|
1
|
Kishikawa H, Nishida J. Gastric cancer in patients with Helicobacter pylori-negative autoimmune gastritis. World J Gastrointest Oncol 2025; 17:101661. [DOI: 10.4251/wjgo.v17.i4.101661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 01/06/2025] [Accepted: 01/20/2025] [Indexed: 03/25/2025] Open
Abstract
Although Helicobacter pylori (H. pylori) is implicated in the development of most cases of gastric cancer with autoimmune gastritis, cases of gastric cancer have been reported in patients testing negative for H. pylori. Here, we aimed to outline the current research status of the factors involved in the development of gastric cancer in H. pylori-negative autoimmune gastritis. Predictive pathological conditions for the development of gastric cancer in H. pylori-negative autoimmune gastritis are postulated to be: (1) Severe atrophy; (2) Hypergastrinemia; (3) Bile reflux; and (4) Low acidity, which are directly related to the pathophysiology of autoimmune gastritis, as well as smoking and family history, which are not related to autoimmune gastritis. In autoimmune gastritis, where there is a possibility of spontaneous disappearance of H. pylori in advanced atrophy, it is difficult to assess H. pylori. Since H. pylori infection begins in the antrum and subsequently progresses to the proximal stomach, it is interpreted as H. pylori-negative autoimmune gastritis if histologically consistent with autoimmune gastritis in the body with spared antrum, and negative for other H. pylori tests. However, it is essential to examine whether the currently prevailing histological interpretation used to evaluate H. pylori infection status is appropriate.
Collapse
Affiliation(s)
- Hiroshi Kishikawa
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, Ichikawa 272-8513, Chiba, Japan
| | - Jiro Nishida
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, Ichikawa 272-8513, Chiba, Japan
| |
Collapse
|
|
2
|
Ma XZ, Zhou N, Luo X, Guo SQ, Mai P. Update understanding on diagnosis and histopathological examination of atrophic gastritis: A review. World J Gastrointest Oncol 2024; 16:4080-4091. [DOI: 10.4251/wjgo.v16.i10.4080] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 08/14/2024] [Accepted: 08/21/2024] [Indexed: 09/26/2024] Open
Abstract
Chronic atrophic gastritis (CAG) is a complex syndrome in which long-term chronic inflammatory stimulation causes gland atrophy in the gastric mucosa, reducing the stomach's ability to secrete gastric juice and pepsin, and interfering with its normal physiological function. Multiple pathogenic factors contribute to CAG incidence, the most common being Helicobacter pylori infection and the immune reactions resulting from gastric autoimmunity. Furthermore, CAG has a broad spectrum of clinical manifestations, including gastroenterology and extra-intestinal symptoms and signs, such as hematology, neurology, and oncology. Therefore, the initial CAG evaluation should involve the examination of clinical and serological indicators, as well as diagnosis confirmation via gastroscopy and histopathology if necessary. Depending on the severity and scope of atrophy affecting the gastric mucosa, a histologic staging system (Operative Link for Gastritis Assessment or Operative Link on Gastritis intestinal metaplasia) could also be employed. Moreover, chronic gastritis has a higher risk of progressing to gastric cancer (GC). In this regard, early diagnosis, treatment, and regular testing could reduce the risk of GC in CAG patients. However, the optimal interval for endoscopic monitoring in CAG patients remains uncertain, and it should ideally be tailored based on individual risk evaluations and shared decision-making processes. Although there have been many reports on CAG, the precise etiology and histopathological features of the disease, as well as the diagnosis of CAG patients, are yet to be fully elucidated. Consequently, this review offers a detailed account of CAG, including its key clinical aspects, aiming to enhance the overall understanding of the disease.
Collapse
Affiliation(s)
- Xiu-Zhen Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
| | - Ni Zhou
- Department of Gastroenterology, Xi'an International Medical Center, Xi’an 710000, Shaanxi Province, China
| | - Xiu Luo
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Si-Qi Guo
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
- The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
| | - Ping Mai
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
| |
Collapse
|
|
3
|
Chapelle N, Martin J, Osmola M, Hémont C, Leroy M, Vibet MA, Tougeron D, Moussata D, Lamarque D, Bigot-Corbel E, Masson D, Blin J, Josien R, Mosnier JF, Matysiak-Budnik T. Serum pepsinogens can help to discriminate between H. pylori-induced and auto-immune atrophic gastritis: Results from a prospective multicenter study. Dig Liver Dis 2023; 55:1345-1351. [PMID: 37085439 DOI: 10.1016/j.dld.2023.03.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/16/2023] [Accepted: 03/20/2023] [Indexed: 04/23/2023]
Abstract
BACKGROUND Serum pepsinogen (PG) testing is recommended by the European guidelines for diagnosis of chronic atrophic gastritis (CAG). However, wide variations in diagnostic performances are observed, due to the differences in the extent of gastric atrophy, and possibly in its origin (Helicobacter pylori-, autoimmune (AIG)). AIM To analyze the diagnostic performances of PGs testing according to these different parameters, using enzyme-linked-immunosorbent serologic assay (ELISA) and chemiluminescent immunoassay (CLEIA). METHODS Serum samples from patients having undergone gastroscopy with biopsies in five French centers were collected prospectively. Sensitivity (Se), specificity (Sp), and Area Under Curve were analyzed according to the extent and origin of CAG. RESULTS Overall, 344 patients (156 males [45%]; mean age 58.8 [±14.2] years) were included, among whom 44 had AIG. Diagnostic performances of PG I for the detection of corpus CAG were excellent, with Se and Sp of 92.7% and 99.1% for ELISA and 90.5% and 98.2% for CLEIA, respectively. For AIG, corresponding values were 97.7% and 97.4% for ELISA, and 95.6% and 97.1% for CLEIA. In multivariate analysis, PG levels were associated with the auto-immune origin (p<0.001) but not with the extent of the atrophic gastritis. CONCLUSIONS Pepsinogens are highly efficient for the diagnosis of corpus-limited CAG and allow to discriminate AIG from H. pylori-induced gastritis.
Collapse
Affiliation(s)
- Nicolas Chapelle
- IMAD, Hepato-Gastroenterology & Digestive Oncology, University Hospital of Nantes, Nantes, France; Université de Nantes, Inserm, CHU Nantes, Centre de Recherche Translationnel en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
| | - Jérôme Martin
- Université de Nantes, Inserm, CHU Nantes, Centre de Recherche Translationnel en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France; CHU Nantes, Laboratoire d'Immunologie, Center for Immuno Monitoring Nantes-Atlantique (CIMNA), F-44000 Nantes, France
| | - Malgorzata Osmola
- Department of Hematology, Transplantation and Internal Medicine, Medical University, Warsaw, Poland
| | - Caroline Hémont
- CHU Nantes, Laboratoire d'Immunologie, Center for Immuno Monitoring Nantes-Atlantique (CIMNA), F-44000 Nantes, France
| | - Maxime Leroy
- Department of Biostatistics, CHU de Nantes, France
| | | | - David Tougeron
- Department of Hepato-Gastroenterology, Poitiers University Hospital and University of Poitiers, Poitiers, France
| | - Driffa Moussata
- Department of Hepato-Gastroenterology, University Hospital of Tours, France
| | - Dominique Lamarque
- Department of Hepato-Gastroenterology, Ambroise-Paré Hospital, AP-HP, Paris Saclay University, UVSQ, INSERM, Infection and Inflammation, Paris, France
| | - Edith Bigot-Corbel
- Department of Biochemistry, University Hospital of Nantes, Nantes, France
| | - Damien Masson
- Department of Biochemistry, University Hospital of Nantes, Nantes, France
| | - Justine Blin
- Department of Biochemistry, University Hospital of Nantes, Nantes, France
| | - Régis Josien
- Université de Nantes, Inserm, CHU Nantes, Centre de Recherche Translationnel en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France; CHU Nantes, Laboratoire d'Immunologie, Center for Immuno Monitoring Nantes-Atlantique (CIMNA), F-44000 Nantes, France
| | | | - Tamara Matysiak-Budnik
- IMAD, Hepato-Gastroenterology & Digestive Oncology, University Hospital of Nantes, Nantes, France; Université de Nantes, Inserm, CHU Nantes, Centre de Recherche Translationnel en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France.
| |
Collapse
|
|
4
|
Allakky A. Exploring the Association of Helicobacter pylori With Anti-intrinsic Factor and Anti-parietal Cell Antibodies in Pernicious Anemia: A Systematic Review. Cureus 2023; 15:e45887. [PMID: 37885562 PMCID: PMC10598509 DOI: 10.7759/cureus.45887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2023] [Indexed: 10/28/2023] Open
Abstract
Pernicious anemia, historically tied to vitamin B12 malabsorption due to intrinsic factor secretion impairment, has evolved in understanding, especially concerning its association with autoimmune gastritis. This systematic review dives deep into the multifaceted relationship between Helicobacter pylori (H. pylori) infection, autoimmune gastritis, and the presence of anti-intrinsic factors and anti-parietal cell antibodies. Comprehensive database searches revealed a higher prevalence of H. pylori infection in pernicious anemia patients, with some studies suggesting a consequential increase in the aforementioned antibodies. Interestingly, eradication of H. pylori displayed potential therapeutic effects; patients showcased reductions in antibody titers, improved histopathological findings, and reversion of atrophic changes in gastric corpus. Such outcomes highlight the conceivable benefits of considering H. pylori infection during the evaluation and management of pernicious anemia and autoimmune gastritis. However, disparities across studies make direct comparisons challenging. It's essential to approach the potential role of H. pylori in these conditions with caution. Further research is warranted to cement conclusions and refine clinical management strategies. This review seeks to prompt new investigative avenues into the intricate link between H. pylori, autoimmune gastritis, and pernicious anemia, ultimately enhancing patient care.
Collapse
|
|
5
|
Abstract
Autoimmune gastritis (AIG) typically exhibits the characteristics of type A gastritis and has been classified as a separate disease from type B gastritis that corresponds to Helicobacter pylori gastritis. However, many reports have suggested the involvement of H. pylori infection in the pathogenesis of AIG. In our two cases, the patients' previous gastritis exhibited a clear pattern in which H. pylori gastritis had progressed over many years, but ultimately transitioned to AIG with its spontaneous disappearance. These findings suggest that some cases of AIG might originate from long-standing H. pylori gastritis.
Collapse
Affiliation(s)
| | | | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Japan
| |
Collapse
|
|
6
|
Rugge M, Bricca L, Guzzinati S, Sacchi D, Pizzi M, Savarino E, Farinati F, Zorzi M, Fassan M, Dei Tos AP, Malfertheiner P, Genta RM, Graham DY. Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients. Gut 2023; 72:30-38. [PMID: 35772926 DOI: 10.1136/gutjnl-2022-327827] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/15/2022] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Autoimmune gastritis (AIG) is an immunomediated disease targeting parietal cells, eventually resulting in oxyntic-restricted atrophy. This long-term follow-up study aimed at elucidating the natural history, histological phenotype(s), and associated cancer risk of patients with AIG consistently tested H. pylori-negative (naïve H. pylori-negative subjects). DESIGN Two-hundred eleven naïve H. pylori-negative patients (tested by serology, histology, molecular biology) with AIG (F:M=3.15:1; p<0.001) were prospectively followed up with paired biopsies (T1 vs T2; mean follow-up years:7.5 (SD:4.4); median:7). Histology distinguished non-atrophic versus atrophic AIG. Atrophy was further subtyped/scored as non-metaplastic versus metaplastic (pseudopyloric (PPM) and intestinal (IM)). Enterochromaffin-like-cell (ECL) status was categorised as diffuse versus adenomatoid hyperplasia/dysplasia, and type 1 neuroendocrine tumours (Type1-NETs). RESULTS Over the long-term histological follow-up, AIG consistently featured oxyntic-predominant-mononuclear inflammation. At T1, PPM-score was greater than IM (200/211 vs 160/211, respectively); IM scores increased from T1 to T2 (160/211 to 179/211), with no changes in the PPM prevalence (T1=200/211; T2=201/211). At both T1/T2, the prevalence of OLGA-III-stage was <5%; no Operative Link on Gastritis Assessment (OLGA)-IV-stage occurred. ECL-cell-status progressed from diffuse to adenomatoid hyperplasia/dysplasia (T1=167/14 vs T2=151/25). Type1-NETs (T1=10; T2=11) always coexisted with extensive oxyntic-atrophy, and ECL adenomatoid-hyperplasia/dysplasia. No excess risk of gastric or other malignancies was found over a cumulative follow-up time of 10 541 person years, except for (marginally significant) thyroid cancer (SIR=3.09; 95% CI 1.001 to 7.20). CONCLUSIONS Oxyntic-restricted inflammation, PPM (more than IM), and ECL-cell hyperplasia/neoplasia are the histological AIG hallmarks. Compared with the general population, corpus-restricted inflammation/atrophy does not increase the GC risk. The excess of GC risk reported in patients with AIG could plausibly result from unrecognised previous/current H. pylori comorbidity.
Collapse
Affiliation(s)
- Massimo Rugge
- Department of Medicine - DIMED, Ringgold ID 9308, Padova, Veneto, Italy
- Veneto Tumor Registry, Azienda Zero, Padova, Veneto, Italy
| | - Ludovica Bricca
- Department of Medicine - DIMED, Ringgold ID 9308, Padova, Veneto, Italy
| | | | - Diana Sacchi
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Ringgold ID 9308, Padova, Italy
| | - Marco Pizzi
- Department of Medicine - DIMED, Ringgold ID 9308, Padova, Veneto, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Ringgold ID 9308, Padova, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Ringgold ID 9308, Padova, Italy
| | - Manuel Zorzi
- Veneto Tumor Registry, Azienda Zero, Padova, Veneto, Italy
| | - Matteo Fassan
- Department of Medicine - DIMED, Ringgold ID 9308, Padova, Veneto, Italy
- Veneto Institute of Oncology - IOV - IRCCS, Padova, Italy
| | | | | | - Robert M Genta
- Department of Pathology, Baylor College of Medicine Houston, Texas, USA, Houston, Texas, USA
- Department of Medicine, Michael E. De Bakey VA Medical Center, Baylor College of Medicine Houston, Houston, Texas, USA
| | - David Y Graham
- Department of Medicine, Michael E. De Bakey VA Medical Center, Baylor College of Medicine Houston, Houston, Texas, USA
| |
Collapse
|
|
7
|
Sánchez Caraballo A, Guzmán Y, Sánchez J, Munera M, Garcia E, Gonzalez-Devia D. Potential contribution of Helicobacter pylori proteins in the pathogenesis of type 1 gastric neuroendocrine tumor and urticaria. In silico approach. PLoS One 2023; 18:e0281485. [PMID: 37098080 PMCID: PMC10128923 DOI: 10.1371/journal.pone.0281485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 01/24/2023] [Indexed: 04/26/2023] Open
Abstract
BACKGROUND Helicobacter pylori has been linked to several diseases such as chronic urticaria, gastritis, and type 1 gastric neuroendocrine tumors (type 1 gNET). Although these diseases seem to have different mechanisms, their relationship with H. pylori suggests a common inflammatory pathway. OBJECTIVE To identify potential cross-reactive antigens between H. pylori and humans involved in chronic urticaria and type 1 gNET. METHODS Alignment was carried out among human proteins associated with urticaria (9 proteins), type 1 gNET (32 proteins), and H. pylori proteome. We performed pairwise alignment among the human and H. pylori antigens with PSI-BLAST. Modeling based on homology was done with the Swiss model server and epitope prediction with the Ellipro server. Epitopes were located on a 3D model using PYMOL software. RESULTS The highest conserved sequence was found between the human HSP 60 antigen and the H. pylori chaperonin GroEL with an identity of 54% and a cover of 92%, followed by the alpha and gamma enolases and two H. pylori phosphopyruvate hydratase, both with an identity and cover of 48% and 96%, respectively. The H/K ATPase (Chain A) showed high identity with two H. pylori proteins (35.21% with both P-type ATPase), but with low cover (only 6%). We observed eight linear and three discontinuous epitopes for human HSP 60 and three lineal and one discontinuous epitope for both alpha-enolase and gamma enolase, high conserved with H. pylori sequences. CONCLUSION Some type 1 gNET antigens shared potential cross-reactive epitopes with H. pylori proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between the infection and this disease. Studies evaluating the functional impact of this relationship are needed.
Collapse
Affiliation(s)
- Andrés Sánchez Caraballo
- Medical Research Group (GINUMED), University Corporation Rafael Núñez, Cartagena, Colombia
- Group of Clinical and Experimental Allergy (GACE), "IPS Universitaria" Clinic, University of Antioquia, Medellín, Colombia
| | - Yenny Guzmán
- Department of Health Services, University of Washington, Seattle, WA, United States of America
| | - Jorge Sánchez
- Group of Clinical and Experimental Allergy (GACE), "IPS Universitaria" Clinic, University of Antioquia, Medellín, Colombia
| | - Marlon Munera
- Medical Research Group (GINUMED), University Corporation Rafael Núñez, Cartagena, Colombia
| | - Elizabeth Garcia
- Facultad de Medicina, Universidad de los Andes, Bogotá, Colombia
- Departamento de Alergología, Fundación Santa Fe de Bogotá, Bogotá, Colombia
- UNIMEQ ORL, Bogotá, Colombia
| | | |
Collapse
|
|
8
|
Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022; 71:gutjnl-2022-327745. [PMID: 35944925 DOI: 10.1136/gutjnl-2022-327745] [Citation(s) in RCA: 537] [Impact Index Per Article: 179.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/21/2022] [Indexed: 01/06/2023]
Abstract
Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.
Collapse
Affiliation(s)
- Peter Malfertheiner
- Medical Department 2, LMU, Munchen, Germany
- Department of Radiology, LMU, Munchen, Germany
| | - Francis Megraud
- INSERM U853 UMR BaRITOn, University of Bordeaux, Bordeaux, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
- Medical School, European University, Nicosia, Cyprus
| | - Javier P Gisbert
- Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Jyh-Ming Liou
- Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Christian Schulz
- Medical Department 2, LMU, Munchen, Germany
- Partner Site Munich, DZIF, Braunschweig, Germany
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy
| | - Richard H Hunt
- Medicine, McMaster University, Hamilton, Ontario, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Colm O'Morain
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy
- Veneto Tumor Registry (RTV), Padova, Italy
| | - Sebastian Suerbaum
- Partner Site Munich, DZIF, Braunschweig, Germany
- Max von Pettenkofer Institute, LMU, Munchen, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical School, Tochigi, Japan
| | - Emad M El-Omar
- Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
| |
Collapse
|
|
9
|
Abstract
Like most solid tumours, the microenvironment of epithelial-derived gastric adenocarcinoma (GAC) consists of a variety of stromal cell types, including fibroblasts, and neuronal, endothelial and immune cells. In this article, we review the role of the immune microenvironment in the progression of chronic inflammation to GAC, primarily the immune microenvironment driven by the gram-negative bacterial species Helicobacter pylori. The infection-driven nature of most GACs has renewed awareness of the immune microenvironment and its effect on tumour development and progression. About 75-90% of GACs are associated with prior H. pylori infection and 5-10% with Epstein-Barr virus infection. Although 50% of the world's population is infected with H. pylori, only 1-3% will progress to GAC, with progression the result of a combination of the H. pylori strain, host susceptibility and composition of the chronic inflammatory response. Other environmental risk factors include exposure to a high-salt diet and nitrates. Genetically, chromosome instability occurs in ~50% of GACs and 21% of GACs are microsatellite instability-high tumours. Here, we review the timeline and pathogenesis of the events triggered by H. pylori that can create an immunosuppressive microenvironment by modulating the host's innate and adaptive immune responses, and subsequently favour GAC development.
Collapse
|
|
10
|
Venerito M, Sulzer S, Jechorek D. [Clinical management of autoimmune gastritis]. Dtsch Med Wochenschr 2022; 147:451-459. [PMID: 35405749 DOI: 10.1055/a-1520-3562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Autoimmune gastritis (AIG) is a chronic immune-mediated inflammation of the gastric corpus/fundus mucosa leading to progressive atrophy of the oxyntic gastric glands (AOM) and their consecutive loss of function. Possible clinical consequences of AIG include iron deficiency anemia, pernicious anemia, gastric neuroendocrine tumors (gNET), and gastric adenocarcinoma. This article provides a review of interdisciplinary aspects of the diagnosis and treatment of AIG.
Collapse
|
|
11
|
Kishikawa H, Nakamura K, Ojiro K, Katayama T, Arahata K, Takarabe S, Sasaki A, Miura S, Hayashi Y, Hoshi H, Kanai T, Nishida J. Relevance of pepsinogen, gastrin, and endoscopic atrophy in the diagnosis of autoimmune gastritis. Sci Rep 2022; 12:4202. [PMID: 35273265 PMCID: PMC8913737 DOI: 10.1038/s41598-022-07947-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 02/28/2022] [Indexed: 02/07/2023] Open
Abstract
Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura–Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.
Collapse
Affiliation(s)
- Hiroshi Kishikawa
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan.
| | - Kenji Nakamura
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Keisuke Ojiro
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Tadashi Katayama
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Kyoko Arahata
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Sakiko Takarabe
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Aya Sasaki
- Department of Pathology and Laboratory Medicine, Ichikawa General Hospital, Tokyo Dental College, Ichikawa, Chiba, Japan
| | - Soichiro Miura
- Graduate School, International University of Health and Welfare, Minato-ku, Tokyo, Japan
| | - Yukie Hayashi
- Center for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, Tokyo, Japan
| | - Hitomi Hoshi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
| | - Jiro Nishida
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| |
Collapse
|
|
12
|
Hoft SG, Noto CN, DiPaolo RJ. Two Distinct Etiologies of Gastric Cancer: Infection and Autoimmunity. Front Cell Dev Biol 2021; 9:752346. [PMID: 34900999 PMCID: PMC8661534 DOI: 10.3389/fcell.2021.752346] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/12/2021] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer is a leading cause of mortality worldwide. The risk of developing gastric adenocarcinoma, which comprises >90% of gastric cancers, is multifactorial, but most associated with Helicobacter pylori infection. Autoimmune gastritis is a chronic autoinflammatory syndrome where self-reactive immune cells are activated by gastric epithelial cell autoantigens. This cause of gastritis is more so associated with the development of neuroendocrine tumors. However, in both autoimmune and infection-induced gastritis, high risk metaplastic lesions develop within the gastric mucosa. This warrants concern for carcinogenesis in both inflammatory settings. There are many similarities and differences in disease progression between these two etiologies of chronic gastritis. Both diseases have an increased risk of gastric adenocarcinoma development, but each have their own unique comorbidities. Autoimmune gastritis is a primary cause of pernicious anemia, whereas chronic infection typically causes gastrointestinal ulceration. Both immune responses are driven by T cells, primarily CD4+ T cells of the IFN-γ producing, Th1 phenotype. Neutrophilic infiltrates help clear H. pylori infection, but neutrophils are not necessarily recruited in the autoimmune setting. There have also been hypotheses that infection with H. pylori initiates autoimmune gastritis, but the literature is far from definitive with evidence of infection-independent autoimmune gastric disease. Gastric cancer incidence is increasing among young women in the United States, a population at higher risk of developing autoimmune disease, and H. pylori infection rates are falling. Therefore, a better understanding of these two chronic inflammatory diseases is needed to identify their roles in initiating gastric cancer.
Collapse
Affiliation(s)
- Stella G Hoft
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States
| | - Christine N Noto
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States
| | - Richard J DiPaolo
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States
| |
Collapse
|
|
13
|
Youssefi M, Tafaghodi M, Farsiani H, Ghazvini K, Keikha M. Helicobacter pylori infection and autoimmune diseases; Is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 54:359-369. [PMID: 32891538 DOI: 10.1016/j.jmii.2020.08.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 07/07/2020] [Accepted: 08/16/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Masoud Youssefi
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Tafaghodi
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hadi Farsiani
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Kiarash Ghazvini
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Masoud Keikha
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
14
|
Ogutmen Koc D, Bektas S. Serum pepsinogen levels and OLGA/OLGIM staging in the assessment of atrophic gastritis types. Postgrad Med J 2020; 98:441-445. [PMID: 33380437 DOI: 10.1136/postgradmedj-2020-139183] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 12/05/2020] [Accepted: 12/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND We assessed the validity of using serum pepsinogen tests (sPGTs) to differentiate autoimmune atrophic gastritis (AAG) from environmental atrophic gastritis (EAG). We also investigated the correlation and prognostic value between disease stage, according to Operative Link for Gastritis Assessment (OLGA)/Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM), and sPGT results in patients with gastric atrophy. METHODS We enroled 115 patients in this prospective study: 95 with atrophic gastritis (16 with AAG and 79 with EAG) and 20 non-atrophic gastritis. These patients, along with 32 control patients, underwent esophagogastroduodenoscopy. Atrophy and intestinal metaplasia of the gastric biopsy specimens were staged according to the OLGA/OLGIM staging systems. RESULTS The median (IQR) age of the patients (83 females (56.5%)) was 58 (46-67) years. Patients in the AAG group represented histologically advanced stages. The AAG group had lower pepsinogen (PG) I and II levels, as well as a lower PGI/PGII ratio, compared with the EAG group (p<0.01, p<0.05 and p<0.01, respectively). The optimal PGI/PGII ratio for predicting AAG was ≤1.9 (100% sensitivity and 100% specificity), and that for predicting EAG was ≤9.2 (47.5% sensitivity and 90.6% specificity). The OLGA/OLGIM stage was negatively correlated with the PGI level and PGI/PGII ratio. In the AAG group, four of five patients with low-grade dysplasia had OLGA/OLGIM stage III-IV disease. CONCLUSIONS sPGT may provide valuable information for differentiating advanced-stage AAG from EAG, and in patients with atrophic gastritis, use of sPGTs and OLGA/OLGIM staging together may predict gastric cancer risk.
Collapse
Affiliation(s)
- Deniz Ogutmen Koc
- Department of Pathology, Gaziosmanpasa Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Sibel Bektas
- Department of Pathology, Gaziosmanpasa Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| |
Collapse
|
|
15
|
Teal E, Dua-Awereh M, Hirshorn ST, Zavros Y. Role of metaplasia during gastric regeneration. Am J Physiol Cell Physiol 2020; 319:C947-C954. [PMID: 32755448 DOI: 10.1152/ajpcell.00415.2019] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Spasmolytic polypeptide/trefoil factor 2 (TFF2)-expressing metaplasia (SPEM) is a mucous-secreting reparative lineage that emerges at the ulcer margin in response to gastric injury. Under conditions of chronic inflammation with parietal cell loss, SPEM has been found to emerge and evolve into neoplasia. Cluster-of-differentiation gene 44 (CD44) is known to coordinate normal and metaplastic epithelial cell proliferation. In particular, CD44 variant isoform 9 (CD44v9) associates with the cystine-glutamate transporter xCT, stabilizes the protein, and provides defense against reactive oxygen species (ROS). xCT stabilization by CD44v9 leads to defense against ROS by cystine uptake, glutathione (GSH) synthesis, and maintenance of the redox balance within the intracellular environment. Furthermore, p38 signaling is a known downstream ROS target, leading to diminished cell proliferation and migration, two vital processes of gastric epithelial repair. CD44v9 emerges during repair of the gastric epithelium after injury, where it is coexpressed with other markers of SPEM. The regulatory mechanisms for the emergence of CD44v9 and the role of CD44v9 during the process of gastric epithelial regeneration are largely unknown. Inflammation and M2 macrophage infiltration have recently been demonstrated to play key roles in the induction of SPEM after injury. The following review proposes new insights into the functional role of metaplasia in the process of gastric regeneration in response to ulceration. Our insights are extrapolated from documented studies reporting oxyntic atrophy and SPEM development and our current unpublished findings using the acetic acid-induced gastric injury model.
Collapse
Affiliation(s)
- Emma Teal
- Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Martha Dua-Awereh
- Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio.,Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, Arizona
| | - Sabrina T Hirshorn
- Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, Arizona
| | - Yana Zavros
- Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, Arizona
| |
Collapse
|
|
16
|
Abstract
PURPOSE OF THE REVIEW Atrophic gastritis is a complex syndrome with gastric atrophy as a common trait. Helicobacter pylori infection and autoimmunity are the two main contexts in which it develops. It is slightly symptomatic, affects various aspects of general health, and remains a predisposing factor for gastric cancer. This review will update current knowledge and progress on atrophic gastritis. RECENT FINDINGS Atrophic gastritis affects mostly adults with persistent dyspepsia, deficient anemia, autoimmunity disease, long-term proton pump inhibitor use, and a family history of gastric cancer. Gastric biopsies, expressed as Sydney system grade and OLGA/OLGIM classifications, represent the gold standard for diagnosis and cancer risk stage, respectively. Recently, electronic chromoendoscopy has allowed "targeted biopsies" of intestinal metaplasia. The associated hypochlorhydria affects the gastric microbiota composition suggesting that non-Helicobacter pylori microbiota may participate in the development of gastric cancer. Physicians should be aware of multifaceted clinical presentation of atrophic gastritis. It should be endoscopically monitored by targeted gastric biopsies. Autoimmune and Helicobacter pylori-induced atrophic gastritis are associated with different gastric microbial profiles playing different roles in gastric tumorigenesis.
Collapse
Affiliation(s)
- Edith Lahner
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035 -, 00189, Rome, Italy
| | - Laura Conti
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035 -, 00189, Rome, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035 -, 00189, Rome, Italy
| | - Vito Domenico Corleto
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035 -, 00189, Rome, Italy.
| |
Collapse
|
|
17
|
Abstract
Introduction: Atrophic gastritis (AG) is a complex syndrome which arises as a consequence of H. pylori infection or in the context of gastric autoimmunity. It often deserves a benign course but may lead to potentially life-threatening complications: cancer and anemia. This review aims to address traditional and innovative knowledge on this often under-diagnosed disorder.Areas covered: This review covers clinical presentation, risk factors, diagnosis, and management of AG and provides an updated resource for clinicians to get insight into this challenging disorder. Updated literature was searched in PubMed. Manual search from reference lists of publications was performed.Expert opinion: A case-finding strategy may be beneficial in individuals with anemia, dyspepsia, autoimmune thyropaties and type 1 diabetes, and family history of gastric cancer. AG is linked to gastric cancer risk and endoscopic surveillance is indicated according to topography of gastric atrophy and risk factors. The direction for future research in AG is summarized.
Collapse
Affiliation(s)
- Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Roma, Italy
| | - Gianluca Esposito
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Roma, Italy
| | - Edith Lahner
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Roma, Italy
| |
Collapse
|
|
18
|
Lahner E, Zagari RM, Zullo A, Di Sabatino A, Meggio A, Cesaro P, Lenti MV, Annibale B, Corazza GR. Chronic atrophic gastritis: Natural history, diagnosis and therapeutic management. A position paper by the Italian Society of Hospital Gastroenterologists and Digestive Endoscopists [AIGO], the Italian Society of Digestive Endoscopy [SIED], the Italian Society of Gastroenterology [SIGE], and the Italian Society of Internal Medicine [SIMI]. Dig Liver Dis 2019; 51:1621-1632. [PMID: 31635944 DOI: 10.1016/j.dld.2019.09.016] [Citation(s) in RCA: 99] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 09/03/2019] [Accepted: 09/23/2019] [Indexed: 02/08/2023]
Abstract
Chronic atrophic gastritis (CAG) is an underdiagnosed condition characterised by translational features going beyond the strict field of gastroenterology as it may manifest itself by a variable spectrum of gastric and extra-gastric symptoms and signs. It is relatively common among older adults in different parts of the world, but large variations exist. Helicobacter pylori-related CAG [multifocal] and autoimmune CAG (corpus-restricted) are apparently two different diseases, but they display overlapping features. Patients with cobalamin and/or iron deficiency anaemia or autoimmune disorders, including autoimmune thyroiditis and type 1 diabetes mellitus, should be offered screening for CAG. Pepsinogens, gastrin-17, and anti-H. pylori antibodies serum assays seem to be reliable non-invasive screening tools for the presence of CAG, helpful to identify individuals to refer to gastroscopy with five standard gastric biopsies in order to obtain histological confirmation of diagnosis. Patients with CAG are at increased risk of developing gastric cancer, and they should be estimated with histological staging systems (OLGA or OLGIM). H. pylori eradication may be beneficial by modifying the natural history of atrophy, but not that of intestinal metaplasia. Patients with advanced stages of CAG (Stage III/IV OLGA or OLGIM) should undergo endoscopic surveillance every three years, those with autoimmune CAG every three-five years. In patients with CAG, a screening for autoimmune thyroid disease and micronutrient deficiencies, including iron and vitamin B12, should be performed. The optimal treatment for dyspeptic symptoms in patients with CAG remains to be defined. Proton pump inhibitors are not indicated in hypochlorhydric CAG patients.
Collapse
Affiliation(s)
- Edith Lahner
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
| | | | - Angelo Zullo
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | - Antonio Di Sabatino
- First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Alberto Meggio
- Department of Gastroenterology, Trento and Rovereto Hospital, Trento, Italy
| | - Paola Cesaro
- Digestive Endoscopy Unit and Gastroenterology, Fondazione Poliambulanza, Brescia, Italy
| | - Marco Vincenzo Lenti
- First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Bruno Annibale
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Gino Roberto Corazza
- First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| |
Collapse
|
|
19
|
Weise F, Vieth M, Reinhold D, Haybaeck J, Goni E, Lippert H, Ridwelski K, Lingohr P, Schildberg C, Vassos N, Kruschewski M, Krasniuk I, Grimminger PP, Waidmann O, Peitz U, Veits L, Kreuser N, Lang H, Bruns C, Moehler M, Lordick F, Gockel I, Schumacher J, Malfertheiner P, Venerito M. Gastric cancer in autoimmune gastritis: A case-control study from the German centers of the staR project on gastric cancer research. United European Gastroenterol J 2019; 8:175-184. [PMID: 32213076 PMCID: PMC7079279 DOI: 10.1177/2050640619891580] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objectives Patients with autoimmune gastritis (AIG) are reported to have an increased
risk of developing gastric cancer (GC). In this study, we assess the
characteristics and outcomes of GC patients with AIG in a multicenter
case-control study. Methods Between April 2013 and May 2017, patients with GC, including cancers of the
esophagogastric junction (EGJ) Siewert type II and III, were recruited.
Patients with histological characteristics of AIG were identified and
matched in a 1:2 fashion for age and gender to GC patients with no AIG.
Presenting symptoms were documented using a self-administered
questionnaire. Results Histological assessment of gastric mucosa was available for 572/759 GC
patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years,
female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be
localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio
(OR) 2.7, 95% confidence interval (CI) 1.0–7.1). In GC patients with AIG,
pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6–187.2),
and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95%
CI 7.2–116.4). GC patients with AIG were more likely to present without
distant metastases (OR 6.2, 95% CI 1.3–28.8) and to be treated with curative
intention (OR 3.0, 95% CI 1.0–9.0). The five-year survival rates with 95% CI
in GC patients with and with no AIG were 84.7% (83.8–85.6) and 53.5%
(50.9–56.1), respectively (OR 0.25, 95% CI 0.08–0.75,
p = 0.001). Conclusions Pernicious anemia leads to earlier diagnosis of GC in AIG patients and
contributes significantly to a better clinical outcome.
Collapse
Affiliation(s)
- Friederike Weise
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | - Dirk Reinhold
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Johannes Haybaeck
- Department of Pathology, Otto-von-Guericke University Hospital, Magdeburg, Germany.,Institute of Pathology, Medical University of Graz, Graz, Austria.,Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria
| | - Elisabetta Goni
- Department of Internal Medicine II, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany
| | - Hans Lippert
- Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Karsten Ridwelski
- Department of General and Visceral Surgery, Klinikum Magdeburg GmbH, Magdeburg, Germany
| | - Philipp Lingohr
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany
| | - Claus Schildberg
- Department of General and Visceral Surgery, Pius Klinikum, University Hospital of Visceral Surgery, Oldenburg, Germany
| | - Nikolaos Vassos
- Division of Surgical Oncology and Thoracic Surgery, Department of Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
| | - Martin Kruschewski
- Department of General and Visceral Surgery, Klinikum Frankfurt (Oder), Germany
| | - Iurii Krasniuk
- Department of General, Visceral and Thoracic Surgery, Städtisches Klinikum Solingen GmbH, Solingen, Germany
| | - Peter P Grimminger
- Department of General, Visceral and Transplant Surgery, Johannes Gutenberg-University of Mainz, Mainz, Germany
| | - Oliver Waidmann
- Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Ulrich Peitz
- Department of Gastroenterology, Raphaelsklinik, Münster, Germany
| | - Lothar Veits
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | - Nicole Kreuser
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany
| | - Christiane Bruns
- Department of General, Visceral and Tumor Surgery, University Hospital Cologne, Cologne, Germany
| | - Markus Moehler
- Department of Internal Medicine I, Johannes Gutenberg-University of Mainz, Mainz, Germany
| | - Florian Lordick
- University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany
| | - Ines Gockel
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
| | | | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.,Department of Internal Medicine II, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany
| | - Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| |
Collapse
|
|
20
|
Waldum HL, Rehfeld JF. Gastric cancer and gastrin: on the interaction of Helicobacter pylori gastritis and acid inhibitory induced hypergastrinemia. Scand J Gastroenterol 2019; 54:1118-1123. [PMID: 31524029 DOI: 10.1080/00365521.2019.1663446] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Gastric cancer, a disease with a reduced frequency for decades, now appears to be on the rise again in young Americans. The epidemiology of gastric cancer differs between tumors in the cardia and those of the more distal parts of the stomach. The tumors are divided into the intestinal type showing glandular growth pattern and the diffuse type with a different pattern. The latter often expresses neuroendocrine and more specifically ECL-cell markers suggesting that they originate from the ECL cell, the target cell for the antral hormone, gastrin. Helicobacter pylori gastritis is accepted as the major cause of gastric cancer, but only after having induced oxyntic atrophy which reduces gastric acid secretion and thus induces hypoacidity leading to hypergastrinemia. Long-term hypergastrinemia is known to induce malignant neoplasia in the stomach of animals as well as man. Recently treatment with proton pump inhibitor after Helicobacter pylori eradication in patients with gastroesophageal reflux disease, has been reported to predispose to gastric cancer. Since profound acid inhibition is a well-known cause of gastric neoplasia, it is to be expected that Helicobacter pylori infection and profound acid inhibition has an additive or possibly potentiating effect on the development of gastric cancer.
Collapse
Affiliation(s)
- Helge L Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology , Trondheim , Norway
| | - Jens F Rehfeld
- Department of Clinical Biochemistry , Rigshospitalet, Copenhagen , Denmark
| |
Collapse
|
|
21
|
Insights Into Pediatric Autoimmune Gastritis: Is There a Role for Helicobacter pylori Infection? J Pediatr Gastroenterol Nutr 2019; 68:e99-e104. [PMID: 30664567 DOI: 10.1097/mpg.0000000000002278] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Autoimmune gastritis (AIG) is a chronic inflammatory condition of the gastric mucosa, mainly described in adults presenting with pernicious anemia. It results from antibody-mediated destruction of parietal cells, but the precise initiating event is unknown. The pathogenicity of Helicobacter pylori (H pylori) has been suggested but not established. This study aimed to better characterize AIG in pediatric patients and to address the possible role of H pylori infection. METHODS Descriptive single-center study, retrospectively describing 20 patients with a diagnosis of AIG based on positivity for anti-parietal cell autoantibodies, in addition to analytical and/or histological findings of oxyntic mucosa atrophy. RESULTS In the majority (18/20), AIG diagnosis was suggested during investigation of refractory iron-deficient anemia. One patient had dyspepsia and none of the others had gastrointestinal symptoms. Fifty-five percent (11/20) were H pylori positive, but there were no significant differences regarding mean hemoglobin values at presentation (10.6 ± 2.5 vs 9.5 ± 1.0 g/dL, P > 0.05), analytical indicators of gastric atrophy (gastrin, 564.4 ± 184 vs 721.2 ± 220.6 pg/mL, P > 0.05), or in the presence or the grade of oxyntic mucosa atrophy. CONCLUSIONS Our findings highlight that AIG may have an age-dependent presentation; thus, we can consider a pediatric phenotype that in contrast to adults, is manifested by refractory iron-deficient anemia and associated with parietal cell autoantibody positivity, but not intrinsic factor autoantibodies. A correlation between H pylori and AIG was not evident in the current study and it is still unclear whether H pylori is a trigger for AIG.
Collapse
|
|
22
|
Han HS, Lee SY, Oh SY, Moon HW, Cho H, Kim JH. Correlations of the Gastric and Duodenal Microbiota with Histological, Endoscopic, and Symptomatic Gastritis. J Clin Med 2019; 8:E312. [PMID: 30841591 PMCID: PMC6462939 DOI: 10.3390/jcm8030312] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 02/21/2019] [Accepted: 02/25/2019] [Indexed: 12/19/2022] Open
Abstract
Mucosal inflammation is characterized by neutrophil and mononuclear cell infiltration. This study aimed to determine the gastric and duodenal microbiota associated with histological, endoscopic, and symptomatic gastritis. Dyspeptic adults who presented for evaluation were included. Subjects with either comorbidities or recent drug intake were excluded. Three endoscopic biopsies were obtained from the antrum, body, and duodenum. Next-generation sequencing for 16S ribosomal RNA V1⁻V2 hypervariable regions was performed. The correlation between the composition of microbiota and the degree of inflammatory cell infiltration, endoscopic findings, and Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) score was analyzed. In 98 included subjects, microbial communities in the antrum and body showed Bray⁻Curtis similarity; however, those in the duodenum showed dissimilarity. Histological and endoscopic gastritis was associated with the abundance of Helicobacter pylori and that of commensal bacteria in the stomach. The abundances of Variovorax paradoxus and Porphyromonas gingivalis were correlated with histological gastritis, but not with endoscopic or symptomatic gastritis. The total PAGI-SYM score showed a stronger correlation with the duodenal microbiota (Prevotella nanceiensis and Alloprevotella rava) than with the gastric microbiota (H. pylori, Neisseria elongate, and Corynebacterium segmentosum). Different correlations of the gastric and duodenal microbiota with histological, endoscopic, and symptomatic gastritis were observed for the first time at the species level. H. pylori-negative gastritis is not associated with endoscopic or symptomatic gastritis. Only H. pylori-induced endoscopic gastritis requires gastric cancer surveillance. Owing to the weak correlation with H. pylori, symptomatic gastritis should be assessed separately from histological and endoscopic gastritis.
Collapse
Affiliation(s)
- Hye Seung Han
- Department of Pathology, Konkuk University School of Medicine, Seoul 05030, Korea.
| | - Sun-Young Lee
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul 05030, Korea.
| | - Seo Young Oh
- Department of Pathology, Konkuk University School of Medicine, Seoul 05030, Korea.
| | - Hee Won Moon
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul 05030, Korea.
| | - Hyunseok Cho
- R&D Center, BioCore. Co. Ltd., Seoul 08511, Korea.
| | - Ji-Hoon Kim
- R&D Center, BioCore. Co. Ltd., Seoul 08511, Korea.
| |
Collapse
|
|
23
|
Black CJ, Houghton LA, Ford AC. Insights into the evaluation and management of dyspepsia: recent developments and new guidelines. Therap Adv Gastroenterol 2018; 11:1756284818805597. [PMID: 30397412 PMCID: PMC6207968 DOI: 10.1177/1756284818805597] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 09/17/2018] [Indexed: 02/04/2023] Open
Abstract
Dyspepsia is a very common gastrointestinal (GI) condition worldwide. We critically examine the recommendations of recently published guidelines for the management of dyspepsia, including those produced jointly by the American College of Gastroenterology and the Canadian Association of Gastroenterology, and those published by the UK National Institute for Health and Care Excellence. Dyspepsia is a symptom complex, characterized by a range of upper GI symptoms including epigastric pain or burning, early satiety, and post-prandial fullness. Although alarm features are used to help prioritize access to upper GI endoscopy, they are of limited utility in predicting endoscopic findings, and the majority of patients with dyspepsia will have no organic pathology identified at upper GI endoscopy. These patients are labelled as having functional dyspepsia (FD). The Rome IV criteria, which are used to define FD, further subclassify patients with FD as having either epigastric pain syndrome or post-prandial distress syndrome, depending on their predominant symptoms. Unfortunately, the Rome criteria perform poorly at identifying FD without the need for upper GI endoscopy. This has led to the investigation of alternative diagnostic approaches, including whether a capsaicin pill or combined serum biomarkers can accurately identify patients with FD. However, there is insufficient evidence to support either of these approaches at the present time. Patients with FD should be tested for H. pylori infection and be prescribed eradication therapy if they test positive. If they continue to have symptoms following this, then a trial of treatment with a proton pump inhibitor (PPI) should be given for up to 8 weeks. In cases where symptoms fail to adequately respond to PPI treatment, a tricyclic antidepressant may be of benefit, and should be continued for 6 to 12 months in patients who respond. Prokinetics demonstrate limited efficacy for treating FD, but could be considered if other strategies have failed. However, there are practical difficulties due to their limited availability in some countries and the risk of serious side effects. Patients with FD who fail to respond to drug treatments should be offered psychological therapy, where available. Overall, with the exception of recommendations relating to H. pylori testing and the prescription of PPIs, which are made on the basis of high-quality evidence, the evidence underpinning other elements of dyspepsia management is largely of low-quality. Consequently, there are still many aspects of the evaluation and management of dyspepsia that require further research.
Collapse
Affiliation(s)
| | - Lesley A. Houghton
- Leeds Gastroenterology Institute, St. James’s University Hospital, Leeds, UK,Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
| | - Alexander C. Ford
- Leeds Gastroenterology Institute, St. James’s University Hospital, Leeds, UK,Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
| |
Collapse
|
|
24
|
The differential diagnosis of Helicobacter pylori negative gastritis. Virchows Arch 2018; 473:533-550. [DOI: 10.1007/s00428-018-2454-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 06/12/2018] [Accepted: 09/05/2018] [Indexed: 02/07/2023]
|
|
25
|
Venerito M, Vasapolli R, Malfertheiner P. [Prevention, early diagnosis and therapy of gastric cancer]. MMW Fortschr Med 2018; 158:39-43. [PMID: 27439829 DOI: 10.1007/s15006-016-8513-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Marino Venerito
- Otto-von-Guericke-Universität Magdeburg Klinik für Gastroenterologie, Hepatologie und Infektiologie, Leipziger Str. 44, D-39120, Magdeburg, Deutschland
| | - Riccardo Vasapolli
- Otto-von-Guericke-Universität Magdeburg Klinik für Gastroenterologie, Hepatologie und Infektiologie, Leipziger Str. 44, D-39120, Magdeburg, Deutschland
| | - Peter Malfertheiner
- Otto-von-Guericke-Universität Magdeburg Klinik für Gastroenterologie, Hepatologie und Infektiologie, Leipziger Str. 44, D-39120, Magdeburg, Deutschland.
| |
Collapse
|
|
26
|
Venerito M, Canbay A, Vieth M. Parietalzellhypertrophie und Drüsenkörperzysten. DER GASTROENTEROLOGE 2018; 13:90-97. [DOI: 10.1007/s11377-018-0235-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
27
|
Abstract
Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.
Collapse
|
|
28
|
Abstract
A substantial decrease in Helicobacter pylori-associated peptic ulcer disease has been observed during the last decades. Drug-related ulcers as well as idiopathic ulcers are becoming predominant and are more refractory to treatment; however, H. pylori infection still plays an important role in ulcer bleeding and recurrence after therapy. The effect of H. pylori eradication upon functional dyspepsia symptoms has been reviewed in this article and generally confirms the results of previous meta-analyses. Additional evidence suggests a lack of impact upon the quality of life, in spite of improvement in symptoms. The association of H. pylori with gastroesophageal reflux disease and Barrett's esophagus remains controversial with a majority of published studies showing a negative association. Furthermore, a strong inverse relationship between the presence of H. pylori and the esophageal eosinophilia was also reported. Several studies and a review addressed the role of H. pylori in autoimmune gastritis and pernicious anemia. The association of the above still remains controversial. Finally, the necessity of routine endoscopy and H. pylori eradication before bariatric surgery is discussed. Several studies suggest the rationale of preoperative upper endoscopy and H. pylori eradication prior to surgery. However, the prevalence of H. pylori infection prior to surgery in these studies generally reflects the overall prevalence of the infection in the particular geographic area. In addition, results on the role of H. pylori in developing postoperative complications remain controversial.
Collapse
Affiliation(s)
- Olga Sjomina
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia.,Riga East University Hospital, Riga, Latvia
| | - Frederic Heluwaert
- Hepato-gastroenterology department, Annecy Genevois Hospital, Pringy, France
| | - Driffa Moussata
- Gastroenterology department, Tours University Hospital, Tours, France
| | - Marcis Leja
- Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia.,Riga East University Hospital, Riga, Latvia.,Digestive Diseases Centre GASTRO, Riga, Latvia
| |
Collapse
|
|
29
|
Venerito M, Link A, Rokkas T, Malfertheiner P. Gastric cancer - clinical and epidemiological aspects. Helicobacter 2016; 21 Suppl 1:39-44. [PMID: 27531538 DOI: 10.1111/hel.12339] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Gastric cancer (GC) ranks fifth for cancer incidence and second for cancer deaths. Epidemiological data showed that survivors of Hodgkin's lymphoma and patients with pernicious anemia etiologically linked to autoimmune gastritis are at increased risk of GC. Screening of patients with autoimmune thyroid disease by means of pepsinogen (PG) I and PG I/II detected autoimmune gastritis with oxyntic gastric atrophy in one of four patients and may be recommended for GC prevention purposes. The International Agency for Research on Cancer reported a positive association between consumption of processed meet and increased GC risk. A new GC risk prediction model based on biological markers, age, gender, smoking status, family history of GC, and consumption of highly salted food showed good predictive performance, and might prompt individuals to modify their lifestyle habits, attend regular check-up visits or participate in screening programs. A novel GC classification based on gene expression of primary resected cancers correlated with clinicopathological features. Noncoding RNA for GC screening remains the focus of multiple studies. Patients with early GC undergoing endoscopic resection are more likely to develop metachronous lesions than patients undergoing surgery and endoscopic surveillance is warranted in this special cohort. The addition of gastrectomy to chemotherapy did not improve survival of patients with advanced GC and a single noncurable factor. Apatinib, a novel oral vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, improved the median overall survival of patients with advanced GC and progressive disease after two or more lines of prior chemotherapy of nearly 3 months.
Collapse
Affiliation(s)
- Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | | | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| |
Collapse
|