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Kroep S, Lansdorp-Vogelaar I, van der Steen A, Inadomi JM, van Ballegooijen M. The Impact of Uncertainty in Barrett's Esophagus Progression Rates on Hypothetical Screening and Treatment Decisions. Med Decis Making 2014; 35:726-33. [PMID: 25277672 DOI: 10.1177/0272989x14551640] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Accepted: 07/30/2014] [Indexed: 01/10/2023]
Abstract
BACKGROUND Estimates for the annual progression rate from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) vary widely. In this explorative study, we quantified how this uncertainty affects the estimates of effectiveness and efficiency of screening and treatment for EAC. DESIGN We developed 3 versions of the University of Washington / Microsimulation Screening Analysis-EAC model. The models differed with respect to the annual progression rate from BE to EAC (0.12% or 0.42%) and the possibility of spontaneous regression of dysplasia (yes or no). All versions of the model were calibrated to the observed Surveillance, Epidemiology, and End Results esophageal cancer incidence rates from 1998 to 2009. To identify the impact of natural history, we estimated the incidence and deaths prevented as well as numbers needed to screen (NNS) and treat (NNT) of a one-time perfect screening at age 65 years that detected all prevalent BE cases, followed by a perfect treatment intervention. RESULTS Assuming a perfect screening and treatment intervention for all patients with BE, the maximum EAC mortality reduction (64%-66%) and the NNS per death prevented (470-510) were similar across the 3 model versions. However, 3 times more people needed to be treated to prevent 1 death (24 v. 8) in the 0.12% regression model compared with the 0.42% progression model. Restricting treatment to those with dysplasia or only high-grade dysplasia resulted in smaller differences in NNT (2-3 to prevent one EAC case) but wider variation in effectiveness (mortality reduction of 15%-24%). CONCLUSION The uncertainty in the natural history of the BE to EAC sequence influenced the estimates of effectiveness and efficiency of BE screening and treatment considerably. This uncertainty could seriously hamper decision making about implementing BE screening and treatment interventions.
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Affiliation(s)
- Sonja Kroep
- Department of Public Health, Erasmus Medical Center University, Rotterdam, the Netherlands (SK, ILV, AVDS, MVB)
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus Medical Center University, Rotterdam, the Netherlands (SK, ILV, AVDS, MVB)
| | - Alex van der Steen
- Department of Public Health, Erasmus Medical Center University, Rotterdam, the Netherlands (SK, ILV, AVDS, MVB)
| | - John M Inadomi
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington, USA (JMI)
| | - Marjolein van Ballegooijen
- Department of Public Health, Erasmus Medical Center University, Rotterdam, the Netherlands (SK, ILV, AVDS, MVB)
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Oryu M, Mori H, Kobara H, Nishiyama N, Fujihara S, Kobayashi M, Yasuda M, Masaki T. Differences in the Characteristics of Barrett's Esophagus and Barrett's Adenocarcinoma between the United States and Japan. ISRN GASTROENTEROLOGY 2013; 2013:840690. [PMID: 23606979 PMCID: PMC3625601 DOI: 10.1155/2013/840690] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Accepted: 03/10/2013] [Indexed: 12/12/2022]
Abstract
In Europe and the United States, the incidence of esophageal adenocarcinoma has increased 6-fold in the last 25 years and currently accounts for more than 50% of all esophageal cancers. Barrett's esophagus is the source of Barrett's adenocarcinoma and is characterized by the replacement of squamous epithelium with columnar epithelium in the lower esophagus due to chronic gastroesophageal reflux disease (GERD). Even though the prevalence of GERD has recently been increasing in Japan as well as in Europe and the United States, the clinical situation of Barrett's esophagus and Barrett's adenocarcinoma differs from that in Western countries. In this paper, we focus on specific differences in the background factors and pathophysiology of these lesions.
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Affiliation(s)
- Makoto Oryu
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan
| | - Hirohito Mori
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan
| | - Noriko Nishiyama
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan
| | - Shintaro Fujihara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan
| | - Mitsuyoshi Kobayashi
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan
| | - Mitsugu Yasuda
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu, Kagawa 761-0793, Japan
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Rees JRE, Lao‐Sirieix P, Wong A, Fitzgerald RC, Cochrane Upper GI and Pancreatic Diseases Group. Treatment for Barrett's oesophagus. Cochrane Database Syst Rev 2010; 2010:CD004060. [PMID: 20091557 PMCID: PMC7163253 DOI: 10.1002/14651858.cd004060.pub2] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Treatments for Barrett's oesophagus, the precursor lesion of adenocarcinoma, are available but whether these therapies effectively prevent the development of adenocarcinoma, and in some cases eradicate the Barrett's oesophagus segment, remains unclear. OBJECTIVES To summarise, quantify and compare the efficacy of pharmacological, surgical and endoscopic treatments for the eradication of dysplastic and non-dysplastic Barrett's oesophagus and prevention of these states from progression to adenocarcinoma. SEARCH STRATEGY We searched CENTRAL (The Cochrane Library 2004, issue 4), MEDLINE (1966 to June 2008) and EMBASE (1980 to June 2008). SELECTION CRITERIA Randomised controlled trials (RCTs) comparing medical, endoscopic or non-resectional surgical treatments for Barrett's oesophagus. The primary outcome measures were complete eradication of Barrett's and dysplasia at 12 months, and reduction in the number of patients progressing to cancer at five years or latest time point. DATA COLLECTION AND ANALYSIS Three authors independently extracted data and assessed the quality of the trials included in the analysis. MAIN RESULTS Sixteen studies, including 1074 patients, were included. The mean number of participants in the studies was small (n = 49; range 8 to 208). Most studies did not report on the primary outcomes. Medical and surgical interventions to reduce symptoms and sequelae of gastro-oesophageal reflux disease (GORD) did not induce significant eradication of Barrett's oesophagus or dysplasia. Endoscopic therapies (photodynamic therapy (PDT with aminolevulinic acid or porfimer sodium), argon plasma coagulation (APC) and radiofrequency ablation (RFA)) all induced regression of Barrett's oesophagus and dysplasia. The data for photodynamic therapy were heterogeneous with a mean eradication rate of 51% for Barrett's oesophagus and between 56% and 100% for dysplasia, depending on the treatment regimens. The variation in photodynamic therapy eradication rates for dysplasia was dependent on the drug, source and dose of light. Radiofrequency ablation resulted in eradication rates of 82% and 94% for Barrett's oesophagus and dysplasia respectively, compared to a sham treatment. Endoscopic treatments were generally well tolerated, however all were associated with some buried glands, particularly following argon plasma coagulation and photodynamic therapy, as well as photosensitivity and strictures induced by porfimer sodium based photodynamic therapy in particular. AUTHORS' CONCLUSIONS Despite their failure to eradicate Barrett's oesophagus, the role of medical and surgical interventions to reduce the troubling symptoms and sequelae of GORD is not questioned. Whether therapies for GORD reduce the cancer risk is not yet known. Ablative therapies have an increasing role in the management of dysplasia within Barrett's and current data would favour the use of radiofrequency ablation compared with photodynamic therapy. Radiofrequency ablation has been shown to yield significantly fewer complications than photodynamic therapy and is very efficacious at eradicating both dysplasia and Barrett's itself. However, long-term follow-up data are still needed before radiofrequency ablation can be used in routine clinical care without the need for very careful post-treatment surveillance. More clinical trial data and in particular randomised controlled trials are required to assess whether or not the cancer risk is reduced in routine clinical practice.
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Affiliation(s)
- Jonathan RE Rees
- Hutchison/MRC Research CentreMRC Cancer Cell UnitHills RoadCambridgeUKCB22 2XZ
| | - Pierre Lao‐Sirieix
- Hutchison/MRC Research CentreMRC Cancer Cell UnitHills RoadCambridgeUKCB22 2XZ
| | - Angela Wong
- Hutchison/MRC Research CentreMRC Cancer Cell UnitHills RoadCambridgeUKCB22 2XZ
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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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Chang EY, Morris CD, Seltman AK, O'Rourke RW, Chan BK, Hunter JG, Jobe BA. The effect of antireflux surgery on esophageal carcinogenesis in patients with barrett esophagus: a systematic review. Ann Surg 2007; 246:11-21. [PMID: 17592284 PMCID: PMC1899200 DOI: 10.1097/01.sla.0000261459.10565.e9] [Citation(s) in RCA: 151] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To determine whether patients with Barrett esophagus who undergo antireflux surgery differ from medically treated patients in incidence of esophageal adenocarcinoma and probability of disease regression/progression. SUMMARY BACKGROUND DATA Barrett esophagus is a risk factor for the development of esophageal adenocarcinoma. A question exists as to whether antireflux surgery reduces this risk. METHODS Query of PubMed (1966 through October 2005) using predetermined search terms revealed 2011 abstracts, of which 100 full-text articles were reviewed. Twenty-five articles met selection criteria. A review of article references and consultation with experts revealed additional articles for inclusion. Studies that enrolled adults with biopsy-proven Barrett esophagus, specified treatment-type rendered, followed up patients with endoscopic biopsies no less than12 months of instituting therapy, and provided adequate extractable data. The incidence of adenocarcinoma and the proportion of patients developing progression or regression of Barrett esophagus and/or dysplasia were extracted. RESULTS In surgical and medical groups, 700 and 996 patients were followed for a total of 2939 and 3711 patient-years, respectively. The incidence rate of esophageal adenocarcinoma was 2.8 (95% confidence interval, 1.2-5.3) per 1000 patient-years among surgically treated patients and 6.3 (3.6-10.1) among medically treated patients (P = 0.034). Heterogeneity in incidence rates in surgically treated patients was observed between controlled studies and case series (P = 0.014). Among controlled studies, incidence rates were 4.8 (1.7-11.1) and 6.5 (2.6-13.8) per 1000 patient-years in surgical and medical patients, respectively (P = 0.320). Probability of progression was 2.9% (1.2-5.5) in surgical patients and 6.8% (2.6-12.1) in medical patients (P = 0.054). Probability of regression was 15.4% (6.1-31.4) in surgical patients and 1.9% (0.4-7.3) in medical patients (P = 0.004). CONCLUSIONS Antireflux surgery is associated with regression of Barrett esophagus and/or dysplasia. However, evidence suggesting that surgery reduces the incidence of adenocarcinoma is largely driven by uncontrolled studies.
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Affiliation(s)
- Eugene Y Chang
- Department of Surgery, Oregon Health & Science University, Portland, OH, USA
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6
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Rubenstein JH, Inadomi JM, Brill JV, Eisen GM. Cost utility of screening for Barrett's esophagus with esophageal capsule endoscopy versus conventional upper endoscopy. Clin Gastroenterol Hepatol 2007; 5:312-8. [PMID: 17368230 DOI: 10.1016/j.cgh.2006.12.008] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Screening for Barrett's esophagus with conventional esophagoduodenoscopy (EGD) is recommended to decrease mortality from esophageal adenocarcinoma. Esophageal capsule endoscopy (ECE) has recently been shown to be accurate in detecting Barrett's esophagus. We aimed to compare the cost-effectiveness of screening by ECE with screening by EGD. METHODS A Markov model of 50-year-old white men with symptoms of gastroesophageal reflux was constructed to compare screening modalities. The model incorporated direct medical costs and indirect costs of lost productivity and followed the patients until age 80 years or death. Outcomes were analyzed from the societal perspective. RESULTS EGD screening prevented 60% of cancer deaths at a cost of $11,254 per quality-adjusted life year gained compared with no screening. ECE prevented 53% of cancer deaths and provided 9 fewer quality-adjusted days at greater cost than EGD. If society were only willing to pay $50,000 per quality-adjusted life year gained, then capsule screening would be preferred if the income of the patient and driver were each greater than $280,682. Otherwise, the findings were robust to all sensitivity analyses. CONCLUSIONS Screening for Barrett's esophagus with either EGD or ECE results in similar outcomes, but EGD is the preferred strategy. Both strategies appear cost-effective, and the model does not take into account patient preferences for screening modality or adherence.
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Affiliation(s)
- Joel H Rubenstein
- Division of Gastroenterology, University of Michigan Medical School, and the Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan 48105, USA.
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7
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Casson AG, Williams L, Guernsey DL. Epidemiology and molecular biology of Barrett esophagus. Semin Thorac Cardiovasc Surg 2006; 17:284-91. [PMID: 16428034 DOI: 10.1053/j.semtcvs.2005.09.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/27/2005] [Indexed: 12/19/2022]
Abstract
Over the past three decades, there has been a marked change in the epidemiology of esophageal malignancy, with an increasing incidence of esophageal adenocarcinoma. The reasons for this are largely unknown and remain controversial, but several lifestyle risk factors have been proposed, including gastroesophageal reflux disease (GERD). It is hypothesized that chronic GERD results in acute mucosal injury, promotes cellular proliferation, and induces specialized columnar metaplasia (Barrett esophagus). Progression of Barrett esophagus to invasive adenocarcinoma is reflected histologically by the metaplasia-dysplasia-carcinoma sequence. Dysplasia is widely regarded as the precursor of invasive cancer, and high-grade dysplasia in Barrett epithelium is frequently associated with esophageal adenocarcinoma. Although several molecular alterations have been described in Barrett esophagus, it is anticipated that relatively few will prove to be clinically useful. To date, biomarkers which currently appear to predict the progression of Barrett esophagus to invasive malignancy include aneuploidy, loss of heterozygosity of 17p (implicating the p53 tumor suppressor gene), and cyclin D1 protein overexpression, and with further validation, will most likely be incorporated into routine clinical practice. It is anticipated that models incorporating objective scores of sociodemographic and lifestyle risk factors (ie, age, gender, body mass index), severity of reflux symptoms, endoscopic and histologic findings, and an assessment of a panel of biomarkers will be developed to further define subsets of patients with Barrett esophagus at increased risk for malignant progression, thereby permitting the development of more rational endoscopic surveillance and screening programs.
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Affiliation(s)
- Alan G Casson
- Department of Surgery, Division of Thoracic Surgery, Dalhousie University and the QEII Health Sciences Centre, Halifax, Nova Scotia, Canada.
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8
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Abstract
Concern over how best to manage individuals with Barrett's esophagus (BE) has grown because of the consistent rise in the incidence of esophageal adenocarcinoma. Since the 1970s, the rate of increase in incidence of esophageal adenocarcinoma has been greater than that for any other cancer in the US population. Patients with BE have increased risk for esophageal cancer, but the rate of progression and potential risk factors in progression remain poorly understood. Much remains to be learned about BE and its association with adenocarcinoma before effective surveillance or management strategies can be defined and implemented. In this article, the relationship between BE and gastroesophageal reflux disease, risk for adenocarcinoma, and prospects for molecular diagnosis are discussed.
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Affiliation(s)
- Robert Bresalier
- Department of Gastrointestinal Medicine and Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
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9
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Abstract
BACKGROUND Diagnosing a potentially life-threatening disease may adversely affect patient quality of life (QOL) independent of biologic effects. It is unknown whether the mere diagnosis of Barrett's esophagus (BE) adversely impacts patients' preferences (health-state utility) sufficiently to impair the cost-effectiveness of endoscopic screening for esophageal adenocarcinoma. GOAL To calculate the threshold impact on utility incurred by diagnosing BE that would allow screening to remain cost-effective. STUDY A Markov model was developed to examine strategies of no screening, and screening with surveillance of BE. Patients were 50-year-old white men with symptoms of gastroesophageal reflux followed until 80 years of age or death. The primary outcomes were the threshold decrements in utility incurred by diagnosing BE based on willingness to pay (WTP) of dollar 50,000 and dollar 100,000 per quality-adjusted life-year (QALY) gained. RESULTS For a WTP of dollar 50,000/QALY, the decrement in utility could be as great as 9%, meaning that screening is cost-effective as long as diagnosing BE does not impair QOL by more than 9%. For a WTP of dollar 100,000, the decrement could be as great as 10.5%. CONCLUSIONS The decrement in utility caused by diagnosing BE may be substantial without compromising the cost-effectiveness of endoscopic screening.
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Affiliation(s)
- Joel H Rubenstein
- Division of Gastroenterology, University of Michigan Health System and Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI 48105, USA.
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10
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Cantù P, Savojardo D, Carmagnola S, Penagini R. Impact of referral for gastro-oesophageal reflux disease on the workload of an academic Gastroenterology Unit. Dig Liver Dis 2005; 37:735-40. [PMID: 16024304 DOI: 10.1016/j.dld.2005.04.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2004] [Accepted: 04/01/2005] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gastro-oesophageal reflux disease is known to be a frequent cause of patients' referral to hospital gastroenterologists. AIM To increase knowledge on referral for reflux disease, in an Italian academic setting. PATIENTS AND METHODS The impact of gastro-oesophageal reflux disease on 1 year's workload, comprising upper endoscopy, outpatients' consultations in the general clinic, oesophageal pH monitoring and oesophageal manometry was retrospectively assessed. Appropriateness of oesophageal pH monitoring and oesophageal manometry was also evaluated. RESULTS Endoscopy: Out of 2269 upper endoscopies reflux symptoms comprised 16.9% (n=386) of referrals; 19.1% only of these 386 patients had erosive oesophagitis at endoscopy and none had oesophagogastric malignancies (68% of the patients were >45 years). Consultations: Thirty-three percent out of 553 patients were referred for reflux symptoms. Upper endoscopy had already been performed before consultation in 64% of them. pH monitoring and oesophageal manometry: Two hundred and sixteen oesophageal pH monitorings and 160 oesophageal manometries were performed and 29% and 28%, respectively, were inappropriate, being performed in the diagnostic work-up of patients with typical reflux symptoms. CONCLUSIONS At an academic Gastroenterology Unit, (a) gastro-oesophageal reflux disease is a frequent referral for upper endoscopy and consultations, (b) prevalence of oesophagitis is low, (c) consultation is preceded by endoscopy in the majority of patients and (d) oesophageal pH monitoring and oesophageal manometry are often inappropriately used.
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Affiliation(s)
- P Cantù
- Department of Medical Sciences, University of Milan, IRCCS Maggiore Hospital, Pad Granelli, Via F Sforza 35, 20122 Milan, Italy
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Ford AC, Forman D, Reynolds PD, Cooper BT, Moayyedi P. Ethnicity, gender, and socioeconomic status as risk factors for esophagitis and Barrett's esophagus. Am J Epidemiol 2005; 162:454-60. [PMID: 16076833 DOI: 10.1093/aje/kwi218] [Citation(s) in RCA: 122] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Barrett's esophagus is thought to be a disease occurring predominantly in White Caucasian males of higher socioeconomic status. There are no published studies simultaneously examining risk of Barrett's esophagus according to ethnicity, gender, and socioeconomic status within a single data set. The authors conducted a retrospective case-control analysis within a cross-sectional study to determine risk of Barrett's esophagus in relation to sociodemographic variables in a large United Kingdom population. All patients undergoing upper gastrointestinal endoscopy at two clinical centers between January 2000 and January 2003 were evaluated. Data on ethnicity, age, gender, socioeconomic status, and the presence of Barrett's esophagus and esophagitis at endoscopy were collected. A total of 20,310 patients were analyzed. Barrett's esophagus was more common in White Caucasians (401/14,095 (2.8%)) than in South Asians (16/5,190 (0.3%)) (adjusted odds ratio (OR)=6.03, 95% confidence interval (CI): 3.56, 10.22), as was esophagitis (2,500/14,095 (17.7%) vs. 557/5,190 (10.7%); adjusted OR=1.76, 95% CI: 1.57, 1.97). Patients with Barrett's esophagus were also more likely to be male (adjusted OR=2.70, 95% CI: 2.18, 3.35) and of higher socioeconomic status (adjusted OR=1.58, 95% CI: 1.16, 2.15 (top tertile vs. bottom tertile)). White Caucasian ethnicity, male gender, and higher socioeconomic status are independent risk factors for Barrett's esophagus.
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Affiliation(s)
- Alexander C Ford
- Centre for Digestive Diseases, Leeds General Infirmary, Leeds, United Kingdom.
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12
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Rubenstein JH, Vakil N, Inadomi JM. The cost-effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma. Aliment Pharmacol Ther 2005; 22:135-46. [PMID: 16011672 DOI: 10.1111/j.1365-2036.2005.02536.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND The recommended surveillance strategy for oesophageal adenocarcinoma may prevent as few as 50% of cancer deaths. Tissue biomarkers have been proposed to identify high-risk patients. AIM To determine performance characteristics of an ideal biomarker, or panel of biomarkers, that would make its use more cost-effective than the current surveillance strategy. METHODS We created a Markov model using data from published literature, and performed a cost-utility analysis. The population consisted of 50-year-old Caucasian men with gastro-oesophageal reflux, who were monitored until age 80. We examined strategies of observation only, current practice (dysplasia-guided surveillance), surveillance every 3 months for patients with a positive biomarker (biomarker-guided surveillance), and oesophagectomy immediately for a positive biomarker (biomarker-guided oesophagectomy). The primary outcome was the threshold cost and performance characteristics needed for a biomarker to be more cost-effective than current practice. RESULTS Regardless of the cost, the biomarker needs to be at least 95% specific for biomarker-guided oesophagectomy to be cost-effective. For biomarker-guided surveillance to be cost-effective, a $100 biomarker could be 80% sensitive and specific. CONCLUSIONS Biomarkers predicting the development of oesophageal adenocarcinoma would need to be fairly accurate and inexpensive to be cost-effective. These results should guide the development of biomarkers for oesophageal adenocarcinoma.
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Affiliation(s)
- J H Rubenstein
- University of Michigan Health System, Ann Arbor, MI, USA.
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Rubenstein JH, Inadomi JM. Dysphagia drives doctors to diagnose a disease: pitfalls in interpreting observational studies. Gastrointest Endosc 2005; 61:809-11. [PMID: 15933680 DOI: 10.1016/s0016-5107(05)00544-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Pisegna J, Holtmann G, Howden CW, Katelaris PH, Sharma P, Spechler S, Triadafilopoulos G, Tytgat G. Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2004; 20 Suppl 9:47-56. [PMID: 15527464 PMCID: PMC6736593 DOI: 10.1111/j.1365-2036.2004.02240.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The major oesophageal complications associated with persistent gastro-oesophageal reflux disease (GERD) include erosive oesophagitis, ulceration, strictures and gastrointestinal (GI) bleeding. Although the causes of these complications are uncertain, studies indicate that erosive oesophagitis may progress to the development of ulcers, strictures and GI bleeding. Pharmacological treatment with proton pump inhibitors is favoured over that with H(2)-receptor antagonists for the treatment of strictures. The treatment of strictures is accomplished with dilation and many favour the concomitant use of proton pump inhibitors. Most gastroenterologists are seeing far fewer oesophageal strictures these days since the introduction of proton pump inhibitors. In addition, research has shown that oesophageal complications have a greater impact on patients suffering from night-time GERD than on those suffering from daytime GERD. Barrett's oesophagus is a significant complication associated with persistent GERD and those at risk generally experience a longer duration of symptoms, especially those with a high degree of severity. In addition, there is a strong relationship between Barrett's oesophagus and oesophageal adenocarcinoma. This is in part due to the association of obesity and the development of hiatal hernias. Furthermore, endoscopic screening is being used to detect Barrett's oesophagus and oesophageal adenocarcinoma in persons suffering from chronic GERD, even though screening may not have an impact on outcomes (Sharma P, McQuaid K, Dent J, et al. A critical review of the diagnosis and management of Barrett's esophagus: The AGA Chicago Workshop. Gastroenterology 2004; 127: 310-30.).
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Affiliation(s)
- J Pisegna
- Division of Gastroenterology and Hepatology, VA Greater Los Angeles Health Care System, Los Angeles, CA 90073, USA.
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Pera M. Trends in incidence and prevalence of specialized intestinal metaplasia, barrett's esophagus, and adenocarcinoma of the gastroesophageal junction. World J Surg 2003; 27:999-1008; discussion 1006-8. [PMID: 12917764 DOI: 10.1007/s00268-003-7052-2] [Citation(s) in RCA: 81] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Most available information on the epidemiology of Barrettacute;s esophagus (BE) relates to patients with long segments (> 3 cm) of specialized intestinal metaplasia (SIM). Its prevalence is 3% in patients undergoing endoscopy for reflux symptoms and 1% in those undergoing endoscopy for any clinical indication. The latter prevalence is similar to the 1% found in autopsy series. A "silent majority" with BE remain unrecognized in the general population. BE is more common in men, and the prevalence rises with age. Recent endoscopic series document a rise in the diagnosis of endoscopically apparent short segments (< 3 cm) of BE (SSBE). The prevalence of SSBE in both unselected and reflux patients is 8% to 12%. Specialized intestinal metaplasia at the cardia, below a normal-appearing squamocolumnar junction, has been reported to vary from 6% to 25% in patients presenting for upper endoscopy. Unlike patients with long segment Barrett's esophagus (LSBE), the role of gastroesophageal reflux disease in the pathogenesis of SSBE and SIM of the cardia is controversial. Recent data suggest that the etiology of SIM of the cardia might be secondary to Helicobacter pylori infection, although the role of other environmental factors cannot be ruled out. The incidence of adenocarcinoma of the esophagus and esophagogastric juction (EGJ) has been increasing over the past 15 years in Western countries. Surgical series and population-based studies show that by 1994 adenocarcinomas of the esophagus accounted for half of all esophageal cancer among white men. LSBE and SSBE predispose to the development of adenocarcinoma of the esophagus and EGJ. The role of SIM of the cardia as a precursor lesion for EGJ adenocarcinoma is still unclear. The prevalences of dysplasia in LSBE and SSBE are around 6% and 8%, respectively. The incidence of adenocarcinoma in patients with LSBE is about 1 in 100 patient-years. Cancer risk for SSBE and SIM at the cardia is unknown. Smoking and obesity increase the risk for esophageal and EGJ adenocarcinomas.
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Affiliation(s)
- Manuel Pera
- Institute of Digestive Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona Medical School, Villarroel 170, Barcelona 08036, Spain.
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Wang LD, Zheng S, Zheng ZY, Casson AG. Primary adenocarcinomas of lower esophagus, esophagogastric junction and gastric cardia: in special reference to China. World J Gastroenterol 2003; 9:1156-64. [PMID: 12800215 PMCID: PMC4611775 DOI: 10.3748/wjg.v9.i6.1156] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cardia adenocarcinoma (GCA) is an under-studied subject. The pathogenesis, molecular changes in the early stage of carcinogenesis and related risk factors have not been well characterized. There is evidence, however, that GCA differs from cancer of the rest of the stomach in terms of natural history and histopathogenesis. Adenocarcinomas of the lower esophagus, esophagogastric junction (EGJ) and gastric cardia have been given much attention because of their increasing incidences in the past decades, which is in striking contrast with the steady decrease in distal stomach adenocarcinoma. In China, epidemiologically, GCA shares very similar geographic distribution with esophageal squamous cell carcinoma (SCC), especially in Linzhou (formerly Linxian County), Henan Province, North China, the highest incidence area of esophageal SCC in the world. Historically, both GCA and SCC in these areas were referred to as esophageal cancer (EC) by the public because of the common syndrome of dysphagia. In Western countries, Barrett's esophagus is very common and has been considered as an important precancerous lesion of adenocarcinoma at EGJ. Because of the low incidence of Barrett's esophagus in China, it is unlikely to be an important factor in early stage of EGJ adenocarcinoma development. However, Z line up-growth into lower esophagus may be one of the characteristic changes in these areas in early stage of GCA development. Whether intestinal metaplasia (IM) is a premalignant lesion for GCA is still not clear. Higher frequency of IM observed at adjacent GCA tissues in Henan suggests the possibility of IM as a precancerous lesion for GCA in these areas. Molecular information on GCA, especially in early stage, is very limited. The accumulated data about the changes of tumor suppressor gene, such as p53 mutation, and ontogeny, such as C-erbB2, especially the similar alterations in GCA and SCC in the same patient, indicated that there might be some similar risk factors, such as nitrosamine, involved in both GCA and SCC in Henan population. The present observations also suggest that GCA should be considered as a distinct entity.
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Affiliation(s)
- Li-Dong Wang
- Cancer Institute, Zhejiang University, Hangzhou 310009, Jiangsu Province, China.
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17
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Abstract
Barrett's oesophagus is usually the result of severe reflux disease. Relief of reflux symptoms is the primary aim of treatment in patients with Barrett's oesophagus who do not have high-grade dysplasia. Some studies with medium-term (2-5 years) follow up show that antireflux surgery can provide good or excellent symptom control, with normal oesophageal acid exposure, in more than 90% of patients with Barrett's oesophagus. Antireflux surgery, but not medical therapy, can also reduce duodenal nonacid reflux to normal levels. There is no conclusive evidence that antireflux surgery can prevent the development of dysplasia or cancer, or that it can reliably induce regression of dysplasia, and patients with Barrett's oesophagus should therefore remain in a surveillance programme after operation. Some data suggest that antireflux surgery can prevent the development of intestinal metaplasia (IM) in patients with reflux disease but no IM. The combination of antireflux surgery plus an endoscopic ablation procedure is a promising treatment for patients with Barrett's oesophagus with low-grade dysplasia.
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Affiliation(s)
- Reginald V N Lord
- Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, California 90089, USA.
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18
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Chen LQ, Hu CY, Der Sarkissian S, Ferraro P, Pera M, deBlois D, Gaboury L, Duranceau AC. Apoptosis in Barrett's oesophagus following antireflux surgery. Br J Surg 2002; 89:1444-9. [PMID: 12390390 DOI: 10.1046/j.1365-2168.2002.02229.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Intestinal metaplasia persists in Barrett's mucosa despite control of reflux. Tissue homeostasis is maintained by the balance between apoptosis and proliferation. There is an unexplained temporary increase in proliferation in patients with Barrett's mucosa after antireflux surgery, and the long-term effect of any therapy in altering this balance remains unclear. The aim of this study was to assess apoptosis in Barrett's oesophagus following antireflux surgery. METHODS Apoptosis was evaluated in endoscopic biopsy specimens from 19 patients with Barrett's oesophagus 4 years after Collis-Nissen gastroplasty using an in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method. RESULTS Intestinal metaplasia had a lower apoptosis index than gastric metaplasia (0.27 versus 2.14 per cent; P < 0.001). After operation there was a steady increase of apoptosis in intestinal metaplasia over time (from 0.23 per cent before operation to 0.42 per cent within 2 years and to 0.59 per cent 4 years after operation; P = 0.015). Patients with persistent acid exposure did not show any increase in apoptosis in comparison with patients without acid exposure (0.41 versus 0.59 per cent; P = 0.91). CONCLUSION Apoptosis is less in intestinal metaplasia than in gastric metaplasia, although there is an increase after antireflux surgery. Persistent acid reflux may predispose to malignancy.
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Affiliation(s)
- L Q Chen
- Department of Surgery, Centre Hospitalier de l'Université de Montréal, Quebec, Canada
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19
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Abstract
Barrett's esophagus is an acquired condition resulting from severe esophageal mucosal injury. It still remains unclear why some patients with gastroesophageal reflux disease develop Barrett's esophagus whereas others do not. The diagnosis of Barrett's esophagus is established if the squamocolumnar junction is displaced proximal to the gastroesophageal junction and if intestinal metaplasia is detected by biopsy. Despite this seemingly simple definition, diagnostic inconsistencies remain a problem, especially in distinguishing short segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. Barrett's esophagus would be of little importance were it not for its well-recognized association with adenocarcinoma of the esophagus. The incidence of esophageal adenocarcinoma continues to increase and the 5-year survival rate for this cancer remains dismal. However, cancer risk for a given patient with Barrett's esophagus is lower than previously estimated. Current strategies for improved survival in patients with esophageal adenocarcinoma focus on cancer detection at an early and potentially curable stage. This can be accomplished either by screening more patients for Barrett's esophagus or with endoscopic surveillance of patients with known Barrett's esophagus. Current screening and surveillance strategies are inherently expensive and inefficient. New techniques to improve the efficiency of cancer surveillance are evolving rapidly and hold the promise to change clinical practice in the future. Treatment options include aggressive acid suppression, antireflux surgery, chemoprevention, and ablation therapy, but there is still no clear consensus on the optimal treatment for these patients.
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Affiliation(s)
- Gary W Falk
- Department of Gastroenterology, Center for Swallowing and Esophageal Disorders, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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20
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Sonnenberg A, Soni A, Sampliner RE. Medical decision analysis of endoscopic surveillance of Barrett's oesophagus to prevent oesophageal adenocarcinoma. Aliment Pharmacol Ther 2002; 16:41-50. [PMID: 11856077 DOI: 10.1046/j.1365-2036.2002.01146.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Barrett's oesophagus is associated with an increased risk of the development of oesophageal adenocarcinoma. Endoscopic surveillance every 2-5 years has been recommended to prevent death from adenocarcinoma. AIM To assess the cost-effectiveness of this strategy. METHODS The incremental cost-effectiveness of surveillance (as compared to no surveillance) was analysed with a computer model of a Markov process. RESULTS Compared to no surveillance, the incremental cost-effectiveness of bi-annual endoscopy is 16,695 dollars per life-year saved. Surveillance is less cost-effective if the incidence rate of oesophageal adenocarcinoma is low and the 5-year survival rate is high. For surveillance to be cost-effective, there should be little reduction in health-related quality of life following surgical oesophagectomy to prevent death. Moreover, endoscopic surveillance and oesophagectomy need to be efficacious in reliably diagnosing high-grade dysplasia and preventing deaths from cancer. If such ideal conditions of surveillance are not met, the cost per life-year saved could rise five-fold. CONCLUSIONS Endoscopic surveillance of patients with Barrett's oesophagus may be a cost-effective means to prevent death from oesophageal adenocarcinoma.
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Affiliation(s)
- A Sonnenberg
- Department of Veterans Affairs Medical Center and The University of New Mexico, Albuquerque, NM 87108, USA.
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21
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Upregulation and differential expression of matrilysin (MMP-7) and metalloelastase (MMP-12) and their inhibitors TIMP-1 and TIMP-3 in Barrett's oesophageal adenocarcinoma. Br J Cancer 2001. [PMID: 11487270 DOI: 10.1054/bjoc.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Oesophageal adenocarcinoma is believed to arise from metaplastic mucosa in the distal oesophagus, a condition also known as Barrett's oesophagus (BE). BE develops as a result of injury caused by refluxing gastric and duodenal contents and is associated with increased risk of malignant transformation. Matrix metalloproteinases (MMPs) have been implicated in all aspects of tumour progression; tumour growth, basement membrane degradation, invasion and metastatic spread. Using in situ hybridization, we investigated the expression patterns of collagenases-1 and -3, stromelysin-2, matrilysin, metalloelastase and TIMPs-1 and -3 in BE, adenocarcinoma and lymph-node metastases. Matrilysin was expressed abundantly in 12/15 tumours and in 4/6 lymph-node metastases and its expression correlated with the histological aggressiveness of tumour. Matrilysin and metalloelastase were upregulated already in BE. Stromelysin-2 and collagenase-3 expression was detected only in a few tumours. Collagenase-1 was expressed by cancer and stromal cells in 9/15 tumours. Tumour-infiltrating macrophages expressed metalloelastase in 13/15 cancers. TIMPs-1 and -3 were expressed in 12/15 and 11/15 tumours, respectively. Laminin-5 and tenascin were abundantly expressed at the invasive front of poorly differentiated tumours, but not in BE. Our results indicate that matrilysin is the principal MMP expressed by tumour cells in oesophageal adenocarcinoma, and further studies are needed to investigate whether matrilysin or tenascin-C could be used as a predictive marker for progression of BE to cancer.
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22
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Salmela MT, Karjalainen-Lindsberg ML, Puolakkainen P, Saarialho-Kere U. Upregulation and differential expression of matrilysin (MMP-7) and metalloelastase (MMP-12) and their inhibitors TIMP-1 and TIMP-3 in Barrett's oesophageal adenocarcinoma. Br J Cancer 2001; 85:383-92. [PMID: 11487270 PMCID: PMC2364078 DOI: 10.1054/bjoc.2001.1929] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2000] [Revised: 03/28/2001] [Accepted: 04/05/2001] [Indexed: 01/08/2023] Open
Abstract
Oesophageal adenocarcinoma is believed to arise from metaplastic mucosa in the distal oesophagus, a condition also known as Barrett's oesophagus (BE). BE develops as a result of injury caused by refluxing gastric and duodenal contents and is associated with increased risk of malignant transformation. Matrix metalloproteinases (MMPs) have been implicated in all aspects of tumour progression; tumour growth, basement membrane degradation, invasion and metastatic spread. Using in situ hybridization, we investigated the expression patterns of collagenases-1 and -3, stromelysin-2, matrilysin, metalloelastase and TIMPs-1 and -3 in BE, adenocarcinoma and lymph-node metastases. Matrilysin was expressed abundantly in 12/15 tumours and in 4/6 lymph-node metastases and its expression correlated with the histological aggressiveness of tumour. Matrilysin and metalloelastase were upregulated already in BE. Stromelysin-2 and collagenase-3 expression was detected only in a few tumours. Collagenase-1 was expressed by cancer and stromal cells in 9/15 tumours. Tumour-infiltrating macrophages expressed metalloelastase in 13/15 cancers. TIMPs-1 and -3 were expressed in 12/15 and 11/15 tumours, respectively. Laminin-5 and tenascin were abundantly expressed at the invasive front of poorly differentiated tumours, but not in BE. Our results indicate that matrilysin is the principal MMP expressed by tumour cells in oesophageal adenocarcinoma, and further studies are needed to investigate whether matrilysin or tenascin-C could be used as a predictive marker for progression of BE to cancer.
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Affiliation(s)
- M T Salmela
- Department of Dermatology, University of Helsinki, Finland
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23
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Eckardt VF, Kanzler G, Bernhard G. Life expectancy and cancer risk in patients with Barrett's esophagus: a prospective controlled investigation. Am J Med 2001; 111:33-7. [PMID: 11448658 DOI: 10.1016/s0002-9343(01)00745-8] [Citation(s) in RCA: 95] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND It has been suggested that patients with Barrett's esophagus have a substantially increased risk of esophageal and possibly extra-esophageal cancers. We compared the incidence of cancer and the survival rates of patients with Barrett's esophagus with those observed in patients with achalasia, with Schatzki's ring, and in the general population. PATIENTS AND METHODS From 1980 through 1994, 60 consecutive patients with newly diagnosed long-segment Barrett's esophagus without dysplasia were seen in a single gastroenterology consultation office and followed until the Fall of 1999. Cancer incidence and survival rates were compared with age- and sex-matched patients with symptomatic Schatzki's ring (n = 60) and achalasia (n = 60). Survival data were also compared with those of the German population. RESULTS During a mean (+/-SD) observation period of 10 +/- 5 years, 2 patients with Barrett's esophagus (3%; 95% confidence interval [CI]: 0% to 11%) developed esophageal cancer, and 9 (15%; 95% CI: 7% to 27%) developed extra-esophageal cancers. These data differed only slightly from those of patients with Schatzki's ring (esophageal cancer: n = 1, 2%; 95% CI: 0% to 9%; extra-esophageal cancers: n = 9, 15%; 95% CI: 7%-27%) and achalasia (no esophageal cancers, extra-esophageal cancers: n = 3, 5%; 95% CI: 1% to 4%). Estimated 10-year survival was similar in patients with Barrett's esophagus (83%), patients with symptomatic Schatzki's ring (80%), patients with achalasia (87%), and in the general population (82%). CONCLUSIONS The cancer risk in patients with Barrett's esophagus has been overestimated. If patients with nondysplastic epithelium are followed, the risk of esophageal cancer is about 1 per 300 patient-years.
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Affiliation(s)
- V F Eckardt
- Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
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Gudlaugsdottir S, van Blankenstein M, Dees J, Wilson JH. A majority of patients with Barrett's oesophagus are unlikely to benefit from endoscopic cancer surveillance. Eur J Gastroenterol Hepatol 2001; 13:639-45. [PMID: 11434588 DOI: 10.1097/00042737-200106000-00005] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Endoscopic cancer surveillance has been advocated for patients with Barrett's oesophagus. However, only a small minority of patients dies from adenocarcinoma in Barrett's oesophagus. It has been calculated that endoscopic cancer surveillance will only add to the quality of life of individuals in whom the incidence of adenocarcinoma in Barrett's oesophagus is greater than 1/200 patient-years. OBJECTIVE To determine the proportion of a consecutive cohort of patients, in whom Barrett's oesophagus was diagnosed over a 5-year period, likely to benefit from endoscopic cancer surveillance. METHODS All patients who had died during the observation period or were over 75 years old and those with diseases likely to impair survival were excluded. Next, all patients in whom the risk of developing adenocarcinoma in Barrett's oesophagus fell below 1/200 patient-years were excluded (including all women, all men under the age of 60 and all men with Barrett's oesophagus of < 3 cm in length). Patients with dysplasia of any degree and/or presence of an ulcer or stricture in Barrett's oesophagus were reinstated. RESULTS Of 335 adult patients diagnosed with Barrett's oesophagus but without adenocarcinoma or high-grade dysplasia, 75 had died from unrelated causes, 47 had other diseases limiting survival and 59 were over 75 years old. After exclusion of all women, all men with Barrett's oesophagus of < 3 cm in length and all men under 60 years old, 15 patients were left. However, 32 were reinstated because of risk factors and another five because of insufficient data, resulting in 52 of the original 335 patients (15.5%) being eligible for endoscopic cancer surveillance. CONCLUSION This study suggests that less than 20% of patients identified with Barrett's oesophagus at routine endoscopy would benefit from endoscopic cancer surveillance. Prospective surveillance programmes should be limited to patients with an increased cancer risk and a good health profile.
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Affiliation(s)
- S Gudlaugsdottir
- Department of Internal Medicine, University Hospital Rotterdam, The Netherlands.
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25
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Rana PS, Johnston DA. Incidence of adenocarcinoma and mortality in patients with Barrett's oesophagus diagnosed between 1976 and 1986: implications for endoscopic surveillance. Dis Esophagus 2001; 13:28-31. [PMID: 11005328 DOI: 10.1046/j.1442-2050.2000.00069.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The objective of this study was to investigate the incidence of oesophageal adenocarcinoma and its contribution to mortality in patients with Barrett's oesophagus, and to identify a subgroup of patients who may benefit from endoscopic surveillance. This was a retrospective study of a cohort of 70 patients diagnosed in the endoscopy unit of a Scottish teaching hospital as having Barrett's oesophagus between 1976 and 1986. Information was obtained from case notes, endoscopy records, histology reports and death certificates. Patients were included if they had: (a) columnar-lined oesophagus of at least 3 cm; (b) histological confirmation; and (c) absence of cancer when endoscopically diagnosed as having Barrett's oesophagus. The main outcome for the patients was development of adenocarcinoma or death. Information was available for 59 of 70 patients (84%). Forty-four patients were confirmed to have Barrett's oesophagus and were followed up for 418 patient-years. Only two patients developed oesophageal adenocarcinoma, resulting in an incidence of one case in 209 patient-years, a 55-fold risk compared with age- and sex-matched population in Scotland. Both these patients had intestinal metaplasia and Barrett's ulcer. The majority (90%) of patients died as a result of causes unrelated to adenocarcinoma of oesophagus. In patients under 70 years with intestinal metaplasia, 189 annual endoscopies would have been required to detect one cancer. Adenocarcinoma is an uncommon cause of mortality in patients with Barrett's oesophagus. Endoscopic surveillance is unlikely to alter overall mortality in patients with Barrett's oesophagus. However, by limiting endoscopic surveillance to patients under 70 years with intestinal metaplasia, the estimated cost per cancer detected can be reduced to ł23000.
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Affiliation(s)
- P S Rana
- Department of Digestive Diseases and Clinical Nutrition, Ninwells Hospital and Medical School, Dundee, UK
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26
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Falk GW. Endoscopic surveillance of Barrett's esophagus. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2000. [DOI: 10.1053/tgie.2000.8941] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Bhargava P, Eisen GM, Holterman DA, Azumi N, Hartmann DP, Hanfelt JJ, Benjamin SB, Lippman ME, Montgomery EA. Endoscopic mapping and surrogate markers for better surveillance in Barrett esophagus. A study of 700 biopsy specimens. Am J Clin Pathol 2000; 114:552-63. [PMID: 11026101 DOI: 10.1309/93wg-errb-pn57-c15a] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
Surveillance methods in Barrett esophagus (BE) using light microscopic examination of random biopsy specimens may miss focal dysplasia. In addition, dysplastic foci identified initially may not be relocated subsequently, making chemoprevention studies difficult. By using a special gastroscope, systematic mapping (4-quadrant biopsy specimens at 1-cm intervals) was performed in 22 patients (33 total mappings yielding 700 biopsy specimens). H&E, immunohistochemistry, and DNA ploidy analysis were performed. c-erbB-2 and positive Ki-67 were detected only in dysplastic sites; thus, their detection did not precede morphologically identifiable dysplasia. On the other hand, aneuploidy and p53 were detected in dysplastic and nondysplastic areas. p53 was correlated with dysplasia, and S-phase narrowly missed correlation, while aneuploidy was not correlated. PCNA and bcl-2 were ubiquitous, limiting their usefulness. On second maps, epithelial type was reidentified with 81% accuracy. A significant correlation was found between p53 and dysplasia. Sites of dysplasia and abnormal biomarkers could be relocated accurately by using endoscopic mapping. Therefore, mapping combined with biomarker studies may provide better surveillance and serve as a useful technique in chemoprevention studies.
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Affiliation(s)
- P Bhargava
- Dept of Pathology, Georgetown University School of Medicine, Washington, DC 20007, USA
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28
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Weston AP, Badr AS, Hassanein RS. Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett's multifocal high-grade dysplasia or adenocarcinoma. Am J Gastroenterol 1999; 94:3413-9. [PMID: 10606296 DOI: 10.1111/j.1572-0241.1999.01602.x] [Citation(s) in RCA: 152] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Our goal was a prospective follow-up of Barrett's esophagus to determine what clinical, endoscopic, and histological features at the time of initial diagnosis are predictive of the development of Barrett's adenocarcinoma or multifocal high-grade dysplasia (HGD). METHODS Newly diagnosed Barrett's esophagus patients were prospectively followed with a standardized endoscopic and bioptic surveillance protocol. Features examined by chi2 and stepwise logistic regression analyses as potential predictors the development of multifocal HGD or adenocarcinoma included age, length of Barrett's segment, hiatal hernia size, severity of dysplasia at diagnosis, severity of dysplasia during surveillance, and type of long-term medical treatment. RESULTS One hundred-eight Barrett's patients have had follow-up ranging from 12 months to 101 months (mean +/- SD, 39.9+/-20.8 months), for a total of 361.8 patient-years. Overall, five patients developed multifocal HGD and five developed adenocarcinoma. The incidence of adenocarcinoma as well as multifocal HGD was 1 per 71.9 patient-years. Chi2 analysis showed progression to Barrett's multifocal HGD/adenocarcinoma was associated with hiatal hernia (p = 0.02), the length of Barrett's (p = 0.001), the presence of dysplasia at diagnoses (p < 0.001) or anytime during surveillance (p < 0.001). Stepwise logistic regression analysis revealed progression to multifocal HGD or adenocarcinoma was significantly and independently associated with presence of dysplasia at diagnosis (p < 0.0001) or anytime during follow-up (p < 0.03), hiatal hernia size (p < 0.02, for hernia > or =3 cm), and length of Barrett's (p = 0.009, >2 cm). CONCLUSIONS Endoscopic and histological features of Barrett's esophagus patients at initial diagnosis are predictive of risk of progression to cancer.
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Affiliation(s)
- A P Weston
- The Veterans Administration Medical Center, Kansas City, Missouri, USA
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29
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Gross CP, Canto MI, Hixson J, Powe NR. Management of Barrett's esophagus: a national study of practice patterns and their cost implications. Am J Gastroenterol 1999; 94:3440-7. [PMID: 10606300 DOI: 10.1111/j.1572-0241.1999.01606.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The optimal management of Barrett's esophagus (BE) is controversial. Little is known about current practice patterns or associated direct medical costs. METHODS In a national cross-sectional survey, we asked a random sample of gastroenterologists how they would manage patients with BE and various degrees of dysplasia. We used logistic regression to identify factors associated with so-called "frequent" (at least every 12 months) surveillance. We calculated direct medical costs using Medicare payments and population-based estimates of the number of BE patients under surveillance. RESULTS Approximately 50% of 555 gastroenterologists responded. More than 96% of respondents recommended endoscopic surveillance for BE. For BE without dysplasia, 30% would perform frequent surveillance; this was the case particularly gastroenterologists older than age 45 yr (odds ratio = 1.91, p = 0.038) or those receiving primarily fee-for-service reimbursement (odds ratio = 2.57, p = 0.004). For BE with low-grade dysplasia, the frequency of endoscopy was highly variable (range, 1-24 months). For BE with high-grade dysplasia, 73% of gastroenterologists recommended esophagectomy and the remainder recommended endoscopic surveillance. Approximately 95% of the gastroenterologists who recommended surveillance for high-grade dysplasia, however, were not in agreement with recommended protocols. We estimated the national annual expenditure for surveillance endoscopy every 24 months for BE without dysplasia to be at least $22 million. Increase in surveillance intensity from low frequency (every 36 months) to high frequency (every 12 months) strategies would escalate costs by $29 million annually. CONCLUSIONS Physician age and reimbursement influence BE surveillance practice, suggesting the influence of nonclinical factors on clinical decision making. The majority of clinicians who would recommend surveillance for high-grade dysplasia may not be using an appropriately aggressive strategy. Variations in surveillance strategies can have large cost implications.
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Affiliation(s)
- C P Gross
- Robert Wood Johnson Clinical Scholars Program, Division of Gastroenterology-Hepatology, Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, USA
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30
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O'Connor JB, Falk GW, Richter JE. The incidence of adenocarcinoma and dysplasia in Barrett's esophagus: report on the Cleveland Clinic Barrett's Esophagus Registry. Am J Gastroenterol 1999; 94:2037-42. [PMID: 10445525 DOI: 10.1111/j.1572-0241.1999.01275.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The reported incidence of adenocarcinoma in Barrett's esophagus is variable. The aim of this study was to determine the incidence of dysplasia and adenocarcinoma in a population of patients with Barrett's esophagus followed prospectively and to compare these findings with other series. METHODS All patients enrolled in the Cleveland Clinic Foundation's Barrett's esophagus registry from 1979 to 1995 were followed. Barrett's esophagus was defined as intestinal metaplasia anywhere in the tubular esophagus. The incidence of dysplasia and adenocarcinoma in these patients was recorded systematically. RESULTS A total of 136 patients (91 male, 45 female) were followed in an endoscopic surveillance program for a mean of 4.2 yr and a total of 570 patient-years of follow-up. Thirty patients (22%) had short segment Barrett's esophagus. Two adenocarcinomas developed during follow-up, yielding an incidence of one per 285 patient-years of follow-up. Low grade dysplasia developed in 24 patients, whereas high grade dysplasia developed in four patients. CONCLUSIONS Our study suggests that the incidence of adenocarcinoma in Barrett's esophagus is lower than initially thought. However, large multicenter studies are required to clarify the epidemiological and clinical factors related to the development of dysplasia and adenocarcinoma in Barrett's esophagus.
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Affiliation(s)
- J B O'Connor
- Center for Swallowing and Esophageal Disorders, Department of Gastroenterology, Cleveland Clinic Foundation, Ohio 44195, USA
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Ortiz-Hidalgo C, De La Vega G, Aguirre-García J. The histopathology and biologic prognostic factors of Barrett's esophagus: a review. J Clin Gastroenterol 1998; 26:324-33. [PMID: 9649022 DOI: 10.1097/00004836-199806000-00024] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
In Barrett's esophagus, stratified squamous mucosa of the lower third of the esophagus is replaced by columnar mucosa, as a complication of chronic gastroesophageal reflux. The presence of Barrett's esophagus appears to be a major factor in the progression to adenocarcinoma of the lower third of the esophagus. Therefore it is crucial to identify the subset of patients at risk for the development of adenocarcinoma. Dysplasia is an important histologic feature to evaluate because it identifies those patients who require follow-up. The diagnosis of biopsies with lesser degrees of abnormalities, however, makes microscopic evaluation less helpful in identifying patients who need more frequent endoscopic biopsy surveillance. DNA ploidy and the use of monoclonal antibodies, such as suppressor gene product p53, oncogene cerbB-2, and Ki-67, have added dramatically to our understanding of the biology of Barrett's metaplasia and have given us objective indicators to predict the presence of an increased risk of developing cancer.
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Affiliation(s)
- C Ortiz-Hidalgo
- Department of Surgical Pathology, The American British Cowdray Hospital, Observatorio, Mexico DF, Mexico
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Abstract
In the United States, the incidence of esophageal adenocarcinoma has risen faster than any other malignancy in recent years, and now represents the most common histologic type of esophageal cancer observed in major institutions. The precise etiology of this malignancy, and the epidermiologic variables responsible for its dramatically rising incidence, remains obscure. Elucidation of the molecular biology of malignant transformation in Barrett's esophagus may improve the management of patients with advanced esophageal adenocarcinomas. Furthermore, appreciation of the molecular events associated with esophageal adenocarcinomas. Furthermore, appreciation of the molecular events associated with esophageal adenocarcinogenesis may facilitate early detection of occult carcinomas, and enable therapeutic interventions designed to prevent these otherwise highly lethal neoplasms.
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Affiliation(s)
- N K Altorki
- Department of Cardiothoracic Surgery, New York Hospital-Cornell Medical Center, New York 10021, USA
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