|
1
|
Zhou B, Szymanski CM, Baylink A. Bacterial chemotaxis in human diseases. Trends Microbiol 2023; 31:453-467. [PMID: 36411201 PMCID: PMC11238666 DOI: 10.1016/j.tim.2022.10.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 10/16/2022] [Accepted: 10/18/2022] [Indexed: 11/21/2022]
Abstract
To infect and cause disease, bacterial pathogens must localize to specific regions of the host where they possess the metabolic and defensive acumen for survival. Motile flagellated pathogens exercise control over their localization through chemotaxis to direct motility based on the landscape of exogenous nutrients, toxins, and molecular cues sensed within the host. Here, we review advances in understanding the roles chemotaxis plays in human diseases. Chemotaxis drives pathogen colonization to sites of inflammation and injury and mediates fitness advantages through accessing host-derived nutrients from damaged tissue. Injury tropism may worsen clinical outcomes through instigating chronic inflammation and subsequent cancer development. Inhibiting bacterial chemotactic systems could act synergistically with antibacterial medicines for more effective and specific eradication.
Collapse
Affiliation(s)
- Bibi Zhou
- University of Georgia, Department of Microbiology and Complex Carbohydrate Research Center, Athens, GA 30602, USA
| | - Christine M Szymanski
- University of Georgia, Department of Microbiology and Complex Carbohydrate Research Center, Athens, GA 30602, USA
| | - Arden Baylink
- Washington State University, Department of Veterinary Microbiology and Pathology, Pullman, WA 99164, USA.
| |
Collapse
|
|
2
|
Vasapolli R, Ailloud F, Suerbaum S, Neumann J, Koch N, Macke L, Schirra J, Mayerle J, Malfertheiner P, Schulz C. Intraprocedural gastric juice analysis as compared to rapid urease test for real-time detection of Helicobacter pylori. World J Gastroenterol 2023; 29:1638-1647. [PMID: 36970593 PMCID: PMC10037247 DOI: 10.3748/wjg.v29.i10.1638] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 01/15/2023] [Accepted: 02/22/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy (UGE) to perform gastric juice analysis and real-time detection of Helicobacter pylori (H. pylori). AIM To assess the diagnostic performance of this technology and its impact on the management of H. pylori in the real-life clinical setting. METHODS Patients undergoing routine UGE were prospectively recruited. Biopsies were taken to assess gastric histology according to the updated Sydney system and for rapid urease test (RUT). Gastric juice sampling and analysis was performed using the Endofaster, and the diagnosis of H. pylori was based on real-time ammonium measurements. Histological detection of H. pylori served as the diagnostic gold standard for comparing Endofaster-based H. pylori diagnosis with RUT-based H. pylori detection. RESULTS A total of 198 patients were prospectively enrolled in an H. pylori diagnostic study by Endofaster-based gastric juice analysis (EGJA) during the UGE. Biopsies for RUT and histological assessment were performed on 161 patients (82 men and 79 women, mean age 54.8 ± 19.2 years). H. pylori infection was detected by histology in 47 (29.2%) patients. Overall, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) for H. pylori diagnosis by EGJA were 91.5%, 93.0%, 92.6%, 84.3%, and 96.4%, respectively. In patients on treatment with proton pump inhibitors, diagnostic sensitivity was reduced by 27.3%, while specificity and NPV were unaffected. EGJA and RUT were comparable in diagnostic performance and highly concordant in H. pylori detection (κ-value = 0.85). CONCLUSION Endofaster allows for rapid and highly accurate detection of H. pylori during gastroscopy. This may guide taking additional biopsies for antibiotic susceptibility testing during the same procedure and then selecting an individually tailored eradication regimen.
Collapse
Affiliation(s)
- Riccardo Vasapolli
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
- Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich 81377, Germany
| | - Florent Ailloud
- Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians University of Munich, Munich 80336, Germany
- National Reference Center for Helicobacter pylori, Munich 81377, Germany
| | - Sebastian Suerbaum
- Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich 81377, Germany
- Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians University of Munich, Munich 80336, Germany
- National Reference Center for Helicobacter pylori, Munich 81377, Germany
| | - Jens Neumann
- Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University of Munich, Munich 81377, Germany
| | - Nadine Koch
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
| | - Lukas Macke
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
- Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich 81377, Germany
| | - Jörg Schirra
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
| | - Julia Mayerle
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
| | - Peter Malfertheiner
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
| | - Christian Schulz
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
- Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich 81377, Germany
| |
Collapse
|
|
3
|
Vasapolli R, Ailloud F, Suerbaum S, Neumann J, Koch N, Macke L, Schirra J, Mayerle J, Malfertheiner P, Schulz C. Intraprocedural gastric juice analysis as compared to rapid urease test for real-time detection of Helicobacter pylori. World J Gastroenterol 2023; 29:1494-1503. [DOI: 10.3748/wjg.v29.i10.1494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/10/2023] Open
Abstract
BACKGROUND Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy (UGE) to perform gastric juice analysis and real-time detection of Helicobacter pylori (H. pylori).
AIM To assess the diagnostic performance of this technology and its impact on the management of H. pylori in the real-life clinical setting.
METHODS Patients undergoing routine UGE were prospectively recruited. Biopsies were taken to assess gastric histology according to the updated Sydney system and for rapid urease test (RUT). Gastric juice sampling and analysis was performed using the Endofaster, and the diagnosis of H. pylori was based on real-time ammonium measurements. Histological detection of H. pylori served as the diagnostic gold standard for comparing Endofaster-based H. pylori diagnosis with RUT-based H. pylori detection.
RESULTS A total of 198 patients were prospectively enrolled in an H. pylori diagnostic study by Endofaster-based gastric juice analysis (EGJA) during the UGE. Biopsies for RUT and histological assessment were performed on 161 patients (82 men and 79 women, mean age 54.8 ± 19.2 years). H. pylori infection was detected by histology in 47 (29.2%) patients. Overall, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) for H. pylori diagnosis by EGJA were 91.5%, 93.0%, 92.6%, 84.3%, and 96.4%, respectively. In patients on treatment with proton pump inhibitors, diagnostic sensitivity was reduced by 27.3%, while specificity and NPV were unaffected. EGJA and RUT were comparable in diagnostic performance and highly concordant in H. pylori detection (κ-value = 0.85).
CONCLUSION Endofaster allows for rapid and highly accurate detection of H. pylori during gastroscopy. This may guide taking additional biopsies for antibiotic susceptibility testing during the same procedure and then selecting an individually tailored eradication regimen.
Collapse
Affiliation(s)
- Riccardo Vasapolli
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany,Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich 81377, Germany
| | - Florent Ailloud
- Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians University of Munich, Munich 80336, Germany,National Reference Center for Helicobacter pylori, Munich 81377, Germany
| | - Sebastian Suerbaum
- Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich 81377, Germany,Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians University of Munich, Munich 80336, Germany,National Reference Center for Helicobacter pylori, Munich 81377, Germany
| | - Jens Neumann
- Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University of Munich, Munich 81377, Germany
| | - Nadine Koch
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
| | - Lukas Macke
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany,Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich 81377, Germany
| | - Jörg Schirra
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
| | - Julia Mayerle
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
| | - Peter Malfertheiner
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany
| | - Christian Schulz
- Medical Department ІІ, University Hospital LMU Munich, Munich 81377, Germany,Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich 81377, Germany
| |
Collapse
|
|
4
|
Holmberg D, Mattsson F, Xie S, Ness-Jensen E, El-Serag H, Lagergren J. Risk of gastric and oesophageal adenocarcinoma following discontinuation of long-term proton-pump inhibitor therapy. J Gastroenterol 2022; 57:942-951. [PMID: 36258093 PMCID: PMC9663349 DOI: 10.1007/s00535-022-01930-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 10/02/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND There is uncertainty whether long-term use of proton-pump inhibitors can cause gastric adenocarcinoma (GAC) and oesophageal adenocarcinoma (OAC). This study aimed to determine how discontinuation of long-term PPI therapy influences the risk of GAC and OAC. METHODS This population-based cohort study included all long-term users of PPI therapy in Sweden in 2005-2018 was based on Swedish nationwide health registry data. The exposure was discontinuation of long-term PPI therapy, defined as no dispensation of PPI following inclusion and used as a time-varying variable, compared to remaining on PPI. Main outcomes were GAC and OAC, while oesophageal squamous cell carcinoma (OSCC) was included as a comparison outcome. Incidence rate ratios (IRR) with 95% CI adjusted for age, sex, comorbidity, obesity, diabetes, hyperlipidaemia, NSAIDs/aspirin, and statins were calculated with Poisson regression. RESULTS Among 730,176 long-term PPI users (mean age 65.6 years, 58.4% females) with 4,210,925 person-years at risk (median 5.5 person-years), 439,390 (60.2%) discontinued PPIs. In total, 495 developed GAC, 598 OAC, and 188 developed OSCC. PPI discontinuation was associated with decreased risk of GAC (IRR 0.81, 95% CI 0.67-0.98) and OAC (IRR 0.80, 95% CI 0.68-0.96), but not OSCC (IRR 1.10, 95% CI 0.82-1.49) compared to continued PPI use. Stratified analyses showed decreased point estimates across most age categories and both sexes for GAC and OAC risk among participants discontinuing PPI therapy. CONCLUSION Discontinuation of long-term PPI therapy may decrease the risk of GAC and OAC, suggesting that physicians should consider ceasing prescribing long-term PPI in patients without continued indication for its use.
Collapse
Affiliation(s)
- Dag Holmberg
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13a, 17177, Stockholm, Sweden.
| | - Fredrik Mattsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13a, 17177, Stockholm, Sweden
| | - Shaohua Xie
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13a, 17177, Stockholm, Sweden
| | - Eivind Ness-Jensen
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13a, 17177, Stockholm, Sweden
- Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
- Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - Hashem El-Serag
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13a, 17177, Stockholm, Sweden
- Department of Medicine, Baylor College of Medicine, Houston, USA
| | - Jesper Lagergren
- School of Cancer and Pharmacological Sciences, King's College London, London, UK
| |
Collapse
|
|
5
|
Brennan DE, O'Morain C, McNamara D, Smith SM. Combined antrum and corpus biopsy protocol improves Helicobacter pylori culture success. World J Gastrointest Pathophysiol 2022; 13:34-40. [PMID: 35116178 PMCID: PMC8788162 DOI: 10.4291/wjgp.v13.i1.34] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/16/2021] [Accepted: 01/14/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) causes chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Eradication rates have fallen, mainly due to antimicrobial resistance. Consensus guidelines recommend that first-line treatment is based on the local prevalence of antimicrobial resistance and that rescue therapies are guided by antimicrobial susceptibility testing (AST). However, H. pylori culture is challenging and culture-based AST is not routinely performed in the majority of hospitals. Optimisation of H. pylori culture from clinical specimens will enable more widespread AST to determine the most appropriate antimicrobials for H. pylori eradication.
AIM To determine whether dual antrum and corpus biopsy sampling is superior to single antrum biopsy sampling for H. pylori culture.
METHODS The study received ethical approval from the joint research ethics committee of Tallaght University Hospital and St. James’s Hospital. Patients referred for upper gastrointestinal endoscopy were invited to participate. Biopsies were collected in tubes containing Dent’s transport medium and patient demographics were recorded. Biopsies were used to inoculate Colombia blood agar plates. Plates were incubated under microaerobic conditions and evaluated for the presence of H. pylori. Statistical analyses were performed using Graphpad PRISM. Continuous variables were compared using the two-tailed independent t-test. Categorical variables were compared using the two-tailed Fisher exact test. In all cases, a P value less than 0.05 was considered significant.
RESULTS In all, samples from 219 H. pylori-infected patients were analysed in the study. The mean age of recruited patients was 48 ± 14.9 years and 50.7% (n = 111) were male. The most common endoscopic finding was gastritis (58.9%; n = 129). Gastric ulcer was diagnosed in 4.6% (n = 10) of patients, while duodenal ulcer was diagnosed in 2.7% (n = 6). Single antrum biopsies were collected from 73 patients, whereas combined antrum and corpus biopsies were collected from 146 patients. There was no significant difference in age, sex or endoscopic findings between the two groups. H. pylori was successfully cultured in a significantly higher number of cases when combined antrum and corpus biopsies were used compared to a single antrum biopsy [64.4% (n = 94/146) vs 49.3% (36/73); P = 0.04)].
CONCLUSION Combined corpus and antrum biopsy sampling improves H. pylori culture success compared to single antrum biopsy sampling.
Collapse
Affiliation(s)
- Denise E Brennan
- Department of Clinical Medicine, Trinity College Dublin, Trinity Centre, Tallaght University Hospital, Dublin D24, Ireland
| | - Colm O'Morain
- Department of Clinical Medicine, Trinity College Dublin, Trinity Centre, Tallaght University Hospital, Dublin D24, Ireland
| | - Deirdre McNamara
- Department of Clinical Medicine, Trinity College Dublin, Trinity Centre, Tallaght University Hospital, Dublin D24, Ireland
| | - Sinead M Smith
- Department of Clinical Medicine, Trinity College Dublin, Trinity Centre, Tallaght University Hospital, Dublin D24, Ireland
| |
Collapse
|
|
6
|
Xu AA, Graham DY. Things We Do for No Reason™: Serum Serologic Helicobacter pylori Testing. J Hosp Med 2021; 16:691-693. [PMID: 34328849 PMCID: PMC8577700 DOI: 10.12788/jhm.3638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 04/14/2021] [Indexed: 11/20/2022]
Affiliation(s)
- Anthony A Xu
- Department of Medicine, Baylor College of Medicine, Houston, Texas
- Corresponding Author: Anthony A Xu, MD; ; Telephone: 512-786-1309; Twitter: @AnthonyXuMD
| | - David Y Graham
- Department of Medicine, Baylor College of Medicine, Houston, Texas
- Section of Gastroenterology, Michael E. Debakey Veteran Affairs Medical Center, Houston, Texas
| |
Collapse
|
|
7
|
Garcés-Durán R, Galdín-Ferreyra M, Delgado-Guillena PG, Cuatrecasas M, Córdova H, García-Rodríguez A, Rodrigo-Calvo MT, Jimeno-Ramiro M, Araujo IK, Ginès A, Llach J, Fernandez-Esparrach G. Diagnosis of Helicobacter pylori Infection by the Arrangement of Collecting Venules Using White Light Endoscopy: Evaluation of Interobserver Agreement. Dig Dis 2021; 40:376-384. [PMID: 34348294 DOI: 10.1159/000518100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 06/25/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Regular arrangement of collecting venules (RAC) in gastric mucosa accurately identifies patients without Helicobacter pylori (H pylori) infection. The aim of our study was to evaluate the reproducibility of RAC using white light endoscopy without magnification, in a European country, and to assess the impact of proton pump inhibitors (PPIs). METHODS A multicenter prospective study with image capture of the distal lesser gastric curvature and gastric biopsies was performed. The presence of starfish-like minute points regularly distributed throughout lesser curvature was considered as RAC positive (RAC+). A set of 20 images was used for the training phase and inter and intra-observer agreements were calculated. RESULTS 174 patients were included and 85 (48.9%) were taking PPIs. Kappa values for interobserver and intra-observer agreements were substantial (0.786) and excellent (0.906), respectively. H. pylori infection was diagnosed in 29 patients (16.7%): 10/85 with PPIs and 19/89 without PPIs (11.8% vs. 21.3%; p = 0.09). All RAC + patients were free of H. pylori infection, with a sensitivity and negative predictive value of 100%, regardless of PPI intake. CONCLUSION The endoscopic diagnosis of H. pylori by RAC is an easy-to-learn and highly reproducible technique, even with PPI intake. Our results warrant RAC as a real-time diagnostic method for H. pylori-negative infection in Western practice.
Collapse
Affiliation(s)
- Rodrigo Garcés-Durán
- Endoscopy Unit, ICMDiM, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain
| | | | | | - Miriam Cuatrecasas
- Pathology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain.,IDIBAPS, Barcelona, Spain.,CIBEREHD, Barcelona, Spain
| | - Henry Córdova
- Endoscopy Unit, ICMDiM, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.,IDIBAPS, Barcelona, Spain.,CIBEREHD, Barcelona, Spain
| | - Ana García-Rodríguez
- Endoscopy Unit, ICMDiM, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain
| | | | | | - Isis Karina Araujo
- Endoscopy Unit, ICMDiM, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Angels Ginès
- Endoscopy Unit, ICMDiM, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.,IDIBAPS, Barcelona, Spain.,CIBEREHD, Barcelona, Spain
| | - Josep Llach
- Endoscopy Unit, ICMDiM, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.,IDIBAPS, Barcelona, Spain
| | - Gloria Fernandez-Esparrach
- Endoscopy Unit, ICMDiM, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.,IDIBAPS, Barcelona, Spain.,CIBEREHD, Barcelona, Spain
| |
Collapse
|
|
8
|
Vasapolli R, Venerito M, Schirrmeister W, Thon C, Weigt J, Wex T, Malfertheiner P, Link A. Inflammatory microRNAs in gastric mucosa are modulated by Helicobacter pylori infection and proton-pump inhibitors but not by aspirin or NSAIDs. PLoS One 2021; 16:e0249282. [PMID: 33857171 PMCID: PMC8049315 DOI: 10.1371/journal.pone.0249282] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 03/15/2021] [Indexed: 12/21/2022] Open
Abstract
Gastric carcinogenesis is associated with alterations of microRNAs (miRNAs) and reversal of these alterations may be a crucial element in cancer prevention. Here we evaluate the influence of H. pylori eradication, low-dose aspirin (LDA), non-steroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPI) on modification of inflammatory mucosal miRNAs miR-155 and miR-223 in Helicobacter pylori-infected and non-infected subjects. The study was performed in two parts: 1) interventional study in 20 healthy subjects with and without H. pylori infection or following eradication (each n = 10) where LDA (100 mg) was given daily for 7 days; 2) prospective case-control observational study (n = 188). MiR-155 and miR-223 expression was strongly linked to H. pylori-infection and in short-term view showed a trend for reversal after eradication. Daily LDA as well as regular NSAIDs showed no influence on miRNAs expression both in healthy subjects and patients, while regular PPI intake was associated with lower miR-155 expression in antrum of patients with chronic gastritis independent of density of neutrophils and mononuclear infiltrate. In summary, PPI but not LDA or NSAIDs were associated with modification of inflammatory miRNAs miR-155 and miR-223 in an H. pylori dependent manner. The functional role of inflammatory miR-155 and miR-223 in understanding of H. pylori-related diseases needs further evaluation.
Collapse
Affiliation(s)
- Riccardo Vasapolli
- 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
| | - Wiebke Schirrmeister
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Cosima Thon
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Jochen Weigt
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Thomas Wex
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
- Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Department of Molecular Genetics, Magdeburg, Germany
| | - Peter Malfertheiner
- 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
- * E-mail:
| |
Collapse
|
|
9
|
Mizukami K, Katsuta M, Okamoto K, Fukuda K, Ogawa R, Kawahara Y, Hirashita Y, Sato Y, Fukuda M, Okimoto T, Kodama M, Fujioka T, Murakami K. Influence of acotiamide on 13C-urea breath test for Helicobacter pylori diagnosis. J Clin Biochem Nutr 2020; 67:332-337. [PMID: 33293776 PMCID: PMC7705081 DOI: 10.3164/jcbn.20-17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 03/31/2020] [Indexed: 02/06/2023] Open
Abstract
The Helicobacter pylori infection and functional dyspepsia are often coexisted. The effect of acotiamide, a drug for functional dyspepsia, on the result of Helicobacter pylori diagnosis has yet to be studied. We evaluated the influence of acotiamide on the results of Helicobacter pylori diagnosis in the 13C-urea breath test. Twenty patients with Helicobacter pylori-positive functional dyspepsia were treated with 100 mg of acotiamide three times a day for two weeks. Changes in 13C-urea breath test were investigated before and after administration, and two weeks after administration as the follow-up period. The 13C-urea breath test and the medical questionnaire of modified frequency scale for the symptoms of gastroesophageal reflux disease were conducted at every period. Nineteen patients were included for analysis. No patients showed negative in 13C-urea breath test at Weeks 2 and 4. On the symptom scale, dyspepsia and total scores decreased from Week 0 to Week 2 and increased from Week 2 to Week 4, and the improvement rates of the dyspepsia score at Week 2 was 63%. In conclusion, we confirmed that acotiamide is unlikely to influence the result of 13C-urea breath test and it may improve the symptoms of functional dyspepsia during Helicobacter pylori eradication treatment.
Collapse
Affiliation(s)
- Kazuhiro Mizukami
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Makoto Katsuta
- Department of Internal Medicine, Takada Chuo Hospital, 1176-1 Shinchi, Bungotakada, Oita 879-0627, Japan
| | - Kazuhisa Okamoto
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Kensuke Fukuda
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Ryo Ogawa
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Yoshinari Kawahara
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Yuka Hirashita
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Yuto Sato
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Masahide Fukuda
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Tadayoshi Okimoto
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Masaaki Kodama
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| | - Toshio Fujioka
- Department of Internal Medicine, Takada Chuo Hospital, 1176-1 Shinchi, Bungotakada, Oita 879-0627, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan
| |
Collapse
|
|
10
|
Macke L, Schulz C, Koletzko L, Malfertheiner P. Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract-evidence from next-generation sequencing studies. Aliment Pharmacol Ther 2020; 51:505-526. [PMID: 31990420 DOI: 10.1111/apt.15604] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Revised: 09/03/2019] [Accepted: 11/13/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI-associated adverse events. In recent years, data from next-generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health. AIM To review the available evidence from next-generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI-induced dysbiosis in health and disease. METHODS A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria. RESULTS Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users). CONCLUSION PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI-induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota.
Collapse
Affiliation(s)
- Lukas Macke
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Leandra Koletzko
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Peter Malfertheiner
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.,Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| |
Collapse
|
|
11
|
Ogasawara K, Nakajima S, Sato H, Sasaki T. Helicobacter pylori Eradication Using Laser Endoscope and Methylene Blue. Laser Ther 2020; 29:19-27. [PMID: 32904076 DOI: 10.5978/islsm.20-or-02] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 02/19/2020] [Indexed: 12/14/2022]
Abstract
Background and Aims Helicobacter pylori (H. pylori) eradication has become increasingly unsuccessful due to the prevalence of antibiotic resistance. To address this global issue, a novel strategy for eradication without antibiotics must be developed. The purpose of this study was to examine the effect of methylene blue (MB) with sodium bicarbonate (NaHCO3) on H. pylori using photodynamic antimicrobial chemotherapy. Materials and Methods MB was basified using NaHCO3. The basic effect of MB with NaHCO3 was examined using an endoscope equipped with a laser light source. H. pylori was smeared on the culture media with basic MB, followed by illumination at approximately 1,100 lux for 10 and 20 seconds.After 4 days of culture, the basic effects were determined according to the bacterial growth. Results The basic effects of MB appeared at a pH from 8.6 to 9.0 and at NaHCO3 concentrations between 2% and 6.5%. MB concentrations of > 0.05% exhibited the basic effects. The duration of irradiation had no remarkable effects. Conclusions Our results showed that the laser endoscope and basic MB were effective for H. pylori eradication.
Collapse
Affiliation(s)
- Kouji Ogasawara
- Sarufutsu Village National Health Insurance Hospital, Japan.,Asahikawa Medical University, Respiratory Center, Japan
| | | | - Hiroshi Sato
- Sarufutsu Village National Health Insurance Hospital
| | | |
Collapse
|
|
12
|
Abstract
A substantial volume of literature exists linking proton pump inhibitor (PPI) use with a multitude of serious adverse events. There is uncertainty, however, over whether these associations are clinically important. Excessive concern about PPI-related adverse events may leave patients at risk of harm by leaving acid-related upper gastrointestinal disease untreated. Conversely, the risk of treatments may outweigh the benefits if any of the purported adverse events are directly caused by PPI use; this is of particular concern where indications for PPI use are not present. In this paper, we review the studies which have reported associations between adverse events and PPI use, discuss the proposed mechanisms of action, grade the confidence in whether these associations are truly causal, and provide advice regarding balancing the benefits of PPI use against their possible harms.
Collapse
Affiliation(s)
- Evan Elias
- Section of Gastroenterology, Department of Internal Medicine, Rady School of Medicine, University of Manitoba, 805G-715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada
| | - Laura E Targownik
- Section of Gastroenterology, Department of Internal Medicine, Rady School of Medicine, University of Manitoba, 805G-715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada.
| |
Collapse
|
|
13
|
Sáenz JB, Vargas N, Mills JC. Tropism for Spasmolytic Polypeptide-Expressing Metaplasia Allows Helicobacter pylori to Expand Its Intragastric Niche. Gastroenterology 2019; 156:160-174.e7. [PMID: 30287170 PMCID: PMC6309511 DOI: 10.1053/j.gastro.2018.09.050] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/10/2018] [Accepted: 09/25/2018] [Indexed: 01/18/2023]
Abstract
BACKGROUND & AIMS In patients with chronic Helicobacter pylori (H pylori) infection, parietal and chief cell atrophy in the gastric corpus, a process known as spasmolytic polypeptide-expressing metaplasia (SPEM), increases the risk for progression to cancer. The relation between H pylori and these metaplastic changes is unclear. We investigated whether H pylori localizes to regions of SPEM. METHODS We developed an in situ adherence assay in which we incubated H pylori with free-floating tissue sections from the gastric corpora of mice; we assessed H pylori distribution along the gastric unit by immunofluorescence. We analyzed the interactions of H pylori with tissue collected from mice with acute SPEM, induced by high-dose tamoxifen. We also evaluated how adhesin-deficient H pylori strains, chemical competition assays, and epithelial glycosylation affected H pylori adhesion to SPEM glands. Mice colonized with the mouse-adapted PMSS1 strain were analyzed for H pylori colonization in vivo during tamoxifen-induced SPEM or after decrease of stomach acid with omeprazole. RESULTS Compared with uninjured glands, H pylori penetrated deep within SPEM glands, in situ, through interaction of its adhesin, SabA, with sialyl-Lewis X, which expanded in SPEM. H pylori markedly increased gastric corpus colonization when SPEM was induced, but this proximal spread reversed in mice allowed to recover from SPEM. Decreasing corpus acidity also promoted proximal spread. However, H pylori penetrated deep within corpus glands in vivo only when sialyl-Lewis X expanded during SPEM. CONCLUSIONS Helicobacter pylori differentially binds SPEM glands in situ and in mice, in large part by interacting with sialyl-Lewis X. Our findings indicate that H pylori expands its niche into the gastric corpus by promoting and exploiting epithelial metaplastic changes that can lead to tumorigenesis.
Collapse
Affiliation(s)
- José B Sáenz
- Division of Gastroenterology, Department of Internal Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri
| | - Nancy Vargas
- Division of Gastroenterology, Department of Internal Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri
| | - Jason C Mills
- Division of Gastroenterology, Department of Internal Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri; Department of Pathology and Immunology, Washington University in St Louis School of Medicine, St Louis, Missouri; Department of Developmental Biology, Washington University in St Louis School of Medicine, St Louis, Missouri.
| |
Collapse
|
|
14
|
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
|
|
15
|
Tepeš B, Malfertheiner P, Labenz J, Aygen S. Modified Helicobacter test using a new test meal and a 13C-urea breath test in Helicobacter pylori positive and negative dyspepsia patients on proton pump inhibitors. World J Gastroenterol 2017; 23:5954-5961. [PMID: 28932087 PMCID: PMC5583580 DOI: 10.3748/wjg.v23.i32.5954] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/25/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the sensitivity and specificity of the 13C-urea breath test (UBT) in patients taking proton pump inhibitors (PPIs), using a new test meal Refex.
METHODS One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori (H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the 13C-UBT with the new test meal was performed the next morning.
RESULTS The sensitivity of the 13C-UBT with a cut off 2.5‰ was 92.45% (95%CI: 81.79%-97.91%) by per-protocol (PP) analysis and 78.13% (95%CI: 66.03%-87.49%) by intention-to-treat (ITT) analysis. The specificity of the 13C-UBT test was 96.00% in the ITT population (95%CI: 86.29%-99.51%) and 97.96% in the PP population (95%CI: 89.15%-99.95%).
CONCLUSION The new test meal based 13C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment.
Collapse
Affiliation(s)
- Bojan Tepeš
- AM DC Rogaška, Prvomajska 29 A, 3250 Rogaška Slatina, Slovenia
| | - Peter Malfertheiner
- Universitätsklinikum Magdeburg A. ö. R Klinik für Gastroenterologie, Hepatologie und Infektiologie, 39120 Magdeburg, Germany
| | - Joachim Labenz
- Department of Internal Medicine and Gastroenterology, Diakonie Klinikum, Jung-Stilling Hospital, 57074 Siegen, Germany
| | - Sitke Aygen
- Institut für Biomedizinische Analytik und NMR-Imaging GmbH (INFAI), Gottfried-Hagen-Str. 6062, 51105 Köln, Germany
| |
Collapse
|
|
16
|
周 林, 赵 阳, 张 伟. 幽门螺杆菌根除治疗在胃癌预防中的现状及前景. Shijie Huaren Xiaohua Zazhi 2017; 25:1327-1337. [DOI: 10.11569/wcjd.v25.i15.1327] [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] [Indexed: 02/06/2023] Open
Abstract
幽门螺杆菌(Helicobacter pylori, H. pylori)与胃癌(gastric cancer, GC)发生发展密切相关, 根除H. pylori可降低GC发生率. 经济学分析表明, 在高危人群中根除治疗H. pylori作为预防GC的策略是成本效益较好的. 即使在GC低风险人群中, H. pylori筛查和治疗也能使上消化道其他非恶性疾病获益. 然而, 广泛开展H. pylori根除治疗可能带来其他问题, 包括抗生素耐药增加和与H. pylori负相关疾病(如胃食管反流病、Barrett食管、哮喘和肥胖等)的患病率升高. 本文将结合近年最新研究, 就上述问题展开论述, 进一步提出H. pylori根除治疗预防GC所面临的挑战以及将来可能的进展方向.
Collapse
|
|
17
|
Abstract
Helicobacter pylori is an important human pathogen, associated with a substantial burden from both malignant and non-malignant diseases. The bacterium is classed as a human carcinogen, being strongly linked with gastric cancer, the third most common cause of cancer death worldwide and is also associated with common conditions such as dyspepsia and peptic ulcer. Eradication of H. pylori reduces the incidence of gastric cancer and peptic ulcer, as well as the prevalence and costs of managing dyspepsia. Economic analyses suggest that eradication of H. pylori as a means of controlling gastric cancer is cost-effective in high-risk populations. Even in populations at low risk of gastric cancer, there might be other benefits arising from screening and treatment, owing to the effects on non-malignant upper gastrointestinal diseases. However, public health authorities have been slow to consider the benefits of population-based screening and treatment as a means of reducing the morbidity and mortality associated with the infection. There are also concerns about widespread use of eradication therapy, including antimicrobial resistance and a rise in the prevalence of diseases that are negatively associated with H. pylori, such as GERD, Barrett oesophagus, asthma and obesity. This Review summarizes these issues.
Collapse
|
|
18
|
Medication-associated gastrointestinal tract injury. Virchows Arch 2017; 470:245-266. [PMID: 28133700 DOI: 10.1007/s00428-017-2077-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 11/05/2016] [Accepted: 01/19/2017] [Indexed: 12/18/2022]
Abstract
Medication-associated gastrointestinal (GI) tract injury has been known for centuries for some medications. The more recently introduced biologicals are a class of drugs that constantly increases, and as such, the spectrum of GI tract side effects is steadily growing. This review covers not only long-known GI tract side effects of drugs but also those more recently described. A comprehensive but concise list of medications used in daily practice and associated with GI tract injury is presented.
Collapse
|
|
19
|
Waldum HL, Kleveland PM, Sørdal ØF. Helicobacter pylori and gastric acid: an intimate and reciprocal relationship. Therap Adv Gastroenterol 2016; 9:836-844. [PMID: 27803738 PMCID: PMC5076771 DOI: 10.1177/1756283x16663395] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Helicobacter pylori (Hp) is the main cause of gastritis, peptic ulcer disease and gastric cancer. There are still unanswered questions related to the interaction between Hp and man, like what determines the susceptibility for the initial infection and the mechanisms for the carcinogenic effect. The initial infection seems to require a temporal gastric hypoacidity. For Hp to survive in the gastric mucous layer, some acidity is necessary. Hp itself is probably not directly carcinogenic. Only when inducing oxyntic mucosal inflammation and atrophy with hypoacidity, Hp predisposes for gastric cancer. Gastrin most likely plays a central role in the Hp pathogenesis of duodenal ulcer and gastric cancer.
Collapse
Affiliation(s)
- Helge L. Waldum
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Per M. Kleveland
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Øystein F. Sørdal
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| |
Collapse
|
|
20
|
Abstract
Helicobacter pylori infects about 50 % of the world's population, causing at a minimum chronic gastritis. A subset of infected patients will ultimately develop gastric or duodenal ulcer disease, gastric adenocarcinoma, or MALT (mucosa-associated lymphoid tissue) lymphoma. Eradication of H. pylori requires complex regimens that include acid suppression and multiple antibiotics. The efficacy of treatment using what were once considered standard regimens have declined in recent years, mainly due to widespread development of antibiotic resistance. Addition of bismuth to standard triple therapy regimens, use of alternate antibiotics, or development of alternative regimens using known therapies in novel combinations have improved treatment efficacy in specific populations, but overall success of eradication remains less than ideal. Novel regimens under investigation either in vivo or in vitro, involving increased acid suppression ideally with fewer antibiotics or development of non-antibiotic treatment targets, show promise for future therapy.
Collapse
Affiliation(s)
- Elizabeth A Marcus
- Department of Pediatrics, DGSOM at UCLA, Los Angeles, CA, USA.
- VA GLAHS, 11301 Wilshire Blvd. Bldg 113 Rm 324, Los Angeles, CA, 90073, USA.
| | - George Sachs
- Department of Physiology, DGSOM at UCLA, Los Angeles, CA, USA
- Department of Medicine, DGSOM at UCLA, Los Angeles, CA, USA
- VA GLAHS, 11301 Wilshire Blvd. Bldg 113 Rm 324, Los Angeles, CA, 90073, USA
| | - David R Scott
- Department of Physiology, DGSOM at UCLA, Los Angeles, CA, USA
- VA GLAHS, 11301 Wilshire Blvd. Bldg 113 Rm 324, Los Angeles, CA, 90073, USA
| |
Collapse
|
|
21
|
Shirin D, Matalon S, Avidan B, Broide E, Shirin H. Real-world Helicobacter pylori diagnosis in patients referred for esophagoduodenoscopy: The gap between guidelines and clinical practice. United European Gastroenterol J 2016; 4:762-769. [PMID: 28408993 DOI: 10.1177/2050640615626052] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 12/13/2015] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND AIMS Histopathology is the most accurate test to detect H. pylori when performed correctly with unknown validity in daily practice clinic settings. We aimed to determine the rate of potentially false-negative H. pylori results that might be due to continued use of proton pump inhibitors (PPIs) in routine endoscopy practice. We also aimed to establish whether gastroenterologists recommend routine cessation of PPIs before esophagogastroduodenoscopy (EGD) and whether they regularly document that biopsies for H. pylori testing have been taken while the patients are on PPI treatment. METHODS Detailed information about three known factors (PPIs, antibiotics and prior H. pylori eradication treatment), which may cause histology or rapid urease test (RUT) to be unreliable, had been prospectively collected through interviews using a questionnaire before each test. Gastric biopsies were stained with H&E for histological analysis. RESULTS A total of 409 individuals at three academic gastroenterology institutions were tested 200 times with histology. Fifty-six per cent (68 of 122) of all negative tests fell in the category of continuing PPI use, which had the potential to make the histology and RUT results unreliable. CONCLUSIONS These data demonstrate a clear and important gap between current guidelines and real-world practice with regards to the diagnosis of H. pylori during EGD. A negative histology or RUT should be considered false negative until potential protocol violations are excluded. Documentation of PPI use during the EGD should be an integral part of the EGD report. The current practice of taking biopsies for H. pylori testing in patients under PPIs should be reevaluated.
Collapse
Affiliation(s)
- Dor Shirin
- The Kamila Gonczarowski Institute of Gastroenterology, Assaf Harofeh Medical Center, Zerifin, Israel
| | - Shay Matalon
- The Kamila Gonczarowski Institute of Gastroenterology, Assaf Harofeh Medical Center, Zerifin, Israel
| | - Benjamin Avidan
- Gastroenterology Institute, Sheba Medical Center, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Efrat Broide
- The Kamila Gonczarowski Institute of Gastroenterology, Assaf Harofeh Medical Center, Zerifin, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Haim Shirin
- The Kamila Gonczarowski Institute of Gastroenterology, Assaf Harofeh Medical Center, Zerifin, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| |
Collapse
|
|
22
|
Malfertheiner P. Diagnostic methods for H. pylori infection: Choices, opportunities and pitfalls. United European Gastroenterol J 2015; 3:429-31. [PMID: 26535120 DOI: 10.1177/2050640615600968] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Magdeburg, Magdeburg, Germany
| |
Collapse
|
|
23
|
Wong A, Ching SS, Long AS. The use of a second biopsy from the gastric body for the detection of Helicobacter pylori using rapid urease test. Singapore Med J 2015; 55:644-7. [PMID: 25630318 DOI: 10.11622/smedj.2014178] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION The use of an additional biopsy from the gastric body may help improve the detection of Helicobacter pylori during endoscopy. This study aimed to determine whether such an additional biopsy is necessary in routine rapid urease test (RUT), and whether acid suppression and antibiotic therapy affect RUT results. METHODS Patients recruited had two gastric mucosal biopsies taken - one from the gastric antrum and the other from the gastric body. Each biopsy was placed into separate RUT kits. Information on previous or current use of proton-pump inhibitors, H2 receptor antagonist, bismuth and antibiotics was obtained. Patients on any of those drugs one week prior to endoscopy were considered to have a positive drug history (PDH). RESULTS Of the 400 patients recruited, 311 had negative RUTs and 89 had at least one positive RUT. Between the PDH and negative drug history (NDH) groups, there was a significant difference in the distribution of the location of the biopsies that yielded positive RUTs (p = 0.023). The NDH group had a higher proportion of patients who had positive RUTs for both locations, whereas the PDH group had a higher proportion of patients who had positive RUTs for only one location. CONCLUSION As RUT results are significantly affected by the use of acid suppression and antibiotic therapies, biopsies for RUT should be taken from both the gastric antrum and body to minimise false negative results.
Collapse
Affiliation(s)
- Andrew Wong
- Department of Surgery, Changi General Hospital, 2 Simei Street 3, Singapore 529889.
| | | | | |
Collapse
|
|
24
|
Lundell L, Vieth M, Gibson F, Nagy P, Kahrilas PJ. Systematic review: the effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology. Aliment Pharmacol Ther 2015; 42:649-63. [PMID: 26177572 DOI: 10.1111/apt.13324] [Citation(s) in RCA: 166] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Revised: 04/03/2015] [Accepted: 06/28/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) have a well-established safety profile. However, concerns have been raised about a potential relationship between PPI-induced hypergastrinaemia and the development of enterochromaffin-like (ECL) cell hyperplasia, neuroendocrine tumours and gastric cancer during long-term therapy. AIM To review the effects of long-term PPI use on serum gastrin levels and gastric histopathology. METHODS A systematic literature search was conducted in PubMed on 21 April 2015 to identify studies reporting the effects of long-term (defined as >3 years) PPI use on gastrin levels and gastric histopathology. RESULTS A total of 16 studies (1920 patients) met the inclusion criteria. During long-term PPI therapy, mean gastrin levels rose to one to three times the upper limit of the normal range (~100 pg/mL), and an increased prevalence of ECL cell hyperplasia was observed (+7.8-52.0%). Helicobacter pylori-positive patients had a significantly increased risk of developing ECL linear/micronodular hyperplasia compared with H. pylori-negative patients [OR: 2.45 (95% CI: 1.47-4.10), P = 0.0006]; however, no evidence of neoplastic changes was found. The risk of corpus atrophy was markedly higher in H. pylori-positive patients than in H. pylori-negative patients [OR: 11.45 (95% CI: 6.25-20.99), P < 0.00001]. Not a single case of gastric adenocarcinoma was found. CONCLUSIONS Long-term PPI therapy induced moderate hypergastrinaemia in most patients and an increased prevalence of ECL cell hyperplasia. H. pylori-positive patients receiving long-term PPI therapy were exposed to a higher risk of corpus atrophy than H. pylori-negative patients. No neuroendocrine tumours or gastric cancers were found.
Collapse
Affiliation(s)
- L Lundell
- Gastrocentrum, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Centre for Digestive Diseases, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - M Vieth
- Institut für Pathologie, Klinikum Bayreuth GmbH, Bayreuth, Germany
| | - F Gibson
- PharmaGenesis London, London, UK
| | - P Nagy
- Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
| | - P J Kahrilas
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| |
Collapse
|
|
25
|
García-Mazcorro JF, Garza-González E, Marroquín-Cardona AG, Tamayo JL. [Characterization, influence and manipulation of the gastrointestinal microbiota in health and disease]. GASTROENTEROLOGIA Y HEPATOLOGIA 2015; 38:445-66. [PMID: 25769877 DOI: 10.1016/j.gastrohep.2015.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/12/2015] [Accepted: 01/26/2015] [Indexed: 01/08/2023]
Abstract
The gastrointestinal tract harbors trillions of microorganisms that are indispensable for health. The gastrointestinal microbiota can be studied using culture and molecular methods. The applications of massive sequencing are constantly increasing, due to their high yield, increasingly accessible costs, and the availability of free software for data analysis. The present article provides a detailed review of a large number of studies on the gastrointestinal microbiota and its influence on human health; particular emphasis is placed on the evidence suggesting a relationship between the gastrointestinal microbial ecosystem and diverse physiological and immune/inflammatory processes. Discussion of the articles analyzed combines a medical approach and current concepts of microbial molecular ecology. The present revision aims to be useful to those interested in the gastrointestinal microbiota and its possible alteration to maintain, re-establish and enhance health in the human host.
Collapse
Affiliation(s)
- José F García-Mazcorro
- Facultad de Medicina Veterinaria, Universidad Autónoma de Nuevo León, General Escobedo, Nuevo León, México; Grupo de investigación Ecobiología Médica, Facultad de Medicina Veterinaria, Universidad Autónoma de Nuevo León, General Escobedo, Nuevo León, México.
| | - Elvira Garza-González
- Servicio de Gastroenterología y Departamento de Patología Clínica, Hospital Universitario «Dr. José Eleuterio González», Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
| | - Alicia G Marroquín-Cardona
- Facultad de Medicina Veterinaria, Universidad Autónoma de Nuevo León, General Escobedo, Nuevo León, México; Grupo de investigación Ecobiología Médica, Facultad de Medicina Veterinaria, Universidad Autónoma de Nuevo León, General Escobedo, Nuevo León, México; Departamento de Fisiología, Farmacología y Toxicología, Facultad de Medicina Veterinaria, Universidad Autónoma de Nuevo León, General Escobedo, Nuevo León, México
| | - José L Tamayo
- Centro de Investigación y Docencia en Ciencias de la Salud, Hospital Civil de Culiacán, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, México
| |
Collapse
|
|
26
|
Lee JY, Kim N. Diagnosis of Helicobacter pylori by invasive test: histology. ANNALS OF TRANSLATIONAL MEDICINE 2015; 3:10. [PMID: 25705642 DOI: 10.3978/j.issn.2305-5839.2014.11.03] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Accepted: 09/26/2014] [Indexed: 12/31/2022]
Abstract
The accurate detection of Helicobacter pylori (H. pylori), a major cause of gastric cancer, is essential for managing infected patients. Among various diagnostic methods, histology plays a pivotal role in detecting H. pylori and it also provided more information about the degree of inflammation and associated pathology, such as, atrophic gastritis (AG), intestinal metaplasia (IM), and gastric cancer. The diagnosis of H. pylori could be performed in hematoxylin and eosin (H&E) staining, however the specificity can be improved by special stains such as modified Giemsa, Warthin-Starry silver, Genta, and immunohistochemical (IHC) stains. Thus, at least two kinds of stain methods are recommended for diagnosis in practice; H&E staining is routine and Giemsa stain seems to have advantage over other stains because of its simplicity and consistency. IHC stain may be useful in special situations. However, histology has several limitations, including higher cost, longer turnaround time, dependence on the skills of the operator, and interobserver variability in assessment. Furthermore, the density of H. pylori can vary at different sites, possibly leading to sampling error, and the sensitivity of histology may decrease in patients taking proton pump inhibitor (PPI). The updated Sydney system recommend to take five biopsy specimens from different sites; however if this is not possible, the gastric body greater curvature could be a better site to detect current H. pylori infections, especially in the presence of peptic ulcer bleeding, AG and IM, or gastric cancer. In the presence of peptic ulcer bleeding, histology is also the most reliable test. PPIs can affect the result of histology and should be stopped 2 weeks before testing. Postbiopsy bleeding may be increased in patients with anticoagulation therapy, so careful precautions should be taken.
Collapse
Affiliation(s)
- Ju Yup Lee
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea ; 2 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Nayoung Kim
- 1 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea ; 2 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
27
|
Shrestha R, Koirala K, Raj KCS, Batajoo KH. Helicobacter pylori infection among patients with upper gastrointestinal symptoms: prevalence and relation to endoscopy diagnosis and histopathology. J Family Med Prim Care 2014; 3:154-8. [PMID: 25161975 PMCID: PMC4139998 DOI: 10.4103/2249-4863.137663] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Aim: To determine the prevalence of H. pylori based on endoscopic biopsy and to investigate the association between H. pylori and endoscopy diagnosis and histopathological diagnosis. Materials and Methods: Over a period of two years, 228 endoscopic biopsies were included. Endoscopy diagnosis, histopathological diagnosis, and colonization with H. pylori were recorded and compared using appropriate statistical tests. Results: The overall prevalence of H. pylori was 68%; 69.6% in males and 66.7% in females. Duodenal and gastric ulcers were seen more in males (63.2% and 60%) compared with females (32.1% and 40%) (P < 0.001). The total rate of colonization of H. pylori in duodenal ulcer and gastric ulcer (85.7% and 84%, respectively) was significantly higher than those in gastritis, duodenitis, and gastric cancer (61.8%, 69.2%, and 60%, respectively) (P = 0.046). Histologically, chronic active gastritis and chronic follicular gastritis was significantly higher in duodenal ulcer and gastric ulcer (57.1%, 44% and 21%, 40%) in comparison to chronic persistent gastritis (21.4%, 16%) with P value < 0.001. Similarly, chronic active gastritis and chronic follicular gastritis had higher prevalence of H. pylori infection in comparison to chronic persistent gastritis (85.3%, 83.3% vs. 41.4%) with P value < 0.001. Conclusion: This study reveals that the overall prevalence of H. pylori infection is high in our setting with no significant difference in gender. Peptic ulcers were common in males. Those with peptic ulcers had higher rates of H. pylori colonization. Chronic active gastritis and chronic follicular gastritis were common histological findings in ulcerative diseases with significantly higher H. pylori positivity.
Collapse
Affiliation(s)
- Roshana Shrestha
- Department of Family Medicine/Emergency, KIST Medical College Hospital, Lalitpur, Nepal
| | - Kamal Koirala
- Department of Surgery, KIST Medical College Hospital, Lalitpur, Nepal
| | - K C Shiv Raj
- Department of Pathology, KIST Medical College Hospital, Lalitpur, Nepal
| | - Kabita Hada Batajoo
- Department of Family Medicine/Emergency, KIST Medical College Hospital, Lalitpur, Nepal
| |
Collapse
|
|
28
|
Gastric biopsies: the gap between evidence-based medicine and daily practice in the management of gastric Helicobacter pylori infection. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2014; 27:e25-30. [PMID: 24106732 DOI: 10.1155/2013/897423] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Many consider histology to be the gold standard for Helicobacter pylori detection. Because the number and distribution of H pylori organisms vary, particularly in patients taking proton pump inhibitors (PPIs), the American Gastroenterological Association recommends discontinuing PPIs two weeks before endoscopy, and taking biopsies from both the body and antrum. OBJECTIVE To assess the influence of clinical practice on the histopathological detection of H pylori infection. METHODS Electronic patient records were evaluated for the sites of gastric sampling and PPI use at endoscopy. One hundred fifty cases with biopsies taken from both antrum and body were randomly selected for pathological re-review with special stains. The gastric regions sampled, H pylori distribution and influence of clinical factors on pathological interpretation were assessed. RESULTS Between 2005 and 2010, 10,268 biopsies were taken to detect H pylori. Only one region was sampled in 60% of patients (antrum 47%, body 13%). Re-review of biopsies taken from both antrum and body indicated that the correct regions were sampled in only 85 (57%) patients. Of these, 54 were H pylori positive and 96 were H pylori negative. H pylori was present in the antrum in only 15% of the patients and body only in 21%. Of 96 H pylori-negative patients, two were reinterpreted as positive. Forty-seven per cent of patients were taking PPIs at endoscopy, contributing to both false-negative and false-positive diagnoses. CONCLUSION Despite national and international guidelines for managing H pylori infection, the American Gastroenterological Association guidelines are infrequently adhered to, with PPIs frequently contributing to false diagnosis; sampling one region only increases the likelihood of missing active infection by at least 15%.
Collapse
|
|
29
|
Wolf EM, Plieschnegger W, Geppert M, Wigginghaus B, Höss GM, Eherer A, Schneider NI, Hauer A, Rehak P, Vieth M, Langner C. Changing prevalence patterns in endoscopic and histological diagnosis of gastritis? Data from a cross-sectional Central European multicentre study. Dig Liver Dis 2014; 46:412-8. [PMID: 24484998 DOI: 10.1016/j.dld.2013.12.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Revised: 12/03/2013] [Accepted: 12/21/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Traditionally, Helicobacter infection is considered to be the most common cause of gastritis. In the cross-sectional Central European histoGERD trial, we assessed the prevalence of different types of gastritis, correlating histological and endoscopic diagnoses. METHODS A total of 1123 individuals participated in an observational multicentre study. Endoscopists classified individuals as positive or negative for gastritis and rendered the putative cause. Pathologists evaluated biopsy specimens based upon the Updated Sydney System. RESULTS Histological diagnosis of gastritis was made in 639 (56.9%) participants. In all, 210 (18.7%) individuals were diagnosed with Helicobacter gastritis, 215 (19.1%) with post Helicobacter gastritis, 234 (20.8%) with reactive gastropathy, 26 (2.3%) with autoimmune gastritis, and 6 (0.5%) with focally enhanced gastritis related to Crohn's disease. In 46 out of 639 (7.2%) individuals diagnosed with gastritis, combinations of different histological subtypes were noted the most common being reactive gastropathy and post Helicobacter gastritis. Endoscopic diagnosis of gastritis was made in 534 (47.6%) individuals. CONCLUSIONS Reactive gastropathy was more common than active Helicobacter gastritis, and the majority of cases attributable to Helicobacter infection were no longer ongoing, i.e. post Helicobacter gastritis. Agreement between histological and endoscopic diagnoses was better in reactive gastropathy than in Helicobacter gastritis.
Collapse
Affiliation(s)
- Eva-Maria Wolf
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Wolfgang Plieschnegger
- Department of Internal Medicine, Krankenhaus der Barmherzigen Brüder, Academic Teaching Hospital, St. Veit/Glan, Austria
| | | | | | - Gabriele M Höss
- Department of Surgery, Division of General Surgery, Medical University of Graz, Graz, Austria
| | - Andreas Eherer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Nora I Schneider
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Almuthe Hauer
- Department of General Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Peter Rehak
- Department of Surgery, Research Unit for Biomedical Engineering & Computing, Medical University of Graz, Graz, Austria
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria.
| |
Collapse
|
|
30
|
Fiocca R, Mastracci L, Attwood SE, Ell C, Galmiche JP, Hatlebakk J, Bärthel A, Långström G, Lind T, Lundell L. Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy: results of a 5-year follow-up in the LOTUS trial. Aliment Pharmacol Ther 2012; 36:959-71. [PMID: 22998687 DOI: 10.1111/apt.12052] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Revised: 03/12/2012] [Accepted: 08/30/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals. AIMS To evaluate gastric exocrine and endocrine cell changes in GERD patients randomised to laparoscopic antireflux surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n = 266). METHODS Antral and corpus biopsies were taken at endoscopy and serum gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5 years' therapy. RESULTS Biopsies were available at each time point for 158 LARS patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal inflammation and activity improved significantly (P < 0.001) and stabilised after 3 years on esomeprazole while no change in inflammation was observed after LARS. Oxyntic mucosal inflammation and activity remained stable on esomeprazole but decreased slightly over time after LARS. Neither intestinal metaplasia nor atrophy developed in the oxyntic mucosa. ECL cell density increased significantly after ESO (P < 0.001), corresponding with an increase in circulating gastrin and chromogranin A. After LARS, there was a significant decrease in ECL cell density (P < 0.05), accompanied by a marginal decrease in gastrin and chromogranin. CONCLUSIONS Antral gastritis improved in H. pylori-infected GERD patients after 5 years on esomeprazole, with little change in laparoscopic antireflux surgery patients, who acted as a control. Despite a continued proliferative drive on enterochromaffin-like cells during esomeprazole treatment, no dysplastic or neoplastic lesions were found and no safety concerns were raised. NCT 00251927.
Collapse
Affiliation(s)
- R Fiocca
- Department of Surgical and Morphological Sciences, University of Genoa, Genoa, Italy.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Garcia-Mazcorro JF, Suchodolski JS, Jones KR, Clark-Price SC, Dowd SE, Minamoto Y, Markel M, Steiner JM, Dossin O. Effect of the proton pump inhibitor omeprazole on the gastrointestinal bacterial microbiota of healthy dogs. FEMS Microbiol Ecol 2012; 80:624-36. [PMID: 22324305 DOI: 10.1111/j.1574-6941.2012.01331.x] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2011] [Revised: 02/02/2012] [Accepted: 02/06/2012] [Indexed: 12/14/2022] Open
Abstract
The effect of a proton pump inhibitor on gastrointestinal (GI) microbiota was evaluated. Eight healthy 9-month-old dogs (four males and four females) received omeprazole (1.1 mg kg(-1) ) orally twice a day for 15 days. Fecal samples and endoscopic biopsies from the stomach and duodenum were obtained on days 30 and 15 before omeprazole administration, on day 15 (last day of administration), and 15 days after administration. The microbiota was evaluated using 16S rRNA gene 454-pyrosequencing, fluorescence in situ hybridization, and qPCR. In the stomach, pyrosequencing revealed a decrease in Helicobacter spp. during omeprazole (median 92% of sequences during administration compared to > 98% before and after administration; P = 0.0336), which was accompanied by higher proportions of Firmicutes and Fusobacteria. FISH confirmed this decrease in gastric Helicobacter (P < 0.0001) and showed an increase in total bacteria in the duodenum (P = 0.0033) during omeprazole. However, Unifrac analysis showed that omeprazole administration did not significantly alter the overall phylogenetic composition of the gastric and duodenal microbiota. In feces, qPCR showed an increase in Lactobacillus spp. during omeprazole (P < 0.0001), which was accompanied by a lower abundance of Faecalibacterium spp. and Bacteroides-Prevotella-Porphyromonas in the male dogs. This study suggests that omeprazole administration leads to quantitative changes in GI microbiota of healthy dogs.
Collapse
Affiliation(s)
- Jose F Garcia-Mazcorro
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, USA
| | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Howson W. Upper gastrointestinal endoscopy in Malawi: an opportunity. Malawi Med J 2011; 22:124-5. [PMID: 21977834 DOI: 10.4314/mmj.v22i4.63950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Will Howson
- Dept of Medicine, Queen Elizabeth Central Hospital, Blantyre
| |
Collapse
|
|
33
|
Abstract
At upper gastrointestinal endoscopy to investigate unexplained diarrhea and iron deficiency anemia, duodenal biopsies are often taken to exclude a diagnosis of coeliac disease. While histology remains the gold standard for this diagnosis, recent developments in serological testing may overtake this as a first line test and biopsy restricted to confirming the diagnosis. Established coeliac disease on biopsy is straightforward, but early lesions may pose a challenge. Newer endoscopic procedures such as push-pull enteroscopy (balloon enteroscopy) with biopsy allow access to the small bowel beyond the second part of the duodenum. Controversy remains as to what constitutes the normal histology of the duodenum, and small bowel. Lymphocytic duodenosis (increased intraepithelial lymphocytes with normal villous architecture) in patients with negative coeliac serology can be associated with Helicobacter pylori, drugs, autoimmune and other diseases including food allergy. Full thickness small intestinal biopsies can aid in investigation of enteric neuropathies in severe dysmotility disorders. Biopsies are also taken to investigate malabsorption due to suspected infectious and metabolic disorders. Despite highly active anti-retroviral therapy (HAART), immunosuppressed patients may be affected by duodenal pathogens. The histology of duodenal mucosa in acid related disorders reflects the damage seen at endoscopy. Although the prevalence of duodenal ulcer disease is decreasing, drugs causing ulceration remain an important disease entity. Recent observations in functional bowel disorders suggest that the duodenum may be a key site for pathology. In functional dyspepsia, patients with early satiety may have excess eosinophil infiltration, and the mast cell is probably a key player in the irritable syndrome in the small intestine.
Collapse
|
|
34
|
Seth AK, Kakkar S, Manchanda GS. Role of Biopsy from Gastric Corpus in Diagnosis of Helicobacter pylori Infection in Patients on Acid Suppression Therapy. Med J Armed Forces India 2011; 59:216-7. [PMID: 27407519 DOI: 10.1016/s0377-1237(03)80010-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
There are reports of migration of Helicobacter pylori from the gastric antrum to the proximal stomach following acid suppression therapy. The diagnosis of H pylori infection is usually based on rapid urease test and histology of gastric antral biopsies. 50 consecutive patients of peptic ulcer, 22 on proton pump inhibitors and 28 on histamine-2 receptor antagonists for at least 4 weeks were subjected to biopsies from the gastric corpus in addition to the antrum at the time of upper gastrointestinal endoscopy. H pylori infection was detected in 42 (84%) patients. The diagnosis was established from both antral and corpus biopsies in 34 (68%) and only antrum in 4 (8%). In 4 patients, 3 on proton pump inhibitors and one on H-2 receptor antagonists, H pylori was isolated only from the corpus. The rapid urease test was positive at a mean time of 67.6 minutes from the antrum as compared to 234.6 minutes from the corpus. Testing for H pylori from the antrum alone and not the corpus would have resulted in a false negative result in 8% patients. Biopsy from the gastric antrum should always be combined with biopsy from gastric corpus for the diagnosis of H pylori infection in patients with dyspepsia on acid suppression therapy.
Collapse
Affiliation(s)
- A K Seth
- Classified Specialist, (Medicine and Gastroenterology), Army Hospital (R&R), Delhi Cantt - 110 010
| | - S Kakkar
- Classified Specialist (Pathology), Command Hospital (Eastern Command), Kolkata - 700 027
| | - G S Manchanda
- Senior Advisor (Pathology), Command Hospital (Eastern Command), Kolkata - 700 027
| |
Collapse
|
|
35
|
Suzuki M, Suzuki H, Hibi T. Proton pump inhibitors and gastritis. J Clin Biochem Nutr 2011; 42:71-5. [PMID: 18385822 PMCID: PMC2266058 DOI: 10.3164/jcbn.2008012] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2007] [Accepted: 11/09/2007] [Indexed: 12/17/2022] Open
Abstract
Proton pump inhibitors (PPIs) are novel compounds that strongly inhibit the H+/K+-ATPase in the gastric parietal cells to cause profound suppression of acid secretion. Acid-generating ATPase, also known as vacuolar-type ATPase, is located in the lysozomes of leukocytes and osteoclasts and its activity is also reportedly influenced by treatment with PPIs. This concept is supported by the results of studies using autoradiography in which 3H-Lansoprazole uptake sites were clearly detected in the cytoplasmic granules of neutrophils infiltrating the gastric mucosa. In vitro studies indicate that PPIs increase the intra-vacuolar pH in the lysosomes of purified neutrophils and attenuate the adherence of neutrophils to the vascular endothelium. In clinical practice, the acidic environment in the stomach plays a critical role in the development of gastritis induced by Helicobacter pylori (H. pylori). This is worthy of note, because persistent gastritis often results in atrophic and metaplastic changes in the gastric mucosa, which are believed to be preneoplastic abnormalities. In patients with H. pylori-infection, PPI therapy causes corpus-predominant gastritis, which is frequently found in the background mucosa in patients with gastric cancer. The efficacy and safety of long-term PPI-treatment have not been conclusive, thus we need to pay more attention to the additional pharmacological actions of PPIs.
Collapse
Affiliation(s)
- Masayuki Suzuki
- Division of Gastroenterology, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan
| | | | | |
Collapse
|
|
36
|
Oak JH, Chung WC, Jung SH, Choi KH, Kim EJ, Kang BK, Kang BR, Kong SE, Paik CN, Lee KM. [Effect of acid pump antagonist (Revaprazan, Revanex(R)) on result of 13C urea breath test in patients with Helicobacter pylori associated peptic ulcer disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2011; 57:8-13. [PMID: 21258195 DOI: 10.4166/kjg.2011.57.1.8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Revaprazan (Revanex(R)) is a novel proton pump inhibitor (PPI) that has a somewhat different effect on proton pump compared with the other PPI's, also (called as 'acid pump antagonist'). We aimed to examine the false negative rate of 13C-urea breath test (UBT) in the patients with Helicobacter pylori (H. pylori) associated peptic ulcer disease who were treated with revaprazan and evaluate the anti-urease activity of revaprazan. METHODS Total 55 patients were enrolled in this study. They received EGD examination between January 2009 and December 2009 and diagnosed histologically as H. pylori associated peptic ulcer disease. All patients took revaprazan only. Three patients were excluded because of underlying chronic disease and inappropriate breath sampling. The remaining 52 patients had UBT at 0, 2 and 4 weeks of revaprazan use. After 2 weeks of the cessation of revaprazan, they had the fourth UBT. RESULTS At 2 and 4 weeks, the false negative rates of UBT were 5.8% and 23.1%, respectively (p=0.05). After 2 weeks of the cessation, the cases of the false negative result were five. Four out of five patients had prolonged negative results on two or three successive tests, and baseline 13C difference value did not predict the false negative results. CONCLUSIONS False negative results of UBT were common and increased with prolonged use of acid pump antagonist. As PPI, it had also anti-urease activity and most patients (47/52, 90.4%) reverted to positive results by 2 weeks after the cessation of taking the medication.
Collapse
Affiliation(s)
- Ju Hyun Oak
- Department of Internal Medicine, The Catholic University of Korea School of Medicine, Seoul, Korea
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci 2011; 56:931-50. [PMID: 21365243 DOI: 10.1007/s10620-010-1560-3] [Citation(s) in RCA: 196] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Accepted: 12/31/2010] [Indexed: 12/12/2022]
Abstract
Proton pump inhibitors have an excellent safety profile and have become one of the most commonly prescribed class of drugs in primary and specialty care. Long-term, sometimes lifetime, use is becoming increasingly common, often without appropriate indications. This paper is a detailed review of the current evidence on this important topic, focusing on the potential adverse effects of long-term proton pump inhibitor use that have generated the greatest concern: B12 deficiency; iron deficiency; hypomagnesemia; increased susceptibility to pneumonia, enteric infections, and fractures; hypergastrinemia and cancer; drug interactions; and birth defects. We explain the pathophysiological mechanisms that may underlie each of these relationships, review the existing evidence, and discuss implications for clinical management. The benefits of proton pump inhibitor use outweigh its risks in most patients. Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from long-term therapy.
Collapse
Affiliation(s)
- Edward Sheen
- Department of Medicine and Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | | |
Collapse
|
|
38
|
Larussa T, Suraci E, Leone I, Nazionale I, Abenavoli L, Galasso O, Amorosi A, Imeneo M, Luzza F. Short-term therapy with celecoxib and lansoprazole modulates Th1/ Th2 immune response in human gastric mucosa. Helicobacter 2010; 15:449-59. [PMID: 21083751 DOI: 10.1111/j.1523-5378.2010.00796.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Selective cyclooxygenase-2 (COX-2) inhibitors and proton pump inhibitors may exert immune-mediated effects in human gastric mucosa. T-cell immune response plays a role in Helicobacter pylori-induced pathogenesis. This study evaluated effects of celecoxib and lansoprazole on T-helper (Th) 1 and Th2 immune response in human gastric mucosa. METHODS Dyspeptic patients with or without osteoarticular pain were given one of the following 4-week therapies: celecoxib 200 mg, celecoxib 200 mg plus lansoprazole 30 mg, and lansoprazole 30 mg daily. Expression of COX-2, T-bet, and pSTAT6 and production of prostaglandin E₂ (PGE₂), interferon (IFN)-γ, and interleukin (IL)-4 were determined in gastric biopsies before and after therapy. Histology was evaluated. RESULTS Cyclooxygenase-2 expression and PGE₂ production was higher, and Th1 signaling pathway was predominant in H. pylori-infected vs. uninfected patients. T-bet expression and IFN-γ production increased, while STAT6 activation and IL-4 production decreased following therapy with celecoxib and celecoxib plus lansoprazole, respectively. Th1 and Th2 signaling pathways down-regulated after therapy with lansoprazole, and this was associated with an improvement of gastritis. Effect of therapy was not affected by H. pylori status. CONCLUSION Celecoxib and lansoprazole modulate Th1/Th2 immune response in human gastric mucosa. The use of these drugs may interfere with long-term course of gastritis.
Collapse
Affiliation(s)
- Tiziana Larussa
- Dipartimento di Medicina Sperimentale e Clinica Dipartimento di Scienze Mediche, Università di Catanzaro "Magna Graecia", Catanzaro, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Kohler JE, Blass AL, Liu J, Tai K, Soybel DI. Antioxidant pre-treatment prevents omeprazole-induced toxicity in an in vitro model of infectious gastritis. Free Radic Biol Med 2010; 49:786-91. [PMID: 20554018 PMCID: PMC2910817 DOI: 10.1016/j.freeradbiomed.2010.05.034] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2010] [Revised: 05/17/2010] [Accepted: 05/29/2010] [Indexed: 01/28/2023]
Abstract
Omeprazole is a mainstay of therapy for gastroesophageal reflux disease (GERD) and gastritis, and is increasingly used as an over-the-counter remedy for dyspepsia. Omeprazole acts by selectively oxidizing thiol targets in the gastric proton pump, but it also appears to be toxic to the gastric mucosa. We hypothesized that omeprazole toxicity is due to non-specific oxidation of cell structures other than the proton pump, and tested the efficacy of antioxidants to prevent omeprazole-induced toxicity in isolated rabbit gastric glands. Toxicity was measured by uptake and converstion of calcein-AM, following three hours of exposure to omeprazole and a non-selective thiol-oxidant, monochloramine. Intracellular concentration of Zn(2+) and the capacity to maintain luminal acidity were monitored using the fluorescent reporters fluozin-3 and Lysosensor DND-160, respectively. Both omeprazole and monochloramine caused marked reduction in cell viability. The toxicity of omeprazole was independent of monochloramine toxicity. The thiol reducing agent dithiothreitol protected gastric glands from injury. The oxidant scavenger Vitamin C also protected, and did not impair the anti-secretory effects of omeprazole. Thus, omeprazole toxicity appears to be oxidative and preventable with antioxidant therapy, including Vitamin C. Vitamin C may be a safe and efficacious addition to treatments requiring the use of PPIs.
Collapse
Affiliation(s)
- Jonathan E Kohler
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | | | | | | | | |
Collapse
|
|
40
|
Epidemiological aspects of gastric adenocarcinoma: are predictive diagnostics and targeted preventive measures possible? EPMA J 2010. [PMID: 23199088 PMCID: PMC3405336 DOI: 10.1007/s13167-010-0043-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The incidence of gastric cancer has witnessed major changes over the past decades. Until recently, gastric cancer was a common malignancy in most countries. A striking decline in incidence in most Western populations has occurred since the 1970s, and elucidating the detailed causes for this trend can potentially be of great value for targeted preventive measures. Furthermore, it can add to the understanding of malignant disease and prevention in general. Moreover, the absolute number of cases worldwide is predicted to increase during many years to come. Gastric cancer is typically diagnosed at an advanced stage in symptomatic patients, and there are often no effective curative or palliative or therapeutic options. This fact highlights the need for research aiming to increase our understanding of the etiology of this cancer, facilitating the design of successful targeted preventive strategies for different populations. The future outlook in terms of decreasing gastric cancer deaths would be to identify such intelligent diagnostic tools. In this article, we present a summary of the epidemiology of gastric cancer, with special focus on its etiology.
Collapse
|
|
41
|
Wiser than we thought: Helicobacter pylori. Med Hypotheses 2010; 75:269. [DOI: 10.1016/j.mehy.2010.03.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2010] [Accepted: 03/17/2010] [Indexed: 11/19/2022]
|
|
42
|
Lodato F, Azzaroli F, Turco L, Mazzella N, Buonfiglioli F, Zoli M, Mazzella G. Adverse effects of proton pump inhibitors. Best Pract Res Clin Gastroenterol 2010; 24:193-201. [PMID: 20227032 DOI: 10.1016/j.bpg.2009.11.004] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2009] [Revised: 10/25/2009] [Accepted: 11/03/2009] [Indexed: 01/31/2023]
Abstract
Proton pump inhibitors (PPI) are very effective drugs used largely in acid related disorders. During the last years concern have been raised regarding their overutilisation in benign condition, such as gastroesophageal reflux disease. The debate focussed also on the risk of adverse events related to long term use of PPI. Apart of the case of Helicobacter Pylori (H. Pylori) positive patients, in whose long term acid suppression lead to the development of corpus predominant atrophic gastritis, precursor of cancer; the other assumed adverse events, have never been demonstrated in prospective studies. The attention should move towards the appropriate prescription of PPI, rather than the fear adverse effects of PPI. In fact, in clinical practise, PPI are often prescribed in patients without a specific acid related disease and continued long term based on their safety profile. This review focus on the main adverse events related to long term PPI use.
Collapse
Affiliation(s)
- Francesca Lodato
- Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy.
| | | | | | | | | | | | | |
Collapse
|
|
43
|
Hunfeld NG, Touw DJ, Mathot RA, Mulder PGH, VAN Schaik RH, Kuipers EJ, Kooiman JC, Geus WP. A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism. Aliment Pharmacol Ther 2010; 31:150-9. [PMID: 19785625 DOI: 10.1111/j.1365-2036.2009.04150.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25-30% of Caucasians) and slow (2-5% of Caucasians) metabolism of PPIs. AIM To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics. METHODS CYP2C19*2, *3, *4, *5 and *17 genotypes were determined in healthy Helicobacter pylori-negative Caucasian subjects. 7 wt/wt, 7 wt/*2, 2 wt/*17, 2 *2/*17 and 1 *2/*2 were included in a randomized investigator-blinded cross-over study with esomeprazole 40 mg and pantoprazole 40 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing. RESULTS A total of 19 subjects (mean age 24 years, 7 male) completed the study. At day 1 and 5, acid-inhibition with esomeprazole was significantly greater and faster than with pantoprazole. Differences in acid-inhibition and pharmacokinetics between wt/wt and wt/*2 genotype were significant for pantoprazole at day 1 and 5. CONCLUSIONS Esomeprazole provides acid-inhibition faster than and superior to pantoprazole after single and repeated administration. The acid-inhibitory effect and the kinetics of pantoprazole are influenced by CYP2C19 genotype.
Collapse
Affiliation(s)
- N G Hunfeld
- Central Hospital Pharmacy and Haga Teaching Hospital, Den Haag, The Netherlands
| | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Abstract
BACKGROUND Helicobacter pylori infection rates in duodenal ulcer (DU) patients may be lower than previously estimated. AIM To review the real prevalence of H. pylori-negative DUs and its possible causes. METHODS Bibliographical searches in MEDLINE looking for the terms 'H. pylori' and 'duodenal ulcer'. RESULTS Mean prevalence of H. pylori infection in DU disease, calculated from studies published during the last 10 years including a total of 16 080 patients, was 81%, and this figure was lower (77%) when only the last 5 years were considered. Associations with H. pylori-negative DU were: (1) False negative results of diagnostic methods, (2) NSAID use (21% in studies with <90% infection rate), (3) Complicated DU (bleeding, obstruction, perforation), (4) Smoking, (5) Isolated H. pylori duodenal colonization, (6) Older age, (7) Gastric hypersecretion, (8) Diseases of the duodenal mucosa, (9) Helicobacter'heilmanii' infection and (10) Concomitant diseases. CONCLUSION In patients with H. pylori-negative DU disease, one should carefully confirm that the assessment of H. pylori status is reliable. In truly H. pylori-negative patients, the most common single cause of DU is, by far, the use of NSAIDs. Ulcers not associated with H. pylori, NSAIDs or other obvious causes should, for the present, be viewed as 'idiopathic'. True idiopathic DU disease only exceptionally exists.
Collapse
Affiliation(s)
- J P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)m, Madrid, Spain.
| | | |
Collapse
|
|
45
|
De Leest HTJI, Steen KS, Bloemena E, Lems WF, Kuipers EJ, Van de Laar MAFJ, Bijlsma JWJ, Janssen M, Houben HHML, Kostense PJ, Boers M, Dijkmans BAC. Helicobacter pylori eradication in patients on long-term treatment with NSAIDs reduces the severity of gastritis: a randomized controlled trial. J Clin Gastroenterol 2009; 43:140-6. [PMID: 18797408 DOI: 10.1097/mcg.0b013e3181595b40] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Maintenance use of nonsteroidal anti-inflammatory drugs (NSAIDs) is often complicated by gastropathy. In non-NSAID users, eradication of Helicobacter pylori is associated with decreased mucosal inflammation, and may halt the progression to atrophy and intestinal metaplasia, but the continuous use of NSAIDs may interfere with these processes. GOAL To investigate the effect of H. pylori eradication on gastric mucosal histology during long-term NSAID use, with and without gastroprotective therapy. STUDY Patients were eligible for inclusion if they were on long-term NSAIDs and were H. pylori-positive on serologic testing. Patients were randomly assigned to either eradication or placebo. Gastritis was assessed according to the updated Sydney classification for activity, chronic inflammation, gastric glandular atrophy, intestinal metaplasia, and H. pylori density. RESULTS Biopsy specimens were available for histology of 305 patients. Of these, 48% were on chronic gastroprotective medication. Significant less active gastritis, inflammation, and H. pylori density was found in the eradication group compared with the placebo group in both corpus and antrum (P<0.001). In the corpus, less atrophy was found in the eradication group compared with the placebo group. CONCLUSIONS H. pylori eradication in patients on long-term NSAID therapy leads to healing of gastritis despite ongoing NSAID therapy.
Collapse
Affiliation(s)
- Helena T J I De Leest
- Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Soylu OB, Ozturk Y. Helicobacter pylori infection: effect on malnutrition and growth failure in dyspeptic children. Eur J Pediatr 2008; 167:557-62. [PMID: 17618457 DOI: 10.1007/s00431-007-0552-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2007] [Revised: 05/25/2007] [Accepted: 06/09/2007] [Indexed: 12/13/2022]
Abstract
There are conflicting reports regarding the association of Helicobacter pylori (H. pylori) infection with growth failure. We evaluated the role of H. pylori infection on malnutrition and growth failure in dyspeptic children. The study cases included 108 dyspeptic children and were evaluated by endoscopic gastric biopsy, while 50 healthy children constituted the control group. The study cases were grouped as H. pylori [+] (n = 57) and H. pylori [-] (n = 51) by the presence or absence of microorganism in gastric tissue, respectively. Age, gender, height for age (H/A), weight for height (W/H), body mass index (BMI), weight and height z scores and the daily calorie intake of the children were recorded. Malnutrition and growth failure were evaluated by the Waterlow criteria and height z score, respectively. Then, the H. pylori [+], H. pylori [-] and control groups were compared in relation to the variables defined above. All groups were similar with respect to gender and age. The daily calorie intake was lower in dyspeptic children. Although anthropometric variables were similar in the H. pylori [+] and [-] groups, the control cases had higher W/H compared to both H. pylori [+] (p = 0.030) and H. pylori [-] (p = 0.000) cases, and higher BMI (p = 0.001) and weight z scores (p = 0.014) than those in the H. pylori [-] group. The malnutrition rate was similar in the H. pylori [+] and [-] groups. However, mild acute (p = 0.033) and general malnutrition rates (p = 0.000) were lower in the control cases compared to the study cases. The short stature rate was not different significantly in all three groups. In conclusion, the results of this study do not support the data that H. pylori infection plays an extra role in malnutrition and growth failure in children presenting with dyspeptic complaints. However, as a major cause of dyspepsia, H. pylori infection might be considered to cause malnutrition secondary to decreased calorie intake associated with dyspepsia.
Collapse
Affiliation(s)
- Ozlem Bekem Soylu
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Dokuz Eylul University Medical Faculty, Camliçay Mahallesi, 5182 sokak, No: 12/A, Urla, 35700 Izmir, Turkey.
| | | |
Collapse
|
|
47
|
Yakoob J, Jafri W, Abbas Z, Abid S, Islam M, Ahmed Z. The diagnostic yield of various tests for Helicobacter pylori infection in patients on acid-reducing drugs. Dig Dis Sci 2008; 53:95-100. [PMID: 17497222 DOI: 10.1007/s10620-007-9828-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2006] [Accepted: 03/16/2007] [Indexed: 01/07/2023]
Abstract
The diagnostic yield of various tests for Helicobacter pylori infection in patients on acid-reducing drugs, such as proton pump inhibitors (PPI) and histamine-2 receptor blocker (H2RB), was compared. Seventy-four consecutive patients on acid-reducing drugs were enrolled: 34 (46%) were on PPIs, 20 (27%) were on H2RBs and 20 (27%) were not on medications. For those patients on PPIs, RUT and histology results from antrum were negative in 28 (82%) and 17 (50%) patients, respectively (OR: 4.7; 95% CI: 1.4-16.6; P = 0.004), while those from the corpus were negative in was 28 (82%) and 18 (53%) patients, respectively (OR: 4.4, 95% CI: 1.3-15.5; P = 0.006). For patients on H2RBs, RUT and histology results from the antrum were negative in 12 (60%) and six (30%) patients, respectively (OR: 3.5; 95% CI: 0.8-16.1; P = 0.05), while those from the corpus were negative in 12 (60%) and nine (45%) patients, respectively (OR: 1.8; 95% CI: 0.4-7.8; P = 0.342). For those patients on PPIs, the diagnostic yield of both RUT and histology was reduced from both the antrum and corpus. In these patients, PCR for H. pylori is more sensitive than RUT and histology.
Collapse
Affiliation(s)
- Javed Yakoob
- Department of Gastroenterology and Pathology, Aga Khan University Hospital, Karachi, Pakistan
| | | | | | | | | | | |
Collapse
|
|
48
|
Pietroiusti A, Forlini A, Magrini A, Galante A, Bergamaschi A. Isolated H. pylori duodenal colonization and idiopathic duodenal ulcers. Am J Gastroenterol 2008; 103:55-61. [PMID: 17764496 DOI: 10.1111/j.1572-0241.2007.01506.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate whether some duodenal ulcers (DU) classified as idiopathic according to standard criteria may be causally related to isolated duodenal colonization by H. pylori. METHODS We studied consecutive ambulatory patients undergoing upper gastrointestinal endoscopy in a secondary care setting. Gastric and duodenal biopsies for diagnosing H. pylori infection were taken from all patients. Independently from the findings of duodenal biopsies, DU patients without gastric infection were classified as having idiopathic ulcers, and underwent urea C13 breath test and subsequent eradication therapy. Endoscopy was repeated 6 months after eradication treatment. RESULTS Among 608 DU patients, 42 (6.9%) were classified as idiopathic: 24 (3.9%) were free from gastric and duodenal infection (group A) and 18 (3.0%) (group B) had isolated duodenal colonization. Urea C13 breath test was positive in one (4.2%) group A patient and in 3 (16.7%) group B patients. After eradication therapy, DU were detected in 14 out of 20 group A patients (70%) (four patients did not perform control endoscopy) and in 2 group B patients (11.1%): OR 18.66, 95% CI 3.23-107.82, P= 0.002. The difference was still detectable after multivariate analysis taking into account possible confounding factors: OR 15.79, 95% CI 2.48-100.53, P= 0.001. CONCLUSIONS Isolated duodenal colonization by H. pylori is detectable in a substantial proportion of patients with so-called idiopathic DU, and eradication therapy is effective in these patients.
Collapse
Affiliation(s)
- Antonio Pietroiusti
- Department of Biopathology-Occupational Medicine, Tor Vergata University, Rome, Italy
| | | | | | | | | |
Collapse
|
|
49
|
TAKAGI A, KABIR AMA, WATANABE S, MIWA T. Gastric Mucosal Interleukin (IL)‐8 Level and IL‐8 mRNA Expression in Endoscopic Biopsy Specimens from Patients with Peptic Ulcers. Dig Endosc 2007. [DOI: 10.1111/j.1443-1661.1997.tb00482.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
Affiliation(s)
- Atsushi TAKAGI
- Sixth Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan
| | - Abu MA KABIR
- Sixth Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan
| | - Sumio WATANABE
- Sixth Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan
| | - Takeshi MIWA
- Sixth Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan
| |
Collapse
|
|
50
|
Alvarez A, Ibiza MS, Andrade MM, Blas-García A, Calatayud S. Gastric antisecretory drugs induce leukocyte-endothelial cell interactions through gastrin release and activation of CCK-2 receptors. J Pharmacol Exp Ther 2007; 323:406-13. [PMID: 17652263 DOI: 10.1124/jpet.107.122754] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Antisecretory drugs are effective antiulcer agents, but its chronic use generates hypergastrinemia and accelerates the development of atrophic gastritis in Helicobacter pylori-positive patients. We have recently shown that gastrin exerts a proinflammatory effect in rats through CCK-2 receptor activation that contributes to the inflammation induced by H. pylori. The present study was designed to examine whether gastrin hypersecretion in response to treatment with antisecretory drugs induces an inflammatory response that could promote mucosal atrophy. The effects of omeprazole or famotidine on leukocyte/endothelial cell interactions in vivo were analyzed in rat mesenteric venules using intravital microscopy. Administration of a single dose of omeprazole or famotidine acutely increased gastrinemia and leukocyte rolling and adhesion, but not emigration into the interstitium. Daily treatment with omeprazole for a short period (3 days) induced a similar response, but when this treatment was extended to 14 days and a steady hyper-gastrinemic state was established, increased leukocyte rolling, adhesion, and emigration was observed. Pretreatment with the CCK-2 receptor antagonist proglumide prevented these inflammatory events in all cases. Leukocytes from rats treated with omeprazole showed increased expression of CD11b/CD18 initially in granulocytes (3-day protocol) and later in monocytes and lymphocytes (14-day protocol). These changes were not observed in animals pretreated with proglumide, and they were not reproduced by incubation of leukocytes from untreated animals in vitro with gastrin. Thus, hypergastrinemia induced by chronic treatment with antisecretory drugs may promote inflammation, which could partly explain their worsening effect in corpus gastritis observed in H. pylori-infected patients.
Collapse
Affiliation(s)
- Angeles Alvarez
- Centro de Investigación Biomédica en Red-Enfermedades Hépaticas y Digestivas, Facultad de Medicina, Universidad de Valencia, Avd. Blasco Ibáñez 15, 46010 Valencia, Spain
| | | | | | | | | |
Collapse
|