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Dore MP, Pes GM. What Is New in Helicobacter pylori Diagnosis. An Overview. J Clin Med 2021; 10:jcm10102091. [PMID: 34068062 PMCID: PMC8152493 DOI: 10.3390/jcm10102091] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/05/2021] [Accepted: 05/11/2021] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori infection remains one of the most prevalent infections worldwide, especially in low-resource countries, and the major risk factor for peptic ulcer and gastric cancer. The “test-and-treat” strategy is recommended by several guidelines and consensus. The choice of testing method is based on patient age, presence of alarm signs and/or symptoms, use of non-steroidal anti-inflammatory drugs, as well as local availability, test reliability, and cost. Culture is the gold standard to detect H. pylori and, possibly, to perform susceptibility testing, however, it requires upper endoscopy and dedicated labs. Recent advances in molecular biology have provided new strategies in detecting infection and antimicrobial resistance without invasive tests. In this review we attempt to offer a comprehensive panorama on the new diagnostic tools and their potential use in clinical settings, in order to accomplish specific recommendations.
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Affiliation(s)
- Maria Pina Dore
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, 07100 Sassari, Italy;
- Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
- Correspondence: ; Tel.: +39-079-229-886
| | - Giovanni Mario Pes
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, 07100 Sassari, Italy;
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2
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Bulbuloglu E, Dagmura H, Daldal E, Deresoy A, Bakir H, Ozsoy U, Saglam AI, Demir O. Can Simple Tests Prior to Endoscopy Predict the OLGA Stage of Gastritis? Healthcare (Basel) 2020; 8:E230. [PMID: 32722268 PMCID: PMC7551436 DOI: 10.3390/healthcare8030230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 07/16/2020] [Accepted: 07/20/2020] [Indexed: 12/24/2022] Open
Abstract
Gastritis is a progressive disease that evolves from a non-atrophic to atrophic state and progresses through intestinal metaplasia, with some cases leading eventually to gastric cancer. Since gastritis by definition is an inflammatory process of the mucosal lining of the stomach and is usually associated with pain, we aimed to identify any association between the severity of gastritis and pain and a simple inflammatory marker derived from a complete blood count (CBC). This was a prospective cross-sectional study which enrolled 155 consecutive adult patients who underwent an upper endoscopy. Prior to the endoscopy, all patients were given a questionnaire, numerical rating scale (NRS) and complete blood count evaluation. The biopsy was obtained from the gastric mucosa according to the modified Sydney classification and scored with the Operative Link for Gastritis Assessment (OLGA) scoring system. The results showed a significant correlation between NRS and intestinal metaplasia (p < 0.01); moreover, a correlation was also found between the NRS and OLGA stage (r = 0.469, p < 0.001). A nonlinear curve was constructed for OLGA stage estimation according to NRS scores (r2 was found to be 0.442, with p < 0.001). The results also showed a correlation between the neutrophil to the lymphocyte ratio (NLR) and OLGA stage (p < 0.01). No correlation was found between the other gastric parameters and NLR (p > 0.05). Helicobacter pylori positivity did not correlate with NRS and NLR. As a conclusion, pain measured by NRS and NLR, which are simply calculated from the CBC prior to endoscopy, may be used to predict OLGA stages and estimate the severity of gastritis in endoscopy patients.
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Affiliation(s)
- Ertan Bulbuloglu
- General Surgery Department, Faculty of Medicine, Kahramanmaras Sutcu Imam University, 46000 Kahramanmaras, Turkey;
| | - Hasan Dagmura
- General Surgery and Surgical Oncology Department, Dumlupinar University Kütahya Evliya Çelebi Training And Research Hospital, 60250 Tokat, Turkey
| | - Emin Daldal
- General Surgery Department, Gaziosmanpasa University, 60250 Tokat, Turkey;
| | - Alev Deresoy
- Pathology Department, Gaziosmanpasa University, 60250 Tokat, Turkey;
| | - Huseyin Bakir
- General Surgery and Surgical Oncology Department, Gaziosmanpasa University, 60250 Tokat, Turkey;
| | - Ugur Ozsoy
- Resident of General Surgery Department, Gaziosmanpasa University, 60250 Tokat, Turkey; (U.O.); (A.I.S.)
| | - Ali Ihsan Saglam
- Resident of General Surgery Department, Gaziosmanpasa University, 60250 Tokat, Turkey; (U.O.); (A.I.S.)
| | - Osman Demir
- Biostatistics Department, Gaziosmanpasa University, 60250 Tokat, Turkey;
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Gawron AJ, Shah SC, Altayar O, Davitkov P, Douglas M, Kevin T, Mustafa RA. AGA Technical Review on Gastric Intestinal Metaplasia-Natural History and Clinical Outcomes. Gastroenterology 2020; 158:705-731.e5. [PMID: 31816300 PMCID: PMC7375032 DOI: 10.1053/j.gastro.2019.12.001] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Andrew J. Gawron
- Salt Lake City Specialty Care Center of Innovation & Gastroenterology Section, VA Salt Lake City Health Care System, Salt Lake City, Utah, USA,Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Shailja C. Shah
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Osama Altayar
- Division of Gastroenterology, Washington University School of Medicine, St Louis, MO
| | - Perica Davitkov
- VA Northeast Ohio Healthcare System,Case Western Reserve University, Cleveland, OH, USA
| | - Morgan Douglas
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Turner Kevin
- University of Texas Southwestern College of Medicine, Dallas, TX, USA.,Inform Diagnostics Research Institute, Irving, TX, USA
| | - Reem A. Mustafa
- Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS, USA
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Quach DT, Hiyama T, Gotoda T. Identifying high-risk individuals for gastric cancer surveillance from western and eastern perspectives: Lessons to learn and possibility to develop an integrated approach for daily practice. World J Gastroenterol 2019; 25:3546-3562. [PMID: 31367156 PMCID: PMC6658388 DOI: 10.3748/wjg.v25.i27.3546] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/28/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
Current evidence shows that individuals with gastric dysplasia, severe and extensive gastric atrophy, extensive gastric intestinal metaplasia and the incomplete subtype of intestinal metaplasia are at high risk for gastric cancer (GC) development. There are several approaches to identifying these subjects, including noninvasive methods, esophagogastroduodenoscopy and histology. The main approach in Western countries is histology-based while that in Eastern countries with a high prevalence of GC is endoscopy-based. Regarding asymptomatic individuals, the key issues in selecting applicable approaches are the ability to reduce GC mortality and the cost-effectiveness of the approach. At present, population-based screening programs have only been applied in a few Asian countries with a high risk of GC. Pre-endoscopic risk assessment based on demographic and clinical features, such as ethnicity, age, gender, smoking and Helicobacter pylori status, is helpful for identifying subjects with high pre-test probability for a possibly cost-effective approach, especially in intermediate- and low-risk countries. Regarding symptomatic patients with indications for esophagogastroduodenoscopy, the importance of opportunistic screening should be emphasized. The combination of endoscopic and histological approaches should always be considered as endoscopy provides a real-time assessment of the patient's risk level. In addition, imaging enhanced endoscopy (IEE) has been shown to facilitate targeted biopsies resulting in better correlation between endoscopic and histological findings. Currently, the use of IEE is recommended for endoscopic examinations, and the Operative Link for Gastric Intestinal Metaplasia or Operative Link on Gastritis Assessment grading systems are recommended for histological examinations whenever available. However, resource limitations are an important barrier in many regions worldwide. Thus, for an approach to be applicable in real-life practice, it should be not only evidence-based but also resource-sensitive. In this review, we discuss the current understanding and approaches to identifying high-risk individuals from western and eastern perspectives, as well as the possibility of an integrated, resource-sensitive approach.
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Affiliation(s)
- Duc Trong Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Hochiminh City, Ho Chi Minh 70000, Vietnam
| | - Toru Hiyama
- Health Service Center, Hiroshima University, Higashihiroshima 739-8514, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo 101-8309, Japan
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El-Serag HB, Kao JY, Kanwal F, Gilger M, LoVecchio F, Moss SF, Crowe S, Elfant A, Haas T, Hapke RJ, Graham DY. Houston Consensus Conference on Testing for Helicobacter pylori Infection in the United States. Clin Gastroenterol Hepatol 2018; 16:992-1002.e6. [PMID: 29559361 PMCID: PMC6913173 DOI: 10.1016/j.cgh.2018.03.013] [Citation(s) in RCA: 189] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 03/02/2018] [Accepted: 03/09/2018] [Indexed: 02/07/2023]
Abstract
Despite guidelines for detection and treatment of Helicobacter pylori infection, recommendations to test patients before and after therapy are commonly not followed in the United States. At the Houston Consensus Conference, 11 experts on management of adult and pediatric patients with H pylori, from different geographic regions of the United States, met to discuss key factors in diagnosis of H pylori infection, including identification of appropriate patients for testing, effects of antibiotic susceptibility on testing and treatment, appropriate methods for confirmation of infection and eradication, and relevant health system considerations. The experts divided into groups that used a modified Delphi panel approach to assess appropriate patients for testing, testing for antibiotic susceptibility and treatment, and test methods and confirmation of eradication. The quality of evidence and strength of recommendations were evaluated using the GRADE system. The results of the individual workshops were presented for a final consensus vote by all panel members. After the Expert Consensus Development meeting, the conclusions were validated by a separate panel of gastroenterologists, who assessed their level of agreement with each of the 29 statements developed at the Expert Consensus Development. The final recommendations are provided, on the basis of the best available evidence, and provide consensus statements with supporting literature to implement testing for H pylori infection at health care systems across the United States.
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Affiliation(s)
- Hashem B. El-Serag
- Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, Texas,Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - John Y. Kao
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medicine, Ann Arbor, Michigan
| | - Fasiha Kanwal
- Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, Texas,Department of Medicine, Baylor College of Medicine, Houston, Texas,Center for Innovation in Quality, Effectiveness, and Safety, Houston, Texas
| | - Mark Gilger
- Baylor College of Medicine, Children’s Hospital of San Antonio, San Antonio, Texas,Department of Pediatrics, Baylor College of Medicine, Houston, Texas
| | - Frank LoVecchio
- Department of Medicine, University of Arizona, Tucson, Arizona
| | | | - Sheila Crowe
- Department of Medicine, University of California, San Diego, La Jolla, California
| | - Adam Elfant
- Cooper Medical School, Rowan University, Camden, New Jersey
| | - Thomas Haas
- Department of Pathology, Mercy Health System, Janesville, Wisconsin
| | - Ronald J. Hapke
- Northwest Gastroenterology Clinic, Department of Gastroenterology, Legacy Emanuel Medical Center, Portland, Oregon
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, Texas,Department of Medicine, Baylor College of Medicine, Houston, Texas
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Šašková B, Daum O, Dubová M, Pivovarčíková K, Švajdler M. Precursors of gastric adenocarcinoma. ONKOLOGIE 2018; 12:56-62. [DOI: 10.36290/xon.2018.012] [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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Dore MP, Pes GM, Bassotti G, Usai-Satta P. Dyspepsia: When and How to Test for Helicobacter pylori Infection. Gastroenterol Res Pract 2016; 2016:8463614. [PMID: 27239194 PMCID: PMC4864555 DOI: 10.1155/2016/8463614] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Accepted: 04/14/2016] [Indexed: 12/31/2022] Open
Abstract
Dyspepsia is defined as symptoms related to the upper gastrointestinal tract. Approximately 25% of western populations complain of dyspeptic symptoms each year. 70% of them do not have an organic cause and symptoms are related to the so-called functional dyspepsia, characterized by epigastric pain, early satiety, and/or fullness during or after a meal occurring at least weekly and for at least 6 months according to ROME III criteria. In order to avoid invasive procedures and adverse effects, to minimize costs, to speed up diagnosis, and to provide the most appropriate treatments, primary care physicians need to recognize functional dyspepsia. Because symptoms do not reliably discriminate between organic and functional forms of the disease, anamnesis, family history of peptic ulcer and/or of gastric cancer, medication history, especially for nonsteroidal anti-inflammatory drugs, age, and physical examination could help the physician in discerning between functional dyspepsia and organic causes. For patients without alarm symptoms, noninvasive testing for H. pylori, with either carbon-13-labeled urea breath testing or stool antigen testing, is recommended as a first-line strategy. In this review, we provide recommendations to guide primary care physicians for appropriate use of diagnostic tests and for H. pylori management in dyspeptic patients.
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Affiliation(s)
- Maria Pina Dore
- Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica, University of Sassari, Viale San Pietro, No. 8, 07100 Sassari, Italy
| | - Giovanni Mario Pes
- Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica, University of Sassari, Viale San Pietro, No. 8, 07100 Sassari, Italy
| | - Gabrio Bassotti
- Dipartimento di Medicina, Sezione di Gastroenterologia, University of Perugia, Piazza Lucio Severi 1, San Sisto, 06132 Perugia, Italy
| | - Paolo Usai-Satta
- Gastrointestinal Unit, P. Brotzu Hospital, 09124 Cagliari, Italy
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Hassan TMM, Al-Najjar SI, Al-Zahrani IH, Alanazi FIB, Alotibi MG. Helicobacter pylori chronic gastritis updated Sydney grading in relation to endoscopic findings and H. pylori IgG antibody: diagnostic methods. J Microsc Ultrastruct 2016; 4:167-174. [PMID: 30023224 PMCID: PMC6014253 DOI: 10.1016/j.jmau.2016.03.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 03/15/2016] [Indexed: 02/08/2023] Open
Abstract
Helicobacter pylori (Hp) inhabits the stomach of > 50% of humans and has been established as a major etiological factor in the pathogenesis of chronic gastritis, gastric atrophy, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. The aim of this study was to provide unequivocal information about Hp-associated gastritis grading according to the Sydney grading system and to compare the histopathological features with the endoscopic findings and anti-Hp immunoglobulin (Ig)G serological status. This analytical study was conducted on 157 patients with dyspeptic gastritis. All patients underwent esophagogastroduodenoscopy, and antrum and corpus biopsies were taken. Blood samples were obtained from all participants. Different stains were performed on formalin-fixed, paraffin-embedded tissue blocks that included hematoxylin and eosin and Giemsa stain for histopathological interpretation. The endoscopic findings of gastritis were observed in 120 patients and most of them showed hyperemia (80 patients), whereas seven patients had normal appearing gastric mucosa. Histologically variable numbers of mononuclear inflammatory cellular infiltrates were seen in 150 cases (95.5%). Most of them showed Grade 1 gastritis (80 patients), whereas Grades 2 and 3 were found in 43 and 27 biopsies, respectively. Hp colonization was observed in most of the examined biopsies (93.7%). Hp-IgG seropositivity was found in 80.9% of cases and 19.1% were seronegative. The relationship between endoscopic and histological findings was significant (p < 0.001).
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Affiliation(s)
- Taha M M Hassan
- Department of Pathology, College of Medicine, Beni Suef University, Egypt
| | - Samia I Al-Najjar
- Department of Pathology, College of Medicine, Beni Suef University, Egypt
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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: 1137] [Impact Index Per Article: 113.7] [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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Pizzi M, Saraggi D, Fassan M, Megraud F, Di Mario F, Rugge M. Secondary prevention of epidemic gastric cancer in the model of Helicobacter pylori-associated gastritis. Dig Dis 2014; 32:265-274. [PMID: 24732192 DOI: 10.1159/000357857] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Irrespective of its etiology, long-standing, non-self-limiting gastric inflammation (mostly in Helicobacter pylori-associated cases) is the cancerization ground on which epidemic (intestinal-type) gastric carcinoma (GC) can develop. The natural history of invasive gastric adenocarcinoma encompasses gastritis, atrophic mucosal changes, and intraepithelial neoplasia (IEN). The topography, the extent and the severity of the atrophic changes significantly correlate with the risk of developing both IEN and GC. In recent years, both noninvasive (serological) tests and invasive (endoscopy/biopsy) procedures have been proposed to stratify patients according to different classes of GC risk. As a consequence, different patient-tailored GC secondary prevention strategies have been put forward. This review summarizes the histological features of H. pylori-related gastritis and the natural history of the disease. Histological and serological strategies to assess GC risk as well as the clinical management of atrophic gastritis patients are also discussed.
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Affiliation(s)
- Marco Pizzi
- General Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy
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Carrasco G, Corvalan AH. Helicobacter pylori-Induced Chronic Gastritis and Assessing Risks for Gastric Cancer. Gastroenterol Res Pract 2013; 2013:393015. [PMID: 23983680 PMCID: PMC3745848 DOI: 10.1155/2013/393015] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2012] [Accepted: 02/25/2013] [Indexed: 12/19/2022] Open
Abstract
Chronic gastritis is an inflammation of the gastric mucosa and has multiple etiologies. Here we discuss the pathological alterations induced by Helicobacter pylori (HP) leading to chronic gastritis and the epigenetic bases underlying these changes. We review the histology of the normal gastric mucosa and overview the role of HP in the multistep cascade of GC. We attempt to define the role of the Operative Link for Gastritis Assessment (OLGA) staging system in assessing the risk of GC. The epigenetic bases of chronic gastritis, mainly DNA methylation, are presented through examples such as (i) the methylation of the promoter region of E-cadherin in HP-induced chronic gastritis and its reversion after HP eradication and (ii) the association of methylation of the promoter region of Reprimo, a p53-mediated cell cycle arrest gene, with aggressive HP strains in high risk areas for GC. In addition, we discuss the finding of RPRM as a circulating cell-free DNA, offering the opportunity for noninvasive risk assessment of GC. Finally, the integration of OLGA and tissue biomarkers, by systems pathology approach, suggests that severe atrophy has a greater risk for GC development if, in addition, overexpressed p73. This trial is registered with ClinicalTrials.gov NCT01774266.
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Affiliation(s)
- Gonzalo Carrasco
- Department of Pathology, Mount Sinai School of Medicine, 1425 Madison Ave, New York, NY 10029, USA
| | - Alejandro H. Corvalan
- Centre for Translational Research in Oncology (CITO) and Department of Hematology and Oncology, Pontificia Universidad Catolica de Chile, Marcoleta 391, 8330074 Santiago, Chile
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Interobserver variation in assessment of gastric premalignant lesions: higher agreement for intestinal metaplasia than for atrophy. Eur J Gastroenterol Hepatol 2013; 25:694-9. [PMID: 23337173 DOI: 10.1097/meg.0b013e32835e3397] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Either atrophy or intestinal metaplasia of the gastric mucosa are considered premalignant lesions. The new operative link for gastritis assessment staging system is based on the detection of atrophy, and the operative link for assessment of intestinal metaplasia staging system is based on the detection of intestinal metaplasia. Good interobserver agreement is necessary for identification of any premalignant condition. AIMS The aim of this study was to compare the agreement between findings of gastric atrophy and intestinal metaplasia by expert and general pathologists and to analyze the possible reasons behind any possible disagreement. METHODS Patients with dyspeptic symptoms, aged 55 years and above, without previous Helicobacter pylori eradication were enrolled and analyzed according to the updated Sydney Classification by two expert pathologists and an experienced general pathologist; the results were compared with the consensus driven by the two experts. RESULTS Gastric biopsy specimens from 121 patients (91 women) were included in the analysis; the mean age of the patients was 67.4 years. H. pylori infection was present in 61.2% of patients. The level of agreement between the general pathologist and the two experts (κ-value) was 0.12, 0.46, and 0.87, respectively, for detecting atrophy in the corpus; 0.77, 0.77, and 0.65, respectively, for detecting intestinal metaplasia in the corpus; 0.06, 0.51, and 0.54, respectively, for detecting atrophy in the antrum; and 0.69, 0.85, and 0.79, respectively, for detecting metaplasia in the antrum. CONCLUSION The agreement was substantially higher for intestinal metaplasia than for atrophy. This could result in discrepancies when the operative link for gastritis assessment and operative link for assessment of intestinal metaplasia staging systems are applied and can be caused by differences in the criteria used to define atrophy.
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Fassan M, Pizzi M, Farinati F, Nitti D, Zagonel V, Genta RM, Rugge M. Lesions indefinite for intraepithelial neoplasia and OLGA staging for gastric atrophy. Am J Clin Pathol 2012; 137:727-732. [PMID: 22523210 DOI: 10.1309/ajcpeu41htgxsjdq] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Gastric intraepithelial neoplasia (IEN; formerly dysplasia) is an advanced precancerous lesion. Lesions indefinite for IEN mimic the IEN phenotype but lack some morphologic attributes of IEN. Indefinite for IEN lesions may arise in native foveolae (atypical foveolar hyperproliferation [aFH]) or intestinalized glands (hyperproliferative intestinal metaplasia [HIM]). The clinicopathologic outcome of such lesions is debated. We retrospectively studied the clinicopathologic behavior of 129 consecutive indefinite for IEN lesions (HIM, 98; aFH, 31; median follow-up, 31 months) and correlated outcome with the extent and topography of mucosal atrophy (assessed by OLGA staging) at the initial endoscopy/biopsy. At enrollment, aFH never coexisted with severe/extensive atrophy (all cases were in low-risk OLGA stages [0-II]), whereas HIM was associated with low- and high-risk OLGA stages (0-II, 73; III-IV, 25). At follow-up, IEN was never documented among cases enrolled as aFH, while follow-up endoscopy/biopsy documented 6 neoplastic intraepithelial lesions among 98 cases of HIM (6%, all had high-risk OLGA stages at initial biopsy). OLGA staging can stratify indefinite for IEN lesions into different risk classes, potentially contributing to decisions for a patient-specific follow-up strategy.
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Affiliation(s)
- Matteo Fassan
- Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Italy
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Jang BI, Li Y, Graham DY, Cen P. The Role of CD44 in the Pathogenesis, Diagnosis, and Therapy of Gastric Cancer. Gut Liver 2011. [PMID: 22195236 DOI: 10.5009/gnl.2 011.5.4.397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
CD44 is a transmembrane glycoprotein and surface receptor for hyaluronan that is involved in the response of cells to their microenvironment. CD44 splice variants play roles in carcinogenesis, differentiation, and lymph node metastasis and are predictive of the prognosis for various carcinomas, including gastric cancer. Current data suggest that gastric tissue stem cells and gastric cancer stem cells both express the splice variant, CD44v9. Overall, the data regarding the alterations that occur in CD44 and its splice variants in response to acute and chronic infection with Helicobacter pylori are scant and poorly elucidated in terms of possible changes in expression that occur in gastric cancer precursor lesions, such as chronic atrophic gastritis, pyloric metaplasia and intestinal metaplasia. In this study, we discuss the available data and suggest which new data would likely be useful in clinical practice. We also discuss the potential for CD44-targeted therapeutic strategies in gastric cancer. CD44 and its splice variants are positively associated with the initiation and progression of gastric cancer and may also play important roles in diagnosis, therapy and prognosis. CD44 research has been active but fragmented, and it may offer new therapeutic approaches to gastric cancer.
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Affiliation(s)
- Byung Ik Jang
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
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Jang BI, Li Y, Graham DY, Cen P. The Role of CD44 in the Pathogenesis, Diagnosis, and Therapy of Gastric Cancer. Gut Liver 2011; 5:397-405. [PMID: 22195236 PMCID: PMC3240781 DOI: 10.5009/gnl.2011.5.4.397] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2011] [Revised: 09/18/2011] [Accepted: 09/30/2011] [Indexed: 01/06/2023] Open
Abstract
CD44 is a transmembrane glycoprotein and surface receptor for hyaluronan that is involved in the response of cells to their microenvironment. CD44 splice variants play roles in carcinogenesis, differentiation, and lymph node metastasis and are predictive of the prognosis for various carcinomas, including gastric cancer. Current data suggest that gastric tissue stem cells and gastric cancer stem cells both express the splice variant, CD44v9. Overall, the data regarding the alterations that occur in CD44 and its splice variants in response to acute and chronic infection with Helicobacter pylori are scant and poorly elucidated in terms of possible changes in expression that occur in gastric cancer precursor lesions, such as chronic atrophic gastritis, pyloric metaplasia and intestinal metaplasia. In this study, we discuss the available data and suggest which new data would likely be useful in clinical practice. We also discuss the potential for CD44-targeted therapeutic strategies in gastric cancer. CD44 and its splice variants are positively associated with the initiation and progression of gastric cancer and may also play important roles in diagnosis, therapy and prognosis. CD44 research has been active but fragmented, and it may offer new therapeutic approaches to gastric cancer.
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Affiliation(s)
- Byung Ik Jang
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
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Rugge M, Fassan M, Pizzi M, Farinati F, Sturniolo GC, Plebani M, Graham DY. Operative link for gastritis assessment vs operative link on intestinal metaplasia assessment. World J Gastroenterol 2011; 17:4596-4601. [PMID: 22147965 PMCID: PMC3225096 DOI: 10.3748/wjg.v17.i41.4596] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2011] [Revised: 06/02/2011] [Accepted: 06/09/2011] [Indexed: 02/06/2023] Open
Abstract
AIM To compare the reliability of gastritis staging systems in ranking gastritis-associated cancer risk in a large series of consecutive patients. METHODS Gastric mucosal atrophy is the precancerous condition in which intestinal-type gastric cancer (GC) most frequently develops. The operative link for gastritis assessment (OLGA) staging system ranks the GC risk according to both the topography and the severity of gastric atrophy (as assessed histologically on the basis of the Sydney protocol for gastric mucosal biopsy). Both cross-sectional and long-term follow-up trials have consistently associated OLGA stages III-IV with a higher risk of GC. A recently-proposed modification of the OLGA staging system (OLGIM) basically incorporates the OLGA frame, but replaces the atrophy score with an assessment of intestinal metaplasia (IM) alone. A series of 4552 consecutive biopsy sets (2007-2009) was retrieved and reassessed according to both the OLGA and the OLGIM staging systems. A set of at least 5 biopsy samples was available for all the cases considered. RESULTS In 4460 of 4552 cases (98.0%), both the high-risk stages (III + IV) and the low-risk stages (0 +I + II) were assessed applying the OLGA and OLGIM criteria. Among the 243 OLGA high-risk stages, 14 (5.8%) were down-staged to a low risk using OLGIM. The 67 (1.5%) incidentally-found neoplastic lesions (intraepithelial or invasive) were consistently associated with high-risk stages, as assessed by both OLGA and OLGIM (P < 0.001 for both). Two of 34 intestinal-type GCs coexisting with a high-risk OLGA stage (stage III) were associated with a low-risk OLGIM stage (stage II). CONCLUSION Gastritis staging systems (both OLGA and OLGIM) convey prognostically important information on the gastritis-associated cancer risk. Because of its clinical impact, the stage of gastritis should be included as a conclusive message in the gastritis histology report. Since it focuses on IM alone, OLGIM staging is less sensitive than OLGA staging in the identification of patients at high risk of gastric cancer.
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Rugge M, Fassan M, Pizzi M, Pennelli G, Nitti D, Farinati F. Operative Link for Gastritis Assessment gastritis staging incorporates intestinal metaplasia subtyping. Hum Pathol 2011; 42:1539-1544. [PMID: 21481917 DOI: 10.1016/j.humpath.2010.12.017] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2010] [Revised: 12/16/2010] [Accepted: 12/21/2010] [Indexed: 12/17/2022]
Abstract
Both sulfomucin-type intestinal metaplasia (ie, types II and III intestinal metaplasia, colonic-type intestinal metaplasia) and gastritis in Operative Link for Gastritis Assessment stages III and IV are associated with an increased risk of intestinal-type gastric cancer. This study aimed to verify the hypothesis that gastritis in Operative Link for Gastritis Assessment stages III and IV (both consistently associated with an increased cancer risk) is associated per se with types II and III intestinal metaplasia. Two hundred consecutive cases of atrophic gastritis (Operative Link for Gastritis Assessment stages I, II, III, and IV) were considered (50 cases for each stage). All cases were stained with high iron diamine, and intestinal metaplasia was subtyped accordingly (type I [ie, small-intestinal type] and types II and III). Helicobacter pylori status was also considered, distinguishing H pylori-positive versus H pylori-negative versus H pylori-eradicated patients. A significant association was found between intestinal metaplasia subtype and the Operative Link for Gastritis Assessment stage of gastritis (the higher the stage, the more the colonic-type of intestinal metaplasia, and vice versa; Wilcoxon, P = .001). The strength of the association between Operative Link for Gastritis Assessment stages and the 3 intestinal metaplasia subtypes was confirmed by logistic regression analysis (P < .001; odds ratio, 4.84; 95% confidence interval, 2.97-7.88). Intestinal metaplasia subtyping also correlated with the patient's age (Kruskal-Wallis, P = .001) and H pylori status (Fisher exact, P < .001). Operative Link for Gastritis Assessment staging incorporates the prognostic message obtainable from histochemical gastric mucin subtyping.
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Affiliation(s)
- Massimo Rugge
- Surgical Pathology & Cytopathology Unit, Department of Diagnostic Medical Sciences & Special Therapies, University of Padova, Italy.
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Rugge M, Pennelli G, Pilozzi E, Fassan M, Ingravallo G, Russo VM, Di Mario F. Gastritis: the histology report. Dig Liver Dis 2011; 43 Suppl 4:S373-S384. [PMID: 21459343 DOI: 10.1016/s1590-8658(11)60593-8] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice.
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Affiliation(s)
- Massimo Rugge
- Department of Medical Diagnostic Sciences & Special Therapies, University of Padova, Padova, Italy.
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Quach DT, Le HM, Nguyen OT, Nguyen TS, Uemura N. The severity of endoscopic gastric atrophy could help to predict Operative Link on Gastritis Assessment gastritis stage. J Gastroenterol Hepatol 2011; 26:281-285. [PMID: 21261717 DOI: 10.1111/j.1440-1746.2010.06474.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS The aims of the present study were to evaluate the role of moderate-to-severe endoscopic gastric atrophy (EGA) on predicting Operative Link on Gastritis Assessment (OLGA) gastritis stage, and to assess the association of high-stage OLGA gastritis with gastric neoplasia in patients with non-ulcer dyspepsia. METHODS A cross-sectional study was carried out on 280 dyspeptic outpatients. EGA was assessed according to the Kimura-Takemoto classification. Gastritis stage was established according to the OLGA staging system and gastric neoplasia was assessed according to the Vienna classification. The pathologists who read the specimens were kept blind to the endoscopic results. RESULTS The mean age of patients was 46.1 years (range 20-78 years) with a male-to-female ratio of 1:1. High-stage gastritis (e.g. stage III or IV) was confirmed in 13 (4.6%) patients. All of these patients were more than 40 years-of-age (P = 0.01), had Helicobacter pylori infection (P = 0.0006) and moderate-to-severe EGA (P < 0.001). Low-grade dysplasia was found in seven patients: 4/13 (30.7%) with high-stage gastritis versus 3/267 (1.1%) with low-stage gastritis (P < 0.001). Six of these patients had moderate-to-severe EGA (P = 0.048). The sensitivity, specificity, positive predictive value and negative predictive value of this endoscopic finding in high-stage gastritis diagnosis were 100%, 57.7%, 10.3% and 100%, respectively. CONCLUSIONS OLGA high-stage gastritis was associated with gastric dysplasia and was mostly diagnosed in patients with moderate-to-severe EGA. The absence of this endoscopic finding could effectively rule out the possibility of having high-stage gastritis.
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Affiliation(s)
- Duc Trong Quach
- Department of Endoscopy, University Medical Center at Ho Chi Minh City, Vietnam
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Carrasco G, Diaz J, Valbuena JR, Ibanez P, Rodriguez P, Araya G, Rodriguez C, Torres J, Duarte I, Aravena E, Mena F, Barrientos C, Corvalan AH. Overexpression of p73 as a tissue marker for high-risk gastritis. Clin Cancer Res 2010; 16:3253-9. [PMID: 20530692 DOI: 10.1158/1078-0432.ccr-09-2491] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE Histologic assessment of high-risk gastritis for the development of gastric cancer is not well defined. The identification of tissue markers together with the integration of histologic features will be required for this assessment. EXPERIMENTAL DESIGN Matched tumor/nontumor adjacent mucosa (NTAM) of 91 early gastric cancer and 148 chronic gastritis cases were evaluated for histologic characteristics (atrophy, intestinal metaplasia, chronic inflammation, polymorphonuclear infiltration, and Helicobacter pylori) by the Sydney System. Atrophy risk assessment was also evaluated by the Operative Link on Gastritis Assessment (OLGA) staging system. Eight tissue markers (BRCA1, HSP90, STAT1, FHIT, EGFR, p73, p53, p16INK4a) and EBV were also evaluated by tissue microarray/immunohistochemistry/in situ hybridization platform. Data were analyzed by contingency tables (2 x 2) using Fisher's exact two-tailed test (P < 0.001) and integrated by Significance Analysis of Microarrays (SAM) and clustering analysis. RESULTS Histologically, NTAM have severe intestinal metaplasia/chronic inflammation and severe atrophy assessed by Sydney and OLGA staging systems. H. pylori infection was similar in both groups, and EBV was found only in 5.5% of the tumor samples. Overexpression of p73 was higher in NTAM (50.5%) than in chronic gastritis (10.8%; P < 0.0001). Integration of histologic features and tissue markers showed that overexpression of p73, severe atrophy, and OLGA stage 4 were the most relevant features in NTAM. Clustering analysis correctly assigned NTAM and control cases (P < 0.0001). CONCLUSIONS Overexpression of p73 should be considered for the assessment of high-risk chronic gastritis. SAM allows the integration of histology and tissue markers for this assessment.
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Affiliation(s)
- Gonzalo Carrasco
- Department of Anatomic Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile
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Abstract
The articles published this last year in the field of Helicobacter pylori diagnosis reported the development of in vivo histology, small improvements in some invasive methods (urease test, culture, and histology) and new kits for the stool antigen tests. They also contributed to increasing our knowledge, by further exploration into specific conditions for the urea breath test and into the significance of cagA antibodies. The role of serum markers of atrophy was also confirmed. Molecular methods are still being developed for direct genotyping, detection of H. pylori and its clarithromycin resistance, either by polymerase chain reaction or fluorescent in-situ hybridization. For the first time, there was a report on a possible interest of magnetic resonance spectroscopy.
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Affiliation(s)
- Lurdes Monteiro
- Departamento de Doenças Infecciosas, Instituto Nacional Saúde Dr Ricardo Jorge, Lisbon, Portugal
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In praise of folly: the Erasmus score for intestinal metaplasia. Gastrointest Endosc 2009; 70:26-8. [PMID: 19559831 DOI: 10.1016/j.gie.2008.10.031] [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: 09/29/2008] [Accepted: 10/18/2008] [Indexed: 02/08/2023]
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Abstract
PURPOSE OF REVIEW The majority of problems in interpreting gastritis remain Helicobacter related, but their nature has changed. The present review covers gastritis historically through cancer risk staging systems. RECENT FINDINGS Key points to remember are: Helicobacter is associated with several forms of gastritis; in the present review, I am focusing on the two ends of the disease, 'Helicobacter pylori infection', that starts with antral predominant gastritis but can continue to oxyntic predominant disease with atrophy; the role Helicobacter pylori plays in autoimmune gastritis with pernicious anemia remains unresolved; gastritis staging systems for cancer risk, namely Baylor and Operative Link on Gastritis Assessment, are currently available. SUMMARY As most gastric carcinomas arise on a background of atrophic gastritis, and the risk increases with the extent of atrophy, an index of atrophy location and extent could be useful in predicting patients at greatest risk for carcinoma. It is now possible to stage patients for cancer risk. Nonetheless, in a field such as gastritis in which many issues remain unresolved, a classification or staging system that is more descriptive will likely prove more useful.
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