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Sun N, Ogulur I, Mitamura Y, Yazici D, Pat Y, Bu X, Li M, Zhu X, Babayev H, Ardicli S, Ardicli O, D'Avino P, Kiykim A, Sokolowska M, van de Veen W, Weidmann L, Akdis D, Ozdemir BG, Brüggen MC, Biedermann L, Straumann A, Kreienbühl A, Guttman-Yassky E, Santos AF, Del Giacco S, Traidl-Hoffmann C, Jackson DJ, Wang DY, Lauerma A, Breiteneder H, Zhang L, O'Mahony L, Pfaar O, O'Hehir R, Eiwegger T, Fokkens WJ, Cabanillas B, Ozdemir C, Kistler W, Bayik M, Nadeau KC, Torres MJ, Akdis M, Jutel M, Agache I, Akdis CA. The epithelial barrier theory and its associated diseases. Allergy 2024; 79:3192-3237. [PMID: 39370939 DOI: 10.1111/all.16318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 10/08/2024]
Abstract
The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.
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Affiliation(s)
- Na Sun
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, P. R. China
| | - Ismail Ogulur
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yasutaka Mitamura
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Duygu Yazici
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yagiz Pat
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Xiangting Bu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Manru Li
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Xueyi Zhu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Huseyn Babayev
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Sena Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Genetics, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey
| | - Ozge Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Division of Food Processing, Milk and Dairy Products Technology Program, Karacabey Vocational School, Bursa Uludag University, Bursa, Turkey
| | - Paolo D'Avino
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Ayca Kiykim
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Pediatrics, Division of Pediatric Allergy and Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Lukas Weidmann
- Department of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Deniz Akdis
- Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | | | - Marie Charlotte Brüggen
- Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Alex Straumann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Andrea Kreienbühl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Emma Guttman-Yassky
- Department of Dermatology, and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alexandra F Santos
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St. Thomas' Hospital, London, UK
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Stefano Del Giacco
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | | | - David J Jackson
- Guy's Severe Asthma Centre, Guy's Hospital, Guy's & St Thomas' NHS Trust, London, UK
- School of Immunology & Microbial Sciences, King's College London, London, UK
| | - De-Yun Wang
- Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore City, Singapore
| | - Antti Lauerma
- Department of Dermatology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Heimo Breiteneder
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Liam O'Mahony
- Department of Medicine and School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Oliver Pfaar
- Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
| | - Robyn O'Hehir
- Allergy, Asthma & Clinical Immunology, The Alfred Hospital, Melbourne, Victoria, Australia
- Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Thomas Eiwegger
- Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria
- Department of Pediatric and Adolescent Medicine, University Hospital St. Pölten, St. Pölten, Austria
| | - Wytske J Fokkens
- Department of Otorhinolaryngology & Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Beatriz Cabanillas
- Department of Allergy, Instituto de Investigación Biosanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Cevdet Ozdemir
- Department of Pediatric Basic Sciences, Institute of Child Health, Istanbul University, Istanbul, Turkey
- Istanbul Faculty of Medicine, Department of Pediatrics, Division of Pediatric Allergy and Immunology, Istanbul University, Istanbul, Turkey
| | - Walter Kistler
- Department of Sports Medicine, Davos Hospital, Davos, Switzerland
- Swiss Research Institute for Sports Medicine (SRISM), Davos, Switzerland
- Medical Committee International Ice Hockey Federation (IIHF), Zurich, Switzerland
| | - Mahmut Bayik
- Department of Internal Medicine and Hematology, Marmara University, Istanbul, Turkey
| | - Kari C Nadeau
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Maria J Torres
- Allergy Unit, IBIMA-Hospital Regional Universitario de Málaga-ARADyAL, UMA, Málaga, Spain
| | - Mübeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Marek Jutel
- Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland
| | - Ioana Agache
- Faculty of Medicine, Department of Allergy and Clinical Immunology, Transylvania University, Brasov, Romania
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
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Barret M, Collier M, Tran VT, Dellagi M, Beeker N. Disease burden of Barrett's esophagus across the Paris metropolitan area. Clin Res Hepatol Gastroenterol 2024; 48:102371. [PMID: 38719146 DOI: 10.1016/j.clinre.2024.102371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 04/25/2024] [Accepted: 05/05/2024] [Indexed: 05/20/2024]
Abstract
INTRODUCTION The prevalence of Barrett's esophagus (BE) in France is unknown. However, the management of dysplastic BE in expert centers is recommended and reduces the risk of developing invasive adenocarcinoma. Our aim was to determine the burden of BE patients in the Paris Region. METHODS We performed a retrospective study using the data from electronic medical records from the data warehouse of the 39 Greater Paris public hospitals (Entrepôt de données de santé de l' Assistance Publique- Hôpitaux de Paris) for the year 2018, and used natural language processing to search for occurrences of Barrett's esophagus in endoscopy and pathology reports. RESULTS we observed a 2.2 % prevalence of Barrett's esophagus. Patients with Barrett's esophagus were older, more frequently males, with a hiatal hernia, proton pump inhibitor users, and less frequently infected by H. Pylori. Gastro-esophageal reflux symptoms were not more frequently encountered in Barrett's patients. Eleven percent of patients with Barrett's esophagus had dysplasia or adenocarcinoma. DISCUSSION Over 200 000 patients with Barrett's esophagus are expected in the Paris Region, of which 11 % harbor dysplasia or adenocarcinoma. This data should be taken into account to tailor healthcare offer in France.
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Affiliation(s)
- Maximilien Barret
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, AP-HP.Centre - Université Paris Cité, France; Université de Paris, France.
| | - Mathis Collier
- Clinical Research Unit, Cochin Hospital, Paris, AP-HP.Centre - Université Paris Cité, France
| | - Viet-Thi Tran
- Université de Paris, France; Epidemiology Department, Hôtel Dieu Hospital, Assistance Publique - Hôpitaux de Paris, France
| | - Mourad Dellagi
- Clinical Research Unit, Cochin Hospital, Paris, AP-HP.Centre - Université Paris Cité, France
| | - Nathanael Beeker
- Clinical Research Unit, Cochin Hospital, Paris, AP-HP.Centre - Université Paris Cité, France
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Qumseya B, Yang S, Guo Y. Trends in prevalence of esophageal adenocarcinoma: Findings from a statewide database of over 6 million patients. Endosc Int Open 2024; 12:E218-E226. [PMID: 38362358 PMCID: PMC10869210 DOI: 10.1055/a-2221-7974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/01/2023] [Indexed: 02/17/2024] Open
Abstract
Esophageal cancer (EC) is a leading cause of cancer-related death in the west 1 . Esophageal squamous cell carcinoma (SCC) is the most common type of EC worldwide. However, in Western countries, including the United States, esophageal adenocarcinoma (EAC) is the most common 2 . EAC is most common in the lower esophagus whereas SCC is most common in the middle and upper esophagus 3 . The incidence of EAC has increased dramatically in western countries over the past few decades. 2 3 The exact reason for this rise in EAC has not been clearly understood. However, an increase in the prevalence of EAC risk factors is postulated as a potential explanation 4 . Although there are many identifiable EAC risk factors, including gastroesophageal reflux disease (GERD), obesity, male sex, White race, and smoking 5 6 7 , Barrett's esophagus (BE) remains the major precursor lesion of esophageal adenocarcinoma. BE develops when there is a change in the normal squamous lining of the esophageal mucosa into intestinal metaplasia 8 9 . The incidence has also increased in the population over the past few decades 10 11 . There is a well-described progression within BE from non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), intramucosal carcinoma (IMC), to invasive EAC 12 13 . Recent data suggest that the increased incidence of EAC may have plateaued 1 . However, we questioned whether the prevalence of EAC is still increasing, especially at younger ages in lieu of recent trends showing an increase in the prevalence of colorectal cancer in younger patients. These findings resulted in a lowering of the colorectal cancer screening age cutoff to 45 years from 50 years 14 15 16 . Therefore, we aimed to assess the time trends in the prevalence and incidence of EAC and some of its risk factors in a large population of patients in Florida and to assess these trends based on age categories. We hypothesized that the prevalence of EAC and BE has increased over time at younger age groups.
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Affiliation(s)
- Bashar Qumseya
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, United States
| | - Shuang Yang
- Division of Gastroenterology, University of Florida, GAINESVILLE, United States
| | - Yi Guo
- Department of Health Outcomes and Biomedical Informatics, University of Florida, GAINESVILLE, United States
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Levy AR, Stock D, Paterson JM, Tamim H, Chateau D, Quail J, Ronksley PE, Carney G, Reynier P, Targownik L. Prescription ranitidine use and population exposure in 6 Canadian provinces, 1996 to 2019: a serial cross-sectional analysis. CMAJ Open 2023; 11:E1033-E1040. [PMID: 37935487 PMCID: PMC10635705 DOI: 10.9778/cmajo.20220131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND Ranitidine was the most prescribed histamine-2 receptor antagonist (H2RA) in Canada when recalled in 2019 because of potential carcinogenicity. We sought to compare geographic and temporal patterns in use of prescription ranitidine and 3 other HRAs and estimated population exposure to ranitidine in 6 provinces between 1996 and 2019. METHODS This population-based serial cross-sectional study used prescription claims for H2RAs dispensed from community pharmacies in Nova Scotia, Ontario, Manitoba, Saskatchewan, Alberta and British Columbia. We estimated the period prevalence of ranitidine use per 100 population by province, age category and sex. We estimated exposure to ranitidine between 2015 and 2019 using defined daily doses (DDDs). RESULTS Overall, 2.4 million ranitidine prescriptions were dispensed to patients aged 65 years and older, and 1.7 million were dispensed to younger adults. Among older adults, the median period prevalence of ranitidine use among females was 16% (interquartile range [IQR] 13%-27%) higher than among males. Among younger adults, the median prevalence was 50% (IQR 37%-70%) higher among females. Among older adults, between 1996 and 1999, use was highest in Nova Scotia (33%) and Ontario (30%), lower in the prairies (Manitoba [18%], Saskatchewan [26%], Alberta [17%]) and lowest in BC (11%). By 2015-2019, use of ranitidine among older adults dropped by at least 50% in all provinces except BC. We estimate that at least 142 million DDDs of prescribed ranitidine were consumed annually in 6 provinces (2015-2019). INTERPRETATION Over the 24-year period in 6 provinces, patients aged 65 years and older were dispensed 2.4 million prescriptions of ranitidine and younger adults were dispensed 1.7 million prescriptions of ranitidine. These estimates of ranitidine exposure can be used for planning studies of cancer risk and identifying target populations for cancer surveillance.
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Affiliation(s)
- Adrian R Levy
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont.
| | - David Stock
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
| | - J Michael Paterson
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
| | - Hala Tamim
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
| | - Dan Chateau
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
| | - Jacqueline Quail
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
| | - Paul E Ronksley
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
| | - Greg Carney
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
| | - Pauline Reynier
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
| | - Laura Targownik
- Department of Community Health and Epidemiology (Levy, Stock), Dalhousie University, Halifax, NS; ICES (Paterson); York University (Tamim), Toronto, Ont.; National Centre for Epidemiology and Population Health (Chateau), College of Health & Medicine, Australian National University, Canberra, AU; Health Quality Council (Quail), Saskatoon, Sask.; Department of Community Health Sciences (Ronksley), University of Calgary, Calgary, Alta.; Therapeutics Initiative (Carney), University of British Columbia, Vancouver, BC; Lady Davis Institute (Reynier), Jewish General Hospital, Montréal, Que.; Department of Medicine (Targownik), University of Toronto, Toronto, Ont
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Chang K, Jackson CS, Vega KJ. Barrett's Esophagus: Diagnosis, Management, and Key Updates. Gastroenterol Clin North Am 2021; 50:751-768. [PMID: 34717869 DOI: 10.1016/j.gtc.2021.08.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Barrett's esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC) development. Unfortunately, BE screening/surveillance has not provided the anticipated EAC reduction benefit. Noninvasive techniques are increasingly available or undergoing testing to screen for BE among those with/without known risk factors, and the use of artificial intelligence platforms to aid endoscopic screening and surveillance will likely become routine, minimizing missed cases or lesions. Management of high-grade dysplasia and intramucosal EAC is clear with endoscopic eradication therapy preferred to surgery. BE with low-grade dysplasia can be managed with removal of visible lesions combined with endoscopic eradication therapy or endoscopic surveillance at present.
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Affiliation(s)
- Karen Chang
- Department of Internal Medicine, University of California, Riverside School of Medicine, 900 University Avenue, Riverside, CA 92521, USA
| | - Christian S Jackson
- Section of Gastroenterology, Loma Linda VA Healthcare System, 11201 Benton Street, 2A-38, Loma Linda, CA 92357, USA
| | - Kenneth J Vega
- Division of Gastroenterology & Hepatology, Augusta University-Medical College of Georgia, 1120 15th Street, AD-2226, Augusta, GA 30912, USA.
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Zhang Z, Curran G, Altinok Dindar D, Wu Y, Wu H, Sharpton T, Zhao L, Lieberman D, Otaki F. Insights Into the Oral Microbiome and Barrett's Esophagus Early Detection: A Narrative Review. Clin Transl Gastroenterol 2021; 12:e00390. [PMID: 34446641 PMCID: PMC8397287 DOI: 10.14309/ctg.0000000000000390] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 07/09/2021] [Indexed: 11/29/2022] Open
Abstract
Barrett's esophagus (BE) prevalence has increased steadily over the past several decades and continues to be the only known precursor of esophageal adenocarcinoma. The exact cause of BE is still unknown. Most evidence has linked BE to gastroesophageal reflux disease, which injures squamous esophageal mucosa and can result in the development of columnar epithelium with intestinal metaplasia. However, this relationship is inconsistent-not all patients with severe gastroesophageal reflux disease develop BE. There is increasing evidence that the host microbiome spanning the oral and esophageal environments differs in patients with and without BE. Several studies have documented the oral and esophageal microbiome's composition for BE with inconsistent findings. The scarcity and inconsistency of the literature and the dynamic phenomena of microbiota all warrant further studies to validate the findings and dissect the effects of oral microbiota, which are considered a viable proxy to represent esophageal microbiota by many researchers. This review aims to summarize the variability of the oral and esophageal microbiome in BE by using the example of Streptococcus to discuss the limitations of the current studies and suggest future directions. Further characterization of the sensitivity and specificity of the oral microbiome as a potential risk prediction or prevention marker of BE is critical, which will help develop noninvasive early detection methods for BE, esophageal adenocarcinoma, and other esophageal diseases.
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Affiliation(s)
- Zhenzhen Zhang
- Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA
| | - Grace Curran
- Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA
| | - Duygu Altinok Dindar
- Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA
| | - Ying Wu
- Department of Integrative Biomedical and Diagnostic Sciences, School of Dentistry, Oregon Health & Science University, Portland, Oregon, USA
| | - Hui Wu
- Department of Integrative Biomedical and Diagnostic Sciences, School of Dentistry, Oregon Health & Science University, Portland, Oregon, USA
| | - Thomas Sharpton
- Department of Microbiology, Oregon State University, Corvallis, Oregon, USA
- Department of Statistics, Oregon State University, Corvallis, Oregon, USA
| | - Lianmei Zhao
- Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China;
| | - David Lieberman
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Oregon Health Sciences University, Portland, Oregon, USA
| | - Fouad Otaki
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Oregon Health Sciences University, Portland, Oregon, USA
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Cook MB, Thrift AP. Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma: Implications for Screening and Surveillance. Gastrointest Endosc Clin N Am 2021; 31:1-26. [PMID: 33213789 PMCID: PMC7887893 DOI: 10.1016/j.giec.2020.08.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
In the United States, the incidence of esophageal adenocarcinoma increased markedly since the 1970s with a recent stabilization. Despite evolving screening and surveillance strategies to diagnose, risk triage, and intervene in Barrett's esophagus patients to prevent esophageal adenocarcinoma, most cases present with advanced disease and poor resultant survival. Epidemiologic studies have identified the main risk factors for these conditions, including increasing age, male sex, white race, gastroesophageal reflux disease, abdominal obesity, cigarette smoking, and lack of infection with Helicobacter pylori. This review summarizes the current epidemiologic evidence with implications for screening and surveillance in Barrett's esophagus and esophageal adenocarcinoma.
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Affiliation(s)
- Michael B Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E430, Rockville, MD 20850, USA.
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, MS: BCM307, Room 621D, Houston, TX 77030, USA
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Marques de Sá I, Marcos P, Sharma P, Dinis-Ribeiro M. The global prevalence of Barrett's esophagus: A systematic review of the published literature. United European Gastroenterol J 2020; 8:1086-1105. [PMID: 32631176 PMCID: PMC7724547 DOI: 10.1177/2050640620939376] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 06/04/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Determining the prevalence of Barrett's esophagus is important for defining screening strategies. We aimed to synthesize the available data, determine Barrett's esophagus prevalence, and assess variability. METHODS Three databases were searched. Subgroup, sensitivity, and meta-regression analyses were conducted and pooled prevalence was computed. RESULTS Of 3510 studies, 103 were included. In the general population, we estimated a prevalence for endoscopic suspicion of Barrett's esophagus of (a) any length with histologic confirmation of intestinal metaplasia as 0.96% (95% confidence interval: 0.85-1.07), (b) ≥1 cm of length with histologic confirmation of intestinal metaplasia as 0.96% (95% confidence interval: 0.75-1.18) and (c) for any length with histologic confirmation of columnar metaplasia as 3.89% (95% confidence interval: 2.25-5.54) . By excluding studies with high-risk of bias, the prevalence decreased to: (a) 0.70% (95% confidence interval: 0.61-0.79) and (b) 0.82% (95% confidence interval: 0.63-1.01). In gastroesophageal reflux disease patients, we estimated the prevalence with afore-mentioned criteria to be: (a) 7.21% (95% confidence interval: 5.61-8.81) (b) 6.72% (95% confidence interval: 3.61-9.83) and (c) 7.80% (95% confidence interval: 4.26-11.34). The Barrett's esophagus prevalence was significantly influenced by time period, region, Barrett's esophagus definition, Seattle protocol, and study design. There was a significant gradient East-West and North-South. There were minimal to no data available for several countries. Moreover, there was significant heterogeneity between studies. CONCLUSION There is a need to reassess the true prevalence of Barrett's esophagus using the current guidelines in most regions. Having knowledge about the precise Barrett's esophagus prevalence, diverse attitudes from educational to screening programs could be taken.
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Affiliation(s)
- Inês Marques de Sá
- Department of Gastroenterology, Portuguese Oncology Institute of
Porto, Porto, Portugal
| | - Pedro Marcos
- Department of Gastroenterology, Centro Hospitalar de Leiria,
Leiria, Portugal
| | - Prateek Sharma
- University of Kansas School of Medicine, Kansas City, USA
- Department of Gastroenterology, Veterans Affairs Medical Center,
Kansas City, USA
| | - Mário Dinis-Ribeiro
- Department of Gastroenterology, Portuguese Oncology Institute of
Porto, Porto, Portugal
- Center for Health Technology and Services Research (CINTESIS),
University of Porto, Porto, Portugal
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9
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Abstract
Because of the rising incidence and lethality of esophageal adenocarcinoma, Barrett's esophagus (BE) is an increasingly important premalignant target for cancer prevention. BE-associated neoplasia can be safely and effectively treated with endoscopic eradication therapy (EET), incorporating tissue resection and ablation. Because EET has proliferated, managing patients after complete eradication of intestinal metaplasia has taken on increasing importance. Recurrence after complete eradication of intestinal metaplasia occurs in 8%-10% of the patients yearly, and the incidence may remain constant over time. Most recurrences occur at the gastroesophageal junction, whereas those in the tubular esophagus are endoscopically visible and distally located. A simplified biopsy protocol limited to the distal aspect of the BE segment, in addition to gastroesophageal junction sampling, may enhance efficiency and cost without significantly reducing recurrence detection. Similarly, research suggests that current surveillance intervals may be excessively frequent, failing to reflect the cancer risk reduction of EET. If validated, longer surveillance intervals could reduce the burden of resource-intensive endoscopic surveillance. Several important questions in post-EET management remain unanswered, including surveillance duration, the significance of gastric cardia intestinal metaplasia, and the role of advanced imaging and nonendoscopic sampling techniques in detecting recurrence. These merit further research to enhance quality of care and promote a more evidence-based approach.
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10
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Bonavina L, Fisichella PM, Gavini S, Lee YY, Tatum RP. Clinical course of gastroesophageal reflux disease and impact of treatment in symptomatic young patients. Ann N Y Acad Sci 2020; 1481:117-126. [PMID: 32266986 DOI: 10.1111/nyas.14350] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 03/19/2020] [Accepted: 03/24/2020] [Indexed: 12/14/2022]
Abstract
In symptomatic young patients with gastroesophageal reflux symptoms, early identification of progressive gastroesophageal reflux disease (GERD) is critical to prevent long-term complications associated with hiatal hernia, increased esophageal acid and nonacid exposure, release of proinflammatory cytokines, and development of intestinal metaplasia, endoscopically visible Barrett's esophagus, and dysplasia leading to esophageal adenocarcinoma. Progression of GERD may occur in asymptomatic patients and in those under continuous acid-suppressive medication. The long-term side effects of proton-pump inhibitors, chemopreventive agents, and radiofrequency ablation are contentious. In patients with early-stage disease, when the lower esophageal sphincter function is still preserved and before endoscopically visible Barrett's esophagus develops, novel laparoscopic procedures, such as magnetic and electric sphincter augmentation, may have a greater role than conventional surgical therapy. A multidisciplinary approach to GERD by a dedicated team of gastroenterologists and surgeons might impact the patients' lifestyle, the therapeutic choices, and the course of the disease. Biological markers are needed to precisely assess the risk of disease progression and to tailor surveillance, ablation, and management.
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Affiliation(s)
- Luigi Bonavina
- Division of General and Foregut Surgery, Department of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Milano, Italy
| | - P Marco Fisichella
- Department of Surgery, Northwestern University, Feinberge School of Medicine, Chicago, Illinois
| | - Sravanya Gavini
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia.,Gut Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.,St George & Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Roger P Tatum
- Department of Surgery, University of Washington School of Medicine and VA Puget Sound Health Care System, Seattle, Washington
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11
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Yamasaki T, Sakiani S, Maradey-Romero C, Mehta R, Sandhu D, Ganocy S, Hemond C, Eisa M, Fass R. Barrett's esophagus patients are becoming younger: analysis of a large United States dataset. Esophagus 2020; 17:190-196. [PMID: 31894428 DOI: 10.1007/s10388-019-00707-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 12/03/2019] [Indexed: 02/03/2023]
Abstract
BACKGROUND Barrett's esophagus (BE), a complication of long-term gastroesophageal reflux disease (GERD), has been reported to affect 6-8% of those with heartburn. Most patients are males, Caucasians and middle aged. However, there are no recent demographic studies that evaluated the proportion trends of BE. We aimed to assess proportion trends of BE over an 11-year period, using a very large national dataset. METHODS This was a population-based analysis of the national Explorys dataset. Explorys is an aggregate of electronic medical record database representing over 54 million patients. Proportions of BE's variables such as age, gender, race, BMI, and treatment with PPI were recorded during an 11-year period. BE patients were classified into seven age groups (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, ≥ 70 years old). Secular trends of the proportion of BE were assessed over time for each age group. RESULTS The majority of patients diagnosed with BE were ≥ 70 years old across all calendar years. However, the proportion of BE patients who were ≥ 70 years old has significantly decreased between 2006 and 2016 (- 19.9%, p < 0.001). The proportion of patients with BE increased in all age groups but most prominently in the age groups, 30-39: 2.07%, 40-49: 3.64%, 50-59: 6.89%, 60-69: 6.18%, p < 0.001. BE was significantly more common in those who were Caucasian and male. PPI usage fell significantly in those who were ≥ 70 years old (- 20.8%, p < 0.001), but increased in the other remaining age groups. CONCLUSIONS The proportion of BE patients who are 70 years and older has significantly dropped. Younger patients' groups have demonstrated the highest increase in the proportion of BE patients, especially those in the age group of 30-39 years old.
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Affiliation(s)
- Takahisa Yamasaki
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA
| | - Sasan Sakiani
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA
| | - Carla Maradey-Romero
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA
| | - Ripple Mehta
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA
| | - Dalbir Sandhu
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA
| | - Stephen Ganocy
- Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Colin Hemond
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA
| | - Mohamed Eisa
- Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA.
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12
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The risk of incident extrahepatic cancers is higher in non-alcoholic fatty liver disease than obesity - A longitudinal cohort study. J Hepatol 2019; 71:1229-1236. [PMID: 31470068 PMCID: PMC6921701 DOI: 10.1016/j.jhep.2019.08.018] [Citation(s) in RCA: 205] [Impact Index Per Article: 34.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 07/22/2019] [Accepted: 08/17/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Cancer is a major cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Obesity is a risk factor for cancers; however, the role of NAFLD in this association is unknown. We investigated the effect of NAFLD versus obesity on incident cancers. METHODS We identified all incident cases of NAFLD in a US population between 1997-2016. Individuals with NAFLD were matched by age and sex to referent individuals from the same population (1:3) on the index diagnosis date. We ascertained the incidence of cancer after index date until death, loss to follow-up or study end. NAFLD and cancer were defined using a code-based algorithm with high validity and tested by medical record review. The association between NAFLD or obesity and cancer risk was examined using Poisson regression. RESULTS A total of 4,722 individuals with NAFLD (median age 54, 46% male) and 14,441 age- and sex-matched referent individuals were followed for a median of 8 (range 1-21) years, during which 2,224 incident cancers occurred. NAFLD was associated with 90% higher risk of malignancy: incidence rate ratio (IRR) = 1.9 (95% CI 1.3-2.7). The highest risk increase was noted in liver cancer, IRR = 2.8 (95% CI 1.6-5.1), followed by uterine IRR = 2.3 (95% CI 1.4-4.1), stomach IRR = 2.3 (95% CI 1.3-4.1), pancreas IRR = 2.0 (95% CI 1.2-3.3) and colon cancer IRR = 1.8 (95% CI 1.1-2.8). In reference to non-obese controls, NAFLD was associated with a higher risk of incident cancers (IRR = 2.0, 95% CI 1.5-2.9), while obesity alone was not (IRR = 1.0, 95% CI 0.8-1.4). CONCLUSIONS NAFLD was associated with increased cancer risk, particularity of gastrointestinal types. In the absence of NAFLD, the association between obesity and cancer risk is small, suggesting that NAFLD may be a mediator of the obesity-cancer association. LAY SUMMARY We studied the incidence of malignancies in a community cohort of adults with non-alcoholic fatty liver disease (NAFLD) in reference to age- and sex-matched adults without NAFLD. After 21 years of longitudinal follow-up, NAFLD was associated with a nearly 2-fold increase in the risk of developing cancers, predominantly of the liver, gastrointestinal tract and uterus. The association with increased cancer risk was stronger in NAFLD than obesity.
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13
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Desai M, Lieberman DA, Kennedy KF, Hamade N, Thota P, Parasa S, Gorrepati VS, Bansal A, Gupta N, Gaddam S, Young PE, Mathur S, Moawad FJ, Cash BD, Sampliner R, Vargo JJ, Falk GW, Sharma P. Increasing prevalence of high-grade dysplasia and adenocarcinoma on index endoscopy in Barrett's esophagus over the past 2 decades: data from a multicenter U.S. consortium. Gastrointest Endosc 2019; 89:257-263.e3. [PMID: 30342028 PMCID: PMC7053563 DOI: 10.1016/j.gie.2018.09.041] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Accepted: 09/24/2018] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE-associated dysplasia on index endoscopy over the past 25 years. METHODS The Barrett's Esophagus Study is a multicenter outcome project of a large cohort of patients with BE. Proportions of patients with index endoscopy findings of no dysplasia (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC were extracted per year of index endoscopy, and 5-yearly patient cohorts were tabulated over years 1990 to 2010+ (2010-current). Prevalent dysplasia and endoscopic findings were trended over the past 25 years using percentage dysplasia (LGD, HGD, EAC, and HGD/EAC) to assess changes in detection of BE-associated dysplasia over the last 25 years. Statistical analysis was done using SAS version 9.4 software (SAS, Cary, NC). RESULTS A total of 3643 patients were included in the analysis with index endoscopy showing NDBE in 2513 (70.1%), LGD in 412 (11.5%), HGD in 193 (5.4%), and EAC in 181 (5.1%). Over time, there was an increase in the mean age of patients with BE (51.7 ± 29 years vs 62.6 ± 11.3 years) and the proportion of males (84% vs 92.6%) diagnosed with BE but a decrease in the mean BE length (4.4±4.3 cm vs 2.9±3.0 cm) as time progressed (1990-1994 to 2010-2016 time periods). The presence of LGD on index endoscopy remained stable over 1990 to 2016. However, a significant increase (148% in HGD and 112% in EAC) in the diagnosis of HGD, EAC, and HGD/EAC was noted on index endoscopy over the last 25 years (P < .001). There was also a significant increase in the detection of visible lesions on index endoscopy (1990-1994, 5.1%; to 2005-2009, 6.3%; and 2010+, 16.3%) during the same period. CONCLUSION Our results suggest that the prevalence of HGD and EAC has significantly increased over the past 25 years despite a decrease in BE length during the same period. This increase parallels an increase in the detection of visible lesions, suggesting that a careful examination at the index examination is crucial.
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Affiliation(s)
- Madhav Desai
- Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas
| | - David A. Lieberman
- Gastroenterology, Oregon Health and Science University, Portland, Oregon
| | - Kevin F. Kennedy
- Gastroenterology, VA Medical Center Kansas City, Kansas City, Missouri
| | - Nour Hamade
- Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas
| | - Prashanthi Thota
- Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio
| | | | | | - Ajay Bansal
- Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas
| | - Neil Gupta
- Gastroenterology, Loyola University Medical Center, Maywood, Illinois
| | - Srinivas Gaddam
- Gastroenterology, Cedar-Sinai Medical Center, Los Angeles, California
| | - Patrick E. Young
- Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Sharad Mathur
- Pathology, VA Medical Center Kansas City, Kansas City, Missouri
| | - Fouad J. Moawad
- Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Brooks D. Cash
- Gastroenterology, University of South Alabama, Mobile, Alabama
| | | | - John J. Vargo
- Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Gary W. Falk
- Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Prateek Sharma
- Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas,Gastroenterology, VA Medical Center Kansas City, Kansas City, Missouri
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14
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Surdea-Blaga T, Negrutiu DE, Palage M, Dumitrascu DL. Food and Gastroesophageal Reflux Disease. Curr Med Chem 2019; 26:3497-3511. [PMID: 28521699 DOI: 10.2174/0929867324666170515123807] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 04/28/2017] [Accepted: 04/28/2017] [Indexed: 02/08/2023]
Abstract
Gastroesophageal reflux disease is a chronic condition with a high prevalence in western countries. Transient lower esophageal sphincter relaxation episodes and a decreased lower esophageal sphincter pressure are the main mechanisms involved. Currently used drugs are efficient on reflux symptoms, but only as long as they are administered, because they do not modify the reflux barrier. Certain nutrients or foods are generally considered to increase the frequency of gastroesophageal reflux symptoms, therefore physicians recommend changes in diet and some patients avoid bothering foods. This review summarizes current knowledge regarding food and gastroesophageal reflux. For example, fat intake increases the perception of reflux symptoms. Regular coffee and chocolate induce gastroesophageal reflux and increase the lower esophageal exposure to acid. Spicy foods might induce heartburn, but the exact mechanism is not known. Beer and wine induce gastroesophageal reflux, mainly in the first hour after intake. For other foods, like fried food or carbonated beverages data on gastroesophageal reflux is scarce. Similarly, there are few data about the type of diet and gastroesophageal reflux. Mediterranean diet and a very low carbohydrate diet protect against reflux. Regarding diet-related practices, consistent data showed that a "short-meal-to-sleep interval" favors reflux episodes, therefore some authors recommend that dinner should be at least four hours before bedtime. All these recommendations should consider patient's weight, because several meta-analyses showed a positive association between increased body mass index and gastroesophageal reflux disease.
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Affiliation(s)
- Teodora Surdea-Blaga
- 2nd Dept. of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj-Napoca, Romania
| | - Dana E Negrutiu
- 2nd Dept. of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj-Napoca, Romania
| | - Mariana Palage
- Department of Therapeutic Chemistry, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj- Napoca, Romania
| | - Dan L Dumitrascu
- 2nd Dept. of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj-Napoca, Romania
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15
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Abstract
In Western countries, the incidence of esophageal adenocarcinoma has increased rapidly in parallel with its premalignant condition, Barrett esophagus (BE). Unlike colonoscopy, endoscopic screening for BE is not currently recommended for all patients; however, surveillance endoscopy is advocated for patients with established BE. Novel imaging and sampling techniques have been developed and investigated for the purpose of improving the detection of Barrett esophagus, dysplasia, and neoplasia. This article discusses several screening and surveillance techniques, including Seattle protocol, chromoendoscopy, electronic chromoendoscopy, wide area transepithelial sampling with 3-dimensional analysis, nonendoscopic sampling devices, and transnasal endoscopy.
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Affiliation(s)
- Yoshihiro Komatsu
- Esophageal and Lung Institute, Allegheny Health Network, Western Pennsylvania Hospital, Suite 158, Mellon Pavilion, 4815 Liberty Avenue, Pittsburgh, PA 15224, USA
| | - Kirsten M Newhams
- Esophageal and Lung Institute, Allegheny Health Network, Western Pennsylvania Hospital, Suite 158, Mellon Pavilion, 4815 Liberty Avenue, Pittsburgh, PA 15224, USA
| | - Blair A Jobe
- Esophageal and Lung Institute, Allegheny Health Network, Western Pennsylvania Hospital, Suite 158, Mellon Pavilion, 4815 Liberty Avenue, Pittsburgh, PA 15224, USA.
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16
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Chilukuri P, Gromski MA, Johnson CS, Ceppa DKP, Kesler KA, Birdas TJ, Rieger KM, Fatima H, Kessler WR, Rex DK, Al-Haddad M, DeWitt JM. Impact of the development of an endoscopic eradication program for Barrett's esophagus with high grade dysplasia or early adenocarcinoma on the frequency of surgery. Endosc Int Open 2018; 6:E1085-E1092. [PMID: 30211296 PMCID: PMC6133650 DOI: 10.1055/a-0640-3030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 03/12/2018] [Indexed: 11/20/2022] Open
Abstract
Background and aims The impact of the advent of an institutional endoscopic eradication therapy (EET) program on surgical practice for Barrett's esophagus (BE)-associated high grade dysplasia (HGD) or suspected T1a esophageal adenocarcinoma (EAC) is unknown. The aims of this study are to evaluate the different endoscopic modalities used during development of our EET program and factors associated with the use of EET or surgery for these patients after its development. Methods Patients who underwent primary endoscopic or surgical treatment for BE-HGD or early EAC at our hospital between January 1992 and December 2014 were retrospectively identified. They were categorized by their initial modality of treatment during the first year, and the impact over time for choice of therapy was assessed by multivariable logistic regression. Results We identified 386 patients and 80 patients who underwent EET and surgery, respectively. EET included single modality therapy in 254 (66 %) patients and multimodal therapy in 132 (34 %) patients. Multivariable logistic regression showed that, for each subsequent study year, EET was more likely to be performed in patients who were older ( P = 0.0009), with shorter BE lengths ( P < 0.0001), and with a pretreatment diagnosis of HGD ( P = 0.0054) compared to surgical patients. The diagnosis of EAC did not increase the utilization of EET compared to surgery as time progressed ( P = 0.8165). Conclusion The introduction of an EET program at our hospital increased the odds of utilizing EET versus surgery over time for initial treatment of patients who were older, had shorter BE lengths or the diagnosis of BE-HGD, but not in patients with EAC.
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Affiliation(s)
- Prianka Chilukuri
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark A. Gromski
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | | | - Duy Khanh P. Ceppa
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Kenneth A. Kesler
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Thomas J. Birdas
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Karen M. Rieger
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Hala Fatima
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - William R. Kessler
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Douglas K. Rex
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mohammad Al-Haddad
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - John M. DeWitt
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA,Corresponding author John M. DeWitt, MD Indiana University School of Medicine550 University BlvdSuite 4100IndianapolisIN 46202-5250USA+1-317-948-8144
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17
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Cook MB, Coburn SB, Lam JR, Taylor PR, Schneider JL, Corley DA. Cancer incidence and mortality risks in a large US Barrett's oesophagus cohort. Gut 2018; 67:418-529. [PMID: 28053055 PMCID: PMC5827961 DOI: 10.1136/gutjnl-2016-312223] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 12/01/2016] [Accepted: 12/04/2016] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Barrett's oesophagus (BE) increases the risk of oesophageal adenocarcinoma by 10-55 times that of the general population, but no community-based cancer-specific incidence and cause-specific mortality risk estimates exist for large cohorts in the USA. DESIGN Within Kaiser Permanente Northern California (KPNC), we identified patients with BE diagnosed during 1995-2012. KPNC cancer registry and mortality files were used to estimate standardised incidence ratios (SIR), standardised mortality ratios (SMR) and excess absolute risks. RESULTS There were 8929 patients with BE providing 50 147 person-years of follow-up. Compared with the greater KPNC population, patients with BE had increased risks of any cancer (SIR=1.40, 95% CI 1.31 to 1.49), which slightly decreased after excluding oesophageal cancer. Oesophageal adenocarcinoma risk was increased 24 times, which translated into an excess absolute risk of 24 cases per 10 000 person-years. Although oesophageal adenocarcinoma risk decreased with time since BE diagnosis, oesophageal cancer mortality did not, indicating that the true risk is stable and persistent with time. Relative risks of cardia and stomach cancers were increased, but excess absolute risks were modest. Risks of colorectal, lung and prostate cancers were unaltered. All-cause mortality was slightly increased after excluding oesophageal cancer (SMR=1.24, 95% CI 1.18 to 1.31), but time-stratified analyses indicated that this was likely attributable to diagnostic bias. Cause-specific SMRs were elevated for ischaemic heart disease (SMR=1.39, 95% CI 1.18 to 1.63), respiratory system diseases (SMR=1.51, 95% CI 1.29 to 1.75) and digestive system diseases (SMR=2.20 95% CI 1.75 to 2.75). CONCLUSIONS Patients with BE had a persistent excess risk of oesophageal adenocarcinoma over time, although their absolute excess risks for this cancer, any cancer and overall mortality were modest.
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Affiliation(s)
- Michael B Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA
| | - Sally B Coburn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA
| | - Jameson R Lam
- Division of Research, Oakland Medical Center, Kaiser Permanente, Oakland, California, USA
| | - Philip R Taylor
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA
| | - Jennifer L Schneider
- Division of Research, Oakland Medical Center, Kaiser Permanente, Oakland, California, USA
| | - Douglas A Corley
- Division of Research, Oakland Medical Center, Kaiser Permanente, Oakland, California, USA
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18
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Thrift AP, Anderson LA, Murray LJ, Cook MB, Shaheen NJ, Rubenstein JH, El-Serag HB, Vaughan TL, Schneider JL, Whiteman DC, Corley DA. Nonsteroidal Anti-Inflammatory Drug Use is Not Associated With Reduced Risk of Barrett's Esophagus. Am J Gastroenterol 2016; 111:1528-1535. [PMID: 27575711 PMCID: PMC5209791 DOI: 10.1038/ajg.2016.348] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Accepted: 07/22/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of esophageal adenocarcinoma. Epidemiological studies examining the association between NSAID use and the risk of the precursor lesion, Barrett's esophagus, have been inconclusive. METHODS We analyzed pooled individual-level participant data from six case-control studies of Barrett's esophagus in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). We compared medication use from 1,474 patients with Barrett's esophagus separately with two control groups: 2,256 population-based controls and 2,018 gastroesophageal reflux disease (GERD) controls. Study-specific odds ratio (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models and were combined using a random-effects meta-analytic model. RESULTS Regular (at least once weekly) use of any NSAIDs was not associated with the risk of Barrett's esophagus (vs. population-based controls, adjusted OR=1.00, 95% CI=0.76-1.32, I2=61%; vs. GERD controls, adjusted OR=0.99, 95% CI=0.82-1.19, I2=19%). Similar null findings were observed among individuals who took aspirin or non-aspirin NSAIDs. We also found no association with highest levels of frequency (at least daily use) and duration (≥5 years) of NSAID use. There was evidence of moderate between-study heterogeneity; however, associations with NSAID use remained non-significant in "leave-one-out" sensitivity analyses. CONCLUSIONS Use of NSAIDs was not associated with the risk of Barrett's esophagus. The previously reported inverse association between NSAID use and esophageal adenocarcinoma may be through reducing the risk of neoplastic progression in patients with Barrett's esophagus.
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Affiliation(s)
- Aaron P. Thrift
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Lesley A. Anderson
- Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland
| | - Liam J. Murray
- Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland
| | - Michael B. Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Nicholas J. Shaheen
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Joel H. Rubenstein
- Center for Clinical Management Research, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan, USA,Barrett's Esophagus Program, Division of Gastroenterology Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Hashem B. El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA,Department of Medicine, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
| | - Thomas L. Vaughan
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Jennifer L. Schneider
- Kaiser Permanente Division of Research, Oakland, California and San Francisco Medical Center, USA
| | - David C. Whiteman
- QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Douglas A. Corley
- Kaiser Permanente Division of Research, Oakland, California and San Francisco Medical Center, USA
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19
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Kim YS, Kim N, Kim GH. Sex and Gender Differences in Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2016; 22:575-588. [PMID: 27703114 PMCID: PMC5056567 DOI: 10.5056/jnm16138] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 09/12/2016] [Accepted: 09/13/2016] [Indexed: 12/13/2022] Open
Abstract
It is important to understand sex and gender-related differences in gastroesophageal reflux disease (GERD) because gender-related biologic factors might lead to better prevention and therapy. Non-erosive reflux disease (NERD) affects more women than men. GERD symptoms are more frequent in patients with NERD than in those with reflux esophagitis. However, men suffer pathologic diseases such as reflux esophagitis, Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) more frequently than women. The prevalence of reflux esophagitis is significantly increased with age in women, especially after their 50s. The mean age of EAC incidence in women is higher than in men, suggesting a role of estrogen in delaying the onset of BE and EAC. In a chronic rat reflux esophagitis model, nitric oxide was found to be an aggravating factor of esophageal injury in a male-predominant way. In addition, the expression of esophageal occludin, a tight junction protein that plays an important role in the esophageal defense mechanism, was up-regulated in women. This explains the male predominance of reflux esophagitis and delayed incidence of BE or EAC in women. Moreover, the symptoms such as heartburn, regurgitation, and extra-esophageal symptoms have been more frequently reported by women than by men, suggesting that sex and gender play a role in symptom perception. Differential sensitivity with augmented symptoms in women might have diagnostic and therapeutic influence. Furthermore, recent studies have suggested that hormone replacement therapy has a protective effect against esophageal cancer. However, an anti-inflammatory role of estrogen remains compelling, which means further study is necessary in this area.
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Affiliation(s)
- Young Sun Kim
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul,
Korea
| | - Nayoung Kim
- Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do,
Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul,
Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan,
Korea
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20
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Abdelmessih R, Packey CD, Lawlor G. Endoscopy in the Elderly: a Cautionary Approach, When to Stop. ACTA ACUST UNITED AC 2016; 14:305-14. [DOI: 10.1007/s11938-016-0101-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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21
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Zhao Z, Pu Z, Yin Z, Yu P, Hao Y, Wang Q, Guo M, Zhao Q. Dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett's esophagus risk: a systematic review and meta-analysis. Sci Rep 2016; 6:27334. [PMID: 27256629 PMCID: PMC4891687 DOI: 10.1038/srep27334] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 05/16/2016] [Indexed: 12/20/2022] Open
Abstract
The relationships between dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett’s esophagus (BE) risk remain inconclusive. We conducted a systematic review and meta-analysis to summarize the available evidence on these issues. PubMed, EMBASE and the Cochrane Library were searched for studies published from inception through October 2015. A total of eight studies were included in this analysis. Fruit intake was not associated with BE risk (OR = 0.65, 95% CI = 0.37–1.13), but vegetable intake was strongly associated with BE risk (OR = 0.45, 95% CI = 0.29–0.71). Saturated fat, red meat and processed meat intakes were not associated with BE risk with OR = 1.25 (95% CI = 0.82–1.91), OR = 0.85 (95% CI = 0.61–1.17) and OR = 1.03 (95% CI = 0.73–1.46), respectively. Dietary vegetable not fruits intake may be associated with decreased BE risk. Fat and red and processed meat intakes may not contribute to an increased BE risk. Well-designed, large prospective studies with better established dose-response relationships are needed to further validate these issues.
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Affiliation(s)
- Zhanwei Zhao
- Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China
| | - Zhongshu Pu
- Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China.,Department of Epidemiology, School of Public Health, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China
| | - Zifang Yin
- Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China.,Shaanxi Maternal and Child Health Hospital, Shaanxi Province, China
| | - Pengfei Yu
- Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China
| | - Yiming Hao
- Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China
| | - Qian Wang
- Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China
| | - Min Guo
- Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China
| | - Qingchuan Zhao
- Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, China
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22
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Asanuma K, Iijima K, Shimosegawa T. Gender difference in gastro-esophageal reflux diseases. World J Gastroenterol 2016; 22:1800-10. [PMID: 26855539 PMCID: PMC4724611 DOI: 10.3748/wjg.v22.i5.1800] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 10/07/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.
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23
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Abstract
Beginning in the 1980s, an alarming rise in the incidence of esophageal adenocarcinoma (EA) led to screening of patients with reflux to detect Barrett's esophagus (BE) and surveillance of BE to detect early EA. This strategy, based on linear progression disease models, resulted in selective detection of BE that does not progress to EA over a lifetime (overdiagnosis) and missed BE that rapidly progresses to EA (underdiagnosis). Here we review the historical thought processes that resulted in this undesired outcome and the transformation in our understanding of genetic and evolutionary principles governing neoplastic progression that has come from application of modern genomic technologies to cancers and their precursors. This new synthesis provides improved strategies for prevention and early detection of EA by addressing the environmental and mutational processes that can determine "windows of opportunity" in time to detect rapidly progressing BE and distinguish it from slowly or nonprogressing BE.
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Affiliation(s)
- Brian J. Reid
- Division of Human Biology, FredHutch, Seattle WA,Division of Public Health Sciences, FredHutch, Seattle WA,Department of Genome Sciences, University of Washington,Department of Medicine, University of Washington,Corresponding author Brian J. Reid, M.D., Ph.D. 1100 Fairview Ave N., C1-157 P.O. Box 19024 Seattle, WA 98109-1024 206-667-4073 (phone) 206-667-6192 (FAX)
| | | | - Xiaohong Li
- Division of Human Biology, FredHutch, Seattle WA
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24
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Nguyen T, Alsarraj A, El-Serag HB. Brief report: the length of newly diagnosed Barrett's esophagus may be decreasing. Dis Esophagus 2015; 28:418-21. [PMID: 24708395 DOI: 10.1111/dote.12216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Few studies have examined the temporal trends of length in newly diagnosed Barrett's esophagus (BE) and arrived at conflicting results. The aim of this study was to identify whether there has been a change over time in the length of BE at the time of diagnosis. This is a retrospective, single-center, observational study from Houston, Texas on newly diagnosed BE between 2008 and 2013. All cases were defined by the presence of endoscopically visible BE and histologic confirmation of intestinalized columnar epithelium with goblet cells. The length of BE was measured using the Prague classification. We examined temporal changes in 1-year intervals in the length of BE at the time of diagnosis. Both the frequency and mean length of BE at diagnosis seemed to decrease over time from February 2008 to July 2013. The proportion of patients diagnosed with BE ≥3 cm per year declined during the study period, while the proportion of patients with BE ≥1 and <3 cm increased, and those with <1 cm remained stable. The mean age and the gender of patients diagnosed with BE ≥3 cm did not differ significantly by BE length or year of diagnosis. The mean length of newly diagnosed BE may be decreasing as a result of a decline in BE ≥3 cm. These observations cannot be explained by changes in age and gender.
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Affiliation(s)
- T Nguyen
- Houston VA HSR&D Center of Excellence, Baylor College of Medicine, Houston, Texas, USA.,Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - A Alsarraj
- Houston VA HSR&D Center of Excellence, Baylor College of Medicine, Houston, Texas, USA
| | - H B El-Serag
- Houston VA HSR&D Center of Excellence, Baylor College of Medicine, Houston, Texas, USA.,Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA.,Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
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25
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Runge TM, Abrams JA, Shaheen NJ. Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterol Clin North Am 2015; 44:203-31. [PMID: 26021191 PMCID: PMC4449458 DOI: 10.1016/j.gtc.2015.02.001] [Citation(s) in RCA: 154] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC), a disease with increasing burden in the Western world, especially in white men. Risk factors for BE include obesity, tobacco smoking, and gastroesophageal reflux disease (GERD). EAC is the most common form of esophageal cancer in the United States. Risk factors include GERD, tobacco smoking, and obesity, whereas nonsteroidal antiinflammatory drugs and statins may be protective. Factors predicting progression from nondysplastic BE to EAC include dysplastic changes on esophageal histology and length of the involved BE segment. Biomarkers have shown promise, but none are approved for clinical use.
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Affiliation(s)
- Thomas M. Runge
- University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, NC
| | - Julian A. Abrams
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY
| | - Nicholas J. Shaheen
- University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, NC
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26
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Rameez MH, Mayberry JF. Epidemiology and risk factors for Barrett's oesophagus. Br J Hosp Med (Lond) 2015; 76:138-41. [DOI: 10.12968/hmed.2015.76.3.138] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
| | - John F Mayberry
- Consultant Gastroenterologist in the Department of Digestive Diseases, University Hospitals of Leicester NHS Trust, Leicester LE5 4PW
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27
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The effect of laparoscopic fundoplication in therapy of Barrett's esophagus. Wideochir Inne Tech Maloinwazyjne 2014; 9:213-8. [PMID: 25097689 PMCID: PMC4105679 DOI: 10.5114/wiitm.2014.41634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 10/18/2013] [Accepted: 11/24/2013] [Indexed: 11/24/2022] Open
Abstract
Introduction Barrett's esophagus is the most significant precancer of the esophagus. Its malignization gives rise to most adenocarcinomas of the esophagus. Therefore selection of adequate therapy for this precancerous condition is of the utmost importance. Aim The authors of the work addressed the question of whether effective therapy of reflux disease alone may halt the process of malignization of Barrett's mucosa or even cause its regression. Material and methods The analyzed set comprised 50 patients with Barrett's esophagus, who in 48 cases underwent laparoscopic fundoplication and in two cases underwent an indirect antireflux procedure in the form of gastric resection with a Roux-en-Y gastrojejunal anastomosis. The effect of the procedure was evaluated by comparing preoperative and postoperative endoscopic examinations, as well as histological analysis by biopsy taken from Barrett's mucosa. Results In 19 patients (38%), Barrett's mucosa was not detected postoperatively. An improved finding in terms of disappearance of mucosal dysplasia was found in 8 (16%) patients. Findings remained unchanged in 18 (36%) patients. In 5 (10%) patients progression of the disease was discovered. Conclusions A surgical antireflux procedure, primarily in the form of laparoscopic fundoplication, is considered an effective method for treating Barrett's esophagus up to the stage of mild dysplasia. If this therapy is unsuccessful, the method of choice is local therapy, either an endoscopic mucosectomy or radiofrequency ablation.
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28
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Zaidi AH, Gopalakrishnan V, Kasi PM, Zeng X, Malhotra U, Balasubramanian J, Visweswaran S, Sun M, Flint MS, Davison JM, Hood BL, Conrads TP, Bergman JJ, Bigbee WL, Jobe BA. Evaluation of a 4-protein serum biomarker panel-biglycan, annexin-A6, myeloperoxidase, and protein S100-A9 (B-AMP)-for the detection of esophageal adenocarcinoma. Cancer 2014; 120:3902-13. [PMID: 25100294 DOI: 10.1002/cncr.28963] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 06/23/2014] [Accepted: 07/22/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Esophageal adenocarcinoma (EAC) is associated with a dismal prognosis. The identification of cancer biomarkers can advance the possibility for early detection and better monitoring of tumor progression and/or response to therapy. The authors present results from the development of a serum-based, 4-protein (biglycan, myeloperoxidase, annexin-A6, and protein S100-A9) biomarker panel for EAC. METHODS A vertically integrated, proteomics-based biomarker discovery approach was used to identify candidate serum biomarkers for the detection of EAC. Liquid chromatography-tandem mass spectrometry analysis was performed on formalin-fixed, paraffin-embedded tissue samples that were collected from across the Barrett esophagus (BE)-EAC disease spectrum. The mass spectrometry-based spectral count data were used to guide the selection of candidate serum biomarkers. Then, the serum enzyme-linked immunosorbent assay data were validated in an independent cohort and were used to develop a multiparametric risk-assessment model to predict the presence of disease. RESULTS With a minimum threshold of 10 spectral counts, 351 proteins were identified as differentially abundant along the spectrum of Barrett esophagus, high-grade dysplasia, and EAC (P<.05). Eleven proteins from this data set were then tested using enzyme-linked immunosorbent assays in serum samples, of which 5 proteins were significantly elevated in abundance among patients who had EAC compared with normal controls, which mirrored trends across the disease spectrum present in the tissue data. By using serum data, a Bayesian rule-learning predictive model with 4 biomarkers was developed to accurately classify disease class; the cross-validation results for the merged data set yielded accuracy of 87% and an area under the receiver operating characteristic curve of 93%. CONCLUSIONS Serum biomarkers hold significant promise for the early, noninvasive detection of EAC.
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Affiliation(s)
- Ali H Zaidi
- Institute for the Treatment of Esophageal and Thoracic Disease, Allegheny Health Network, Pittsburgh, Pennsylvania
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29
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Masclee GMC, Coloma PM, de Wilde M, Kuipers EJ, Sturkenboom MCJM. The incidence of Barrett's oesophagus and oesophageal adenocarcinoma in the United Kingdom and The Netherlands is levelling off. Aliment Pharmacol Ther 2014; 39:1321-30. [PMID: 24738722 DOI: 10.1111/apt.12759] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Revised: 03/20/2014] [Accepted: 03/27/2014] [Indexed: 01/02/2023]
Abstract
BACKGROUND Barrett's oesophagus (BO) is a risk factor for oesophageal adenocarcinoma (OAC). Several studies report increasing incidences of BO with substantial variation. AIM To determine age- and sex-stratified incidence rates (IR) of BO and OAC. METHODS Cohort study using two primary care databases in the United Kingdom (UK) and the Netherlands (NL) (2000-2012). BO and OAC cases were identified using disease-specific READ codes (UK) and free-text search with manual validation (NL). Age- and sex-specific incidence rates (IRs) were calculated for both BO and OAC. RESULTS From the study population of 6,885,420 subjects in the UK, we identified 12,312 incident BO and 40 (0.3%) subsequent incident OAC cases. There were 1383 incident BO, and subsequent 5 (0.4%) incident OAC cases among the 1,487,191 subjects in the NL. The IR of BO increased linearly with age: 15.6/100,000 PYs (UK) and 23.7/100,000 PYs (NL) for patients aged 40-44 years, increasing to 85.6/100,000 PYs (UK) and 87.0/100,000 PYs (NL) for 70-74 years. In both the UK and the NL, IR of BO was 2-4 times higher in males than females across all age groups. With respect to calendar time, the IR of BO increased by 35% (UK) and 41% (NL) from 2000 to 2003, after which IRs remained stable until 2012. CONCLUSIONS The incidence rates of BO in the UK and the NL increased until 2003, but levelled off thereafter. Around 0.3% of patients with BO developed OAC at least 1 year after BO diagnosis. These findings may help tailor endoscopic surveillance strategies among patients with BO.
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Affiliation(s)
- G M C Masclee
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
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30
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Influence of Life Style Factors on Barrett's Oesophagus. Gastroenterol Res Pract 2014; 2014:408470. [PMID: 24971090 PMCID: PMC4058172 DOI: 10.1155/2014/408470] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2014] [Accepted: 03/23/2014] [Indexed: 01/10/2023] Open
Abstract
Background. Since the incidence of adenocarcinoma of the oesophagus is rising, the prognosis is poor, and surveillance programs are expensive and mostly cost ineffective, there is a need to increase the knowledge of risk factors in Barrett's oesophagus and oesophageal cancer in order to be able to give attention to medical prevention and/or surveillance programs. Aim. To study if there is a correlation between the development of Barrett's oesophagus and GOR (gastro oesophageal reflux), family history of GOR, and life style factors, such as alcohol, smoking habits, and mental stress. Methods. Fifty-five consecutively selected patients with Barrett's oesophagus (BO) examined at Linköping University Hospital's Oesophageal Laboratory were matched by sex, age, and duration of reflux symptoms with 55 GOR patients without Barrett's oesophagus at the Oesophageal Laboratory. The medical charts in respective groups were examined for comparison of life style factors, mental stress, medication, duration of gastroesophageal acid reflux at 24 hr-pH-metry, and incidence of antireflux surgery and of adenocarcinoma of the oesophagus (ACO). Also, potential gender differences and diagnosis of ACO were studied. Results. Mean percentage reflux time on 24 hr-pH-metry was higher for the Barrett's oesophagus group, 18% for women and 17% for men compared to 4% for women and 4% for men in the control group (P < 0.05). Family history of GOR was more frequent in Barrett's oesophagus patients (62%) than in the control group (35%) (P < 0.05). Male patients with Barrett's oesophagus had medical therapy for their GOR symptoms to a higher extent (38%) than male controls (65%) (P < 0.05). No difference was found in the number of tobacco users or former tobacco users between Barrett's oesophagus patients and controls. Barrett's oesophagus patients had the same level of alcohol consumption and the same average BMI as the control subjects. Female patients with Barrett's oesophagus rated themselves as more mentally stressed (67%) than the female controls (38%) (P < 0.05). In the five-year medical chart follow-up, five of 55 patients developed adenocarcinoma among the Barrett's oesophagus patients, none in the control group. Conclusions. Long reflux time and family clustering of GOR seem to influence the development of Barrett's oesophagus. Smoking habits, alcohol consumption and BMI do not seem to have any impact on the development of Barrett's oesophagus.
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31
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Hyland PL, Hu N, Rotunno M, Su H, Wang C, Wang L, Pfeiffer RM, Gherman B, Giffen C, Dykes C, Dawsey SM, Abnet CC, Johnson KM, Acosta RD, Young PE, Cash BD, Taylor PR. Global changes in gene expression of Barrett's esophagus compared to normal squamous esophagus and gastric cardia tissues. PLoS One 2014; 9:e93219. [PMID: 24714516 PMCID: PMC3979678 DOI: 10.1371/journal.pone.0093219] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Accepted: 03/03/2014] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Barrett's esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE. DESIGN We performed gene expression analysis using HG-U133A Affymetrix chips on fresh frozen tissue samples of Barrett's metaplasia and matched normal mucosa from squamous esophagus (NE) and gastric cardia (NC) in 40 BE patients. RESULTS Using a cut off of 2-fold and P<1.12E-06 (0.05 with Bonferroni correction), we identified 1324 differentially-expressed genes comparing BE vs NE and 649 differentially-expressed genes comparing BE vs NC. Except for individual genes such as the SOXs and PROM1 that were dysregulated only in BE vs NE, we found a subset of genes (n = 205) whose expression was significantly altered in both BE vs NE and BE vs NC. These genes were overrepresented in different pathways, including TGF-β and Notch. CONCLUSION Our findings provide additional data on the global transcriptome in BE tissues compared to matched NE and NC tissues which should promote further understanding of the functions and regulatory mechanisms of genes involved in BE development, as well as insight into novel genes that may be useful as potential biomarkers for the diagnosis of BE in the future.
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Affiliation(s)
- Paula L. Hyland
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
- Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Nan Hu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Melissa Rotunno
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Hua Su
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Chaoyu Wang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Lemin Wang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Ruth M. Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | | | - Carol Giffen
- Information Management Services, Inc, Silver Spring, Maryland, United States of America
| | - Cathy Dykes
- Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America
| | - Sanford M. Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Christian C. Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Kathryn M. Johnson
- Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America
| | - Ruben D. Acosta
- Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America
| | - Patrick E. Young
- Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America
| | - Brooks D. Cash
- Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America
| | - Philip R. Taylor
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
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Gajamer VR, Tiwari HK. Prevalence of Gastrointestinal Disease and Its Associated Risk Factors in Sikkim and Darjeeling Districts. J Community Health 2014; 39:767-74. [DOI: 10.1007/s10900-014-9826-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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de Jonge PJF, van Blankenstein M, Grady WM, Kuipers EJ. Barrett's oesophagus: epidemiology, cancer risk and implications for management. Gut 2014; 63:191-202. [PMID: 24092861 PMCID: PMC6597262 DOI: 10.1136/gutjnl-2013-305490] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Although endoscopic surveillance of patients with Barrett's oesophagus has been widely implemented, its effectiveness is debateable. The recently reported low annual oesophageal adenocarcinoma risk in population studies, the failure to identify most Barrett's patients at risk of disease progression, the poor adherence to surveillance and biopsy protocols, and the significant risk of misclassification of dysplasia all tend to undermine the effectiveness of current management, in particular, endoscopic surveillance programmes, to prevent or improve the outcomes of patients with oesophageal adenocarcinoma. The ongoing increase in incidence of Barrett's oesophagus and consequent growth of the surveillance population, together with the associated discomfort and costs of endoscopic surveillance, demand improved techniques for accurately determining individual risk of oesophageal adenocarcinoma. More accurate techniques are needed to run efficient surveillance programmes in the coming decades. In this review, we will discuss the current knowledge on the epidemiology of Barrett's oesophagus, and the challenging epidemiological dilemmas that need to be addressed when assessing the current screening and surveillance strategies.
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Affiliation(s)
- Pieter Jan F de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, , Rotterdam, The Netherlands
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Sauk J, Coron E, Kava L, Suter M, Gora M, Gallagher K, Rosenberg M, Ananthakrishnan A, Nishioka N, Lauwers G, Woods K, Brugge W, Forcione D, Bouma BE, Tearney G. Interobserver agreement for the detection of Barrett's esophagus with optical frequency domain imaging. Dig Dis Sci 2013; 58:2261-5. [PMID: 23508980 PMCID: PMC3732518 DOI: 10.1007/s10620-013-2625-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2012] [Accepted: 02/26/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND Optical frequency domain imaging (OFDI) is a second-generation form of optical coherence tomography (OCT) providing comprehensive cross-sectional views of the distal esophagus at a resolution of ~7 μm. AIM Using validated OCT criteria for squamous mucosa, gastric cardia mucosa, and Barrett's esophagus (BE), the objective of this study was to determine the inter- and intra-observer agreements by a large number of OFDI readers for differentiating these tissues. METHODS OFDI images were obtained from nine subjects undergoing screening and surveillance for BE. Sixty-four OFDI image regions of interest were randomly selected for review. A training set of 19 images was compiled distinguishing squamous mucosa from gastric cardia and BE using previously validated OCT criteria. The ten readers then interpreted images in a test set of 45 different images of squamous mucosa (n = 15), gastric cardia (n = 15), or BE (n = 15). Interobserver agreement differentiating the three tissue types and BE versus non-BE mucosa was determined using multi-rater Fleiss's κ value. The images were later randomized again and four readers repeated the test 3 weeks later to assess intraobserver reliability. RESULTS All ten readers showed excellent agreement for the differentiation of BE versus non-BE mucosa (κ = 0.811 p < 0.0001) and for differentiating BE versus gastric cardia versus squamous mucosa (κ = 0.866, p < 0.0001). For the four readers who repeated the test, the median intraobserver agreement (BE vs. non-BE) was high (κ = 0.975, IQR: 0.94, 1.0). CONCLUSIONS Trained readers have a high interobserver agreement for differentiating BE, squamous, and gastric cardia mucosa using OFDI.
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Affiliation(s)
- J Sauk
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts,Gastroenterology Division, Massachusetts General Hospital; Boston, Massachusetts
| | - E Coron
- Department of Gastroenterology and Hepatology; University Hospital; Nantes, France
| | - L Kava
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts
| | - M Suter
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts
| | - M Gora
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts
| | - K Gallagher
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts
| | - M Rosenberg
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts
| | - A Ananthakrishnan
- Gastroenterology Division, Massachusetts General Hospital; Boston, Massachusetts
| | - N Nishioka
- Gastroenterology Division, Massachusetts General Hospital; Boston, Massachusetts
| | - G Lauwers
- Department of Pathology, Massachusetts General Hospital; Boston, Massachusetts
| | - K Woods
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts,Gastroenterology Division, Massachusetts General Hospital; Boston, Massachusetts,Digestive Diseases, Interventional Endoscopy, Emory University School of Medicine; Atlanta, Georgia
| | - W Brugge
- Gastroenterology Division, Massachusetts General Hospital; Boston, Massachusetts
| | - D Forcione
- Gastroenterology Division, Massachusetts General Hospital; Boston, Massachusetts
| | - BE Bouma
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts
| | - G Tearney
- Wellman Center for Photomedicine; Harvard Medical School; Massachusetts General Hospital; Boston, Massachusetts,Department of Pathology, Massachusetts General Hospital; Boston, Massachusetts
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Temporal trends of Barrett's oesophagus and gastro-oesophageal reflux and related oesophageal cancer over a 10-year period in England and Wales and associated proton pump inhibitor and H2RA prescriptions: a GPRD study. Eur J Gastroenterol Hepatol 2013; 25:15-21. [PMID: 23022985 DOI: 10.1097/meg.0b013e3283595086] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION There is an increasing burden of gastro-oesophageal reflux disease (GORD) and Barrett's oesophagus (BO), paralleled by an increasing incidence of oesophageal adenocarcinoma. METHODS Using the General Practice Research Database, we derived the incidence GORD and BO and incidence of oesophageal cancer (OC) populations, between 1996 and 2005. Acid suppression treatment over the study period was also studied. RESULTS There were 5860 patients with BO and 1 25 519 with GORD. The incidence of BO increased from 0.11 to 0.24/1000 men and from 0.06 to 0.11/1000 women. The incidence of GORD diagnosed in general practice remained stable. There were 69 incident OCs in patients with BOs and 183 incident OCs in patients with GORD occurring more than a year after the GORD diagnosis. The cumulative incidence of OC was 3.00/1000 BO patient years and 0.30/1000 GORD patient years. There was a progressive decrease in H2RA prescriptions from 39 to 14.5% and an increase in proton pump inhibitor prescriptions from 52 to 79% in patients with a new diagnosis of GORD. CONCLUSION The incidence of BO has doubled from 1996 to 2005, whereas the incidence of GORD has remained stable. OC occurred 10 times more commonly in patients with BO than those with GORD. Proton pump inhibitor prescribing increased gradually over the study period. These trends have significant implications for healthcare planning and financing in the UK and other countries.
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Prevalence and predictors of columnar lined esophagus in gastroesophageal reflux disease (GERD) patients undergoing upper endoscopy. Am J Gastroenterol 2012; 107:1655-61. [PMID: 23032983 DOI: 10.1038/ajg.2012.299] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Chronic gastroesophageal reflux disease (GERD) is a risk factor for Barrett's esophagus (BE), the most important surrogate marker for the development of esophageal adenocarcinoma (EAC). The need to document the presence of intestinal metaplasia in esophageal biopsies from a columnar lined esophagus (CLE) to diagnose BE is debated. The objective of this study was to prospectively evaluate the prevalence and risk factors of CLE in a large cohort of GERD patients undergoing upper endoscopy. METHODS Consecutive patients presenting to the endoscopy unit at a tertiary referral center for their index upper endoscopy for evaluation of GERD symptoms were enrolled in this prospective cohort study. Patients were asked to complete a validated GERD questionnaire that documents the onset of GERD symptoms (heartburn and acid regurgitation) and grades the frequency and severity of symptoms experienced over the past year. Demographic information, body mass index, and use of aspirin/nonsteroidal antiinflammatory drugs were recorded. Endoscopic details including length of CLE, presence and size of hiatal hernia were noted. Patients with CLE (cases) were compared with those without CLE (controls) using Fischer's exact test and t-test. All factors that were statistically significant (P<0.05) were then entered into stepwise logistic regression to evaluate for independent predictors of CLE. RESULTS A total of 1058 patients with GERD symptoms were prospectively enrolled. On index endoscopy, the prevalence of CLE was 23.3%, whereas of CLE with documented intestinal metaplasia was 14.1%. On univariate analysis, male gender, Caucasian race, heartburn duration of >5 years, presence and size of hiatal hernia were significantly associated with the presence of CLE compared with controls (P<0.05). On multivariate analysis, heartburn duration >5 years (odds ratio (OR): 1.50, 95% confidence interval (CI): 1.07-2.09, P=0.01), Caucasian race (OR: 2.40, 95% CI: 1.42-4.03, P=0.001), and hiatal hernia (OR: 2.07, 95% CI: 1.50-2.87, P<0.01) were found to be independent predictors for CLE. CLE length was significantly associated with the presence of intestinal metaplasia (P<0.001). CONCLUSIONS If BE is defined by the presence of CLE alone on upper endoscopy, up to 25% of GERD patients are diagnosed with this lesion. Enrolling all these patients in surveillance programs would have significant ramifications on health-care resources.
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Shariff MK, Bird-Lieberman EL, O'Donovan M, Abdullahi Z, Liu X, Blazeby J, Fitzgerald R. Randomized crossover study comparing efficacy of transnasal endoscopy with that of standard endoscopy to detect Barrett's esophagus. Gastrointest Endosc 2012; 75:954-961. [PMID: 22421496 DOI: 10.1016/j.gie.2012.01.029] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Accepted: 01/19/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Unsedated transnasal endoscopy (TNE) may be safer and less expensive than standard endoscopy (SE) for detecting Barrett's esophagus (BE). Emerging technologies require robust evaluation before routine use. OBJECTIVE To evaluate the sensitivity, specificity, and acceptability of TNE in diagnosing BE compared with those of SE. DESIGN Prospective, randomized, crossover study. SETTING Single, tertiary-care referral center. PATIENTS This study enrolled consecutive patients with BE or those referred for diagnostic assessment. INTERVENTION All patients underwent TNE followed by SE or the reverse. Spielberger State-Trait Anxiety Inventory short-form questionnaires, a visual analogue scale, and a single question addressing preference for endoscopy type were administered. MAIN OUTCOME MEASUREMENTS Diagnostic accuracy and tolerability of TNE were compared with those of SE. RESULTS Of 95 patients randomized, 82 completed the study. We correctly diagnosed 48 of 49 BE cases by TNE for endoscopic findings of columnar lined esophagus compared with the criterion standard, SE, giving a sensitivity and specificity of 0.98 and 1.00, respectively. The BE median length was 3 cm (interquartile range [IQR] 1-5 cm) with SE and 3 cm (IQR 2-4 cm) with TNE, giving high correlations between the two modalities (R(2) = 0.97; P < .001). The sensitivity and specificity for detecting intestinal metaplasia by TNE compared with those by SE was 0.91 and 1.00, respectively. The mean (± standard deviation) post-endoscopy Spielberger State-Trait Anxiety Inventory short-form score for TNE (30.0 ± 1.10 standard error of the mean [SEM]) was lower than that for SE (30.7 ± 1.29 SEM), (P = .054). The visual analogue scale scores were no different (P = .07). The majority of patients (59%) expressed a preference for TNE. LIMITATIONS This is a small study, with limited generalizability, a high prevalence of patients with BE, differential drop-out between the two procedures, and use of sedation. CONCLUSION TNE is an accurate and well-tolerated method for diagnosing BE compared with SE. TNE warrants further evaluation as a screening tool for BE.
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Affiliation(s)
- M Kareem Shariff
- MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Cambridge, United Kingdom
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Cook MB, Shaheen NJ, Anderson LA, Giffen C, Chow WH, Vaughan TL, Whiteman DC, Corley DA. Cigarette smoking increases risk of Barrett's esophagus: an analysis of the Barrett's and Esophageal Adenocarcinoma Consortium. Gastroenterology 2012; 142:744-53. [PMID: 22245667 PMCID: PMC3321098 DOI: 10.1053/j.gastro.2011.12.049] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2011] [Revised: 12/07/2011] [Accepted: 12/31/2011] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett's esophagus. We investigated whether tobacco smoking and other factors increase risk for Barrett's esophagus. METHODS We analyzed data from 5 case-control studies included in the international Barrett's and Esophageal Adenocarcinoma Consortium. We compared data from subjects with Barrett's esophagus (n = 1059) with those from subjects with gastroesophageal reflux disease (gastroesophageal reflux disease controls, n = 1332), and population-based controls (n = 1143), using multivariable logistic regression models to test associations with cigarette smoking. We also tested whether cigarette smoking has synergistic effects with other exposures, which might further increase risk for Barrett's esophagus. RESULTS Subjects with Barrett's esophagus were significantly more likely to have ever smoked cigarettes than the population-based controls (odds ratio [OR] = 1.67; 95% confidence interval [CI]: 1.04-2.67) or gastroesophageal reflux disease controls (OR = 1.61; 95% CI: 1.33-1.96). Increasing pack-years of smoking increased the risk for Barrett's esophagus. There was evidence of a synergy between ever-smoking and heartburn or regurgitation; the attributable proportion of disease among individuals who ever smoked and had heartburn or regurgitation was estimated to be 0.39 (95% CI: 0.25-0.52). CONCLUSIONS Cigarette smoking is a risk factor for Barrett's esophagus. The association was strengthened with increased exposure to smoking until ∼20 pack-years, when it began to plateau. Smoking has synergistic effects with heartburn or regurgitation, indicating that there are various pathways by which tobacco smoking might contribute to development of Barrett's esophagus.
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Affiliation(s)
| | | | | | | | - Wong-Ho Chow
- Division of Cancer Epidemiology and Genetics, NCI
| | - Thomas L. Vaughan
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA
| | | | - Douglas A. Corley
- Division of Research and Oakland Medical Center, Kaiser Permanente, CA
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Abstract
Gastroesophageal reflux (GER) affects ∼10-20% of American adults. Although symptoms are equally common in men and women, we hypothesized that sex influences diagnostic and therapeutic approaches in patients with GER. PubMed database between 1997 and October 2011 was searched for English language studies describing symptoms, consultative visits, endoscopic findings, use and results of ambulatory pH study, and surgical therapy for GER. Using data from Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, we determined the sex distribution for admissions and reflux surgery between 1997 and 2008. Studies on symptoms or consultative visits did not show sex-specific differences. Even though women are less likely to have esophagitis or Barrett's esophagus, endoscopic studies enrolled as many women as men, and women were more likely to undergo ambulatory pH studies with a female predominance in studies from the US. Surgical GER treatment is more commonly performed in men. However, studies from the US showed an equal sex distribution, with Nationwide Inpatient Sample data demonstrating an increase in women who accounted for 63% of the annual fundoplications in 2008. Despite less common or severe mucosal disease, women are more likely to undergo invasive diagnostic testing. In the US, women are also more likely to undergo antireflux surgery. These results suggest that healthcare-seeking behavior and socioeconomic factors rather than the biology of disease influence the clinical approaches to reflux disease.
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Sehdev V, Peng D, Soutto M, Washington MK, Revetta F, Ecsedy J, Zaika A, Rau TT, Schneider-Stock R, Belkhiri A, El-Rifai W. The aurora kinase A inhibitor MLN8237 enhances cisplatin-induced cell death in esophageal adenocarcinoma cells. Mol Cancer Ther 2012; 11:763-74. [PMID: 22302096 DOI: 10.1158/1535-7163.mct-11-0623] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal adenocarcinomas are poorly responsive to chemotherapeutics. This study aimed to determine the levels of Aurora kinase A (AURKA) and the therapeutic potential of MLN8237, an investigational AURKA inhibitor, alone and in combination with cisplatin. Using quantitative real-time PCR, we detected frequent AURKA gene amplification (15 of 34, 44%) and mRNA overexpression (37 of 44, 84%) in esophageal adenocarcinomas (P < 0.01). Immunohistochemical analysis showed overexpression of AURKA in more than two-thirds of esophageal adenocarcinoma tissue samples (92 of 132, 70%; P < 0.001). Using FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, with constitutive AURKA overexpression and mutant p53, we observed inhibition of colony formation with a single treatment of 0.5 μmol/L MLN8237 (P < 0.05). This effect was further enhanced in combination with 2.5 μmol/L cisplatin (P < 0.001). Twenty-four hours after treatment with the MLN8237 or MLN8237 and cisplatin, cell-cycle analyses showed a sharp increase in the percentage of polyploid cells (P < 0.001). This was followed by an increase in the percentage of cells in the sub-G(1) phase at 72 hours, concordant with the occurrence of cell death (P < 0.001). Western blot analysis showed higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP with the combined treatment, as compared with a single-agent treatment. Using xenograft models, we showed an enhanced antitumor role for the MLN8237 and cisplatin combination, as compared with single-agent treatments (P < 0.001). In conclusion, this study shows frequent overexpression of AURKA and suggests that MLN8237 could be an effective antitumor agent, which can be combined with cisplatin for a better therapeutic outcome in esophageal adenocarcinomas.
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Affiliation(s)
- Vikas Sehdev
- Department of Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2215 Garland Avenue, Nashville, TN 37232, USA
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Simonka Z, Paszt A, Abrahám S, Pieler J, Tajti J, Tiszlavicz L, Németh I, Izbéki F, Rosztóczy A, Wittmann T, Rárosi F, Lázár G. The effects of laparoscopic Nissen fundoplication on Barrett's esophagus: long-term results. Scand J Gastroenterol 2012; 47:13-21. [PMID: 22150083 DOI: 10.3109/00365521.2011.639081] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The aim of our study was to conduct a retrospective investigation of the efficacy of laparoscopic Nissen fundoplication in patients with Barrett's esophagus. MATERIAL AND METHODS A total of 78 patients with Barrett's esophagus underwent surgery. Patients were divided into three groups on the basis of the preoperative endoscopic biopsies: a non-intestinal group (n = 63) with fundic or cardiac metaplasia, an intestinal group (n = 18) with intestinal metaplasia, and a dysplastic group (n = 7) with low-grade dysplasia. Clinical follow-up was available in the case of 64 patients at a mean of 42 ± 16.9 months after surgery. RESULTS Check-up examination revealed total regression of Barrett's metaplasia in 10 patients. Partial regression was seen in 9 cases, no further progression in 34 patients, and progression into cardiac or intestinal metaplasia in 11 patients. No cases of dysplastic or malignant transformation were registered. Where we observed the regression of BE, among the postoperative functional examinations results of manometry (pressure of lower esophageal sphincter) and pH-metry were significantly better compared with those groups where no changes occurred in BE, or progression of BE was found. Discussion. Our results highlight the importance of the cases of fundic and cardiac metaplasia, which can also transform into intestinal metaplasia. CONCLUSIONS Antireflux surgery can appropriately control the reflux disease in a majority of the patients who had unsuccessful medical treatment, and it may inhibit the progression and induce the regression of Barrett's metaplasia in a significant proportion of these patients.
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Affiliation(s)
- Zsolt Simonka
- Department of Surgery, University of Szeged, Szeged, Hungary
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Chang JY, Talley NJ, Locke GR, Katzka DA, Schleck CD, Zinsmeister AR, Dunagan KT, Wu TT, Wang KK, Prasad GA. Population screening for barrett esophagus: a prospective randomized pilot study. Mayo Clin Proc 2011; 86:1174-80. [PMID: 22134936 PMCID: PMC3228617 DOI: 10.4065/mcp.2011.0396] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To assess the feasibility of unsedated transnasal endoscopy (uTNE) and video capsule endoscopy (VCE) as alternatives to sedated endoscopy (sEGD) as screening tools for Barrett esophagus (BE) and to obtain preliminary estimates of participation rates for sEGD, uTNE, and VCE when used for community BE screening in a population cohort. PATIENTS AND METHODS From February 1, 2009, to May 31, 2010, patients from Olmsted County, Minnesota, who were older than 50 years and had no history of known BE were randomized (stratified by age, sex, reflux symptoms noted in a validated questionnaire) into 3 groups for esophageal evaluation with sEGD, uTNE, or VCE. Participation rates and safety profiles were estimated. RESULTS We contacted 127 patients to recruit 20 for each procedure arm (60 total). The probability of participation was 38% (95% confidence interval [CI], 26%-51%) for sEGD, 50% (95% CI, 35%-65%) for uTNE, and 59% (95% CI, 42%-74%) for VCE. Both uTNE and VCE were well tolerated without adverse effects. BE was identified in 3 patients and esophagitis in 8. CONCLUSION Unsedated techniques may be acceptable, feasible, and safe alternatives to sEGD to screen for BE in the community. TRIAL REGISTRATION clinicaltrials.gov identifier: NCT00943280.
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Affiliation(s)
- Joseph Y Chang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
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Kadri S, Lao-Sirieix P, Fitzgerald RC. Developing a nonendoscopic screening test for Barrett's esophagus. Biomark Med 2011; 5:397-404. [PMID: 21657849 DOI: 10.2217/bmm.11.40] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Barrett's esophagus (BE) arises as a complication of chronic gastro-esophageal reflux disease and is the precursor lesion for esophageal adenocarcinoma. The prevalence of esophageal adenocarcinoma has been increasing in Western countries and the overall prognosis from this cancer remains dismal. Surveillance for BE is highly controversial since although early cancer detection through surveillance programs benefits individuals, surveillance has not been proven to reduce population mortality from the disease. One factor contributing to this apparent paradox is that an estimated >80% cases of BE are undiagnosed and, therefore, do not have the benefit of surveillance. Some form of screening modality is required to achieve more comprehensive detection of BE, which in turn, may lead to early detection of cancerous lesions and early intervention in order to reduce progression to invasive and symptomatic cancer. The advent of endoscopic therapy makes this paradigm attractive. A number of methods could be considered for screening. These include a nonendoscopic sampling method using a Cytosponge that needs to be coupled with a biomarker to obtain required levels of sensitivity and specificity. For screening to be recommended consideration needs to be given to the point of delivery, cost and acceptability to patients.
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Affiliation(s)
- Sudarshan Kadri
- MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Cambridge, UK
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Schouten LJ, Steevens J, Huysentruyt CJR, Coffeng CE, Keulemans YCA, van Leeuwen FE, Driessen ALC, van den Brandt PA. Total cancer incidence and overall mortality are not increased among patients with Barrett's esophagus. Clin Gastroenterol Hepatol 2011; 9:754-61. [PMID: 21570484 DOI: 10.1016/j.cgh.2011.04.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2011] [Revised: 03/30/2011] [Accepted: 04/05/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Barrett's esophagus (BE) increases risk for esophageal adenocarcinoma, but it is not clear how it affects risk for other cancers or overall mortality. We analyzed data from a population-based cohort of subjects with BE. METHODS The Netherlands Cohort Study was initiated in 1986 and included 120,852 participants (55-69 years old at baseline). Until December 2002, 626 incident cases of BE (excluding nonintestinal metaplasia) were identified by record linkage with the nationwide Pathology Registry. This cohort was followed for a median period of 5.7 years; data on cancer and mortality were obtained from record linkage to the Netherlands Cancer Registry and Statistics Netherlands. The expected number of cases was calculated using national cancer incidence and mortality data. RESULTS In the BE cohort, 13 individuals developed esophageal cancer and 5 developed gastric cancer. The ratio of observed:expected (O:E) incidence of esophageal and gastric cancer was 10.0 (95% confidence interval [CI], 5.3-17.1) and 1.8 (95% CI, 0.6-4.2), respectively. Total cancer incidence (excluding esophageal and gastric cancer) increased in the BE cohort, although not by a statistically significant amount (O:E, 1.3; 95% CI, 1.0-1.6). Of cancer subtypes, incidences of small intestinal and pancreatic cancer increased in subjects with BE, but not by a statistically significant amount, after exclusion of data from the first 6 months of follow-up. During the follow-up period, 225 individuals with BE died. Mortality from all causes (excluding esophageal and gastric cancer) was not increased among subjects with BE (O:E, 1.0; 95% CI, 0.9-1.2), nor was mortality from specific causes of death. CONCLUSIONS The incidence of esophageal cancer was increased in a population-based cohort of subjects with BE. However, when esophageal and gastric cancers were excluded, total cancer incidence and overall mortality were not increased among subjects with BE.
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Affiliation(s)
- Leo J Schouten
- Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
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Coleman HG, Bhat S, Murray LJ, McManus D, Gavin AT, Johnston BT. Increasing incidence of Barrett's oesophagus: a population-based study. Eur J Epidemiol 2011; 26:739-745. [PMID: 21671079 DOI: 10.1007/s10654-011-9596-z] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2011] [Accepted: 06/01/2011] [Indexed: 12/20/2022]
Abstract
Oesophageal adenocarcinoma, a highly fatal cancer, has risen in incidence in Western societies, but it is unclear whether this is due to increasing incidence of its pre-cursor condition, Barrett's oesophagus (BO) or whether the proportion of BO patients undergoing malignant progression has increased in the face of unchanged BO incidence. Data from population-based studies of BO incidence is limited, with equivocal results to date difficult to distinguish from changes in endoscopic practices. The aim of this study was to assess population trends in Barrett's oesophagus (BO) diagnoses in relation to endoscopy and biopsy rates over a 13 year period. The Northern Ireland Barrett's oesophagus Register (NIBR) is a population-based register of all 9,329 adults diagnosed with columnar epithelium of the oesophagus in Northern Ireland between 1993 and 2005, of whom 58.3% were male. European age-standardised annual BO incidence rates were calculated per 100,000 of the population, per 100 endoscopies and per 100 endoscopies including an oesophageal biopsy. Average annual BO incidence rates rose by 159% during the study period, increasing from 23.9/100,000 during 1993-1997 to 62.0/100,000 during 2002-2005. This elevation far exceeded corresponding increases in rates of endoscopies and oesophageal biopsies being conducted. BO incidence increased most markedly in individuals aged < 60 years, and most notably amongst males aged < 40 years. This study points towards a true increase in the incidence of BO which would appear to be most marked in young males. These findings have significant implications for future rates of oesophageal adenocarcinoma and surveillance programmes.
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Affiliation(s)
- Helen G Coleman
- Cancer Epidemiology & Health Services Research Group, Centre for Public Health, Queen's University Belfast, Northern Ireland, UK.
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Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study. Am J Gastroenterol 2011; 106:1447-55; quiz 1456. [PMID: 21483461 PMCID: PMC3150349 DOI: 10.1038/ajg.2011.130] [Citation(s) in RCA: 149] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Population-based data on the epidemiology and outcomes of subjects with intestinal metaplasia of the gastroesophageal junction (IMGEJ) and Barrett's esophagus (BE) are limited. The objectives of this study were to (i) estimate the incidence of IMGEJ and BE diagnosed from clinically indicated endoscopy in Olmsted County, MN, over three decades (1976-2006) and prevalence as of 1 January 2007, (ii) compare baseline characteristics of subjects with IMGEJ and BE, and (iii) study the natural history and survival of both cohorts. METHODS This was a population-based cohort study. The study setting was Olmsted County, MN. Patients with BE (columnar segment >1 cm with intestinal metaplasia) and IMGEJ (intestinal metaplasia in biopsies from the gastroesophageal junction) from 1976 to 2006 in Olmsted County, MN, were identified using Rochester Epidemiology Project resources. Demographic and clinical data were abstracted from medical records and pathology confirmed by gastrointestinal pathologists. The association of baseline characteristics with overall and progression-free survival was assessed using proportional hazards regression models. Outcome measures were baseline characteristics and overall survival of subjects with IMGEJ compared to those with BE. RESULTS In all, 487 patients (401 with BE and 86 with IMGEJ) were identified and followed for a median interval of 7 (BE subjects) to 8 (IMGEJ subjects) years. Subjects with BE were older, heavier, reported reflux symptoms more often, and had higher prevalence of advanced neoplasia than those with IMGEJ. No patient with IMGEJ progressed to esophageal adenocarcinoma (EAC) in contrast to BE subjects who had a cumulative risk of progression of 7% at 10 years and increased risk of death from EAC (standardized mortality ratio 9.62). The overall survival of subjects with BE and IMGEJ did not differ from that expected in similar age- and sex-distributed white Minnesota populations. CONCLUSIONS Subjects with IMGEJ appear to have distinct clinical characteristics and substantially lower cancer progression risk compared to those with BE.
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Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, Murray LJ. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst 2011; 103:1049-1057. [PMID: 21680910 PMCID: PMC3632011 DOI: 10.1093/jnci/djr203] [Citation(s) in RCA: 513] [Impact Index Per Article: 36.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Revised: 05/09/2011] [Accepted: 05/09/2011] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005. SUBJECTS AND METHODS We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests. RESULTS After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P < .001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P < .001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P < .001). CONCLUSION We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective.
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Affiliation(s)
- Shivaram Bhat
- Centre for Public Health, Queens University Belfast, Institute of Clinical Sciences Building, Belfast BT12 6BA, Northern Ireland, UK.
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Mathew P, Joshi AS, Shukla A, Bhatia SJ. Risk factors for Barrett's esophagus in Indian patients with gastroesophageal reflux disease. J Gastroenterol Hepatol 2011; 26:1151-6. [PMID: 21375585 DOI: 10.1111/j.1440-1746.2011.06714.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Barrett's esophagus (BE) is reported to be infrequent in Asians, with no data from India regarding its prevalence and risk factors. We investigated the frequency and risk factors of columnar mucosa with or without specialized intestinal metaplasia (SIM) in Indian patients with gastroesophageal reflux disease (GERD). METHODS A total of 278 GERD patients over 2 years underwent gastroscopy and completed a questionnaire for possible BE risk factors. Patients with columnar mucosa on endoscopy underwent four-quadrant biopsy; BE was histologically defined as columnar mucosa with or without SIM. Patients without columnar mucosa at endoscopy were considered as controls and compared to patients with BE and those with SIM. RESULTS Forty-six patients with GERD had columnar mucosa on histology (16.54%); 25 (8.99%) of these had SIM. The risk factors for BE were the presence of hiatus hernia (odds ratio [OR]: 3.14; 95% confidence interval [CI]: 1.2-8.17) and a history of eructation (OR: 2.28; CI: 1.11-4.66). The risk factors for SIM were age ≥ 45 years (OR: 2.63; CI: 1.03-6.71), hiatus hernia (OR: 3.95; CI: 1.24-12.56), and a history of eructation (OR: 3.41; CI: 1.19-9.78). Sex, severity of symptoms, dietary factors, tobacco or alcohol use, and body mass index were not associated with BE. The median circumferential segment length was 2 (1-10) cm, and the maximal length was 3 (2-11) cm in both groups. CONCLUSION BE is not an uncommon finding among Indian GERD patients. Age ≥ 45 years, history of eructation, and the presence of hiatus hernia are associated with SIM.
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Affiliation(s)
- Praveen Mathew
- Department of Gastroenterology, Seth GS Medical College and King Edward Memorial Hospital, Mumbai, India
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Jacobson BC, Giovannucci EL, Fuchs CS. Smoking and Barrett's esophagus in women who undergo upper endoscopy. Dig Dis Sci 2011; 56:1707-17. [PMID: 21448698 PMCID: PMC3100531 DOI: 10.1007/s10620-011-1672-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2010] [Accepted: 03/08/2011] [Indexed: 01/11/2023]
Abstract
BACKGROUND Cigarette use is associated with esophageal adenocarcinoma, and cross-sectional studies suggest an association between smoking and Barrett's esophagus. AIMS We sought to examine prospectively the effect of smoking on the risk for Barrett's esophagus. METHODS This was a prospective cohort study among 20,863 women within the Nurses' Health Study who underwent upper gastrointestinal endoscopy for any reason between 1980 and 2006. We assessed the association between smoking and pathologically-confirmed Barrett's esophagus (n = 377). Self-reported data on smoking and potential confounding variables were collected from biennial questionnaires. RESULTS Compared with women who never smoked, former smokers of 1-24 cigarettes/day had a multivariate odds ratio for Barrett's esophagus of 1.25 (95% CI 0.99-1.59), former smokers of ≥ 25 cigarettes/day had a multivariate odds ratio of 1.52 (95% CI 1.04-2.22), current smokers of 1-24 cigarettes/day had a multivariate odds ratio of 0.89 (95% CI 0.54-1.45), and current smokers of ≥ 25 cigarettes/day had a multivariate odds ratio of 0.92 (95% CI 0.34-2.54). The risk for Barrett's esophagus increased significantly with increasing pack-years smoked among former (P = 0.008) but not current smokers (P = 0.99), especially when considering exposure ≥ 25 years before index endoscopy. Results were similar among women reporting regular heartburn/acid-reflux one or more times a week, and were not accounted for by changes in weight. CONCLUSIONS Heavy, remote smoking is associated with an increased risk for Barrett's esophagus. This finding suggests a long latency period between exposure and development of the disease, even after discontinuation of smoking.
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