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Mohamed SH, Hamed M, Alamoudi HA, Jastaniah Z, Alakwaa FM, Reda A. Multi-omics analysis of Helicobacter pylori-associated gastric cancer identifies hub genes as a novel therapeutic biomarker. Brief Bioinform 2025; 26:bbaf241. [PMID: 40445003 PMCID: PMC12123523 DOI: 10.1093/bib/bbaf241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 04/16/2025] [Accepted: 05/04/2025] [Indexed: 06/02/2025] Open
Abstract
Helicobacter pylori infection is one of the most common gastric pathogens; however, the molecular mechanisms driving its progression to gastric cancer remain poorly understood. This study aimed to identify the key transcriptomic drivers and therapeutic targets of H. pylori-associated gastric cancer through an integrative transcriptomic analysis. This analysis integrates microarray and RNA-seq datasets to identify significant differentially expressed genes (DEGs) involved in the progression of H. pylori-associated gastric cancer. In addition to independent analyses, data were integrated using ComBat to detect consistent expression patterns of hub genes. This approach revealed distinct clustering patterns and stage-specific transcriptional changes in common DEGs across disease progression, including H. pylori infection, gastritis, atrophy, and gastric cancer. Genes such as TPX2, MKI67, EXO1, and CTHRC1 exhibited progressive upregulation from infection to cancer, highlighting involvement in cell cycle regulation, DNA repair, and extracellular matrix remodeling. These findings provide insights into molecular shifts linking inflammation-driven infection to malignancy. Furthermore, network analysis identified hub genes, including CXCL1, CCL20, IL12B, and STAT4, which are enriched in immune pathways such as chemotaxis, leukocyte migration, and cytokine signaling. This emphasizes their role in immune dysregulation and tumor development. Expression profiling demonstrated the upregulation of hub genes in gastric cancer and stage-specific changes correlating with disease progression. Finally, drug-gene interaction analysis identified therapeutic opportunities, with hub genes interacting with approved drugs like abatacept and zoledronic acid, as well as developmental drugs such as adjuvant and relapladib. These findings highlight the key role of these hub genes as biomarkers and therapeutic targets, providing a foundation for advancing precision medicine in H. pylori-associated gastric cancer. Overall, this study paves the way for advancing precision medicine in H. pylori-associated gastric cancer by providing insights into the development of early detection biomarkers, risk stratification, and targeted therapies. This supports the clinical translation of precision medicine strategies in H. pylori-associated gastric cancer.
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Affiliation(s)
- Sara H Mohamed
- Department of Microbiology, Egyptian Drug Authority (EDA), formerly National Organization for Drug Control and Research (NODCAR), Giza 14281, Egypt
| | - Mohamed Hamed
- Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Rostock University Medical Center, Rostock 18057, Germany
- Faculty of Media Engineering and Technology, German University in Cairo, Cairo 11835, Egypt
| | - Hussain A Alamoudi
- Radiation Oncology Department, Oncology Center in East Jeddah Hospital (Jeddah First Health Cluster), Rabigh, Saudi Arabia
- Center of Nanotechnology, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Zayd Jastaniah
- Center of Nanotechnology, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia
| | - Fadhl M Alakwaa
- Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, United States
| | - Asmaa Reda
- Center of Nanotechnology, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Zoology Department, Computational Biology and Bioinformatics Division, Faculty of Science, Benha University, Benha 12613, Egypt
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Zhao P, Wang J, Zou C. Synergistic anticancer potential of biogenic nanoparticles and cryptomeridiol from Sphaeranthus indicus: targeting gastric cancer through apoptosis and cell cycle arrest. Front Pharmacol 2025; 16:1565308. [PMID: 40248096 PMCID: PMC12003266 DOI: 10.3389/fphar.2025.1565308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 03/25/2025] [Indexed: 04/19/2025] Open
Abstract
Background S. indicus has demonstrated promising therapeutic potential due to its bioactive compounds. This study investigated the cytotoxic and pro-apoptotic effects of Sphaeranthus indicus extract, its active fraction, and biosynthesized silver nanoparticles (AgNPs) on human gastric cancer (HGT-1) cells. Methods The plant was collected and subjected to Soxhlet extraction using ethanol, followed by sequential solvent partitioning and silica gel column chromatography to isolate bioactive fractions. Green synthesis of AgNPs was conducted using S. indicus extract. Structural characterization was conducted via UV- spectroscopy, FTIR, XRD, and FESEM. Cytotoxicity was assessed using MTT and CCK-8 assays, while apoptosis induction was evaluated through qPCR and Western blot analysis of key apoptotic markers. Results The ethanolic extract exhibited moderate cytotoxicity against HGT-1 cells, whereas biosynthesized AgNPs demonstrated enhanced anticancer activity with reduced toxicity to normal hepatocytes. The active fraction, identified as cryptomeridiol, showed the highest selectivity and potency against cancer cells. qPCR revealed significant upregulation of p21 and downregulation of CDK2, suggesting cell cycle arrest. Western blot analysis confirmed increased expression of caspase-3 and caspase-9 and a reduction in XIAP, indicating apoptosis activation. Conclusion This study underscores the potential of S. indicus bioactive compounds and AgNPs as therapeutic agents, particularly against gastric cancer. The findings provide a basis for further exploration into their mechanism of action and broader pharmacological applications. Keywords: S. indicus, Bioactive compounds, Silver nanoparticles (AgNPs), Gastric cancer-HGT-1, Apoptosis.
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Affiliation(s)
- Pan Zhao
- School of Medicine, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
- Department of Central Laboratory, Shenzhen People’s Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Jigang Wang
- School of Medicine, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Chang Zou
- Department of Central Laboratory, Shenzhen People’s Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
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Jeong S, Liao YT, Tsai MH, Wang YK, Wu IC, Liu CJ, Wu MS, Chan TS, Chen MY, Hu PJ, Kao WY, Liu HC, Tsai MJ, Liu CY, Chang CC, Wu DC, Hsu YH. Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study. BMC Microbiol 2024; 24:139. [PMID: 38658841 PMCID: PMC11040827 DOI: 10.1186/s12866-024-03219-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 02/08/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.
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Affiliation(s)
- Sohyun Jeong
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Yi-Tyng Liao
- Development Center for Biotechnology, Taipei, Taiwan
| | - Min-Hsuan Tsai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 TzYou 1st Rd, Kaohsiung City, 80756, Taiwan
| | - Yao-Kuang Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 TzYou 1st Rd, Kaohsiung City, 80756, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - I-Chen Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 TzYou 1st Rd, Kaohsiung City, 80756, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Jung Liu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 TzYou 1st Rd, Kaohsiung City, 80756, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Shun Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, No.252, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tze-Sian Chan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, No.252, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Ming-Yao Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, No.252, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Ping-Jen Hu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, No.252, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, 110, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, No.252, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan
| | | | - Ming-Ju Tsai
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA
| | | | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, 110, Taiwan.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan.
- TMU Research Center for Digestive Medicine, Taipei Medical University, No.252, Wuxing St., Xinyi Dist, Taipei, 110, Taiwan.
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 TzYou 1st Rd, Kaohsiung City, 80756, Taiwan.
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Yi-Hsiang Hsu
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA.
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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Sugano K, Moss SF, Kuipers EJ. Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer? Gastroenterology 2023; 165:1352-1366.e1. [PMID: 37652306 DOI: 10.1053/j.gastro.2023.08.028] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 08/16/2023] [Accepted: 08/22/2023] [Indexed: 09/02/2023]
Abstract
Gastric intestinal metaplasia (GIM), which denotes conversion of gastric mucosa into an intestinal phenotype, can occur in all regions of the stomach, including cardiac, fundic, and pyloric mucosa. Since the earliest description of GIM, its association with gastric cancer of the differentiated (intestinal) type has been a well-recognized concern. Many epidemiologic studies have confirmed GIM to be significantly associated with subsequent gastric cancer development. Helicobacter pylori, the principal etiologic factor for gastric cancer, plays the most important role in predisposing to GIM. Although the role of GIM in the stepwise progression model of gastric carcinogenesis (the so-called "Correa cascade") has come into question recently, we review the scientific evidence that strongly supports this long-standing model and propose a new progression model that builds on the Correa cascade. Eradication of H pylori is the most important method for preventing gastric cancer globally, but the effect of eradication on established GIM, is limited, if any. Endoscopic surveillance for GIM may, therefore, be necessary, especially when there is extensive corpus GIM. Recent advances in image-enhanced endoscopy with integrated artificial intelligence have facilitated the identification of GIM and neoplastic lesions, which will impact preventive strategies in the near future.
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Affiliation(s)
| | - Steven F Moss
- Alpert Medical School of Brown University, Providence, Rhode Island
| | - Ernst J Kuipers
- Erasmus Medical Center, Rotterdam and Minister, Ministry of Health, Welfare, and Sport, Hague, The Netherlands
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Abstract
BACKGROUND This study aimed to systematically analyze the association between long-term use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). METHODS We performed a systematic search of articles on the relationship between long-term use of PPIs and the risk of GC from PubMed and EMBASE. We calculated the pooled odds ratio of GC in PPI users compared to non-PPI users using random-effects models. RESULTS This meta-analysis included 18 studies from 20 different databases with 4348,905 patients enrolled. In the random effects model, we found that an increased risk of GC among PPI users (OR = 1.94; 95% CI [1.43, 2.64]). The long-term use of PPIs compared with histamine-2 receptor antagonist users did not increase the risk of GC (OR = 1.65; 95% CI [0.92, 2.97]). Stratified analysis showed that PPI users had a significantly increased risk of noncardia GC (OR = 2.53; 95% CI [2.03, 3.15]), but had a relatively small relationship with the risk of gastric cardia cancer. (OR = 1.79; 95% CI [1.06, 3.03]). With the extension of PPI use time, the estimated risk value decreases (<1 year: OR = 6.33, 95% CI [3.76, 10.65]; 1-3 years: OR = 1.82, 95% CI [1.30, 2.55]; >3 years: OR = 1.25, 95% CI [1.00, 1.56]). Despite Helicobacter pylori eradication, the long-term use of PPIs did not alter the increased risk of GC (OR = 2.29; 95% CI [1.57, 3.33]). CONCLUSION Our meta-analysis found that PPI use may be associated with an increased risk of GC. Further research on the causal relationship between these factors is necessary.
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Affiliation(s)
- Huiqin Gao
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Lunan Li
- Department of Gastroenterology, NO.2 People’s Hospital of Fuyang City, Fuyang, Anhui, China
| | - Ke Geng
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Changzheng Teng
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Yuanyuan Chen
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Fei Chu
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Yi Zhao
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
- *Correspondence: Yi Zhao, Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, No. 189 Xiangyang Road, Guoyang 233600, Anhui, China (e-mail: )
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Kim SY, Park JM. Quality indicators in esophagogastroduodenoscopy. Clin Endosc 2022; 55:319-331. [PMID: 35656624 PMCID: PMC9178133 DOI: 10.5946/ce.2022.094] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 04/22/2022] [Indexed: 11/25/2022] Open
Abstract
Esophagogastroduodenoscopy (EGD) has been used to diagnose a wide variety of upper gastrointestinal diseases. In particular, EGD is used to screen high-risk subjects of gastric cancer. Quality control of EGD is important because the diagnostic rate is examiner-dependent. However, there is still no representative quality indicator that can be uniformly applied in EGD. There has been growing awareness of the importance of quality control in improving EGD performance. Therefore, we aimed to review the available and emerging quality indicators for diagnostic EGD.
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Affiliation(s)
- Sang Yoon Kim
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea
| | - Jae Myung Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Catholic Photomedicine Research Institute, The Catholic University of Korea, Seoul, Korea
- Correspondence: Jae Myung Park Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea E-mail:
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[Analysis of endoscopic and pathological features of gastric adenomatous polyps and risk factors for canceration]. BEIJING DA XUE XUE BAO. YI XUE BAN = JOURNAL OF PEKING UNIVERSITY. HEALTH SCIENCES 2021; 53. [PMID: 34916692 PMCID: PMC8695160 DOI: 10.19723/j.issn.1671-167x.2021.06.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVE To investigate the endoscopic and pathological characteristics of gastric adenomatous polyps and to assess the potential risk factors for canceration of gastric adenomatous polyps. METHODS The endoscopic and pathological characteristics of the patients with gastric adenomatous polyps from January 1, 2005 to December 31, 2019 were summarized retrospectively, and the risk factors of canceration were analyzed. RESULTS A total of 125 patients with gastric adenomatous polyps were included, 51.20% of whom were females. The average age was (66.7±12.3) years. 64.80% of patients with gastric adenomatous polyps equal or more than 65 years old, and only 5.60% of the patients less than 45 years old. Adenomatous polyps were mostly distributed in the corpus and antrum with 40.80% and 32.80%, respectively. The majority of them were single (90.40%) and sessile (76.81%). 65.4% of adenomatous polyps were no more than 1.0 cm in diameter, and 23.20% of patients with adenomatous polyps were combined with hyperplastic polyps and/or fundus glandular polyps, and 1.60% had both pathological types of polyps. 58.62% (17/29) patients with hyperplastic polyps and/or fundus glandular polyps had multiple polyps. 1.60% (2/125) of the patients had gastric neuroendocrine tumor of G1 stage. Synchronous gastric cancer was detected in 13.60% (17/125) of the patients with adenomatous polyps, and the proportion of low-grade intraepithelial neoplasia was 18.40% (23/125). The main types of synchronous gastric cancer were progressive (70.59%) and undifferentiated (66.67%). Chronic atrophic gastritis with intestinal metaplasia was found in 52.80% of the patients, and autoimmune gastritis accounted for 11.20%. The positive rate of Helicobacter pylori was 21.60%. The canceration rate of gastric adenomatous polyps was 20.80%. The cancer was mainly differentiated, but there was sigmoid ring cell carcinoma as well. Diameter of >1.0 cm (OR=5.092, 95%CI: 1.447-17.923, P=0.011), uneven surface morphology and erosion (OR=13.749, 95%CI: 1.072-176.339, P=0.044) were independent risk factors of adenomatous polyps. CONCLUSION The synchronous gastric cancer is common and the canceration of gastric adenomatous polyps is high with diameter and surface morphology as independent risk factors. We should pay attention to the identification of the pathological types of polyps and the evaluation of the whole gastric mucosa during the endoscopic examination.
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Okamoto Y, Kanzaki H, Tanaka T, Sakae H, Abe M, Iwamuro M, Kawano S, Kawahara Y, Okada H. Gastric Adenoma: A High Incidence Rate of Developing Carcinoma and Risk of Metachronous Gastric Cancer according to Long-Term Follow-Up. Digestion 2021; 102:878-886. [PMID: 33839721 DOI: 10.1159/000515213] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 02/12/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Gastric adenomas are histologically defined as benign epithelial tumors. While some of them remain adenomas for a long time, others progress to carcinomas. However, long-term outcomes of such cases are not entirely clear. Here, we explored the risk factors and incidence of developing carcinoma from gastric adenoma as well as metachronous gastric cancer. METHODS This study was conducted at a facility that adopted a follow-up strategy for gastric adenoma. Lesions histologically diagnosed as gastric intestinal-type adenomas between January 2004 and December 2016 were analyzed. Clinicopathological data were collected from patients' medical records, and histological changes from adenoma to carcinoma during endoscopic follow-up and risk factors of cancer development were evaluated. RESULTS This study involved 409 lesions from 376 patients. The analysis of the development of gastric cancer from adenoma and metachronous gastric cancer was ultimately performed for 282 lesions from 258 patients and 269 lesions from 246 patients, respectively, due to different follow-up periods. The 5-year rate of carcinoma development was 34.0%. Risk factors for carcinoma development upon multivariate analysis were lesion size ≥15 mm and morphological depression. All cases with both factors developed gastric carcinoma, and 50.5% of those with either factor developed carcinoma within 5 years. Gastric adenoma was accompanied by metachronous gastric cancer in 1.5% of the patients annually. The only risk factor for metachronous gastric carcinoma was primary adenoma progressing to carcinoma during the follow-up period. DISCUSSION/CONCLUSION Given the high rate of carcinoma development in patients with risk factors, resection of gastric adenoma should be considered during the initial examination. Careful observation and follow-up should also be conducted to detect not only changes in the primary adenoma but also the occurrence of metachronous carcinoma, especially in cases of adenoma progressing to carcinoma.
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Affiliation(s)
- Yuki Okamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hiromitsu Kanzaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Takehiro Tanaka
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Sakae
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Makoto Abe
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Seiji Kawano
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Yoshiro Kawahara
- Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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Cui J, Cui H, Yang M, Du S, Li J, Li Y, Liu L, Zhang X, Li S. Tongue coating microbiome as a potential biomarker for gastritis including precancerous cascade. Protein Cell 2019; 10:496-509. [PMID: 30478535 PMCID: PMC6588651 DOI: 10.1007/s13238-018-0596-6] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 10/23/2018] [Indexed: 02/06/2023] Open
Abstract
The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progress. In this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrence and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.
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Affiliation(s)
- Jiaxing Cui
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Hongfei Cui
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
- Institute for Artificial Intelligence and Department of Computer Science and Technology, Tsinghua University, Beijing, 100084, China
| | - Mingran Yang
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Shiyu Du
- China-Japan Friendship Hospital, Beijing, 100029, China
| | - Junfeng Li
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Yingxue Li
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Liyang Liu
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Xuegong Zhang
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China.
- School of Life Sciences and Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China.
| | - Shao Li
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China.
- School of Life Sciences and Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China.
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10
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Minami T, Yuasa N, Takeuchi E, Miyake H, Nagai H, Miyata K, Kiriyama A. Superficially Spreading Signet-Ring Cell Carcinoma Perpendicularly Colliding with Gastric Adenoma: a Rare Case Report. J Gastrointest Cancer 2018; 50:609-612. [PMID: 29441461 DOI: 10.1007/s12029-018-0076-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
- Takayuki Minami
- Department of Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan.
| | - Norihiro Yuasa
- Department of Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Eiji Takeuchi
- Department of Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Hideo Miyake
- Department of Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Hidemasa Nagai
- Department of Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Kanji Miyata
- Department of Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Ayami Kiriyama
- Department of Pathology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
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11
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Na HK, Cho CJ, Bae SE, Lee JH, Park YS, Ahn JY, Kim DH, Choi KD, Song HJ, Lee GH, Jang SJ, Jung HY. Atrophic and Metaplastic Progression in the Background Mucosa of Patients with Gastric Adenoma. PLoS One 2017; 12:e0169456. [PMID: 28072871 PMCID: PMC5225017 DOI: 10.1371/journal.pone.0169456] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 12/16/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND In patients with adenoma, assessing premalignant changes in the surrounding mucosa is important for surveillance. This study evaluated atrophic and metaplastic progression in the background mucosa of adenoma or early gastric cancer (EGC) cases. METHODS Among 146 consecutive patients who underwent endoscopic resection for intestinal-type gastric neoplasia, the adenoma group included 56 patients with low-grade dysplasia and the ECG group included 90 patients with high-grade dysplasia or invasive carcinoma. For histology, 3 paired biopsies were obtained from the antrum, corpus lesser curvature (CLC), and corpus greater curvature (CGC). Serological atrophy was determined based on pepsinogen A (PGA), progastricsin (PGC), gastrin-17, and total ghrelin levels. Topographic progression of atrophy and/or metaplasia was staged using the operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia assessment (OLGIM) systems. RESULTS Rates of moderate-to-marked histological atrophy/metaplasia in patients with adenoma were 52.7%/78.2% at the antrum (vs. 58.8%/76.4% in EGC group), 63.5%/75.0% at the CLC (vs. 60.2%/69.7% in EGC group), and 10.9%/17.9% at the CGC (vs. 5.6%/7.8% in EGC group). Serological atrophy indicated by PGA and PGC occurred in 23.2% and 15.6% of cases in the adenoma and ECG groups, respectively (p = 0.25). Mean serum gastrin-17 concentrations of the adenoma group and EGC group were 10.4 and 9.0 pmol/L, respectively (p = 0.54). Mean serum total ghrelin levels were 216.6 and 209.5 pg/mL, respectively (p = 0.71). Additionally, between group rates of stage III-IV OLGA and OLGIM were similar (25.9% vs. 25.0%, p = 0.90; 41.8% vs. 44.9%, p = 0.71, respectively). CONCLUSIONS Atrophic and metaplastic progression is extensive and severe in gastric adenoma patients. A surveillance strategy for metachronous tumors should be applied similarly for patients with adenoma or EGC.
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Affiliation(s)
- Hee Kyong Na
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Charles J. Cho
- Department of Biomedical Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Suh Eun Bae
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Jeong Hoon Lee
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Young Soo Park
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Ji Yong Ahn
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Do Hoon Kim
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Kee Don Choi
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Ho June Song
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
- * E-mail:
| | - Gin Hyug Lee
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Se Jin Jang
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Hwoon-Yong Jung
- Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
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12
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Molaei M, Ehtiati A, Mashayekhi R, Rafizadeh M, Zojaji H, Mirsattari D, Kishani Farahani R. Gastric atrophy: use of OLGA staging system in practice. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2016; 9:25-9. [PMID: 26744611 PMCID: PMC4702038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
AIM This study used the OLGA system to characterize the histology pattern of gastritis in dyspeptic outpatients with a mean age of 45 years from regions with different gastric cancer risks. BACKGROUND Several classification systems have been purposed for understanding the status of the gastric mucosa. Currently, the Sydney system is the most widely employed. Nevertheless, the applicability of the Sydney system in therapeutic and prognostic areas is a matter of debate. Given this shortcoming an international group of gastroenterologists and pathologists developed a new system named Operative Link on Gastritis Assessment (OLGA). PATIENTS AND METHODS In this cross-sectional comparative study the OLGA system was used to characterize the histology pattern of gastritis in 685 dyspeptic patients referring to the department of gastroenterology of a training hospital. RESULTS No significant correlation was found between active inflammation and total OLGA score (P > 0.05). Also, no statistically significant correlation was found between activity and intestinal metaplasia, dysplasia, atrophy, and cancer (P > 0.05). Even though, there is a positive correlation between mild chronic inflammation and total OLGA score, no correlation has been identified between chronicity and dysplasia or cancer (P > 0.05). Nearly, In all cases with no dysplasia OLGA score was zero but all patients with gastric cancer OLGA score was more than two. CONCLUSION Generally, the activity is not a useful factor in predicting prognosis and its loss of relation with total OLGA score does not make OLGA score any less predictable.
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Affiliation(s)
- Mahsa Molaei
- Pathology Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ara Ehtiati
- Department of Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Mashayekhi
- Pathology Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mitra Rafizadeh
- Department of Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Homayoun Zojaji
- Pathology Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Dariush Mirsattari
- Pathology Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Roya Kishani Farahani
- Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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13
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Ko Y, Tang J, Sanagapalli S, Kim BSM, Leong RW. Safety of proton pump inhibitors and risk of gastric cancers: review of literature and pathophysiological mechanisms. Expert Opin Drug Saf 2015; 15:53-63. [PMID: 26560097 DOI: 10.1517/14740338.2016.1118050] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Despite being an overall safe drug, several long-term adverse effects are associated with proton pump inhibitors (PPIs). The link between PPI use and gastric neuroendocrine tumors (NETs), gastric adenocarcinomas and Barrett's esophagus progression gastric cancers has been investigated due to PPI-induced hypergastrinemia. AREAS COVERED The pathophysiological mechanisms underlying PPI exposure and gastric NETs, gastric adenocarcinomas and Barrett's esophagus progression are discussed. The quality of randomized control studies, cohort studies and case reports investigating the link between gastric cancers and PPIs are examined. Recommendations for clinicians are provided. EXPERT OPINION PPIs cause a hypergastrinemic state, increasing enterochromaffin-like cell dysplasia and risk of gastric NET development, increasing gastritis severity in the context of Helicobacter pylori infection, and progression of carcinogenesis in a certain predisposed subset of Barrett's esophagus patients. There are case reports of PPI-induced gastric NETs and adenocarcinomas as consequences of these effects. In pernicious anemia and chronic gastritis, clinicians should be aware of potential increased risk of gastric NET development with chronic PPI use in these patients. Eradication status of H. pylori prior to commencing long-term PPI therapy should be established to reduce the risk of severe atrophic gastritis and development of gastric dysplasia.
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Affiliation(s)
- Yanna Ko
- a Gastroenterology and Liver Service , Concord Hospital , Sydney , Australia
| | | | - Santosh Sanagapalli
- a Gastroenterology and Liver Service , Concord Hospital , Sydney , Australia
| | | | - Rupert W Leong
- a Gastroenterology and Liver Service , Concord Hospital , Sydney , Australia
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14
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Lahner E, Zullo A, Hassan C, Perri F, Dinis-Ribeiro M, Esposito G, Di Giulio E, Buscarini E, Bianco MA, De Boni M, Annibale B. Detection of gastric precancerous conditions in daily clinical practice: a nationwide survey. Helicobacter 2014; 19:417-424. [PMID: 25231208 DOI: 10.1111/hel.12149] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The burden of gastric precancerous conditions and factors associated with their detection have not been fully investigated in community-based settings. Little is known about adherence to Sydney system for histopathology of gastric biopsies. OBJECTIVE We aimed to investigate what really happens in clinical practice with regard to the detection of gastric atrophy and intestinal metaplasia in dyspeptic patients. METHODS We performed a nationwide survey of 979 consecutive patients (50-65 years old) with dyspeptic symptoms, examined at 24 gastrointestinal endoscopy units throughout Italy. Clinical information was collected from questionnaires; a standard bioptic mapping was performed in each unit, biopsies from each patient were analyzed by histopathology performed according to daily clinical practice in each local histopathology center. RESULTS Separate descriptions of antral and corporal biopsies were included in 679 pathology reports (69%), whereas Sydney system was applied in 324 reports (33%). Gastric atrophy without intestinal metaplasia (GA) and gastric atrophy with intestinal metaplasia (GIM) were detected in 322 (33%) patients. The full adherence to Sydney system significantly increased the probability of detecting GIM (OR 9.6, 95% CI 5.5-16.7), GA (OR 1.92, 95% CI 1.07-3.44), and either of the conditions (OR 6.67, 95% CI 4.36-10.19). CONCLUSIONS This nationwide survey showed that in one-third of dyspeptic patients, gastric precancerous conditions are detected. In daily routine practice, only 1/3 of histology reports were worked out adhering to Sydney system showing that international guidelines are poorly observed in clinical practice. This may represent a critical element for surveillance strategies for gastric cancer.
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Affiliation(s)
- Edith Lahner
- Department of Digestive and Liver Disease, Sant'Andrea Hospital, II School of Medicine, University Sapienza of Rome, Rome, Italy
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15
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Kasuga A, Yamamoto Y, Fujisaki J, Okada K, Omae M, Ishiyama A, Hirasawa T, Chino A, Tsuchida T, Igarashi M, Hoshino E, Yamamoto N, Kawaguchi M, Fujita R. Clinical characterization of gastric lesions initially diagnosed as low-grade adenomas on forceps biopsy. Dig Endosc 2012; 24:331-8. [PMID: 22925285 DOI: 10.1111/j.1443-1661.2012.01238.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM The aim of this study was to elucidate characteristics of gastric lesions that are initially diagnosed as low-grade adenomas and to establish appropriate treatment. METHODS We retrospectively reviewed 231 lesions initially diagnosed as gastric adenomas. All forceps biopsy samples were histologically diagnosed as category 3 low-grade adenomas according to the revised Vienna Classification. All patients underwent endoscopic resection with endoscopic findings and post-resection diagnoses evaluated subsequently. RESULTS Sixty-three lesions were initially diagnosed as depressed adenomas, and 168 lesions were diagnosed as protruding adenomas. The depressed lesions were significantly smaller (11.6 ± 5.0 mm) than the protruding lesions (17.0 ± 10.8 mm) (P < 0.001). Diagnoses reclassified to category 4 mucosal high-grade neoplasia (i.e. high-grade adenoma, adenocarcinoma in adenoma and adenocarcinoma) were more frequent among depressed lesions (52.4%) than among protruding lesions (31.0%) (P = 0.004). Multivariate analysis of all 231 lesions showed that lesion size larger than 20 mm (P < 0.001) and depressed appearance (including central depression) (P < 0.001) were significant independent factors suggesting cancer. For the 168 protruding lesions, lesion size larger than 20 mm (P < 0.001) and central depression (P < 0.001) were significant independent factors suggesting cancer. For the 63 depressed lesions, lesion size larger than 15 mm (P = 0.016) and a moth-eaten appearance (P = 0.017) were significant independent factors in the pre-treatment diagnosis of cancer. CONCLUSIONS Adenocarcinoma lesions were often found in depressed lesions and protruding lesions with central depression. Endoscopic resection for total biopsy is recommended, even if forceps biopsy indicates low-grade adenoma, as pre-treatment biopsy may be inadequate for an accurate histological diagnosis.
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Affiliation(s)
- Akiyoshi Kasuga
- Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.
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16
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Yin Y, Liu Q, Wang B, Chen G, Xu L, Zhou H. Expression and function of heme oxygenase-1 in human gastric cancer. Exp Biol Med (Maywood) 2012; 237:362-371. [PMID: 22490514 DOI: 10.1258/ebm.2011.011193] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Heme oxygenase-1 (HO-1) potently influences tumor growth and metastasis. To date, no study has been performed on HO-1 expression pattern and its clinicopathological significance in human gastric cancer (GC) cases. In this study, the expression of HO-1 in human GC tissues (n = 74) and matched non-tumoral adjacent parenchyma (n = 46) was investigated by immunohistochemistry. The correlation of HO-1 with the clinicopathological characteristics was analyzed. Results showed that HO-1 was expressed in 62 GC tissues from 74 cases (83.8%), which is significantly higher than non-tumoral adjacent parenchyma (20/46, 43.8%, P < 0.05). A high HO-1 expression rate showed a close association with well/moderate histological differentiation and negative lymph node metastasis (P < 0.05). The expression of matrix metallopeptidase 9 (MMP9) and vascular endothelial growth factor A (VEGF-A) as well as chemosensitivity to cisplatin of MKN-45 cell lines with genetically altered HO-1 status were then determined by realtime polymerase chain reaction and 3-(4,5 dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), respectively. Whether the induction or inhibition of HO-1 by cobalt-protoporphyrin-IX (CoPP) or zinc-protoporphyrin-IX (ZnPP) could affect the sensitivity of MKN-45 cells to cisplatin was also studied. Results showed that the expression of MMP9 and VEGF-A were up-regulated in MKN-45 cells overexpressing HO-1, and down-regulated in HO-1 interfered cells. HO-1 overexpression could lead to an increased resistance to cisplatin, whereas down-regulation of HO-1 expression by siRNA or chemical inhibition of HO-1 could lead to increased chemosensitivity to cisplatin in MKN-45 cells. HO-1 may have multiple effects on protection against carcinogenesis and progression in GC.
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Affiliation(s)
- Yujing Yin
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
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17
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Sugimoto M, Ohno T, Graham DY, Yamaoka Y. Helicobacter pylori outer membrane proteins on gastric mucosal interleukin 6 and 11 expression in Mongolian gerbils. J Gastroenterol Hepatol 2011; 26:1677-1684. [PMID: 21679252 PMCID: PMC3407248 DOI: 10.1111/j.1440-1746.2011.06817.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND AND AIM The levels of interleukin (IL)-6 and IL-11 in the gastric mucosa are related to mucosal inflammation; however, the chronological changes in cytokine expression during different phases of Helicobacter pylori infection and the effects of H. pylori virulence factors, particularly those of outer membrane proteins, remain obscure. The aim of this study was to clarify the chronological changes in cytokine levels in relation to several H. pylori outer membrane proteins. METHODS We studied Mongolian gerbils inoculated with wild-type H. pylori 7.13 for up to 48 weeks and then examined animals infected with oipA, babA, or alpAB isogenic mutants for 12 weeks. Mucosal IL-6 and IL-11 mRNA levels were measured using real-time reverse transcription-polymerase chain reactions. RESULTS High levels of gastric mucosal IL-6 and IL-11 mRNA in gerbils infected with wild-type H. pylori were observed during the chronic phase of infection, reaching maximums at 12 and 6 months, respectively. Infection with oipA and babA mutants resulted in significantly reduced cytokine levels and inflammatory cell infiltrations compared to gerbils infected with wild-type strains, and this persisted throughout the observation period. The alpAB mutants did not infect gerbils. Mucosal IL-6 and IL-11 levels were significantly associated with the grade of inflammatory cell infiltration. CONCLUSIONS OipA and BabA result in more severe H. pylori infection and increased IL-6 and IL-11 levels, which in turn may increase the risk of developing H. pylori-induced gastrointestinal diseases.
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Affiliation(s)
- Mitsushige Sugimoto
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas USA
| | - Tomoyuki Ohno
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas USA
| | - David Y Graham
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas USA
| | - Yoshio Yamaoka
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas USA
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
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18
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Rugge M, Pennelli G, Pilozzi E, Fassan M, Ingravallo G, Russo VM, Di Mario F. Gastritis: the histology report. Dig Liver Dis 2011; 43 Suppl 4:S373-S384. [PMID: 21459343 DOI: 10.1016/s1590-8658(11)60593-8] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice.
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Affiliation(s)
- Massimo Rugge
- Department of Medical Diagnostic Sciences & Special Therapies, University of Padova, Padova, Italy.
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19
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Malfertheiner P, Bornschein J, Selgrad M. Role of Helicobacter pylori infection in gastric cancer pathogenesis: a chance for prevention. J Dig Dis 2010; 11:2-11. [PMID: 20132425 DOI: 10.1111/j.1751-2980.2009.00408.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastric cancer in the absence of strategies implemented for early detection continues to have a dismal prognosis. There are limited options for a curative therapy once patients present with clinical manifestations of this malignant disease. Helicobacter pylori (H. pylori) infection plays a key role in gastric carcinogenesis, supported by epidemiological, preclinical and clinical studies. The recognition of H. pylori infection as a critical risk factor in the development of gastric cancer opens the chance for new venues in prevention strategies.
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Affiliation(s)
- Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger, Magdeburg, Germany.
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20
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Sugimoto M, Ohno T, Graham DY, Yamaoka Y. Gastric mucosal interleukin-17 and -18 mRNA expression in Helicobacter pylori-induced Mongolian gerbils. Cancer Sci 2009; 100:2152-2159. [PMID: 19694753 PMCID: PMC3128813 DOI: 10.1111/j.1349-7006.2009.01291.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2009] [Revised: 07/09/2009] [Accepted: 07/15/2009] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori infection causes characteristic mucosal infiltration of inflammatory cells, resulting in the development of peptic ulcers and gastric cancer in approximately 10% of cases. Different clinical expressions of the infection may reflect different patterns of cytokine expression. Interleukin (IL)-1ss, tumor necrosis factor (TNF)-alpha, IL-17, and IL-18 have been reported to be involved in H. pylori-induced gastric mucosal inflammation, but the details and relation to different patterns of inflammation remain unclear. Moreover, the proinflammatory virulence factor outer inflammatory protein (OipA) was reported to be associated with gastric mucosal inflammatory cytokine levels. To clarify these findings, Mongolian gerbils were infected for up to 12 months with wild-type H. pylori 7.13 or with isogenic oipA mutants for 3 months, and mucosal cytokines (IL-1ss, IL-17, IL-18, and TNF-alpha) mRNA levels were then assessed using real-time RT-PCR. Antral mucosal IL-1beta and IL-18 mRNA levels peaked 1 month after infection, whereas the peak of TNF-alpha mRNA was at 6-12 months; IL-17 levels peaked at 12 months. The inflammatory cell infiltration and mRNA levels of all cytokines studied were significantly lower in oipA mutants than in wild-type-infected gerbils. Mucosal IL-1ss, IL-17, and TNF-alpha expression, but not that of IL-18, were significantly associated with the grade of inflammatory cell infiltration. The pattern of increased inflammatory cytokines differed relative to the phase of the infection and pattern of inflammation. OipA appears to play a role in IL-1ss, IL-17, and TNF-alpha expression and the resulting inflammation.
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Affiliation(s)
- Mitsushige Sugimoto
- Department of Medicine - Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
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21
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Zhao Y, Zhou T, Li A, Yao H, He F, Wang L, Si J. A potential role of collagens expression in distinguishing between premalignant and malignant lesions in stomach. Anat Rec (Hoboken) 2009; 292:692-700. [PMID: 19306436 DOI: 10.1002/ar.20874] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Lack of clinical biomarkers for early gastric cancer without specific early symptoms leads to delayed diagnosis, which contributes to high mortality of gastric cancer. Here, we used oligonucleotide microarray to systematically examine differential gene expression among 33 samples from normal, premalignant, and malignant lesions in stomach. A focal adhesion pathway mainly composed of collagen genes was found to have a significantly different expression profile in gastric cancers compared to premalignant lesions. A subset of collagen genes efficiently separated malignant from premalignant tissues, and two representative genes COL11A1 and COL1A1 were validated in 42 tissue samples with quantitative reverse transcription-PCR and in situ hybridization. The data above suggest that focal adhesion pathway may have a role in the pathogenesis of gastric cancer, and the expression profile of collagen genes may be a potential biomarker to distinguish malignant from premalignant lesions in stomach.
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Affiliation(s)
- Yuan Zhao
- Gastroenterology laboratory, The Institute of Clinic Medical Research, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
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22
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Rugge M, Correa P, Di Mario F, El-Omar E, Fiocca R, Geboes K, Genta RM, Graham DY, Hattori T, Malfertheiner P, Nakajima S, Sipponen P, Sung J, Weinstein W, Vieth M. OLGA staging for gastritis: a tutorial. Dig Liver Dis 2008; 40:650-658. [PMID: 18424244 DOI: 10.1016/j.dld.2008.02.030] [Citation(s) in RCA: 211] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2008] [Accepted: 02/18/2008] [Indexed: 02/07/2023]
Abstract
Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for (intestinal-type) gastric cancer development and the extent/topography of the atrophic changes significantly correlates with the degree of cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. The histology report consequently does not give clinical practitioners and gastroenterologists an explicit message of use in orienting an individual patient's clinical management. Building on current knowledge of the biology of gastritis and incorporating experience gained worldwide by applying the Sydney System for more than 15 years, an international group of pathologists (Operative Link for Gastritis Assessment) has proposed a system for reporting gastritis in terms of stage (the OLGA staging system). Gastritis staging arranges the histological phenotypes of gastritis along a scale of progressively increasing gastric cancer risk, from the lowest (stage 0) to the highest (stage IV). This tutorial aims to provide unequivocal information on how to consistently apply the OLGA staging system in routine diagnostic histology practice.
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Affiliation(s)
- M Rugge
- Department of Medical Diagnostic Sciences & Special Therapies, Pathology Section, University of Padova, Italy.
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Satoh K, Osawa H, Yoshizawa M, Nakano H, Hirasawa T, Kihira K, Sugano K. Assessment of atrophic gastritis using the OLGA system. Helicobacter 2008; 13:225-9. [PMID: 18466398 DOI: 10.1111/j.1523-5378.2008.00599.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND An international group of gastroenterologists and pathologists (Operative Link for Gastritis Assessment (OLGA)) proposed the staging system of atrophy. The aim of this study was to assess the severity of atrophic gastritis using the OLGA system. MATERIALS AND METHODS The subjects comprised 163 H. pylori-positive patients: 18 with early gastric cancers of the intestinal type (GC), 55 with atrophic gastritis (AG), 49 with gastric ulcers or scars (GU), and 41 with duodenal ulcers or scars (DU). Biopsies were taken from the lesser and greater curvatures of the antrum and middle body. The OLGA gastritis stage (0-IV) (the severity and topography of atrophy) was obtained by combining antral with body atrophy scores. The gastritis grade (the severity and topography of inflammation) was obtained by combining antral and body inflammation scores. RESULTS Most (84%) of patients with GC showed stage III or IV. Gastritis stages were significantly higher in patients with GC than in those with AG, GU, and DU. Gastritis stage became higher with age. Gastritis grades were slightly higher in patients with AG than in others. CONCLUSIONS Our results indicate that higher stages are found in patients with GC using the OLGA staging system and that the high risk of GC can be recognized. It is simple to use and useful for the assessment of the severity of atrophic gastritis.
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Affiliation(s)
- Kiichi Satoh
- Division of Gastroenterology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
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Rigoli L, Di Bella C, Verginelli F, Falchetti M, Bersiga A, Rocco A, Nardone G, Mariani-Costantini R, Caruso RA. Histological heterogeneity and somatic mtDNA mutations in gastric intraepithelial neoplasia. Mod Pathol 2008; 21:733-741. [PMID: 18425082 DOI: 10.1038/modpathol.2008.58] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Somatic mutations of mitochondrial DNA (mtDNA) are associated with various types of human cancer. To elucidate their role in gastric carcinogenesis, we analyzed mutations in the displacement loop region of mtDNA in 24 paraffin-embedded gastric intraepithelial neoplasias (formerly dysplasia) from a high gastric cancer risk area in northern Italy. Helicobacter pylori infection was assessed by histological examination (Giemsa staining). Gastritis was classified according to the guidelines of the Updated Sydney System. The mtDNA displacement loop region was amplified and sequenced from gastric intraepithelial neoplasia samples and adjacent non-neoplastic gastric mucosa. The gastric intraepithelial neoplasias were divided into two groups by their association with H. pylori gastritis. Group A with lesions arising on a background of H. pylori-positive gastritis contained 7 patients, and group B with lesions associated with H. pylori-negative gastritis contained 17 patients. Group A had a larger proportion of high-grade lesions than group B and showed a foveolar phenotype (type II dysplasia). Group B had a larger proportion of cases with mtDNA displacement loop region mutations than group A (P=0.004, Fisher's exact test) and exhibited an intestinal phenotype. No evidence of heteroplasmic variants in the mtDNA displacement loop, suggestive of mutations, was detected in gastric biopsies from 25 H. pylori-negative subjects and 60 cancer-unaffected H. pylori-positive patients. These results provide further evidence for the morphologic and mtDNA biomolecular differences of gastric intraepithelial neoplasias, and suggest the existence of two distinct pathways to gastric cancer--corpus-dominant H. pylori gastritis and the atrophy-metaplasia pathway.
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Affiliation(s)
- Luciana Rigoli
- Department of Pediatrics, University Hospital, Messina, Italy
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25
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Sotoudeh M, Derakhshan MH, Abedi-Ardakani B, Nouraie M, Yazdanbod A, Tavangar SM, Mikaeli J, Merat S, Malekzadeh R. Critical role of Helicobacter pylori in the pattern of gastritis and carditis in residents of an area with high prevalence of gastric cardia cancer. Dig Dis Sci 2008; 53:27-33. [PMID: 17492381 DOI: 10.1007/s10620-007-9817-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2006] [Accepted: 02/25/2007] [Indexed: 12/18/2022]
Abstract
We have investigated the role of Helicobacter pylori infection and of other risk factors of gastritis and carditis in residents of a high-risk area for gastric cardia cancer. During a national population-based endoscopic survey, 508 randomly-selected participants aged > or =40 were enrolled. Mucosal biopsies were obtained from six standard sites. Polymorphonuclear (PMN) and mononuclear (MN) infiltration and combined inflammatory scores (CIS) for chronic gastritis and H.pylori were assessed. Relationships of H.pylori and reflux esophagitis with these variables were calculated for cardia and non-cardia subsites. Both PMN and MN infiltrations correlated strongly with H.pylori infection. For PMN the relationship was maximum for the antrum (odds ratio (OR) = 9.4 (5.2-17.1)) and minimum for the gastric body (OR = 1.7 (1.0-2.9)). There was a significant relationship between carditis and H.pylori (OR = 2.8 (1.7-4.9)). A similar relationship was obtained for MN infiltration. In 56% of subjects the mean MN score for the corpus was equal to or greater than that for the antrum. For 59% of subjects the MN score for the cardia was greater than or equal to the antral score. Use of logistic regression revealed that was the main risk factor for gastritis and carditis in all sites. There was an inverse relationship between reflux esophagitis and carditis. H.pylori is the main risk factor for gastritis for all sites of the stomach including the cardia; but this relationship is stronger for the antrum and cardia than for the body. Continuous cardia inflammation may contribute to the high incidence of gastric cardia cancer in this region.
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Affiliation(s)
- Masoud Sotoudeh
- Digestive Diseases Research Centre, Medical Sciences/University of Tehran, Shariati Hospital Kargar, Tehran, Iran
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26
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Lo SS, Lin SC, Wu CW, Chen JH, Yeh WI, Chung MY, Lui WY. Heme oxygenase-1 gene promoter polymorphism is associated with risk of gastric adenocarcinoma and lymphovascular tumor invasion. Ann Surg Oncol 2007; 14:2250-6. [PMID: 17520317 DOI: 10.1245/s10434-006-9290-7] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2006] [Revised: 09/27/2006] [Accepted: 09/28/2006] [Indexed: 11/18/2022]
Abstract
PURPOSE Heme oxygenase-1 (HO-1) gene, which encodes an oxidative response protein, plays a role in cytoprotection. A (GT)n dinucleotide repeat in HO-1 promoter is polymorphic and modulates the transcriptional activity of the gene. A HO-1 gene promoter polymorphism was reported to be associated with the risks of lung adenocarcinoma and oral squamous cancer. In this study, the correlation between the HO-1 gene promoter polymorphism and the clinicopathological characteristics, along with the risk of gastric cancer, was analyzed. EXPERIMENTAL DESIGN We examined the genotypic frequencies of (GT)n repeats in 183 gastric cancer patients and 250 control subjects by PCR-based genotyping and DNA sequencing. The length polymorphisms of (GT)n repeats were classified into short (S) component (n <or= 25), medium (M) component (26 <or= n <or= 30) and long (L) component (n >or= 31). The distribution of S, M and L components in patient and control groups were evaluated to determine the correlation with susceptibility and clinicopathological characteristics of gastric adenocarcinoma. RESULTS Higher frequencies of L-allele, L-allele carrier (S/L, M/L, L/L) and S/L genotype were found in gastric cancer patients. The frequencies of M-allele, M-allele carrier (M/M, M/L, M/S) and M/M genotype were significantly lower in patients with gastric cancer than controls. Furthermore, the frequency of lymphovascular tumor invasion was significantly lower in M-allele carriers compared to non-M-allele carriers (S/S, S/L, L/L) (p = 0.009). CONCLUSIONS These findings suggest that the long (GT)n repeat of HO-1 gene promoter was associated with a higher frequency of gastric adenocarcinoma, and the medium (GT)n repeat might possess protective effect against gastric adenocarcinoma with a lower frequency of lymphovascular invasion in tumors.
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Affiliation(s)
- Su-Shun Lo
- Division of General Surgery, Taipei Veterans General Hospital and National Yang Ming University, No 201, Sec 2, Shih-Pai Rd, Taipei, Taiwan.
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Abstract
Gastric polyps exist in a wide variety of types, most often benign. Endoscopic discovery of gastric polyps necessitates biopsies - not only of the lesion but also of the antral and fundic mucosa to determine the therapeutic strategy and subsequent surveillance. Fundic gland polyps are the most frequent type; they are asymptomatic with no malignant potential. They require neither treatment nor surveillance. Hyperplastic polyps, adenomas and tumors must be totally resected. Biopsies alone are insufficient to assess the extent of malignancy of adenomas and of hyperplastic polyps more than 5 mm in diameter. These polyps are associated with an elevated frequency of precancerous alterations of the gastric mucosa and consequently by an elevated risk of synchronous or metachronous cancer. Eradication of Helicobacter pylorus may reduce the risk of metachronous gastric cancer and recurrence after resection. Carcinoid tumors of the fundus most often occur in patients with hypergastrinemia during atrophic gastritis of autoimmune origin; they are not serious. The advantages and procedures for endoscopic surveillance of patients with a precancerous condition of the gastric mucosa have not yet been clearly established in populations with a low incidence of cancer.
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Affiliation(s)
- Thierry Vallot
- Service d' hépato-gastroentérolgie, CHU Bichat Claude Bernard, Paris.
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Rugge M, Meggio A, Pennelli G, Piscioli F, Giacomelli L, De Pretis G, Graham DY. Gastritis staging in clinical practice: the OLGA staging system. Gut 2007; 56:631-6. [PMID: 17142647 PMCID: PMC1942143 DOI: 10.1136/gut.2006.106666] [Citation(s) in RCA: 345] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The available classifications of gastritis are inconsistently used, possibly because none provides immediate prognostic/therapeutic information to clinicians. As histology reporting of hepatitis in terms of stage is clinically useful and widely accepted, an international group (Operative Link on Gastritis Assessment (OLGA)) proposed an equivalent staging system for reporting gastric histology. Gastritis staging integrates the atrophy score (obtained by biopsy) and the atrophy topography (achieved through directed biopsy mapping). AIM To test in a prospective cross-sectional study whether OLGA staging consistently stratified patients according to their cancer risk and provided clear prognostic/therapeutic information. METHODS OLGA staging for gastric cancer risk (0-IV) and gastritis grading (overall score of the inflammatory infiltrate, grade 1-4) were applied in 439 prospectively enrolled, consecutive, dyspeptic outpatients who underwent endoscopy with standardised biopsy sampling. Incidental neoplastic lesions and coexisting peptic ulcers were recorded. Results were presented as stage (including antral (A) and corpus (C) atrophy scores) and H pylori status (eg, A = 3; C = 2: stage IV; Hp+ve). RESULTS Benign conditions (including duodenal ulcers; p<0.001) consistently clustered in stages 0-II, whereas all neoplastic (invasive and non-invasive) lesions clustered in stages III-IV (p<0.001). CONCLUSIONS Gastritis staging, combined with H pylori status, provided clinically relevant information on the overall status of the gastric mucosa with implications for prognosis, therapy and management.
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Affiliation(s)
- Massimo Rugge
- Anatomia Patologica, Università degli Studi di Padova, Istituto Oncologico del Veneto IOV-IRCCS, Via Aristide Gabelli, 61, 35121 Padova, Italia.
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Yilmaz O, Dursun H, Gürsan N, Pirim I, Yilmaz A, Okcu N. Effects of the myeloperoxidase 463 gene polymorphisms on development of atrophy in H pylori infected or noninfected gastroduodenal disease. World J Gastroenterol 2007; 13:1243-6. [PMID: 17451207 PMCID: PMC4147001 DOI: 10.3748/wjg.v13.i8.1243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [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 investigate the relationship between myelo-peroxidase polymorphisms as a host-related factor and atrophy caused by H pylori.
METHODS: Our study enrolled 77 patients. Biopsy materials obtained during gastrointestinal endoscopies were evaluated for the presence of H pylori. Polymerase chain reaction-restriction fragment length polymorphism assay was used to characterize myeloperoxidase genotypes.
RESULTS: Forty four patients (57.1%) were Hp (+) and 33 (42.9%) were Hp (-). Sixty six (85.7%) had GG genotype, 10 (12.9%) had GA genotype and 1 (1.29%) had AA genotype. The change in atrophy in relation to neutrophil infiltration was significant in Hp (+) patients (P = 0.0001). The change in atrophy in relation to neutrophil infiltration in patients with GG genotype was significant (P = 0.002). However, the change in atrophy in relation to neutrophil infiltration was not significiant in patients with Hp (+) GG genotype (r = 0.066, P = 0.63).
CONCLUSION: Myeloperoxidase genotype is critical for development of atrophy in relation to the severity of inflammation. However, it is interesting to note that, H pylori does not show any additive effect on development of atrophy.
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Affiliation(s)
- Omer Yilmaz
- Department of Gastroenterology, University of Atatürk, Erzurum 25070, Turkey.
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30
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Abstract
The number of patients with gastric cancer has more than doubled since 1985 in developing countries. Thus, the questions of whether it can be predicted from gastritis morphology, who is at risk and who has a lower risk of developing gastric carcinoma are raised. H pylori-infection leads to erosions, ulcerations, carcinoma, mucosa associated lymphoid tissue (MALT)-lymphoma and extragastric diseases only in some individuals. The frequency of ulcerations among H pylori-infected individuals is estimated to be 13%, gastric cancer about 1% and MALT lymphoma around 0.1%. In the literature a multistep model from chronic active H pylori-infection through multifocal atrophy, intestinal metaplasia, dysplasia (intraepithelial neoplasia) and carcinoma has been described. But this model cannot be applied to all routine cases. Since risk factors such as metaplasia and atrophy are paracancerous rather than precancerous conditions, this raises the question whether there is a better morphological marker. Differences in topography, grade and activity of Helicobacter gastritis in the antrum and corpus might be good markers for identifying those who are at risk of developing gastric cancer. It is known that the so-called corpus dominant
H pylori gastritis is found more frequently among individuals with early and advanced gastric cancer and within high risk populations. This is valid both for first-degree relatives of gastric cancer patients and for patients with gastric adenoma and hyperplastic polyps. In conclusion, corpus-dominant H pylori gastritis is significantly more common in patients with advanced and early gastric cancer, first-degree relatives of patients with gastric cancer, patients with gastric adenoma and gastric hyperplastic polyps. Therefore, all these patients are at risk of developing gastric cancer. Next, the question of who is at risk of developing corpus-dominant gastritis is raised. It appears that patients with a low acid output more frequently develop gastric cancer. Eradication therapy is never performed too early but probably sometimes too late after the patients pass a “point of no return”. Large prospective long term studies are necessary to prove this and identify new reliable markers for gastric cancer development.
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Affiliation(s)
- Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Preuschwitzer Str. 101, 95445 Bayreuth, Germany
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31
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Han FC, Li XJ, Jiang H, Qin LP, Li D, Guo YH, Liu ZG, Zhang L, Yan XJ. Detection of H pylori antibody profile in serum by protein array. World J Gastroenterol 2006; 12:4044-8. [PMID: 16810756 PMCID: PMC4087718 DOI: 10.3748/wjg.v12.i25.4044] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To detect multiple H pylori antibodies in serum samples of individuals who carryH pylori by protein array.
METHODS: Recombinant H pylori antigens, urease B subunit (UreB), vacuolating toxin A (VacA) and cytotoxin associated gene A protein (CagA), were prepared and immobilized in matrixes on nitrocellulose membrane by robotics to bind the specific immunoglobulin G (IgG) antibodies in serum. Staphylococcus protein A (SPA) labeled by colloid gold was used to integrate the immuno-complex and gave red color signal. The scanner based on charge-coupled device (CCD) could collect the image signal and convert it into digital signal.
RESULTS: When human IgG was printed on the membrane in increasing concentrations and incubated with immunogold, a linear dose response curve was obtained and the detection limit for IgG was about 0.025 ng. The cutoff values, which were defined as the mean grey level plus 3 times of standard deviation, were 27.183, 28.546 and 27.402, for anti-UreB IgG, anti-CagA IgG and anti-VacA IgG, respectively, as 400 human serum samples with negative H pylori antibodies were detected by the protein array. When 180 serum samples from patients in hospital were employed for detection of IgG against UreB, CagA and VacA, the sensitivity of the protein array was 93.4%, 95.4%, 96.0%, and the specificity was 94.8%, 94.4% and 97.5%, respectively, as compared with the results obtained by ELISA. The assay also showed high reproducibility, uniformity and stability, and the results were available within 30 min.
CONCLUSION: The protein array is a very practical method for rapid detection of multiple antibodies in serum samples. It is especially useful for large scale epidemiological investigation of the infection of H pylori.
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Affiliation(s)
- Feng-Chan Han
- Institute of Genetic Diagnosis, The Fourth Military Medical University, 17 West Changle Road, Xi'an 710032, Shaanxi Province, China.
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Stolte M, Müller H, Talley NJ, O'morain C, Bolling-Sternevald E, Sundin M, Eriksson S, Blum A. In patients with Helicobacter pylori gastritis and functional dyspepsia, a biopsy from the incisura angularis provides useful diagnostic information. Pathol Res Pract 2006; 202:405-413. [PMID: 16678357 DOI: 10.1016/j.prp.2006.01.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2005] [Accepted: 01/27/2006] [Indexed: 11/25/2022]
Abstract
The aim of this study was to assess whether the taking of an additional biopsy from the incisura angularis increases the chance of detecting maximal degrees of atrophy and intestinal metaplasia (IM) in patients with Helicobacter pylori gastritis and functional dyspepsia. At entry into a randomised trial, biopsies were taken from 328 patients (mean age 48 years), two from both the gastric antrum and corpus, and one from the incisura angularis, and comparative grading of gastritis variables was carried out. Biopsy material from the gastric antrum, corpus, and the incisura angularis revealed no notable differences in atrophy or an incidence of IM and mucosa-associated lymphatic tissue. However, when the incisura biopsies were classified histologically, 58% contained antral mucosa (AM), 18% corpus mucosa (CM), and 24% intermediate zone mucosa. AM at the incisura was associated with considerably more severe gastritis in both the incisura and antrum (14% atrophy, 20% IM) than in CM of incisura (2% atrophy, 6% IM). Corpus atrophy and IM were rare in the AM group and absent from the CM group. Incisura angularis biopsy in patients with H. pylori gastritis and functional dyspepsia does give additional information regarding the severity of gastritis expected in the corpus and antrum. Antral-type mucosa in the incisura angularis region seems to indicate an increased risk for the development of atrophy and/or IM.
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Stolte M, Vieth M. Gastritis and gastric cancer: which morphological type of Helicobacter gastritis is a precancerous risk? ACTA ACUST UNITED AC 2005; 6:110-1. [PMID: 16045597 DOI: 10.1111/j.1443-9573.2005.00210.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- M Stolte
- Institut für Pathologie, Klinikum Bayreuth, Bayern, Germany.
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Ali M, Khan AA, Tiwari SK, Ahmed N, Rao LV, Habibullah CM. Association between cag-pathogenicity island in Helicobacter pylori isolates from peptic ulcer, gastric carcinoma, and non-ulcer dyspepsia subjects with histological changes. World J Gastroenterol 2005; 11:6815-22. [PMID: 16425389 PMCID: PMC4725035 DOI: 10.3748/wjg.v11.i43.6815] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2005] [Revised: 04/26/2005] [Accepted: 04/30/2005] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the presence of the cag-pathogenicity island and the associated histological damage caused by strains with complete cag-PAI and with partial deletions in correlation to the disease status. METHODS We analyzed the complete cag-PAI of 174 representative Helicobacter pylori (H pylori ) clinical isolates obtained from patients with duodenal ulcer, gastric ulcer, gastric cancer, and non-ulcer dyspepsia using eight different oligonucleotide primers viz cagA1, cagA2, cagAP1, cagAP2, cagE, cagT, LEC-1, LEC-2 spanning five different loci of the whole cag-PAI by polymerase chain reaction (PCR). RESULTS The complete screening of the genes comprising the cag-PAI showed that larger proportions of subjects with gastric ulcer (97.8%) inhabited strains with complete cag-PAI, followed by gastric cancer (85.7%), non-ulcer dyspepsia (7.1%), and duodenal ulcer (6.9%), significant differences were found in the percentage distribution of the genes in all the clinical groups studied. It was found that strains with complete cag-PAI were able to cause severe histological damage than with the partially deleted ones. CONCLUSION The cag-PAI is a strong virulent marker in the disease pathogenesis as it is shown that a large number of those infected with strain with complete cag-PAI had one or the other of the irreversible gastric pathologies and interestingly 18.5% of them developed gastric carcinoma. The presence of an intact cag-PAI correlates with the development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease. Partial deletions of the cag-PAI appear to be sufficient to render the organism less pathogenic.
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Affiliation(s)
- Mahaboob Ali
- Center for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500 058, Andhra Pradesh, India
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Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: increase in the signet ring cell type. Arch Pathol Lab Med 2004; 128:765-70. [PMID: 15214826 DOI: 10.5858/2004-128-765-dtitia] [Citation(s) in RCA: 288] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
CONTEXT During the last 50 years, the incidence and mortality of gastric cancer has declined in many countries. This decline has primarily included the intestinal type (Lauren classification). However, there is an impression among pathologists that the diffuse type, especially the signet ring cell subtype, has become more prevalent. OBJECTIVES Using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, we analyzed the trends of the 2 primary types (intestinal and diffuse) of gastric carcinomas from 1973 through 2000. DESIGN Trends in age-adjusted rates were determined for gastric carcinomas through the SEER statistical program (SEER*Stat), which is available on the Internet to the public. RESULTS During the period studied, the intestinal type continued to decline in males, females, African Americans, and whites. The intestinal type was more common in males than in females and more common in African Americans than in whites. In contrast, a consistent increase in the rate of the diffuse type of gastric carcinoma was seen during this period. The rate increased from 0.3 cases per 100 000 persons in 1973 to 1.8 cases per 100 000 persons in 2000. This increase was seen in males, females, African Americans, and whites. The predominant increase occurred in the signet ring type. CONCLUSIONS The results indicate a progressive decrease in the incidence of the intestinal type of gastric cancer and an increase in the diffuse type of gastric carcinoma, especially the signet ring cell type. The clinical implications of the increase are considered.
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Affiliation(s)
- Donald Earl Henson
- Department of Pathology and the Office of Cancer Prevention and Control, The George Washington University Cancer Institute, Washington, DC 20037, USA.
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36
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Weiss MM, Kuipers EJ, Postma C, Snijders AM, Stolte M, Vieth M, Pinkel D, Meuwissen SGM, Albertson D, Meijer GA. Genome wide array comparative genomic hybridisation analysis of premalignant lesions of the stomach. Mol Pathol 2004; 56:293-8. [PMID: 14514924 PMCID: PMC1187341 DOI: 10.1136/mp.56.5.293] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Gastric cancer is one of the most frequent malignancies in the world, ranking fifth in the Netherlands as a cause of cancer death. Surgery is the only curative treatment for advanced cases, but results of gastrectomy largely depend on the stage of the disease. A better understanding of the mechanisms of progression from a preneoplastic condition through intraepithelial neoplasia to invasive cancer may provide information relevant to designing focused prevention strategies. METHODS Because the pattern of chromosomal aberrations in precursors of gastric cancer is unclear, 11 gastric polyps with intraepithelial neoplasia (three hyperplastic polyps and eight adenomas) were analysed by microarray comparative genomic hybridisation to study chromosomal instability in precursors of gastric cancer. RESULTS Chromosomal aberrations were detected in all specimens. Adenomas showed no more chromosomal aberrations than did the hyperplastic polyps. The most frequent aberrations were gain of 7q36 and 20q12, and loss of 5q14-q21 in the adenomas, and loss of 15q11-14, 1p21-31, and 21q11-21.2 in the hyperplastic polyps. The most frequent chromosomal aberration in common to both types was loss of 9p21.3. CONCLUSION Hyperplastic polyps showed many chromosomal aberrations, confirming that neoplastic transformation can occur in these lesions. These observations are consistent with the existence of two morphologically and genetically distinct pathways to gastric cancer-the hyperplastic polyp pathway and the (intestinal type) adenoma pathway. The relative contribution of each to gastric carcinogenesis in general, and how they compare to patterns of chromosomal aberrations in the more prevalent flat foci of intraepithelial neoplasia remain to be determined.
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Affiliation(s)
- M M Weiss
- Department of Pathology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
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Han FC, Ng HC, Ho B. Stability of randomly amplified polymorphic DNA fingerprinting in genotyping clinical isolates of Helicobacter pylori. World J Gastroenterol 2003; 9:2021-4. [PMID: 12970898 PMCID: PMC4656666 DOI: 10.3748/wjg.v9.i9.2021] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: H pylori genomes are highly diversified. This project was designed to genotype H pylori isolates by the polymerase chain reaction (PCR)-based randomly amplified polymorphic DNA (RAPD) fingerprinting technique and to verify its stability by Southern blotting and DNA sequencing.
METHODS: Clinical isolates of H pylori were cultured from gastric antra and cardia of 73 individuals, and genomic DNA was prepared for each isolate. RAPD was carried out under optimized conditions. 23S rDNA was regarded as an internal control, and a 361 bp rDNA fragment (RDF) was used as a probe to screen the RAPD products by Southern blotting. Ten RDFs from different clinical isolates and the flanking regions (both upstream and downstream) of four RDFs were amplified and sequenced.
RESULTS: H pylori isolates from different individuals had different RAPD profiles, but the profiles for isolates cultured from different gastric sites of a given individual were identical in all but one case. Isolates from 27 individuals were RDF positive by Southern blotting. Sequences of the RDFs and their flanking regions were almost the same between the RDF positive and negative isolates as determined by Southern blotting. There was no binding site for random PCR primer inside the sequences.
CONCLUSION: RAPD is very useful in genotyping H pylori grossly on a large scale. However, it seems unstable in amplification of low yield fragments, especially those that do not appear as visible bands on the agarose gel stained with EB, since the primer is partially matched to the template.
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Affiliation(s)
- Feng-Chan Han
- Department of Microbiology, Faculty of Medicine, National University of Singapore, Republic of Singapore.
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Han FC, Gong M, Ng HC, Ho B. Identification of H. pylori strain specific DNA sequences between two clinical isolates from NUD and gastric ulcer by SSH. World J Gastroenterol 2003; 9:1747-51. [PMID: 12918113 PMCID: PMC4611536 DOI: 10.3748/wjg.v9.i8.1747] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: The genomes of Helicobacter pylori (H. pylori) from different individuals are different. This project was to identify the strain specific DNA sequences between two clinical H. pylori isolates by suppression subtractive hybridization (SSH).
METHODS: Two clinical H. pylori isolates, one from gastric ulcer (GU, tester) and the other from non-ulcer dyspepsia (NUD, driver), were cultured and the genomic DNA was prepared and submitted to Alu I digestion. Then two different adaptors were ligated respectively to the 5’-end of two aliquots of the tester DNA fragments and SSH was made between the tester and driver DNA. The un-hybridized tester DNA sequences were amplified by two sequential PCR and cloned into pGEM-T-Easy Vector. The tester strain specific inserts were screened and disease related DNA sequences were identified by dot blotting.
RESULTS: Among the 240 colonies randomly chosen, 50 contained the tester strain specific DNA sequences. Twenty three inserts were sequenced and the sizes ranged from 261 bp to 1036 bp. Fifteen inserts belonged to the H.pylori plasmid pHPO100 that is about 3.5 kb and codes a replication protein A. Other inserts had patches of homologous to the genes of H.pylori in GenBank. Various patterns of dot blots were given and no GU strain unique DNA sequences were found when 4 inserts were used as probes to screen the genomic DNA from 27 clinical isolates, 8 from GU, 12 from duodenum ulcer (DU), 4 from GU-DU, 2 from NUD and 1 from gastric cancer (GC). But a 670 bp DNA fragment (GU198) that was a bit homologous to the 3’-end of the gene of thymidylate kinase was positive in 7 GU strains (7/8), 3 GU-DU strains (3/4) and 3 DU strains (3/12). A 384 bp fragment (GU79) of the replication gene A (repA) was positive only in 4 H.pylori isolates, 2 from GU and 2 from GU-DU.
CONCLUSION: Differences exist in the genes of different H.pylori isolates. SSH is very effective to screen H.pylori strain specific DNA sequences between two clinical isolates, and some of these sequences may have clinical significance.
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Affiliation(s)
- Feng-Chan Han
- Department of Microbiology, Faculty of Medicine, National University of Singapore.
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