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Cheung KS, Chan AOO, Yu Wong BC. Intestinal‐type Gastric Cancer. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:120-138. [DOI: 10.1002/9781119756422.ch7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Risk assessment of metachronous gastric cancer development using OLGA and OLGIM systems after endoscopic submucosal dissection for early gastric cancer: a long-term follow-up study. Gastric Cancer 2023; 26:298-306. [PMID: 36609936 DOI: 10.1007/s10120-022-01361-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 12/27/2022] [Indexed: 01/09/2023]
Abstract
BACKGROUND Metachronous gastric cancer (MGC) may develop in patients undergoing curative endoscopic submucosal dissection for early gastric cancer. As gastritis and intestinal metaplasia are notable precursors to gastric cancer, we assessed MGC risk using the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM) systems. METHODS This retrospective cohort study classified the OLGA and OLGIM stages for 916 patients who had undergone endoscopic submucosal dissection for early gastric cancer between 2005 and 2015. MGC development was followed up until 2020 and risk factors were evaluated using the Cox proportional hazards regression analysis. RESULTS During a median follow-up of 94 months, MGC developed in 120 subjects. OLGA stages II ~ IV were significantly associated with increased MGC risk (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.05-3.19; HR 2.31, 95% CI 1.22-4.38; HR 2.36, 95% CI 1.16-4.78) in multivariable analysis, even after adjusting for the well-known positive predictor of Helicobacter pylori eradication. OLGIM stages II ~ IV also showed significant association (HR 2.86, 95% CI 1.29-6.54; HR 2.94, 95% CI 1.34-6.95; HR 3.64, 95% CI 1.60-8.29). 5-year cumulative incidence increased with each stage. Helicobacter pylori-eradicated patients with OLGIM stages 0 ~ II had significantly less MGC than non-eradicated patients (4.5% vs 11.8%, p = 0.022), which was not observed with OLGIM stages III ~ IV. CONCLUSIONS High OLGA and OLGIM stages are independent risk factors for metachronous gastric cancer, with the OLGIM staging system being a better predictor. Patients with OLGIM stages 0 ~ II are a subgroup that may benefit more from Helicobacter pylori eradication.
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Sakin A, Sahin S, Sakin A, Aldemir MN, Sakoglu N, Bayram I, Kotan MC. Factors affecting survival in operated gastric cancer. Surg Oncol 2023; 46:101887. [PMID: 36455334 DOI: 10.1016/j.suronc.2022.101887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/21/2022] [Accepted: 11/22/2022] [Indexed: 11/27/2022]
Abstract
In this study, our aim was to determine the possible effects of Helicobacter pylori(HP), chronic atrophic gastritis (CAG), and gastrointestinal metaplasia (GIM) on survival in operated bowel type gastric cancer patients (INT-GC). Among 548 patients, 347(63.3%) were male. The median age was 57 years. Disease-free survival (DFS) and overall survival (OS) were significantly shorter in patients with GIM than those in patients without GIM (log rank, P = 0.003 and log rank P = 0.003, respectively). Multivariate analysis showed that presence of GIM (HR, 2.1) was found to be an independent factor of worse DFS. In our study, stage pIII patients with GIM had significantly shorter DFS and OS than those without GIM (log rank p = 0.008 and log rank p = 0.001, respectively). However, in subgroup analysis of patients with GIM, there was no significant DFS and OS difference between patients with stage pI and pII disease (log rank p = 0.999, log rank p = 0.184 vs. log rank p = 0.409, log rank p = 0.281, respectively).
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Affiliation(s)
- Aysegul Sakin
- Department of Internal Medicine, University of Health Sciences, Taksim Research and Training Hospital, Istanbul, Turkey.
| | - Suleyman Sahin
- Department of Medical Oncology, University of Health Sciences, Van Research and Training Hospital, Van, Turkey.
| | - Abdullah Sakin
- Department of Medical Oncology, Yuzuncu Yil University Medical School, 65030, Van, Turkey; İstanbul Medipol University, Medical Oncology Department, Istanbul, Turkey.
| | - Mehmet Naci Aldemir
- Department of Medical Oncology, Yuzuncu Yil University Medical School, 65030, Van, Turkey.
| | - Nevin Sakoglu
- İstanbul Medipol University, General Surgery Department, Istanbul, Turkey.
| | - Irfan Bayram
- Department of Pathology, Yuzuncu Yil University Medical School, 65030, Van, Turkey.
| | - Mehmet Cetin Kotan
- Department of General Surgery, Yuzuncu Yil University Medical School, 65030, Van, Turkey.
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He Q, Liu L, Wei J, Jiang J, Rong Z, Chen X, Zhao J, Jiang K. Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review. Cell Death Dis 2022; 8:158. [PMID: 35379788 PMCID: PMC8979943 DOI: 10.1038/s41420-022-00962-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 12/13/2022]
Abstract
Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research.
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Affiliation(s)
- Qijin He
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Limin Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Jingge Wei
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Jiaying Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Zheng Rong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
| | - Jingwen Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
| | - Kui Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
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Fang JH, Zhou G, Yu W, Chen X, Sun YT, Li GX. Clinicopathological characteristics of gastric intraepithelial neoplasia: Analysis of 653 cases. Shijie Huaren Xiaohua Zazhi 2021; 29:1064-1070. [DOI: 10.11569/wcjd.v29.i18.1064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The high mortality rate of gastric carcinoma (GC) is becoming a serious public concern around the world. Gastric intraepithelial neoplasia (GIN) is believed to be the pre-invasive lesions of GC. Therefore, this study aimed to investigate the clinicopathological characteristics of GIN and explore the risk factors for gastric precancerous lesions.
AIM To analyze the clinical and pathological characteristics of GIN and identify its risk factors, so as to better guide the clinical diagnosis and treatment of GIN.
METHODS A total of 653 Chinese patients undergoing diagnostic gastroscopy at a single center from June 2010 to October 2020 were included. The demographic, endoscopic, and pathological characteristics were collected to identify the risk factors associated with GIN.
RESULTS There were 536 cases with low-grade gastric intraepithelial neoplasia (LGIN) (82.08%) and 117 cases with high-grade gastric intraepithelial neoplasia (HGIN) (17.92%). The gastric antrum was the most common location for GIN lesions (58.35%). The incidence of GIN lesions > 2 cm in the HGIN group (27/117, 23.08%) was twice as high as that of the LGIN group (56/536, 10.45%). The positive rate of atrophy and intestinal metaplasia improved as the age increased among patients 50-80 years old and > 60 years old, respectively. In addition, no statistical difference was observed in Helicobacter pylori infection rate between the LGIN and HGIN groups (P = 0.162).
CONCLUSION Advanced age, lesion located at the antrum, lesion size > 1 cm, and presence of atrophy or intestinal metaplasia in the gastric mucosa are risk factors for HGIN. LGIN patients with these risk factors are more likely to develop into HGIN. H. pylori infection has no statistical correlations with LGIN and HGIN.
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Affiliation(s)
- Jia-Heng Fang
- Department of Gastroenterology, Hangzhou Normal University Affiliated Hospital, Hangzhou 310015, Zhejiang Province, China
| | - Gang Zhou
- Department of Gastroenterology, Hangzhou Normal University Affiliated Hospital, Hangzhou 310015, Zhejiang Province, China
| | - Wei Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Xin Chen
- Department of Gastroenterology, Hangzhou Normal University Affiliated Hospital, Hangzhou 310015, Zhejiang Province, China
| | - Yi-Tian Sun
- Department of Gastroenterology, Hangzhou Normal University Affiliated Hospital, Hangzhou 310015, Zhejiang Province, China
| | - Guo-Xiong Li
- Department of Gastroenterology, Hangzhou Normal University Affiliated Hospital, Hangzhou 310015, Zhejiang Province, China
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Liu Y, Wang W, Li Y, Liu F, Zhang L, Tang T, Zang M, Zhang Y, Ding X. Risk assessment models of integrative medicine indicators for malignant transformation of chronic atrophic gastritis: A registry study protocol. JOURNAL OF TRADITIONAL CHINESE MEDICAL SCIENCES 2019. [DOI: 10.1016/j.jtcms.2019.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
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Dore MP, Cipolli A, Ruggiu MW, Manca A, Bassotti G, Pes GM. Helicobacter pylori eradication may influence timing of endoscopic surveillance for gastric cancer in patients with gastric precancerous lesions: A retrospective study. Medicine (Baltimore) 2018; 97:e9734. [PMID: 29369216 PMCID: PMC5794400 DOI: 10.1097/md.0000000000009734] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 01/05/2018] [Accepted: 01/09/2018] [Indexed: 02/07/2023] Open
Abstract
Chronic atrophic gastritis and intestinal metaplasia related to Helicobacter pylori infection, are major risk factors for gastric adenocarcinoma. Eradication of H pylori and endoscopy surveillance of precancerous lesions may reduce the risk and/or lead to early detection of gastric cancer improving survival. In this study, the progression of precancerous lesions after H pylori treatment was evaluated.Patients with incomplete or complete intestinal metaplasia and/or gastric atrophy at the index endoscopy, were examined for the extension/histological worsening of precancerous lesions at the endoscopy surveillance for gastric cancer. Progression of lesions was evaluated according to H pylori status, age, and sex. Cox proportional hazard regression model and Kaplan-Meier curves were used to evaluate the strength of predictors for lesions progression.Among 105 patients (61 women) H pylori negative patients showed a milder worsening of gastric lesions between index and surveillance endoscopy compared with patients positive for the infection (log-rank test: P < .0001, P = .012, and P = .032 for antrum, angulus, and corpus, respectively). The Cox regression model showed persistence of H pylori infection (hazard ratio = 4.436; P < .0001) as the only relevant factor for lesion progression, whereas age >65 years and sex were not significant predictors.According to literature our results demonstrate that H pylori eradication is the major factor able to delay gastric precancerous lesions progression. Time interval for endoscopic surveillance in patients negative for H pylori infection and with gastric precancerous lesions may be extended.
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Affiliation(s)
- Maria Pina Dore
- Dipartimento di Medicina Clinica e Sperimentale
- Baylor College of Medicine, Houston, Texas
| | | | - Matteo Walter Ruggiu
- Dipartimento di Scienze Chirurgiche e Microchirurgiche, University of Sassari, Sassari
| | - Alessandra Manca
- Dipartimento di Scienze Chirurgiche e Microchirurgiche, University of Sassari, Sassari
| | - Gabrio Bassotti
- Dipartimento di Medicina Clinica e Sperimentale, University of Perugia, Perugia, Italy
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Uotani T, Sugimoto M, Ichikawa H, Tanaka S, Nagashima H, Uchida T, Graham DY, Yamaoka Y. Prostate stem cell antigen gene TT genotype and development of intestinal metaplasia in Helicobacter pylori infection. J Dig Dis 2016; 17:20-27. [PMID: 26706772 PMCID: PMC4783456 DOI: 10.1111/1751-2980.12309] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 12/18/2015] [Accepted: 12/20/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Gastric cancer is etiologically related to interactions between Helicobacter pylori (H. pylori) infection, environmental and host factors. Gastric carcinoma is associated with a cascade of increasing atrophic gastric mucosal damage. Prostate stem cell antigen (PSCA) polymorphisms have been associated with an increased risk of gastric cancer. We aimed to examine the interaction between PSCA polymorphisms and H. pylori in the progression of H. pylori-related gastritis. METHODS The genotypes (TT, TC and CC) of PSCA single nucleotide polymorphism rs2294008 among H. pylori infected and uninfected Bhutanese were compared with the severity of H. pylori-related gastritis [neutrophils, monocytes, atrophy scores, H. pylori density, and the presence and extent of intestinal metaplasia (IM)] using the updated Sydney system. RESULTS Biopsies from 339 participants were included. The proportion of biopsies with IM was significantly (P < 0.05) greater in those with the TT genotype than in either those with the CT or CC genotype. Although no significant differences were found in inflammation or H. pylori density scores, the scores for IM at both gastric corpus and antrum among participants infected by H. pylori with the TT genotype was significantly (P < 0.05) greater than in the C allele carriers. CONCLUSION PSCA TT genotype is associated with a more than a threefold increase in the prevalence and the extent of gastric mucosal IM compared to C allele carriers among H. pylori-infected Bhutanese.
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Affiliation(s)
- Takahiro Uotani
- Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, USA
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Japan
| | - Hitomi Ichikawa
- First department of Medicine, Hamamatsu University school of Medicine, Hamamatsu, Japan
| | - Shingo Tanaka
- Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, USA
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | | | - Tomohisa Uchida
- Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu, Japan
| | - David Y. Graham
- Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, USA
| | - Yoshio Yamaoka
- Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, USA
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
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RAD51 G135C genetic polymorphism and their potential role in gastric cancer induced by Helicobacter pylori infection in Bhutan. Epidemiol Infect 2015; 144:234-40. [PMID: 26119522 DOI: 10.1017/s0950268815001430] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan--a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients.
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Hwang JJ, Lee DH, Lee AR, Yoon H, Shin CM, Park YS, Kim N. Characteristics of gastric cancer in peptic ulcer patients with Helicobacter pylori infection. World J Gastroenterol 2015; 21:4954-4960. [PMID: 25945009 PMCID: PMC4408468 DOI: 10.3748/wjg.v21.i16.4954] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 11/26/2014] [Accepted: 01/16/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the incidence and clinical characteristics of gastric cancer (GC) in peptic ulcer patients with Helicobacter pylori (H. pylori) infection.
METHODS: Between January 2003 and December 2013, the medical records of patients diagnosed with GC were retrospectively reviewed. Those with previous gastric ulcer (GU) and H. pylori infection were assigned to the HpGU-GC group (n = 86) and those with previous duodenal ulcer (DU) disease and H. pylori infection were assigned to the HpDU-GC group (n = 35). The incidence rates of GC in the HpGU-GC and HpDU-GC groups were analyzed. Data on demographics (age, gender, peptic ulcer complications and cancer treatment), GC clinical characteristics [location, pathological diagnosis, differentiation, T stage, Lauren’s classification, atrophy of surrounding mucosa and intestinal metaplasia (IM)], outcome of eradication therapy for H. pylori infection, esophagogastroduodenoscopy number and the duration until GC onset were reviewed. Univariate and multivariate analyses were performed to identify factors influencing GC development. The relative risk of GC was evaluated using a Cox proportional hazards model.
RESULTS: The incidence rates of GC were 3.60% (86/2387) in the HpGU-GC group and 1.66% (35/2098) in the HpDU-GC group. The annual incidence was 0.41% in the HpGU-GC group and 0.11% in the HpDU-GC group. The rates of moderate-to-severe atrophy of the surrounding mucosa and IM were higher in the HpGU-GC group than in the HpDU-GC group (86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P < 0.05). In the univariate analysis, atrophy of surrounding mucosa, IM and eradication therapy for H. pylori infection were significantly associated with the development of GC (P < 0.05). There was no significant difference in the prognosis of GC patients between the HpGU-GC and HpDU-GC groups (P = 0.347). The relative risk of GC development in the HpGU-GC group compared to that of the HpDU-GC group, after correction for age and gender, was 1.71 (95%CI: 1.09-2.70; P = 0.02).
CONCLUSION: GU patients with H. pylori infection had higher GC incidence rates and relative risks. Atrophy of surrounding mucosa, IM and eradication therapy were associated with GC.
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Shen XR, Chai J, Feng R, Liu TZ, Tong GX, Cheng J, Li KC, Xie SY, Shi Y, Wang DB. Refining and validating a two-stage and web-based cancer risk assessment tool for village doctors in China. Asian Pac J Cancer Prev 2015; 15:10683-90. [PMID: 25605159 DOI: 10.7314/apjcp.2014.15.24.10683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
The big gap between efficacy of population level prevention and expectations due to heterogeneity and complexity of cancer etiologic factors calls for selective yet personalized interventions based on effective risk assessment. This paper documents our research protocol aimed at refining and validating a two-stage and web- based cancer risk assessment tool, from a tentative one in use by an ongoing project, capable of identifying individuals at elevated risk for one or more types of the 80% leading cancers in rural China with adequate sensitivity and specificity and featuring low cost, easy application and cultural and technical sensitivity for farmers and village doctors. The protocol adopted a modified population-based case control design using 72, 000 non-patients as controls, 2, 200 cancer patients as cases, and another 600 patients as cases for external validation. Factors taken into account comprised 8 domains including diet and nutrition, risk behaviors, family history, precancerous diseases, related medical procedures, exposure to environment hazards, mood and feelings, physical activities and anthropologic and biologic factors. Modeling stresses explored various methodologies like empirical analysis, logistic regression, neuro-network analysis, decision theory and both internal and external validation using concordance statistics, predictive values, etc..
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Affiliation(s)
- Xing-Rong Shen
- School of Health Service Management, Anhui Medical University, Hefei, Anhui, China E-mail :
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Yu CH, Jeon SW, Kim SK, Lee HS, Heo J, Kwon YH, Kim GY, Kim SZ, Bae HI. Endoscopic resection as a first therapy for gastric epithelial atypia: is it reasonable? Dig Dis Sci 2014; 59:3012-20. [PMID: 24927801 DOI: 10.1007/s10620-014-3249-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 06/04/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Gastric atypical cell (GAC), an indefinite pathologic finding, often requires repeated biopsy or other diagnostic treatments, such as endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or operation (OP). The aim of this study was to analyze the initial endoscopic and histologic findings of GAC and to discuss the necessity of EMR/ESD at establishing a correct diagnosis. METHODS This retrospective study enrolled 96 patients proven as GAC on index forceps biopsy. ESD (17/96, 17.7%), EMR (5/96, 5.2%), OP (20/96, 20.8%), and other treatment or follow-up (54/96, 56.3%) were performed. We analyzed the initial endoscopic and histologic characteristics of GAC lesions, predictive of neoplasm. RESULTS After diagnostic modalities, the final pathologic diagnoses were cancer (36/96, 37.6%), dysplasia (9/96, 9.4%), and non-neoplasm (51/96, 53.0%). In univariate analysis, age [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.07], lesion size of 10 mm or greater (OR 3.94, 95% CI 1.61-9.61), lesion with depressed type (OR 2.50, 95% CI 1.09-5.72), and presence of H. pylori (OR 2.83, 95% CI 1.11-7.25) were risk factors for neoplasm. In multivariate analysis, lesion size of 10 mm or greater (OR 3.63, 95% CI 1.23-10.66), lesion with depressed type (OR 2.86, 95% CI 1.11-7.38) were independent risk factors for cancer. CONCLUSION Considering the neoplastic risk of GAC, which could be missed on biopsy, more comprehensive tissue sampling via EMR/ESD might be necessary to establish a definite diagnosis.
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Affiliation(s)
- Chung Hoon Yu
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
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Cho SJ, Choi IJ, Kook MC, Nam BH, Kim CG, Lee JY, Ryu KW, Kim YW. Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems. Aliment Pharmacol Ther 2013; 38:1292-302. [PMID: 24134499 DOI: 10.1111/apt.12515] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Revised: 08/04/2013] [Accepted: 09/10/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. AIM To validate the OLGA and OLGIM staging systems in a region with high risk of GC. METHODS This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. RESULTS More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P < 0.001), particularly among patients with intestinal-type GCs (62.2%) compared with diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. CONCLUSION As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer.
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Affiliation(s)
- S-J Cho
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
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Mastoraki S, Mastoraki A, Lefantzis N, Safioleas P, Sakorafas G, Safioleas M. Controversies and challenging therapeutic modalities in gastric cancer. Indian J Surg 2012; 73:251-5. [PMID: 22851836 DOI: 10.1007/s12262-011-0285-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2010] [Accepted: 01/15/2011] [Indexed: 11/29/2022] Open
Abstract
Gastric cancer is still the fourth common neoplasm worldwide. Gastric ulcers, adenomatous polyps, and intestinal metaplasia have been associated with an increased relative risk. Tissue diagnosis and anatomic localization of the primary tumor are best obtained by upper gastrointestinal endoscopy. Despite new screening techniques peritoneal tumor spread and occult liver and lymph node metastases are only detected intra-operatively. Therapy is becoming more and more complex comprising surgical resection, investigational neoadjuvant, adjuvant or palliative chemotherapy, or supportive care. Complete surgical eradication of a tumor with resection of adjacent lymph nodes represents the best chance for long-term survival. The choice of operation depends upon the location of the tumor, the clinical stage, and the histologic type. Chemotherapy can provide symptom palliation, improve quality of life, and prolong survival in patients with advanced gastric cancer. Preoperative radiation therapy may allow for tumor downstaging and reduced probability of residual microscopic disease at surgery.
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15
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Fan YF, Wei MX. Precancerous lesions of gastric cancer: Research progress and preventive strategies. Shijie Huaren Xiaohua Zazhi 2012; 20:1807-1812. [DOI: 10.11569/wcjd.v20.i20.1807] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [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
The development of precancerous lesions of gastric cancer is a critical stage of the evolution of gastric cancer. Early detection and intervention for these lesions are of considerable significance in reducing the morbidity of gastric cancer. The development of precancerous lesions of gastric cancer is controlled by multiple factors such as Helicobacter priori infection, DNA methylation, microsatellite instability, and p53 status. Because of high malignancy and unclear etiology of gastric cancer, there are certain difficulties in carrying out successful primary prevention. This review aims to review the recent advances in understanding the pathogenesis of and preventive strategies for gastric precancerous lesions.
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Kang GH. CpG island hypermethylation in gastric carcinoma and its premalignant lesions. KOREAN JOURNAL OF PATHOLOGY 2012; 46:1-9. [PMID: 23109971 PMCID: PMC3479707 DOI: 10.4132/koreanjpathol.2012.46.1.1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2011] [Revised: 11/15/2011] [Accepted: 11/21/2011] [Indexed: 12/13/2022]
Abstract
Gastric cancers arise through a multistep process characterized by the progressive accumulation of molecular alterations in which genetic and epigenetic mechanisms have been implicated. Gastric cancer is one of the human malignancies in which aberrant promoter CpG island hypermethylation is frequently found. Helicobacter pylori and Epstein-Barr virus, which are known carcinogens for gastric cancer, are closely associated with enhanced hypermethylation of CpG island loci in gastric non-neoplastic epithelial cells and cancer cells, respectively. Aberrant CpG island hypermethylation occurs early in the multistep cascade of gastric carcinogenesis and tends to increase with the step-wise progression of the lesion. Approximately 400 genes that are actively expressed in normal gastric epithelial cells are estimated to be inactivated in gastric cancers as a result of promoter CpG island hypermethylation. In this review, a variety of information is summarized regarding CpG island hypermethylation in gastric cancer.
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Affiliation(s)
- Gyeong Hoon Kang
- Department of Pathology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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17
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Tanaka A, Kamada T, Inoue K, Shiotani A, Kusunoki H, Manabe N, Ito M, Hata J, Haruma K. Histological evaluation of patients with gastritis at high risk of developing gastric cancer using a conventional index. Pathol Res Pract 2011; 207:354-358. [PMID: 21664555 DOI: 10.1016/j.prp.2011.03.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2010] [Revised: 03/13/2011] [Accepted: 03/16/2011] [Indexed: 02/09/2023]
Abstract
Although gastric cancer (GCa) is strongly associated with Helicobacter pylori infection, only some H. pylori-positive subjects develop gastric cancer. The aim of this study is to identify H. pylori-positive subjects at high risk of developing GCa by assessment of the histopathological findings in the non-cancer-containing mucosa of patients with and without GCa. The subjects were 35 patients with diffuse-type gastric cancer (D-GCa), 55 with intestinal-type gastric cancer (I-GCa), and 99 H. pylori-positive controls without GCa. Two specimens were taken from the greater curvature of the antrum and the middle body. Histopathological gradings were evaluated using the updated Sydney System, and the risk of GCa was evaluated using a modified Meining's gastric cancer risk index (GCRI). Among the H. pylori-positive controls, corpus gastritis was seen in 98.0% (97/99) and corpus atrophic gastritis in 78.8% (78/99). The mean GCRI for the D-GCa (5.514±2.03) and I-GCa (6.836±2.08) groups was significantly greater than that for the H. pylori-positive controls (4.071±2.07; p=0.0005, p<0.0001). In addition, the mean GCRI for the I-GCa group was significantly greater than that for the D-GCa group (p<0.005). The GCRI-positive rate was significantly higher in subjects with GCa than in H. pylori-positive controls (D-GCa: p<0.005, I-GCa: p<0.0001). Many H. pylori-positive Japanese still carry a high risk for gastric cancer. However, H. pylori-positive patients at high risk of developing GCa (not only intestinal-type but also diffuse-type) may be detected using a simple GCRI.
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Affiliation(s)
- Aki Tanaka
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan
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18
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Cho SJ, Choi IJ, Kim CG, Kook MC, Lee JY, Kim BC, Ryu KH, Nam SY, Kim YW. Risk factors associated with gastric cancer in patients with a duodenal ulcer. Helicobacter 2010; 15:516-23. [PMID: 21073608 DOI: 10.1111/j.1523-5378.2010.00805.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although gastric cancer (GC) and duodenal ulcer (DU) are both strongly associated with Helicobacter pylori infection, a DU is negatively associated with the risk of GC. The aim of the study is to evaluate histologic risk factors for GC among patients with a DU. MATERIALS AND METHODS A total of 541 consecutive patients with GC were prospectively evaluated for the presence of a DU. Control patients with only a DU (n = 89) were recruited from health screening population. Histologic grading was assessed using the updated Sydney system for six gastric biopsies from three regions. GC risk among patients with a DU was evaluated using logistic regression analysis. RESULTS Among patients with GC, 7.6% (41/541) had a concomitant DU or an ulcer scar. Corpus-predominant/pangastritis were more frequently found in concomitant GC patients with a DU (90%) than in patients with a DU alone (62%) (p = .001). In patients with a DU, moderate-severe chronic inflammation at the lesser and greater curvatures of corpus was associated with GC risk (OR, 3.70; 95% CI, 1.46-9.36, and OR, 7.72; 95% CI, 3.18-18.7, respectively). Additionally, moderate-severe intestinal metaplasia (IM) at the antrum and corpus lesser curvature was associated with GC risk (OR, 7.52; 95% CI, 3.06-18.5, and OR, 9.25, 95% CI, 2.39-35.8, respectively). CONCLUSIONS A DU is not rare in patients with GC in a high-risk region of GC. Patients with a DU with chronic corpus gastritis and IM have an increased risk of GC, thus those patients should be followed up for GC development.
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Affiliation(s)
- Soo-Jeong Cho
- Center for Gastric Cancer Center for Cancer Prevention and Detection, National Cancer Center, Gyeonggi, Korea
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19
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Ye RJ, Huang ZG, Wang H, Wang N, Wang SY, Chen XM. Detection of IL-1B-1473 single nucleotide polymorphism in atrophic gastritis using SNaPshot technique. Shijie Huaren Xiaohua Zazhi 2009; 17:1202-1206. [DOI: 10.11569/wcjd.v17.i12.1202] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [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 evaluate the correlation between IL-1B-1473 gene and atrophic gastritis.
METHODS: Blood samples from 100 patients with atrophic gastritis and 100 patients with non-atrophic gastritis and related epidemiological data were collected. Sample DNA was extracted and IL-1B-1473 single nucleotide polymorphism were genotyped using Multiplex SNaPshot technique.
RESULTS: No significant difference was seen in genotype distribution frequency between the atrophy group and the non-atrophy group. The IL-1B-1473 gene and the atrophic degree of atrophic gastritis were not significantly correlated. Compared with IL-1B-1473C/C, it had a risk increase of 32% for atrophy (OR = 1.32, 95%CI: 0.55-3.16) for IL-1B-1473G/G, but not a significant increase.
CONCLUSION: The IL-1B-1473 gene may have the susceptibility to atrophic gastritis.
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20
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Adán Merino L, Gomez Senent S, Alonso Gamarra E. Estrategia diagnóstica y terapéutica en el adenocarcinoma gástrico. Med Clin (Barc) 2009; 132:230-6. [DOI: 10.1016/j.medcli.2008.07.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2008] [Accepted: 07/09/2008] [Indexed: 10/20/2022]
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Forné M, Fernández-Bañares F, González-Mínguez C, Casalots J, Poblet-Mas N, Garcia-Gil LJ, Esteve M, Rosinach M, Espinós J, Loras C, Salas A, Viver JM. Lack of clinical usefulness of Das-1 monoclonal antibody and mucin expression as risk markers of gastric carcinoma in patients with gastric intestinal metaplasia. Am J Clin Pathol 2009; 131:99-105. [PMID: 19095572 DOI: 10.1309/ajcpnp7bk3kuuojl] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Our aim was to evaluate the usefulness of the monoclonal antibody Das-1 as a premalignant marker of gastric intestinal metaplasia (GIM) associated with gastric cancer and its association with mucin expression. We evaluated Das-1 and mucin expression in 4 groups: 1 (n = 50), gastric carcinoma, paired samples of the cancer area and GIM away from the tumor; 2 (n = 25), gastric or duodenal ulcer with Helicobacter pylori infection with GIM and chronic gastritis; 3 (n = 25),H pylori- autoimmune chronic atrophic gastritis with GIM; and 4 (n = 25),H pylori- chronic gastritis without GIM. Das-1 immunostaining was observed in 20 (40%) of 50 cases in cancer areas. The expression of Das-1 in GIM from group 1 cases away from the cancer area was different from that in GIM from nontumor cases (groups 2 and 3): 13 (26%) of 50 vs 2 (8%) and 0 (0%) of 25 (P = .004). There was no association between Das-1 and mucin expression. Das-1 expression was associated with GIM from patients with gastric cancer. However, this relation was weaker than previously reported, precluding clinical usefulness as a premalignant marker of GIM.
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Affiliation(s)
- Montserrat Forné
- Departments of Gastroenterology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | | | | | - Jaume Casalots
- Pathology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Núria Poblet-Mas
- Laboratory of Molecular Microbiology, Department of Biology, University of Girona, Girona, Spain
| | - L. Jesús Garcia-Gil
- Laboratory of Molecular Microbiology, Department of Biology, University of Girona, Girona, Spain
| | - Maria Esteve
- Departments of Gastroenterology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Mercè Rosinach
- Departments of Gastroenterology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Jorge Espinós
- Departments of Gastroenterology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Carme Loras
- Departments of Gastroenterology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Antonio Salas
- Pathology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Josep M. Viver
- Departments of Gastroenterology, Hospital Universitari Mútua Terrassa, Terrassa, Spain
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22
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Con SA, Con-Wong R, Con-Chin GR, Con-Chin VG, Takeuchi H, Valerín AL, Echandi G, Mena F, Brenes F, Yasuda N, Araki K, Sugiura T. Serum pepsinogen levels, Helicobacter pylori CagA Status, and cytokine gene polymorphisms associated with gastric premalignant lesions in Costa Rica. Cancer Epidemiol Biomarkers Prev 2008; 16:2631-6. [PMID: 18086767 DOI: 10.1158/1055-9965.epi-07-0215] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The detection of gastric premalignant lesions, atrophic gastritis, corpus atrophic gastritis, and intestinal metaplasia, using several potential markers was examined in Costa Rica. Depending on the lesion investigated, from a total of 223 dyspeptic patients, 58 (26.0%), 31 (13.9%), or 23 (10.3%) were histologically diagnosed with atrophic gastritis, corpus atrophic gastritis, or intestinal metaplasia, respectively. Sera were used for the measurement of pepsinogen (PG) and Helicobacter pylori CagA antibody (CagA-ab) levels by ELISA, and human genomic DNAs were used for the genotyping of interleukin (IL)-1beta (-511 and +3954), IL-10 (-1082 and -592), and IL-1RN intron 2 by PCR and RFLP. Multivariate analysis was done adjusting for sex, age, and H. pylori seropositivity. Low PG levels (L-PG; PG I < or = 70 microg/L + PG I/II < or = 3), very low PG levels (VL-PG; PG I < or = 30 microg/L + PG I/II < or = 2), and CagA-ab were individually associated with all premalignant lesions whereas IL-1beta +3954T-carrier and IL-1RN homozygous 2 allele were associated with intestinal metaplasia. VL-PG, for corpus atrophic gastritis detection, was the single marker with the highest combination of test characteristics, sensitivity (77.4%), specificity (80.7%), positive predictive value (39.3%), negative predictive value (95.7%), and seropositivity rate (27.4%), expected to improve after periodic measurements. Combined examinations of VL-PG and CagA-ab improved the specificity (92.7%) and positive predictive value (62.2%), with similar sensitivity (74.2%) and negative predictive value (95.7%). In conclusion, corpus atrophic gastritis detection with periodic measurements of serum PG, alone or in combination with CagA-ab status, to identify high gastric cancer risk, seems to be the method best suited for mass screening in Costa Rica.
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Affiliation(s)
- Sergio A Con
- Centro Digestivo Doctores Con-Mediplaza, Pavas, San José, Costa Rica.
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Li K, Tang ZP, Zheng FJ, Hong YS. Discussion on the reversibility of gastric intestinal metaplasia. Shijie Huaren Xiaohua Zazhi 2007; 15:140-144. [DOI: 10.11569/wcjd.v15.i2.140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [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
Gastric intestinal metaplasia (IM), as precancerous lesion of the stomach, is closely associated with the development of gastric cancer. Whether gastric IM can be reversed is still in controversy. Epidemiological evidence showed that IM was reversible after long-term following up, but the reversed degree was low. Besides H pylori infection, deficiency of vitamin C in the gastric mucosa, shortage of gastric acid and/or bile reflux can cause this precancerous condition. The pathogenesis of gastric IM, in which H pylori virulence factors, intestine-specific transcription factors, and microsatellite instability are involved, is being investigated at the present time, but it can't be affirmed that IM is a kind of phenotype alteration in gastric epithelial cells induced by stem cell mutation. It is fairly difficult to make diagnosis for IM unless careful endoscopic evaluation is performed and proper biopsy sites are selected. Eradication of H pylori alone may not be enough to reverse IM, and its combination with other chemopreventive agents and/or Chinese medicine may be an effective strategy.
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24
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Ko S, Chu KM, Luk JMC, Wong BWY, Yuen ST, Leung SY, Wong J. CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach. J Pathol 2005; 205:615-22. [PMID: 15732140 DOI: 10.1002/path.1741] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
CDX2 and liver-intestine (LI)-cadherin are intestine-specific markers and both are physiologically expressed in the small intestine and colon. Recent studies have demonstrated that CDX2 regulates LI-cadherin gene (CDH17) expression in colorectal cancer. The present study investigated the relationship of CDX2 and LI-cadherin expression in gastric cancer. One hundred and nine pairs of tumour and non-cancerous gastric mucosa were collected from gastrectomy specimens. Protein expression levels of CDX2 and LI-cadherin were determined by immunohistochemical staining. Semi-quantitative RT-PCR showed that the mRNAs of both CDX2 and CDH17 were highly expressed in tumour compared with non-cancerous mucosa. Overexpression of CDX2 was significantly associated with CDH17 in gastric adenocarcinoma. Furthermore, the expression of CDX2 and LI-cadherin proteins was strongly coupled in intestinal metaplasia. In conclusion, overexpression of CDH17 is significantly associated with CDX2.
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Affiliation(s)
- Samuel Ko
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China
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25
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Nardone G, Rocco A, Malfertheiner P. Review article: helicobacter pylori and molecular events in precancerous gastric lesions. Aliment Pharmacol Ther 2004; 20:261-70. [PMID: 15274662 DOI: 10.1111/j.1365-2036.2004.02075.x] [Citation(s) in RCA: 106] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Gastric cancer can be divided into intestinal type and diffuse type that differ substantially in epidemiology and pathogenesis. The most important aetiological factor associated both with intestinal and diffuse gastric cancer, is Helicobacter pylori. Exposure of gastric epithelial cells to H. pylori results in an inflammatory reaction with the production of reactive oxygen species and nitric oxide that, in turn, deaminates DNA causing mutations. The complex interplay between H. pylori strain, inflammation and host characteristics may directly promote diffuse type gastric cancer or induce a cascade of morphological events, i.e. atrophy, intestinal metaplasia and dysplasia, finally leading to intestinal type gastric cancer. Two mechanisms, genetic and epigenetic have been held to play a role in the molecular alterations underlying gastric carcinogenesis. The former, comprising changes in the DNA sequence, is irreversible; the latter, involving DNA methylation, is potentially reversible by eliminating the triggering agents. If H. pylori is eradicated before development of stable mutations, the risk of gastric cancer will likely be prevented. Thus, eradication of H. pylori might immediately reduce the risk of diffuse type gastric cancer, whereas prevention of intestinal type gastric cancer may be less effective if patients are treated later in the evolution of the carcinogenic process.
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Affiliation(s)
- G Nardone
- Department of Clinical and Experimental Medicine, Gastroenterology Unit, Federico II University, Naples, Italy.
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26
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Walker MM. Cyclooxygenase-2 expression in early gastric cancer, intestinal metaplasia and Helicobacter pylori infection. Eur J Gastroenterol Hepatol 2002; 14:347-9. [PMID: 11943943 DOI: 10.1097/00042737-200204000-00001] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Cyclooxygenase (COX) is the crucial enzyme for synthesis of prostaglandins and occurs in two isoforms COX-1 and COX-2. Whilst COX-1 is constantly expressed in the gastrointestinal tract in large quantities and probably maintains mucosal integrity through constant generation of prostaglandins, COX-2 is induced principally during inflammation. In early gastric cancer and in intestinal metaplasia the expression of COX-2 in patients infected by Helicobacter pylori is increased in intestinal type compared to diffuse type gastric cancer and in intestinal metaplasia. In tumours of mixed type, COX-2 is also increased in the intestinal component compared to the diffuse component. Whilst there has been success of COX-2 inhibition for chemoprevention in colon cancer, a similar role in gastric cancer needs to be carefully assessed in the light of reported adverse effects and whether the precancerous condition, intestinal metaplasia, can truly regress.
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Affiliation(s)
- Marjorie M Walker
- Department of Histopathology, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
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Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG. CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res 2001; 219:410-6. [PMID: 11306456 DOI: 10.1002/path.2596] [Citation(s) in RCA: 90] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
There are limited reports on methylation analysis of the premalignant lesions of gastric carcinoma thus far. This is despite the fact that gastric carcinoma is one of the tumors with a high frequency of CpG island hypermethylation. To determine the frequency and timing of hypermethylation during multistep gastric carcinogenesis, non-neoplastic gastric mucosa (n = 118), adenomas (n = 61), and carcinomas (n = 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1), death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP-3) methylation status using methylation-specific PCR. Three different classes of methylation behaviors were found in the five tested genes. DAP-kinase was methylated at a similar frequency in all four stages, whereas hMLH1 and p16 were methylated in cancer samples (20.3% and 42.2%, respectively) more frequently than in intestinal metaplasia (6.3% and 2.1%, respectively) or adenomas (9.8% and 11.5%, respectively). However, hMLH1 and p16 were not methylated in chronic gastritis. THBS-1 and TIMP-3 were methylated in all stages but showed a marked increase in hypermethylation frequency from chronic gastritis (10.1% and 14.5%, respectively) to intestinal metaplasia (34.7% and 36.7%, respectively; P < 0.05) and from adenomas (28.3% and 26.7%, respectively) to carcinomas (48.4% and 57.4%, respectively: P < 0.05). The hMLH1, THBS1, and TIMP-3 hypermethylation frequencies were similar in both intestinal metaplasia and adenomas, but the p16 hypermethylation frequency tended to be higher in adenomas (11.5%) than in intestinal metaplasia (2.1%; P = 0.073). The average number of methylated genes was 0.6, 1.1, 1.1, and 2.0 per five genes per sample in chronic gastritis, intestinal metaplasia, adenomas, and carcinomas, respectively. This shows a marked increase in methylated genes from non-metaplastic mucosa to intestinal metaplasia (P = 0.001) as well as from premalignant lesions to carcinomas (P = 0.002). These results suggest that CpG island hypermethylation occur early in multistep gastric carcinogenesis and tend to accumulate along the multistep carcinogenesis.
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Affiliation(s)
- G H Kang
- Department of Pathology, Seoul National University College of Medicine and Cancer Research Institute, Korea.
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Shimoyama T, Fukuda S, Tanaka M, Nakaji S, Fukuda Y, Munakata A. Evaluation of the association between serum anti-Lewis X antibody and inflammatory infiltration into the gastric mucosa infected with Helicobacter pylori. Dig Liver Dis 2001; 33:326-9. [PMID: 11432510 DOI: 10.1016/s1590-8658(01)80086-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Lipopolysaccharides of Helicobacter pylori have an antigenic structure that mimics Lewis X occurring in gastric mucosa. The pathogenic role of antigenic mimicry in Helicobacter pylori-induced gastritis has been of recent interest. AIM To examine whether this molecular mimicry affects gastric mucosal inflammation in patients infected with Helicobacter pylori. PATIENTS A total of 59 patients (mean age 58.0 years, 35 males, 24 females) were studied. METHODS Serum samples were collected to measure IgG antibodies to Helicobacter pylori and Lewis X. Biopsy specimens were obtained from the antrum and corpus for the grading of gastritis. Correlation coefficients between serum Lewis X antibody titre and histological grades of inflammatory infiltration were determined. RESULTS There was no significant correlation between anti-Lewis X antibody titre and the grade of mononuclear or polymorphonuclear cell infiltration. High titre of anti-Lewis X antibody was seen only in patients who had increased inflammatory infiltration in the corpus. CONCLUSIONS Serum anti-Lewis X antibody, possibly induced by Helicobacter pylori infection, does not seem to play a major role in gastric mucosal inflammation in patients with Helicobacter pylori infection.
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Affiliation(s)
- T Shimoyama
- First Department of Internal Medicine, Hirosaki University School of Medicine, Japan.
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29
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Miehlke S, Kirsch C, Dragosics B, Gschwantler M, Oberhuber G, Antos D, Dite P, Läuter J, Labenz J, Leodolter A, Malfertheiner P, Neubauer A, Ehninger G, Stolte M, Bayerdörffer E. Helicobacter pylori and gastric cancer: current status of the Austrain-Czech-German gastric cancer prevention trial (PRISMA-Study). World J Gastroenterol 2001; 7:243-7. [PMID: 11819768 PMCID: PMC4723530 DOI: 10.3748/wjg.v7.i2.243] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease.
METHODS: It is a prospective, randomized, double blind, placebo controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are randomized to receive a 7 day course of omeprazole 2 × 20 mg, clarithromycin 2 × 500 mg, and amoxicillin 2 × 1 g for 7 days, or omeprazole 2 × 20 mg plus placebo. Follow-up endoscopy is scheduled 3 months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, and death.
RESULTS: Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus dominant type of H. pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (n = 86), H. pylori infection infection was cured in 88.9% of patients. Currently, the cumulative follow-up time is 3046 months (253. 38 patient years, median follow up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three (1.8%) patients reached study endpoints other than gastric cancer.
CONCLUSION: Among men between 55 and 65 years of age, the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected. Further follow up and continuing recruitment are necessary to fulfil the main aim of the study.
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Affiliation(s)
- S Miehlke
- Medical Department I, Technical University Hospital Carl Gustav Carus, Fetscherstrabetae 74, D 01307 Dresden, Germany
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Fukuda S, Tanaka M, Soma Y, Shimoyama T, Mikami T, Crabtree JE, Saito H, Munakata A, Yoshida Y. Histological analysis of gastritis and Helicobacter pylori infection in patients with early gastric cancer: a case-control study. J Gastroenterol Hepatol 2000; 15:1370-6. [PMID: 11197045 DOI: 10.1046/j.1440-1746.2000.02355.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIMS Infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. However, most patients with H. pylori infection will not develop gastric cancer. The aims of the present study were to examine which histological features, including H. pylori infection, would increase the risk of gastric cancer using a case-control study. METHODS Three gastric biopsy specimens were taken from 72 patients with early gastric cancer and 72 age- and sex-matched control subjects. The grade of gastritis was examined according to the updated Sydney System. The presence of H. pylori infection was determined by serology and histology. Odds ratio (OR) of developing gastric cancer was calculated for H. pylori positivity and histological features using conditional logistic regression. For patients with H. pylori infection, histological features in cancer patients and control subjects were compared. RESULTS The OR of the presence of mononuclear cell infiltration in the corpus and intestinal metaplasia in the angulus were significantly elevated. The grade of mononuclear cell infiltration in the corpus and antrum was significantly higher in both types of cancer patients than controls. Glandular atrophy and intestinal metaplasia were increased in patients with intestinal-type cancer in the angulus and antrum. Bacterial density in the corpus and polymorphonuclear cell infiltration in the antrum were increased in patients with diffuse-type cancer. CONCLUSIONS Severe chronic gastritis induced by H. pylori infection seems to be associated with diffuse-type gastric cancer. Glandular atrophy and intestinal metaplasia, which occur in gastric mucosa with chronic inflammation, are significantly associated with intestinal-type cancer.
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Affiliation(s)
- S Fukuda
- First Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
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