Affiliation(s)
- Athanasios Koulis
- Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.,The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia
| | - Natasha Di Costanzo
- Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.,The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia
| | - Catherine Mitchell
- Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Stephen Lade
- Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - David Goode
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.,Computational Cancer Biology Program, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Rita A Busuttil
- Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.,The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.,Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia
| | - Alex Boussioutas
- Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia. .,The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia. .,Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia. .,Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Parkville, VIC, 3050, Australia.
| |
Collapse
|
|
23
|
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.
Collapse
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.)
| |
Collapse
|
|
24
|
Goldenring JR, Mills JC. Cellular Plasticity, Reprogramming, and Regeneration: Metaplasia in the Stomach and Beyond. Gastroenterology 2022; 162:415-430. [PMID: 34728185 PMCID: PMC8792220 DOI: 10.1053/j.gastro.2021.10.036] [Citation(s) in RCA: 81] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 10/21/2021] [Accepted: 10/24/2021] [Indexed: 02/03/2023]
Abstract
The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface cells with histopathologic changes like foveolar hyperplasia. Deeper, usually chronic, injury/inflammation, most frequently induced by the carcinogenic bacteria Helicobacter pylori, elicits glandular histopathologic alterations, initially manifesting as pyloric (also known as pseudopyloric) metaplasia. In this pyloric metaplasia, corpus glands become antrum (pylorus)-like with loss of acid-secreting parietal cells (atrophic gastritis), expansion of foveolar cells, and reprogramming of digestive enzyme-secreting chief cells into deep antral gland-like mucous cells. After acute parietal cell loss, chief cells can reprogram through an orderly stepwise progression (paligenosis) initiated by interleukin-13-secreting innate lymphoid cells (ILC2s). First, massive lysosomal activation helps mitigate reactive oxygen species and remove damaged organelles. Second, mucus and wound-healing proteins (eg, TFF2) and other transcriptional alterations are induced, at which point the reprogrammed chief cells are recognized as mucus-secreting spasmolytic polypeptide-expressing metaplasia cells. In chronic severe injury, glands with pyloric metaplasia can harbor both actively proliferating spasmolytic polypeptide-expressing metaplasia cells and eventually intestine-like cells. Gastric glands with such lineage confusion (mixed incomplete intestinal metaplasia and proliferative spasmolytic polypeptide-expressing metaplasia) may be at particular risk for progression to dysplasia and cancer. A pyloric-like pattern of metaplasia after injury also occurs in other gastrointestinal organs including esophagus, pancreas, and intestines, and the paligenosis program itself seems broadly conserved across tissues and species. Here we discuss aspects of metaplasia in stomach, incorporating data derived from animal models and work on human cells and tissues in correlation with diagnostic and clinical implications.
Collapse
Affiliation(s)
- James R Goldenring
- Nashville Veterans Affairs Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
| | - Jason C Mills
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
| |
Collapse
|
|
25
|
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]
|
|
26
|
Wada Y, Kodama M, Mizukami K, Okimoto T, Fuchino T, Tsutsumi K, Fukuda M, Hirashita Y, Fukuda K, Okamoto K, Ogawa R, Kushima R, Murakami K. Differences in Regression Patterns of Complete and Incomplete Intestinal Metaplasia at Ten Years after Helicobacter pylori Eradication. Acta Histochem Cytochem 2021; 54:185-194. [PMID: 35023881 PMCID: PMC8727845 DOI: 10.1267/ahc.21-00069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 10/01/2021] [Indexed: 11/22/2022] Open
Abstract
This study was conducted to reveal the reversibility of subtype of intestinal metaplasia (IM) and Paneth cells after H. pylori eradication (HPE). Among 75 patients, we retrospectively examined the proportions of patients with complete type of IM (CIM), incomplete type of IM (IIM) and Paneth cells in their biopsy specimens obtained from the greater curvature of the antrum (A2) and the greater curvature of the middle corpus (B2) before and during a follow-up period of 10 years after HPE. Immunohistochemistry was used to determine IM type. Compared to before HPE, the proportion of patients with CIM did not decrease significantly during the 10-year follow-up after HPE both in A2 (32% vs. 21.3%, P = 0.13) and in B2 (6.7% vs. 2.7%, P = 0.60). IIM rates in A2 was significantly lower during this time (26.7% vs. 10.7%, P = 0.04), whereas no patients showed IIM in B2 before HPE. The proportion of patients with Paneth cells decreased significantly in A2 after 3, 8, and 9 years of HPE and in B2 after 4, 6 and 9 years of HPE (P < 0.05 for all). Thus, IIM and Paneth cells regressed during a period of 10 years after HPE.
Collapse
Affiliation(s)
- Yasuhiro Wada
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Masaaki Kodama
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
- Faculty of Welfare and Health Science, Oita University, Oita, Japan
| | - Kazuhiro Mizukami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Tadayoshi Okimoto
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Takafumi Fuchino
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Koshiro Tsutsumi
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Masahide Fukuda
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Yuka Hirashita
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Kensuke Fukuda
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Kazuhisa Okamoto
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Ryo Ogawa
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan
| |
Collapse
|
|
27
|
Ivashkin VT, Maev IV, Lapina TL, Fedorov ED, Sheptulin AA, Trukhmanov AS, Kononov AV, Abdulkhakov RA, Alexeeva OP, Alekseenko SA, Andreev DN, Baranskaya EK, Dekhnich NN, Klyaritskaya IL, Kozlov RS, Kogan EA, Korolev MP, Korochanskaya NV, Kurilovich SA, Livsan MA, Osipenko MF, Pavlov PV, Pirogov SS, Sarsenbaeva AS, Simanenkov VI, Tertychny AS, Tkachev AV, Uspensky YP, Khlynov IB, Tsukanov VV. Clinical Recommendations of Russian Gastroenterological Association and RENDO Endoscopic Society on Diagnosis and Treatment of Gastritis and Duodenitis. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2021; 31:70-99. [DOI: 10.22416/1382-4376-2021-31-4-70-99] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Aim.The clinical guidelines are intended to supplement specialty decision-making for improved aid quality in patients with gastritis and duodenitis though acknowledging the latest clinical evidence and principles of evidencebased medicine.Key points.Gastritis is an inflammatory disease of stomach mucosa, with a separate definition of acute and chronic gastritis. Chronic gastritis is a cohort of chronic diseases uniting a typical morphology of persistent inflammatory infiltration, impaired cellular renewal with emergent intestinal metaplasia, atrophy and epithelial dysplasia of gastric mucosa. Oesophagogastroduodenoscopy (OGDS) or high-resolution OGDS with magnified or non-magnified virtual chromoendoscopy, including targeted biopsy for atrophy and intestinal metaplasia grading and neoplasia detection, are recommended to verify gastritis and duodenitis, precancer states and/or gastric mucosal changes. All chronic gastritis patients positive for H. рylori should undergo eradication therapy as aetiological and subsidiary for gastric cancer prevention. Chronic gastritis patients with symptoms of dyspepsia (epigastric pain, burning and congestion, early satiety), also combined with functional dyspepsia, are recommended proton pump inhibitors, prokinetics, rebamipide and bismuth tripotassium dicitrate in symptomatic treatment. With focal restricted intestinal metaplasia, follow-up is not required in most cases, mainly when advanced atrophic gastritis is ruled out in high-quality endoscopy with biopsy. However, a familial history of gastric cancer, incomplete intestinal metaplasia and persistent H. pylori infection render endoscopy monitoring with chromoendoscopy and targeted biopsy desirable once in three years. Patients with advanced atrophic gastritis should have high-quality endoscopy every 3 years, and once in 1–2 years if complicated with a familial history of gastric cancer.Conclusion.The recommendations condense current knowledge on the aetiology and pathogenesis of gastritis and duodenitis, as well as laboratory and instrumental diagnostic techniques, main approaches to aetiological H. pylori eradication and treatment of dyspeptic states.
Collapse
Affiliation(s)
- V. T. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - I. V. Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - T. L. Lapina
- Sechenov First Moscow State Medical University (Sechenov University)
| | - E. D. Fedorov
- Pirogov Russian National Research Medical University
| | - A. A. Sheptulin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Trukhmanov
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | | | - D. N. Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - E. K. Baranskaya
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - E. A. Kogan
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | - S. A. Kurilovich
- Research Institute of Therapy and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
| | | | - M. F. Osipenko
- Research Institute of Therapy and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
| | - P. V. Pavlov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - S. S. Pirogov
- Hertsen Moscow Oncology Research Center — Branch of the National Medical Research Radiology Center
| | | | | | - A. S. Tertychny
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - V. V. Tsukanov
- Research Institute for Medical Problems in the North — Division of Krasnoyarsk Scientific Centre of Siberian Branch of the RAS
| |
Collapse
|
|
28
|
Advances in the Aetiology & Endoscopic Detection and Management of Early Gastric Cancer. Cancers (Basel) 2021; 13:cancers13246242. [PMID: 34944861 PMCID: PMC8699285 DOI: 10.3390/cancers13246242] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/06/2021] [Accepted: 12/10/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Gastric adenocarcinoma has remained a highly lethal disease. Awareness and recognition of preneoplastic conditions (including gastric atrophy and intestinal metaplasia) using high-resolution white-light endoscopy as well as chromoendoscopy is therefore essential. Helicobacter pylori, a class I carcinogen, remains the main contributor to the development of sporadic distal gastric neoplasia. Management of early gastric neoplasia with endoscopic resections should be in line with standard indications. A multidisciplinary approach to any case of an early gastric neoplasia is imperative. Hereditary forms of gastric cancer require a tailored approach and individua-lized surveillance. Abstract The mortality rates of gastric carcinoma remain high, despite the progress in research and development in disease mechanisms and treatment. Therefore, recognition of gastric precancerous lesions and early neoplasia is crucial. Two subtypes of sporadic gastric cancer have been recognized: cardia subtype and non-cardia (distal) subtype, the latter being more frequent and largely associated with infection of Helicobacter pylori, a class I carcinogen. Helicobacter pylori initiates the widely accepted Correa cascade, describing a stepwise progression through precursor lesions from chronic inflammation to gastric atrophy, gastric intestinal metaplasia and neoplasia. Our knowledge on He-licobacter pylori is still limited, and multiple questions in the context of its contribution to the pathogenesis of gastric neoplasia are yet to be answered. Awareness and recognition of gastric atrophy and intestinal metaplasia on high-definition white-light endoscopy, image-enhanced endoscopy and magnification endoscopy, in combination with histology from the biopsies taken accurately according to the protocol, are crucial to guiding the management. Standard indications for endoscopic resections (endoscopic mucosal resection and endoscopic submucosal dissection) of gastric dysplasia and intestinal type of gastric carcinoma have been recommended by multiple societies. Endoscopic evaluation and surveillance should be offered to individuals with an inherited predisposition to gastric carcinoma.
Collapse
|
|
29
|
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.
Collapse
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;
| |
Collapse
|
|
30
|
Management of gastric intestinal metaplasia in patients undergoing routine endoscopy before bariatric surgery. Updates Surg 2021; 74:1383-1388. [PMID: 34586611 DOI: 10.1007/s13304-021-01181-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 09/22/2021] [Indexed: 10/20/2022]
Abstract
Routine preoperative endoscopic evaluation for bariatric surgery is controversial; however, for patients undergoing endoscopy, some findings may alter surgical management. Gastric intestinal metaplasia (GIM) is found in up to 11.7% of the general population. When associated with determined risk factors, GIM has a risk of progressing to gastric cancer. The aim of our study was to assess the prevalence of GIM and possible associated factors in those undergoing bariatric surgery. We performed a retrospective chart review of patients who underwent primary sleeve gastrectomy or Roux-en-Y gastric bypass at our institution between January 1, 2016 and June 30, 2020. Baseline characteristics and preoperative endoscopic findings were obtained from all patients. Histopathologic analysis of sleeve gastrectomy specimens was reviewed. We identified 753 patients. Mean (SD) age and body mass index were 49.0 (13.1) years and 43.9 (7.1) kg/m2, respectively. Procedures consisted of 411 (54.6%) gastric bypasses and 342 (45.4%) sleeve gastrectomies. Esophagitis and Barrett esophagus were found in 18.1% and 5.0% of patients, respectively. Preoperative gastric biopsy identified Helicobacter pylori in 6.4% and GIM in 2.7%. Regression analysis found an association of Barrett esophagus (odds ratio 4.60; 95% CI 1.25-16.82) and age ≥ 60 years (odds ratio 2.67; 95% CI 1.04-6.90) with preoperative findings of GIM. Histopathologic analysis of sleeve gastrectomy specimens identified H. pylori in 1.8% and GIM in 0.9%. Older age and Barrett esophagus were associated with GIM in preoperative gastric biopsy. This association emphasizes the importance of a diligent examination during preoperative endoscopy.
Collapse
|
|
31
|
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.
Collapse
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;
| |
Collapse
|
|
32
|
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.
Collapse
|
|
33
|
Gómez A, Pato ML, Bujanda L, Sala N, Companioni O, Cosme Á, Tufano M, Hanly DJ, García N, Sanz-Anquela JM, Gisbert JP, López C, Elizalde JI, Cuatrecasas M, Andreu V, Paules MJ, Martín-Arranz MD, Ortega L, Poves E, Barrio J, Torres MÁ, Muñoz G, Ferrández Á, Ramírez-Lázaro MJ, Lario S, González CA, Esteller M, Berdasco M. Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions. Cancers (Basel) 2021; 13:2760. [PMID: 34199386 PMCID: PMC8199626 DOI: 10.3390/cancers13112760] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 12/31/2022] Open
Abstract
To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature.
Collapse
Affiliation(s)
- Antonio Gómez
- Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), 08908 Barcelona, Spain; (A.G.); (M.L.P.); (M.T.); (D.J.H.)
| | - Miguel L. Pato
- Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), 08908 Barcelona, Spain; (A.G.); (M.L.P.); (M.T.); (D.J.H.)
- Epigenetic Therapies Group, Experimental and Clinical Hematology Program (PHEC), Josep Carreras Leukaemia Research Institute, 08916 Barcelona, Spain
| | - Luis Bujanda
- Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBEREHD, 20014 San Sebastián, Spain; (L.B.); (Á.C.)
| | - Núria Sala
- Unit of Nutrition, Environment and Cancer, Institut Català d’Oncología, 08908 Barcelona, Spain; (N.S.); (O.C.); (N.G.); (C.A.G.)
- Translational Research Laboratory, Catalan Institute of Oncology (ICO)-IDIBELL, 08908 Barcelona, Spain
| | - Osmel Companioni
- Unit of Nutrition, Environment and Cancer, Institut Català d’Oncología, 08908 Barcelona, Spain; (N.S.); (O.C.); (N.G.); (C.A.G.)
| | - Ángel Cosme
- Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBEREHD, 20014 San Sebastián, Spain; (L.B.); (Á.C.)
| | - Martina Tufano
- Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), 08908 Barcelona, Spain; (A.G.); (M.L.P.); (M.T.); (D.J.H.)
| | - David J. Hanly
- Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), 08908 Barcelona, Spain; (A.G.); (M.L.P.); (M.T.); (D.J.H.)
- Epigenetic Therapies Group, Experimental and Clinical Hematology Program (PHEC), Josep Carreras Leukaemia Research Institute, 08916 Barcelona, Spain
| | - Nadia García
- Unit of Nutrition, Environment and Cancer, Institut Català d’Oncología, 08908 Barcelona, Spain; (N.S.); (O.C.); (N.G.); (C.A.G.)
- Translational Research Laboratory, Catalan Institute of Oncology (ICO)-IDIBELL, 08908 Barcelona, Spain
| | - José Miguel Sanz-Anquela
- Department of Pathology, Hospital Universitario Príncipe de Asturias, 28805 Alcalá de Henares, Spain;
| | - Javier P. Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain; (J.P.G.); (C.L.)
| | - Consuelo López
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain; (J.P.G.); (C.L.)
| | - José Ignacio Elizalde
- Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS and CIBEREHD, 08036 Barcelona, Spain;
| | - Miriam Cuatrecasas
- Department of Pathology, Hospital Clínic de Barcelona, IDIBAPS and CIBEREHD, 08036 Barcelona, Spain;
| | - Victoria Andreu
- Department of Gastroenterology, Hospital de Viladecans, 08840 Barcelona, Spain;
| | - María José Paules
- Department of Pathology, Hospital Universitari de Bellvitge, 08907 L’Hospitalet de Llobregat, Spain;
| | - María Dolores Martín-Arranz
- Department of Gastroenterology, Hospital Universitario La Paz, Instituto de Investigación Sanitaria La Paz (IdiPaz), 28046 Madrid, Spain;
| | - Luis Ortega
- Department of Gastroenterology, Hospital Clínico San Carlos, 28040 Madrid, Spain;
| | - Elvira Poves
- Department of Gastroenterology, Hospital Universitario Príncipe de Asturias, 28805 Alcalá de Henares, Spain;
| | - Jesús Barrio
- Department of Gastroenterology, Hospital Universitario Río Hortega, 47012 Valladolid, Spain;
| | - María Ángeles Torres
- Department of Pathology, Hospital Universitario Río Hortega, 47012 Valladolid, Spain;
| | - Guillermo Muñoz
- Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain; (G.M.); (Á.F.)
| | - Ángel Ferrández
- Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain; (G.M.); (Á.F.)
| | - María José Ramírez-Lázaro
- Department of Medicine, Digestive Diseases Service, Institut Universitari Parc Taulí, 08201 Sabadell, Spain; (M.J.R.-L.); (S.L.)
| | - Sergio Lario
- Department of Medicine, Digestive Diseases Service, Institut Universitari Parc Taulí, 08201 Sabadell, Spain; (M.J.R.-L.); (S.L.)
| | - Carlos A González
- Unit of Nutrition, Environment and Cancer, Institut Català d’Oncología, 08908 Barcelona, Spain; (N.S.); (O.C.); (N.G.); (C.A.G.)
| | - Manel Esteller
- Cancer Epigenetics Group, Cancer and Leukemia Epigenetics and Biology Program (PEBCL), Josep Carreras Leukaemia Research Institute (IJC), 08916 Barcelona, Spain;
- Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029 Madrid, Spain
- Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
- Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
| | - María Berdasco
- Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), 08908 Barcelona, Spain; (A.G.); (M.L.P.); (M.T.); (D.J.H.)
- Epigenetic Therapies Group, Experimental and Clinical Hematology Program (PHEC), Josep Carreras Leukaemia Research Institute, 08916 Barcelona, Spain
| |
Collapse
|
|
34
|
High-risk individuals for gastric cancer would be missed for surveillance without subtyping of intestinal metaplasia. Virchows Arch 2021; 479:679-686. [PMID: 33990867 DOI: 10.1007/s00428-021-03116-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 05/02/2021] [Accepted: 05/04/2021] [Indexed: 10/21/2022]
Abstract
The use of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Assessment based on Intestinal Metaplasia (OLGIM) staging system is recommended for identifying subjects at risk for developing gastric cancer; usually high-risk lesions are considered only as stages III and IV. Accumulating evidence suggests that incomplete intestinal metaplasia (IM) is important in the development of gastric cancer. Our aim has been to identify the prevalence of incomplete IM in patients with low-risk OLGA/OLGIM stages among a high-risk general population. Healthy adult volunteers aged 40-64 years were invited to undergo upper endoscopy within a regional GISTAR pilot study in Kazakhstan (n = 166). Gastric lesions were staged according to OLGA/OLGIM staging system. High iron diamine-alcian blue (HID-AB) was used for subtyping IM. IM prevalence overall was 45.8%. Incomplete IM was present in 52.6% (type II in 30.3% and type III in 22.3%), whereas complete IM was found in 47.4% individuals. The prevalence of OLGIM I and II stage were 39.8 and 4.8%, respectively, whereas OLGIM III was observed in 1.2%. The prevalence of incomplete IM in patients stratified to OLGIM I was 54.5% (type II in 31.8% and type III in 22.7%). High prevalence of incomplete IM was detected not only in subjects with extensive IM, but in those stratified as at the OLGIM I stage. Without IM subtyping, patients with high risk of gastric cancer development would be missed for surveillance.
Collapse
|
|
35
|
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.
Collapse
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.
| |
Collapse
|
|
36
|
Shu X, Wu G, Zhang Y, Wang Y, Zheng Y, Guo Q, Ji R, Zhou Y. Diagnostic value of linked color imaging based on endoscopy for gastric intestinal metaplasia: a systematic review and meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:506. [PMID: 33850903 PMCID: PMC8039702 DOI: 10.21037/atm-21-1051] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background The diagnostic value of linked color imaging based on endoscopy for gastric intestinal metaplasia has shown variable results. Therefore, this meta-analysis sought to systematically evaluate the value of linked color imaging (LCI) based on the blue laser endoscopy system for the diagnosis of gastric intestinal metaplasia (GIM). Methods Literature searches were conducted of electronic databases including PubMed, Embase, the Cochrane Library, and Web of Science to screen diagnostic tests of LCI. The random-effects model was adopted to calculate the diagnostic efficacy of LCI for GIM. Meta-DiSc 1.40 software was applied for the calculation of sensitivity, specificity, and likelihood ratios; symmetric receiver operator characteristic (SROC) curves were drawn, and the areas under the SROC curves (AUCs) were computed. Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool. Results Six original studies involving 700 participants were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of LCI for diagnosing GIM were 0.87 (0.83–0.91), 0.86 (0.82–0.89), 5.72 (3.63–8.99), and 0.17 (0.08–0.36), respectively. SROC curve analysis showed that the AUC value was 0.9283. Discussion Our study shows that LCI can be used for the accurate diagnosis of GIM. Considering weaknesses of available studies in terms of design, further studies with rigorous design are in need for further validating the findings of this meta-analysis.
Collapse
Affiliation(s)
- Xiaochuang Shu
- The First Clinical Medical College of Lanzhou University, Lanzhou, China.,Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Guozhi Wu
- The First Clinical Medical College of Lanzhou University, Lanzhou, China.,Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yanjun Zhang
- General Internal Medicine Department of Donggang Branch, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yuping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Ya Zheng
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Qinghong Guo
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Rui Ji
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| |
Collapse
|
|
37
|
Piazuelo MB, Bravo LE, Mera RM, Camargo MC, Bravo JC, Delgado AG, Washington MK, Rosero A, Garcia LS, Realpe JL, Cifuentes SP, Morgan DR, Peek RM, Correa P, Wilson KT. The Colombian Chemoprevention Trial: 20-Year Follow-Up of a Cohort of Patients With Gastric Precancerous Lesions. Gastroenterology 2021; 160:1106-1117.e3. [PMID: 33220252 PMCID: PMC7956231 DOI: 10.1053/j.gastro.2020.11.017] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 11/10/2020] [Accepted: 11/12/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Helicobacter pylori eradication and endoscopic surveillance of gastric precancerous lesions are strategies to reduce gastric cancer (GC) risk. To our knowledge, this study is the longest prospective cohort of an H pylori eradication trial in a Hispanic population. METHODS A total of 800 adults with precancerous lesions were randomized to anti-H pylori treatment or placebo. Gastric biopsy samples taken at baseline and 3, 6, 12, 16, and 20 years were assessed by our Correa histopathology score. A generalized linear mixed model with a participant-level random intercept was used to estimate the effect of H pylori status on the score over time. Logistic regression models were used to estimate progression by baseline diagnosis and to estimate GC risk by intestinal metaplasia (IM) subtype and anatomic location. RESULTS Overall, 356 individuals completed 20 years of follow-up. Anti-H pylori therapy (intention-to-treat) reduced progression of the Correa score (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.38-0.93). H pylori-negative status had a beneficial effect on the score over time (P = .036). Among individuals with IM (including indefinite for dysplasia) at baseline, incidence rates per 100 person-years were 1.09 (95% CI, 0.85-1.33) for low-grade/high-grade dysplasia and 0.14 (95% CI, 0.06-0.22) for GC. Incomplete-type (vs complete-type) IM at baseline presented higher GC risk (OR, 13.4; 95% CI, 1.8-103.8). Individuals with corpus (vs antrum-restricted) IM showed an OR of 2.1 (95% CI, 0.7-6.6) for GC. CONCLUSIONS In a high-GC-risk Hispanic population, anti-H pylori therapy had a long-term beneficial effect against histologic progression. Incomplete IM is a strong predictor of GC risk.
Collapse
Affiliation(s)
- M. Blanca Piazuelo
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA,Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Luis E. Bravo
- Department of Pathology, Universidad del Valle School of Medicine, Cali, Valle del Cauca, Colombia
| | - Robertino M. Mera
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - M. Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Juan C. Bravo
- Department of Pathology, Universidad del Valle School of Medicine, Cali, Valle del Cauca, Colombia
| | - Alberto G. Delgado
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - M. Kay Washington
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Luz S. Garcia
- Department of Pathology, Universidad del Valle School of Medicine, Cali, Valle del Cauca, Colombia
| | | | | | - Douglas R. Morgan
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA,Division of Gastroenterology, Department of Medicine, University of Alabama, Birmingham, AL, USA
| | - Richard M. Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA,Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA,Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Pelayo Correa
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Keith T. Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA,Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA,Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA,Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA
| |
Collapse
|
|
38
|
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.
Collapse
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
| |
Collapse
|
|
39
|
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]
|
|
40
|
Loughrey MB, Shepherd NA. The indications for biopsy in routine upper gastrointestinal endoscopy. Histopathology 2020; 78:215-227. [PMID: 33382487 DOI: 10.1111/his.14213] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 07/15/2020] [Indexed: 12/11/2022]
Abstract
This review describes the indications and contraindications for endoscopic biopsy, in routine practice, of the upper gastrointestinal (GI) tract. We accept that this review provides grounds for controversy, as our stance in certain situations is counter to some national guidelines. Nevertheless, we provide evidence to support our viewpoints, especially on efficiency and economic grounds. We describe the particular controversies concerning the biopsy assessment of Barrett's oesophagus, chronic gastritis and the duodenum in the investigation of coeliac disease. We accept that there are indications for more extensive upper GI biopsy protocols in children than in adults; the latter constitute our main focus in this article. We would encourage detailed discussion between pathologists and their endoscopy colleagues about the indications, or lack of them, for routine upper GI endoscopic biopsy, as studies have shown that adherence to agreed guidelines has resulted in a very considerable diminution in the biopsy workload without compromising patient management. Furthermore, where biopsy is indicated, we emphasise the importance of accompanying clinical information provided to the pathologist, in particular regarding biopsy site(s), and regular feedback to endoscopists to improve and maintain the quality of such information. Finally, local dialogue is also advised, when necessary, to indicate to endoscopists the need to appropriately segregate biopsies into separate, individually labelled specimens, to maximise the information that can be derived by pathological evaluation and thereby improve the quality of the final pathology report.
Collapse
Affiliation(s)
- Maurice B Loughrey
- Department of Cellular Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK
| | - Neil A Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, UK
| |
Collapse
|
|
41
|
Gastric cancer screening in low incidence populations: Position statement of AEG, SEED and SEAP. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 44:67-86. [PMID: 33252332 DOI: 10.1016/j.gastrohep.2020.08.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/06/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023]
Abstract
This positioning document, sponsored by the Asociación Española de Gastroenterología, the Sociedad Española de Endoscopia Digestiva and the Sociedad Española de Anatomía Patológica, aims to establish recommendations for the screening of gastric cancer (GC) in low incidence populations, such as the Spanish. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates screening in the general population, individuals with relatives with GC and subjects with GC precursor lesions (GCPL). The goal of the interventions should be to reduce GC related mortality. We recommend the use of the OLGIM classification and determine the intestinal metaplasia (IM) subtype in the evaluation of GCPL. We do not recommend to establish endoscopic mass screening for GC or Helicobacter pylori. However, the document strongly recommends to treat H.pylori if the infection is detected, and the investigation and treatment in individuals with a family history of GC or with GCPL. Instead, we recommend against the use of serological tests to detect GCPL. Endoscopic screening is suggested only in individuals that meet familial GC criteria. As for individuals with GCPL, endoscopic surveillance is only suggested in extensive IM associated with additional risk factors (incomplete IM and/or a family history of GC), after resection of dysplastic lesions or in patients with dysplasia without visible lesion after a high quality gastroscopy with chromoendoscopy.
Collapse
|
|
42
|
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.
Collapse
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
| |
Collapse
|
|
43
|
Beresniak A, Malfertheiner P, Franceschi F, Liebaert F, Salhi H, Gisbert JP. Helicobacter pylori "Test-and-Treat" strategy with urea breath test: A cost-effective strategy for the management of dyspepsia and the prevention of ulcer and gastric cancer in Spain-Results of the Hp-Breath initiative. Helicobacter 2020; 25:e12693. [PMID: 32285569 DOI: 10.1111/hel.12693] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 03/08/2020] [Accepted: 03/09/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Data from clinical trials comparing Helicobacter pylori (H. pylori) management strategies in patients with dyspepsia are limited. Cost-effectiveness simulation models might help to identify the optimal strategy. OBJECTIVE To assess the cost-effectiveness of the H. pylori "Test and Treat" (T&T) strategy including the use of urea breath test (UBT) vs symptomatic treatment (ST) and vs upper gastrointestinal endoscopy (UGE) as a first procedure in patients with dyspepsia. METHODS Three main strategies: "T&T" strategy including the use of UBT, "UGE" and "ST" have been compared using cost-effectiveness models developed in accordance with the Spanish medical practice. For the model simulations, a time horizon of 4 weeks was considered for the endpoint "Dyspepsia symptoms relief" and 10 years when using "Peptic ulcer avoided" and "Gastric cancer avoided" endpoints. RESULTS For the endpoint "Dyspepsia symptoms relief", T&T strategy appears to be the most cost-effective (883€/success) compared to UGE strategy and to ST strategy (respectively 1628€ and 990€/success). For the endpoint "Probability of peptic ulcer", the T&T strategy appears to be the most cost-effective (421€/peptic ulcer avoided/y) compared to UGE strategy and ST strategy (respectively 728€ and 632€/peptic ulcer avoided/y). For the endpoint "Gastric cancer avoided", the T&T strategy appears to be the most cost-effective (524€/gastric cancer avoided/y) compared to UGE strategy and "ST" strategy (respectively 716€ and 696€/gastric cancer avoided/y). CONCLUSIONS T&T strategy including the use of UBT is the most cost-effective medical approach for management of dyspepsia and for the prevention of ulcer and gastric cancer.
Collapse
Affiliation(s)
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.,Department of Medicine II, University Hospital, LMU, Munich, Germany
| | - Francesco Franceschi
- Department of Gastroenterology and Internal Medicine, Catholic University, Rome, Italy
| | | | | | - Javier P Gisbert
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| |
Collapse
|
|
44
|
Waddingham W, Nieuwenburg SAV, Carlson S, Rodriguez-Justo M, Spaander M, Kuipers EJ, Jansen M, Graham DG, Banks M. Recent advances in the detection and management of early gastric cancer and its precursors. Frontline Gastroenterol 2020; 12:322-331. [PMID: 34249318 PMCID: PMC8223672 DOI: 10.1136/flgastro-2018-101089] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 04/02/2020] [Accepted: 04/13/2020] [Indexed: 02/06/2023] Open
Abstract
Despite declines in incidence, gastric cancer remains a disease with a poor prognosis and limited treatment options due to its often late stage of diagnosis. In contrast, early gastric cancer has a good to excellent prognosis, with 5-year survival rates as high as 92.6% after endoscopic resection. There remains an East-West divide for this disease, with high incidence countries such as Japan seeing earlier diagnoses and reduced mortality, in part thanks to the success of a national screening programme. With missed cancers still prevalent at upper endoscopy in the West, and variable approaches to assessment of the high-risk stomach, the quality of endoscopy we provide must be a focus for improvement, with particular attention paid to the minority of patients at increased cancer risk. High-definition endoscopy with virtual chromoendoscopy is superior to white light endoscopy alone. These enhanced imaging modalities allow the experienced endoscopist to accurately and robustly detect high-risk lesions in the stomach. An endoscopy-led staging strategy would mean biopsies could be targeted to histologically confirm the endoscopic impression of premalignant lesions including atrophic gastritis, gastric intestinal metaplasia, dysplasia and early cancer. This approach to quality improvement will reduce missed diagnoses and, combined with the latest endoscopic resection techniques performed at expert centres, will improve early detection and ultimately patient outcomes. In this review, we outline the latest evidence relating to diagnosis, staging and treatment of early gastric cancer and its precursor lesions.
Collapse
Affiliation(s)
- William Waddingham
- Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK,Research Department of Pathology, UCL Cancer Institute, London, UK
| | - Stella A V Nieuwenburg
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Sean Carlson
- Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | | | - Manon Spaander
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Ernst J Kuipers
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Marnix Jansen
- Research Department of Pathology, UCL Cancer Institute, London, UK,Pathology, University College London Hospitals NHS Foundation Trust, London, UK
| | - David G Graham
- Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Matthew Banks
- Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| |
Collapse
|
|
45
|
Riera KM, Jang B, Min J, Roland JT, Yang Q, Fesmire WT, Camilleri-Broet S, Ferri L, Kim WH, Choi E, Goldenring JR. Trop2 is upregulated in the transition to dysplasia in the metaplastic gastric mucosa. J Pathol 2020; 251:336-347. [PMID: 32432338 PMCID: PMC8010636 DOI: 10.1002/path.5469] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 04/20/2020] [Accepted: 05/09/2020] [Indexed: 12/27/2022]
Abstract
Intestinal-type gastric adenocarcinoma arises in a field of pre-existing metaplasia. While biomarkers of cancer and metaplasia have been identified, the definition of dysplastic transition as a critical point in the evolution of cancer has remained obscure. We have evaluated Trop2 as a putative marker of the transition from metaplasia to dysplasia in the stomach in multiple mouse models of metaplasia induction and progression. In addition, TROP2 expression was evaluated in human samples by immunostaining tissue microarrays for metaplasia, dysplasia, and gastric cancer. Dysplastic mouse organoids were evaluated in vitro following shRNA knockdown of Trop2 expression. In mouse models, no Trop2 was observed in the normal corpus and Trop2 was not induced in acute models of metaplasia induction with either L635 or DMP-777. In Mist1-Kras mice, Trop2 expression was not observed in metaplasia at 1 month after Kras induction, but was observed in dysplastic glands at 3-4 months after Kras induction. In human tissues, no Trop2 was observed in normal corpus mucosa or SPEM, but Trop2 expression was observed in incomplete intestinal metaplasia, with significantly less expression in complete intestinal metaplasia. Trop2 expression was observed in all dysplastic and 84% of gastric cancer lesions, although expression levels were variable. Dysplastic mouse organoids from Mist1-Kras mice expressed Trop2 strongly. Knockdown of Trop2 with shRNA markedly reduced organoid growth and budding behavior, and induced the upregulation of apical villin expression. We conclude that Trop2 is upregulated in the transition to dysplasia in the stomach and promotes dysplastic cell behaviors. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Collapse
Affiliation(s)
- Katherine M. Riera
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
| | - Bogun Jang
- Department of Pathology, Jeju National University School of Medicine, Jeju, Korea
| | - Jimin Min
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- Epithelial Biology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
| | - Joseph T. Roland
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- Epithelial Biology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
| | - Qing Yang
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- Epithelial Biology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- Institute of Pathogen Biology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China
| | - William T. Fesmire
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
| | | | - Lorenzo Ferri
- Department of Surgery, McGill University, Montreal, Canada
| | - Woo Ho Kim
- Department of Pathology, Seoul National University, Seoul, Korea
| | - Eunyoung Choi
- Nashville VA Medical Center, Nashville, Tennessee
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- Epithelial Biology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
| | - James R. Goldenring
- Nashville VA Medical Center, Nashville, Tennessee
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
- Epithelial Biology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
| |
Collapse
|
|
46
|
Sugai T, Uesugi N, Habano W, Sugimoto R, Eizuka M, Fujita Y, Osakabe M, Toya Y, Suzuki H, Matsumoto T. The clinicopathological and molecular features of sporadic gastric foveolar type neoplasia. Virchows Arch 2020; 477:835-844. [PMID: 32533343 PMCID: PMC7683467 DOI: 10.1007/s00428-020-02846-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 04/15/2020] [Accepted: 05/13/2020] [Indexed: 12/18/2022]
Abstract
Gastric intraepithelial foveolar type neoplasia (IEFN) is not well defined. In addition, atrophic mucosa (AM) is an important issue to consider when evaluating gastric tumorigenesis. Here, we assessed the clinicopathological characteristics and molecular alterations contributing to the development of IEFN compared with intestinal type neoplasia. We examined the clinicopathological and molecular features of 42 cases of IEFN with low-grade dysplasia (LGD) and those of 77 cases of intraepithelial intestinal type neoplasia (IEIN) with LGD. The clinicopathological and molecular features examined included the AM status, mucin phenotype expression, CDX2 expression, p53 overexpression, β-catenin intranuclear accumulation, microsatellite instability (MSI), DNA methylation status (low methylation epigenotype [LME], intermediate ME, or high ME), allelic imbalances (AIs), and APC promoter 1B mutations. There were no differences in the frequencies of AM and rates of CDX2 expression between IEFN and IEIN cases. Although no differences in the frequencies of p53 overexpression and MSI were observed between the two histological types, intranuclear expression of β-catenin was significantly higher in IEIN than in IEFN. In addition, although the rate of LME was significantly higher in IEFN cases than in IEIN cases, IEFN was characterized by AIs at multiple foci. Finally, mutation of the APC promoter 1B, which is a characteristic of gastric adenocarcinoma and proximal polyposis of the stomach (potentially resembling IEFN), was detected in only one IEFN case. These findings suggested that IEFN may be an independent entity in terms of molecular alterations including the presence of multiple AIs and LME.
Collapse
Affiliation(s)
- Tamotsu Sugai
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan.
| | - Noriyuki Uesugi
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan
| | - Wataru Habano
- Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan
| | - Ryo Sugimoto
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan
| | - Makoto Eizuka
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan
| | - Yasuko Fujita
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan
| | - Mitsumasa Osakabe
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan
| | - Yosuke Toya
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan
| | - Hiromu Suzuki
- Department of Molecular Biology, School of Medicine, Sapporo Medical University, Sapporo, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan
| |
Collapse
|
|
47
|
Effectiveness of Helicobacter pylori eradication in preventing metachronous gastric cancer and preneoplastic lesions. A systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2020; 32:686-694. [PMID: 32355093 DOI: 10.1097/meg.0000000000001740] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Helicobacter pylori is a significant risk factor for gastric cancer. Recent trials show eradication decreases the incidence of gastric cancer in patients with early-stage gastric cancer. However, data on gastric cancer prevention are inconsistent for patients with precancerous lesions such as atrophic gastritis and intestinal metaplasia. AIM The aim of the study is to assess the efficacy of H. pylori eradication in gastric cancer prevention in patients with varying risk factors for gastric cancer at baseline. METHODS A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Medline, and Google Scholar were searched from inception through March 2019 for randomized controlled trials (RCTs) studying H. pylori eradication on gastric cancer prevention. We estimated the odds ratio (OR) with 95% confidence interval (CI) for each outcome using a random-effects model. P values of less than 0.05 were considered significant. RESULTS Nine RCTs with total of 6967 patient were included in the analysis. There was significant reduction in gastric cancer incidence in the H. pylori group for patients with early gastric cancer status post endoscopic mucosal resection OR, 0.47; 95% CI, 0.33-0.67; P < 0.0001; I = 0%. There was no difference in gastric cancer incidence in patients with atrophic gastritis and intestinal metaplasia at baseline for H. pylori arm OR, 0.67; 95% CI, 0.42-1.07; P = 0.09; I = 0%). Atrophic gastritis and intestinal metaplasia improved from baseline in the H. pylori arm compared to placebo OR, 2.61; 95% CI, 1.41-4.81; P = 0.002; I = 88 and OR, 2.61; 95% CI, 1.66-4.11; P ≤ 0.0001; I = 0%, respectively. CONCLUSIONS H. pylori eradication is associated with reduced gastric cancer incidence in patients with early-stage gastric cancer and improvement in atrophic gastritis and intestinal metaplasia. There was no difference in gastric cancer incidence in patients with atrophic gastritis and intestinal metaplasia at baseline.
Collapse
|
|
48
|
Estifan E, Cavanagh Y, Grossman MA. Hybrid Argon Plasma Coagulation for Treatment of Gastric Intestinal Metaplasia. Cureus 2020; 12:e7427. [PMID: 32337147 PMCID: PMC7182158 DOI: 10.7759/cureus.7427] [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] [Indexed: 12/14/2022] Open
Abstract
Hybrid argon plasma coagulation (HybridAPC® [HAPC]) is an evolution of the standard argon plasma coagulation (APC) technology, where the application of APC is preceded by high-pressure needleless submucosal injection. APC is indicated for the ablation of benign and dysplastic mucosal lesions, such as vascular malformations or Barrett's mucosa. HAPC offers safety and efficacy advantages over standard APC because the submucosal injection acts as a heat sink that disperses energy. This ensures that the underlying muscularis propria remains unaffected, and only the mucosal layer is coagulated in its entirety. An 81-year-old Hispanic male was found to have a 1.2-cm mucosal nodule along the incisura of the stomach. Pathology of the biopsy specimen revealed high-grade dysplasia, and he subsequently underwent endoscopic ultrasound examination, which confirmed the presence of an isolated gastric nodule with no deep invasion of the muscularis propria, consistent with a uT1N0Mx endosonographic staging. He then underwent endoscopic submucosal dissection of the lesion. Pathology of the excised specimen confirmed the presence of multifocal high-grade dysplasia, arising in the background of extensive intestinal metaplasia. The deep margin was clear; however, the lateral resection margins showed focal involvement of intestinal metaplasia with low-grade dysplasia. Surveillance endoscopy confirmed the persistence of diffuse intestinal metaplasia. He was then treated with widespread HAPC due to the presence of underlying diffuse intestinal metaplasia in the stomach. HAPC is an effective and efficient treatment modality for mucosal lesions. In one series of 50 patients, 96% achieved complete macroscopic remission of Barrett's mucosa after a median of 3.5 APC sessions, and 85% achieved complete histological remission. HAPC is a promising therapeutic modality as a thermal injury is targeted, and the depth of injury is contained. This provides immediate procedural efficacy and safety benefits, and reduces subsequent complications when compared with standard APC. We anticipate that the applications of HAPC will continue to grow, as this modality is adopted into common procedural parlance. This case appears to be the first to describe the use of HAPC for definitive treatment of diffuse intestinal metaplasia.
Collapse
Affiliation(s)
- Elias Estifan
- Internal Medicine, St. Joseph's University Medical Center, Paterson, USA
| | - Yana Cavanagh
- Interventional Gastroenterology, St. Joseph's University Medical Center, Paterson, USA
| | - Matthew A Grossman
- Interventional Gastroenterology, St. Joseph's University Medical Center, Paterson, USA
| |
Collapse
|
|
49
|
Ieni A, Cardia R, Pizzimenti C, Zeppa P, Tuccari G. HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies. J Pers Med 2020; 10:jpm10010010. [PMID: 32098203 PMCID: PMC7151629 DOI: 10.3390/jpm10010010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 02/06/2020] [Accepted: 02/12/2020] [Indexed: 12/15/2022] Open
Abstract
Human epidermal growth factor receptor-2 (HER2)-expression gastro-oesophageal adenocarcinomas (GEA) gained interest as an important target for therapy with trastuzumab. In the current review, we focused the current knowledge on HER2 status in dysplastic and neoplastic gastric conditions, analyzing the methodological procedures to identify HER2 expression/amplification, as well as the proposed scoring recommendations. One of the most relevant questions to evaluate the useful impact of HER2 status on therapeutic choice in GEAs is represented by the significant heterogeneity of HER2 protein and gene expression that may affect the targeted treatment selection. Future development of biotechnology will continue to evolve in order to offer more powerful detection systems for the assessment of HER2 status. Finally, liquid biopsy as well as mutation/amplification of several additional genes may furnish an early detection of secondary HER2 resistance mechanisms in GEAs with a better monitoring of the treatment response.
Collapse
Affiliation(s)
- Antonio Ieni
- Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Pathology, University of Messina, 98125 Messina, Italy; (R.C.); (C.P.); (G.T.)
- Correspondence: ; Tel.: +39-90-221-2536; Fax: +39-90-292-8150
| | - Roberta Cardia
- Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Pathology, University of Messina, 98125 Messina, Italy; (R.C.); (C.P.); (G.T.)
| | - Cristina Pizzimenti
- Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Pathology, University of Messina, 98125 Messina, Italy; (R.C.); (C.P.); (G.T.)
| | - Pio Zeppa
- Department of Medicine and Surgery, University of Salerno, 84131 Salerno, Italy;
| | - Giovanni Tuccari
- Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Pathology, University of Messina, 98125 Messina, Italy; (R.C.); (C.P.); (G.T.)
| |
Collapse
|
|
50
|
Davitkov P, Altayar O, Shah SC, Gawron AJ, Mustafa RA, Morgan D, Morgan DR. Advancing the Science in Gastric Pre-Neoplasia: Study Design Considerations. Gastroenterology 2020; 158:751-759. [PMID: 31887260 PMCID: PMC7354093 DOI: 10.1053/j.gastro.2019.12.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Affiliation(s)
- Perica Davitkov
- Veterans Administration, Northeast Ohio Healthcare System, Celveland, OH, USA,Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Osama Altayar
- Division of Gastroenterology, Washington University School of Medicine, St Louis, MO, USA
| | - Shailja C. Shah
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Andrew J. Gawron
- Salt Lake City Specialty Care Center of Innovation & Gastroenterology Section, VA Salt Lake City Health Care System, Salt Lake City, Utah, USA,Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Reem A. Mustafa
- Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS, USA
| | - Douglas Morgan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Douglas R Morgan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
| |
Collapse
|