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Vavallo M, Cingolani S, Cozza G, Schiavone FP, Dottori L, Palumbo C, Lahner E. Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective. Int J Mol Sci 2024; 25:6818. [PMID: 38999928 PMCID: PMC11241626 DOI: 10.3390/ijms25136818] [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: 05/12/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/14/2024] Open
Abstract
Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological-psychiatric up to gastrointestinal and less commonly to gynecological-obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.
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Affiliation(s)
| | | | | | | | | | | | - Edith Lahner
- Gastroenterology Unit, Sant’Andrea University Hospital, Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy (G.C.); (F.P.S.)
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Smith SI, Schulz C, Ugiagbe R, Ndip R, Dieye Y, Leja M, Onyekwere C, Ndububa D, Ajayi A, Jolaiya TF, Jaka H, Setshedi M, Gunturu R, Otegbayo JA, Lahbabi-Amrani N, Arigbabu AO, Kayamba V, Nashidengo PA. Helicobacter pylori Diagnosis and Treatment in Africa: The First Lagos Consensus Statement of the African Helicobacter and Microbiota Study Group. Dig Dis 2024; 42:240-256. [PMID: 38493766 DOI: 10.1159/000537878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 02/14/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is the most prevalent type of bacterial infection. Current guidelines from different regions of the world neglect specific African conditions and requirements. The African Helicobacter and Microbiota Study Group (AHMSG), founded in 2022, aimed to create an Africa-specific consensus report reflecting Africa-specific issues. SUMMARY Eighteen experts from nine African countries and two European delegates supported by nine African collaborators from eight other countries prepared statements on the most important African issues in four working groups: (1) epidemiology, (2) diagnosis, (3) indications and prevention, and (4) treatment. Limited resources, restricted access to medical systems, and underdeveloped diagnostic facilities differ from those of other regions. The results of the individual working groups were presented for the final consensus voting, which included all board members. KEY MESSAGES There is a need for further studies on H. pylori prevalence in Africa, with diagnosis hinged on specific African situation. Treatment of H. pylori in the African setting should be based on accessibility and reimbursement, while indication and prevention should be defined in specific African countries.
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Affiliation(s)
- Stella I Smith
- Molecular Biology and Biotechnology Department, Nigerian Institute of Medical Research, Lagos, Nigeria
| | - Christian Schulz
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
| | - Rose Ugiagbe
- Department of Medicine, University of Benin Teaching Hospital, Benin, Nigeria
| | - Roland Ndip
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
| | - Yakhya Dieye
- Pole of Microbiology, Institut Pasteur de Dakar, Dakar, Senegal
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Charles Onyekwere
- Department of Medicine, Lagos State University Teaching Hospital, Ikeja, Nigeria
| | - Dennis Ndububa
- Department of Medicine, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
| | - Abraham Ajayi
- Molecular Biology and Biotechnology Department, Nigerian Institute of Medical Research, Lagos, Nigeria
| | | | - Hyasinta Jaka
- Department of Internal Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
| | - Mashiko Setshedi
- Departments of Medicine, Division of Gastroenterology, University of Cape Town, Cape Town, South Africa
| | - Revathi Gunturu
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | | | - Naima Lahbabi-Amrani
- Faculty of Medicine and Pharmacy in Rabat, University Mohammed V, Rabat, Morocco
| | | | - Violet Kayamba
- Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia
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Lahner E, Dilaghi E, Dottori L, Annibale B. Not all that is corpus restricted is necessarily autoimmune. Gut 2023; 72:2384-2385. [PMID: 36357166 DOI: 10.1136/gutjnl-2022-328959] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 10/29/2022] [Indexed: 11/12/2022]
Affiliation(s)
- Edith Lahner
- Department of Medical-Surgical Sciences and Translational Medicine, University of Rome La Sapienza, Rome, Lazio, Italy
| | - Emanuele Dilaghi
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, School of Medicine, University Sapienza, University of Rome La Sapienza, Rome, Italy
| | - Ludovica Dottori
- Department of Medical-Surgical Sciences and Translational Medicine, University of Rome La Sapienza, Rome, Lazio, Italy
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Kim N, Yoon H. Atrophic Gastritis and Intestinal Metaplasia. HELICOBACTER PYLORI 2023:641-659. [DOI: 10.1007/978-981-97-0013-4_55] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Yang H, Zhou X, Hu B. The 'reversibility' of chronic atrophic gastritis after the eradication of Helicobacter pylori. Postgrad Med 2022; 134:474-479. [PMID: 35382697 DOI: 10.1080/00325481.2022.2063604] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/31/2022] [Indexed: 02/07/2023]
Abstract
Gram-negative bacterium Helicobacter pylori (H. pylori) infection is lifelong and usually acquired in childhood, which is etiologically linked to gastric cancer (GC). H. pylori gastritis is defined as an infectious disease with varying severity in virtually all infected subjects. Chronic atrophic gastritis (CAG) is the precancerous condition with the decrease or the loss of gastric glands, which can further be replaced by metaplasia or fibrosis. Patients with advanced stages of CAG are at higher risk of GC and should be followed up with a high-quality endoscopy every 3 years. H. pylori infection is the most common cause and its eradication is recommended, which may contribute to the regression of CAG. However, it is controversial whether CAG is reversible after eradication therapy. In the review, we discuss recent studies which provide important insights into whether CAG is 'reversibility' and when it may progress into GC after eradicating H. pylori.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xinyue Zhou
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Shahini E, Maida M. Surveillance strategies for precancerous gastric conditions after Helicobacter pylori eradication: There is still need for a tailored approach. World J Gastroenterol 2021; 27:8033-8039. [PMID: 35046629 PMCID: PMC8678819 DOI: 10.3748/wjg.v27.i46.8033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 10/03/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Prevailing evidence declares that Helicobacter pylori (H. pylori) eradication therapy could shift precancerous gastric conditions (PGC) and positively confines gastric cancer (GC) risk during long-term endoscopic follow-up. Nonetheless, there is a yet unsolved controversy regarding the best-individualized surveillance strategies following H. pylori eradication, based on malignant risk stratification. This last dispute is due to the uncertainty of contemporary evidence and the role of H. pylori inflammatory changes in underestimating PGC at the index endoscopy. However, the current state of the art suggests that it is reasonable that high-quality endoscopy with histological assessment for the most accurate diagnosis of PGC may be delayed in selected high-risk patients without alarm signs for malignancy, following the eradication of H. pylori. Notwithstanding, these aspects need to be further examined in the next future to establish and optimize the most beneficial and cost-effective strategies for recognizing and managing H. pylori-positive patients with PGC in the short- and long-term follow-up. Accordingly, additional studies are yet required to sharpen the hazard stratification of patients with the greatest chance of GC evolution, also recognizing the evolving racial, ethnic, immigration factors and the necessity of novel biomarkers to limit GC development or accomplish a diagnosis of malignancy at an early stage.
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Affiliation(s)
- Endrit Shahini
- Division of Gastroenterology, National Institute of Research "Saverio De Bellis", Castellana Grotte (Bari) 70013, Italy
| | - Marcello Maida
- Section of Gastroenterology, S.Elia - Raimondi Hospital, Caltanissetta 93017, Italy
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Bloomquist MS, Powell J, Masand RP, Dhall D, Karamchandani DM, Jain S. Lack of uniformity in reporting autoimmune gastritis among a diverse group of pathologists. Ann Diagn Pathol 2021; 56:151840. [PMID: 34773775 DOI: 10.1016/j.anndiagpath.2021.151840] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 10/06/2021] [Indexed: 12/21/2022]
Abstract
Autoimmune gastritis (AIG) is a clinicopathologic diagnosis requiring characteristic histopathology and correlation with laboratory work-up. To better understand how the diagnosis of AIG is made and reported in the pathology community, we conducted an anonymous web-based survey which was circulated among a diverse group of pathologists. Excluding trainees there were 64 respondents: 25 academic gastrointestinal pathologists (AGI, 39%), 22 academic general pathologists (AGP, 34%), 17 private general pathologists (PP, 27%). Our survey results highlighted variations in work-up and sign-out practices. The type of metaplasia needed to diagnose AIG lacked consensus. There was variation in accurate interpretation of immunostains with a trend towards more accurate diagnosis of enterochromaffin-like (ECL) cell hyperplasia by AGI (92%) and AGP (95%) than PP (71%) (p = 0.07). G-cells in antrum on neuroendocrine immunostain, a mimicker of ECL cell hyperplasia, was more frequently misdiagnosed by PP/ AGP (44%), versus AGI (12%) (p = 0.02). A triple immunostain panel (H. pylori, neuroendocrine, gastrin) was used in the work-up of AIG by 72% of AGI versus 23% AGP and 12% PP (p = 0.000061). The less-specific term "atrophic gastritis" was used in the diagnostic line more by respondents with >10 years sign-out experience compared with others (p = 0.04). In conclusion, the survey results highlighted deficiencies in the interpretation of neuroendocrine immunostains which is crucial for AIG diagnosis, as well as variation in reporting practices and definitions. Uniform criteria and terminology are needed in this field to improve communication with clinicians, resulting in appropriate testing and follow-up.
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Affiliation(s)
- M Suzanne Bloomquist
- Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
| | - John Powell
- Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
| | - Ramya P Masand
- Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
| | - Deepti Dhall
- University of Alabama at Birmingham, 619 19th St S, Birmingham, AL 35233, USA.
| | - Dipti M Karamchandani
- Penn State Health Milton S. Hershey Medical Center, 500 University Dr., Hershey, PA 17033, USA.
| | - Shilpa Jain
- Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
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Weng CY, Xu JL, Sun SP, Wang KJ, Lv B. Helicobacter pylori eradication: Exploring its impacts on the gastric mucosa. World J Gastroenterol 2021; 27:5152-5170. [PMID: 34497441 PMCID: PMC8384747 DOI: 10.3748/wjg.v27.i31.5152] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 06/14/2021] [Accepted: 07/15/2021] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infects approximately 50% of all humans globally. Persistent H. pylori infection causes multiple gastric and extragastric diseases, indicating the importance of early diagnosis and timely treatment. H. pylori eradication produces dramatic changes in the gastric mucosa, resulting in restored function. Consequently, to better understand the importance of H. pylori eradication and clarify the subsequent recovery of gastric mucosal functions after eradication, we summarize histological, endoscopic, and gastric microbiota changes to assess the therapeutic effects on the gastric mucosa.
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Affiliation(s)
- Chun-Yan Weng
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Jing-Li Xu
- Department of Gastrointestinal Surgery, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Shao-Peng Sun
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Kai-Jie Wang
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Bin Lv
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
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Marubashi K, Takakusagi S, Yokoyama Y, Kizawa K, Kosone T, Tojima H, Takagi H. Changes of 18 F-fluoro-2-deoxyglucose position-emission tomography findings by the eradication of Helicobacter pylori in the stomach. Helicobacter 2021; 26:e12797. [PMID: 33682972 DOI: 10.1111/hel.12797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 02/13/2021] [Accepted: 02/19/2021] [Indexed: 12/09/2022]
Abstract
PURPOSE Helicobacter pylori (HP) infection is reported to increase 18 F-fluoro-2-deoxyglucose (FDG) accumulation in the stomach. The accumulation of FDG by positron-emission tomography (FDG-PET) in the stomach for the voluntary health examinees of cancer checkup was examined before and after the HP eradication. SUBJECTS AND METHODS From March 2013 to October 2015, eighty-one subjects were performed FDG-PET to detect cancer at the health checkup. All of them were also surveyed by esophagogastroduodenoscopy. Subjects were classified as the 33 cases of HP positive (group A), 38 cases of originally negative (group B), and the 10 negative cases by HP eradication therapy (group C). Group A was treated by combination of amoxicillin, clarithromycin, and proton pump inhibitor for a week, and all of them eradicated HP. A part of group A (n = 7) was serially performed FDG-PET one to five years after the treatment and compared the maximum standard uptake value of FDG (SUV) around the fundic gland region. RESULTS SUV of group A (3.55 ± 0.69) was significantly higher than those of both group B (2.96 ± 0.72) and group C (2.89 ± 0.51) (p < 0.01, respectively). Groups B and C are almost comparable and showed no significant difference during the course. In group A, HP eradication significantly decreased the SUV to 3.1 ± 0.43 (P < .01). SUV after the eradication was significantly reduced (P < .01) in the mild to moderate atrophy (C1-C3) group according to Kimura and Takemoto classification of chronic gastritis of group A. Although SUV in the advanced atrophy group (O1-O3) tended to decline after the eradication, the change was not significant. CONCLUSION HP-infected stomach showed higher FDG uptake in the fundic gland region and HP eradication decreased the uptake in the mild to moderate atrophic gastritis but not in the severe atrophic gastritis.
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Affiliation(s)
- Kyoko Marubashi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Japan
| | - Satoshi Takakusagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Japan
| | - Yozo Yokoyama
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Japan
| | - Kazuko Kizawa
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Japan
| | - Takashi Kosone
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Japan
| | - Hiroki Tojima
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Hitoshi Takagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Japan
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Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells. Cancers (Basel) 2020; 12:cancers12113477. [PMID: 33266504 PMCID: PMC7700139 DOI: 10.3390/cancers12113477] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/19/2020] [Accepted: 11/21/2020] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Generally, we know that cancers represent genetic changes in tumour cells, but we most often do not know the causes of cancers or how they develop. Our knowledge of the regulation of gastric acid secretion is well known, with the gastric hormone gastrin maintaining gastric acidity by stimulation of the enterochromaffin-like (ECL) cell to release histamine, which subsequently augments acid secretion. Furthermore, it seems to be a general principle that stimulation of function (which, for the ECL cell, is release of histamine) in a parallel way stimulates the proliferation of the same cell. Long-term hyperstimulation of cell division predisposes to genetic changes and, thus, development of tumours. All conditions with reduced gastric acidity result in an increased risk of gastric tumours due to elevated gastrin in order to restore gastric acidity. It is probable that Helicobacter pylori infection (the most important cause of gastric cancer), as well as drugs inhibiting gastric acid secretion induce gastric cancer in the long-term, due to an elevation of gastrin caused by reduced gastric acidity. Gastric carcinomas have been shown to express ECL cell markers, further strengthening this relationship. Abstract The stomach is an ideal organ to study because the gastric juice kills most of the swallowed microbes and, thus, creates rather similar milieu among individuals. Combined with a rather easy access to gastric juice, gastric physiology was among the first areas to be studied. During the last century, a rather complete understanding of the regulation of gastric acidity was obtained, establishing the central role of gastrin and the histamine producing enterochromaffin-like (ECL) cell. Similarly, the close connection between regulation of function and proliferation became evident, and, furthermore, that chronic overstimulation of a cell with the ability to proliferate, results in tumour formation. The ECL cell has long been acknowledged to give rise to neuroendocrine tumours (NETs), but not to play any role in carcinogenesis of gastric adenocarcinomas. However, when examining human gastric adenocarcinomas with the best methods presently available (immunohistochemistry with increased sensitivity and in-situ hybridization), it became clear that many of these cancers expressed neuroendocrine markers, suggesting that some of these tumours were of neuroendocrine, and more specifically, ECL cell origin. Thus, the ECL cell and its main regulator, gastrin, are central in human gastric carcinogenesis, which make new possibilities in prevention, prophylaxis, and treatment of this cancer.
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Yoon K, Kim N. Significance of Helicobacter pylori Eradication on Atrophic Gastritis and Intestinal Metaplasia. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2020. [DOI: 10.7704/kjhugr.2020.0018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
There has been an accumulation of data regarding the chemopreventive effects of <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication. However, it remains unclear how <i>H. pylori</i> infection causes gastric cancer (GC) and how <i>H. pylori</i> eradication can prevent GC. Atrophic gastritis (AG) and intestinal metaplasia (IM) are known as precancerous lesions which mainly lead to intestinal-type GC but to some extent, can also lead to diffuse-type GC. The most important mechanism of AG/IM is <i>H. pylori</i>-induced chronic gastritis. Thus, the reversibility of AG and IM by <i>H. pylori</i> eradication therapy is very important in the prevention of GC. There have been many studies providing data supporting the improvement of AG by the eradication of <i>H. pylori</i> to some extent. In contrast, IM has been regarded as “the point of no return.” However, more recent studies have implied the improvement of IM after eradication, suggesting the importance of early eradication therapy in reversible histological status. In this review, we focused on the reversibility of AG and IM by <i>H. pylori</i> eradication and tried to investigate the predicting factors for the improvement of AG and IM including age, sex, smoking, and diet, as well as <i>H. pylori</i> infection.
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12
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Kumar S, Metz DC, Kaplan DE, Goldberg DS. The association of Helicobacter pylori with pancreatic cancer. ACTA ACUST UNITED AC 2020; 2:157-164. [PMID: 33692655 DOI: 10.1002/ygh2.398] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background & Aims Infection with Helicobacter pylori (HP) affects 50% of the world. Previous studies have suggested an association between HP and pancreatic adenocarcinoma (PC). These association studies have been limited in their ability to identify the incidence and risk factors of PC among HP infected individuals and the impact of HP eradication on PC. Methods Retrospective cohort study within the Veterans Administration of 103,595 patients (median age 62.3; 92.0% male) with HP diagnosis based on pathology, stool antigen, urea breath test, or serum antibody between 1/1/1994-12/31/2018. Primary outcome was future PC diagnosis. A time to event with competing risk analysis was performed, evaluating patient demographics and history, method of HP diagnosis, and whether the patient received HP treatment. Secondary analysis of those treated evaluated whether confirmed eradication was associated with PC. Results The cumulative incidence of PC at 5 and 10 years was 0.37% and 0.54%, respectively. Patients who developed PC were older, male, reside in areas with higher poverty. Preceding diabetes and chronic pancreatitis were strongly associated with PC. Factors not associated with PC included receiving an eradication regimen, diagnosis of an active infection (versus prior exposure alone), and eradication of HP. Conclusions PC after HP is rare. Chronic pancreatitis is the main risk factor for PC. Active HP infection, treatment of HP infection, or eradication of HP are not associated with future PC. This study calls into question the association between PC and HP.
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Affiliation(s)
- Shria Kumar
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania
| | - David C Metz
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania
| | - David E Kaplan
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania.,Division of Gastroenterology, Veterans Health Administration
| | - David S Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine
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Lin HC, Hsu HY, Lin HL, Uang YS, Ho Y, Wang LH. Association Between Acid-Suppressive Agents’ Use and Risk of Hepatocellular Carcinoma. Dose Response 2020; 18:1559325820907530. [PMID: 35185412 PMCID: PMC8851131 DOI: 10.1177/1559325820907530] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 01/01/2020] [Accepted: 01/16/2020] [Indexed: 01/02/2023] Open
Abstract
Background: Acid-suppressive agents (ASAs), which are mostly used in patients with upper gastrointestinal diseases (UGIDs), may influence the risk of hepatocellular carcinoma (HCC). Methods: A population-based retrospective cohort study was conducted. Patients with UGID who used ASAs and those who did not receive ASAs were identified. Patients without UGIDs were randomly selected and matched (comparison group). All groups were followed up for 6 years. A Cox proportional hazard model was used to estimate the risk of HCC among the different groups. Results: Patients with UGID who used ASAs had a significantly elevated HCC risk (adjusted hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.32-1.76] compared to those who did not use ASAs. Patients with UGID who used more than 540 defined daily doses of ASAs had a significantly higher risk of HCC (adjusted HR 2.04; 95% CI, 1.62-2.58). Moreover, the dose effect on HCC risk exhibited a significant increasing trend ( P < .01). Furthermore, patients with UGID who did not use ASAs had a significantly elevated HCC risk (adjusted HR 1.94; 95% CI, 1.59-2.36) compared to the comparison group. Conclusion: The use of ASAs increased the risk of HCC in patients with UGIDs, and the effect of ASAs was dose dependent. In addition, UGIDs alone increased the risk of HCC.
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Affiliation(s)
- Hsiu C. Lin
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei
- Department of Clinical Pathology, Taipei Medical University Hospital, Taipei
| | - Huan Y. Hsu
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei
| | - Hsiu L. Lin
- Department of Neurology, General Cathay Hospital, Sijhih Branch, New Taipei City
| | - Yow S. Uang
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei
| | - Yi Ho
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei
| | - Li H. Wang
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei
- Department of Pharmacy, Taipei Medical University Hospital, Taipei
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Kumar S, Metz DC, Ellenberg S, Kaplan DE, Goldberg DS. Risk Factors and Incidence of Gastric Cancer After Detection of Helicobacter pylori Infection: A Large Cohort Study. Gastroenterology 2020; 158:527-536.e7. [PMID: 31654635 PMCID: PMC7010558 DOI: 10.1053/j.gastro.2019.10.019] [Citation(s) in RCA: 186] [Impact Index Per Article: 37.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/13/2019] [Accepted: 10/16/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nearly all studies of gastric adenocarcinoma in the United States have relied on national cancer databases, which do not include data on Helicobacter pylori infection, the most well-known risk factor for gastric cancer. We collected data from a large cohort of patients in the United States to calculate the incidence of and risk factors for nonproximal gastric adenocarcinomas after detection of H pylori. Secondary aims included identifying how treatment and eradication affect cancer risk. METHODS We performed a retrospective cohort study, collecting data from the Veterans Health Administration on 371,813 patients (median age 62 years; 92.3% male) who received a diagnosis of H pylori infection from January 1, 1994, through December 31, 2018. The primary outcome was a diagnosis of distal gastric adenocarcinoma 30 days or more after detection of H pylori infection. We performed a time to event with competing risk analysis (with death before cancer as a competing risk). RESULTS The cumulative incidence of cancer at 5, 10, and 20 years after detection of H pylori infection was 0.37%, 0.5%, and 0.65%, respectively. Factors associated with cancer included older age at time of detection of H pylori infection (subhazard ratio [SHR], 1.13; 95% confidence interval [CI], 1.11-1.15; P < .001), black/African American race (SHR, 2.00; 95% CI, 1.80-2.22), Asian race (SHR, 2.52; 95% CI, 1.64-3.89) (P < .001 for race), Hispanic or Latino ethnicity (SHR, 1.59; 95% CI, 1.34-1.87; P < .001), and history of smoking (SHR, 1.38; 95% CI, 1.25-1.52; P < .001). Women had decreased risk of gastric adenocarcinoma compared with men (SHR, 0.52; 95% CI, 0.40-0.68; P < .001); patients whose H pylori infection was detected based on serum antibody positivity also had a reduced risk of cancer (SHR 0.74; 95% CI, 0.54-1.04; P = .04). Patients who received treatment for their H pylori infection still had an increased risk of gastric cancer (SHR, 1.16; 95% CI, 0.74-1.83; P = .51) but confirmed H pylori eradication after treatment reduced risk of gastric cancer (SHR, 0.24; 95% CI, 0.15-0.41; P < .001). CONCLUSIONS In a study of 371,813 veterans with a diagnosis of H pylori infection, we found significantly higher risks of gastric cancer in racial and ethnic minorities and smokers. Treatment of H pylori infection decreased risk only if eradication was successful. Studies are needed on the effects of screening high-risk persons and to identify quality measures for diagnosis, resistance patterns, and treatment efficacy.
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Affiliation(s)
- Shria Kumar
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
| | - David C. Metz
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania
| | - Susan Ellenberg
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania
| | - David E. Kaplan
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania,Division of Gastroenterology, Veterans Health Administration
| | - David S. Goldberg
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania,Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine
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15
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Abstract
Gastric acid secretion (i) facilitates digestion of protein as well as absorption of micronutrients and certain medications, (ii) kills ingested microorganisms, including Helicobacter pylori, and (iii) prevents bacterial overgrowth and enteric infection. The principal regulators of acid secretion are the gastric peptides gastrin and somatostatin. Gastrin, the major hormonal stimulant for acid secretion, is synthesized in pyloric mucosal G cells as a 101-amino acid precursor (preprogastrin) that is processed to yield biologically active amidated gastrin-17 and gastrin-34. The C-terminal active site of gastrin (Trp-Met-Asp-Phe-NH2 ) binds to gastrin/CCK2 receptors on parietal and, more importantly, histamine-containing enterochromaffin-like (ECL) cells, located in oxyntic mucosa, to induce acid secretion. Histamine diffuses to the neighboring parietal cells where it binds to histamine H2 -receptors coupled to hydrochloric acid secretion. Gastrin is also a trophic hormone that maintains the integrity of gastric mucosa, induces proliferation of parietal and ECL cells, and is thought to play a role in carcinogenesis. Somatostatin, present in D cells of the gastric pyloric and oxyntic mucosa, is the main inhibitor of acid secretion, particularly during the interdigestive period. Somatostatin exerts a tonic paracrine restraint on gastrin secretion from G cells, histamine secretion from ECL cells, and acid secretion from parietal cells. Removal of this restraint, for example by activation of cholinergic neurons during ingestion of food, initiates and maximizes acid secretion. Knowledge regarding the structure and function of gastrin, somatostatin, and their respective receptors is providing novel avenues to better diagnose and manage acid-peptic disorders and certain cancers. Published 2020. Compr Physiol 10:197-228, 2020.
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Affiliation(s)
- Mitchell L Schubert
- Division of Gastroenterology, Department of Medicine, Virginia Commonwealth University Health System, Richmond, Virginia, USA.,Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA
| | - Jens F Rehfeld
- Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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16
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Suicide journey of H. pylori through gastric carcinogenesis: the role of non-H. pylori microbiome and potential consequences for clinical practice. Eur J Clin Microbiol Infect Dis 2019; 38:1591-1597. [PMID: 31114971 DOI: 10.1007/s10096-019-03564-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 04/09/2019] [Indexed: 12/24/2022]
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17
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Selgrad M, Bornschein J, Kandulski A, Weigt J, Roessner A, Wex T, Malfertheiner P. Combined Gastric and Colorectal Cancer Screening-A New Strategy. Int J Mol Sci 2018; 19:E3854. [PMID: 30513960 PMCID: PMC6321419 DOI: 10.3390/ijms19123854] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 11/21/2018] [Accepted: 11/29/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates. METHODS Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 (61.6%) also underwent gastroscopy to correlate the results for serum pepsinogen I and II (sPG-I and sPG-II), sPG-I/II ratio, and anti-H. pylori antibodies with gastric histopathology findings (graded according to the updated Sydney classification and the Operative Link of Gastritis Assessment (OLGA) and the Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) systems). RESULTS H. pylori was found in 85 patients (30.5%). Chronic atrophic gastritis was diagnosed in 89 (31.9%) patients. High-risk OLGA (III⁻IV) stages were present in 24 patients, and high-risk OLGIM stages were present in 14 patients. There was an inverse correlation of sPG-I with the degree of atrophy and intestinal metaplasia (IM), as well as with the respective OLGA (r = -0.425; p < 0.001) and OLGIM (r = -0.303; p < 0.001) stages. A pathological sPG-I result was associated with a relative risk (RR) of 12.2 (95% confidence interval: 6.29⁻23.54; p < 0.001) for gastric preneoplastic changes. CONCLUSIONS The assessment of serum pepsinogen allows the identification of patients at increased risk of gastric cancer. A prevention strategy of combining a screening colonoscopy with a serological screening for preneoplastic gastric changes should be considered in the general population.
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Affiliation(s)
- Michael Selgrad
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
- Department of Internal Medicine I, University Hospital of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
| | - Jan Bornschein
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford University Hospitals, Headley Way, Oxford OX3 9DU, UK.
| | - Arne Kandulski
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
- Department of Internal Medicine I, University Hospital of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
| | - Jochen Weigt
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
| | - Albert Roessner
- Department of Pathology, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
| | - Thomas Wex
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
- Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Department of Molecular Genetics, Schwiesaustr. 12, 39124 Magdeburg, Germany.
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
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18
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Autoimmunity and Gastric Cancer. Int J Mol Sci 2018; 19:ijms19020377. [PMID: 29373557 PMCID: PMC5855599 DOI: 10.3390/ijms19020377] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 01/23/2018] [Accepted: 01/24/2018] [Indexed: 12/27/2022] Open
Abstract
Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms.
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Galli G, Purchiaroni F, Lahner E, Sacchi MC, Pilozzi E, Corleto VD, Di Giulio E, Annibale B. Time trend occurrence of duodenal intraepithelial lymphocytosis and celiac disease in an open access endoscopic population. United European Gastroenterol J 2017; 5:811-818. [PMID: 29026595 PMCID: PMC5625866 DOI: 10.1177/2050640616680971] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 10/30/2016] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Duodenal intraepithelial lymphocytosis (DIL) is a histological finding characterized by the increase of intraepithelial CD3T-lymphocytes over the normal value without villous atrophy, mostly associated to coeliac disease (CD), Helicobacter pylori (Hp) gastritis and autoimmune diseases. OBJECTIVE To assess the occurrence of DIL, CD and Hp gastritis in an endoscopic population over a 13 year period. METHODS From 2003 to 2015 we included adult patients who consecutively underwent oesophago-gastro-duodenoscopy (OGD) with duodenal biopsies assessing the overall and annual occurrence of DIL and CD and the prevalence of Hp gastritis. RESULTS 160 (2.3%) patients with DIL and 275 (3.9%) with CD were detected among 7001 patients. CD occurrence was higher from 2003 to 2011, while since 2012 DIL occurrence gradually increased significantly compared to CD (p = 0.03). DIL patients were more frequently female (p = 0.0006) and underwent OGD more frequently for dyspepsia (p = 0.002) and for indications not related to gastrointestinal symptoms than CD patients (p = 0.0003). Hp gastritis occurred similarly in CD and DIL patients but the latter had higher frequency of atrophic body gastritis (p = 0.005). CONCLUSIONS DIL is a condition increasing in the general endoscopic population mainly diagnosed by chance. Concomitant gastric histological evaluation is able in one third of DIL patients to identify associated possible causes of DIL, such as Hp and atrophic gastritis.
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Affiliation(s)
- Gloria Galli
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Flaminia Purchiaroni
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Edith Lahner
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Maria Carlotta Sacchi
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Emanuela Pilozzi
- Clinical Molecular Medicine Department, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Vito Domenico Corleto
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Emilio Di Giulio
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Bruno Annibale
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
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20
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Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond. Int J Mol Sci 2017; 18:ijms18081699. [PMID: 28771198 PMCID: PMC5578089 DOI: 10.3390/ijms18081699] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 07/31/2017] [Accepted: 07/31/2017] [Indexed: 12/15/2022] Open
Abstract
Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.
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21
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Helicobacter pylori-Induced Changes in Gastric Acid Secretion and Upper Gastrointestinal Disease. Curr Top Microbiol Immunol 2017; 400:227-252. [PMID: 28124156 DOI: 10.1007/978-3-319-50520-6_10] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Appropriate management of Helicobacter pylori infection of the human stomach is evolving and remains a significant clinical challenge. Acute infection results in hypochlorhydria, whereas chronic infection results in either hypo- or hyperchlorhydria, depending upon the anatomic site of infection. Acute hypochlorhydria facilitates survival of the bacterium and its infection of the stomach. Interestingly, most patients chronically infected with H. pylori manifest a pangastritis with reduced acid secretion due to bacterial virulence factors, inflammatory cytokines, and various degrees of gastric atrophy. While these patients are predisposed to develop gastric adenocarcinoma (~1%), there is increasing evidence from population studies that they are also protected from gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Eradication of H. pylori, in these patients, may provoke GERD in predisposed individuals and may be a contributory factor for the rising incidence of refractory GERD, BE, and EAC observed in Westernized societies. Only ~10% of chronically infected patients, mainly the young, manifest an antral predominant gastritis with increased acid secretion due to a decrease in somatostatin and increase in gastrin secretion; these patients are predisposed to develop peptic ulcer disease. H. pylori-induced changes in acid secretion, in particular hypochlorhydria, may allow ingested microorganisms to survive transit through the stomach and colonize the distal intestine and colon. Such perturbation of gut microbiota, i.e. dysbiosis, may influence human health and disease.
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22
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Zhang Y, Wang H, Bi C, Xiao Y, Liu Z. Expression of CDX2 in gastric cardia adenocarcinoma and its correlation with H. pylori and cell proliferation. Oncotarget 2016; 7:54973-54982. [PMID: 27384681 PMCID: PMC5342395 DOI: 10.18632/oncotarget.10362] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2015] [Accepted: 06/12/2016] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastric cardia cancer (GCC) is located in the distal stomach, and strongly correlates with atrophic gastritis and Helicobacter pylori (H.pylori) infection. Caudal-related homeobox transcription factor 2 (CDX2) is homeobox gene encoding an intestine-specific transcription factor usually expressed in the intestinal epithelium cells. However, in several recent published papers, CDX2 was found to be aberrantly expressed in gastric, thyroid and ovarian cancer. RESULTS Higher expression of CDX2 was found in GCC tissues in comparison with non-malignant cardia mucosa (p<0.05). Moreover, immunohistochemical analysis demonstrated that CDX2 expression correlated with lymphatic metastasis. In addition, we found that CDX2 expression progressively increased with the level of H. pylori infection (p<0.05), and also correlated with cell proliferation, based on Ki67 staining. METHODS To investigate the relationship between CDX2, cell proliferation and H. pylori infection, we detected CDX2, Ki62 and H.pylori expression in 83 non-malignant gastric cardia mucosacases and 60 GCC specimens in the Chaoshan area, a high-risk region for esophageal and gastric cardia cancer. CONCLUSION These findings provide pathological evidence that H. pylori infectionis a driving force of gastric cardia carcinogenesis by upregulating CDX2 and inducing inflammation. These results provide new pathological evidence that H. pylori infection induces GCC tumorigenesis.
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Affiliation(s)
- Ying Zhang
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Hu Wang
- Department of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Chao Bi
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Yinping Xiao
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Zhaoyong Liu
- Department of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
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23
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Atrophic Gastritis and Intestinal Metaplasia. HELICOBACTER PYLORI 2016. [DOI: 10.1007/978-981-287-706-2_52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015; 64:1353-1367. [PMID: 26187502 PMCID: PMC4552923 DOI: 10.1136/gutjnl-2015-309252] [Citation(s) in RCA: 1161] [Impact Index Per Article: 116.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Revised: 06/25/2015] [Accepted: 06/26/2015] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. DESIGN Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. RESULTS All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. CONCLUSIONS A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject.
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Affiliation(s)
- Kentaro Sugano
- Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherland
| | - David Y Graham
- Department of Medicine, Michael E DeBakery VA Medical Center, Baylor College of Medicine, Houston, USA
| | - Emad M El-Omar
- Division of Applied Medicine, Institute of Medical Sciences, Aberdeen University, Aberdeen, UK
| | | | - Ken Haruma
- Department of Gastroenterology, Kawasaki Medical School, Kurashiki, Japan
| | - Masahiro Asaka
- Department of Cancer Preventive Medicine, Hokkaido University, Sapporo, Japan
| | - Naomi Uemura
- Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Japan
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Song H, Ekheden IG, Zheng Z, Ericsson J, Nyrén O, Ye W. Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population. BMJ 2015; 351:h3867. [PMID: 26215280 PMCID: PMC4516137 DOI: 10.1136/bmj.h3867] [Citation(s) in RCA: 202] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/03/2015] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To accurately measure the incidence of gastric cancer among patients with gastric precancerous lesions, and to quantify the excess incidence in comparison with people with normal mucosa on endoscopy and a general population. DESIGN Population based cohort study. SETTING Population of Sweden using data from its national disease registers. PARTICIPANTS 405,172 patients who had gastric biopsy samples taken for non-malignant indications between 1979 and 2011. MAIN OUTCOME MEASURES Incidence of gastric cancer, reported separately for patients with different mucosal changes in biopsy samples. Standardised incidence ratios provided estimation of the relative risk, using the general Swedish population as reference; and hazard ratios were derived from Cox regression modelling for internal comparisons with patients with normal gastric mucosa. RESULTS After excluding the first two years of follow-up, 1599 cases of gastric cancer were identified. The annual crude incidence of gastric cancer was 20 × 10(-5) for those in the normal mucosa group (standardised incidence ratio 1.0), 42 × 10(-5) for those with minor changes (1.5), 59 × 10(-5) for the gastritis group (1.8), 100 × 10(-5) for the atrophic gastritis group (2.8), 129 × 10(-5) for the intestinal metaplasia group (3.4), and 263 × 10(-5) for the dysplasia group (6.5). Cox regression modelling confirmed that excess risks increased monotonically with progressive severity of gastric lesions, with the highest hazard ratio of 10.9 (dysplasia versus normal mucosa, 95% confidence interval 7.7 to 15.4). The increased incidence was stable throughout the follow-up period, and the gaps between cumulative incidence curves grew continuously. CONCLUSIONS Among patients who undergo gastroscopy with biopsy for clinical indications, approximately 1 in 256 with normal mucosa, 1 in 85 with gastritis, 1 in 50 with atrophic gastritis, 1 in 39 with intestinal metaplasia, and 1 in 19 with dysplasia will develop gastric cancer within 20 years. These numbers, along with cost-benefit analyses, should guide future surveillance policies for these particular patient groups.
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Affiliation(s)
- Huan Song
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Isabella Guncha Ekheden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Zongli Zheng
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Jan Ericsson
- Department of Pathology, Karolinska Hospital, Sweden
| | - Olof Nyrén
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
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Park YH, Kim N. Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion of gastric cancer. J Cancer Prev 2015; 20:25-40. [PMID: 25853101 PMCID: PMC4384712 DOI: 10.15430/jcp.2015.20.1.25] [Citation(s) in RCA: 204] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2015] [Revised: 03/18/2015] [Accepted: 03/18/2015] [Indexed: 12/14/2022] Open
Abstract
Atrophic gastritis (AG) and intestinal metaplasia (IM) are the main precursor lesions of gastric cancer as the incidence of gastric cancer increases in the gastric mucosa involved with AG and IM. The prevalence of AG and IM vary depending on countries, even it represents diverse results in the same nation. Usually AG is antecedent of IM but the etiologies of AG and IM are not always the same. The sensitivity and specificity of diagnostic methods to detect AG and IM are different. Furthermore, the management strategy of AG and IM has not been established, yet. Helicobacter pylori infection has been proved as the most important cause of AG and IM. Thus the eradication of H. pylori is very important to prevent the progression to gastric cancer which is still placed in the high rank in morbidity and mortality among cancers. However, the reversibility of AG and IM by eradication of H. pylori which was assumed to be certain by meta-analysis is; however, controversial now. Therefore, the understanding and early diagnosis of AG and IM are very important, especially, in high incidence area of gastric cancer such as Republic of Korea.
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Affiliation(s)
- Yo Han Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Lu B, Li M. Helicobacter pylori eradication for preventing gastric cancer. World J Gastroenterol 2014; 20:5660-5. [PMID: 24914325 PMCID: PMC4024774 DOI: 10.3748/wjg.v20.i19.5660] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Revised: 11/15/2013] [Accepted: 01/03/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC) development, which is one of the most challenging malignant diseases worldwide with limited treatments. In the multistep pathogenesis of GC, H. pylori infection slowly induces chronic active gastritis, which progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia, and then finally to GC. Although eradication of H. pylori is a reasonable approach for the prevention of GC, there have been some contradictory reports, with only some long-term follow-up data showing efficacy of this approach. The inconsistencies are likely due to the insufficient number of participants, relatively short follow-up periods, poor quality of study designs, and the degree and extent of preneoplastic changes at the time of H. pylori eradication. This review analyzes recent high-quality studies to resolve the discrepancies regarding the eradication of H. pylori for GC prevention. The relationship between H. pylori eradication and GC/precancerous lesions/metachronous GC is examined, and the cost-effectiveness of this strategy in the prevention of GC is assessed. Although it is assumed that eradication of H. pylori has the potential to prevent GC, the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined. As a result, additional well-designed trials with longer follow-up periods are needed to clarify this issue.
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Kong YJ, Yi HG, Dai JC, Wei MX. Histological changes of gastric mucosa after Helicobacter pylori eradication: a systematic review and meta-analysis. World J Gastroenterol 2014; 20:5903-11. [PMID: 24914352 PMCID: PMC4024801 DOI: 10.3748/wjg.v20.i19.5903] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Revised: 12/13/2013] [Accepted: 01/08/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review pathological changes of gastric mucosa in gastric atrophy (GA) and intestinal metaplasia (IM) after Helicobacter pylori (H. pylori) eradication. METHODS A systematic search was made of PubMed, Web of Science, EMBASE, ClinicalTrials.gov, OVID and the Cochran Library databases for articles published before March 2013 pertaining to H. pylori and gastric premalignant lesions. Relevant outcomes from articles included in the meta-analysis were combined using Review Manager 5.2 software. A Begg's test was applied to test for publication bias using STATA 11 software. χ(2) and I(2) analyses were used to assess heterogeneity. Analysis of data with no heterogeneity (P > 0.1, I (2) < 25%) was carried out with a fixed effects model, otherwise the causes of heterogeneity were first analyzed and then a random effects model was applied. RESULTS The results of the meta-analysis showed that the pooled weighted mean difference (WMD) with 95%CI was 0.23 (0.18-0.29) between eradication and non-eradication of H. pylori infection in antral IM with a significant overall effect (Z = 8.19; P <0.00001) and no significant heterogeneity (χ(2) = 27.54, I(2) = 16%). The pooled WMD with 95%CI was -0.01 (-0.04-0.02) for IM in the corpus with no overall effect (Z = 0.66) or heterogeneity (χ(2) = 14.87, I(2) =0%) (fixed effects model). In antral GA, the pooled WMD with 95% CI was 0.25 (0.15-0.35) with a significant overall effect (Z = 4.78; P < 0.00001) and significant heterogeneity (χ(2) = 86.12, I(2) = 71%; P < 0.00001). The pooled WMD with 95% CI for GA of the corpus was 0.14 (0.04-0.24) with a significant overall effect (Z = 2.67; P = 0.008) and significant heterogeneity (χ(2) = 44.79, I(2) = 62%; P = 0.0003) (random effects model). CONCLUSION H. pylori eradication strongly correlates with improvement in IM in the antrum and GA in the corpus and antrum of the stomach.
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Farinati F, Cardin R, Piciocchi M, Rodríguez-Castro K, Maddalo G, Rugge M. Helicobacter pylori Infection – The Link Between Oxidative Damage, Cell Proliferation, Apoptosis, and Gastric Cancer. SYSTEMS BIOLOGY OF FREE RADICALS AND ANTIOXIDANTS 2014:1871-1891. [DOI: 10.1007/978-3-642-30018-9_211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Chung WC, Jung SH, Joo KR, Kim MJ, Youn GJ, Kim Y, Lee JS, Lee H, Jung JH, Lee YK. An inverse relationship between the expression of the gastric tumor suppressor RUNX3 and infection with Helicobacter pylori in gastric epithelial dysplasia. Gut Liver 2013; 7:688-95. [PMID: 24312710 PMCID: PMC3848534 DOI: 10.5009/gnl.2013.7.6.688] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Revised: 06/13/2013] [Accepted: 06/17/2013] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.
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Affiliation(s)
- Woo Chul Chung
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Korea
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Abstract
The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values<4 were capable of sterilizing the stomach. H. pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota.
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Cho SJ, Choi IJ. Commentary: H. pylori eradication therapy after subtotal gastrectomy for gastric cancer - can the qualitative be quantified? Authors' reply. Aliment Pharmacol Ther 2013; 38:991. [PMID: 24074310 DOI: 10.1111/apt.12486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 08/22/2013] [Indexed: 12/08/2022]
Affiliation(s)
- S-J Cho
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
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Shi WJ, Liu W, Zhou XY, Ye F, Zhang GX. Associations of Helicobacter pylori infection and cytotoxin-associated gene A status with autoimmune thyroid diseases: a meta-analysis. Thyroid 2013; 23:1294-300. [PMID: 23544831 DOI: 10.1089/thy.2012.0630] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Helicobacter pylori infection is reportedly associated with extradigestive diseases such as immune thrombocytopenic purpura and coronary heart disease. The risk factors for autoimmune thyroid diseases (ATDs) remain largely unknown, and whether H. pylori infection is associated with ATDs is still controversial. The aim of this meta-analysis was to determine the association between H. pylori infection and ATDs. METHODS Studies comparing the prevalence rate of H. pylori infection in patients with ATDs and healthy controls, published in English, were identified through a systematic search in MEDLINE and EMBAS up to June 2012. Serological or nonserological tests were used to confirm H. pylori infection and the presence of cytotoxin-associated gene A (CagA) antigens. The odds ratios (OR) and associated 95% confidence intervals [CI] were obtained. RESULTS Seven studies involving a total of 862 patients met the inclusion criteria and thus were included in our meta-analysis. Overall, H. pylori infection was associated with ATDs (OR 1.92 [CI 1.41-2.61]); the association was significant for Graves' disease (OR 4.35 [CI 2.48-7.64]) but not for Hashimoto's thyroiditis (OR 1.45 [CI 0.92-2.26], p=0.11). No association was observed in the subanalysis of studies using only enzyme-linked immunosorbent assay to detect H. pylori infection (OR 1.38 [CI 0.86-2.19], p=0.18). Five of the seven articles reported the association of CagA seroprevalence and ATDs. CagA seropositivity significantly increased the risk for ATDs by 2.24-fold [CI 1.06-4.75]. CONCLUSIONS Both the prevalence of H. pylori infection and the seroprevalence of CagA-positive strains are associated with ATDs. These findings suggest that H. pylori infection potentially plays a part in the development of ATDs.
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Affiliation(s)
- Wei-Jia Shi
- 1 Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University , Nanjing, Jiangsu, China
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Shin CM, Kim N, Lee HS, Park JH, Ahn S, Kang GH, Kim JM, Kim JS, Lee DH, Jung HC. Changes in aberrant DNA methylation after Helicobacter pylori eradication: a long-term follow-up study. Int J Cancer 2013; 133:2034-42. [PMID: 23595635 DOI: 10.1002/ijc.28219] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Accepted: 04/03/2013] [Indexed: 12/12/2022]
Abstract
Changes of DNA methylation in gastric mucosae after eradication of Helicobacter pylori have not been clarified yet. From this background, we investigated time course of DNA methylation following H. pylori eradication in 221 successfully H. pylori eradicated subjects with endoscopic follow-up at least for 6 months, including 114 controls, 53 subjects with gastric dysplasia and 54 patients with early gastric cancer. All dysplasia and gastric cancer patients underwent endoscopic resection at the time of enrollment. The methylation levels in LOX, APC and MOS genes from noncancerous gastric mucosae using quantitative methylation-specific PCR, as well as the histologic findings of gastric mucosae, were compared before and after eradication. Average follow-up duration was 26.0 months (range: 6 to 76 months). H. pylori eradication decreased methylation levels in LOX (p-value for slope < 0.001) but not in APC. In MOS, decrease of its methylation level following H. pylori eradication was significant among controls without intestinal metaplasia (IM) (p-value for slope < 0.05); however, it was not observed among patients with IM or those with dysplasia or gastric cancer. After H. pylori eradication, methylation level in MOS persistently increased in patients with dysplasia or gastric cancer (p < 0.01). In conclusion, H. pylori eradication decreases aberrant DNA methylation with gene-specific manner. Methylation level in MOS is associated with IM and may be used as a surrogate marker for gastric cancer risk, regardless of H. pylori eradication history.
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Affiliation(s)
- Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
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Selgrad M, Bornschein J, Rokkas T, Malfertheiner P. Helicobacter pylori: gastric cancer and extragastric intestinal malignancies. Helicobacter 2012; 17 Suppl 1:30-5. [PMID: 22958153 DOI: 10.1111/j.1523-5378.2012.00980.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The greatest challenge in Helicobacter pylori-related diseases continues to remain prevention of gastric cancer. New evidence supports the beneficial effect of H. pylori eradication not only on prevention of gastric cancer but also on the regression of preneoplastic conditions of the gastric mucosa. Concerning early detection of gastric cancer there are still no adequate means and there is urgent need to define appropriate markers, for example, by genome-wide research approaches. Currently, the best available method is the "serologic" biopsy based on pepsinogen I and the pepsinogen I/II ratio for identification of patients with severe gastric atrophy at increased risk for gastric cancer development. The treatment of early gastric cancer by endoscopic techniques can be performed safely and efficiently, but patients need meticulous follow-up for detection of metachronous lesions. In case of advanced disease, laparoscopically assisted surgical procedures are safe and favorable compared to open surgery. Two phase III trials support the role of adjuvant systemic treatment with different regimens. Unfortunately, there is still only slow progress in the development of palliative treatment regimens or modification of the existing therapy protocols. There is accumulating evidence for a role of H. pylori infection also in colorectal carcinogenesis. Seropositive individuals are at higher risk for the development of colorectal adenomas and consequently adenocarcinomas of this anatomical region. This phenomenon can partly be attributed to the increase of serum gastrin as response to atrophic changes of the gastric mucosa.
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Affiliation(s)
- Michael Selgrad
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany
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Abadir A, Streutker C, Brezden-Masley C, Grin A, Kim YI. Intestinal metaplasia and the risk of gastric cancer in an immigrant asian population. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2012; 5:43-50. [PMID: 24833933 PMCID: PMC3987763 DOI: 10.4137/cgast.s10070] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The development of intestinal metaplasia (IM) has been purported to be a critical step in the pathogenesis of gastric cancer. However, the natural history of IM in migrant human populations has not been well elucidated. The purpose of this study was to determine the risk of gastric cancer posed by IM in Asian immigrants undergoing gastric cancer screening. A retrospective review of Asian immigrants found to have IM during screening was conducted over an 18-month period. In total, 222 patients were found to have IM. Altogether, 24% had a history of smoking, 48% had a family history of gastric cancer, and 52% had a history of Helicobacter pylori (H. pylori) infection with a 96% eradication rate. Patients with stable IM (SIM) were then compared with those who developed high risk pathology (HRP), specifically dysplasia and/or adenocarcinoma. Thirty-five patients (16%) were included in the HRP group, 31 with dysplasia (14%) and 4 with adenocarcinoma (2%). Of those with dysplasia, 55% demonstrated regression to IM over the course of follow-up. Patients in the SIM group were more likely to be female (60% vs. 31%, P = 0.002) and more likely to have had a normal biopsy during follow-up (32% vs. 9%, P = 0.005). Odds ratios for IM stability were 3.3 (95% CI 1.5-7.0) and 5.0 (95% CI 1.5-17.1) for female gender and presence of a normal biopsy, respectively. Intestinal metaplasia in immigrant Asian populations is predominantly a stable histologic finding associated with a low rate of persistent dysplasia and adenocarcinoma.
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Affiliation(s)
- Amir Abadir
- Division of Gastroenterology, Department of Medicine, University of Toronto
| | - Catherine Streutker
- Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto
| | | | - Andrea Grin
- Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto
| | - Young-In Kim
- Division of Gastroenterology, Department of Medicine, University of Toronto. ; Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
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Helicobacter pylori and autoimmune diseases. Biomed Pharmacother 2012; 67:347-9. [PMID: 23583190 DOI: 10.1016/j.biopha.2011.09.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2011] [Accepted: 09/06/2011] [Indexed: 12/20/2022] Open
Abstract
It is now widely accepted that Helicobacter pylori may play a role in several extra-gastric diseases. In particular, H. pylori infection seems to be implicated in various autoimmune diseases. Many recent studies have shown a healing or an improvement in different autoimmune disorders after H. pylori eradication therapy in infected patients. The exact mechanisms behind this relationship remain under discussion, but molecular mimicry is a consistent hypothesis. This subject is particularly relevant taking into consideration the high prevalence of H. pylori infection, the existence of inexpensive and noninvasive diagnostic methods, as the urea breath test or the stool antigen test, and the low cost and toxicity of eradication treatment. If this connection becomes confirmed, it can change the diagnostic and therapeutic approach of some autoimmune diseases.
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Ten-year prospective follow-up of histological changes at five points on the gastric mucosa as recommended by the updated Sydney system after Helicobacter pylori eradication. J Gastroenterol 2012; 47:394-403. [PMID: 22138891 DOI: 10.1007/s00535-011-0504-9] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2011] [Accepted: 10/24/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND Atrophic gastritis and intestinal metaplasia (IM) are well known as precancerous lesions of gastric cancer. The present study evaluated the gastric mucosa for 10 years after H. pylori eradication at five points of the stomach as recommended by the updated Sydney system to clarify the relationship between H. pylori eradication and gastric cancer prevention. METHODS Among the comprised 373 patients, 323 were H. pylori-positive while 50 patients were H. pylori-negative. Patients with successful eradication underwent follow-up endoscopic examination every year. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system, and were evaluated for the degree of gastritis prospectively. RESULTS Two hundred ninety-four out of the 323 H. pylori-positive patients successfully achieved eradication. Of the 197 patients on whom five-point biopsy was performed, the courses of 30 patients were able to be observed every year for 10 years after successful eradication. Inflammation, activity, and atrophy score at all five points were significantly reduced half a year to 6 years after eradication. IM scores fluctuated intensely up and down during all observation periods; however, IM score of the lesser curvature of the corpus continued decreasing gradually and showed a significant decrease 6 years after (0.97 ± 0.09 to 0.42 ± 0.17, P < 0.05). CONCLUSION In 10 years after H. pylori eradication, atrophy at all sites and IM in the lesser curvature of the corpus gradually and significantly decreased. These results suggest that the improvement of gastric atrophy and IM might have association with the reduction of gastric cancer occurrence.
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Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O’Connor A, Pereira C, Pimentel-Nunes P, Correia R, Ensari A, Dumonceau JM, Machado JC, Macedo G, Malfertheiner P, Matysiak-Budnik T, Megraud F, Miki K, O’Morain C, Peek RM, Ponchon T, Ristimaki A, Rembacken B, Carneiro F, Kuipers EJ. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Virchows Arch 2011; 460:19-46. [PMID: 22190006 DOI: 10.1007/s00428-011-1177-8] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2011] [Revised: 10/13/2011] [Accepted: 10/19/2011] [Indexed: 12/16/2022]
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Bugdaci MS, Zuhur SS, Sokmen M, Toksoy B, Bayraktar B, Altuntas Y, Altuntas Y. The role of Helicobacter pylori in patients with hypothyroidism in whom could not be achieved normal thyrotropin levels despite treatment with high doses of thyroxine. Helicobacter 2011; 16:124-30. [PMID: 21435090 DOI: 10.1111/j.1523-5378.2011.00830.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Helicobacter pylori infection is a most frequent cause of chronic gastritis. H. pylori may decrease absorption of oral thyroxine by decreasing gastric acid secretion in the stomach. In this study, we aimed to investigate the change in thyroid function tests of the cases after H. pylori eradication who were not responding to high doses of thyroxine treatment before H. pylori eradication. METHODS Hypothyroid cases who were not responding to high doses of thyroxine among the ones presented to Endocrinology and Gastroenterohepatology Clinics of Sisli Etfal Training and Research Hospital between 2009 and 2010 were included in the study. Thyroid function tests were performed two times in all cases before and after H. pylori eradication. Duodenal, antral and corporal biopsies, and jejunal aspirates and biopsies were taken during upper gastrointestinal system endoscopies performed in all patients. Cases without intestinal pathology were included in the study. RESULTS Serum thyrotropin (TSH), free T3, and free T4 values before H. pylori eradication were 30.5 ± 28.8 IU/mL, 2.64 ± 0.56 pg/mL, and 0.92 ± 0.32 ng/mL, respectively, and after eradication were found to be 4.2 ± 10.6 IU/mL, 3.02 ± 0.61 pg/mL, and 1.3 ± 0.34 ng/mL, respectively (p values <.001, .002, and <.001, respectively). After H. pylori eradication treatment, TSH decreased in all of the cases, factitious thyrotoxicosis developed in % 21 of these cases. CONCLUSION In hypothyroid cases, H. pylori gastritis may be responsible for an inadequate response to the treatment. H. pylori eradication in the cases receiving high doses of thyroxine has a risk for thyrotoxicosis.
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Affiliation(s)
- Mehmet Sait Bugdaci
- Gastroenterohepatology Endocrinology Microbiology Clinics, Sisli Etfal Training and Research Hospital, Sisli, Istanbul, Turkey.
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Tan VPY, Wong BCY. Helicobacter pylori and gastritis: Untangling a complex relationship 27 years on. J Gastroenterol Hepatol 2011; 26 Suppl 1:42-5. [PMID: 21199513 DOI: 10.1111/j.1440-1746.2010.06593.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Since its' introduction by Warren and Marshall 27 years ago, Helicobacter pylori (HP) has become the linchpin in our understanding of important gastric conditions including gastritis, intestinal metaplasia (IM), gastric/duodenal ulcers (GU/DU), Mucosal Associated Lymphoid Tumour (MALToma) and gastric cancer. Initially named Campylobacter pyloridis, it was re-named HP when biochemical and genetic characterization of the organism showed that it was not a member of the Campylobacter genus. The finding in 1983 was seminal. It is now recognized that HP is the most common chronic human bacterial infection and it is the most common cause of gastritis. It is strongly implicated in the development of peptic ulcer disease and gastric neoplasms. In the years since its' discovery, much headway has been made in the understanding of this ubiquitous organism that had remained elusive, with much work focused on eradication, in part driven by pharmaceutical research and development. Standard triple therapy emerged to eradicate HP. However, with the emergence of HP resistance, newer regimes have been put forth that include quadruple therapy, sequential therapy and a dizzying array of other combinations bent on eradicating HP. Much less is known about the natural history of HP, the different faces of HP internationally, HP eradication and its effect on gastritis, IM, GU/DU and gastric cancer. This review will address the changing face of HP in 2011.
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Lahner E, Spoletini M, Buzzetti R, Corleto VD, Vannella L, Petrone A, Annibale B. HLA-DRB1*03 and DRB1*04 are associated with atrophic gastritis in an Italian population. Dig Liver Dis 2010; 42:854-859. [PMID: 20627832 DOI: 10.1016/j.dld.2010.04.011] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2009] [Revised: 02/19/2010] [Accepted: 04/23/2010] [Indexed: 02/08/2023]
Abstract
BACKGROUND Atrophic gastritis (AG) is often considered an autoimmune disorder and is associated with other autoimmune diseases. HLA-DRB1 alleles are often associated with autoimmune diseases, however HLA-DRB1 genotyping data in AG patients are lacking. The objective of the study was to evaluate the prevalence of HLA-DRB1 in AG patients. METHODS The occurrence of HLA-DRB1 alleles was assessed in 89 Italian AG patients (69.1% female) and 313 controls (47.3% females). Genomic DNA was extracted from peripheral venous blood, PCR-coamplified for HLA-DRB1 and typed using a reverse line-blot assay. RESULTS Compared to controls, prevalence of HLA-DRB1*03 (28.1% vs. 15.9%, p=0.01) and HLA-DRB1*04 (25.8% vs. 14.4%, p=0.01) was greater in AG patients, conferring an OR of 2.05 and 2.07, respectively. HLA-DRB1*01 occurred more frequently in controls than in AG patients (11.5% vs. 3.4%, p=0.01) conferring an OR of 0.27. AG patients carrying the HLA-DRB1*03 or *04 alleles were characterised by having more frequently autoimmune thyroid disease (70.4% vs. 42.2%, p=0.01) and intestinal metaplasia (86.4% vs. 62.2%, p=0.01). CONCLUSIONS In our population, over 50% of AG patients carry the HLA-DRB1*03 or *04 alleles associated with autoimmune diseases, suggesting that this subset of AG patients has a genetic predisposition to autoimmunity.
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Affiliation(s)
- Edith Lahner
- Digestive and Liver Disease Unit, 2nd Medical School, Sapienza University, Rome, Italy
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Iijima K, Koike T, Sekine H, Abe Y, Asanuma K, Ara N, Uno K, Imatani A, Ohara S, Shimosegawa T. Sustained epithelial proliferation in a functionally irreversible fundic mucosa after Helicobacter pylori eradication. J Gastroenterol 2009; 44:47-55. [PMID: 19159072 DOI: 10.1007/s00535-008-2270-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2008] [Accepted: 07/28/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND We recently reported the expansion of the acid-secreting mucosa following Helicobacter pylori eradication with Congo red chromoendoscopy for a short-term follow-up of up to 7 months. We aimed to extend the observation period and to clarify the characteristic features of acid-secreting and non-acid-secreting mucosa. METHODS In 24 H. pylori-positive patients with fundic atrophy, Congo red chromoendoscopy was performed prior to, 1 month, 7 months, and finally more than 2 years after the eradication. The areas of the acid-secreting mucosa were evaluated semiquantitatively. Two gastric biopsy specimens were taken from the acid-secreting and non-acid-secreting areas at the final chromoendoscopy and were subjected to histologic evaluation and immunohistochemistry for Ki-67 as a proliferation index. RESULTS After a gradual increase in acid-secreting areas for up to 7 months after eradication, they further increased in 79% subjects between 7 months and the final observation at a mean follow-up of 62 months. However, there still existed non-acid-secreting mucosa in the fundic area in all subjects, indicating that the expansion of acid-secreting mucosa remained partial. Compared with the neighboring acid-secreting area, the non-acid-secreting area was characterized histologically by higher degrees of residual inflammation, mucosal atrophy, and intestinal metaplasia, and by sustained hyperproliferation as well. CONCLUSIONS Functionally irreversible (non-acid-secreting) gastric mucosa after eradication was associated with extensive intestinal metaplasia and sustained hyperproliferation, suggesting that such mucosa still possesses malignant potential. Congo red chromoendoscopy may be useful for estimating the risk of subsequent development of gastric cancer following successful H. pylori eradication by determining the distribution of functionally irreversible mucosa.
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Affiliation(s)
- Katsunori Iijima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai, 980-8574, Japan
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Graham DY, Kato M, Asaka M. Gastric endoscopy in the 21st century: appropriate use of an invasive procedure in the era of non-invasive testing. Dig Liver Dis 2008; 40:497-503. [PMID: 18403275 PMCID: PMC2525514 DOI: 10.1016/j.dld.2008.02.032] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2008] [Accepted: 02/18/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND The acceptance of the premise that Helicobacter pylori infection is aetiologically related to gastric cancer and peptic ulcer and that the risk of gastric cancer among Helicobacter pylori infected individuals is related to the extent, severity and duration of atrophic gastritis has led to major changes in medical and endoscopic practices. The development of non-invasive methods to detect Helicobacter pylori and to estimate the extent and severity of gastritis has reduced the need for diagnostic endoscopy in asymptomatic individuals. METHODS AND RESULTS Here we provide recommendations regarding deciding whether non-invasive and endoscopic assessment of the gastric mucosa is preferred. We also include specific recommendations and caveats regarding the preferred biopsy number and sites as well as the identification of specimens, to allow the pathologist to reliable stage the severity and extent of gastritis, and thus provide prognostic information needed for patient managements (e.g., whether endoscopic surveillance is recommended). CONCLUSION In summary, while there is clearly a role for gastric endoscopy and endoscopic biopsy in the Helicobacter pylori era, obtaining useful diagnostic and prognostic information is critically dependent upon attention to detail with regard to biopsy site and identification as to the location from where the specimen was taken.
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Affiliation(s)
- D Y Graham
- Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
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Abstract
Gastric cancer is the second commonest fatal malignancy in the world with a high incidence in China. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have shown a strong causal relationship between H. pylori infection and gastric cancer. Animal studies also show that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori-related gastric carcinogenesis. H. pylori eradication leads to regression and prevents the progression of gastric precancerous lesions, but only in a minority of cases. H. pylori eradication appears to be the most promising approach in gastric cancer prevention. The current available data in human studies showed that H. pylori eradication can reduce the risk of developing gastric cancer and this strategy is more useful in patients without atrophic gastritis or intestinal metaplasia. A longer follow-up and additional studies are needed for better understanding this issue.
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De Block CEM, De Leeuw IH, Van Gaal LF. Autoimmune gastritis in type 1 diabetes: a clinically oriented review. J Clin Endocrinol Metab 2008; 93:363-71. [PMID: 18029461 DOI: 10.1210/jc.2007-2134] [Citation(s) in RCA: 128] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
CONTEXT Autoimmune gastritis and pernicious anemia are common autoimmune disorders, being present in up to 2% of the general population. In patients with type 1 diabetes or autoimmune thyroid disease, the prevalence is 3- to 5-fold increased. This review addresses the epidemiology, pathogenesis, diagnosis, clinical consequences, and management of autoimmune gastritis in type 1 diabetic patients. SYNTHESIS Autoimmune gastritis is characterized by: 1) atrophy of the corpus and fundus; 2) autoantibodies to the parietal cell and to intrinsic factor; 3) achlorhydria; 4) iron deficiency anemia; 5) hypergastrinemia; 6) pernicious anemia may result from vitamin B12 deficiency; and 7) in up to 10% of patients, autoimmune gastritis may predispose to gastric carcinoid tumors or adenocarcinomas. This provides a strong rationale for screening, early diagnosis, and treatment. The management of patients with autoimmune gastritis implies yearly determination of gastrin, iron, vitamin B12 levels, and a complete blood count. Iron or vitamin B12 should be supplemented in patients with iron deficiency or pernicious anemia. Whether regular gastroscopic surveillance, including biopsies, is needed in patients with autoimmune gastritis/pernicious anemia is controversial. The gastric carcinoids that occur in these patients generally do not pose a great threat to life, whereas the danger of developing carcinoma is controversial. Nevertheless, awaiting a consensus statement, we suggest performing gastroscopy and biopsy at least once in patients with autoantibodies to the parietal cell, iron-, or vitamin B12-deficiency anemia, or high gastrin levels. CONCLUSION The high prevalence of autoimmune gastritis in type 1 diabetic patients and its possible adverse impact on the health of the patient provide a strong rationale for screening, early diagnosis, periodic surveillance by gastroscopy, and treatment.
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MESH Headings
- Anemia, Pernicious/complications
- Anemia, Pernicious/immunology
- Anemia, Pernicious/pathology
- Anemia, Pernicious/therapy
- Autoantibodies/blood
- Diabetes Mellitus, Type 1/complications
- Diabetes Mellitus, Type 1/immunology
- Diabetes Mellitus, Type 1/pathology
- Diabetes Mellitus, Type 1/therapy
- Gastritis, Atrophic/complications
- Gastritis, Atrophic/immunology
- Gastritis, Atrophic/pathology
- Gastritis, Atrophic/therapy
- Humans
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Affiliation(s)
- Christophe E M De Block
- Department of Diabetology-Endocrinology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium.
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Dinis-Ribeiro M, da Costa-Pereira A, Lopes C, Moreira-Dias L. Feasibility and cost-effectiveness of using magnification chromoendoscopy and pepsinogen serum levels for the follow-up of patients with atrophic chronic gastritis and intestinal metaplasia. J Gastroenterol Hepatol 2007; 22:1594-604. [PMID: 17845687 DOI: 10.1111/j.1440-1746.2007.04863.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia may lead to early diagnosis of gastric cancer. However, to-date no cost-effective model has been proposed. Improved endoscopic examination using magnification chromoendoscopy together with non-invasive functional assessment with pepsinogen serum levels are accurate in the diagnosis of intestinal metaplasia (extension) and minute dysplastic lesions. The aim of this study was to assess the feasibility and cost-effectiveness of a follow-up model for patients with atrophic chronic gastritis and intestinal metaplasia based on gastric mucosal status using magnification chromoendoscopy and pepsinogen. METHODS A cohort of patients with lesions as severe as atrophic chronic gastritis were followed-up according to a standardized protocol using magnification chromoendoscopy with methylene blue and measurement of serum pepsinogen I and II levels. A single node decision tree and Markov chain modeling were used to define cost-effectiveness of this follow-up model versus its absence. Transition rates were considered time-independent and calculated using primary data following cohort data analysis. Costs, quality of life and survival were estimated based on published data and extensive sensitivity analysis was performed. RESULTS A total of 100 patients were successfully followed-up over 3 years. Seven cases of dysplasia were diagnosed during follow-up, all among patients with incomplete intestinal metaplasia at baseline, six of whom had extensive (pepsinogen I to II ratio <3) incomplete intestinal metaplasia. For those individuals with atrophic chronic gastritis or complete intestinal metaplasia, a yearly measurement of pepsinogen levels or an endoscopic examination on a 3-yearly basis would cost 455 euros per quality-adjusted life year (QALY) gain. Endoscopic examination and pepsinogen serum level measurement on a yearly basis would cost 1868 euros per QALY for patients with extensive intestinal metaplasia. CONCLUSIONS The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia is both feasible and cost-effective if improved accurate endoscopic examination of gastric mucosa together with non-invasive assessment of gastric mucosal status are used to identify individuals at high-risk for development of gastric cancer.
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Affiliation(s)
- Mário Dinis-Ribeiro
- Department of Gastroenterology, Portuguese Oncology Institute, Porto, Portugal.
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Orlando LA, Lenard L, Orlando RC. Chronic hypergastrinemia: causes and consequences. Dig Dis Sci 2007; 52:2482-9. [PMID: 17415644 DOI: 10.1007/s10620-006-9419-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2006] [Accepted: 04/30/2006] [Indexed: 12/23/2022]
Abstract
The hormone gastrin plays 2 important roles in gastrointestinal physiology--1 as a major factor in meal-stimulated gastric acid secretion and the other as a trophic hormone for epithelial and enterochromaffin cells. These roles are exaggerated to the point of pathology under conditions of chronic hypergastrinemia as exemplified by the Zollinger-Ellison syndrome and pernicious anemia. More recently, the concern about the potential risk of chronic hypergastrinemia has risen because of the widespread use of proton pump inhibitors for maintenance therapy in reflux esophagitis. For this reason, we present a concise overview of the origin, causes, and potential risks of chronic hypergastrinemia.
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Affiliation(s)
- Lori A Orlando
- Duke University Center for Clinical Health Policy and Durham VA, Durham, North Carolina, USA.
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Abstract
AIM: To perform a long culture passage of H pylori without serum, taking into account its cytotoxicity and the presence of the probable new cytotoxic factor.
METHODS: One sample of H pylori 60190 (ATCC 49503) was grown on Brain Heart Infusion (BHI) agar containing 0.5% 2,6-di-O-methyl-β-cyclodextrin without any serum, being passaged 70-100 times every 3-4 d for approximately 2 h, while another sample of H pylori contained 70 mL/L fetal calf serum without 2,6-di-O-methyl-β-cyclodextrin. Their supernatant and extract after 16 h in culture were evaluated for changes in cell morphology and for cell viability using HeLa cells. Furthermore, the characteristics of the probable cytotoxic factor in the extract were examined on partial purification studies and its cytotoxicity was evaluated in various human cells.
RESULTS: The supernatant and the extract of the bacterium grown on serum-free medium had strong cytotoxicity compared with those grown on serum-containing medium. They irreversibly damaged HeLa cells without vacuolation that was altogether different from that of the bacterium when grown with serum. Their cytotoxicity was easily measured by cell viability assay. The probable cytotoxic factor partially purified and detected by chromatography had characteristics difference from that of vacuolating toxin and a broad cytotoxicity toward various cell lines.
CONCLUSION: Serum-free long culture method of H pylori makes its supernatant and its extract cytotoxic enough to be easily measured by cell viability assay. The probable cytotoxic factor has a unique characteristic and might be a new cytotoxin.
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Affiliation(s)
- Hiroyuki Ohno
- Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
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Abstract
Gastric cancer is the second most common fatal malignancy in the world. Its incidence is high in East Asia. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have established a strong causal relationship between H. pylori infection and gastric cancer. H. pylori eradication is therefore likely to be one of the most promising approaches to gastric cancer prevention. Animal studies have shown that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori-related gastric carcinogenesis. However, the available data from human studies show that H. pylori eradication does not completely prevent gastric cancer and that it might be useful only in patients without atrophic gastritis or intestinal metaplasia at baseline. Longer follow-up and additional studies are needed to clarify this issue.
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Affiliation(s)
- Ting Kin Cheung
- Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China
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