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Authors, Collaborators. S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1786-1852. [PMID: 39389106 DOI: 10.1055/a-2344-6282] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
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Black EL, Ococks E, Devonshire G, Ng AWT, O'Donovan M, Malhotra S, Tripathi M, Miremadi A, Freeman A, Coles H, Fitzgerald RC. Understanding the malignant potential of gastric metaplasia of the oesophagus and its relevance to Barrett's oesophagus surveillance: individual-level data analysis. Gut 2024; 73:729-740. [PMID: 37989565 PMCID: PMC11041591 DOI: 10.1136/gutjnl-2023-330721] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 11/01/2023] [Indexed: 11/23/2023]
Abstract
OBJECTIVE Whether gastric metaplasia (GM) of the oesophagus should be considered as Barrett's oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance. DESIGN We performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC). RESULTS We found that 58 of 77 short-segment (<3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was significantly lower than in the IM-only cases (Kaplan-Meier, p=0.03). Genomic analysis revealed that the mutation burden in GM is significantly lower than in IM (p<0.01). Moreover, GM does not bear the mutational hallmarks of OAC, with an absence of associated signatures and driver gene mutations. Finally, we established that GM found adjacent to OAC is evolutionarily distant from cancer. CONCLUSION SS-GM is a distinct entity from SS-IM and the malignant potential of GM is lower than IM. It is questionable whether SS-GM warrants inclusion in BO surveillance.
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Affiliation(s)
- Emily L Black
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Emma Ococks
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Ginny Devonshire
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | - Alvin Wei Tian Ng
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | - Maria O'Donovan
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Shalini Malhotra
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Monika Tripathi
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Ahmad Miremadi
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Adam Freeman
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Hannah Coles
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Rebecca C Fitzgerald
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK
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Autorinnen/Autoren, Collaborators:. S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:862-933. [PMID: 37494073 DOI: 10.1055/a-2060-1069] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
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Beydoun AS, Stabenau KA, Altman KW, Johnston N. Cancer Risk in Barrett's Esophagus: A Clinical Review. Int J Mol Sci 2023; 24:ijms24076018. [PMID: 37046992 PMCID: PMC10094310 DOI: 10.3390/ijms24076018] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/21/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence and is associated with a poor prognosis. Barrett's esophagus (BE) is a known precursor of esophageal adenocarcinoma. This review aims to explore Barrett's esophagus, esophageal adenocarcinoma, and the progression from the former to the latter. An overview of the definition, diagnosis, epidemiology, and risk factors for both entities are presented, with special attention being given to the areas of debate in the literature. The progression from Barrett's esophagus to esophageal adenocarcinoma is reviewed and the relevant molecular pathways are discussed. The definition of Barrett's esophagus remains debated and without international consensus. This, alongside other factors, has made establishing the true prevalence of Barrett's esophagus challenging. The degree of dysplasia can be a histological challenge, but is necessary to guide clinical management. The progression of BE to EAC is likely driven by inflammatory pathways, pepsin exposure, upregulation of growth factor pathways, and mitochondrial changes. Surveillance is maintained through serial endoscopic evaluation, with shorter intervals recommended for high-risk features.
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Affiliation(s)
- Ahmed Sam Beydoun
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Kaleigh A Stabenau
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Kenneth W Altman
- Department of Otolaryngology-Head & Neck Surgery, Geisinger Medical Center, Danville, PA 17822, USA
| | - Nikki Johnston
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol 2022; 117:559-587. [PMID: 35354777 DOI: 10.14309/ajg.0000000000001680] [Citation(s) in RCA: 229] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 02/04/2022] [Indexed: 02/07/2023]
Abstract
Barrett's esophagus (BE) is a common condition associated with chronic gastroesophageal reflux disease. BE is the only known precursor to esophageal adenocarcinoma, a highly lethal cancer with an increasing incidence over the last 5 decades. These revised guidelines implement Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the definition and diagnosis of BE, screening for BE and esophageal adenocarcinoma, surveillance of patients with known BE, and the medical and endoscopic treatment of BE and its associated early neoplasia. Important changes since the previous iteration of this guideline include a broadening of acceptable screening modalities for BE to include nonendoscopic methods, liberalized intervals for surveillance of short-segment BE, and volume criteria for endoscopic therapy centers for BE. We recommend endoscopic eradication therapy for patients with BE and high-grade dysplasia and those with BE and low-grade dysplasia. We propose structured surveillance intervals for patients with dysplastic BE after successful ablation based on the baseline degree of dysplasia. We could not make recommendations regarding chemoprevention or use of biomarkers in routine practice due to insufficient data.
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Ishimura N, Okimoto E, Shibagaki K, Ishihara S. Endoscopic diagnosis and screening of Barrett's esophagus: Inconsistency of diagnostic criteria between Japan and Western countries. DEN OPEN 2022; 2:e73. [PMID: 35310704 PMCID: PMC8828243 DOI: 10.1002/deo2.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/10/2021] [Accepted: 10/16/2021] [Indexed: 11/11/2022]
Abstract
Barrett's esophagus (BE) is an endoscopically identifiable premalignant condition for esophageal adenocarcinoma (EAC). To diagnose BE precisely, careful inspection of the anatomic landmarks, including the esophagogastric junction and the squamocolumnar junction is important. The distal end of the palisade vessels and the proximal end of the gastric folds are used as the landmark of the esophagogastric junction in endoscopic diagnosis, with the latter solely used internationally, except in some Asian countries, including Japan. In addition, the diagnostic criteria adopted internationally for BE are inconsistent, particularly between Japan and Western countries. Recently updated guidelines in Western countries have included length criteria, with a 1‐cm threshold of columnar epithelium by endoscopic observation and/or histologic confirmation of the presence of specialized intestinal metaplasia. Since BE is endoscopically diagnosed at any length without histologic assessment in Japan, the reported prevalence of short‐segment BE is very high in Japan compared with that in Western countries. Although guidelines on screening exist for BE, the current strategies based on the presence of chronic gastroesophageal reflux disease with multiple risk factors may miss the opportunity for early detection of EAC. Indeed, up to 40% of patients with EAC have no history of chronic gastroesophageal reflux disease. To discuss BE on the same footing worldwide, standardization of diagnostic criteria, screening indication, and establishment of effective techniques for detecting dysplastic lesions are eagerly awaited. Japanese guidelines for BE should be revised regarding the length criteria, including the minimum length and long‐segment BE, in line with the recently updated Western guidelines.
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Affiliation(s)
- Norihisa Ishimura
- Second Department of Internal Medicine Shimane University Faculty of Medicine Shimane Japan
| | - Eiko Okimoto
- Second Department of Internal Medicine Shimane University Faculty of Medicine Shimane Japan
| | - Kotaro Shibagaki
- Division of Gastrointestinal Endoscopy Shimane University Hospital Shimane Japan
| | - Shunji Ishihara
- Second Department of Internal Medicine Shimane University Faculty of Medicine Shimane Japan
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Tullie L, Kelay A, Bethell GS, Major C, Hall NJ. Barrett's oesophagus and oesophageal cancer following oesophageal atresia repair: a systematic review. BJS Open 2021; 5:6346856. [PMID: 34370830 PMCID: PMC8405903 DOI: 10.1093/bjsopen/zrab069] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/17/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Concern exists that patients born with oesophageal atresia (OA) may be at high risk for Barrett's oesophagus (BO), a known malignant precursor to the development of oesophageal adenocarcinoma. Screening endoscopy has a role in early BO identification but is not universal in this population. This study aimed to determine prevalence of BO after OA repair surgery, to quantify the magnitude of this association and inform the need for screening and surveillance. METHODS A systematic review, undertaken according to PRISMA guidelines, was preregistered on PROSPERO (CRD42017081001). PubMed and EMBASE were interrogated using a standardized search strategy on 31 July 2020. Included papers, published in English, reported either: one or more patients with either BO (gastric/intestinal metaplasia) or oesophageal cancer in patients born with OA; or long-term (greater than 2 years) follow-up after OA surgery with or without endoscopic screening or surveillance. RESULTS Some 134 studies were identified, including 19 case reports or series and 115 single- or multi-centre cohort studies. There were 13 cases of oesophageal cancer (9 squamous cell carcinoma, 4 adenocarcinoma) with a mean age at diagnosis of 40.5 (range 20-47) years. From 6282 patients under long-term follow-up, 317 patients with BO were reported. Overall prevalence of BO was 5.0 (95 per cent c.i. 4.5 to 5.6) per cent, with a mean age at detection of 13.8 years (range 8 months to 56 years). Prevalence of BO in series reporting endoscopic screening or surveillance was 12.8 (95 per cent c.i. 11.3 to 14.5) per cent. CONCLUSION Despite a limited number of cancers, the prevalence of BO in patients born with OA is relatively high. While limited by the quality of available evidence, this review suggests endoscopic screening and surveillance may be warranted, but uncertainties remain over the design and effectiveness of any putative programme.
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Affiliation(s)
- L Tullie
- Department of Paediatric Surgery and Urology, Southampton Children's Hospital, Southampton, UK.,National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London Great Ormond Street Institute for Child Health, London, UK.,Stem Cell and Cancer Biology Laboratory, The Francis Crick Institute, London, UK
| | - A Kelay
- Department of Paediatric Surgery and Urology, Southampton Children's Hospital, Southampton, UK
| | - G S Bethell
- Department of Paediatric Surgery and Urology, Southampton Children's Hospital, Southampton, UK.,University Surgery Unit, Faculty of Medicine, University of Southampton, Southampton, UK
| | - C Major
- Department of Paediatric Surgery and Urology, Southampton Children's Hospital, Southampton, UK
| | - N J Hall
- Department of Paediatric Surgery and Urology, Southampton Children's Hospital, Southampton, UK.,University Surgery Unit, Faculty of Medicine, University of Southampton, Southampton, UK
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Loughrey MB, Shepherd NA. The indications for biopsy in routine upper gastrointestinal endoscopy. Histopathology 2020; 78:215-227. [PMID: 33382487 DOI: 10.1111/his.14213] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 07/15/2020] [Indexed: 12/11/2022]
Abstract
This review describes the indications and contraindications for endoscopic biopsy, in routine practice, of the upper gastrointestinal (GI) tract. We accept that this review provides grounds for controversy, as our stance in certain situations is counter to some national guidelines. Nevertheless, we provide evidence to support our viewpoints, especially on efficiency and economic grounds. We describe the particular controversies concerning the biopsy assessment of Barrett's oesophagus, chronic gastritis and the duodenum in the investigation of coeliac disease. We accept that there are indications for more extensive upper GI biopsy protocols in children than in adults; the latter constitute our main focus in this article. We would encourage detailed discussion between pathologists and their endoscopy colleagues about the indications, or lack of them, for routine upper GI endoscopic biopsy, as studies have shown that adherence to agreed guidelines has resulted in a very considerable diminution in the biopsy workload without compromising patient management. Furthermore, where biopsy is indicated, we emphasise the importance of accompanying clinical information provided to the pathologist, in particular regarding biopsy site(s), and regular feedback to endoscopists to improve and maintain the quality of such information. Finally, local dialogue is also advised, when necessary, to indicate to endoscopists the need to appropriately segregate biopsies into separate, individually labelled specimens, to maximise the information that can be derived by pathological evaluation and thereby improve the quality of the final pathology report.
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Affiliation(s)
- Maurice B Loughrey
- Department of Cellular Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK
| | - Neil A Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, UK
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Huang Q, Read M, Gold JS, Zou XP. Unraveling the identity of gastric cardiac cancer. J Dig Dis 2020; 21:674-686. [PMID: 32975049 DOI: 10.1111/1751-2980.12945] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 08/11/2020] [Accepted: 09/21/2020] [Indexed: 12/11/2022]
Abstract
The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC.
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Affiliation(s)
- Qin Huang
- Department of Pathology, Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China.,Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Matthew Read
- Department of Surgery, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Jason S Gold
- Department of Surgery, Veterans Affairs Boston Healthcare System, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Xiao Ping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
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Badgery H, Chong L, Iich E, Huang Q, Georgy SR, Wang DH, Read M. Recent insights into the biology of Barrett's esophagus. Ann N Y Acad Sci 2020; 1481:198-209. [PMID: 32681541 DOI: 10.1111/nyas.14432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/04/2020] [Accepted: 06/17/2020] [Indexed: 12/21/2022]
Abstract
Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), an aggressive cancer with a poor prognosis. Our understanding of the pathogenesis and Barrett's metaplasia is incomplete, and this has limited the development of new therapeutic targets and agents, risk stratification ability, and management strategies. This review outlines current insights into the biology of BE and addresses controversies surrounding cell of origin, cellular reprogramming theories, updates on esophageal epithelial barrier function, and the significance of goblet cell metaplasia and its association with malignant change. Further research into the basic biology of BE is vital as it will underpin novel therapies and improve our ability to predict malignant progression and help identify the minority of patients who will develop EAC.
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Affiliation(s)
- Henry Badgery
- Department of Upper Gastrointestinal Surgery, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Lynn Chong
- Department of Upper Gastrointestinal Surgery, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Elhadi Iich
- Cancer Biology and Surgical Oncology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Qin Huang
- Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System and Harvard Medical School, West Roxbury, Massachusetts
| | - Smitha Rose Georgy
- Department of Anatomic Pathology, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - David H Wang
- Department of Hematology and Oncology, UT Southwestern Medical Centre and VA North Texas Health Care System, Dallas, Texas
| | - Matthew Read
- Department of Upper Gastrointestinal Surgery, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Surgery, The University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia
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Que J, Garman KS, Souza RF, Spechler SJ. Pathogenesis and Cells of Origin of Barrett's Esophagus. Gastroenterology 2019; 157:349-364.e1. [PMID: 31082367 PMCID: PMC6650338 DOI: 10.1053/j.gastro.2019.03.072] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 03/22/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023]
Abstract
In patients with Barrett's esophagus (BE), metaplastic columnar mucosa containing epithelial cells with gastric and intestinal features replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease. This condition is estimated to affect 5.6% of adults in the United States, and is a major risk factor for esophageal adenocarcinoma. Despite the prevalence and importance of BE, its pathogenesis is incompletely understood and there are disagreements over the cells of origin. We review mechanisms of BE pathogenesis, including transdifferentiation and transcommitment, and discuss potential cells of origin, including basal cells of the squamous epithelium, cells of esophageal submucosal glands and their ducts, cells of the proximal stomach, and specialized populations of cells at the esophagogastric junction (residual embryonic cells and transitional basal cells). We discuss the concept of metaplasia as a wound-healing response, and how cardiac mucosa might be the precursor of the intestinal metaplasia of BE. Finally, we discuss shortcomings in current diagnostic criteria for BE that have important clinical implications.
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Affiliation(s)
- Jianwen Que
- Division of Digestive and Liver Diseases and Center for Human Development, Department of Medicine, Columbia University, New York, New York.
| | - Katherine S. Garman
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine. Durham, NC
| | - Rhonda F. Souza
- Center for Esophageal Diseases, Department of Medicine, Baylor University Medical Center at Dallas, and Center for Esophageal Research, Department of Medicine, Baylor Scott & White Research Institute, Dallas, TX
| | - Stuart Jon Spechler
- Center for Esophageal Diseases, Department of Medicine, Baylor University Medical Center at Dallas, Dallas, Texas; Center for Esophageal Research, Department of Medicine, Baylor Scott & White Research Institute, Dallas, Texas.
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Peters Y, Honing J, Kievit W, Kestens C, Pestman W, Nagtegaal ID, van der Post RS, Siersema PD. Incidence of Progression of Persistent Nondysplastic Barrett's Esophagus to Malignancy. Clin Gastroenterol Hepatol 2019; 17:869-877.e5. [PMID: 30213587 DOI: 10.1016/j.cgh.2018.08.033] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 07/23/2018] [Accepted: 08/09/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The risk of esophageal adenocarcinoma (EAC) in patients with non-dysplastic Barrett's esophagus (NDBE) is low, so there is debate over the role of ongoing surveillance for patients with NDBE. It is important to identify patients at low risk for progression. We assessed cancer risk based on the subsequent number of endoscopies showing persistence of NDBE in a nationwide study in the Netherlands. METHODS In a population-based study, patients with a first diagnosis of NDBE were selected from the Dutch nationwide registry of histopathology. We calculated incidence rates and incidence rate ratios (IRR) for high-grade dysplasia (HGD) and EAC to determine whether the number of endoscopies negative for dysplasia and the persistence of NDBE over time associate with progression to malignancy. RESULTS We identified 12,728 patients with NDBE during 2003 and 2013. HGD or EAC developed in 436 patients (3.4%) during 64,537 person-years of follow up (median, 4.9 years). The rate of progression to HGD or EAC was 0.68 (95% CI, 0.61-0.74) per 100 person-years. In patients with 2 consecutive endoscopies showing NDBE, the rate of progression to HGD or EAC decreased to 0.55 (95% CI, 0.46-0.64) per 100 person-years (IRR, 0.72; 95% CI, 0.60-0.87). Overall, the incidence of HGD or EAC decreased by 14% for each year of progression-free follow-up (IRR, 0.86; 95% CI, 0.81-0.92). CONCLUSION In a population-based study in the Netherlands, we found patients with stable NDBE to have a low risk of progression to HGD or EAC. These findings indicate that surveillance intervals might be lengthened or even discontinued in subgroups patients with persistent NDBE.
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Affiliation(s)
- Yonne Peters
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.
| | - Judith Honing
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Wietske Kievit
- Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Christine Kestens
- Department of Gastroenterology and Hepatology, UMC Utrecht, Utrecht, the Netherlands
| | - Wiebe Pestman
- Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Rachel S van der Post
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
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Abstract
This review has provided a summary of the biology of goblet cell metaplasia in CLE as it pertains to BE. Goblet cells are terminally differentiated nonproliferative cells that have many overlapping histochemical characteristics with mucinous columnar cells and pseudogoblet cells. There is an abundance of evidence that suggests that use of goblet cells as a biomarker of BE, and its progression to malignancy, is problematic. Some of these limitations include the fact that the background non-goblet epithelium in most patients with CLE is biologically intestinalized and contains molecular abnormalities similar to goblet cell CLE, goblet cells fluctuate with time and decrease in number with progression of neoplasia, and pathologists have problems with interpretation, and distinction, of goblet cells from other types of cells in the esophagus. Sampling error results in sensitivity and specificity issues that limit its positive predictive value. Goblet cells are fewest in number in the same population of patients with CLE that are hardest to detect endoscopically (i.e., those with short or ultrashort CLE). Nevertheless, the risk of cancer in patients with short-segment BE, a condition difficult to distinguish from the stomach, is very low regardless of the presence or absence of goblet cells so it is unclear what the role of goblet cells is in these patients as a biomarker. Nevertheless, if the answer to the following question, "Would you as a gastroenterologist recommend surveillance for a patient with clear endoscopic evidence of CLE, particularly if it is ≥ 3 cm in length, but in which goblet cells were not reported to be present by the pathologist," is yes, then the US requirement for goblet cells as part of the criteria for "BE" is superfluous.
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Abstract
Over the past two decades, evidence has accumulated to challenge the traditional view that cardiac mucosa, which is comprised exclusively of mucus glands, is the normal lining of the most proximal portion of the stomach (the gastric cardia). There is now considerable evidence to suggest that cardiac mucosa develops as a GERD-induced, squamous-to-columnar esophageal metaplasia in some, if not all, cases. Although cardiac mucosa lacks the goblet cells commonly required for a histologic diagnosis of intestinal metaplasia, cardiac mucosa has many molecular features of an intestinal-type mucosa, and appears to be the precursor of intestinal metaplasia with goblet cells. In apparently normal individuals, cardiac mucosa is commonly found in a narrow band, less than 3 mm in extent, on the columnar side of the squamo-columnar junction at the end of the esophagus. A greater extent of cardiac mucosa can be found in GERD patients, and the magnitude of that extent appears to be an index of GERD severity. Presently, the risk of adenocarcinoma imposed by cardiac mucosa is not clear, but appears to be far less than that of intestinal metaplasis with goblet cells. The British Society of Gastroenterology accepts an esophagus lined by cardiac mucosa as a "Barrett's esophagus". However, if one defines Barrett's esophagus as a metaplasia that predisposes to cancer, then only intestinal metaplasia clearly fulfills that criterion at this time. Well-designed, prospective studies are needed to establish the malignant potential of cardiac mucosa.
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Bellizzi AM, Hafezi‐Bakhtiari S, Westerhoff M, Marginean EC, Riddell RH. Gastrointestinal pathologists’ perspective on managing risk in the distal esophagus: convergence on a pragmatic approach. Ann N Y Acad Sci 2018; 1434:35-45. [DOI: 10.1111/nyas.13680] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 02/13/2018] [Accepted: 02/24/2018] [Indexed: 12/20/2022]
Affiliation(s)
- Andrew M. Bellizzi
- Department of PathologyUniversity of Iowa Hospitals and Clinics and Carver College of Medicine Iowa City Iowa
| | | | - Maria Westerhoff
- Department of PathologyUniversity of Michigan Ann Arbor Michigan
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DE Carli DM, Araujo AFD, Fagundes RB. LOW PREVALENCE OF BARRETT'S ESOPHAGUS IN A RISK AREA FOR ESOPHAGEAL CANCER IN SOUTH OF BRAZIL. ARQUIVOS DE GASTROENTEROLOGIA 2017; 54:305-307. [PMID: 28954045 DOI: 10.1590/s0004-2803.201700000-45] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 07/04/2017] [Indexed: 10/17/2023]
Abstract
BACKGROUND Barrett's esophagus a complication of gastroesophageal reflux disease (GERD) is a precursor of esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma has been increasing in most Western countries. Rio Grande do Sul (RS), the Southernmost state of Brazil has the highest rates of esophageal cancer with low prevalence of esophageal adenocarcinoma. OBJECTIVE To investigate the prevalence of Barrett's esophagus among patients underwent to upper gastrointestinal endoscopy in the last 5 years. METHODS The records of patients underwent upper gastrointestinal endoscopy between 2011 and 2015 were analyzed. Demographic data, GERD symptoms, endoscopic findings, extension and histological diagnosis of columnar epithelia of the esophagus were recorded. Significance among the variables was accessed by chi-square test and Fisher's exact test with 95% CI. RESULTS A total of 5996 patients underwent to upper gastrointestinal endoscopy in the period were included. A total of 1769 (30%) patients with GERD symptoms or esophagitis and 107 (1.8%) with columnar lined esophagus were identified. Except for eight patients, the others with columnar lined esophagus had GERD symptoms or esophagitis. Barrett's esophagus defined by the presence of intestinal metaplasia occurred in 47 patients; 20 (43%) with segments over 3 cm and 27 (57%) with segments shorter than 3 cm. The global prevalence of Barrett's esophagus was 0.7% and in GERD patients 2.7%. The odds ratio for the occurrence of columnar lined esophagus in patients with GERD was 30 (95%CI=15.37-63.34). The odds ratio for the presence of intestinal metaplasia in long segments was 8 (95%CI=2.83-23.21). CONCLUSION GERD patients had a risk 30-folds greater to present columnar lined esophagus than patients without GERD symptoms. Long segments of columnar lined esophagus, had a risk eight-folds higher to have Barrett's esophagus than short segments. Barrett's esophagus overall prevalence was 0.7%. In GERD patients, the prevalence was 2.7%. Long Barrett's esophagus represented globally 0.3% and 1.1% in GERD patients.
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Affiliation(s)
- Diego Michelon DE Carli
- Serviço de Gastroenterologia, Hospital Universitário, Universidade Federal de Santa Maria, RS, Brazil
| | | | - Renato Borges Fagundes
- Serviço de Gastroenterologia, Hospital Universitário, Universidade Federal de Santa Maria, RS, Brazil
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Gatenby P, Bhattacharjee S, Wall C, Caygill C, Watson A. Risk stratification for malignant progression in Barrett’s esophagus: Gender, age, duration and year of surveillance. World J Gastroenterol 2016; 22:10592-10600. [PMID: 28082811 PMCID: PMC5192270 DOI: 10.3748/wjg.v22.i48.10592] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 10/17/2016] [Accepted: 11/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To clarify risk based upon segment length, diagnostic histological findings, patient age and year of surveillance, duration of surveillance and gender.
METHODS Patients registered with the United Kingdom Barrett’s Oesophagus Registry from 9 United Kingdom centers were included. The outcome measures were (1) development of all grades of dysplasia; (2) development of high-grade of dysplasia or adenocarcinoma; and (3) development of adenocarcinoma. Prevalent cases and subjects with < 1 year of follow-up were excluded. The covariates examined were segment length, previous biopsy findings, age at surveillance, duration of surveillance, year of surveillance and gender.
RESULTS One thousand and one hundred thirty six patients were included (total 6474 patient-years). Fifty-four patients developed adenocarcinoma (0.83% per annum), 70 developed high-grade dysplasia/adenocarcinoma (1.1% per annum) and 190 developed any grade of dysplasia (3.5% per annum). High grade dysplasia and adenocarcinoma increased with age and duration of surveillance. The risk of low-grade dysplasia development was not dependent on age at surveillance. Segment length and previous biopsy findings were also significant factors for development of dysplasia and adenocarcinoma.
CONCLUSION The risk of development of low-grade dysplasia is independent of age at surveillance, but high-grade dysplasia and adenocarcinoma were more commonly found at older age. Segment length and previous biopsy findings are also markers of risk. This study did not demonstrate stabilisation of the metaplastic segment with prolonged surveillance.
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Abstract
This review provides a summary of our current understanding of, and the controversies surrounding, the diagnosis, pathogenesis, histopathology, and molecular biology of Barrett's esophagus (BE) and associated neoplasia. BE is defined as columnar metaplasia of the esophagus. There is worldwide controversy regarding the diagnostic criteria of BE, mainly with regard to the requirement to histologically identify goblet cells in biopsies. Patients with BE are at increased risk for adenocarcinoma, which develops in a metaplasia-dysplasia-carcinoma sequence. Surveillance of patients with BE relies heavily on the presence and grade of dysplasia. However, there are significant pathologic limitations and diagnostic variability in evaluating dysplasia, particularly with regard to the more recently recognized unconventional variants. Identification of non-morphology-based biomarkers may help risk stratification of BE patients, and this is a subject of ongoing research. Because of recent achievements in endoscopic therapy, there has been a major shift in the treatment of BE patients with dysplasia or intramucosal cancer away from esophagectomy and toward endoscopic mucosal resection and ablation. The pathologic issues related to treatment and its complications are also discussed in this review article.
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Intestinal Metaplasia is Present in Most if Not All Patients Who Have Undergone Endoscopic Mucosal Resection for Esophageal Adenocarcinoma. Am J Surg Pathol 2016; 40:537-43. [PMID: 26813746 DOI: 10.1097/pas.0000000000000601] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Barrett esophagus is presently defined in the United States by the presence of intestinal metaplasia in columnar-lined esophagus based on the premise that the risk for adenocarcinoma depends on the presence of intestinal metaplasia. Recently, arguments have been made that nonintestinalized cardiac epithelium is also at risk and should be included in the definition of Barrett esophagus, as it is in England and Japan. One of these arguments is that residual intestinal metaplasia is frequently absent around early adenocarcinomas removed by endoscopic mucosal resection (EMR). We reviewed 27 EMRs performed in 21 patients. Residual intestinal metaplasia was absent in 10/27 (37%) EMR specimens. An in-depth study of these 10 cases showed that 3 had intestinal metaplasia in a concurrent second EMR specimen, 4 had intestinal metaplasia in prior biopsy material available in our unit, and 2 had intestinal metaplasia in an esophagectomy that followed the EMR. The single patient in whom no intestinal metaplasia was found, neither in biopsies nor in EMR, and who did not undergo an esophagectomy had been under surveillance for Barrett esophagus for over 20 years. We conclude that the frequent absence of residual intestinal metaplasia around an adenocarcinoma in an EMR specimen is the result of sampling error. When evaluated in depth by looking at history, biopsies preceding the EMR, and esophagectomy following the EMR, all of these patients with adenocarcinoma had intestinal metaplasia in their columnar-lined esophagus. This indicates that intestinal metaplasia is a necessary precursor to adenocarcinoma of the esophagus.
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Pohl H, Pech O, Arash H, Stolte M, Manner H, May A, Kraywinkel K, Sonnenberg A, Ell C. Length of Barrett's oesophagus and cancer risk: implications from a large sample of patients with early oesophageal adenocarcinoma. Gut 2016; 65:196-201. [PMID: 26113177 DOI: 10.1136/gutjnl-2015-309220] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 05/30/2015] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Although it is well understood that the risk of oesophageal adenocarcinoma increases with Barrett length, transition risks for cancer associated with different Barrett lengths are unknown. We aimed to estimate annual cancer transition rates for patients with long-segment (≥3 cm), short-segment (≥1 to <3 cm) and ultra-short-segment (<1 cm) Barrett's oesophagus. DESIGN We used three data sources to estimate the annual cancer transition rates for each Barrett length category: (1) the distribution of long, short and ultra-short Barrett's oesophagus among a large German cohort with newly diagnosed T1 oesophageal adenocarcinoma; (2) population-based German incidence of oesophageal adenocarcinoma; and (3) published estimates of the population prevalence of Barrett's oesophagus for each Barrett length category. RESULTS Among 1017 patients with newly diagnosed T1 oesophageal adenocarcinoma, 573 (56%) had long-segment, 240 (24%) short-segment and 204 (20%) ultra-short-segment Barrett's oesophagus. The base-case estimates for the prevalence of Barrett's oesophagus among the general population were 1.5%, 5% and 14%, respectively. The annual cancer transition rates for patients with long, short and ultra-short Barrett's oesophagus were 0.22%, 0.03% and 0.01%, respectively. To detect one cancer, 450 patients with long-segment Barrett's oesophagus would need to undergo annual surveillance endoscopy; in short segment and ultra-short segment, the corresponding numbers of patients would be 3440 and 12,364. Similar results were obtained when applying US incidence data. CONCLUSIONS The large number of patients, who need to undergo endoscopic surveillance to detect one cancer, raises questions about the value of surveillance endoscopy in patients with short segment or ultra-short segment of Barrett's oesophagus.
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Affiliation(s)
- Heiko Pohl
- Department of Gastroenterology, VA Medical Center, White River Junction, Vermont, USA Department of Gastroenterology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Oliver Pech
- Department of Gastroenterology and Interventional Endoscopy, Krankenhaus Barmherzige Brueder, Regensburg, Germany
| | - Haris Arash
- Department of Internal Medicine 2, HSK Wiesbaden, Wiesbaden, Germany
| | - Manfred Stolte
- Department of Pathology, Klinikum Kulmbach, Kulmbach, Germany
| | - Hendrik Manner
- Department of Internal Medicine 2, HSK Wiesbaden, Wiesbaden, Germany
| | - Andrea May
- Department of Internal Medicine 2, HSK Wiesbaden, Wiesbaden, Germany Department of Gastroenterology, Sana-Klinikum Offenbach, Offenbach, Germany
| | - Klaus Kraywinkel
- Centre for Cancer Registry Data, Robert Koch-Institute, Berlin, Germany
| | - Amnon Sonnenberg
- Department of Gastroenterology, VA Medical Center, Portland, Oregon, USA
| | - Christian Ell
- Department of Internal Medicine 2, HSK Wiesbaden, Wiesbaden, Germany Department of Gastroenterology, Sana-Klinikum Offenbach, Offenbach, Germany
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Mastracci L, Piol N, Molinaro L, Pitto F, Tinelli C, De Silvestri A, Fiocca R, Grillo F. Interobserver reproducibility in pathologist interpretation of columnar-lined esophagus. Virchows Arch 2016; 468:159-167. [PMID: 26563401 DOI: 10.1007/s00428-015-1878-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 10/13/2015] [Accepted: 11/03/2015] [Indexed: 02/06/2023]
Abstract
Confirmation of endoscopically suspected esophageal metaplasia (ESEM) requires histology, but confusion in the histological definition of columnar-lined esophagus (CLE) is a longstanding problem. The aim of this study is to evaluate interpathologist variability in the interpretation of CLE. Thirty pathologists were invited to review three ten-case sets of CLE biopsies. In the first set, the cases were provided with descriptive endoscopy only; in the second and the third sets, ESEM extent using Prague criteria was provided. Moreover, participants were required to refer to a diagnostic chart for evaluation of the third set. Agreement was statistically assessed using Randolph's free-marginal multirater kappa. While substantial agreement in recognizing columnar epithelium (K = 0.76) was recorded, the overall concordance in clinico-pathological diagnosis was low (K = 0.38). The overall concordance rate improved from the first (K = 0.27) to the second (K = 0.40) and third step (K = 0.46). Agreement was substantial when diagnosing Barrett's esophagus (BE) with intestinal metaplasia or inlet patch (K = 0.65 and K = 0.89), respectively, in the third step, while major problems in interpretation of CLE were observed when only cardia/cardia-oxyntic atrophic-type epithelium was present (K = 0.05-0.29). In conclusion, precise endoscopic description and the use of a diagnostic chart increased consistency in CLE interpretation of esophageal biopsies. Agreement was substantial for some diagnostic categories (BE with intestinal metaplasia and inlet patch) with a well-defined clinical profile. Interpretation of cases with cardia/cardia-oxyntic atrophic-type epithelium, with or without ESEM, was least consistent, which reflects lack of clarity of definition and results in variable management of this entity.
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Affiliation(s)
- Luca Mastracci
- Department of Surgical and Diagnostic Sciences (DISC), Pathology Unit, University of Genoa, Via De Toni 14, 16132, Genoa, Italy.
- IRCCS AOU S. Martino-IST, Largo Benzi 10, 16132, Genoa, Italy.
| | - Nataniele Piol
- Department of Surgical and Diagnostic Sciences (DISC), Pathology Unit, University of Genoa, Via De Toni 14, 16132, Genoa, Italy
- IRCCS AOU S. Martino-IST, Largo Benzi 10, 16132, Genoa, Italy
| | - Luca Molinaro
- Department of Biomedical Sciences and Human Oncology, University of Turin, Via Santena 7, 10126, Turin, Italy
| | - Francesca Pitto
- Department of Surgical and Diagnostic Sciences (DISC), Pathology Unit, University of Genoa, Via De Toni 14, 16132, Genoa, Italy
- IRCCS AOU S. Martino-IST, Largo Benzi 10, 16132, Genoa, Italy
| | - Carmine Tinelli
- Clinical Epidemiology and Biometric Unit, Foundation IRCCS Policlinico S. Matteo, Via Golgi 19, 27100, Pavia, Italy
| | - Annalisa De Silvestri
- Clinical Epidemiology and Biometric Unit, Foundation IRCCS Policlinico S. Matteo, Via Golgi 19, 27100, Pavia, Italy
| | - Roberto Fiocca
- Department of Surgical and Diagnostic Sciences (DISC), Pathology Unit, University of Genoa, Via De Toni 14, 16132, Genoa, Italy
- IRCCS AOU S. Martino-IST, Largo Benzi 10, 16132, Genoa, Italy
| | - Federica Grillo
- Department of Surgical and Diagnostic Sciences (DISC), Pathology Unit, University of Genoa, Via De Toni 14, 16132, Genoa, Italy
- IRCCS AOU S. Martino-IST, Largo Benzi 10, 16132, Genoa, Italy
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Lowes H, Somarathna T, Shepherd NA. Definition, Derivation, and Diagnosis of Barrett’s Esophagus: Pathological Perspectives. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 908:111-36. [DOI: 10.1007/978-3-319-41388-4_7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Predictors of Progression to High-Grade Dysplasia or Adenocarcinoma in Barrett's Esophagus. Gastroenterol Clin North Am 2015; 44:299-315. [PMID: 26021196 PMCID: PMC4449455 DOI: 10.1016/j.gtc.2015.02.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The prevalence of esophageal adenocarcinoma is increasing dramatically. Barrett's esophagus remains the most well-established risk factor for the development of esophageal adenocarcinoma. There are multiple clinical, endoscopic, and pathologic factors that increase the risk of neoplastic progression to high-grade dysplasia or esophageal adenocarcinoma in Barrett's esophagus. This article reviews both risk and protective factors for neoplastic progression in patients with Barrett's esophagus.
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Expression of SOX9 and CDX2 in nongoblet columnar-lined esophagus predicts the detection of Barrett's esophagus during follow-up. Mod Pathol 2015; 28:654-61. [PMID: 25412842 DOI: 10.1038/modpathol.2014.157] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 09/23/2014] [Accepted: 09/23/2014] [Indexed: 12/19/2022]
Abstract
The diagnosis of Barrett's esophagus in the United States requires both endoscopically evident columnar-lined esophagus and the presence of goblet cells by histology. Currently, there is no consensus on how patients with nongoblet columnar-lined esophagus should be followed. In this study, we investigated whether biomarkers can be used to predict the detection of goblet cells in follow-up biopsies. Patients with nongoblet columnar-lined esophagus were identified. In 13 of these cases, goblet cells were detected in subsequent follow-up endoscopic biopsies (Barrett's group). Additionally, 26 cases that remained negative for goblet cells in follow-up biopsies served as controls. Immunohistochemistry for CDX2, SOX9, BMP4, SHH, and MUC2 was performed on the initial biopsies and graded independently by at least two pathologists in a masked manner. CDX2 was positive in the nongoblet columnar epithelium of 7/13 cases in the Barrett's group and in 4/26 controls (sensitivity 54%, specificity of 85%, odds ratio (OR) 6.4). Strong and diffuse immunoreactivity for SOX9 was detected in 10/13 cases in the Barrett's group and in 1/26 controls (sensitivity 77%, specificity 96%, OR 83.3). Combining CDX2 and SOX9 as a panel increased sensitivity to 85%, although the specificity decreased to 85% (OR 30.3). SHH, BMP4, and MUC2 expression showed no significant difference between the Barrett's and control groups. In patients with nongoblet columnar-lined esophagus, SOX9 and CDX2 may be useful in identifying a subset of patients who have a higher risk of being diagnosed for Barrett's esophagus (developing goblet cells) and need closer follow-up.
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Bennett C, Moayyedi P, Corley DA, DeCaestecker J, Falck-Ytter Y, Falk G, Vakil N, Sanders S, Vieth M, Inadomi J, Aldulaimi D, Ho KY, Odze R, Meltzer SJ, Quigley E, Gittens S, Watson P, Zaninotto G, Iyer PG, Alexandre L, Ang Y, Callaghan J, Harrison R, Singh R, Bhandari P, Bisschops R, Geramizadeh B, Kaye P, Krishnadath S, Fennerty MB, Manner H, Nason KS, Pech O, Konda V, Ragunath K, Rahman I, Romero Y, Sampliner R, Siersema PD, Tack J, Tham TCK, Trudgill N, Weinberg DS, Wang J, Wang K, Wong JYY, Attwood S, Malfertheiner P, MacDonald D, Barr H, Ferguson MK, Jankowski J. BOB CAT: A Large-Scale Review and Delphi Consensus for Management of Barrett's Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia. Am J Gastroenterol 2015; 110:662-683. [PMID: 25869390 PMCID: PMC4436697 DOI: 10.1038/ajg.2015.55] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 02/03/2015] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.
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Affiliation(s)
- Cathy Bennett
- Centre for Technology Enabled Health Research, Coventry University, Coventry, UK
| | | | | | | | - Yngve Falck-Ytter
- Case Western Reserve University School of Medicine, Case and VA Medical Center Cleveland, Cleveland, Ohio, USA
| | - Gary Falk
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Nimish Vakil
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | | | | | - John Inadomi
- University of Washington School of Medicine, Seattle, Washington, USA
| | | | - Khek-Yu Ho
- National University Health System, Singapore, Singapore
| | - Robert Odze
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | - Eamonn Quigley
- Weill Cornell Medical College and Houston Methodist Hospital, Houston, Texas, USA
| | | | | | | | | | - Leo Alexandre
- Norwich Medical School, University of East Anglia, Norwich, UK
| | - Yeng Ang
- University of Manchester, Manchester, UK
| | - James Callaghan
- Department of Gastroenterology, University Hospital Southampton, Southampton, UK
| | | | - Rajvinder Singh
- Lyell McEwin Hospital/University of Adelaide, Adelaide, South Australia, Australia
| | | | | | - Bita Geramizadeh
- Department of Pathology, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Philip Kaye
- Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Sheila Krishnadath
- Gastrointestinal Oncology Research Group, AMC, Amsterdam, The Netherlands
| | | | - Hendrik Manner
- Department of Gastroenterology HSK Wiesbaden, Wiesbaden, Germany
| | - Katie S Nason
- University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Oliver Pech
- Krankenhaus Barmherzige Brueder, Regensburg, Germany
| | - Vani Konda
- University of Chicago, Chicago, Illinois, USA
| | - Krish Ragunath
- Queens Medical Centre, University of Nottingham, Nottingham, UK
| | | | | | | | | | - Jan Tack
- University of Leuven, Leuven, Belgium
| | | | - Nigel Trudgill
- Sandwell and West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | | | - Jean Wang
- Washington University School of Medicine, Saint Louis, Missouri, USA
| | | | - Jennie Y Y Wong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | | | - David MacDonald
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Hugh Barr
- Gloucestershire Royal Hospital, Gloucester, UK
| | | | - Janusz Jankowski
- University Hospitals Coventry and Warwickshire and University of Warwick, Coventry, UK
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Is Carcinoma in Columnar-lined Esophagus Always Located Adjacent to Intestinal Metaplasia? Am J Surg Pathol 2015; 39:188-96. [DOI: 10.1097/pas.0000000000000350] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Naini BV, Chak A, Ali MA, Odze RD. Barrett's oesophagus diagnostic criteria: endoscopy and histology. Best Pract Res Clin Gastroenterol 2015; 29:77-96. [PMID: 25743458 DOI: 10.1016/j.bpg.2014.11.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 10/27/2014] [Accepted: 11/02/2014] [Indexed: 02/07/2023]
Abstract
This review summarizes the endoscopic and histologic features of Barrett's oesophagus(BO) as well as some of the recent advancements and controversies. BO represents metaplastic conversion of normal squamous epithelium of tubular oesophagus to columnar epithelium. The diagnosis of BO requires a combination of endoscopic and histopathologic findings. There is worldwide controversy regarding the exact definition of BO, particularly with regard to the requirement to histologically identify goblet cells in biopsies. The presence and detectability of goblet cells might vary depending on a variety of factors and is subject to sampling error. Therefore, a systematic biopsy sampling with sufficient number of biopsies is currently recommended to limit the likelihood of a false negative result for detection of goblet cells. There are both endoscopic and pathologic challenges in evaluating gastro-oesophageal junction biopsies in patients with irregular Z lines to determine the exact location of the sample (i.e., oesophagus versus stomach). Recently, several novel endoscopic techniques have been developed to improve BO detection. However, none have been validated yet in clinical practice. The surveillance of patients with BO relies on histologic evaluation of dysplasia. However, there are significant pathologic limitations and diagnostic variability in evaluating the presence and grading of BO dysplasia, particularly with regard to the more recently recognized non-intestinal types of dysplasia. All BO dysplasia samples should be reviewed by an expert gastrointestinal pathologist to confirm the diagnosis. Finally, it is important to emphasize that close interaction between gastroenterologists and pathologists is essential to ensure proper evaluation of endoscopic biopsies in order to optimize the surveillance and clinical management of patients with BO.
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Affiliation(s)
- Bita V Naini
- David Geffen School of Medicine at UCLA, Department of Pathology & Lab Medicine, BOX 951732, 1P-172 CHS, 10833 Le Conte Ave, Los Angeles, CA 90095-1732, USA.
| | - Amitabh Chak
- University Hospitals Case Medical Ctr, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
| | - Meer Akbar Ali
- University Hospitals Case Medical Ctr, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
| | - Robert D Odze
- Brigham & Women's Hospital, Pathology Department, 75 Francis St. Boston, MA 02115, USA.
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Goldblum JR. Current issues in Barrett's esophagus and Barrett's-related dysplasia. Mod Pathol 2015; 28 Suppl 1:S1-6. [PMID: 25560595 DOI: 10.1038/modpathol.2014.125] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Accepted: 05/16/2014] [Indexed: 12/13/2022]
Abstract
Surgical pathologists frequently encounter biopsies in patients with Barrett's esophagus (BE), defined as replacement of the normal stratified squamous epithelium of the distal esophagus by metaplastic columnar epithelium containing goblet cells. Thus, one of the primary roles of the pathologist is to definitively identify goblet cells, best done on routine stained sections. It has recently been questioned as to whether goblet cells should be absolutely necessary to render a diagnosis of BE, given immunohistochemical and flow cytometric similarities between columnar-lined esophagus with and without goblet cells. Once a diagnosis of BE is rendered, the pathologist must state, using a simple classification, whether the biopsy is negative for dysplasia or shows dysplasia (low-grade dysplasia or high-grade dysplasia). However, there are a number of known pitfalls in distinguishing dysplasia from reactive epithelium, and it can be similarly difficult to distinguish low-grade dysplasia from high-grade dysplasia. In addition, there are some cases in which the distinction of high-grade dysplasia from intramucosal adenocarcinoma can be challenging. All of these issues are summarized in this paper.
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Affiliation(s)
- John R Goldblum
- Department of Pathology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA
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31
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McDonald SA, Graham TA, Lavery DL, Wright NA, Jansen M. The Barrett's Gland in Phenotype Space. Cell Mol Gastroenterol Hepatol 2015; 1:41-54. [PMID: 28247864 PMCID: PMC5301147 DOI: 10.1016/j.jcmgh.2014.10.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023]
Abstract
Barrett's esophagus is characterized by the erosive replacement of esophageal squamous epithelium by a range of metaplastic glandular phenotypes. These glandular phenotypes likely change over time, and their distribution varies along the Barrett's segment. Although much recent work has addressed Barrett's esophagus from the genomic viewpoint-its genotype space-the fact that the phenotype of Barrett's esophagus is nonstatic points to conversion between phenotypes and suggests that Barrett's esophagus also exists in phenotype space. Here we explore this latter concept, investigating the scope of glandular phenotypes in Barrett's esophagus and how they exist in physical and temporal space as well as their evolution and their life history. We conclude that individual Barrett's glands are clonal units; because of this important fact, we propose that it is the Barrett's gland that is the unit of selection in phenotypic and indeed neoplastic progression. Transition between metaplastic phenotypes may be governed by neutral drift akin to niche turnover in normal and dysplastic niches. In consequence, the phenotype of Barrett's glands assumes considerable importance, and we make a strong plea for the integration of the Barrett's gland in both genotype and phenotype space in future work.
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Affiliation(s)
- Stuart A.C. McDonald
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Trevor A. Graham
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Danielle L. Lavery
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Nicholas A. Wright
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Marnix Jansen
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands
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Uno G, Ishimura N, Tada Y, Tamagawa Y, Yuki T, Matsushita T, Ishihara S, Amano Y, Maruyama R, Kinoshita Y. Simplified classification of capillary pattern in Barrett esophagus using magnifying endoscopy with narrow band imaging: implications for malignant potential and interobserver agreement. Medicine (Baltimore) 2015; 94:e405. [PMID: 25621687 PMCID: PMC4602634 DOI: 10.1097/md.0000000000000405] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The classification of Barrett esophagus (BE) using magnifying endoscopy with narrow band imaging (ME-NBI) is not widely used in clinical settings because of its complexity. To establish a new simplified available classification using ME-NBI.We conducted a cross-sectional study in a single-referral center. One hundred eight consecutive patients with BE using ME-NBI and crystal violet (CV) chromoendoscopy, and histological findings were enrolled. BE areas observed by ME-NBI were classified as type I or II on the basis of capillary pattern (CP), and as closed or open type on the basis of a mucosal pit pattern using CV chromoendoscopy; then, biopsy samples were obtained. We evaluated the relation between CP and pit pattern, expression of the factors with malignant potential, percentage of microvascular density, and interobserver agreement.One hundred thirty lesions from 91 patients were analyzed. Type II CP had more open type pit pattern areas and significantly greater microvascular density than type I. The presence of dysplasia, specialized intestinal metaplasia, expressions of COX-2, CDX2, and CD34, and PCNA index were significantly higher in type II, whereas the multivariate analysis showed that type II was the best predictor for the presence of dysplasia (OR 11.14), CD34 expression (OR 3.60), and PCNA (OR 3.29). Interobserver agreement for this classification was substantial (κ = 0.66).A simplified CP classification based on observation with ME-NBI is presented. Our results indicate that the classification may be useful for surveillance of BE with high malignant potential.
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Affiliation(s)
- Goichi Uno
- From the Department of Gastroenterology and Hepatology (GU, NI, Y. Tada, Y. Tamagawa, SI, YK), Shimane University School of Medicine; Division of Endoscopy (TY), Shimane University Hospital; Department of Pathology (TM, RM), Shimane University School of Medicine, Izumo; Division of Endoscopy (YA), Kaken Hospital, International University of Health and Welfare, Ichikawa, Japan; and Department of Internal Medicine (Y. Tamagawa), University of Texas Southwestern Medical Center, Dallas, TX
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McDonald SAC, Lavery D, Wright NA, Jansen M. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol 2015; 12:50-60. [PMID: 25365976 DOI: 10.1038/nrgastro.2014.181] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Barrett oesophagus develops when the lower oesophageal squamous epithelium is replaced with columnar epithelium, which shows both intestinal and gastric differentiation. No consensus has been reached on the origin of Barrett oesophagus. Theories include a direct origin from the oesophageal-stratified squamous epithelium, or by proximal migration of the gastric cardiac epithelium with subsequent intestinalization. Variations of this theory suggest the origin is a distinctive cell at the squamocolumnar junction, the oesophageal gland ducts, or circulating bone-marrow-derived cells. Much of the supporting evidence comes from experimental models and not from studies of Barrett mucosa. In this Perspectives article, we look at the Barrett lesion itself: at its phenotype, its complexity, its clonal architecture and its stem cell organization. We conclude that Barrett glands are unique structures, but share many similarities with gastric glands undergoing the process of intestinal metaplasia. We conclude that current evidence most strongly supports an origin from stem cells in the cardia.
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Affiliation(s)
- Stuart A C McDonald
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1 2AD, UK
| | - Danielle Lavery
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1 2AD, UK
| | - Nicholas A Wright
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1 2AD, UK
| | - Marnix Jansen
- Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1 2AD, UK
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Affiliation(s)
- Stuart J Spechler
- From the Esophageal Diseases Center, Department of Medicine, Veterans Affairs (VA) North Texas Health Care System, and the University of Texas Southwestern Medical Center, Dallas
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Gatenby P, Caygill C, Wall C, Bhatacharjee S, Ramus J, Watson A, Winslet M. Lifetime risk of esophageal adenocarcinoma in patients with Barrett's esophagus. World J Gastroenterol 2014; 20:9611-9617. [PMID: 25071359 PMCID: PMC4110596 DOI: 10.3748/wjg.v20.i28.9611] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 12/27/2013] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the lifetime risk of development of esophageal adenocarcinoma and/or high-grade dysplasia in patients diagnosed with Barrett’s esophagus.
METHODS: Data were extracted from the United Kingdom National Barrett’s Oesophagus Registry on date of diagnosis, patient age and gender of 7877 patients from who had been registered from 35 United Kingdom centers. Life expectancy was evaluated from United Kingdom National Statistics data based upon gender and age at year at diagnosis. These data were then used with published estimates of annual adenocarcinoma and high-grade dysplasia incidences from meta-analyses and large population-based studies to estimate overall lifetime risk of development of these study endpoints.
RESULTS: The mean age at diagnosis of Barrett’s esophagus was 61.6 years in males and 67.3 years in females. The mean life expectancy at diagnosis was 23.1 years in males, 20.7 years in females and 22.2 years overall. Using data from published meta-analyses, the lifetime risk of development of adenocarcinoma was between 1 in 8 and 1 in 14 and the lifetime risk of high-grade dysplasia or adenocarcinoma was 1 in 5 to 1 in 6. Using data from 3 large recent population-based cohort studies the lifetime risk of adenocarcinoma was between 1 in 10 and 1 in 37 and of the combined end-point of high-grade dysplasia and adenocarcinoma was between 1 in 8 and 1 in 20. Age at Barrett’s esophagus diagnosis is reducing and life expectancy is increasing, which will partially counter-balance lower annual cancer incidence.
CONCLUSION: There is a significant lifetime risk of development of high-grade dysplasia and adenocarcinoma in Barrett’s esophagus.
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Dunbar KB, Spechler SJ. Controversies in Barrett esophagus. Mayo Clin Proc 2014; 89:973-84. [PMID: 24867396 DOI: 10.1016/j.mayocp.2014.01.022] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Revised: 01/06/2014] [Accepted: 01/22/2014] [Indexed: 02/06/2023]
Abstract
Barrett esophagus develops when metaplastic columnar epithelium predisposed to develop adenocarcinoma replaces esophageal squamous epithelium damaged by gastroesophageal reflux disease. Although several types of columnar metaplasia have been described in Barrett esophagus, intestinal metaplasia with goblet cells currently is required for a definitive diagnosis in the United States. Studies indicate that the risk of adenocarcinoma for patients with nondysplastic Barrett esophagus is only 0.12% to 0.38% per year, which is substantially lower than previous studies had suggested. Nevertheless, the incidence of esophageal adenocarcinoma continues to rise at an alarming rate. Regular endoscopic surveillance for dysplasia is the currently recommended cancer prevention strategy for Barrett esophagus, but a high-quality study has found no benefit of surveillance in preventing deaths from esophageal cancer. Medical societies currently recommend endoscopic screening for Barrett esophagus in patients with multiple risk factors for esophageal adenocarcinoma, including chronic gastroesophageal reflux disease, age of 50 years or older, male sex, white race, hiatal hernia, and intra-abdominal body fat distribution. However, because the goal of screening is to identify patients with Barrett esophagus who will benefit from endoscopic surveillance and because such surveillance may not be beneficial, the rationale for screening might be made on the basis of faulty assumptions. Endoscopic ablation of dysplastic Barrett metaplasia has been reported to prevent its progression to cancer, but the efficacy of endoscopic eradication of nondysplastic Barrett metaplasia as a cancer preventive procedure is highly questionable. This review discusses some of these controversies that affect the physicians and surgeons who treat patients with Barrett esophagus. Studies relevant to controversial issues in Barrett esophagus were identified using PubMed and relevant search terms, including Barrett esophagus, ablation, dysplasia, radiofrequency ablation, and endoscopic mucosal resection.
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Affiliation(s)
- Kerry B Dunbar
- Department of Medicine, VA North Texas Healthcare System, and the Department of Medicine, Division of Gastroenterology and Hepatology, University of Texas Southwestern Medical Center at Dallas.
| | - Stuart Jon Spechler
- Department of Medicine, VA North Texas Healthcare System, and the Department of Medicine, Division of Gastroenterology and Hepatology, University of Texas Southwestern Medical Center at Dallas
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Triadafilopoulos G. Revis(it)ing Barrett's esophagus. Gastrointest Endosc 2014; 79:574-6. [PMID: 24630083 DOI: 10.1016/j.gie.2013.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Accepted: 11/06/2013] [Indexed: 02/08/2023]
Affiliation(s)
- George Triadafilopoulos
- Clinical Professor of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Editor-in-Chief Emeritus, Gastrointestinal Endoscopy, Stanford, California, USA
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Abstract
The incidence of esophageal adenocarcinoma and associated mortality has risen dramatically over the past several decades, and, thus, it is increasingly important to understand its pathogenesis and risk factors. Barrett esophagus is the established precursor to esophageal adenocarcinoma that progresses through a metaplasia-dysplasia-carcinoma sequence. Its risk of transforming to carcinoma is not as high as previously reported and there appears to be a biological heterogeneity among patients with this disease. The overall prevalence of Barrett esophagus in the United States ranges from 1% to 25% and is closer to 5% in patients with gastroesophageal reflux disease. Because of the frequency of Barrett esophagus and associated implications, it is important for the practicing pathologist to have a thorough understanding of this disease and its diagnostic pitfalls. In this review, we will discuss issues associated with the diagnosis of Barrett esophagus, including the definition of Barrett esophagus and its distinction from carditis with intestinal metaplasia. We will also discuss challenges in the grading of dysplasia and new variants of dysplasia, including crypt dysplasia and foveolar-type dysplasia. Finally, we will touch upon the evaluation of dysplasia in endoscopic mucosal resection specimens.
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Affiliation(s)
- Catherine E Hagen
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Gregory Y Lauwers
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
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Barrett's esophagus suspected at endoscopy but no specialized intestinal metaplasia on biopsy, what's next? Am J Gastroenterol 2014; 109:178-82. [PMID: 24343550 PMCID: PMC4046947 DOI: 10.1038/ajg.2013.408] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 10/21/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES There are no guidelines regarding the best practice for when Barrett's esophagus (BE) is suspected but not confirmed by histology. The aim of this study was to examine the value of endoscopic follow-up for individuals with endoscopic only BE at index endoscopy. METHODS We performed a longitudinal study of patients diagnosed with suspected columnar lined esophagus (CLE) (suspected BE in the absence of histological confirmation of specialized intestinal metaplasia (IM)). We examined three possible outcomes (definite BE defined as CLE plus IM in targeted biopsies, suspected CLE, or no suspected CLE) on repeat endoscopy within 2 years after the index endoscopy and their predictors (clinical, demographic as well as endoscopists' identity). RESULTS A total of 107 of 1,844 patients had suspected CLE (101 were <3 cm), and 80 underwent a repeat endoscopy within 2 years. Approximately, 71% (95% confidence interval (CI) 61.1-80.9%) had suspected CLE confirmed at repeat endoscopy and only 29% (95% CI 19.1-38.9%) had IM. The length of CLE on the index esophagogastroduodenoscopies was slightly longer among patients with definite BE on repeat endoscopy than those with suspected CLE and no IM or no CLE (1.6 cm (s.d. 1.3) vs. 1.5 cm (s.d. 1.4), and 1.4 cm (s.d. 1.2), respectively P>0.1). Patient demographics, body mass index, gastro-esophageal reflux disease symptoms, hiatal hernia, and endoscopists' identity were not significantly associated with the outcome on the repeat endoscopy. CONCLUSIONS Most (71%) patients with suspected CLE remain negative for IM in the 2 years following the index endoscopy. The findings support withholding BE diagnosis for individuals with suspected CLE.
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Grin A, Streutker CJ. Histopathology in barrett esophagus and barrett esophagus-related dysplasia. Clin Endosc 2014; 47:31-9. [PMID: 24570881 PMCID: PMC3928489 DOI: 10.5946/ce.2014.47.1.31] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Accepted: 12/14/2013] [Indexed: 12/22/2022] Open
Abstract
Pathologic specimens, both biopsies and endoscopic mucosal resections, for Barrett esophagus and Barrett-associated dysplasia and malignancy are common for pathologists in North America, and the incidence in South Asian countries seems to be increasing. Dysplasia and malignancy arising in intestinalized gastric-type mucosa raises issues in the interpretation of dysplasia and the evaluation of the depth of invasion of malignancies that are not seen in squamous dysplasia and squamous cell carcinoma. We review the North American approach to these lesions.
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Affiliation(s)
- Andrea Grin
- Division of Pathology, Department of Laboratory Medicine, The Li Ka Shing Knowledge Institute, St. Michael's Hospital, the University of Toronto Faculty of Medicine, Toronto, ON, Canada
| | - Catherine J Streutker
- Division of Pathology, Department of Laboratory Medicine, The Li Ka Shing Knowledge Institute, St. Michael's Hospital, the University of Toronto Faculty of Medicine, Toronto, ON, Canada
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Abstract
Barrett's esophagus (BE) is defined as the metaplastic conversion of the distal esophageal squamous epithelium to intestinalized columnar epithelium. It is a premalignant condition associated with esophageal adenocarcinoma (EAC) and is the major risk factor for EAC. Recent studies suggest that the molecular mechanisms responsible for the pathogenesis of BE are closely related to transcription factors, signaling proteins and microRNAs (miRNAs). MiRNAs are expected to be used as novel biomarkers for the diagnosis, prognosis assessment and targeted treatment of EAC. This article summarizes recent results involving stem cells, immune factors, transcription factors, DNA methylation, nitric oxide, signaling pathways, microRNAs in the development of BE. Understanding of the molecular mechanisms behind the pathogenesis of BE has important implications for improved management of BE and EAC.
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Bansal A, McGregor DH, Anand O, Singh M, Rao D, Cherian R, Wani SB, Rastogi A, Singh V, House J, Jones PG, Sharma P. Presence or absence of intestinal metaplasia but not its burden is associated with prevalent high-grade dysplasia and cancer in Barrett's esophagus. Dis Esophagus 2013; 27:751-6. [PMID: 24165297 DOI: 10.1111/dote.12151] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Universal agreement on the inclusion of intestinal metaplasia to diagnose Barrett's esophagus (BE) is lacking. Our aim was to determine the association of intestinal metaplasia and its density with the prevalence of dysplasia/cancer in columnar lined esophagus (CLE). Patients with CLE but no intestinal metaplasia (CLE-no IM) were identified by querying the clinical pathology database using SNOMED codes for distal esophageal biopsies. CLE-IM patients were identified from a prospectively maintained database of BE patients. Subsequently, relative risks for prevalent dysplasia and cancer were calculated. Since patients with CLE-no IM are not usually enrolled in surveillance, only prevalent dysplasia/cancer on index endoscopy was analyzed. Goblet cell density and percent intestinal metaplasia were estimated. All biopsy slides were reviewed for dysplasia by two experienced gastrointestinal pathologists. Two hundred sixty-two CLE-IM and 260 CLE-no IM patients were included (age 64±12 vs. 60±11 years, P=0.001; whites 92% vs. 82%, P=0.001; males 99.7% vs. 99.3%, P=NS; CLE length 3.4±3.2 vears 1.4±0.4 cm, P=0.001 and hiatus hernia 64% vs. 56%, P=0.013). The odds of finding low-grade dysplasia and of high-grade dysplasia (HGD)/cancer were 12.5-fold (2.9-53.8, P=0.007) and 4.2-fold (95% CI 1.4-13, P=0.01) higher, respectively, in the CLE-IM group. Reanalysis after controlling for important variables of age, race, and length did not significantly alter the overall results. In CLE-IM group, when patients with high (>50/LPF) versus low goblet cell density (<50/LPF) and <10% versus >10% intestinal metaplasia were compared, the odds of HGD/cancer, OR 1.5 (0.5-4.9, P=0.5) and 1.97 (0.54-7.22), respectively, were not significantly higher. Demonstration of intestinal metaplasia continues to be an essential element in the definition of BE, but its quantification may not be useful for risk stratification of HGD/cancer in BE.
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Affiliation(s)
- A Bansal
- Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center, University of Kansas Medical Center, Kansas City, Missouri, USA; Kansas Cancer Institute, Veterans Affairs Medical Center, University of Kansas Medical Center, Kansas City, Missouri, USA
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Watari J, Hori K, Toyoshima F, Kamiya N, Yamasaki T, Okugawa T, Asano H, Li ZL, Kondo T, Ikehara H, Sakurai J, Tomita T, Oshima T, Fukui H, Miwa H. Association between obesity and Barrett's esophagus in a Japanese population: a hospital-based, cross-sectional study. BMC Gastroenterol 2013; 13:143. [PMID: 24070185 PMCID: PMC3849380 DOI: 10.1186/1471-230x-13-143] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2013] [Accepted: 09/20/2013] [Indexed: 02/06/2023] Open
Abstract
Background The association between obesity and Barrett’s esophagus (BE) in the Japanese population remains unclear. The prevalence of BE and its associated risk factors was examined. Methods A cross-sectional study of 1581 consecutive individuals who underwent upper gastrointestinal endoscopy was conducted. The prevalence of endoscopically suspected BE (ESBE) was evaluated. Obesity was evaluated by body mass index (BMI, ≥ 25 kg/m2) and waist circumference (WC) (males, ≥ 85 cm; females, ≥ 90 cm). Because endoscopic diagnosis of ultra-short ESBE (<1 cm in extent) is difficult and highly unreliable, this type of ESBE was excluded from the study. Results In proton pump inhibitor (PPI) non-users, the prevalence of ESBE ≥ 1 cm was 5.6%. In univariate analysis, male sex and reflux esophagitis (RE) were significantly associated with BE, but BMI, WC, and reflux symptoms were not. In multivariate logistic regression analysis, only RE (odds ratio [OR] = 3.48, 95% confidence interval [CI] 1.89-6.41, p < 0.0001) was an independent risk factor for BE; obesity and the other factors were not. In contrast, RE (OR 5.67, p = 0.0004) and large WC (OR 5.09, p = 0.0005) were significant risk factors for ESBE ≥ 1 cm in PPI users. Only male sex, but not obesity or the other risk factors, was associated with an increased risk of RE in patients not taking PPIs. Conclusions RE, but not obesity, may have an independent association with the risk of ESBE in the Japanese population. Furthermore, obesity measures were not independent risks for RE. Interestingly, PPI-refractory RE and large WC were risk factors for ESBE ≥1 cm in patients taking PPIs.
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Affiliation(s)
- Jiro Watari
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8501, Japan.
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Tytgat GNJ. Editorial: discrepancies and pitfalls in diagnosis and therapy of esophageal columnar metaplasia/Barrett's esophagus: a personal view. J Dig Dis 2013; 14:405-8. [PMID: 23672505 DOI: 10.1111/1751-2980.12071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Abstract
The American Gastroenterological Association (AGA) defines Barrett's esophagus as the condition in which any extent of metaplastic columnar epithelium that predisposes to cancer development replaces the squamous epithelium that normally lines the distal esophagus. Although cardiac mucosa may be metaplastic, its malignant predisposition is not clear, and the AGA still requires the demonstration of intestinal metaplasia (with goblet cells) for a diagnosis of Barrett's esophagus. The AGA generally recommends endoscopic eradication therapy for patients with high-grade dysplasia, who otherwise develop esophageal adenocarcinoma at the rate of 6% per year. Endoscopic therapy is often curative for mucosal neoplasms in Barrett's esophagus because the risk of lymph node metastases is only 1-2%. American gastroenterologists generally do not recommend endoscopic therapy for patients whose neoplasms involve any portion of the submucosa because of the high rate of lymph node metastases that has been described in these cases. The management of low-grade dysplasia is disputed because of poor agreement among pathologists on the diagnosis and because of contradictory data on the natural history, but the AGA recommends that radiofrequency ablation (RFA) should be a therapeutic option for patients with confirmed low-grade dysplasia in Barrett's esophagus. Arguments for using RFA to treat nondysplastic Barrett's metaplasia are based on the premise that RFA decreases cancer risk, but no study has established that premise. In the absence of definitive data, concerns about the frequency and importance of buried metaplastic glands and recurrent metaplasia should temper enthusiasm for treating nondysplastic Barrett's esophagus with RFA.
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Affiliation(s)
- Stuart Jon Spechler
- Department of Medicine, VA North Texas Healthcare System, and The University of Texas Southwestern Medical Center at Dallas, Dallas, Tex., USA.
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Spechler SJ. Barrett's esophagus: is the goblet half empty? Clin Gastroenterol Hepatol 2012; 10:1237-8. [PMID: 22902774 PMCID: PMC3496258 DOI: 10.1016/j.cgh.2012.08.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2012] [Accepted: 08/06/2012] [Indexed: 02/07/2023]
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