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1
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Esophageal abnormalities and the risk for gastroesophageal cancers-a histopathology-register-based study in Sweden. Eur J Epidemiol 2022; 37:401-411. [PMID: 34978667 PMCID: PMC9187549 DOI: 10.1007/s10654-021-00833-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 12/13/2021] [Indexed: 02/07/2023]
Abstract
Background The poor survival of patients with gastroesophageal cancers may improve if additional esophageal precursor lesions to Barrett’s esophagus and squamous dysplasia are identified. We estimated the risk for gastroesophageal cancers among patients with various histopathological abnormalities in the esophagus, including Barrett’s esophagus, subdivided by histopathological types. Methods Histopathology data from esophageal biopsies obtained 1979–2014 were linked with several national population-based registers in Sweden. Patients were followed from 2 years after the first biopsy date until cancer, death, emigration, esophagectomy/gastrectomy or end of follow-up, 31st of December 2016, whichever came first. We estimated standardized incidence ratios (SIRs) as measures of relative risk with the Swedish general population as reference. Results In total 367 esophageal adenocarcinoma (EAC) cases were ascertained during 831,394 person-years of follow-up. The incidence rate (IR) for EAC was 0.1 per 1000 person-years for normal morphology, 0.2–0.5 for inflammatory changes, and 0.8–2.9 for metaplasia. The IR was 1.0 per 1000 person-years (95% confidence interval 0.7–1.3) among patients with non-dysplastic intestinal metaplasia, 0.9 (0.8–1.1) in non-dysplastic gastric/glandular metaplasia and 2.9 (2.0–4.2) among columnar metaplasia patients with low-grade dysplasia. The SIRs were 11.7 (95% confidence interval 8.6–15.5), 12.0 (10.0–14.2) and 30.2 (20.5–42.8), respectively. The SIRs for gastric cardia adenocarcinoma (GCA) were moderately elevated. Conclusions For the first time, we demonstrate that patients with esophageal inflammatory and other metaplastic abnormalities than Barrett’s esophagus have an increased risk of EAC and GCA compared to the general population. Moreover, patients with different histopathologic subtypes of Barrett’s esophagus have a comparable risk for EAC. Supplementary Information The online version contains supplementary material available at 10.1007/s10654-021-00833-6.
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Zhang L, Sun B, Zhou X, Wei Q, Liang S, Luo G, Li T, Lü M. Barrett's Esophagus and Intestinal Metaplasia. Front Oncol 2021; 11:630837. [PMID: 34221959 PMCID: PMC8252963 DOI: 10.3389/fonc.2021.630837] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 05/31/2021] [Indexed: 02/05/2023] Open
Abstract
Intestinal metaplasia refers to the replacement of the differentiated and mature normal mucosal epithelium outside the intestinal tract by the intestinal epithelium. This paper briefly describes the etiology and clinical significance of intestinal metaplasia in Barrett’s esophagus. This article summarizes the impact of intestinal metaplasia on the diagnosis, monitoring, and treatment of Barrett’s esophagus according to different guidelines. We also briefly explore the basis for the endoscopic diagnosis of intestinal metaplasia in Barrett’s esophagus. The identification techniques of goblet cells in Barrett’s esophagus are also elucidated by some scholars. Additionally, we further elaborate on the current treatment methods related to Barrett’s esophagus.
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Affiliation(s)
- Lu Zhang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou City, China
| | - Binyu Sun
- Department of Endoscope, Public Health Clinical Medical Center of Chengdu, Chengdu City, China
| | - Xi Zhou
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou City, China
| | - QiongQiong Wei
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou City, China
| | - Sicheng Liang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou City, China
| | - Gang Luo
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou City, China
| | - Tao Li
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu City, China
| | - Muhan Lü
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou City, China
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3
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Savarino E, de Bortoli N, De Cassan C, Della Coletta M, Bartolo O, Furnari M, Ottonello A, Marabotto E, Bodini G, Savarino V. The natural history of gastro-esophageal reflux disease: a comprehensive review. Dis Esophagus 2017; 30:1-9. [PMID: 27862680 DOI: 10.1111/dote.12511] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastroesophageal reflux disease (GERD) is a common disorder of the upper gastrointestinal tract which is typically characterized by heartburn and acid regurgitation. These symptoms are widespread in the community and range from 2.5% to more than 25%. Economic analyses showed an increase in direct and indirect costs related to the diagnosis, treatment and surveillance of GERD and its complications. The aim of this review is to provide current information regarding the natural history of GERD, taking into account the evolution of its definition and the worldwide gradual change of its epidemiology. Present knowledge shows that there are two main forms of GERD, that is erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter comprises the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, which is considered as a pre-cancerous lesion. Although data from medical literature on the natural history of this disease are limited and mainly retrospective, they seem to indicate that both NERD and mild esophagitis tend to remain as such with time and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur in a small proportion of patients, ranging from 0 to 30%, 10 to 22% and 1 to 13% of cases, respectively. It is necessary to stress that these data are strongly influenced by the use of powerful antisecretory drugs (PPIs). Further studies are needed to better elucidate this matter and overcome the present limitations represented by the lack of large prospective longitudinal investigations, absence of homogeneous definitions of the various forms of GERD, influence of different treatments, clear exclusion of patients with functional disorders of the esophagus.
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Affiliation(s)
- E Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - N de Bortoli
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - C De Cassan
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - M Della Coletta
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - O Bartolo
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - M Furnari
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - A Ottonello
- Department of Surgical Medical Sciences and Integrated Diagnostic, University of Genoa, Genoa, Italy
| | - E Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - G Bodini
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - V Savarino
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
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4
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Whiteman DC, Kendall BJ. Barrett's oesophagus: epidemiology, diagnosis and clinical management. Med J Aust 2016; 205:317-24. [DOI: 10.5694/mja16.00796] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 08/09/2016] [Indexed: 12/20/2022]
Affiliation(s)
| | - Bradley J Kendall
- QIMR Berghofer Medical Research Institute, Brisbane, QLD
- University of Queensland, Brisbane, QLD
- Princess Alexandra Hospital, Brisbane, QLD
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5
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Coman RM, Gotoda T, Forsmark CE, Draganov PV. Prospective evaluation of the clinical utility of endoscopic submucosal dissection (ESD) in patients with Barrett's esophagus: a Western center experience. Endosc Int Open 2016; 4:E715-21. [PMID: 27556083 PMCID: PMC4993890 DOI: 10.1055/s-0042-101788] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 01/23/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Endoscopic submucosal dissection (ESD) carries significant advantages over endoscopic mucosal resection. As such, ESD is an established therapy for esophageal squamous cell carcinoma but there are only limited data on ESD as therapy for Barrett's esophagus (BE). Thus, we prospectively evaluated the outcomes of ESD in patients with BE with high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) performed in a Western center. PATIENTS AND METHODS This is a prospective cohort study. Indications for ESD included: (1) early EAC defined as lesions with intramucosal cancer or superficial submucosal invasion; (2) early EAC with positive lateral margin after EMR; and (3) nodularity with HGD that could not be removed en-bloc with EMR Results: From October 2013 to July 2015, 36 consecutive patients (median age 69, 32 males) underwent ESD at our center. Median procedure time was 88 minutes, with median maximal diameter of resected specimens of 49 mm. En-bloc, R0, and curative resection rates were 100 %, 81 %, and 69 %, respectively. Intramucosal EAC was found in 13 patients (36 %), and submucosal invasion in 13 patients (36 %). In 59 % of the cases, there was discrepancy in the pre- and post-ESD histopathologic diagnosis. Adverse events occurred in 8 patients (22 %), including one episode of bleeding treated with endoscopy and seven esophageal strictures, which were successfully managed with dilations. CONCLUSIONS ESD for BE with HGD/early EAC is feasible and safe with resulting very high en-bloc and R0 resection rates. ESD provided for more accurate pathologic evaluation and significant discrepancy between the pre- and post-ESD histopathological diagnosis was noted.
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Affiliation(s)
- Roxana M. Coman
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, United States
| | - Takuji Gotoda
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Christopher E. Forsmark
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, United States
| | - Peter V. Draganov
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, United States,Corresponding author Peter V. Draganov, MD University of FloridaDivision of Gastroenterology, Hepatology, and Nutrition1329 SW 16th Archer RoadPO Box 100214Gainesville, FL 32610
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6
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Martinucci I, de Bortoli N, Russo S, Bertani L, Furnari M, Mokrowiecka A, Malecka-Panas E, Savarino V, Savarino E, Marchi S. Barrett’s esophagus in 2016: From pathophysiology to treatment. World J Gastrointest Pharmacol Ther 2016; 7:190-206. [PMID: 27158534 PMCID: PMC4848241 DOI: 10.4292/wjgpt.v7.i2.190] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 11/05/2015] [Accepted: 03/18/2016] [Indexed: 02/06/2023] Open
Abstract
Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett’s esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.
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Lawler M, Gavin A, Salto‐Tellez M, Kennedy RD, Van Schaeybroeck S, Wilson RH, Harkin DP, Grayson M, Boyd RE, Hamilton PW, McArt DG, James J, Robson T, Ladner RD, Prise KM, O'Sullivan JM, Harrison T, Murray L, Johnston PG, Waugh DJ. Delivering a research-enabled multistakeholder partnership for enhanced patient care at a population level: The Northern Ireland Comprehensive Cancer Program. Cancer 2016; 122:664-73. [PMID: 26695702 PMCID: PMC4864440 DOI: 10.1002/cncr.29814] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 10/28/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023]
Abstract
The last 20 years have seen significant advances in cancer care in Northern Ireland, leading to measureable improvements in patient outcomes. Crucial to this transformation has been an ethos that recognizes the primacy role of research in effecting heath care change. The authors' model of a cross‐sectoral partnership that unites patients, scientists, health care professionals, hospital trusts, bioindustry, and government agencies can be truly transformative, empowering tripartite clinical‐academic‐industry efforts that have already yielded significant benefit and will continue to inform strategy and its implementation going forward.
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Affiliation(s)
- Mark Lawler
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
| | - Anna Gavin
- Northern Ireland Cancer Registry, Centre for Public HealthQueen's University BelfastBelfastUnited Kingdom
| | - Manuel Salto‐Tellez
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
| | - Richard D. Kennedy
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- Almac DiagnosticsCraigavonUnited Kingdom
| | | | - Richard H. Wilson
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- Northern Ireland Cancer CentreBelfastUnited Kingdom
| | - Denis Paul Harkin
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- Almac DiagnosticsCraigavonUnited Kingdom
| | - Margaret Grayson
- Northern Ireland Cancer Research Consumer ForumBelfastUnited Kingdom
| | - Ruth E. Boyd
- Northern Ireland Cancer Research Consumer ForumBelfastUnited Kingdom
| | - Peter W. Hamilton
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- PathXL, Innovation Centre, Northern Ireland Science ParkBelfastUnited Kingdom
| | - Darragh G. McArt
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
| | - Jacqueline James
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- Northern Ireland Biobank, Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
| | - Tracy Robson
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- School of PharmacyQueen's University BelfastBelfastUnited Kingdom
| | - Robert D. Ladner
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- CV6 Therapeutics, Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
| | - Kevin M. Prise
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
| | - Joe M. O'Sullivan
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- Northern Ireland Cancer CentreBelfastUnited Kingdom
| | - Timothy Harrison
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
- Almac DiscoveryCraigavonUnited Kingdom
| | - Liam Murray
- Centre for Public Health, Queen's University BelfastBelfastUnited Kingdom
| | - Patrick G. Johnston
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
| | - David J. Waugh
- Centre for Cancer Research and Cell BiologyQueen's University BelfastBelfastUnited Kingdom
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8
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Salemme M, Villanacci V, Cengia G, Cestari R, Missale G, Bassotti G. Intestinal metaplasia in Barrett's oesophagus: An essential factor to predict the risk of dysplasia and cancer development. Dig Liver Dis 2016; 48:144-147. [PMID: 26614646 DOI: 10.1016/j.dld.2015.10.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2015] [Revised: 10/08/2015] [Accepted: 10/20/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND To date, there is still uncertainty on the role of specialized intestinal metaplasia in the carcinogenic process of Barrett's oesophagus (BE); this fact seems of importance for planning adequate surveillance programs. AIMS To predict the risk of progression towards dysplasia/cancer based on typical morphological features by evaluating the importance of intestinal metaplasia in BE patients. METHODS 647 cases with a histological diagnosis of BE, referred to the Endoscopy Unit of a tertiary centre between 2000 and 2012 were retrospectively identified, and divided into two groups according to the presence/absence of intestinal metaplasia. For each patient, all histological reports performed during a follow-up of 4-8 years were analyzed. RESULTS Overall, 537 cases (83%) with intestinal metaplasia and 110 cases (17%) without intestinal metaplasia were included. During the follow-up period, none of the patients without intestinal metaplasia developed dysplasia/cancer nor progressed to metaplasia, whereas 72 patients with intestinal metaplasia (13.4%) showed histological progression of the disease. CONCLUSION The histological identification of intestinal metaplasia seems to be an essential factor for the progression towards dysplasia and cancer in BE patients.
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Affiliation(s)
| | | | - Gianpaolo Cengia
- Department of Surgery and Endoscopy Unit, University of Brescia, Spedali Civili, Brescia, Italy
| | - Renzo Cestari
- Department of Surgery and Endoscopy Unit, University of Brescia, Spedali Civili, Brescia, Italy
| | - Guido Missale
- Department of Surgery and Endoscopy Unit, University of Brescia, Spedali Civili, Brescia, Italy
| | - Gabrio Bassotti
- Gastroenterology Section, Department of Medicine, University of Perugia School of Medicine, Perugia, Italy.
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9
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Abstract
Although there are many unanswered questions with Barrett esophagus, we can safely say that the incidence is increasing, chemoprevention strategies for the prevention of Barrett metaplasia and its progression to adenocarcinoma may be in the offing, surveillance should be considered for all patients who are discovered to have Barrett esophagus, RFA is the treatment of choice for those with HGD and strongly considered in those with LGD, EMR should be the treatment of choice for patients with nodular high-grade Barrett esophagus, and, finally, vagal-sparing esophagectomy reserved for patients with persistent HGD or a strong suspicion of carcinoma, with consideration of a concomitant fundoplication.
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Affiliation(s)
- Mark Splittgerber
- Division of General Surgery, University of South Florida, Tampa, FL, USA
| | - Vic Velanovich
- Division of General Surgery, University of South Florida, Tampa, FL, USA.
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10
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Singh R, Yeap SP, Cheong KL. Detection and characterization of early malignancy in the esophagus: what is the best management algorithm? Best Pract Res Clin Gastroenterol 2015; 29:533-544. [PMID: 26381300 DOI: 10.1016/j.bpg.2015.06.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Revised: 05/11/2015] [Accepted: 06/08/2015] [Indexed: 02/06/2023]
Abstract
Barrett's esophagus is a known precursor for esophageal adenocarcinoma. Early detection of dysplasia provides a window of opportunity for curative intervention. Several image-enhanced technologies have been developed to improve visualization of neoplasia. These however have not been found to be superior to the standard four quadrant random biopsy protocol. Patients are risk-stratified based on the degree of dysplasia found on biopsies and undergo either surveillance or treatment. Endoscopic therapy has become the mainstay of treatment for early neoplasia.
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Affiliation(s)
- Rajvinder Singh
- The Lyell McEwin Hospital & University of Adelaide Endoscopy Unit, Haydown Road, Elizabeth Vale, SA 5112, Australia.
| | - Sze Pheh Yeap
- The Lyell McEwin Hospital & University of Adelaide Endoscopy Unit, Haydown Road, Elizabeth Vale, SA 5112, Australia
| | - Kuan Loong Cheong
- The Lyell McEwin Hospital & University of Adelaide Endoscopy Unit, Haydown Road, Elizabeth Vale, SA 5112, Australia
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11
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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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12
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Whiteman DC, Appleyard M, Bahin FF, Bobryshev YV, Bourke MJ, Brown I, Chung A, Clouston A, Dickins E, Emery J, Eslick GD, Gordon LG, Grimpen F, Hebbard G, Holliday L, Hourigan LF, Kendall BJ, Lee EY, Levert-Mignon A, Lord RV, Lord SJ, Maule D, Moss A, Norton I, Olver I, Pavey D, Raftopoulos S, Rajendra S, Schoeman M, Singh R, Sitas F, Smithers BM, Taylor AC, Thomas ML, Thomson I, To H, von Dincklage J, Vuletich C, Watson DI, Yusoff IF. Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma. J Gastroenterol Hepatol 2015; 30:804-820. [PMID: 25612140 DOI: 10.1111/jgh.12913] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/19/2014] [Indexed: 12/11/2022]
Abstract
Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.
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Affiliation(s)
- David C Whiteman
- QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
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13
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Dolak W, Mesteri I, Asari R, Preusser M, Tribl B, Wrba F, Schoppmann SF, Hejna M, Trauner M, Häfner M, Püspök A. A pilot study of the endomicroscopic assessment of tumor extension in Barrett's esophagus-associated neoplasia before endoscopic resection. Endosc Int Open 2015; 3:E19-28. [PMID: 26134766 PMCID: PMC4423329 DOI: 10.1055/s-0034-1377935] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 07/15/2014] [Indexed: 10/29/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Barrett's esophagus (BE) - associated neoplasia can be treated endoscopically, but accurate assessment before intervention is challenging. This study aimed to investigate the role of confocal laser endomicroscopy (CLE) as an adjunct in the endoscopic treatment of BE-associated neoplasia by assessing lateral tumor and subsquamous tumor (SST) extension. PATIENTS AND METHODS In the context of a prospective, single-arm pilot clinical trial, patients referred for endoscopic resection of BE-associated neoplasia (high grade dysplasia and esophageal adenocarcinoma) underwent high definition, white light endoscopy with narrow-band imaging (NBI). Then, CLE mapping of suspected neoplastic lesions was performed by another endoscopist, partially blinded to the previous findings, before the patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), depending on lesion size and anticipated histology. RESULTS In 7 of 38 patients (18 %), CLE revealed additional neoplastic tissue compared with prior white light endoscopy and NBI: 2 concomitant lesions, 2 cases of lateral tumor extension within the Barrett's epithelium, and 3 cases of previously undetected SST extension. Overall, en bloc resection (tumor-free lateral margin) was achieved in 28 of 34 neoplastic lesions (82 %), and complete resection (tumor-free lateral and basal margins) in 21 of 34 neoplastic lesions (62 %). CONCLUSIONS CLE-assisted endoscopic resection of BE-associated neoplasia was safe and effective in this study, as proved by a high additional diagnostic yield of CLE (including visualization of occult SST extension) and a favorable rate of en bloc resection. The clinical value of CLE for assisting endoscopic therapy of BE-associated neoplasia deserves further evaluation in randomized controlled trials.
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Affiliation(s)
- Werner Dolak
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria,Corresponding author Werner Dolak, MD Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaWaehringer Guertel 18-201090 ViennaAustria+43 1 40400 47350
| | - Ildiko Mesteri
- Clinical Institute of Pathology, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Reza Asari
- Department of Surgery, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Matthias Preusser
- Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Barbara Tribl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Friedrich Wrba
- Clinical Institute of Pathology, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Sebastian F. Schoppmann
- Department of Surgery, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Michael Hejna
- Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Michael Häfner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
| | - Andreas Püspök
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, and Gastroesophageal Tumor Unit, Comprehensive Cancer Center, Vienna, Austria
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Watanabe G, Ajioka Y, Takeuchi M, Annenkov A, Kato T, Watanabe K, Tani Y, Ikegami K, Yokota Y, Fukuda M. Intestinal metaplasia in Barrett's oesophagus may be an epiphenomenon rather than a preneoplastic condition, and CDX2-positive cardiac-type epithelium is associated with minute Barrett's tumour. Histopathology 2014; 66:201-14. [PMID: 25040564 DOI: 10.1111/his.12486] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 06/23/2014] [Indexed: 12/20/2022]
Abstract
AIMS Although intestinal-type epithelium in Barrett's oesophagus has been traditionally recognized as having a distinct malignant potential, whether this also holds true for cardiac-type epithelium remains controversial. The aim of this study was to identify a type of epithelium that is highly associated with Barrett's tumour. METHODS AND RESULTS We analysed tumours and the corresponding background mucosa with special regard to tumour size in 40 cases of superficial Barrett's tumour by using immunohistochemical staining for CDX2, CD10, MUC2, MUC5AC, and MUC6. Intestinal metaplasia in tumour-adjacent mucosa was not associated with tumour size, but was significantly correlated with the extent of Barrett's oesophagus (P < 0.001). The majority (69.2%, 9/13) of small tumours (≤10 mm) had no intestinal metaplasia in adjacent non-neoplastic mucosae. Minute (≤5 mm) tumours were significantly associated with a gastric immunophenotype (P < 0.001). Purely gastric-immunophenotype tumour cells expressed CDX2, and cardiac-type epithelium adjacent to small tumours also showed low-level CDX2 expression. CONCLUSIONS Our data suggest that intestinal metaplasia in Barrett's oesophagus is an epiphenomenon rather than a preneoplastic condition, and that CDX2-positive cardiac-type epithelium is highly associated with minute Barrett's tumour. Further prospective studies are needed to evaluate the risk of malignancy of cardiac-type epithelium with regard to sub-morphological intestinalization.
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Affiliation(s)
- Gen Watanabe
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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15
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Khalaf N, Nguyen T, Ramsey D, El-Serag HB. Nonsteroidal anti-inflammatory drugs and the risk of Barrett's esophagus. Clin Gastroenterol Hepatol 2014; 12:1832-9.e6. [PMID: 24793026 PMCID: PMC4214884 DOI: 10.1016/j.cgh.2014.04.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 04/16/2014] [Accepted: 04/21/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested to protect against esophageal adenocarcinoma (EAC). This study examined the effect of NSAIDs on the risk of developing Barrett's esophagus (BE), the precursor lesion to EAC. METHODS We conducted a case-control study among eligible patients scheduled for either elective esophagogastroduodenoscopy (EGD) or recruited from primary care clinics to undergo a study EGD. We compared 323 patients with BE (296 nondysplastic and 27 dysplastic) with 2 separate control groups: 1347 patients from the elective EGD group (endoscopy controls) and 502 patients from the primary care group (primary care controls) with no endoscopic or histopathologic BE. Use of aspirin products and 23 nonaspirin NSAIDs was ascertained from detailed, self-reported questionnaires. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models. RESULTS There were no significant differences in self-reported NSAID use between all BE cases and all controls (58.2% vs 54.6%; P = .33); this was seen for aspirin products (43.0% vs 37.4%; P = .08) and nonaspirin NSAIDs (7.7% vs 8.9%; P = .46). These findings persisted in the multivariable model for any NSAIDs (adjusted OR, 0.89; 95% CI, 0.75-1.28), aspirin (adjusted OR, 1.16; 95% CI, 0.90-1.51), and nonaspirin NSAIDs (adjusted OR, 0.88; 95% CI, 0.55-1.39). Use of a combination of aspirin and nonaspirin NSAIDs was reported in 7.4% of cases and 8.3% of controls, and a nonsignificant inverse association with BE was seen (adjusted OR, 0.70; 95% CI, 0.44-1.11). There was no significant association between BE and daily NSAID use (adjusted OR, 1.03; 95% CI, 0.78-1.37). Similar findings were observed for comparisons involving nondysplastic or dysplastic BE cases, and endoscopy or primary care control groups separately or combined. CONCLUSIONS The use of NSAIDs was not associated with a reduced risk of BE. It is likely that the protective mechanism of NSAIDs on EAC occurs subsequent to the development of BE.
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Affiliation(s)
- Natalia Khalaf
- Houston Veterans Affairs (VA) Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas
| | - Theresa Nguyen
- Houston Veterans Affairs (VA) Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas
| | - David Ramsey
- Houston Veterans Affairs (VA) Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas
| | - Hashem B El-Serag
- Houston Veterans Affairs (VA) Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas; Section of Gastroenterology and Hepatology, Michael E. DeBakey VA Medical Center, Houston, Texas.
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16
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Singh S, Manickam P, Amin AV, Samala N, Schouten LJ, Iyer PG, Desai TK. Incidence of esophageal adenocarcinoma in Barrett's esophagus with low-grade dysplasia: a systematic review and meta-analysis. Gastrointest Endosc 2014; 79:897-909.e4; quiz 983.e1, 983.e3. [PMID: 24556051 DOI: 10.1016/j.gie.2014.01.009] [Citation(s) in RCA: 155] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Accepted: 01/03/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND The natural history of low-grade dysplasia (LGD) in patients with Barrett's esophagus (BE) is unclear. OBJECTIVE We performed a systematic review and meta-analysis of studies that reported the incidence of esophageal adenocarcinoma (EAC) and/or high-grade dysplasia (HGD) among patients with BE with LGD. DESIGN Systematic review and meta-analysis of cohort studies. PATIENTS Patients with BE-LGD, with mean cohort follow-up ≥ 2 years. MAIN OUTCOME MEASUREMENTS Pooled incidence rates with 95% confidence intervals (CI) of EAC and/or BE-HGD. RESULTS We identified 24 studies reporting on 2694 patients with BE-LGD, with 119 cases of EAC. Pooled annual incidence rates of EAC alone and EAC and/or HGD in patients with BE-LGD were 0.54% (95% CI, 0.32-0.76; 24 studies) and 1.73% (95% CI, 0.99-2.47; 17 studies). The results were stable across study setting and location and in high-quality studies. Substantial heterogeneity was observed, which could be explained by stratifying based on LGD/BE ratio as a surrogate for quality of pathology; the pooled annual incidence rates of EAC were 0.76% (95% CI, 0.44-1.09; 14 studies) for LGD/BE ratio <0.15 and 0.32% (95% CI, 0.07-0.58; 10 studies) for LGD/BE ratio >0.15. The annual rate of mortality not related to esophageal disease in patients with BE-LGD was 4.7% (95% CI, 3.2-6.2; 4 studies). LIMITATIONS Substantial heterogeneity was observed in the overall analysis. CONCLUSION The incidence of EAC among patients with BE-LGD is 0.54% annually. The LGD/BE ratio appears to explain the variation observed in the reported incidence of EAC in different cohorts. Conditions not related to esophageal disease are a major cause of mortality in patients with BE-LGD, although additional studies are warranted.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Palaniappan Manickam
- Department of Internal Medicine, William Beaumont Hospital/Oakland University School of Medicine, Royal Oak, Michigan, USA
| | - Anita V Amin
- Department of Internal Medicine, William Beaumont Hospital/Oakland University School of Medicine, Royal Oak, Michigan, USA
| | - Niharika Samala
- Department of Internal Medicine, William Beaumont Hospital/Oakland University School of Medicine, Royal Oak, Michigan, USA
| | - Leo J Schouten
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, The Netherlands
| | - Prasad G Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Tusar K Desai
- Department of Internal Medicine, William Beaumont Hospital/Oakland University School of Medicine, Royal Oak, Michigan, USA
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17
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Gordon LG, Mayne GC, Hirst NG, Bright T, Whiteman DC, Watson DI. Cost-effectiveness of endoscopic surveillance of non-dysplastic Barrett's esophagus. Gastrointest Endosc 2014; 79:242-56.e6. [PMID: 24079411 DOI: 10.1016/j.gie.2013.07.046] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2013] [Accepted: 07/29/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Endoscopic surveillance for non-dysplastic Barrett's esophagus (BE) is contentious and its cost effectiveness unclear. OBJECTIVE To perform an economic analysis of endoscopic surveillance strategies. DESIGN Cost-utility analysis by using a simulation Markov model to synthesize evidence from large epidemiologic studies and clinical data for surveillance, based on international guidelines, applied in a coordinator-managed surveillance program. SETTING Tertiary care hospital, South Australia. PATIENTS A total of 2040 patient-years of follow-up. INTERVENTION (1) No surveillance, (2) 2-yearly endoscopic surveillance of patients with non-dysplastic BE and 6-monthly surveillance of patients with low-grade dysplasia, (3) a hypothetical strategy of biomarker-modified surveillance. MAIN OUTCOME MEASUREMENTS U.S. cost per quality-adjusted life year (QALY) ratios. RESULTS Compared with no surveillance, surveillance produced an estimated incremental cost per QALY ratio of $60,858. This was reduced to $38,307 when surveillance practice was modified by a hypothetical biomarker-based strategy. Sensitivity analyses indicated that the likelihood that surveillance alone was cost-effective compared with no surveillance was 16.0% and 60.6% if a hypothetical biomarker-based strategy was added to surveillance, at an acceptability threshold of $100,000 per QALY gained. LIMITATIONS Treatment options for BE that overlap those for symptomatic GERD were omitted. CONCLUSION By using best available estimates of the malignant potential of BE, endoscopic surveillance of patients with non-dysplastic BE is unlikely to be cost-effective for the majority of patients and depends heavily on progression rates between dysplasia grades. However, strategies that modify surveillance according to cancer risk might be cost-effective, provided that high-risk individuals can be identified and prioritized for surveillance.
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Affiliation(s)
- Louisa G Gordon
- Centre for Applied Health Economics, Griffith Health Institute, Griffith University, Logan Campus, University Dr, Meadowbrook, Queensland, Australia; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
| | - George C Mayne
- Flinders University Department of Surgery, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Nicholas G Hirst
- Centre for Applied Health Economics, Griffith Health Institute, Griffith University, Logan Campus, University Dr, Meadowbrook, Queensland, Australia
| | - Timothy Bright
- Flinders University Department of Surgery, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - David C Whiteman
- QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
| | - David I Watson
- Flinders University Department of Surgery, Flinders Medical Centre, Bedford Park, South Australia, Australia
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18
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Picardo SL, O'Brien MP, Feighery R, O'Toole D, Ravi N, O'Farrell NJ, O'Sullivan JN, Reynolds JV. A Barrett's esophagus registry of over 1000 patients from a specialist center highlights greater risk of progression than population-based registries and high risk of low grade dysplasia. Dis Esophagus 2014; 28:121-6. [PMID: 24428806 DOI: 10.1111/dote.12166] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Barrett's esophagus (BE) arising from chronic gastro-oesophageal reflux (GERD) is the main pathologic precursor of esophageal adenocarcinoma (EAC). The risk of progression to high-grade dysplasia (HGD) and EAC is unclear, and recent population studies from Denmark and Northern Ireland suggest that this has been overestimated in the past. No data exist from the Republic of Ireland. A detailed clinical, endoscopic, and pathologic database was established in one center as a proposed pilot for a national registry, and initial and follow-up data were abstracted by a data manager. One thousand ninety-three patients were registered, 60 patients with HGD were excluded, leaving 1033, with a median age of 59 and 2 : 1 male to female ratio, and 3599 person-years of follow-up. The overall incidence of HGD/EAC was 1.33% per year overall, 0.85% if the first year is excluded. Within the first year after index endoscopy, 18 cases of HGD or EAC were identified, and 30 following the first year. Low-grade dysplasia (LGD) on index endoscopy was associated with an incidence of progression of 6.5% per year, and 3.1% when tertiary referrals were excluded. These data provide important demographic and clinical information on the population of Irish patients with BE, with incidence rates of progression higher than recently published population-based registry series, perhaps relating to sampling and pathological assessment. Low-grade dysplasia on initial biopsy is a significant proxy marker of risk of progression.
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Affiliation(s)
- S L Picardo
- Department of Surgery, Trinity Center for Health Sciences, St. James's Hospital and Trinity College Dublin, Dublin, Ireland
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19
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Gordon LG, Mayne GC. Cost-effectiveness of Barrett's oesophagus screening and surveillance. Best Pract Res Clin Gastroenterol 2013; 27:893-903. [PMID: 24182609 DOI: 10.1016/j.bpg.2013.08.019] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 07/19/2013] [Accepted: 08/26/2013] [Indexed: 02/08/2023]
Abstract
Endoscopic screening and surveillance of patients with Barrett's oesophagus to detect oesophageal cancer at earlier stages is contentious. As a consequence, their cost-effectiveness is also debatable. Current health economic evidence shows mixed results for demonstrating their value, mainly due to varied assumptions around progression rates to cancer, quality of life and treatment pathways. No randomized controlled trial exists to definitively support the efficacy of surveillance programs and one is unlikely to be undertaken. Contemporary treatment, cost and epidemiological data to contribute to cost-effectiveness analyses are needed. Risk assessment to stratify patients at low- or high-risk of developing cancer should improve cost-effectiveness outcomes as higher gains will be seen for those at higher risk, and medical resource use will be avoided in those at lower risk. Rapidly changing technologies for imaging, biomarker testing and less-invasive endoscopic treatments also promise to lower health system costs and avoid adverse events in patients.
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Affiliation(s)
- Louisa G Gordon
- Centre for Applied Health Economics, Griffith Health Institute, Griffith University, Logan Campus, University Dr, Meadowbrook, Queensland 4131, Australia.
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20
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Estores D, Velanovich V. Barrett esophagus: epidemiology, pathogenesis, diagnosis, and management. Curr Probl Surg 2013; 50:192-226. [PMID: 23601575 DOI: 10.1067/j.cpsurg.2013.01.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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21
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Yang S, Wu S, Huang Y, Shao Y, Chen XY, Xian L, Zheng J, Wen Y, Chen X, Li H, Yang C. Screening for oesophageal cancer. Cochrane Database Syst Rev 2012; 12:CD007883. [PMID: 23235651 PMCID: PMC11091427 DOI: 10.1002/14651858.cd007883.pub2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Oesophageal cancer is a global heath problem. The prognosis for advanced oesophageal cancer is generally unfavourable, but early-stage asymptomatic oesophageal cancer is basically curable and could achieve better survival rates. The two most commonly used tests are cytologic examination and endoscopy with mucosal iodine staining. The efficacy of the screening tests is controversial, and the true benefit and efficacy of screening remains uncertain because of the potential lead-time and length-time biases. This review was conducted to examine the evidence for the efficacy of screening for oesophageal cancer (squamous cell carcinoma and adenocarcinoma). OBJECTIVES To determine the efficacy of early screening, using endoscopy with iodine staining or cytologic examination, in reducing mortality from oesophageal cancer in asymptomatic individuals from high-risk and general populations. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 8), The Cochrane Library (2012, Issue 8), MEDLINE (1950 to August 2012), EMBASE (1980 to August 2012), Allied and Complementary Medicine (AMED) (1985 to August 2012), Chinese Biomedical Database (CBM) (January 1975 to August 2012), VIP Database (January 1989 to August 2012), China National Knowledge Infrastructure (CNKI) (January 1979 to August 2012), and the Internet. We also searched reference lists, conference proceedings, and databases of ongoing trials. There was no restriction on language or publication status in the search for trials. SELECTION CRITERIA We included only randomised controlled trials (RCT) of screening versus no screening for oesophageal cancer. Randomisation of groups or clusters of individuals was acceptable. DATA COLLECTION AND ANALYSIS Two review authors independently scanned the titles and abstracts from the initial search for potential trials for inclusion. We did not find any trials that met the inclusion criteria. MAIN RESULTS The electronic search identified 3482 studies. Two authors independently reviewed the references. The reports of 18 studies were retrieved for further investigation. None met the eligibility criteria for a RCT investigation of the effects of screening versus no screening for oesophageal cancer. AUTHORS' CONCLUSIONS There were no RCTs that determined the efficacy of screening for oesophageal cancer. Non-RCTs showed a high incidence and the reported better survival after screening could be caused by selection bias, lead-time and length-time biases. RCTs are needed to determine the efficacy of screening for oesophageal cancer.
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Affiliation(s)
- Shujuan Yang
- West China School of Public Health, Sichuan University, Chengdu, China.
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23
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Bird-Lieberman EL, Dunn JM, Coleman HG, Lao-Sirieix P, Oukrif D, Moore CE, Varghese S, Johnston BT, Arthur K, McManus DT, Novelli MR, O'Donovan M, Cardwell CR, Lovat LB, Murray LJ, Fitzgerald RC. Population-based study reveals new risk-stratification biomarker panel for Barrett's esophagus. Gastroenterology 2012; 143:927-35.e3. [PMID: 22771507 DOI: 10.1053/j.gastro.2012.06.041] [Citation(s) in RCA: 134] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 06/20/2012] [Accepted: 06/22/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS The risk of progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is low and difficult to calculate. Accurate tools to determine risk are needed to optimize surveillance and intervention. We assessed the ability of candidate biomarkers to predict which cases of BE will progress to EAC or high-grade dysplasia and identified those that can be measured in formalin-fixed tissues. METHODS We analyzed data from a nested case-control study performed using the population-based Northern Ireland BE Register (1993-2005). Cases who progressed to EAC (n = 89) or high-grade dysplasia ≥ 6 months after diagnosis with BE were matched to controls (nonprogressors, n = 291), for age, sex, and year of BE diagnosis. Established biomarkers (abnormal DNA content, p53, and cyclin A expression) and new biomarkers (levels of sialyl Lewis(a), Lewis(x), and Aspergillus oryzae lectin [AOL] and binding of wheat germ agglutinin) were assessed in paraffin-embedded tissue samples from patients with a first diagnosis of BE. Conditional logistic regression analysis was applied to assess odds of progression for patients with dysplastic and nondysplastic BE, based on biomarker status. RESULTS Low-grade dysplasia and all biomarkers tested, other than Lewis(x), were associated with risk of EAC or high-grade dysplasia. In backward selection, a panel comprising low-grade dysplasia, abnormal DNA ploidy, and AOL most accurately identified progressors and nonprogressors. The adjusted odds ratio for progression of patients with BE with low-grade dysplasia was 3.74 (95% confidence interval, 2.43-5.79) for each additional biomarker and the risk increased by 2.99 for each additional factor (95% confidence interval, 1.72-5.20) in patients without dysplasia. CONCLUSIONS Low-grade dysplasia, abnormal DNA ploidy, and AOL can be used to identify patients with BE most likely to develop EAC or high-grade dysplasia.
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24
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Booth CL, Thompson KS. Barrett's esophagus: A review of diagnostic criteria, clinical surveillance practices and new developments. J Gastrointest Oncol 2012; 3:232-42. [PMID: 22943014 DOI: 10.3978/j.issn.2078-6891.2012.028] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2012] [Accepted: 04/18/2012] [Indexed: 12/25/2022] Open
Abstract
Barrett's esophagus is defined by metaplastic glandular changes to the distal esophagus and is linked to an increased risk of esophageal adenocarcinoma. Controversy exists whether the definition should be limited to intestinal type glands with goblet cells or should be expanded to include non-goblet cell columnar epithelium. Barrett's esophagus may be asymptomatic in a large proportion of the population but screening should be considered for those with certain clinical findings. The diagnosis of Barrett's should be based on the combination of careful endoscopic evaluation and histologic review of the biopsy material. Continued surveillance biopsies may be necessary in cases of indeterminate or low grade dysplasia. Clinical follow-up of patients with high grade dysplasia should be tailored to the individual patient. Development of newer endoscopy techniques including chemoendoscopy, chromoendoscopy and use of biomarkers on frozen tissue have shown some promise of identifying patients at risk for malignancy.
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Affiliation(s)
- Cassie L Booth
- Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, California, USA
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25
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Wray A, Rice P, Love M. Endoscopic ultrasound in Barrett's oesophagitis with dysplasia. THE ULSTER MEDICAL JOURNAL 2012; 81:70-3. [PMID: 23526576 PMCID: PMC3605537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/30/2012] [Indexed: 11/24/2022]
Abstract
PURPOSE With the advent of conservative therapies including photodynamic therapy and endoscopic mucosal resection for Barrett's and high grade dysplasia, accurate staging has become increasingly important. We report our experience with endoscopic ultrasound (EUS) in these patients. MATERIALS AND METHODS Retrospective review of 25 consecutive patients referred for EUS for assessment of Barrett's with high grade dysplasia and /or stricture or polyp. The findings were compared with subsequent surgical pathology, or endoscopy and biopsy follow up. RESULTS Nine patients were found to have invasive tumour on EUS and this was confirmed in all 9 either by oesophagectomy, OGD and oncology follow up, or by endoscopic mucosal resection. Eight patients underwent oesophagectomy, 5 for invasive tumour and 3 for dysplasia only, with pathological agreement with EUS findings in 7 out of 8 cases. The one discrepancy was a EUS case of mucosal thickening only with no invasion, but pathology showed a T1 lesion. Thirteen patients with no evidence of invasion were managed conservatively, with 11 patients being followed up for 6-12 months with serial OGD and biopsy, and no cases of more invasive disease occurring. Therefore, in our experience the sensitivity, specificity and positive predictive value of EUS in complex Barrett's is 90%, 100% and 100% respectively. CONCLUSION EUS is valuable in the assessment of high grade dysplasia in cases where conservative therapy is being considered, defining those with more deeply invasive tumour for whom radical treatment is the only option.
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Affiliation(s)
- Andrew Wray
- Imaging Centre, The Royal Victoria HospitalGrosvenor Road, Belfast BT12 6BA
| | - Paul Rice
- Department of Radiology, Craigavon Area Hospital68 Lurgan Road, Portadown, BT63 5QQ
| | - Mark Love
- Imaging Centre, The Royal Victoria HospitalGrosvenor Road, Belfast BT12 6BA,Correspondence to Dr Love
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Divergent expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in dysplasia and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to carcinogenesis in Barrett Esophagus? Am J Surg Pathol 2012; 36:331-42. [PMID: 22261707 DOI: 10.1097/pas.0b013e31823d08d6] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Dysplasia in Barrett esophagus has been recognized to be morphologically heterogenous, featuring adenomatous, foveolar, and hybrid phenotypes. Recent studies have suggested a tumor suppressor role for CDX-2 in the metaplasia-dysplasia-carcinoma sequence. The phenotypic stability and role of CDX-2 in the neoplastic progression of different types of dysplasias have not been evaluated. Thirty-eight endoscopic mucosal resections with dysplasia and/or intramucosal carcinoma (IMC) arising in Barrett esophagus were evaluated for the expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2. The background mucosa was also evaluated. The results were correlated with morphologic classification and clinicopathologic parameters. Of 38 endoscopic mucosal resections, 23 had IMC and dysplasia, 8 had IMC only, and 7 had dysplasia only. Among dysplastic lesions, 73% were foveolar, 17% were adenomatous, and 10% were hybrid. Twenty of 23 cases with dysplasia and adjacent IMC showed an identical immunophenotype of dysplasia and IMC comprising 16 gastric, 3 intestinal, and 1 mixed immunophenotype. Three cases showed discordance of dysplasia and IMC immunophenotype. These findings suggest that most Barrett-related IMC cases are either gastric or intestinal, with phenotypic stability during progression supporting separate gastric and intestinal pathways of carcinogenesis. CDX-2 showed gradual downregulation of expression during progression in adenomatous dysplasia but not in foveolar or hybrid dysplasia, supporting a tumor suppressor role, at least in the intestinal pathway. CDX-2 was also found to be expressed to a greater degree in intestinal metaplasia compared with nonintestinalized columnar metaplasia. Consistent with CDX-2 as a tumor suppressor, this suggests that nonintestinalized columnar metaplasia may be an unstable intermediate state at risk for neoplastic progression.
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Columnar-lined esophagus without intestinal metaplasia has no proven risk of adenocarcinoma. Am J Surg Pathol 2012; 36:1-7. [PMID: 21959311 DOI: 10.1097/pas.0b013e31822a5a2c] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Intestinal metaplasia in the columnar-lined esophagus (CLE) has long been recognized as the most significant histologic risk indicator for esophageal adenocarcinoma. Recent concern has been expressed, however, that nonintestinalized metaplastic columnar epithelia (cardiac epithelium in the esophagus) may also indicate risk. Of 2586 consecutive patients undergoing endoscopy and biopsy in the Foregut Surgery Department, we selected (a) 214 patients with a visible CLE who had systemic 4-quadrant biopsies at 1 to 2 cm intervals, with the most proximal biopsy straddling the squamocolumnar junction, and (b) 109 patients without systematic biopsy who had dysplasia or adenocarcinoma. In the first group, 187 (87.4%) patients had intestinal metaplasia, and 27 (12.6%) had cardiac epithelium. Dysplasia or adenocarcinoma was present in 55 patients, all with intestinal metaplasia; its presence was significantly higher than in the cardiac epithelium group, none of whom had dysplasia or adenocarcinoma (P=0.01). In the second group with limited sampling, 49 had only tumor tissue in the biopsy. Of 60 patients with nontumor epithelium, only 34 (56.7%) had residual intestinal metaplasia. We conclude that systematic biopsies of CLE as described in this study separate patients into those with and without intestinal metaplasia in such a manner as to remove the possibility of false-negative diagnosis of intestinal metaplasia. When intestinal metaplasia is absent using this biopsy protocol, the patient is at no or extremely low risk for dysplasia and cancer. When biopsies have a lower level of sampling of the segment of CLE, the absence of intestinal metaplasia cannot be interpreted as a true negative for intestinal metaplasia. Inadequate sampling is a powerful reason why the near absolute association between intestinal metaplasia and adenocarcinoma is not seen in some studies.
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Hvid-Jensen F, Pedersen L, Drewes AM, Sørensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med 2011; 365:1375-83. [PMID: 21995385 DOI: 10.1056/nejmoa1103042] [Citation(s) in RCA: 976] [Impact Index Per Article: 69.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Accurate population-based data are needed on the incidence of esophageal adenocarcinoma and high-grade dysplasia among patients with Barrett's esophagus. METHODS We conducted a nationwide, population-based, cohort study involving all patients with Barrett's esophagus in Denmark during the period from 1992 through 2009, using data from the Danish Pathology Registry and the Danish Cancer Registry. We determined the incidence rates (numbers of cases per 1000 person-years) of adenocarcinoma and high-grade dysplasia. As a measure of relative risk, standardized incidence ratios were calculated with the use of national cancer rates in Denmark during the study period. RESULTS We identified 11,028 patients with Barrett's esophagus and analyzed their data for a median of 5.2 years. Within the first year after the index endoscopy, 131 new cases of adenocarcinoma were diagnosed. During subsequent years, 66 new adenocarcinomas were detected, yielding an incidence rate for adenocarcinoma of 1.2 cases per 1000 person-years (95% confidence interval [CI], 0.9 to 1.5). As compared with the risk in the general population, the relative risk of adenocarcinoma among patients with Barrett's esophagus was 11.3 (95% CI, 8.8 to 14.4). The annual risk of esophageal adenocarcinoma was 0.12% (95% CI, 0.09 to 0.15). Detection of low-grade dysplasia on the index endoscopy was associated with an incidence rate for adenocarcinoma of 5.1 cases per 1000 person-years. In contrast, the incidence rate among patients without dysplasia was 1.0 case per 1000 person-years. Risk estimates for patients with high-grade dysplasia were slightly higher. CONCLUSIONS Barrett's esophagus is a strong risk factor for esophageal adenocarcinoma, but the absolute annual risk, 0.12%, is much lower than the assumed risk of 0.5%, which is the basis for current surveillance guidelines. Data from the current study call into question the rationale for ongoing surveillance in patients who have Barrett's esophagus without dysplasia. (Funded by the Clinical Institute, University of Aarhus, Aarhus, Denmark.).
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Affiliation(s)
- Frederik Hvid-Jensen
- Department of Surgical Gastroenterology L, Aarhus University Hospital, Aarhus, Denmark
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Gatenby PA, Caygill CP, Watson A, Murray L, Romero Y. Barrett's esophagus registries. Ann N Y Acad Sci 2011; 1232:405-10. [DOI: 10.1111/j.1749-6632.2011.06059.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Orloff M, Peterson C, He X, Ganapathi S, Heald B, Yang YR, Bebek G, Romigh T, Song JH, Wu W, David S, Cheng Y, Meltzer SJ, Eng C. Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma. JAMA 2011; 306:410-9. [PMID: 21791690 PMCID: PMC3574553 DOI: 10.1001/jama.2011.1029] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
CONTEXT Barrett esophagus (BE) occurs in 1% to 10% of the general population and is believed to be the precursor of esophageal adenocarcinoma (EAC). The incidence of EAC has increased 350% in the last 3 decades without clear etiology. Finding predisposition genes may improve premorbid risk assessment, genetic counseling, and management. Genome-wide multiplatform approaches may lead to the identification of genes important in BE/EAC development. OBJECTIVE To identify risk alleles or mutated genes associated with BE/EAC. DESIGN, SETTING, AND PATIENTS Model-free linkage analyses of 21 concordant-affected sibling pairs with BE/EAC and 11 discordant sibling pairs (2005-2006). Significant germline genomic regions in independent prospectively accrued series of 176 white patients with BE/EAC and 200 ancestry-matched controls (2007-2010) were validated and fine mapped. Integrating data from these significant genomic regions with somatic gene expression data from 19 BE/EAC tissues yielded 12 "priority" candidate genes for mutation analysis (2010). Genes that showed mutations in cases but not in controls were further screened in an independent prospectively accrued validation series of 58 cases (2010). MAIN OUTCOME MEASURES Identification of germline mutations in genes associated with BE/EAC cases. Functional interrogation of the most commonly mutated gene. RESULTS Three major genes, MSR1, ASCC1, and CTHRC1 were associated with BE/EAC (all P < .001). In addition, 13 patients (11.2%) with BE/EAC carried germline mutations in MSR1, ASCC1, or CTHRC1. MSR1 was the most frequently mutated, with 8 of 116 (proportion, 0.069; 95% confidence interval [CI], 0.030-0.130; P < .001) cases with c.877C>T (p.R293X). An independent validation series confirmed germline MSR1 mutations in 2 of 58 cases (proportion, 0.035; 95% CI, 0.004-0.120; P = .09). MSR1 mutation resulted in CCND1 up-regulation in peripheral-protein lysate. Immunohistochemistry of BE tissues in MSR1-mutation carriers showed increased nuclear expression of CCND1. CONCLUSION MSR1 was significantly associated with the presence of BE/EAC in derivation and validation samples, although it was only present in a small percentage of the cases.
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Affiliation(s)
- Mohammed Orloff
- Genomic Medicine Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
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Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, Murray LJ. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst 2011; 103:1049-1057. [PMID: 21680910 PMCID: PMC3632011 DOI: 10.1093/jnci/djr203] [Citation(s) in RCA: 513] [Impact Index Per Article: 36.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Revised: 05/09/2011] [Accepted: 05/09/2011] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005. SUBJECTS AND METHODS We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests. RESULTS After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P < .001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P < .001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P < .001). CONCLUSION We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective.
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Affiliation(s)
- Shivaram Bhat
- Centre for Public Health, Queens University Belfast, Institute of Clinical Sciences Building, Belfast BT12 6BA, Northern Ireland, UK.
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Jacobson BC, Giovannucci EL, Fuchs CS. Smoking and Barrett's esophagus in women who undergo upper endoscopy. Dig Dis Sci 2011; 56:1707-17. [PMID: 21448698 PMCID: PMC3100531 DOI: 10.1007/s10620-011-1672-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2010] [Accepted: 03/08/2011] [Indexed: 01/11/2023]
Abstract
BACKGROUND Cigarette use is associated with esophageal adenocarcinoma, and cross-sectional studies suggest an association between smoking and Barrett's esophagus. AIMS We sought to examine prospectively the effect of smoking on the risk for Barrett's esophagus. METHODS This was a prospective cohort study among 20,863 women within the Nurses' Health Study who underwent upper gastrointestinal endoscopy for any reason between 1980 and 2006. We assessed the association between smoking and pathologically-confirmed Barrett's esophagus (n = 377). Self-reported data on smoking and potential confounding variables were collected from biennial questionnaires. RESULTS Compared with women who never smoked, former smokers of 1-24 cigarettes/day had a multivariate odds ratio for Barrett's esophagus of 1.25 (95% CI 0.99-1.59), former smokers of ≥ 25 cigarettes/day had a multivariate odds ratio of 1.52 (95% CI 1.04-2.22), current smokers of 1-24 cigarettes/day had a multivariate odds ratio of 0.89 (95% CI 0.54-1.45), and current smokers of ≥ 25 cigarettes/day had a multivariate odds ratio of 0.92 (95% CI 0.34-2.54). The risk for Barrett's esophagus increased significantly with increasing pack-years smoked among former (P = 0.008) but not current smokers (P = 0.99), especially when considering exposure ≥ 25 years before index endoscopy. Results were similar among women reporting regular heartburn/acid-reflux one or more times a week, and were not accounted for by changes in weight. CONCLUSIONS Heavy, remote smoking is associated with an increased risk for Barrett's esophagus. This finding suggests a long latency period between exposure and development of the disease, even after discontinuation of smoking.
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Desai TK, Samala N. The incidence of esophageal adenocarcinoma among patients with nondysplastic Barrett's esophagus has been overestimated. Clin Gastroenterol Hepatol 2011; 9:363-4; author reply 364-5. [PMID: 21115135 DOI: 10.1016/j.cgh.2010.11.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2010] [Accepted: 11/12/2010] [Indexed: 02/07/2023]
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Hirst NG, Gordon LG, Whiteman DC, Watson DI, Barendregt JJ. Is endoscopic surveillance for non-dysplastic Barrett's esophagus cost-effective? Review of economic evaluations. J Gastroenterol Hepatol 2011; 26:247-254. [PMID: 21261712 DOI: 10.1111/j.1440-1746.2010.06506.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Several health economic evaluations have explored the cost-effectiveness of endoscopic surveillance for patients with non-dysplastic Barrett's esophagus, with conflicting results. By comparing results across studies and highlighting key methodological and data limitations a platform for future, more rigorous analyses, can be developed. METHODS A systematic literature review was undertaken of studies evaluating cost-effectiveness of surveillance for non-dysplastic Barrett's esophagus. Articles were included if they assessed both cost and health outcomes for surveillance versus no surveillance. A descriptive review was undertaken and the quality of the studies appraised against best-practice recommendations for economic evaluations and modeling studies. RESULTS Seven publications met the inclusion criteria. All used decision-analytic Markov models. Half of the evaluations found surveillance was not cost-effective. At best, surveillance produced improved outcomes at a cost of US$16 640 per quality-adjusted life-year, and at worst it did more harm than good and at a greater cost. The quality of the evaluations and generalizability to the Asia-Pacific region was diminished as a result of inadequate or inconsistent evidence supporting parameter estimates, such as quality of life, endoscopic sensitivity and specificity and cancer recurrence rates. CONCLUSIONS Unless newly emerging technologies improve the quality-adjusted survival benefit conferred by endoscopic surveillance, this strategy is unlikely to be cost-effective. Obsolete assumptions and incomplete analyses reduce the quality of published evaluations. For these reasons new evaluations are required that encompass the growing evidence base for new technologies, such as new endoscopic therapies for high-grade dysplasia and intramucosal cancer.
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Affiliation(s)
- Nicholas G Hirst
- Genetics and Population Health Division, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Australia
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Abstract
Esophageal adenocarcinoma is increasing in incidence. The main risk factor is the premalignant condition of Barrett's esophagus. There is great interest in chemoprevention to prevent or slow malignant transformation. There are many agents proposed as playing a role in chemoprevention; however, none is licensed for this role as yet. Aspirin possesses many favorable qualities for chemoprevention and is the focus of the largest randomized control trial in this field.
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Ladanchuk TC, Johnston BT, Murray LJ, Anderson LA. Risk of Barrett's oesophagus, oesophageal adenocarcinoma and reflux oesophagitis and the use of nitrates and asthma medications. Scand J Gastroenterol 2010; 45:1397-403. [PMID: 20626305 DOI: 10.3109/00365521.2010.503968] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To investigate the relationship between use of asthma medication and nitrates and risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. MATERIAL AND METHODS Data were collected on use of asthma medication and nitrates at least 1 year before interview from patients with reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. Associations between use of asthma medications and nitrates and the risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma were estimated using multiple logistic regression. RESULTS Nine hundred and forty-one subjects were recruited: 230 reflux oesophagitis, 224 Barrett's oesophagus, 227 oesophageal adenocarcinoma patients and 260 population controls. Barrett's oesophagus patients were more likely than controls to have had a diagnosis of asthma (odds ratio 2.15, 95% confidence interval 1.15-4.03) and to have used asthma medications (odds ratio 2.13, 95% confidence interval 1.09-4.16). No significant associations were observed between use of asthma medication or nitrates and reflux oesophagitis or oesophageal adenocarcinoma. CONCLUSIONS Gastro-oesophageal reflux symptoms appear to confound the association between asthma medication use and Barrett's oesophagus. However, it is possible that asthma medications may increase the risk of Barrett's oesophagus by other mechanisms.
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Affiliation(s)
- Todd C Ladanchuk
- Centre for Public Health, Queen's University, and Royal Group of Hospitals, Belfast, Northern Ireland, UK
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Abu-Sneineh A, Tam W, Schoeman M, Fraser R, Ruszkiewicz AR, Smith E, Drew PA, Dent J, Holloway RH. The effects of high-dose esomeprazole on gastric and oesophageal acid exposure and molecular markers in Barrett's oesophagus. Aliment Pharmacol Ther 2010; 32:1023-30. [PMID: 20937048 DOI: 10.1111/j.1365-2036.2010.04428.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Acid reflux is often difficult to control medically. AIM To assess the effect of 40 mg twice daily esomeprazole (high-dose) on gastric and oesophageal pH and symptoms, and biomarkers relevant to adenocarcinoma, in patients with Barrett's oesophagus (BO). METHODS Eighteen patients, treated with proton pump inhibitors as prescribed by their treating doctor, had their therapy increased to high-dose esomeprazole for 6 months. RESULTS At entry into the study, 9/18 patients had excessive 24-h oesophageal acid exposure, and gastric pH remained <4 for >16 h in 8/18. With high-dose esomeprazole, excessive acid exposure occurred in 2/18 patients, and gastric pH <4 was decreased from 38% of overall recording time and 53% of the nocturnal period to 15% and 17%, respectively (P < 0.001). There was a reduction in self-assessed symptoms of heartburn (P = 0.0005) and regurgitation (P < 0.0001), and inflammation and proliferation in the Barrett's mucosa. There was no significant change in p53, MGMT or COX-2 expression, or in aberrant DNA methylation. CONCLUSIONS High-dose esomeprazole achieved higher levels of gastric acid suppression and control of oesophageal acid reflux and symptoms, with significant decreases in inflammation and epithelial proliferation. There was no reversal of aberrant DNA methylation.
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Affiliation(s)
- A Abu-Sneineh
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, SA, Australia
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Intestinal differentiation in metaplastic, nongoblet columnar epithelium in the esophagus. Am J Surg Pathol 2010; 33:1006-15. [PMID: 19363439 DOI: 10.1097/pas.0b013e31819f57e9] [Citation(s) in RCA: 115] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Barrett esophagus (BE) is defined by the presence of metaplastic esophageal columnar epithelium with goblet cells within endoscopically recognizable areas of the esophagus. However, some carcinomas in BE, or from the gastroesophageal junction region, develop within mucosa devoid of goblet cells. However, the biologic properties, pathogenesis, and risk of malignancy of metaplastic, esophageal nongoblet columnar epithelium, is, essentially, unknown. In this study, 89 patients with metaplastic esophageal columnar epithelium were evaluated immunohistochemically for markers of intestinal differentiation, such as MUC2, DAS-1, Villin, and CDX2, a marker of gastric differentiation (MUC5AC), and Ki67, a marker of cell proliferation. Of the 89 patients, 59 had columnar metaplasia with goblet cells (BE), which were further separated into low-density goblet cell and high-density goblet cell groups based on the percentage of crypts with goblet cells, and 30 patients had columnar metaplasia of the esophagus without goblet cells. As controls, gastric biopsies from 19 age and sex matched patients without esophageal or gastric pathology were used. The rate of positivity of the markers and the location of Ki67 staining was evaluated only in non-goblet columnar epithelium from all patient groups. Patients with metaplastic esophageal columnar epithelium without goblet cells showed positivity for MUC5AC, MUC2, DAS-1, Villin, and CDX2 in 100%, 0%, 30%, 17%, and 43% of cases, respectively. 17% of cases showed aberrant surface Ki67 positivity. These values were significantly higher than gastric controls, which showed absence of staining for all markers except MUC5AC (100%). In patients with metaplastic esophageal columnar epithelium with goblet cells (BE) a significant increased rate of staining was observed for all markers, except MUC5AC. In addition, both MUC2 and surface Ki67 staining were significantly increased in BE patients with high-density goblet cells versus those with low-density goblet cells. In a separate analysis in which metaplastic esophageal nongoblet epithelium was evaluated in areas of mucosa devoid of goblet cells compared with areas of mucosa with goblet cells, from patients who had goblet cells elsewhere in the mucosa (N=59), no significant differences were observed with regard to the percentage of cases that stained with any of the markers in the nongoblet epithelium in areas devoid of goblet cells, similar to the patient group with metaplastic esophageal epithelium without goblet cells (N=30). Similar to above, in all cases, expression of intestinal markers increased in areas of mucosa adjacent to goblet cells. This study provides evidence that metaplastic esophageal columnar epithelium without goblet cells shows phenotypic evidence of intestinal differentiation and supports the theory that squamous epithelium converts initially to nongoblet columnar epithelium before goblet cell metaplasia. Further prospective studies are needed to evaluate the pathogenetic sequence, natural history, and risk of malignancy of metaplastic esophageal nongoblet epithelium.
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Abstract
OBJECTIVE Excess body mass is associated with symptoms of gastro-oesophageal reflux disease, and cross-sectional studies suggest an association between body mass index (BMI) and Barrett's oesophagus. The present study sought prospectively to examine the influence of BMI and other anthropomorphic measures on the risk for Barrett's oesophagus among women. METHODS This was a prospective study of 15 861 women who participated in the Nurses' Health Study, without a history of cancer, who underwent upper gastrointestinal endoscopy for any reason between 1986 and 2004. The main outcome measures were 261 cases of pathologically confirmed specialised intestinal metaplasia within the oesophagus (Barrett's oesophagus). Self-reported data on weight were collected from biennial questionnaires. Self-reported height was collected in 1976, and self-reported waist and hip circumferences were collected in 1986. RESULTS Compared with women with a BMI of 20-24.9 kg/m(2), women with a BMI of 25-29.9 had a multivariate OR for Barrett's oesophagus of 0.92 (95% CI 0.66 to 1.27), women with a BMI > or =30 had a multivariate OR of 1.52 (95% CI 1.02 to 2.28) and women with a BMI <20 had a multivariate OR of 0.92 (95% CI 0.65 to 1.31). Results were similar when controlling for symptoms of gastro-oesophageal reflux, and among the entire Nurses' Health Study cohort (n = 93 609) regardless of a history of endoscopy. In contrast, waist-to-hip ratio, waist circumference and height did not appear to be associated with Barrett's oesophagus. CONCLUSIONS Obese, but not overweight, women appear to be at increased risk for Barrett's oesophagus.
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Affiliation(s)
- B C Jacobson
- Section of Gastroenterology, Department of Medicine, Boston University Medical Center, 88 East Concord Street, Room 7721, Boston, MA 02118, USA.
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Michalak J, Bansal A, Sharma P. Screening and surveillance of Barrett's esophagus. Curr Gastroenterol Rep 2009; 11:195-201. [PMID: 19463219 DOI: 10.1007/s11894-009-0031-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Esophageal adenocarcinoma (EAC) is the most rapidly increasing cancer in the Western world and Barrett's esophagus (BE) is the only known precursor lesion for this lethal cancer. Long-term survival may be improved if EAC is diagnosed early, providing an opportunity for early intervention. Screening for BE in patients with gastroesophageal reflux disease is not routinely recommended; however, if diagnosed, enrollment into a surveillance program may be beneficial. Surveillance of all patients with known BE is probably not cost-effective and factors predictive of BE progression to dysplasia/EAC are poorly understood. Screening and surveillance examinations are also faced with challenges in the endoscopic detection of intestinal metaplasia and dysplasia. Future application of molecular biomarkers may help identify the patients with BE most likely to progress, and the use of novel imaging methods may improve outcomes of BE screening and surveillance.
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Affiliation(s)
- Jeff Michalak
- University of Kansas School of Medicine and Veterans Affairs Medical Center, Kansas City, MO 64128, USA
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[Esophageal adenoma-carcinoma and Barrett's esophagus. Gastric adenocarcinoma and Helicobacter pylori]. GASTROENTEROLOGIA Y HEPATOLOGIA 2009; 31 Suppl 4:66-9. [PMID: 19434870 DOI: 10.1016/s0210-5705(08)76633-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In the last two decades, the incidence of esophageal cancer has progressively increased, especially that of adenocarcinomas localized in the esophagogastric junction. The incidence of gastric cancer has decreased in the last few decades, although this decrease shows wide geographical variations. Thus, the prevalence of gastric cancer continues to be high in countries such as Chile, Colombia and Ireland and this disease remains the most frequent neoplasm in both sexes in China and Japan. In the meeting of the American Gastroenterological Association, notable among all the studies presented on the prevention and treatment of esophageal and gastric cancer were the following contributions: the use of clinical practice guidelines for the prevention and surveillance of Barrett's esophagus (BE) should be improved; treatment with proton pump inhibitors does not seem to reduce the risk of esophageal cancer; endoscopic therapy of intramucosal cancer through complete mucosal resection is effective; Helicobacter pylori eradication prevents the development of metachronous gastric cancer in patients treated for a first intramucosal adenocarcinoma through endoscopic resection; the risk of developing gastric cancer is 6 times higher in patients with mucosa-associated lymphoid tissue (MALT) lymphoma than in the general population; and photodynamic therapy may be an alternative for the treatment of "invisible" gastric adenocarcinoma, which should be followed-up endoscopically.
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Alcedo J, Ferrández A, Arenas J, Sopeña F, Ortego J, Sainz R, Lanas A. Trends in Barrett's esophagus diagnosis in Southern Europe: implications for surveillance. Dis Esophagus 2009; 22:239-48. [PMID: 19425201 DOI: 10.1111/j.1442-2050.2008.00908.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma has increased in Western countries in recent decades. The aim of this study is to describe the changes in incidence and prevalence of BE diagnosis, dysplasia, and adenocarcinoma development in BE patients in a South-European Mediterranean area. Retrospective population-based analyses of endoscopy and pathology reports from 1976 to 2001 was performed. Data from patients with diagnosis of BE and/or esophageal carcinoma were collected. The study period was divided in four quartiles for statistical calculations; parametric and nonparametric tests were used. A 6.9-fold increase was found in the diagnosis of long-segment BE from the first to the fourth quartile, and a 9.3-fold increase in short-segment BE from 1995 to 2000, in contrast to a much smaller increase of 1.9-fold increase in the number of upper gastrointestinal endoscopies. The adjusted incidence of BE diagnosis increased from 0.73 to 9.73 cases/100,000 (first to fourth quartile, respectively) and the adjusted prevalence from 6.51 to 76.04 cases/100,000 (1985-2001). The incidence of dysplasia was 2.13% per year (95% confidence interval: 0.05-11.3%) - 1.78% for low-grade dysplasia and 0.36% for high-grade dysplasia - giving a total incidence of 1 per 47 patient-years. The incidence of adenocarcinoma during follow-up was 0.48% per year (95% confidence interval: 0.006-2.62%), for an incidence of 1 per 210 patient-years. Nineteen patients with BE (14 long-segment BE, 5 short-segment BE) were diagnosed with esophageal adenocarcinoma, with eight being diagnosed during endoscopic surveillance. Only 14 (8%) adenocarcinoma patients diagnosed during the study period had a history of BE. BE diagnosis has dramatically increased over recent decades in our population, unrelated to an increase in endoscopies. Progression to low-grade dysplasia and adenocarcinoma is rare. Surveillance may have a low impact on the survival of adenocarcinoma patients in Southern Europe.
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Affiliation(s)
- Javier Alcedo
- Service of Digestive Diseases, Clínico Lozano Blesa Hospital, Institute of Health Sciences, CIBERehd, University of Zaragoza, Zaragoza, Spain.
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Liu W, Hahn H, Odze RD, Goyal RK. Metaplastic esophageal columnar epithelium without goblet cells shows DNA content abnormalities similar to goblet cell-containing epithelium. Am J Gastroenterol 2009; 104:816-24. [PMID: 19293780 PMCID: PMC2722438 DOI: 10.1038/ajg.2009.85] [Citation(s) in RCA: 144] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The mucosa of patients with columnar-lined esophagus recognized on endoscopy usually shows epithelium with and without goblet cells. Columnar epithelium with goblet cells ("Barrett's esophagus") is generally believed to represent a premalignant lesion and has been shown to contain DNA abnormalities. However, the biological properties of non-goblet columnar epithelium remain unknown. The purpose of this study was to determine the DNA content properties of non-goblet epithelium in patients with metaplastic columnar epithelium of the esophagus. METHODS Mucosal biopsies of the esophagus from 68 patients with columnar metaplasia of the esophagus (22 without goblet cells and 46 with goblet cells) and 19 patients with normal gastric mucosa (controls) were histologically evaluated for the density of goblet cells. The latter group was divided into low-density, high-density, and very high-density goblet cell subgroups. Tissue sections of non-goblet epithelium and goblet cell epithelium (where present) were evaluated by image cytometry, and high-fidelity DNA histograms were created to indicate the G0/G1 peak DNA index (DI), DNA content heterogeneity index (HI), and the percentage of cells with DNA exceeding 5N (5N-EC). G0/G1 peaks with DI>1.1 were considered aneuploid. RESULTS Normal gastric controls showed a mean peak DI of 1.02+/-0.03 and an HI of 11.6+/-0.7. None of the controls revealed aneuploidy or 5N-EC. Patients with metaplastic columnar epithelium with goblet cells showed a DI of 1.15+/-0.12, HI of 18.2+/-2.1, mild aneuploidy in 54% of the cases, and 5N-EC in 15% of the cases, all of which were significantly higher than in controls. Patients with metaplastic columnar epithelium without goblet cells showed DNA content results statistically similar to those of patients with metaplastic columnar epithelium with goblet cells, and also revealed significantly higher values compared with those of controls. Furthermore, there were no significant differences in any of the key DNA content abnormalities between non-goblet and goblet cell-containing epithelium in patients with metaplastic columnar epithelium with goblet cells, or between these two types of epithelium according to the density of goblet cells. CONCLUSIONS DNA content abnormalities occur with equal frequency and extent in metaplastic columnar epithelium of the esophagus without goblet cells compared with metaplastic columnar epithelium with goblet cells. These findings suggest that metaplastic non-goblet columnar epithelium of the esophagus may have neoplastic potential.
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Affiliation(s)
- Weitian Liu
- Pathology Department, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA,Division of Gastroenterology, Department of Medicine, VA Boston Healthcare System, Harvard Medical School, West Roxbury, Massachusetts, USA
| | - Hejin Hahn
- Pathology Department, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Robert D. Odze
- Pathology Department, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Raj K. Goyal
- Pathology Department, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Wani S, Puli SR, Shaheen NJ, Westhoff B, Slehria S, Bansal A, Rastogi A, Sayana H, Sharma P. Esophageal adenocarcinoma in Barrett's esophagus after endoscopic ablative therapy: a meta-analysis and systematic review. Am J Gastroenterol 2009; 104:502-13. [PMID: 19174812 DOI: 10.1038/ajg.2008.31] [Citation(s) in RCA: 141] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The extent of reduction of esophageal adenocarcinoma (EAC) incidence in Barrett's esophagus (BE) patients after endoscopic ablation is not known. The objective of this study was to determine the cancer incidence in BE patients after ablative therapy and compare these rates to cohort studies of BE patients not undergoing ablation. METHODS A MEDLINE search of the literature on the natural history and ablative modalities in BE patients was performed. Patients with nondysplastic BE (NDBE), low-grade dysplasia (LGD), or high-grade dysplasia (HGD) and follow-up of at least 6 months were included. The rate of cancer in patients undergoing ablation and from the natural history data was calculated using weighted-average incidence rates (WIR). RESULTS A total of 53 articles met the inclusion criteria for the natural history data. Pooled natural history data showed cancer incidence of 5.98/1,000 patient-years (95% CI 5.05-6.91) in NDBE; 16.98/1,000 patient-years (95% CI 13.1-20.85) in LGD; and 65.8/1,000 patient-years (95% CI 49.7-81.8) in HGD patients. A total of 65 articles met the inclusion criteria for BE patients undergoing ablation (1,457 patients, NDBE; 239 patients, LGD; and 611 patients, HGD). The WIR for cancer was 1.63/1,000 patient-years (95% CI 0.07-3.34) for NDBE; 1.58/1,000 patient-years (95% CI 0.66-3.84) for LGD; and 16.76/1,000 patient-years (95% CI 10.6-22.9) for HGD patients. CONCLUSIONS Compared to historical reports of the natural history of BE, ablation may be associated with a reduction in cancer incidence, although such a comparison is limited by likely heterogeneity between treatment and natural history studies. The greatest benefit of ablation was observed in BE patients with HGD.
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Affiliation(s)
- Sachin Wani
- Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center, University of Kansas School of Medicine, Kansas City, Missouri, USA
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Bird-Lieberman EL, Lao-Sirieix P, Saeed I, Khoo D, Burnham R, Fitzgerald R. The definition and management of Barrett's oesophagus: a case report, review of the literature and a suggestion for the future. BMJ Case Rep 2009; 2009:bcr07.2008.0450. [PMID: 21686804 DOI: 10.1136/bcr.07.2008.0450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
The definition of Barrett's oesophagus continues to evolve and there has been divergence in the diagnostic criteria internationally, which has implications for surveillance practices and research inclusion criteria. Here we describe the case of a 69-year-old female with 10 cm of gastric-type columnar-lined oesophagus confirmed on histochemical staining. Surveillance biopsies, performed according to protocol, revealed an intramucosal adenocarcinoma. The patient was successfully treated with a transhiatal oesophagectomy and a detailed examination of the entire surgical specimen confirmed that the columnar oesophagus was lined by gastric villiform mucosa complicated by intramucosal carcinoma, on the background of dysplasia with no intestinal metaplasia. This highlights the spectrum of metaplastic epithelia that can harbour malignant potential. There is a need for an international consensus on the classification of Barrett's oesophagus to aid research progress. Therefore, we propose a new classification for Barrett's oesophagus based on a combination of endoscopic and histopathological features.
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Abstract
Barrett's esophagus is an important step in the pathway to esophageal adenocarcinoma. Since most patients with Barrett's esophagus are undiagnosed and patients present with advanced adenocarcinoma de novo, prognosis for this disease remains poor. To identify those people with Barrett's esophagus who are at particular risk many new technologies are being developed. In association with these advances in risk stratification, progress is being made in the endoscopic treatment of Barrett's. Chemoprevention is also an area of interest and trials are underway.
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Tower RL, Spector LG. The Epidemiology of Childhood Leukemia with a Focus on Birth Weight and Diet. Crit Rev Clin Lab Sci 2008; 44:203-42. [PMID: 17453918 DOI: 10.1080/10408360601147536] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Leukemia is the most common childhood cancer and a major source of morbidity and mortality. The etiology of childhood leukemia remains largely unknown. Cytogenetic abnormalities determine disease subtypes, prognosis, clinical presentation, and course and may help in discovering etiological factors. Epidemiologic investigations of leukemia are complicated by many factors, including the rarity of the disease, necessitating careful study design. Two emerging areas of interest in leukemia etiology are birth weight and diet. High birth weight has been associated with increased risk of childhood leukemia. The biological mechanism behind this association may involve insulin-like growth factor I (IGF-I), which is associated with high birth weight. IGF-I may act by increasing the absolute number of stem cells available for transformation, stimulating the growth of cells that are already transformed, or a combination of effects. Diet has been linked with leukemia. Maternal dietary DNA topoisomerase II (DNAt2) inhibitor intake is associated with infant acute myeloid leukemia (AML) with the MLL gene translocation. Increased intake of fruits and vegetables has been associated with decreased leukemia risk and, relatedly, lack of maternal folate supplementation has been associated with increased childhood leukemia risk, possibly by causing DNA hypomethylation and increased DNA strand breaks. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms modify this risk.
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Affiliation(s)
- Richard L Tower
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA
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Smith E, De Young NJ, Pavey SJ, Hayward NK, Nancarrow DJ, Whiteman DC, Smithers BM, Ruszkiewicz AR, Clouston AD, Gotley DC, Devitt PG, Jamieson GG, Drew PA. Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal adenocarcinoma. Mol Cancer 2008; 7:75. [PMID: 18831746 PMCID: PMC2567345 DOI: 10.1186/1476-4598-7-75] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2008] [Accepted: 10/02/2008] [Indexed: 02/06/2023] Open
Abstract
Background Barrett's esophagus (BE) is the metaplastic replacement of squamous with columnar epithelium in the esophagus, as a result of reflux. It is the major risk factor for the development of esophageal adenocarcinoma (EAC). Methylation of CpG dinucleotides of normally unmethylated genes is associated with silencing of their expression, and is common in EAC. This study was designed to determine at what stage, in the progression from BE to EAC, methylation of key genes occurs. Results We examined nine genes (APC, CDKN2A, ID4, MGMT, RBP1, RUNX3, SFRP1, TIMP3, and TMEFF2), frequently methylated in multiple cancer types, in a panel of squamous (19 biopsies from patients without BE or EAC, 16 from patients with BE, 21 from patients with EAC), BE (40 metaplastic, seven high grade dysplastic) and 37 EAC tissues. The methylation frequency, the percentage of samples that had any extent of methylation, for each of the nine genes in the EAC (95%, 59%, 76%, 57%, 70%, 73%, 95%, 74% and 83% respectively) was significantly higher than in any of the squamous groups. The methylation frequency for each of the nine genes in the metaplastic BE (95%, 28%, 78%, 48%, 58%, 48%, 93%, 88% and 75% respectively) was significantly higher than in the squamous samples except for CDKN2A and RBP1. The methylation frequency did not differ between BE and EAC samples, except for CDKN2A and RUNX3 which were significantly higher in EAC. The methylation extent was an estimate of both the number of methylated alleles and the density of methylation on these alleles. This was significantly greater in EAC than in metaplastic BE for all genes except APC, MGMT and TIMP3. There was no significant difference in methylation extent for any gene between high grade dysplastic BE and EAC. Conclusion We found significant methylation in metaplastic BE, which for seven of the nine genes studied did not differ in frequency from that found in EAC. This is also the first report of gene silencing by methylation of ID4 in BE or EAC. This study suggests that metaplastic BE is a highly abnormal tissue, more similar to cancer tissue than to normal epithelium.
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Affiliation(s)
- Eric Smith
- School of Nursing and Midwifery, Flinders University, Bedford Park, South Australia 5042, Australia
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Armstrong D. Should patients with Barrett's oesophagus be kept under surveillance? The case for. Best Pract Res Clin Gastroenterol 2008; 22:721-39. [PMID: 18656826 DOI: 10.1016/j.bpg.2008.03.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Oesophageal adenocarcinoma is associated with high mortality rates and its incidence is increasing more rapidly than any other gastrointestinal cancer in the Western world. Several factors, including gastro-oesophageal reflux disease, smoking, alcohol and male gender, are associated with oesophageal adenocarcinoma but none can be used to identify accurately those individuals who will develop adenocarcinoma. It is generally accepted that oesophageal adenocarcinoma arises predominantly in Barrett's oesophagus and it is arguable that Barrett's oesophagus is currently the only clinically useful predictor of oesophageal adenocarcinoma. Surveillance - periodic testing to detect adenocarcinoma or its precursor, high grade dysplasia - is widely recommended for patients with Barrett's oesophagus with the aim of reducing mortality from oesophageal adenocarcinoma. The annual incidence of oesophageal adenocarcinoma in patients with Barrett's oesophagus is 0.5%-1.0% although there is marked variation between studies, attributable variously to publication bias, concurrent acid suppression therapy and differences in patient characteristics. There is limited evidence that surveillance reduces the incidence of oesophageal adenocarcinoma or consequent mortality and the cause of death for patients undergoing surveillance is often unrelated to oesophageal disease. There are, nonetheless, observational studies which suggest that surveillance is associated with earlier detection of malignancy and a reduction in mortality; in addition, data from modelling studies suggest that surveillance can be cost-effective. Furthermore, the advent of new, non-surgical treatments (endoscopic mucosal resection, photodynamic therapy, argon plasma coagulation) for high grade dysplasia and early cancer has reduced the risks associated with therapy for disease detected during surveillance. Surveillance programs have high drop out rates and, for patients who continue surveillance, adherence to standard, published protocols is highly variable. The establishment of specialist Barrett's oesophagus surveillance programs, with coordinator support, has considerable potential to improve adherence to current guidelines, pending the acquisition and publication of data from ongoing studies of chemoprophylaxis and surveillance in the management of Barrett's oesophagus. In consequence, although there is a paucity of data providing unequivocal demonstration of benefit, there is no proof that surveillance is ineffective. It is, therefore, appropriate to offer surveillance for Barrett's oesophagus in accordance with locally-applicable published guidelines after a full informed discussion of the risks and benefits of surveillance and therapy; continued participation should be reviewed regularly to accommodate changes in the patient's health and expectations.
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Affiliation(s)
- David Armstrong
- HSC-2F55, Division of Gastroenterology, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
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Yousef F, Cardwell C, Cantwell MM, Galway K, Johnston BT, Murray L. The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis. Am J Epidemiol 2008; 168:237-49. [PMID: 18550563 DOI: 10.1093/aje/kwn121] [Citation(s) in RCA: 307] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Barrett's esophagus is a well-recognized precursor of esophageal adenocarcinoma. Surveillance of Barrett's esophagus patients is recommended to detect high-grade dysplasia (HGD) or early cancer. Because of wide variation in the published cancer incidence in Barrett's esophagus, the authors undertook a systematic review and meta-analysis of cancer and HGD incidence in Barrett's esophagus. Ovid Medline (Ovid Technologies, Inc., New York, New York) and EMBASE (Elsevier, Amsterdam, the Netherlands) databases were searched for papers published between 1950 and 2006 that reported the cancer/HGD risk in Barrett's esophagus. Where possible, early incident cancers/HGD were excluded, as were patients with HGD at baseline. Forty-seven studies were included in the main analysis, and the pooled estimate for cancer incidence in Barrett's esophagus was 6.1/1,000 person-years, 5.3/1,000 person-years when early incident cancers were excluded, and 4.1/1,000 person-years when both early incident cancer and HGD at baseline were excluded. Corresponding figures for combined HGD/cancer incidence were 10.0 person-years, 9.3 person-years, and 9.1/1,000 person-years. Compared with women, men progressed to cancer at twice the rate. Cancer or HGD/cancer incidences were lower when only high-quality studies were analyzed (3.9/1,000 person-years and 7.7/1,000 person-years, respectively). The pooled estimates of cancer and HGD incidence were low, suggesting that the cost-effectiveness of surveillance is questionable unless it can be targeted to those with the highest cancer risk.
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Affiliation(s)
- Fouad Yousef
- Cancer Epidemiology and Prevention Research Group, Centre for Clinical and Population Sciences, Queen's University of Belfast, Belfast, Northern Ireland, United Kingdom.
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