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Sun HT. Helicobacter pylori-related serum indicators: Cutting-edge advances to enhance the efficacy of gastric cancer screening. World J Gastrointest Oncol 2025; 17:100739. [PMID: 40092953 PMCID: PMC11866254 DOI: 10.4251/wjgo.v17.i3.100739] [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: 08/30/2024] [Revised: 12/08/2024] [Accepted: 01/03/2025] [Indexed: 02/14/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection induces pathological changes via chronic inflammation and virulence factors, thereby increasing the risk of gastric cancer development. Compared with invasive examination methods, H. pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer (GC); however, large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking. Therefore, a comprehensive review and analysis of recent advances in this field is necessary. In this review, we systematically analyze the relationship between H. pylori and GC and discuss the application of new molecular biomarkers in GC screening. We also summarize the screening potential and application of anti-H. pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk. These indicators provide early warning of infection and enhance screening accuracy. Additionally, we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening. Although this review may lack sufficient evidence due to limitations in existing studies, including small sample sizes, regional variations, and inconsistent testing methods, it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.
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Affiliation(s)
- Hao-Tian Sun
- Cancer Institute, University College London, London WC1E 6BT, United Kingdom
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2
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Huang Y, Yang H, Ding R, Wang L, Li J, Li W, Qin X, Xu Y, Qian J. Reference Ranges and Comparison of Pepsinogen by Chemiluminescence Immunoassay and Enzyme-Linked Immunosorbent Assay in Chinese Population. Cancer Manag Res 2024; 16:921-931. [PMID: 39099764 PMCID: PMC11296369 DOI: 10.2147/cmar.s459568] [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: 04/08/2024] [Accepted: 07/08/2024] [Indexed: 08/06/2024] Open
Abstract
Objective Serum pepsinogen (PG) is a good indicator of atrophic changes in the gastric mucosa. Gastric mucosal atrophy is a high-risk factor for gastric cancer. Serological testing for PG combined with endoscopy can help to improve gastric cancer screening. In this study, we established the reference ranges of serum PG-I, PG-II, and the PG-I/II ratio (PGR) in the Chinese population by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). Besides, in the real world, doctors are often confused by the results of different testing platforms. Thus, a comparison of methods CLIA and ELISA was performed. Methods 2904 individuals were enrolled from six regions in China as part of the Chinese Adult Digestive Diseases Surveillance (2016) program. The individuals completed questionnaires and volunteered to undergo examinations, including gastroscopy, urea breath test, abdominal ultrasound examination and routine serologic tests. Serum was collected to measure PGs (including PG-I, PG-II and PGR) by CLIA and ELISA. Participants who were found obvious abnormalities or absent from the examinations were excluded. Ultimately, 747 healthy individuals were enrolled in this study. The Kolmogorov-Smirnov test was used to assess the distribution of variables. The Kruskal-Wallis H or Mann-Whitney U-tests were used to compare different sex, age, and geographical groups. The 95% reference ranges of PGs obtained by the two methods were established according to document CLSI-EP28-A3, with covariates of sex, age, and region. Spearman correlation analysis, linear regression analysis and allowable total error (ATE) zone analysis were utilized for comparing the two methods. Results On overall, the 95% reference ranges of PG-I, PG-II, and PGR measured by CLIA were 23.00-110.64 ng/mL, 2.50-19.13 ng/mL, and 3.87-13.30, respectively. Meanwhile, the reference ranges of PG-I, PG-II, and PGR measured by ELISA were 36.93-205.06 ng/mL, 1.65-17.96 ng/mL, and 7.50-33.60, respectively. Both PG-I and PG-II levels measured by the two platforms were found to be influenced by sex and age. PGR measured by CLIA was influenced by age but not by sex, while PGR measured by ELISA was not affected by either age or sex. Regional factors did not significantly impact the PG results, except for PG-I detected by ELISA. Ultimately, reference ranges for PGs were established based on age and sex stratification. Additionally, the Spearman correlation analysis revealed that the correlation coefficients for PG-I, PG-II, and PGR detected by the two methods were 0.899, 0.887, and 0.777, respectively, indicating a strong correlation between the two methods. The regression equation for the PG levels detected by two methods was obtained through linear regression analysis. The ATE analysis provided a visual depiction of the consistency between the two methods, clearly indicating the poor agreement between them. Conclusion This study established the reference ranges of PGs by strict and intact enrollment standard. In addition, the results indicated a strong linear relationship between the two methods, yet with a clear bias, which was valuable for laboratory interpretation.
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Affiliation(s)
- Yuan Huang
- Department of Laboratory Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Rui Ding
- Department of Laboratory Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Li Wang
- Department of Epidemiology and Health Statistics, Institute of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Wenbo Li
- Department of Ultrasound, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Xuzhen Qin
- Department of Laboratory Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Yingchun Xu
- Department of Laboratory Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
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Fischbach W, Bornschein J, Hoffmann JC, Koletzko S, Link A, Macke L, Malfertheiner P, Schütte K, Selgrad DM, Suerbaum S, Schulz C. Update S2k-Guideline Helicobacter pylori and gastroduodenal ulcer disease of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:261-321. [PMID: 38364851 DOI: 10.1055/a-2181-2225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
| | - Jan Bornschein
- Translational Gastroenterology Unit John, John Radcliffe Hospital Oxford University Hospitals, Oxford, United Kingdom
| | - Jörg C Hoffmann
- Medizinische Klinik I, St. Marien- und St. Annastiftskrankenhaus, Ludwigshafen, Deutschland
| | - Sibylle Koletzko
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU-Klinikum Munich, Munich, Deutschland
- Department of Paediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Alexander Link
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
| | - Lukas Macke
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Peter Malfertheiner
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
| | - Kerstin Schütte
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken Marienhospital Osnabrück, Osnabrück, Deutschland
| | - Dieter-Michael Selgrad
- Medizinische Klinik Gastroenterologie und Onkologie, Klinikum Fürstenfeldbruck, Fürstenfeldbruck, Deutschland
- Klinik für Innere Medizin 1, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Sebastian Suerbaum
- Universität Munich, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Munich, Deutschland
- Nationales Referenzzentrum Helicobacter pylori, Pettenkoferstr. 9a, 80336 Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Christian Schulz
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
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Dottori L, Pivetta G, Annibale B, Lahner E. Update on Serum Biomarkers in Autoimmune Atrophic Gastritis. Clin Chem 2023; 69:1114-1131. [PMID: 37680186 DOI: 10.1093/clinchem/hvad082] [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: 12/28/2022] [Accepted: 05/05/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important. CONTENT The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods. SUMMARY Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.
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Affiliation(s)
- Ludovica Dottori
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Giulia Pivetta
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Edith Lahner
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
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Aktualisierte S2k-Leitlinie Helicobacter
pylori und gastroduodenale Ulkuskrankheit der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – Juli 2022 – AWMF-Registernummer: 021–001. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:544-606. [PMID: 37146633 DOI: 10.1055/a-1975-0414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
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Huang RJ, Laszkowska M, In H, Hwang JH, Epplein M. Controlling Gastric Cancer in a World of Heterogeneous Risk. Gastroenterology 2023; 164:736-751. [PMID: 36706842 PMCID: PMC10270664 DOI: 10.1053/j.gastro.2023.01.018] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 01/12/2023] [Accepted: 01/17/2023] [Indexed: 01/29/2023]
Abstract
Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review also highlights existing knowledge gaps in GC prevention as well as the role of emerging technologies for early detection and risk stratification.
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Affiliation(s)
- Robert J Huang
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.
| | - Monika Laszkowska
- Gastroenterology, Hepatology, and Nutrition Service, Department of Subspecialty Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Haejin In
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Joo Ha Hwang
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Meira Epplein
- Duke University, Department of Population Health Sciences, and Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, Durham, North Carolina
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Conti CB, Agnesi S, Scaravaglio M, Masseria P, Dinelli ME, Oldani M, Uggeri F. Early Gastric Cancer: Update on Prevention, Diagnosis and Treatment. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:2149. [PMID: 36767516 PMCID: PMC9916026 DOI: 10.3390/ijerph20032149] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 01/22/2023] [Accepted: 01/23/2023] [Indexed: 06/17/2023]
Abstract
Gastric cancer (GC) is a relevant public health issue as its incidence and mortality rates are growing worldwide. There are recognized carcinogen agents, such as obesity, tobacco, meat, alcohol consumption and some dietary protective factors. Strategies of early diagnosis through population-based surveillance programs have been demonstrated to be effective in lowering the morbidity and mortality related to GC in some countries. Indeed, the detection of early lesions is very important in order to offer minimally invasive treatments. Endoscopic resection is the gold standard for lesions with a low risk of lymph node metastasis, whereas surgical mini-invasive approaches can be considered in early lesions when endoscopy is not curative. This review outlines the role of lifestyle and prevention strategies for GC, in order to reduce the patients' risk factors, implement the surveillance of precancerous conditions and, therefore, improve the diagnosis of early lesions. Furthermore, we summarize the available treatments for early gastric cancer.
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Affiliation(s)
- Clara Benedetta Conti
- Interventional Endoscopy, Foundation IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Stefano Agnesi
- Department of Surgery and Translational Medicine, Foundation IRCCS San Gerardo dei Tintori, University of Milano-Bicocca, 20900 Monza, Italy
| | - Miki Scaravaglio
- Interventional Endoscopy, Foundation IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Pietro Masseria
- Department of Surgery and Translational Medicine, Foundation IRCCS San Gerardo dei Tintori, University of Milano-Bicocca, 20900 Monza, Italy
| | - Marco Emilio Dinelli
- Interventional Endoscopy, Foundation IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Massimo Oldani
- General Surgery Unit, Foundation IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Fabio Uggeri
- Department of Surgery and Translational Medicine, Foundation IRCCS San Gerardo dei Tintori, University of Milano-Bicocca, 20900 Monza, Italy
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Faria L, Silva JC, Rodríguez-Carrasco M, Pimentel-Nunes P, Dinis-Ribeiro M, Libânio D. Gastric cancer screening: a systematic review and meta-analysis. Scand J Gastroenterol 2022; 57:1178-1188. [PMID: 35531944 DOI: 10.1080/00365521.2022.2068966] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Gastric cancer (GC) screening is recommended in high-risk populations, although screening methods and intervals vary. In intermediate-risk populations, screening through esophagogastroduodenoscopy (EGD) may be considered depending on local resources. The aim of this study was to compare GC screening methods regarding effect on mortality, diagnostic yield and adherence. METHODS Systematic review and meta-analysis including studies evaluating population-based GC screening. Search was conducted in three online databases (MEDLINE, Scopus and clinicaltrials.gov), along with manual search. RESULTS Forty-four studies were included. Studies in upper gastrointestinal series (UGIS) demonstrated that GC screening was associated with significantly lower GC mortality rates (OR 0.63, 95% CI 0.55 - 0.73). Benefits on mortality were also found in EGD and serum pepsinogen (PG) studies. EGD was associated with significantly higher GC (0.55%, 95% CI 0.39 - 0.75%) and early-GC (EGC) detection rates (0.48%, 95% CI 0.34 - 0.65%) when compared to UGIS (GC 0.19%, 95% CI 0.10 - 0.31%; EGC 0.08%, 95% CI 0.04 - 0.13%) and PG (GC 0.10%, 95% CI 0.05 - 0.16%; EGC 0.10%, 95% CI 0.04 - 0.19%). Non-invasive methods tended to higher adherence rates when compared to EGD. Regardless of the screening method, individualized recruitment performed better. DISCUSSION Screening positively impacted GC mortality rates. EGD was associated with higher diagnostic yield, while UGIS and PG tended to higher adherence rates. Screening uptake was predominantly impacted by recruitment strategies independently of the adopted method.
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Affiliation(s)
- Lídia Faria
- Faculty of Medicine, University of Porto, Porto, Portugal
| | - João Carlos Silva
- Faculty of Medicine, University of Porto, Porto, Portugal.,Gastroenterology Department, Centro Hospitalar Vila Nova de Gaia e Espinho (CHVNG/E), Porto, Portugal
| | | | - Pedro Pimentel-Nunes
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal.,MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Mário Dinis-Ribeiro
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal.,MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Diogo Libânio
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal.,MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
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In H, Sarkar S, Ward J, Friedmann P, Parides M, Yang J, Epplein M. Serum Pepsinogen as a Biomarker for Gastric Cancer in the United States: A Nested Case-Control Study Using the PLCO Cancer Screening Trial Data. Cancer Epidemiol Biomarkers Prev 2022; 31:1426-1432. [PMID: 35534235 PMCID: PMC9268394 DOI: 10.1158/1055-9965.epi-21-1328] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 02/16/2022] [Accepted: 04/14/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer. METHODS The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed gastric cancer and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I ≤ 70 μg/L and pepsinogen I/II ratio ≤3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for gastric cancer are reported. RESULTS Gastric cancer cases were more likely to be PG+ (31.4% vs. 5.5%, P < 0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for gastric cancer [95% confidence interval (CI) = 3.8-19.4]. This risk remained significant after adjusting for Helicobacter pylori, family history of gastric cancer, education, smoking, and BMI (aOR, 10.6; 95% CI, 4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia gastric cancer (OR, 11.1; 95% CI, 4.3-28.8); conversely, they were not significantly more likely to develop cardia gastric cancer (OR, 2.0; 95% CI = 0.3-14.2). PG+ status yielded low sensitivity but high specificity for both noncardia (44.3%; 93.6%) and cardia gastric cancer (5.7%; 97.2%). CONCLUSIONS Prediagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of gastric cancer, particularly noncardia gastric cancer. IMPACT PG status may identify individuals at higher risk of noncardia gastric cancer for targeted screening or interventions. See related commentary by Zhou and Huang, p. 1257.
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Affiliation(s)
- Haejin In
- Montefiore Medical Center/Albert Einstein College of Medicine, Department of Surgery, Bronx, NY, USA,Albert Einstein College of Medicine, Department of Epidemiology and Population Health, Bronx, NY, USA,Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Srawani Sarkar
- Montefiore Medical Center/Albert Einstein College of Medicine, Department of Surgery, Bronx, NY, USA,Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Jessica Ward
- Albert Einstein College of Medicine, Bronx, NY, USA
| | - Patricia Friedmann
- Montefiore Medical Center/Albert Einstein College of Medicine, Department of Surgery, Bronx, NY, USA,Montefiore Medical Center/Albert Einstein College of Medicine, Department of Cardiothoracic and Vascular Surgery, Bronx, NY, USA
| | - Michael Parides
- Montefiore Medical Center/Albert Einstein College of Medicine, Department of Surgery, Bronx, NY, USA,Montefiore Medical Center/Albert Einstein College of Medicine, Department of Cardiothoracic and Vascular Surgery, Bronx, NY, USA,Hospital for Special Surgery, Research Institute
| | - Julie Yang
- Montefiore Medical Center/Albert Einstein College of Medicine, Division of Gastroenterology, Bronx, NY, USA
| | - Meira Epplein
- Duke University, Department of Population Health Sciences, and Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, Durham, NC, USA
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10
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Oana SM, Claudia B, Lelia RA, Simona M, Claudia C, Daniela DE. Differential Expression of Tissular miRNA-155 in Pediatric Gastritis. J Clin Med 2022; 11:3351. [PMID: 35743416 PMCID: PMC9224896 DOI: 10.3390/jcm11123351] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/01/2022] [Accepted: 06/09/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND MicroRNA molecules, among them the intensely studied miRNA-155 (miR-155), are regarded as potential biomarkers of chronic gastric inflammation and premalignant lesion progression. However, literature data are scarce in terms of pediatric studies and in the evaluation of the predictive role of miRNA in early gastric inflammation. This study aims to assess the differential expression of miR-155 in relation to pediatric gastritis. METHODS The present research was conducted on 192 patients with chronic dyspeptic symptoms who underwent upper digestive endoscopy. Bioptic samples were harvested for histopathological analysis and tissue miR-155 depiction. MiR-155 expression analysis was carried out through quantitative real-time polymerase chain reaction (qRT-PCR). The study population was divided into two groups: controls (93 patients) and study group (99 patients) with inflammatory modifications. RESULTS MiR-155 expression was augmented in patients with gastritis but did not differ significantly from controls (p = 0.16). An increase in miR-155 expression was noted in relation to chronic gastritis, H. pylori infection, or increase in gastritis severity, but these variations were not important (p = 0.30, p = 0.44, and p = 0.45, respectively). CONCLUSIONS According to our study, pediatric gastritis increases, but does not greatly influence, miR-155 expression. Dynamic evaluation of miR-155 might enlighten its prognostic role in pediatric gastritis.
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Affiliation(s)
- Săsăran Maria Oana
- Department of Pediatrics III, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
| | - Bănescu Claudia
- Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
| | - Riza Anca Lelia
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, Petru Rareș Street No 2, 200349 Craiova, Romania;
| | - Mocan Simona
- Pathology Department, County Emergency Clinical Hospital of Targu Mures, Gheorghe Marinescu Street No 50, 540136 Targu Mures, Romania;
| | - Cârstea Claudia
- Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
| | - Dobru Ecaterina Daniela
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No 38, 540136 Targu Mures, Romania;
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11
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Abstract
PURPOSE OF REVIEW Gastric intestinal metaplasia (GIM) is an attractive target for surveillance and treatment as it can progress to gastric adenocarcinoma (GAC). Yet, GIM remains a challenging area for clinicians as most patients do not progress to cancer, and there are conflicting data regarding the benefits of surveillance and therapy. This review aims to summarize recently published GIM surveillance guidelines, to discuss, which patients with GIM may benefit from treatment, and to review pivotal and recent literature on GIM therapy. RECENT FINDINGS Guidelines published by American, British, and European gastroenterology societies do not recommend universal surveillance, but do suggest endoscopic surveillance in patients with risk factors for progression to GAC. Although light examination for at least 7 min and mapping biopsies may increase yield for dysplasia and GAC. In randomized trials, Helicobacter pylori eradication reduced risk of dysplasia and cancer. In GIM with visible dysplasia and early-stage GAC, endoscopic resection improves quality of life without reducing survival compared with surgery. Endoscopic ablation therapies have shown promise for invisible or extensive dysplasia. SUMMARY Endoscopic resection is appropriate for visible dysplasia and early-stage GAC without high-risk features that persists despite H. pylori eradication therapy. Prospective studies are needed to assess the utility of endoscopic ablation in GIM.
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Affiliation(s)
- Thaer Abdelfattah
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University
- Division of Gastroenterology and Hepatology, McGuire VA Medical Center, Richmond, Virginia, USA
| | - Omer Shahab
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University
- Division of Gastroenterology and Hepatology, McGuire VA Medical Center, Richmond, Virginia, USA
| | - Tilak U Shah
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University
- Division of Gastroenterology and Hepatology, McGuire VA Medical Center, Richmond, Virginia, USA
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Han XL, Yi CL, Ma JD, He Y, Wu LM, Wang YF, Yang HJ, Liang DY, Shi JF. Clinical Value of Pepsinogen in the Screening, Prevention, and Diagnosis of Gastric Cancer. Lab Med 2021; 53:71-77. [PMID: 34508270 DOI: 10.1093/labmed/lmab035] [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] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES To compare the levels of serum pepsinogen (PG) in patients with gastric cancer (GC), patients with atrophic gastritis (AG), and healthy donors. Also, we explored the clinical value of PG detection for the diagnosis and treatment of GC. METHODS The PG level in peripheral blood from patients and heathy donors was determined using an Abbott automatic chemiluminescence instrument. The study included 117 patients with GC confirmed by gastroscopy and histopathology, of whom 13 patients had cancer at stage I, 47 at stage II, 41 at stage III, and 16 at stage IV. The AG group included 122 patients, and the control group had 120 healthy donors. The relationship between serum PG levels and the occurrence and development of GC, as well as the evaluation of the clinical value of diagnostic tests based on serum PG detection, were investigated by receiver operating characteristic (ROC) curve analyses. RESULTS Pepsinogen I (PGI) levels gradually decreased from the control group, the AG group, and the GC group. PGI exhibited high diagnostic value for GC (area under the curve [AUC], 0.834; cutoff, 51.2 ng/mL, sensitivity, 81.7%; specificity, 68.4%), PGII (AUC, 0.587; cutoff value, 13.05 ng/mL; sensitivity, 65.8%; specificity, 53.8%), and PGR (AUC, 0.752; cutoff, 5.65; sensitivity, 54.2%; specificity, 87.2%). The occurrence of GC was negatively correlated with serum levels of PGI (B = -0.054; OR = 0.947; 95% confidence interval [CI], 0.925-0.970; P <.001) and PGR (B = -0.420; OR = 0.657; 95% CI, 0.499-0.864; P = .003). CONCLUSIONS The combined detection of PGI, PGII, and PGR has important clinical value for the screening, prevention, and diagnosis of GC and could allow for earlier detection, diagnosis, and treatment of GC.
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Affiliation(s)
- Xiao-Lei Han
- Department of Clinical Laboratory, Anting Hospital, Jiading District, Shanghai, China.,Department of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chang-Lin Yi
- Department of Clinical Laboratory, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
| | - Jin-Dan Ma
- Department of Clinical Laboratory, Anting Hospital, Jiading District, Shanghai, China
| | - Yanhong He
- Department of Clinical Laboratory, Anting Hospital, Jiading District, Shanghai, China
| | - La-Mei Wu
- Department of Clinical Laboratory, Anting Hospital, Jiading District, Shanghai, China
| | - Yun-Feng Wang
- Digestive Internal Medicine, Kunshan Branch of Shanghai Cancer Hospital, Shanghai, China
| | - Hui-Jian Yang
- Department of Clinical Laboratory, Dongfang Hospital affiliated to Tongji University, Shanghai, China
| | - Dong-Yu Liang
- Department of Clinical Laboratory, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Jin-Fang Shi
- Department of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
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13
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Trivanovic D, Plestina S, Honovic L, Dobrila-Dintinjana R, Vlasic Tanaskovic J, Vrbanec D. Gastric cancer detection using the serum pepsinogen test method. TUMORI JOURNAL 2021; 108:386-391. [PMID: 33993805 DOI: 10.1177/03008916211014961] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Gastric cancer (GC) is the eighth most common cause of cancer deaths in Croatia and one of the most common causes of cancer deaths worldwide. A reliable diagnostic tool for the early detection of GC is essential. OBJECTIVE We previously suggested a pepsinogen test method to reduce the mortality from GC by allowing early detection. Here, we report an updated analysis from a prospective single-center clinical study to evaluate the sensitivity and specificity of the pepsinogen test method and to determine whether this test can be used as a part of routine laboratory assessment of high-risk patients. METHODS We present mature data of the pepsinogen test method in the Croatian population after a median follow-up of 36 months. Statistical analyses were performed using a Mann-Whitney U test, multiple logistic regression, and receiver operating characteristics (ROC) to evaluate the predictive power of the assayed biomarkers. RESULTS Of the 116 patients, 25 patients had GC and 91 demonstrated a nonmalignant pathology based on tissue biopsy. Cutoff values were pepsinogen I ⩽70 and pepsinogen I/II ratio ⩽3.0. Using ROC curve analysis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were determined to be 87.22%, 78.12%, 90.10%, 71.43%, and 92.86%, respectively, for the diagnosis of GC. The area under the curve was 0.700 (95% confidence interval 0.57-0.83). CONCLUSION Pepsinogen tests are valuable for screening a population in need of further diagnosis and could help to avoid unnecessary invasive endoscopic procedures.
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Affiliation(s)
- Dragan Trivanovic
- Department of Oncology and Medical Faculty, General Hospital Pula, Pula, Croatia
| | - Stjepko Plestina
- Department of Oncology and Radiotherapy, Clinical Hospital Zagreb, Zagreb, Croatia
| | - Lorena Honovic
- Department of Clinical Chemistry and Medical Faculty, General Hospital Pula, Pula, Croatia
| | | | | | - Damir Vrbanec
- Department of Oncology and Medical Faculty, General Hospital Pula, Pula, Croatia
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14
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Arribas Anta J, Dinis-Ribeiro M. Early gastric cancer and Artificial Intelligence: Is it time for population screening? Best Pract Res Clin Gastroenterol 2020; 52-53:101710. [PMID: 34172244 DOI: 10.1016/j.bpg.2020.101710] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 10/18/2020] [Accepted: 11/05/2020] [Indexed: 02/08/2023]
Abstract
Gastric cancer is a common cause of death worldwide and its early detection is crucial to improve its prognosis. Its incidence varies throughout countries, and screening has been found to be cost-effective at least in high-incidence regions. Identification of individuals harbouring preneoplastic lesions and their surveillance or of those with early gastric cancer are extremely important processes and endoscopy play a key role for this purpose. Unfortunately, also quality and accuracy for endoscopic detection varies among centres and endoscopists. Recent studies about Artificial Intelligence applied to endoscopic imaging show that these technologies perform very well and could be extremely useful for endoscopists to achieve the accuracy needed for gastric cancer screening. Nonetheless, as its introduction in this field is very recent, most studies are carried out offline and its results in clinical practice need to be further validated namely by incorporating all the components/dimensions of endoscopy from pre to post-assessment.
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Affiliation(s)
- Julia Arribas Anta
- Department of Gastroenterology and Hepatology, University Hospital Doce de Octubre, Madrid, Spain.
| | - Mario Dinis-Ribeiro
- Department of Gastroenterology, Portuguese Oncology Institute of Porto, Porto, Portugal
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15
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Xu Y, Miremadi A, Link A, Malfertheiner P, Fitzgerald RC, Bornschein J. Feasibility of combined screening for upper gastrointestinal adenocarcinoma risk by serology and Cytosponge testing: the SUGAR study. J Clin Pathol 2019; 72:825-829. [PMID: 31235543 PMCID: PMC6874497 DOI: 10.1136/jclinpath-2019-205700] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 05/18/2019] [Indexed: 01/11/2023]
Abstract
AIMS Aim was to assess the feasibility of serum markers to identify individuals at risk for gastro-oesophageal adenocarcinoma to reduce the number of individuals requiring invasive assessment by endoscopy. METHODS Blood samples from 56 patients with Barrett's oesophagus and 202 non-Barrett controls who previously took part in a trial assessing the accuracy of the Cytosponge for Barrett's oesophagus were assessed for serum pepsinogen (PG) 1 and 2, gastrin-17, trefoil factor 3 (TFF3) and Helicobacter pylori infection. RESULTS PG1 was pathological (<50 ng/mL) in 26 patients (10.1%), none of whom had Barrett's oesophagus (p<0.001). Smoking and drinking had no influence on these results. Pathological PG1 was associated with stomach pain (p=0.029), disruption of sleep (p=0.027) and disruption of diet by symptoms (p=0.019). Serum TFF3 was not associated with any clinical parameter. CONCLUSIONS Assessment of serum PG1 could be combined with a test for Barrett's oesophagus to identify additional patients requiring endoscopy.
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Affiliation(s)
- Yiwang Xu
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK
| | - Ahmad Miremadi
- Histopathology Department, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Alexander Link
- Dept. of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University, Magdeburg, Germany
| | - Peter Malfertheiner
- Dept. of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University, Magdeburg, Germany
| | - Rebecca C Fitzgerald
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK
| | - Jan Bornschein
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK
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16
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Zhou B, Chen X, Huang B, Hu Y, Tang G, Zhang J, Lin Q. Changes in serum pepsinogen levels and their value as a predictor of treatment outcomes in children with peptic ulcer. J Paediatr Child Health 2019; 55:1103-1106. [PMID: 30659684 DOI: 10.1111/jpc.14365] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 11/13/2018] [Accepted: 12/05/2018] [Indexed: 12/12/2022]
Abstract
AIM To investigate pepsinogen secretion from the neonatal stage to childhood and its diagnostic value for peptic ulcer (PU) in children. METHODS In this study, 2114 'healthy' children and 51 children with PUs undergoing a medical examination by gastroscopy were selected as subjects. The serum content of pepsinogen I (PGI) and serum pepsinogen II (PGII) was tested for each of the subjects using time-resolved fluorescence immunoassay, which is characterised by high sensitivity and a wide measuring range. RESULTS The serum PGI and PGII levels were found to increase with age, becoming stable and similar to those of adults at the age of 16. In 51 children with PUs, PGI was 201.03 ± 30.74 ng/mL before treatment and 187.92 ± 19.86 ng/mL after treatment (P > 0.05); PGII was 17.36 ± 1.47 ng/mL before treatment and 17.20 ± 3.98 ng/mL after treatment (P > 0.05). CONCLUSIONS It is difficult to establish the normal range of PG in children owing to its variance by age. However, if the normal reference range for individual age groups is known, it may still serve as a useful diagnosis system as well as a detecting indicator during the course of PU treatment. There are significant differences in PGI expression in children with PU before and after PU is cured, whereas other indicators show no differences before and after treatment.
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Affiliation(s)
- Bin Zhou
- Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China
| | - Xintao Chen
- Department of Gastroenterology, Wuxi Children's Hospital, Wuxi, China
| | - Biao Huang
- Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China
| | - Yonghong Hu
- The Synergetic Innovation Center for Advanced Materials, State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Guorong Tang
- Department of Gastroenterology, Wuxi Children's Hospital, Wuxi, China
| | - Jue Zhang
- Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China
| | - Qiong Lin
- Department of Gastroenterology, Wuxi Children's Hospital, Wuxi, China
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17
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Banks M, Graham D, Jansen M, Gotoda T, Coda S, di Pietro M, Uedo N, Bhandari P, Pritchard DM, Kuipers EJ, Rodriguez-Justo M, Novelli MR, Ragunath K, Shepherd N, Dinis-Ribeiro M. British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut 2019; 68:1545-1575. [PMID: 31278206 PMCID: PMC6709778 DOI: 10.1136/gutjnl-2018-318126] [Citation(s) in RCA: 362] [Impact Index Per Article: 60.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 05/06/2019] [Accepted: 05/17/2019] [Indexed: 12/11/2022]
Abstract
Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer-in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met.
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Affiliation(s)
- Matthew Banks
- University College London Hospital, University College London Hospitals NHS Foundation Trust, London, UK.,Research Department of Targeted Intervention, University College London, London, UK
| | - David Graham
- University College London Hospital, University College London Hospitals NHS Foundation Trust, London, UK.,Division of Surgery and Interventional Science, University College London Division of Biosciences, London, UK
| | - Marnix Jansen
- Department of Histopathology, University College London, London, UK
| | - Takuji Gotoda
- Gastroenterology, Nihon University School of Medicine Graduate School of Medicine, Itabashi-ku, Tokyo, Japan
| | | | - Massimiliano di Pietro
- MRC Cancer Unit, University of Cambridge, Cambridge, UK.,Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Endoscopic Training and Learning Center, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
| | | | - D Mark Pritchard
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | | | | | - Marco R Novelli
- Department of Histopathology, University College London, London, UK
| | - Krish Ragunath
- Nottingham Digestive Diseases Centre, Nottingham University Hospital, Nottingham, UK
| | - Neil Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, Gloucestershire, UK
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18
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Quach DT, Hiyama T, Gotoda T. Identifying high-risk individuals for gastric cancer surveillance from western and eastern perspectives: Lessons to learn and possibility to develop an integrated approach for daily practice. World J Gastroenterol 2019; 25:3546-3562. [PMID: 31367156 PMCID: PMC6658388 DOI: 10.3748/wjg.v25.i27.3546] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 05/28/2019] [Accepted: 06/23/2019] [Indexed: 02/06/2023] Open
Abstract
Current evidence shows that individuals with gastric dysplasia, severe and extensive gastric atrophy, extensive gastric intestinal metaplasia and the incomplete subtype of intestinal metaplasia are at high risk for gastric cancer (GC) development. There are several approaches to identifying these subjects, including noninvasive methods, esophagogastroduodenoscopy and histology. The main approach in Western countries is histology-based while that in Eastern countries with a high prevalence of GC is endoscopy-based. Regarding asymptomatic individuals, the key issues in selecting applicable approaches are the ability to reduce GC mortality and the cost-effectiveness of the approach. At present, population-based screening programs have only been applied in a few Asian countries with a high risk of GC. Pre-endoscopic risk assessment based on demographic and clinical features, such as ethnicity, age, gender, smoking and Helicobacter pylori status, is helpful for identifying subjects with high pre-test probability for a possibly cost-effective approach, especially in intermediate- and low-risk countries. Regarding symptomatic patients with indications for esophagogastroduodenoscopy, the importance of opportunistic screening should be emphasized. The combination of endoscopic and histological approaches should always be considered as endoscopy provides a real-time assessment of the patient’s risk level. In addition, imaging enhanced endoscopy (IEE) has been shown to facilitate targeted biopsies resulting in better correlation between endoscopic and histological findings. Currently, the use of IEE is recommended for endoscopic examinations, and the Operative Link for Gastric Intestinal Metaplasia or Operative Link on Gastritis Assessment grading systems are recommended for histological examinations whenever available. However, resource limitations are an important barrier in many regions worldwide. Thus, for an approach to be applicable in real-life practice, it should be not only evidence-based but also resource-sensitive. In this review, we discuss the current understanding and approaches to identifying high-risk individuals from western and eastern perspectives, as well as the possibility of an integrated, resource-sensitive approach.
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Affiliation(s)
- Duc Trong Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Hochiminh City, Ho Chi Minh 70000, Vietnam
| | - Toru Hiyama
- Health Service Center, Hiroshima University, Higashihiroshima 739-8514, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo 101-8309, Japan
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19
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Bang CS, Lee JJ, Baik GH. Prediction of Chronic Atrophic Gastritis and Gastric Neoplasms by Serum Pepsinogen Assay: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy. J Clin Med 2019; 8:jcm8050657. [PMID: 31083485 PMCID: PMC6572271 DOI: 10.3390/jcm8050657] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 05/06/2019] [Accepted: 05/08/2019] [Indexed: 12/16/2022] Open
Abstract
Serum pepsinogen assay (sPGA), which reveals serum pepsinogen (PG) I concentration and the PG I/PG II ratio, is a non-invasive test for predicting chronic atrophic gastritis (CAG) and gastric neoplasms. Although various cut-off values have been suggested, PG I ≤70 ng/mL and a PG I/PG II ratio of ≤3 have been proposed. However, previous meta-analyses reported insufficient systematic reviews and only pooled outcomes, which cannot determine the diagnostic validity of sPGA with a cut-off value of PG I ≤70 ng/mL and/or PG I/PG II ratio ≤3. We searched the core databases (MEDLINE, Cochrane Library, and Embase) from their inception to April 2018. Fourteen and 43 studies were identified and analyzed for the diagnostic performance in CAG and gastric neoplasms, respectively. Values for sensitivity, specificity, diagnostic odds ratio, and area under the curve with a cut-off value of PG I ≤70 ng/mL and PG I/PG II ratio ≤3 to diagnose CAG were 0.59, 0.89, 12, and 0.81, respectively and for diagnosis of gastric cancer (GC) these values were 0.59, 0.73, 4, and 0.7, respectively. Methodological quality and ethnicity of enrolled studies were found to be the reason for the heterogeneity in CAG diagnosis. Considering the high specificity, non-invasiveness, and easily interpretable characteristics, sPGA has potential for screening of CAG or GC.
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Affiliation(s)
- Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Sakju-ro 77, Chuncheon, Gangwon-do 24253, Korea.
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24253, Korea.
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24253, Korea.
| | - Jae Jun Lee
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24253, Korea.
- Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Chuncheon 24253, Korea.
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Sakju-ro 77, Chuncheon, Gangwon-do 24253, Korea.
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24253, Korea.
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20
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Pizzi MP, Bartelli TF, Pelosof AG, Freitas HC, Begnami MD, de Abrantes LLS, Sztokfisz C, Valieris R, Knebel FH, Coelho LGV, da Costa WL, Coimbra FJF, da Silva IT, de Amorim MG, Nunes DN, Dias-Neto E. Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow-up. Int J Cancer 2019; 145:1090-1098. [PMID: 30779121 DOI: 10.1002/ijc.32217] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 01/09/2019] [Accepted: 02/04/2019] [Indexed: 12/12/2022]
Abstract
Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next-generation deep sequencing of TP53-a highly mutated and informative gene in GAC-to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash-GW). We evaluated their potential to reveal tumor-derived mutations, useful for monitoring mutational dynamics at diagnosis, progression and treatment. Exon-capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post-treatment (196 samples), with high vertical coverage >8,000×. At diagnosis, we detected TP53 mutations in 15/46 biopsies (32.6%), 7/46 GW- (15.2%) and 6/46 PL-samples (13%). Biopsies and GW were concordant in 38/46 cases (82.6%) for the presence/absence of mutations and, furthermore, four GW-exclusive mutations were identified, suggesting tumor heterogeneity. Considering the combined analysis of GW and PL, TP53 mutations found in biopsies were also identified in 9/15 (60%) of cases, the highest detection level reported for GAC. Our study indicates that GW could be useful to track DNA alterations, especially if anchored to a comprehensive gene-panel designed for this malignancy.
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Affiliation(s)
- Melissa Pool Pizzi
- Laboratory of Medical Genomics, A.C.Camargo Cancer Center, São Paulo, SP, Brazil
| | | | | | - Helano Carioca Freitas
- Laboratory of Medical Genomics, A.C.Camargo Cancer Center, São Paulo, SP, Brazil.,Department of Clinical Oncology, A.C.Camargo Cancer Center, São Paulo, SP, Brazil
| | | | | | | | - Renan Valieris
- Laboratory of Computational Biology, A.C.Camargo Cancer Center, São Paulo, SP, Brazil
| | | | - Luiz Gonzaga Vaz Coelho
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Wilson Luiz da Costa
- Department of Abdominal Surgery, A.C.Camargo Cancer Center, São Paulo, SP, Brazil
| | - Felipe J F Coimbra
- Department of Abdominal Surgery, A.C.Camargo Cancer Center, São Paulo, SP, Brazil
| | - Israel Tojal da Silva
- Laboratory of Computational Biology, A.C.Camargo Cancer Center, São Paulo, SP, Brazil
| | | | - Diana Noronha Nunes
- Laboratory of Medical Genomics, A.C.Camargo Cancer Center, São Paulo, SP, Brazil
| | - Emmanuel Dias-Neto
- Laboratory of Medical Genomics, A.C.Camargo Cancer Center, São Paulo, SP, Brazil.,Laboratory of Neurosciences Alzira Denise Hertzog Silva (LIM-27), Instituto de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
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21
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The Value of Pepsinogen in GC Screening: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2019; 2019:7087232. [PMID: 30804996 PMCID: PMC6360615 DOI: 10.1155/2019/7087232] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 08/22/2018] [Accepted: 10/20/2018] [Indexed: 12/20/2022] Open
Abstract
Background The current gold standard for gastric cancer (GC) screening is pathology or a barium meal followed by X-ray. This is not applicable to a wide range of screening capabilities due to the lack of operability. This article used a meta-analysis to evaluate the value of pepsinogen (PG) screening for GC. Methods PubMed, EMbase, the Cochrane Library, CNKI, WanFang, VIP, and CBM databases were systematically searched for published studies that used serum PG to diagnose GC. Articles were searched from January 2003 to January 2018. Two reviewers independently screened the literature according to specified inclusion and exclusion criteria. The data were extracted and evaluated, and the quality of the methodologies evaluated using the QUADAS entry. The meta-analysis (MA) was performed using Meta-DiSc 1.4 software. Stata 12.0 software was used to assess publication bias. Results A total of 19 studies were finally included from a total of 169,009 cases. The MA showed a combined sensitivity and specificity of 0.56 (95% CI (0.53-0.59), P < 0.01) and 0.71 (95% CI (0.70-0.71), P < 0.01), respectively. The combined likelihood ratios were +LR = 2.82 (95% CI (2.06-3.86), P < 0.01) and -LR = 0.56 (95% CI (0.45-0.68), P < 0.01). The combined DOR was 5.41 (95% CI (3.64~ 8.06), P < 0.01), and the area under the SROC curve was 0.7468. Conclusions Serum PG provides medium levels of sensitivity and specificity for GC assessment. To be used in a clinical setting, further high-quality research must be performed and verified.
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22
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Selgrad M, Bornschein J, Kandulski A, Weigt J, Roessner A, Wex T, Malfertheiner P. Combined Gastric and Colorectal Cancer Screening-A New Strategy. Int J Mol Sci 2018; 19:E3854. [PMID: 30513960 PMCID: PMC6321419 DOI: 10.3390/ijms19123854] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 11/21/2018] [Accepted: 11/29/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates. METHODS Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 (61.6%) also underwent gastroscopy to correlate the results for serum pepsinogen I and II (sPG-I and sPG-II), sPG-I/II ratio, and anti-H. pylori antibodies with gastric histopathology findings (graded according to the updated Sydney classification and the Operative Link of Gastritis Assessment (OLGA) and the Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) systems). RESULTS H. pylori was found in 85 patients (30.5%). Chronic atrophic gastritis was diagnosed in 89 (31.9%) patients. High-risk OLGA (III⁻IV) stages were present in 24 patients, and high-risk OLGIM stages were present in 14 patients. There was an inverse correlation of sPG-I with the degree of atrophy and intestinal metaplasia (IM), as well as with the respective OLGA (r = -0.425; p < 0.001) and OLGIM (r = -0.303; p < 0.001) stages. A pathological sPG-I result was associated with a relative risk (RR) of 12.2 (95% confidence interval: 6.29⁻23.54; p < 0.001) for gastric preneoplastic changes. CONCLUSIONS The assessment of serum pepsinogen allows the identification of patients at increased risk of gastric cancer. A prevention strategy of combining a screening colonoscopy with a serological screening for preneoplastic gastric changes should be considered in the general population.
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Affiliation(s)
- Michael Selgrad
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
- Department of Internal Medicine I, University Hospital of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
| | - Jan Bornschein
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford University Hospitals, Headley Way, Oxford OX3 9DU, UK.
| | - Arne Kandulski
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
- Department of Internal Medicine I, University Hospital of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
| | - Jochen Weigt
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
| | - Albert Roessner
- Department of Pathology, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
| | - Thomas Wex
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
- Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Department of Molecular Genetics, Schwiesaustr. 12, 39124 Magdeburg, Germany.
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
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23
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Wilhelmsen M, Christensen IJ, Jørgensen LN, Madsen MR, Vilandt J, Hillig T, Klærke M, Nielsen KT, Laurberg S, Gawel S, Yang X, Davis G, Heijboer AM, Martens F, Nielsen HJ. Clean Colorectum at Diagnostic Colonoscopy: Subsequent Detection of Extracolonic Malignancies by Plasma Protein Biomarkers? BIOMARKERS IN CANCER 2018; 10:1179299X18776974. [PMID: 29872358 PMCID: PMC5977429 DOI: 10.1177/1179299x18776974] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 04/15/2018] [Indexed: 12/20/2022]
Abstract
Introduction Most of the subjects undergoing diagnostic colonoscopy do not have neoplastic bowel lesions. Potentially, some of the symptoms may therefore be caused by extracolonic malignancy, and subjects with persisting symptoms may need subsequent examinations. Blood-based, cancer-associated biomarkers may aid in directing the examinations for other specific malignant diseases. Methods EDTA plasma samples available from a previous prospective study of subjects undergoing diagnostic colonoscopy were used for analysis of 18 protein biomarkers. The study population of 3732 subjects included 400 patients with colorectal cancer (CRC) and 177 patients with extracolonic malignancies. Univariable analysis of the association of specific biomarkers and extracolonic cancers included those with 10 or more cases. Subsequently, reduced models of 4 or 6 biomarkers, respectively, were established by choosing those with the highest likelihood; age and sex were included as well. Results Univariable analyses showed that CyFra21-1 had an area under curve (AUC) of 0.87 for lung cancers (n = 33), CA19-9 had an AUC of 0.85 for pancreatic cancer (n = 22), CA125 had an AUC of 0.95 for ovary cancer (n = 16), B2M had an AUC of 0.81 for non-Hodgkin lymphoma (n = 12), and total prostate-specific antigen had an AUC of 0.99 for prostate cancer (n = 10). The multivariable analysis of 4 or 6 biomarkers plus age and sex as explanatory variables showed AUCs of 0.82 to 0.85 both for extracolonic cancers and CRC. The 4 biomarkers included in the model for detection of extracolonic cancers were CA125, hsCRP, CA19-9, and CyFra21-1; the 2 additional for the 6 biomarkers model were CEA and Galectin-3. Similarly, the 4 biomarkers included in the model for detection of CRC were CEA, CyFra21-1, Ferritin, and HE4; the two additional for the 6 biomarkers model were hsCRP and Pepsinogen 2. Conclusions Results of this study indicate that it may be possible to detect subjects that have an increased risk of extracolonic cancer following a colonoscopy without findings of neoplastic lesions. Combinations of various protein biomarkers may direct subsequent examination after colonoscopy with clean colorectum. The results, although preliminary, may form the basis for additional research directed both for primary examinations of subjects with symptoms of malignancy and subsequent examinations after colonoscopy.
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Affiliation(s)
- Michael Wilhelmsen
- Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Ib J Christensen
- Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Lars N Jørgensen
- Department of Surgical Gastroenterology, Bispebjerg Hospital, Copenhagen, Denmark
| | | | - Jesper Vilandt
- Department of Surgery, Hillerød Hospital, Hillerød, Denmark
| | - Thore Hillig
- Department of Clinical Biochemistry, Hillerød Hospital, Hillerød, Denmark
| | - Michael Klærke
- Department of Surgery, Horsens Hospital, Horsens, Denmark
| | - Knud T Nielsen
- Department of Surgery, Randers Hospital, Randers, Denmark
| | - Søren Laurberg
- Department of Surgical Gastroenterology, Aarhus Hospital THG, Aarhus, Denmark
| | - Susan Gawel
- Abbott Cancer Core R&D, Abbott Diagnostics Division, Abbott Park, Chicago, IL, USA
| | - Xiaoping Yang
- Abbott Cancer Core R&D, Abbott Diagnostics Division, Abbott Park, Chicago, IL, USA
| | - Gerard Davis
- Abbott Cancer Core R&D, Abbott Diagnostics Division, Abbott Park, Chicago, IL, USA
| | | | - Frans Martens
- Department of Clinical Chemistry, VUMC, Amsterdam, The Netherlands
| | - Hans J Nielsen
- Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
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24
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Kim JH, Lee SY, Lee SP, Kim JH, Sung IK, Park HS, Shim CS, Han HS. The histologic detection of Helicobacter pylori in seropositive subjects is affected by pathology and secretory ability of the stomach. Helicobacter 2018. [PMID: 29520884 DOI: 10.1111/hel.12480] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Helicobacter pylori is unevenly distributed in hypochlorhydric environments. The study aim was to elucidate the risk factors for a negative Giemsa staining finding in seropositive subjects by measuring the secretory ability of the stomach. METHODS Subjects aged over 18 years were included consecutively after endoscopic biopsy at gastric lesions with color or structural changes. Blood was sampled for the serum pepsinogen (PG) assay and H. pylori serology test. After excluding the subjects with past H. pylori eradication, the risk factors for a negative Giemsa staining finding in seropositive subjects were analyzed. RESULTS Among 872 included subjects, a discrepancy between the serum anti-H. pylori IgG and Giemsa staining findings was found in 158 (18.1%) subjects, including 145 Giemsa-negative, seropositive subjects. Gastric adenocarcinoma/adenoma (OR = 11.090, 95% CI = 3.490-35.236) and low serum PG II level (OR = 0.931, 95% CI = 0.899-0.963) were the independent risk factors for a negative Giemsa staining finding in seropositive subjects. The cutoff value of serum PG II level was 7.45 ng/mL (area under curve [AUC] = 0.904, 95% CI = 0.881-0.927). Follow-up studies of Giemsa staining at different sites of the stomach revealed that 75% of the Giemsa-negative seropositive subjects with adenocarcinoma are positive, whereas none of those with low serum PG II level of <7.45 ng/mL revealed positive findings. CONCLUSIONS The risk of a negative Giemsa staining finding in seropositive subjects is increased in gastric adenocarcinoma/adenoma specimens and in subjects with a diminished gastric secretory ability with low serum PG II level of <7.45 ng/mL. A false-negative Giemsa staining finding is common in subjects with adenocarcinoma, and therefore, additional biopsies at different sites should be performed in these subjects.
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Affiliation(s)
- Jun-Hyun Kim
- Departments of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Sun-Young Lee
- Departments of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Sang Pyo Lee
- Departments of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jeong Hwan Kim
- Departments of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - In-Kyung Sung
- Departments of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Hyung Seok Park
- Departments of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Chan Sup Shim
- Departments of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Hye Seung Han
- Departments of Pathology, Konkuk University School of Medicine, Seoul, Korea
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25
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COELHO LGV, MARINHO JR, GENTA R, RIBEIRO LT, PASSOS MDCF, ZATERKA S, ASSUMPÇÃO PP, BARBOSA AJA, BARBUTI R, BRAGA LL, BREYER H, CARVALHAES A, CHINZON D, CURY M, DOMINGUES G, JORGE JL, MAGUILNIK I, MARINHO FP, MORAES-FILHO JPD, PARENTE JML, PAULA-E-SILVA CMD, PEDRAZZOLI-JÚNIOR J, RAMOS AFP, SEIDLER H, SPINELLI JN, ZIR JV. IVTH BRAZILIAN CONSENSUS CONFERENCE ON HELICOBACTER PYLORI INFECTION. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:97-121. [PMID: 30043876 DOI: 10.1590/s0004-2803.201800000-20] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 02/22/2018] [Indexed: 02/06/2023]
Abstract
ABSTRACT Significant progress has been obtained since the III Brazilian Consensus Conference on H. pylori infection held in 2012, in Bento Gonçalves, Brazil, and justify a fourth meeting to establish updated guidelines on the current management of H. pylori infection. Therefore, the Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM), association linked to Brazilian Federation of Gastroenterology (FBG) held its fourth meeting again in Bento Gonçalves, RS, Brazil, on August 25-27, 2017. Twenty-six delegates, including gastroenterologists, endoscopists, and pathologists from the five regions of Brazil as well as one international guest from the United States, participated in the meeting. The participants were invited based on their knowledge and contribution to the study of H. pylori infection. The meeting sought to review different aspects of treatment for infection; establish a correlation between infection, dyspepsia, intestinal microbiota changes, and other disorders with a special emphasis on gastric cancer; and reassess the epidemiological and diagnostic aspects of H. pylori infection. Participants were allocated into four groups as follows: 1) Epidemiology and Diagnosis, 2) Dyspepsia, intestinal microbiota and other afections, 3) Gastric Cancer, and, 4) Treatment. Before the consensus meeting, participants received a topic to be discussed and prepared a document containing a recent literature review and statements that should be discussed and eventually modified during the face-to-face meeting. All statements were evaluated in two rounds of voting. Initially, each participant discussed the document and statements with his group for possible modifications and voting. Subsequently, during a second voting in a plenary session in the presence of all participants, the statements were voted upon and eventually modified. The participants could vote using five alternatives: 1) strongly agree; 2) partially agree; 3) undecided; 4) disagree; and 5) strongly disagree. The adopted consensus index was that 80% of the participants responded that they strongly or partially agreed with each statement. The recommendations reported are intended to provide the most current and relevant evidences to management of H. pylori infection in adult population in Brazil.
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Abstract
BACKGROUND Even though mass gastric cancer screening is controversial in Western countries, diverse strategies have been proposed in intermediate-risk to high-risk areas. AIM The aim of this study was to determine the long-term accuracy of the pepsinogen test (PG) for early diagnosis of gastric cancer. PARTICIPANTS AND METHODS A cohort of inhabitants from the Northern part of Portugal, aged between 40 and 74 years (n=5913), subjected to the PG test (PGI≤70 ng/ml and PGI/PGII≤3), were followed up between November 2006 and December 2015. The diagnosis of gastric cancer was determined through linkage to the population-based registry of cancer [North Region Cancer Registry of Portugal (RORENO)]. RESULTS Twenty-six gastric cancers were diagnosed (0.4%): nine (4%) among individuals 'positive' for the PG test (n=225) and 15 (0.3%) among those who were 'negative' (n=5688) [hazard ratio=12.7; 95% confidence interval (CI): 5.6-28.6]. Individuals with a 'negative PG test' had a 3-year risk of gastric cancer of 0.1%, representing a sensitivity of 35% (95% CI: 17-56%), globally, and of 58% (95% CI: 28-85%) at 3 years follow-up. The median survival rate in both groups was over 24 months. CONCLUSION The PG test was found to be suboptimal as a screening test and, if used (before upper gastrointestinal endoscopy), it is mandatory to repeat it after 3 years.
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27
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Song M, Camargo MC, Weinstein SJ, Murphy G, Freedman ND, Koshiol J, Stolzenberg-Solomon RZ, Abnet CC, Männistö S, Albanes D, Rabkin CS. Serum pepsinogen 1 and anti-Helicobacter pylori IgG antibodies as predictors of gastric cancer risk in Finnish males. Aliment Pharmacol Ther 2018; 47:494-503. [PMID: 29243850 PMCID: PMC5776724 DOI: 10.1111/apt.14471] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 10/29/2017] [Accepted: 11/23/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Serum pepsinogen 1 (SPG1) and anti-Helicobacter pylori serology have been used for gastric risk stratification in Asia. AIM To assess utility of these markers in a Western population. METHODS SPG1 measurements were available for 21 895 Finnish male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We used Cox proportional hazards models adjusted for potential confounders to estimate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI) for low SPG1 (<25 μg/L). In a subset (n = 3555) with anti-H. pylori serology, these markers jointly defined the following: Group A (H. pylori[-], SPG1[normal]; reference group), Group B (H. pylori[+], SPG1[normal]), Group C (H. pylori[+], SPG1[low]) and Group D (H. pylori[-], SPG1[low]). Odds ratios (ORs) and 95% CI were calculated using multivariate logistic regression. RESULTS There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Pre-diagnostic low SPG1 was significantly associated with increased gastric cancer risk (HR 2.68, 95% CI 1.99-3.61). Among subjects with both SPG1 and H. pylori serology, groups B, C and D had increased gastric cancer ORs (95% CI) of 1.79 (1.21-2.64), 3.85 (2.36-6.28) and 6.35 (2.20-18.34), respectively. CagA seropositives had significantly higher ORs than CagA seronegatives within group B (Pheterogeneity = 0.01). For groups B and C, repeat SPG1 level at 3 years did not further stratify gastric cancer risk. CONCLUSIONS Low SPG1 was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.
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Affiliation(s)
- Minkyo Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - M. Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Stephanie J. Weinstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Gwen Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Neal D. Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Jill Koshiol
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Rachael Z. Stolzenberg-Solomon
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Christian C. Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Satu Männistö
- Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland
| | - Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Charles S. Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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28
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Trends in gastric cancer mortality and in the prevalence of Helicobacter pylori infection in Portugal. Eur J Cancer Prev 2018; 25:275-81. [PMID: 26186469 DOI: 10.1097/cej.0000000000000183] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Portugal has the highest gastric cancer mortality rates in Western Europe, along with high prevalences of Helicobacter pylori infection. Monitoring their trends is essential to predict the burden of this cancer. We aimed to quantify time trends in gastric cancer mortality in Portugal and in each administrative region, and to compute short-term predictions, as well as to describe the prevalence of H. pylori infection, through a systematic review. Joinpoint analyses were used to identify significant changes in sex-specific trends in gastric cancer age-standardized mortality rates (ASMR) and to estimate annual percent changes (APC). The most recent trends were considered to compute estimates up to 2020 by adjusting Poisson regression models. We searched PubMed and IndexRMP to identify studies carried out in Portugal reporting the prevalence of H. pylori. Gastric cancer mortality has been decreasing in Portugal since 1971 in men (from ASMR=55.3/100 000; APC=-2.4, 95% confidence interval: -2.5 to -2.3) and since 1970 in women (from ASMR=28.0/100 000; APC=-2.8, 95% confidence interval: -2.9 to -2.7), although large regional differences were observed. Predicted ASMR for 2015 and 2020 were 18.8/100 000 and 16.7/100 000 for men and 8.5/100 000 and 7.4/100 000 for women, respectively. The prevalence of H. pylori varied from almost 5% at 0.5-2 years to just over 90% at 70 years or more. No consistent variation was observed since the 1990s. The downward trends in mortality rates are expected to remain in the next decades. The high prevalence of H. pylori infection across age groups and studies from different periods shows a large potential for decrease in the burden of gastric cancer in Portugal.
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29
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Loong TH, Soon NC, Nik Mahmud NRK, Naidu J, Rani RA, Abdul Hamid N, Elias MH, Mohamed Rose I, Tamil A, Mokhtar NM, Raja Ali RA. Serum pepsinogen and gastrin-17 as potential biomarkers for pre-malignant lesions in the gastric corpus. Biomed Rep 2017; 7:460-468. [PMID: 29181158 DOI: 10.3892/br.2017.985] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 08/21/2017] [Indexed: 02/07/2023] Open
Abstract
There is a lack of non-invasive screening modalities to diagnose chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). Thus, the aim of the present study was to determine the sensitivity and specificity of serum pepsinogen I (PGI), PGI:II, the PGI:II ratio and gastrin-17 (G-17) in diagnosing CAG and IM, and the correlations between these serum biomarkers and pre-malignant gastric lesions. A cross-sectional study of 72 patients (82% of the calculated sample size) who underwent oesophageal-gastro-duodenoscopy for dyspepsia was performed in the present study. The mean age of the participants was 56.2±16.2 years. Serum PGI:I, PGI:II, G-17 and Helicobacter pylori antibody levels were measured by enzyme-linked immunosorbent assay. Median levels of PGI:I, PGI:II, the PGI:II ratio and G-17 for were 129.9 µg/l, 10.3 µg/l, 14.7 and 4.4 pmol/l, respectively. Subjects with corpus CAG/IM exhibited a significantly lower PGI:II ratio (7.2) compared with the control group (15.7; P<0.001). Histological CAG and IM correlated well with the serum PGI:II ratio (r=-0.417; P<0.001). The cut-off value of the PGI:II ratio of ≤10.0 demonstrated high sensitivity (83.3%), specificity (77.9%) and area under the receiver operating characteristic curve of 0.902 in detecting the two conditions. However, the sensitivity was particularly low at a ratio of ≤3.0. The serum PGI:II ratio is a sensitive and specific marker to diagnose corpus CAG/IM, but at a high cut-off value. This ratio may potentially be used as an outpatient, non-invasive biomarker for detecting corpus CAG/IM.
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Affiliation(s)
- Tan Han Loong
- Unit of Gastroenterology and Hepatology, Department of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
| | - Ngiu Chai Soon
- Unit of Gastroenterology and Hepatology, Department of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
| | - Nik Ritza Kosai Nik Mahmud
- Unit of Upper Gastrointestinal and Bariatric Surgery, Department of Surgery, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
| | - Jeevinesh Naidu
- Unit of Gastroenterology and Hepatology, Department of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
| | - Rafiz Abdul Rani
- Unit of Gastroenterology and Hepatology, Department of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia.,Faculty of Medicine, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
| | - Nazefah Abdul Hamid
- Department of Physiology, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia.,Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, 71800 Negeri Sembilan, Malaysia
| | - Marjanu Hikmah Elias
- Department of Physiology, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
| | - Isa Mohamed Rose
- Department of Pathology, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
| | - Azmi Tamil
- Department of Community Health, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
| | - Norfilza M Mokhtar
- Department of Physiology, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
| | - Raja Affendi Raja Ali
- Unit of Gastroenterology and Hepatology, Department of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia
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30
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Leja M, Camargo MC, Polaka I, Isajevs S, Liepniece-Karele I, Janciauskas D, Rudzite D, Kikuste I, Vanags A, Kojalo I, Folkmanis V, Kirsners A, Tolmanis I, Rabkin CS. Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays. Helicobacter 2017; 22:10.1111/hel.12393. [PMID: 28557128 PMCID: PMC5847288 DOI: 10.1111/hel.12393] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy. METHODS We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs histological diagnosis were calculated using both the manufacturers' and optimized cutoffs. RESULTS Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all P-values<.01). Based on manufacturers' cutoffs, sensitivities, specificities and areas under the ROC curve for detecting moderate to severe histological corpus atrophy by PgI/PgII were 44%/91%/0.70, 56%/84%/0.76, and 52%/90%/0.77 for Biohit, Vector Best and Eiken, respectively. Cutoffs optimized by ROC or data mining analyses did not substantially improve test performance. CONCLUSIONS Commercial assays for pepsinogen have good relative agreement but are imperfect tests for clinical diagnosis of gastric atrophy. IMPACT Pepsinogen testing alone does not provide sufficient information for gastric cancer risk stratification. Future investigations should focus on other potential markers, in combination with pepsinogens.
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Affiliation(s)
- Marcis Leja
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia,Department of Research, Riga East University Hospital, Riga, Latvia,Digestive Diseases Centre GASTRO, Riga, Latvia
| | - M. Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, United States
| | - Inese Polaka
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia,Faculty of Computer Sciences and Information Technology, Riga Technical University, Latvia
| | - Sergejs Isajevs
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia,Department of Research, Riga East University Hospital, Riga, Latvia,Academic Histology laboratory, Riga, Latvia
| | - Inta Liepniece-Karele
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia,Department of Research, Riga East University Hospital, Riga, Latvia,Academic Histology laboratory, Riga, Latvia
| | | | - Dace Rudzite
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia,Department of Research, Riga East University Hospital, Riga, Latvia
| | - Ilze Kikuste
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia,Digestive Diseases Centre GASTRO, Riga, Latvia
| | | | - Ilona Kojalo
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia,Department of Research, Riga East University Hospital, Riga, Latvia
| | - Valdis Folkmanis
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Arnis Kirsners
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia,Department of Research, Riga East University Hospital, Riga, Latvia,Faculty of Computer Sciences and Information Technology, Riga Technical University, Latvia
| | | | - Charles S. Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, United States
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31
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Tong Y, Wu Y, Song Z, Yu Y, Yu X. The potential value of serum pepsinogen for the diagnosis of atrophic gastritis among the health check-up populations in China: a diagnostic clinical research. BMC Gastroenterol 2017; 17:88. [PMID: 28728545 PMCID: PMC5520218 DOI: 10.1186/s12876-017-0641-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 06/29/2017] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The aim of this study is to assess the validity of the measurement of pepsinogen as a screening test for chronic atrophic gastritis (AG) in health check-up populations in China. METHODS Patients from consecutive regular health check-up were enrolled from January 2014 to June 2015. Endoscopy, combined with monitoring the Helicobacter pylori (Hp) infections, and measuring the serum pepsinogen (PG) were used to determine the diagnostic accuracy of PG for the screening of atrophic gastritis. Histopathology was assessed by the Operative Link on Gastritis Assessment (OLGA) system. Statistical analysis was performed using SPSS statistical software. RESULTS The total Hp infection rate was 40%. Based on pathology, the 996 participants were divided into three groups: non-atrophic (NAG), mild-moderate atrophic (MAG): stage I and II of the OLGA classification, and severe atrophic (SAG): stage III and IV of the OLGA classification. Compared with NAG and MAG groups, PGR decreased significantly in SAG group (p < 0.05). PGI and PGII levels were significantly elevated in Hp-positive group, while the PGR was markedly decreased (p < 0.01). When MAG and SAG groups were combined and compared with NAG group, the best cutoff value for atrophy diagnosis was PGI ≤50.3 ng/ml; the cutoff value in Hp-negative group was absolutely higher than in Hp-positive group. When NAG and MAG groups were combined and compared with the SAG group, the best cutoff value for diagnosis of severe atrophy was at PGR ≤4.28. The cutoff values in Hp-negative and Hp-positive groups were calculated at PGR ≤6.28 and ≤4.28, respectively. CONCLUSIONS Pepsinogens play an important role in the identification of patients with atrophic gastritis and severe AG. Use of different cutoff values of PG for Hp-negative and Hp-positive groups may offer greater efficacy in the diagnosis of AG.
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Affiliation(s)
- Yuling Tong
- International HealthCare Center, The Second Affiliated Hospital of Zhejiang University, School of Medicine, NO.88 Jiefang Road, Hangzhou, Zhejiang Province, People's Republic of China
| | - Yulian Wu
- General Surgery Department, The Second Affiliated Hospital of Zhejiang University, School of Medicine, NO.88 Jiefang Road, Hangzhou, Zhejiang Province, People's Republic of China.
| | - Zhenya Song
- International HealthCare Center, The Second Affiliated Hospital of Zhejiang University, School of Medicine, NO.88 Jiefang Road, Hangzhou, Zhejiang Province, People's Republic of China.
| | - Yingying Yu
- International HealthCare Center, The Second Affiliated Hospital of Zhejiang University, School of Medicine, NO.88 Jiefang Road, Hangzhou, Zhejiang Province, People's Republic of China
| | - Xinyan Yu
- International HealthCare Center, The Second Affiliated Hospital of Zhejiang University, School of Medicine, NO.88 Jiefang Road, Hangzhou, Zhejiang Province, People's Republic of China
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Areia M, Spaander MC, Kuipers EJ, Dinis-Ribeiro M. Endoscopic screening for gastric cancer: A cost-utility analysis for countries with an intermediate gastric cancer risk. United European Gastroenterol J 2017; 6:192-202. [PMID: 29511549 DOI: 10.1177/2050640617722902] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 07/03/2017] [Indexed: 12/21/2022] Open
Abstract
Background Endoscopic screening for gastric cancer is debatable in countries with an intermediate risk. Objective The objective of this article is to determine the cost-utility of screening strategies for gastric cancer in a European country. Methods We conducted a cost-utility analysis using a Markov model comparing three screening strategies versus no screening: stand-alone upper endoscopy, endoscopy combined with a colorectal cancer screening colonoscopy after a positive faecal occult blood test or pepsinogens serologic screening. Clinical data were collected from systematic reviews, costs from published national data and utilities as quality-adjusted life years (QALY). The primary outcome was the incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were performed. The threshold was set at €37,000 (2016 prices). Results Upper endoscopy combined with screening colonoscopy (every 10 or 5 years) had an ICER of 15,407/QALY and €30,908/QALY respectively, stand-alone endoscopic screening (every five years) an ICER of €70,693/QALY and pepsinogens screening an ICER of €143,344/QALY. Sensitivity analyses revealed that only endoscopic costs <€75, a provision of only three endoscopies per patient or a gastric cancer risk >25/100,000 would make stand-alone endoscopic screening cost-effective. Conclusion Endoscopic gastric cancer screening in Europe can be cost-effective if combined with a screening colonoscopy in countries with a gastric cancer risk ≥10 per 100,000.
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Affiliation(s)
- Miguel Areia
- Center for Research in Health Technologies and Information Systems (CINTESIS), Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
- Gastroenterology Department, Portuguese Oncology Institute of Coimbra, Coimbra, Portugal
| | - Manon Cw Spaander
- Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, Zuid-holland, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, Zuid-holland, The Netherlands
| | - Mário Dinis-Ribeiro
- Center for Research in Health Technologies and Information Systems (CINTESIS), Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
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Nam SY, Jeon SW, Lee HS, Kwon YH, Park H, Choi JW. Long-term follow-up of pepsinogen I/II ratio after eradication of Helicobacter pylori in patients who underwent endoscopic mucosal resection for gastric cancer. Dig Liver Dis 2017; 49:500-506. [PMID: 28057446 DOI: 10.1016/j.dld.2016.12.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 12/06/2016] [Accepted: 12/09/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Although the pepsinogen I/II (PGI/II) ratio after Helicobacter pylori eradication is recovered at short-term follow-up, long-term follow-up studies of PGI/II are rare. METHODS A total of 773 patients with gastric cancer who underwent endoscopic resection and pepsinogen and H. pylori tests were enrolled. H. pylori was eradicated in these patients. Endoscopic and pepsinogen tests were performed every year. A low PGI/II ratio was defined as ≤3. RESULTS The PGI/II ratio was higher in non-infected patients (n=275, 4.99) than infected patients (n=498, 3.53). After H. pylori eradication, the PGI/II ratio increased to 5.81 and 5.63 after 1 and 2 years (each p<0.05). The PGI/II ratio in the non-eradication group decreased to 3.94 and 2.75 after 1 and 2 years. The PGI/II ratio in the H. pylori eradication group became similar to that of the H. pylori-negative group at 3 (4.48 vs. 4.34), 4 (4.88 vs. 4.34), and 5 years (4.89 vs. 4.23). The adjusted odds ratios for a lower PG I/II ratio in the non-eradication group compared to the eradication group were 4.78 (95% CI 2.15-10.67) after 1year and 8.13 (95% CI 2.56-25.83) after 2 years. CONCLUSIONS After H. pylori eradication, the PGI/II ratio increased and was similar to that of H. pylori-negative controls for up to 5 years of follow-up.
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Affiliation(s)
- Su Youn Nam
- Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, South Korea
| | - Seong Woo Jeon
- Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, South Korea.
| | - Hyun Seok Lee
- Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, South Korea
| | - Yong Hwan Kwon
- Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, South Korea
| | - Haeyoon Park
- Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, South Korea
| | - Jin Woo Choi
- Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, South Korea
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Wu F, Mao M, Cen Y, Yang H, Qin Z, Ma L. Copolymerization of Eu(TTA)3Phen doped styrene and methyl methacrylate nanoparticles and use in quantitative detection of pepsinogen. RSC Adv 2017. [DOI: 10.1039/c6ra27071a] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
High fluorescence intensity nanoparticles were prepared by copolymerization of Eu(TTA)3Phen doped styrene and methyl methacrylate.
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Affiliation(s)
- Feng Wu
- Division of Life Science and Health
- Graduate School at Shenzhen
- Tsinghua University
- Shenzhen
- P. R. China
| | - Mao Mao
- Division of Life Science and Health
- Graduate School at Shenzhen
- Tsinghua University
- Shenzhen
- P. R. China
| | - Yu Cen
- Division of Life Science and Health
- Graduate School at Shenzhen
- Tsinghua University
- Shenzhen
- P. R. China
| | - Hongtian Yang
- Shenzhen College of International Education
- Shenzhen
- P. R. China
| | - Zhifeng Qin
- Shenzhen Entry-Exit Inspection and Quarantine Bureau of the People's Republic of China (SZCIQ)
- Shenzhen
- P. R. China
| | - Lan Ma
- Division of Life Science and Health
- Graduate School at Shenzhen
- Tsinghua University
- Shenzhen
- P. R. China
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Huang RG, Xiao HL, Zhou B, Song XH, Zhang J, Wang CM, Jiang YH, Chen DZ, Huang B. Serum Pepsinogen Levels Are Correlated With Age, Sex and the Level of Helicobacter pylori Infection in Healthy Individuals. Am J Med Sci 2016; 352:481-486. [DOI: 10.1016/j.amjms.2016.08.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Revised: 08/08/2016] [Accepted: 08/09/2016] [Indexed: 12/20/2022]
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Miftahussurur M, Sharma RP, Shrestha PK, Maharjan RK, Shiota S, Uchida T, Sato H, Yamaoka Y. Helicobacter pylori Infection and Gastric Mucosal Atrophy in Two Ethnic Groups in Nepal. Asian Pac J Cancer Prev 2016; 16:7911-6. [PMID: 26625820 DOI: 10.7314/apjcp.2015.16.17.7911] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Serum anti-Helicobacter pylori antibodies and pepsinogens (PGs) have been used as gastric cancer screening and gastric mucosal status markers. Nepal is a low risk country for gastric cancer. However, the mountainous populace in the northern region culturally linked to Tibet as well as Bhutan, a neighboring country, have a high risk of GC. We collected gastric biopsy specimens and sera from 146 dyspeptic patients living in Kathmandu, Nepal. We also examined the sera of 80 volunteers living in the mountainous regions of the Himalayas. The optimal cut-off was calculated for serum biomarkers against the histology. Kathmandu patients (43.8%) were serologically positive for H. pylori infection, which was significantly lower than that for the mountainous (61.3%, P = 0.01). The same results also found in the prevalence of PG-positivity, PG I levels and PG I/II ratios (P = 0.001, P <0.0001 and P = 0.03, respectively). Moreover, the PG I/II ratios were significantly, and inversely correlated with the OLGA score (r = -0.33, P <0.009). The low incidence of gastric cancer in Nepal can be attributed to low gastric mucosal atrophy. However, the mountainous subjects have high-risk gastric mucosal status, which could be considered a high-risk population in Nepal.
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Affiliation(s)
- Muhammad Miftahussurur
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan E-mail :
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Rugge M, Genta RM, Graham DY, Di Mario F, Vaz Coelho LG, Kim N, Malfertheiner P, Sugano K, Tsukanov V, Correa P. Chronicles of a cancer foretold: 35 years of gastric cancer risk assessment. Gut 2016; 65:721-5. [PMID: 26927528 PMCID: PMC4853570 DOI: 10.1136/gutjnl-2015-310846] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Accepted: 12/15/2015] [Indexed: 12/14/2022]
Affiliation(s)
- Massimo Rugge
- Department of Medicine DIMED Pathology and Cytopathology Unit, University of Padova, Padova, Italy,Tumor Registry of the Veneto Region, Padova, Italy
| | - Robert M Genta
- Miraca Life Sciences Research Institute, Irving, Texas, USA,University of Texas Southwestern Medical School, Dallas, Texas, USA
| | - David Y Graham
- Department of Medicine, Michael E. De Bakey Veterans Affairs Medical Center, and Baylor College of Medicine, Houston, Texas, USA
| | - Francesco Di Mario
- Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy
| | - Luiz Gonzaga Vaz Coelho
- Institute Alfa of Gastroenterology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, South Korea
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology & Infectious Diseases, Otto-von-Guericke University, University Medical Center of Magdeburg, Magdeburg, Germany
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Vladislav Tsukanov
- State Scientific Medical Research Institute for Northern Problems of Siberian Division of Russian Academy of Medical Sciences, Krasnoyarsk, Russia
| | - Pelayo Correa
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Yeh JM, Hur C, Ward Z, Schrag D, Goldie SJ. Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis. Gut 2016; 65:563-74. [PMID: 25779597 PMCID: PMC4573370 DOI: 10.1136/gutjnl-2014-308588] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Accepted: 02/21/2015] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To estimate the cost-effectiveness of noncardia gastric adenocarcinoma (NCGA) screening strategies based on new biomarker and endoscopic technologies. DESIGN Using an intestinal-type NCGA microsimulation model, we evaluated the following one-time screening strategies for US men: (1) serum pepsinogen to detect gastric atrophy (with endoscopic follow-up of positive screen results), (2) endoscopic screening to detect dysplasia and asymptomatic cancer (with endoscopic mucosal resection (EMR) treatment for detected lesions) and (3) Helicobacter pylori screening and treatment. Screening performance, treatment effectiveness, cancer and cost data were based on published literature and databases. Subgroups included current, former and never smokers. Outcomes included lifetime cancer risk and incremental cost-effectiveness ratios (ICERs), expressed as cost per quality-adjusted-life-year (QALY) gained. RESULTS Screening the general population at age 50 years reduced the lifetime intestinal-type NCGA risk (0.24%) by 26.4% with serum pepsinogen screening, 21.2% with endoscopy and EMR and 0.2% with H. pylori screening/treatment. Targeting current smokers reduced the lifetime risk (0.35%) by 30.8%, 25.5%, and 0.1%, respectively. For all subgroups, serum pepsinogen screening was more effective and more cost-effective than all other strategies, although its ICER varied from $76,000/QALY (current smokers) to $105,400/QALY (general population). Results were sensitive to H. pylori prevalence, screen age and serum pepsinogen test sensitivity. Probabilistic sensitivity analysis found that at a $100,000/QALY willingness-to-pay threshold, the probability that serum pepsinogen screening was preferred was 0.97 for current smokers. CONCLUSIONS Although not warranted for the general population, targeting high-risk smokers for serum pepsinogen screening may be a cost-effective strategy to reduce intestinal-type NCGA mortality.
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Affiliation(s)
- Jennifer M. Yeh
- Center for Health Decision Science, Harvard School of Public Health, Boston, MA, USA
| | - Chin Hur
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA, USA
| | - Zachary Ward
- Center for Health Decision Science, Harvard School of Public Health, Boston, MA, USA
| | - Deborah Schrag
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Sue J. Goldie
- Center for Health Decision Science, Harvard School of Public Health, Boston, MA, USA
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Cho EJ, Kim HK, Jeong TD, Ko DH, Bae SE, Lee JS, Lee W, Choe JW, Chun S, Jung HY, Min WK. Method evaluation of pepsinogen I/II assay based on chemiluminescent immunoassays and comparison with other test methods. Clin Chim Acta 2016; 452:149-54. [PMID: 26585753 DOI: 10.1016/j.cca.2015.11.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 11/03/2015] [Accepted: 11/12/2015] [Indexed: 01/19/2023]
Abstract
BACKGROUND Serum pepsinogen (PG) I and the PG I/PG II ratio have been used for atrophic gastritis (AG) diagnosis for decades. Low levels of PG I and/or PG I/PG II are closely related to AG and predict the risk of gastric cancer. We evaluated the performance of the chemiluminescent immunoassay-based Architect Pepsinogen I/II assay. METHODS The evaluation consisted of determination of the precision, linearity, limit of blank (LoB), limit of detection (LoD) and method comparison with Eiken and Biohit assays. RESULTS The total CVs were below 5% for both PG I and PG II. Acceptable linearity was observed for PG I and PG II in their respective reportable ranges. The PG I LoB was 0.317ng/mL and the PG II LoB was 0.418ng/mL, and LoDs were 0.412ng/mL and 0.497ng/mL, respectively. Correlation analysis indicated that results of the Architect assay were comparable to those of the Eiken and Biohit assays, but the three methods lead to different estimations of the cancer risk. CONCLUSION The overall analytical performance of Architect Pepsinogen I/II assay is acceptable for the detection of patients with suspected AG. The categorization results of gastric cancer risk showed some difference among test methods suggesting the need for harmonization among the methods from vendors.
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Affiliation(s)
- Eun-Jung Cho
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyun-Ki Kim
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Tae-Dong Jeong
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dae-Hyun Ko
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Suh Eun Bae
- Health Screening & Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jong-Soo Lee
- Health Screening & Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Woochang Lee
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Jae Won Choe
- Health Screening & Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sail Chun
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hwoon-Yong Jung
- Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Won-Ki Min
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Huang YK, Yu JC, Kang WM, Ma ZQ, Ye X, Tian SB, Yan C. Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis. PLoS One 2015; 10:e0142080. [PMID: 26556485 PMCID: PMC4640555 DOI: 10.1371/journal.pone.0142080] [Citation(s) in RCA: 122] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2015] [Accepted: 10/16/2015] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection. METHODS We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar's test. Meta-regression and subgroup analyses were performed to explore study heterogeneity. RESULTS In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60-0.76), 0.73 (95% CI: 0.62-0.82), 2.57 (95% CI: 1.82-3.62), and 0.43 (95% CI: 0.34-0.54), 0.76 (95% CI: 0.72-0.80) and 6.01 (95% CI: 3.69-9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55-0.80), 0.88 (95% CI: 0.77-0.94), 5.80 (95% CI: 3.06-10.99), and 0.35 (95% CI: 0.24-0.51), 0.85 (95% CI: 0.82-0.88) and 16.50 (95% CI: 8.18-33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66-0.75), specificity of 0.79 (95% CI: 0.79-0.80), DOR of 6.92 (95% CI: 4.36-11.00), and AUC of 0.78 (95% CI: 0.72-0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51-0.60), specificity of 0.79 (95% CI: 0.76-0.82), DOR of 6.88 (95% CI: 2.30-20.60), and AUC of 0.77 (95% CI: 0.73-0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52-0.83), specificity of 0.84 (95% CI: 0.68-0.93), DOR of 11.51 (95% CI: 6.14-21.56), and AUC of 0.83 (95% CI: 0.80-0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72-0.85), specificity of 0.89 (95% CI: 0.85-0.93), DOR of 24.64 (95% CI: 6.95-87.37), and AUC of 0.87 (95% CI: 0.81-0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38-0.54), specificity of 0.93 (95% CI: 0.91-0.95), DOR of 19.86 (95% CI: 0.86-456.91), and AUC of 0.86 (95% CI: 0.52-1.00). CONCLUSION SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future.
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Affiliation(s)
- Ya-kai Huang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jian-chun Yu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- * E-mail:
| | - Wei-ming Kang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhi-qiang Ma
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Ye
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shu-bo Tian
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chao Yan
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Kishikawa H, Kimura K, Takarabe S, Kaida S, Nishida J. Helicobacter pylori Antibody Titer and Gastric Cancer Screening. DISEASE MARKERS 2015; 2015:156719. [PMID: 26494936 PMCID: PMC4606161 DOI: 10.1155/2015/156719] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Accepted: 09/06/2015] [Indexed: 02/07/2023]
Abstract
The "ABC method" is a serum gastric cancer screening method, and the subjects were divided based on H. pylori serology and atrophic gastritis as detected by serum pepsinogen (PG): Group A [H. pylori (-) PG (-)], Group B [H. pylori (+) PG (-)], Group C [H. pylori (+) PG (+)], and Group D [H. pylori (-) PG (+)]. The risk of gastric cancer is highest in Group D, followed by Groups C, B, and A. Groups B, C, and D are advised to undergo endoscopy, and the recommended surveillance is every three years, every two years, and annually, respectively. In this report, the reported results with respect to further risk stratification by anti-H. pylori antibody titer in each subgroup are reviewed: (1) high-negative antibody titer subjects in Group A, representing posteradicated individuals with high risk for intestinal-type cancer; (2) high-positive antibody titer subjects in Group B, representing active inflammation with high risk for diffuse-type cancer; and (3) low-positive antibody titer subjects in Group C, representing advanced atrophy with increased risk for intestinal-type cancer. In these subjects, careful follow-up with intervals of surveillance of every three years in (1), every two years in (2), and annually in (3) should be considered.
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Affiliation(s)
- Hiroshi Kishikawa
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
| | - Kayoko Kimura
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
| | - Sakiko Takarabe
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
| | - Shogo Kaida
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
| | - Jiro Nishida
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan
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Nejadi-Kelarijani F, Roshandel G, Semnani S, Ahmadi A, Faghani B, Besharat S, Akhavan-Tabib A, Amiriani T. Diagnostic values of serum levels of pepsinogens and gastrin-17 for screening gastritis and gastric cancer in a high risk area in northern Iran. Asian Pac J Cancer Prev 2015; 15:7433-6. [PMID: 25227854 DOI: 10.7314/apjcp.2014.15.17.7433] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is the second cause of cancer related death in the world. It may develop by progression from its precancerous condition, called gastric atrophy (GA) due to gastritis. The aim of this study was to evaluate the accuracy of serum levels of pepsinogens (Pg) and gastrin-17 (G17) as non-invasive methods to discriminate GA or GC (GA/GC) patients. MATERIALS AND METHODS Subjects referred to gastrointestinal clinics of Golestan province of Iran during 2010 and 2011 were invited to participate. Serum levels of PgI, PgII and G17 were measured using a GastroPanel kit. Based on the pathological examination of endoscopic biopsy samples, subjects were classified into four groups: normal, non-atrophic gastritis, GA, and GC. Receiver operating curve (ROC) analysis was used to determine cut-off values. Indices of validity were calculated for serum markers. RESULTS Study groups were normal individuals (n=74), non-atrophic gastritis (n=90), GA (n=31) and GC patients (n=30). The best cut-off points for PgI, PgI/II ratio, G17 and HP were 80 μg/L, 10, 6 pmol/L, and 20 EIU, respectively. PgI could differentiate GA/GC with high accuracy (AUC=0.83; 95%CI: 0.76-0.89). The accuracy of a combination of PgI and PgI/II ratio for detecting GA/GC was also relatively high (AUC=0.78; 95%CI: 0.70-0.86). CONCLUSIONS Our findings suggested PgI alone as well as a combination of PgI and PgI/II ratio are valid markers to differentiate GA/GC. Therefore, Pgs may be considered in conducting GC screening programs in high-risk areas.
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Affiliation(s)
- Fatemeh Nejadi-Kelarijani
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran E-mail :
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Areia M, Dinis-Ribeiro M, Rocha Gonçalves F. Cost-utility analysis of endoscopic surveillance of patients with gastric premalignant conditions. Helicobacter 2014; 19:425-36. [PMID: 25164596 DOI: 10.1111/hel.12150] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Progression of extensive gastric premalignant conditions to cancer might warrant surveillance programms. Recent guidelines suggest a 3-yearly endoscopic follow-up for these patients. Our aim was to determine the cost utility of endoscopic surveillance of patients with extensive gastric premalignant conditions such as extensive atrophy or intestinal metaplasia. MATERIALS AND METHODS A cost-utility economic analysis was performed from a societal perspective in Portugal using a Markov model to compare two strategies: surveillance versus no surveillance. Clinical data were collected from a systematic review of the literature, costs from published national data, and community utilities derived from a population study by the EuroQol questionnaire in terms of quality-adjusted life years (QALY). Population started at age 50, for a time horizon of 25 years and an annual discount rate of 3% was used for cost and effectiveness. Primary outcome was the incremental cost-effectiveness ratio (ICER) of a 3-yearly endoscopic surveillance versus no surveillance for a base case scenario and in deterministic and probabilistic sensitivity analysis. Secondary outcomes were ICER of 5- and 10-yearly endoscopic surveillance versus no surveillance. RESULTS Endoscopic surveillance every 3 years provided an ICER of € 18,336, below the adopted threshold of € 36,575 which corresponds to the proposed guideline limit of USD 50,000 and this strategy dominated surveillance every 5 or 10 years. Utilities for endoscopic treatment were relevant in deterministic analysis, while probabilistic analysis showed that in 78% of cases the model was cost-effective. CONCLUSIONS Endoscopic surveillance every 3 years of patients with premalignant conditions is cost-effective.
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Affiliation(s)
- Miguel Areia
- CINTESIS - Center for Research in Health Technologies and Information Systems, Faculty of Medicine, Porto University, Porto, Portugal; Gastroenterology Department, Portuguese Oncology Institute - Coimbra, Coimbra, Portugal
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Pasechnikov V, Chukov S, Fedorov E, Kikuste I, Leja M. Gastric cancer: prevention, screening and early diagnosis. World J Gastroenterol 2014; 20:13842-62. [PMID: 25320521 PMCID: PMC4194567 DOI: 10.3748/wjg.v20.i38.13842] [Citation(s) in RCA: 294] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2014] [Revised: 04/28/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach.
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Hamashima C. Current issues and future perspectives of gastric cancer screening. World J Gastroenterol 2014; 20:13767-13774. [PMID: 25320514 PMCID: PMC4194560 DOI: 10.3748/wjg.v20.i38.13767] [Citation(s) in RCA: 135] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Revised: 02/14/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries, which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques, namely, upper gastrointestinal endoscopy, serological testing, and “screen and treat” method were extensively reviewed. Moreover, the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand, serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date, the effectiveness of new techniques for gastric cancer screening has remained limited. However, endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening. To effectively introduce new techniques for gastric cancer screening in a community, incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies. In addition to effectiveness evaluation, the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening.
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Kishikawa H, Kaida S, Takarabe S, Miyoshi J, Matsukubo T, Miyauchi J, Tanaka Y, Miura S, Nishida J. Fundic gland polyps accurately predict a low risk of future gastric carcinogenesis. Clin Res Hepatol Gastroenterol 2014; 38:505-12. [PMID: 24637176 DOI: 10.1016/j.clinre.2014.01.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 01/14/2014] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Few reports have analyzed the clinical importance of sporadic fundic gland polyps (FGPs). The aim of this study was to investigate the relationship between sporadic FGPs and condition of the gastric mucosa stratified by serum pepsinogen levels and Helicobacter pylori antibody level. METHODS Three hundred and seventy-five subjects undergoing gastrointestinal endoscopy were enrolled. Subjects on proton pump inhibitors were excluded. Pathologically proven FGPs, and other endoscopic findings (reflux esophagitis, gastric and duodenal ulcer) were examined and serum pepsinogen levels, H. pylori antibody concentration and gastric juice pH were measured simultaneously. Subjects with normal serum pepsinogen and negative H. pylori antibodies were defined as having "low risk" stomachs, suggesting low risk of gastric carcinogenesis. RESULTS Of the 375 subjects, 44 showed FGPs. The prevalence of "low risk" stomach in subjects with and without FGPs was 98% and 48%, respectively. Multivariable logistic regression analysis indicated three variables as independent factors positively associated with "low risk" stomachs: FGPs (odds ratio [OR] 38.6), reflux esophagitis (OR 4.8), and age<60 years (OR 1.89). Gastric juice pH, which is associated with mucosal atrophy grade and low pH indicates less mucosal atrophy, was significantly lower in subjects with (1.64 ± 0.64) than without FGPs in "low risk" (1.94 ± 1.12) and "high risk" stomachs (3.99 ± 2.31). CONCLUSIONS Sporadic FGPs tend to be related to the least atrophic mucosa among non-gastric atrophy subjects without H. pylori infection, and can be used as predictors of a low risk of gastric carcinogenesis.
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Affiliation(s)
- Hiroshi Kishikawa
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, 272-8513 Chiba, Japan.
| | - Shogo Kaida
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, 272-8513 Chiba, Japan
| | - Sakiko Takarabe
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, 272-8513 Chiba, Japan
| | - Jun Miyoshi
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, 272-8513 Chiba, Japan
| | - Takashi Matsukubo
- Department of Epidemiology and Public Health, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, 261-8502 Chiba, Japan
| | - Jun Miyauchi
- Department of Pathology and Laboratory Medicine, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, 272-8513 Chiba, Japan
| | - Yoichi Tanaka
- Department of Pathology and Laboratory Medicine, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, 272-8513 Chiba, Japan
| | - Soichiro Miura
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513 Saitama, Japan
| | - Jiro Nishida
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, 272-8513 Chiba, Japan
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Lin JY, Huang ZS, Deng YB. Meta-analysis on validity of serum pepsinogen measurement for mass screening of gastric carcinoma in the high-risk population. Shijie Huaren Xiaohua Zazhi 2014; 22:3300-3306. [DOI: 10.11569/wcjd.v22.i22.3300] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the validity of measurement of serum pepsinogen as a screening test for gastric carcinoma in the high-risk population.
METHODS: We searched the databases including PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Data, VIP Journal Integration Platform and China Biology Medicine disc (CBM disc) for diagnostic tests using the serum pepsinogen test with pathological biopsy or X-ray examination (golden criteria) before January 2013. Two reviewers in-dependently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies according to quality assessment of diagnostic accuracy studies (QUADAS) items. The Meta-DiSc software (version 1.4) was used to conduct pooling on sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Heterogeneity test was performed and the summary receiver operating characteristic curve was plotted for calculating the area under the curve (AUC).
RESULTS: A total of 15 studies involving 184600 subjects were included. The results of meta-analysis showed that specificity, sensitivity, positive likelihood ratio, negative likelihood ratio and diagnostic ratio were 0.55 (95%CI: 0.51-0.58), 0.67 (95%CI: 0.67-0.68), 2.23 (95%CI: 1.71-2.92), 0.58 (95%CI: 0.46-0.73), and 4.33 (95%CI: 3.17-5.92), respectively. The AUC of the summary receiver operating characteristic curve was 0.73.
CONCLUSION: Current evidence shows that serum pepsinogen has a low sensitivity and a low specificity in the diagnosis of gastric carcinoma, and its diagnostic efficiency is medium.
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Choi HS, Lee SY, Kim JH, Sung IK, Park HS, Shim CS, Jin CJ. Combining the serum pepsinogen level and Helicobacter pylori antibody test for predicting the histology of gastric neoplasm. J Dig Dis 2014; 15:293-8. [PMID: 24602176 DOI: 10.1111/1751-2980.12144] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To determine whether the combination test of serum pepsinogen (PG) levels and Helicobacter pylori (H. pylori) antibody was effective for predicting the incidence and histology of gastric neoplasms. METHODS This study included asymptomatic Korean adults who underwent esophagogastroduodenoscopy with blood tests for PG levels and H. pylori immunoglobulin G antibody test on the same day. Participants with extragastric malignancy, history of H. pylori eradication or gastric neoplasms, or recent antacid medication were excluded. Gastric atrophy was defined as a serum PG I/II ratio ≤3.0 and PG I ≤70 ng/mL. The participants were classified into four groups according to the presence (+) or absence (-) of gastric atrophy and H. pylori infection. RESULTS Of the 3328 included participants, 17 were incidentally diagnosed as having either gastric adenoma or carcinoma. The incidence of gastric neoplasm was highest in the gastric atrophy (+)/H. pylori (-) group (4.17%; OR 25.8, P = 0.009), but the neoplasm exhibited the least advanced histology. The gastric atrophy (-)/H. pylori (-) group exhibited the lowest incidence of gastric neoplasm (0.17%) but the most advanced histology. CONCLUSION A combination of serum PG levels and H. pylori antibody test is useful for detecting gastric neoplasms based on the slow gastric carcinogenesis pathway progressing from gastric adenoma to Lauren's intestinal-type gastric cancer, but not for those with advanced histology such as Lauren's diffuse-type gastric cancer.
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Affiliation(s)
- Hong Seok Choi
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Farina A. Proximal fluid proteomics for the discovery of digestive cancer biomarkers. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 2014; 1844:988-1002. [DOI: 10.1016/j.bbapap.2013.10.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2013] [Revised: 09/15/2013] [Accepted: 10/22/2013] [Indexed: 12/13/2022]
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Abstract
Several reports of estimates for precancerous conditions for gastric adenocarcinoma can be found in the current literature. Our aim was to systematically review and estimate the prevalence of gastric precancerous conditions. Four databases (PubMed, Scopus, Web of Knowledge and EBSCO Academic Search Complete) were searched for original manuscripts addressing the presence of chronic atrophic gastritis (CAG) or intestinal metaplasia (IM). Subgroup analysis was carried out on methods of diagnosis, type of population, incidence of gastric cancer, sex, Helicobacter pylori status, age and extent of conditions. Overall, 107 studies were included. The worldwide prevalence of CAG in the general population was 33% (95% confidence interval: 26-41%) when considering biopsies (n=20 912) and 24% (19-29%) if serology (n=51 886) was used, whereas IM was found in 25% (19-30%) (n=30 960). Estimates for CAG were higher in countries with a high incidence of gastric cancer (42 vs. 23%), men (32 vs. 28%), H. pylori positive (46 vs. 17%) and if aged 40 years or older (48 vs. 22%). The prevalence of extensive conditions was 16% (12-20%) for CAG and 13% (9.0-17%) for IM. When comparing countries with high versus low to moderate incidence of gastric cancer, significant differences were achieved for CAG: 27% (12-36%) versus 7.3% (5.6-9.0%). Worldwide, one-third and one-fourth of individuals may harbour CAG and IM, respectively. In countries with a high incidence of gastric cancer, the prevalence of extensive conditions may increase up to 27% and these patients represent a high-risk population to whom endoscopic surveillance should be offered according to recent guidelines.
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