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Qu HT, Li Q, Hao L, Ni YJ, Luan WY, Yang Z, Chen XD, Zhang TT, Miao YD, Zhang F. Esophageal cancer screening, early detection and treatment: Current insights and future directions. World J Gastrointest Oncol 2024; 16:1180-1191. [PMID: 38660654 PMCID: PMC11037049 DOI: 10.4251/wjgo.v16.i4.1180] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/09/2024] [Accepted: 02/19/2024] [Indexed: 04/10/2024] Open
Abstract
Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.
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Affiliation(s)
- Hong-Tao Qu
- Department of Emergency, Yantai Mountain Hospital, Yantai 264000, Shandong Province, China
| | - Qing Li
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Liang Hao
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Yan-Jing Ni
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Wen-Yu Luan
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Zhe Yang
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Xiao-Dong Chen
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Tong-Tong Zhang
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Yan-Dong Miao
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Fang Zhang
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
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White JR, Ragunath K, Whitton A, Marsh E, Kaye P, Knight G. Study to investigate the prevalence of human papillomavirus in Barrett's oesophagus using a novel screening methodology. BMJ Open Gastroenterol 2022; 9:e000840. [PMID: 35379652 PMCID: PMC8981274 DOI: 10.1136/bmjgast-2021-000840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 01/25/2022] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Human papillomavirus (HPV) is strongly associated with Barrett's dysplasia and oesophageal cancer suggesting a role in carcinogenesis. HPV persistence predicts treatment failure after endotherapy for Barrett's dysplasia. This pilot study applies a novel HPV screening tool (previously only used in the oropharynx) to detect HPV DNA directly and determine the prevalence rates in Barrett's oesophagus (BO). METHOD DNA was extracted from 20 formalin-fixed BO samples. HPV DNA was detected using real-time PCR and gel electrophoresis. RESULTS 5 out of 20 patients were identified as positive for HPV. Prevalence was 25% in patients with BO. CONCLUSION This method can be used in BO's tissue to determine HPV infection. Adoption of this as a screening test could potentially revolutionise future research in this area. If a clear link between HPV and Barrett's dysplasia can be confirmed, this qPCR method has the potential to aid in monitoring and/or dysplasia detection by stratifying those most at risk and aid in the development of new therapies.
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Affiliation(s)
- Jonathan Richard White
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Krish Ragunath
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Aimee Whitton
- School of Human Sciences, University of Derby, Derby, UK
| | | | - Philip Kaye
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Gillian Knight
- School of Engineering and Applied Science, Aston University, Birmingham, UK
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Effect of nonsteroidal anti-inflammatory drugs on Barrett's esophagus risk: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2021; 45:101552. [PMID: 33268293 DOI: 10.1016/j.clinre.2020.09.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 09/14/2020] [Accepted: 09/24/2020] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Conflicting evidence exists regarding the effect of NSAIDs on the risk of Barrett's esophagus. The purpose of this study is to systematically assess this effect through a meta-analysis. METHODS Accordingly, clinical studies on NSAID use and Barrett's esophagus risk were searched on PubMed, Embase, and the Cochrane Library. Following this, meta-analyses were conducted using the RevMan 5.3 software. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used as the effect size. RESULTS Seven eligible studies (one cohort study and six case-control studies) were included for the present meta-analysis by adopting a fixed-effect model, which demonstrated that NSAIDs could reduce Barrett's esophagus risk (OR: 0.84, 95%CI:0.75-0.94, P＜0.05). Moreover, subgroup analyses done according to sex showed that NSAIDs could reduce Barrett's esophagus risk in females (OR 0.85; 95% CI 0.73-0.99; P = 0.04), without heterogeneity between studies (P = 1.00 and I2 = 0%). However, this relationship was not evident in males (OR 0.85; 95% CI 0.68-1.07; P = 0.16). CONCLUSIONS Overall, this meta-analysis provided high quality evidence that use of NSAIDs is associated with a reduced risk of Barrett's esophagus. However, the presence of a sex-dependent difference remains to be clarified.
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Abstract
Incidence of oesophageal adenocarcinoma has increased exponentially in the West over the past few decades. Following detection of advanced cancers, 5-year survival rates remain bleak, making identification of early neoplasia, which has a better outcome, important. Detection of subtle oesophageal lesions during endoscopy can be challenging, and advanced imaging techniques might improve their detection. High-definition endoscopy has become a standard in most endoscopy centres, and this technology probably provides better delineation of mucosal features than standard-definition endoscopy. Various image enhancement techniques are now available with the development of new electronics and software systems. Image enhancement with chromoendoscopy using dyes has been a cost-effective option for many years, yet these techniques have been replaced in some contexts by electronic chromoendoscopy, which can be used with the press of a button. However, Lugol's chromoendoscopy remains the gold standard to identify squamous dysplasia. Identification and characterization of subtle neoplastic lesions could help to target biopsies and perform endoscopic resection for better local staging and definitive therapy. In vivo histology with techniques such as confocal endomicroscopy could make endotherapy feasible within a shorter timescale than when relying on histology on tissue samples. Once early neoplasia is identified, treatments include endoscopic resection, endoscopic submucosal dissection or various ablative techniques. Endotherapy has the advantage of being a less invasive technique than oesophagectomy, and is associated with lower mortality and morbidity. Endoscopic ablation therapies have evolved over the past few years, with radiofrequency ablation showing the best results in terms of success rates and complications in Barrett dysplasia.
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Affiliation(s)
- Jayan Mannath
- University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry, CV2 2DX, UK
| | - Krish Ragunath
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, Queens Medical Centre, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, NG7 2UH, UK
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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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Yang CS, Chen X, Tu S. Etiology and Prevention of Esophageal Cancer. Gastrointest Tumors 2016; 3:3-16. [PMID: 27722152 DOI: 10.1159/000443155] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2015] [Accepted: 12/07/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Esophageal cancer (EC) occurs commonly, especially in Asia, and is the sixth leading cause of cancer deaths worldwide. Recently, great progress has been made in research on the etiology and prevention of EC. SUMMARY The major risk factors for esophageal squamous cell carcinoma (ESCC) are tobacco smoking and alcohol drinking, which act synergistically. Dietary parameters, including dietary carcinogens and insufficiency of micronutrients, could also be important risk factors in certain areas. A common etiological factor for both EC and some other cancers are low levels of intake of fruits and vegetables. With improvements in diet and drinking water in developing countries, the incidence of ESCC decreased. However, in economically well-developed countries, the incidence of esophageal adenocarcinoma (EAC) has markedly increased in the past 40 years. The major etiological factor for EAC is gastroesophageal reflux, which is also an etiological factor for gastric cardia adenocarcinoma (GCA). In certain areas of China, the occurrence of GCA is closely related to ESCC. Susceptibility genes for EC are starting to be discovered, and this may help to identify high-risk groups that have more need for preventive measures. Mitigation of the risk factors, early detection and treatment of precancerous lesions are effective approaches for prevention. Smoking cessation, avoidance of excessive alcohol, meat and caloric consumption, increasing physical activity and frequent consumption of vegetables and fruits are prudent lifestyle modifications for the prevention of EC as well as other diseases. KEY MESSAGE The etiology of EC includes tobacco smoking, alcohol drinking, low levels of intake of fruits and vegetables as well as gastroesophageal reflux and susceptibility genes. PRACTICAL IMPLICATIONS A healthy lifestyle including smoking cessation, increasing physical activity, consumption of vegetables as well as reduction of alcohol intake and caloric consumption are major approaches to the prevention of EC.
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Affiliation(s)
- Chung S Yang
- Department of Chemical Biology, Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, N.J, USA
| | - Xiaoxin Chen
- Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, N.C, USA; Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, N.C., USA
| | - Shuiping Tu
- Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China
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Wang Y, McManus DT, Arthur K, Johnston BT, Kennedy AJ, Coleman HG, Murray LJ, Hamilton PW. Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus. J Transl Med 2015; 95:1319-1330. [PMID: 26237272 DOI: 10.1038/labinvest.2015.98] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Revised: 06/12/2015] [Accepted: 06/15/2015] [Indexed: 12/20/2022] Open
Abstract
Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Both low-grade dysplasia (LGD) and high-grade dysplasia (HGD) are associated with an increased risk of progression to EAC. However, histological interpretation and grading of dysplasia (particularly LGD) is subjective and poorly reproducible. This study has combined whole slide imaging with DNA image cytometry to provide a novel method for the detection of abnormal DNA content through image analysis of tissue sections. A total of 20 cases were evaluated, including 8 negative for dysplasia (NFD), 6 LGD, and 6 HGD. Feulgen-stained esophageal sections were scanned in their entirety. Barrett's mucosa was interactively chosen for automatic nuclei segmentation where irrelevant cell types were ignored. The combined DNA content histogram for all nuclei within selected image regions was then obtained. In addition, three histogram measurements were computed, including xER-5C, 2cDI, and DNA-MG. Visual evaluation suggested the shape of DNA content histograms from NFD, LGD, and HGD cases exhibiting identifiable differences. The histogram measurements, xER-5C, 2cDI, and DNA-MG, were shown to be effective in differentiating metaplastic from dysplastic cases with statistical significance. Moreover, they also successfully separated NFD, LGD, and HGD patients with statistical significance. Whole slide image cytometry is a novel and effective method for the detection of abnormal DNA content in BE. Compared with histological review, it is more objective. Compared with flow cytometry and cytology-preparation image cytometry, it is low cost, simple to use, only requires a single 1 μm section, and facilitates selection of tissue and topographical correlation. Whole slide image cytometry can detect differences in DNA content between NFD, LGD, and HGD patients in this cross-sectional study. Abnormal DNA content detection by whole slide image cytometry is a promising biomarker of progression that could affect future diagnostics in BE.
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Affiliation(s)
- Yinhai Wang
- Finland Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland
| | - Damian T McManus
- Belfast HSC Trust, Belfast, UK
- Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, UK
| | - Kenneth Arthur
- Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, UK
| | | | | | - Helen G Coleman
- Centre for Public Health, Queen's University Belfast, Belfast, UK
| | - Liam J Murray
- Centre for Public Health, Queen's University Belfast, Belfast, UK
| | - Peter W Hamilton
- Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, UK
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Schneider JL, Corley DA. A review of the epidemiology of Barrett's oesophagus and oesophageal adenocarcinoma. Best Pract Res Clin Gastroenterol 2015; 29:29-39. [PMID: 25743454 PMCID: PMC5648333 DOI: 10.1016/j.bpg.2014.11.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 11/24/2014] [Indexed: 02/07/2023]
Abstract
While the incidence rates of many cancers have decreased in past decades, the incidence of oesophageal adenocarcinoma continues to increase. The only known precursor for oesophageal adenocarcinoma is Barrett's oesophagus. Studies conducted have identified white race, male sex, GORD, cigarette smoking, obesity, and the absence of Helicobacter pylori status as risk factors for oesophageal adenocarcinoma. Other potential associations include dietary factors and the absence of non-steroidal anti-inflammatory drug use. Many individual studies have been limited by sample size and several meta-analyses have pooled data from studies to address this limitation. In this review we present a synthesis of these studies and summarize current knowledge of risk factors for both oesophageal adenocarcinoma and Barrett's oesophagus.
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Affiliation(s)
- Jennifer L Schneider
- Kaiser Permanente Northern California, Division of Research, 2000 Broadway, Oakland, CA 94612, USA.
| | - Douglas A Corley
- Kaiser Permanente Northern California, Division of Research, 2000 Broadway, Oakland, CA 94612, USA.
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Schneider JL, Zhao WK, Corley DA. Aspirin and nonsteroidal anti-inflammatory drug use and the risk of Barrett's esophagus. Dig Dis Sci 2015; 60:436-43. [PMID: 25213077 PMCID: PMC4304909 DOI: 10.1007/s10620-014-3349-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 08/30/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND The use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of esophageal adenocarcinoma; however, it is unknown where these agents may act in the proposed pathway from normal mucosa to Barrett's esophagus to esophageal adenocarcinoma. AIM The aim of the study was to evaluate the association between aspirin and NSAID use and Barrett's esophagus in a case-control study within a large community-based population. METHODS We conducted a case-control study of aspirin/NSAID use and Barrett's esophagus within the Kaiser Permanente Northern California population. Cases had a new diagnosis of Barrett's esophagus between October 2002 and September 2005; controls were members without a diagnosis of Barrett's esophagus. RESULTS Persons with Barrett's esophagus were less likely to use aspirin than population controls [odds ratio (OR) 0.59, 95 % confidence interval (CI) 0.39-0.87]; a stronger association was found among cases and controls with reflux symptoms (OR 0.49, 95 % CI 0.32-0.75; p value interaction = 0.004). Similar associations were found with the use of either aspirin and/or non-aspirin NSAIDs (OR 0.53, 95 % CI 0.35-0.81), although NSAID use alone was not significantly associated with Barrett's esophagus (OR 0.74, 95 % CI 0.47-1.16). The strength of the association was highest among persons with at least moderate-to-high total medication intake. CONCLUSIONS Regular use of aspirin or NSAIDs was associated with a decreased risk of Barrett's esophagus, particularly among persons with gastroesophageal reflux disease symptoms. These findings have implications for chemoprevention, as some of the previously described protective association between aspirin/NSAIDs and esophageal adenocarcinoma may be explained by events that occur prior to the development of Barrett's esophagus.
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Affiliation(s)
- Jennifer L. Schneider
- Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612, Fax: 510-891-3802 Phone: 510-891-5910
| | - Wei K. Zhao
- Kaiser Permanente Division of Research Oakland, CA
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E-cadherin expression in Barrett’s esophagus and esophageal carcinoma. Esophagus 2014. [DOI: 10.1007/s10388-014-0424-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Fitzgerald RC, di Pietro M, Ragunath K, Ang Y, Kang JY, Watson P, Trudgill N, Patel P, Kaye PV, Sanders S, O'Donovan M, Bird-Lieberman E, Bhandari P, Jankowski JA, Attwood S, Parsons SL, Loft D, Lagergren J, Moayyedi P, Lyratzopoulos G, de Caestecker J. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut 2014; 63:7-42. [PMID: 24165758 DOI: 10.1136/gutjnl-2013-305372] [Citation(s) in RCA: 866] [Impact Index Per Article: 78.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.
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Watari J, Oshima T, Fukui H, Tomita T, Miwa H. Carcinogenesis of Barrett's esophagus: a review of the clinical literature. Clin J Gastroenterol 2013; 6:399-414. [PMID: 26182128 DOI: 10.1007/s12328-013-0412-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2013] [Accepted: 07/25/2013] [Indexed: 11/25/2022]
Abstract
Barrett's esophagus (BE) is a premalignant condition of esophageal adenocarcinoma (EAC). Although the incidence of BE has risen rapidly in the West, it is rare in Asia despite a recent increase in the prevalence of gastroesophageal reflux disease. Controversies over the definition of BE are presented because most cases show short-segment BE, especially ultra-short BE, in Asia. Here we review possible risk factors for the development of EAC, particularly possible roles of ethnicity, specialized intestinal metaplasia (SIM), BE length, and environmental factors, such as Helicobacter pylori infection and obesity. Additionally, we summarize recent studies on the effect of chemoprevention including proton pump inhibitors, nonsteroidal anti-inflammatory drugs or aspirin in order to reduce the risk of neoplastic progression in BE patients. Although substantial knowledge of risk factors of dysplasia/EAC in BE is shown, the risk for neoplastic development may be influenced by geographic variation, study population, the presence or absence of SIM or dysplasia at baseline, and the small number of BE patients investigated. Recently, the efficiency of surveillance for BE patients has been discussed from the standpoint of cost-effectiveness. It may be too difficult to draw conclusions because no randomized clinical trials of BE surveillance have been performed.
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Affiliation(s)
- Jiro Watari
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Tadayuki Oshima
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hirokazu Fukui
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Toshihiko Tomita
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hiroto Miwa
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
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Bajpai M, Kessel R, Bhagat T, Nischal S, Yu Y, Verma A, Das KM. High resolution integrative analysis reveals widespread genetic and epigenetic changes after chronic in-vitro acid and bile exposure in Barrett's epithelium cells. Genes Chromosomes Cancer 2013; 52:1123-32. [PMID: 24123713 DOI: 10.1002/gcc.22106] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2013] [Revised: 07/31/2013] [Accepted: 08/01/2013] [Indexed: 12/12/2022] Open
Abstract
Barrett's epithelium (BE) is a premalignant condition resulting from chronic gastroesophageal reflux that may progress to esophageal adenocarcinoma (EAC). Early intervention holds promise in preventing BE progression. However, identification of high-risk BE patients remains challenging due to inadequate biomarkers for early diagnosis. We investigated the effect of prolonged chronic acid and bile exposure on transcriptome, methylome, and mutatome of cells in an in-vitro BE carcinogenesis (BEC) model. Twenty weeks acid and bile exposed cells from the BEC model (BEC20w) were compared with their naïve predecessors HiSeq Illumina based RNA sequencing was performed on RNA from both the cells for gene expression and mutational analysis. HELP Tagging Assay was performed for DNA methylation analysis. Ingenuity pathway, Gene Ontology, and KEGG PATHWAY analyses were then performed on datasets. Widespread aberrant genetic and epigenetic changes were observed in the BEC20w cells. Combinatorial analyses revealed 433 from a total of 863 downregulated genes had accompanying hypermethylation of promoters. Simultaneously, 690 genes from a total of 1,492 were upregulated with accompanying promoter hypomethylation. In addition, 763 mutations were identified on 637 genes. Ingenuity pathway analysis, Gene Ontology, and KEGG PATHWAY analyses associated the genetic and epigenetic changes in BEC20w cells with cellular and biological functions. Integration of high resolution comparative analyses of naïve BAR-T and BEC20w cells revealed striking genetic and epigenetic changes induced by chronic acid and bile exposure that may disrupt normal cellular functions and promote carcinogenesis. This novel study reveals several potential targets for future biomarkers and therapeutic development.
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Affiliation(s)
- Manisha Bajpai
- Division of Gastroenterology and Hepatology, Department of Medicine, RUTGERS Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
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Xu E, Gu J, Hawk ET, Wang KK, Lai M, Huang M, Ajani J, Wu X. Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma. Carcinogenesis 2013; 34:2750-6. [PMID: 23996928 DOI: 10.1093/carcin/bgt286] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina's Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC.
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Affiliation(s)
- Enping Xu
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Xu E, Gong Y, Gu J, Jie L, Ajani JA, Wu X. Risk assessment of esophageal adenocarcinoma using γ-H2AX assay. Cancer Epidemiol Biomarkers Prev 2013; 22:1797-804. [PMID: 23904462 DOI: 10.1158/1055-9965.epi-13-0485] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Mutagen-induced DNA damage as measured in peripheral blood lymphocytes (PBL) has been associated with increased risks of cancers. The formation of γ-H2AX is an early cellular response to DNA double-strand breaks (DSB). We hypothesize that higher level of radiation-induced γ-H2AX in PBLs may be associated with an increased risk of esophageal adenocarcinoma. METHODS Laser scanning cytometer-based immunocytochemical method was used to measure baseline and irradiation-induced γ-H2AX levels in PBLs from 211 patients with esophageal adenocarcinoma and 211 healthy controls. The ratio of induced γ-H2AX level to baseline level was used to evaluate individual susceptibility to DSBs. Relative risks for esophageal adenocarcinoma associated with γ-H2AX were assessed by multivariable logistic regression analysis. RESULTS Radiation-induced γ-H2AX level and the γ-H2AX ratio were significantly higher in cases than in controls. Dichotomized at the median in controls, a significantly increased risk for esophageal adenocarcinoma was observed in association with high γ-H2AX ratio [OR = 2.94; 95% confidence interval (CI), 1.83-4.72]. Quartile analyses showed significant dose-response associations between higher γ-H2AX ratio and increased risk of esophageal adenocarcinoma (Ptrend, 1.64E-06). In addition, joint effect between γ-H2AX ratio and smoking was observed: smokers who had high γ-H2AX ratio exhibited the highest risk of esophageal adenocarcinoma (OR = 5.53; 95% CI, 2.71-11.25) compared with never smokers with low γ-H2AX ratio. CONCLUSION Radiation-induced DNA damage assessed by γ-H2AX ratio is associated with an increased risk of esophageal adenocarcinoma. IMPACT γ-H2AX assay is a new and robust method to measure DSB damage in PBLs, which can be used to assess mutagen sensitivity and esophageal adenocarcinoma risk.
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Affiliation(s)
- Enping Xu
- Authors' Affiliations: Departments of Epidemiology and Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
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Singh R, Shahzad MA, Tam W, Goda K, Yu LHK, Fujishiro M, Uedo N, Ruszkiewicz A. Preliminary feasibility study using a novel narrow-band imaging system with dual focus magnification capability in Barrett's esophagus: is the time ripe to abandon random biopsies? Dig Endosc 2013; 25 Suppl 2:151-156. [PMID: 23617668 DOI: 10.1111/den.12106] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Accepted: 02/22/2013] [Indexed: 12/20/2022]
Abstract
This preliminary feasibility study assessed the utility of a novel narrow-band imaging (NBI) system (Olympus Exera III; 190 series) both as a detection and as a characterization tool in patients undergoing surveillance endoscopy for Barrett's esophagus (BE). Two hundred and twenty-one areas in 40 patients with BE were examined prospectively. The BE segment was initially evaluated with NBI overview as a 'red flag' technique. Abnormal areas identified with NBI overview were then further interrogated with NBI and a dual focus (DF) magnification system (NBI-DF) in order to aid characterization. Normal areas on NBI overview were also systematically assessed with NBI-DF systematically (four quadrants every 2 cm). A confidence system was utilized when each area was assessed with NBI-DF. All areas on NBI-DF were classified into three easily distinguishable mucosal patterns: (i) regular pits with regular microvasculature (no dysplasia); (ii) irregular pits with irregular microvasculature (early cancer/high-grade dysplasia [HGD]); and (iii) equivocal, where the endoscopist was not sure about the pattern (this could be areas with increased brownish discoloration on NBI overview and dilated vasculature but no change in caliber on NBI-DF [likely inflammation or low-grade dysplasia: LGD]). Corresponding biopsies of each area were then taken. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of both modes (NBI overview and NBI-DF) were then compared with the final histopathological diagnosis. One hundred and eighty-three of 221 areas (82.8%) did not exhibit any dysplasia on final histopathological assessment. NBI overview and NBI-DF accurately called all these areas as non-dysplastic. The 38 areas that appeared suspicious on NBI overview were also further assessed with NBI-DF: seven of seven were accurately predicted as harboring no dysplasia; nine areas were predicted as irregular, of which four harbored early cancer, one HGD, three LGD and one inflammation on final histopathology assessment. Twenty-two areas were deemed to be equivocal (final histology: 18 LGD and four inflammation). The Sn, Sp, PPV and NPV for the prediction of dysplasia/early cancer using NBI overview and NBI-DF were thus 100%, 93.8%, 68.6%, 100% and 100%, 86.2%, 73.3%, 100%, respectively. If NBI-DF was used in addition to NBI overview, biopsies would have been avoided in 190 areas (86%). In addition, all early cancers and HGD could be accurately identified.
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Affiliation(s)
- Rajvinder Singh
- Lyell McEwin Hospital, Adelaide, South Australia, Australia.
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Coron E, Robaszkiewicz M, Chatelain D, Svrcek M, Fléjou JF. Advanced precancerous lesions in the lower oesophageal mucosa: high-grade dysplasia and intramucosal carcinoma in Barrett's oesophagus. Best Pract Res Clin Gastroenterol 2013; 27:187-204. [PMID: 23809240 DOI: 10.1016/j.bpg.2013.03.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2013] [Accepted: 03/08/2013] [Indexed: 01/31/2023]
Abstract
Adenocarcinoma developed in Barrett's oesophagus is a tumour with an increasing incidence and still a poor prognosis. The only marker that can be used for surveillance remains dysplasia (intraepithelial neoplasia), especially when it is high-grade, that precedes intramucosal carcinoma. New forms of dysplasia have been described in complement to the classical intestinal type (foveolar dysplasia, basal crypt dysplasia). High-grade dysplasia and intramucosal carcinoma are diagnosed on biopsies taken during endoscopy. Standard endoscopy is now challenged by various techniques that represent recent major technical improvements (chromoendoscopy, virtual chromoendoscopy, optical frequency domain imaging, confocal laser endomicroscopy). In numerous cases, high-grade dysplasia and intramucosal carcinoma can be treated by endoscopic procedures, allowing a precise histopathological diagnosis on the resected specimen (endoscopic mucosal resection, submucosal endoscopic dissection) or destroying the neoplastic tissue. Radiofrequency ablation is currently considered as the best available technique for treatment of flat high grade dysplasia and for eradication of residual Barrett's mucosa after focal endoscopic mucosal resection.
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Affiliation(s)
- Emmanuel Coron
- Institut des maladies de l'appareil digestif, CHU de Nantes, Nantes, France
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Bajpai M, Aviv H, Das KM. Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett's epithelium. Mol Cytogenet 2012. [PMID: 23194200 PMCID: PMC3564717 DOI: 10.1186/1755-8166-5-43] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Abstract Barrett’s esophagus (BE) is an asymptomatic, pre-malignant condition of the esophagus that can progress to esophageal adenocarcinoma (EAC). BE arises typically in individuals with long-standing gastroesophageal reflux disease (GERD). The neoplastic progression of BE has been extensively studied histologically and defined as a metaplasia- dyplasia- carcinoma sequence. However the genetic basis of this process is poorly understood. It is conceived that preclinical models of BE may facilitate discovery of molecular markers due to ease of longitudinal sampling. Clinical markers to stratify the patients at higher risk are vital to institute appropriate therapeutic intervention since EAC has very poor prognosis. We developed a dynamic in-vitro BE carcinogenesis (BEC) model by exposing naïve Barrett’s epithelium cell line (BAR-T) to acid and bile at pH4 (B4), 5min/day for a year. The BEC model acquired malignant characteristics after chronic repeated exposure to B4 similar to the sequential progression of BE to EAC in vivo. Aim To study cytogenetic changes during progressive transformation in the BEC model. Results We observed that the BAR-T cells progressively acquired several chromosomal abnormalities in the BEC model. Evidence of chromosomal loss (-Y) rearrangements [t(10;16) and dup (11q)] and clonal selection appeared during the early stages of the BEC model. Clonal selection resulted in a stabilized monoclonal population of cells that had a changed morphology and formed colony in soft agar. BAR-T cells grown in parallel without any exposure did not show any of these abnormalities. Conclusions Prolonged acid and bile exposure induced chromosomal aberrations and clonal selection in benign BAR-T cells. Since aneuploidy preceded morphological/dysplastic changes in the BEC model, chromosomal aberrations may be an early predictor of BE progression. The [t(10;16) and dup(11q)] aberrations identified in this study harbor several genes associated with cancer and may be responsible for neoplastic behavior of cells. After further validation, in-vivo, they may be clinically useful for diagnosis of BE, progressing to dysplasia/esophageal adenocarcinoma.
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Affiliation(s)
- Manisha Bajpai
- Division of Gastroenterology and Hepatology, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place, New Brunswick, NJ, 08903, USA.
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Su Z, Gay LJ, Strange A, Palles C, Band G, Whiteman DC, Lescai F, Langford C, Nanji M, Edkins S, van der Winkel A, Levine D, Sasieni P, Bellenguez C, Howarth K, Freeman C, Trudgill N, Tucker AT, Pirinen M, Peppelenbosch MP, van der Laan LJW, Kuipers EJ, Drenth JPH, Peters WH, Reynolds JV, Kelleher DP, McManus R, Grabsch H, Prenen H, Bisschops R, Krishnadath K, Siersema PD, van Baal JWPM, Middleton M, Petty R, Gillies R, Burch N, Bhandari P, Paterson S, Edwards C, Penman I, Vaidya K, Ang Y, Murray I, Patel P, Ye W, Mullins P, Wu AH, Bird NC, Dallal H, Shaheen NJ, Murray LJ, Koss K, Bernstein L, Romero Y, Hardie LJ, Zhang R, Winter H, Corley DA, Panter S, Risch HA, Reid BJ, Sargeant I, Gammon MD, Smart H, Dhar A, McMurtry H, Ali H, Liu G, Casson AG, Chow WH, Rutter M, Tawil A, Morris D, Nwokolo C, Isaacs P, Rodgers C, Ragunath K, MacDonald C, Haigh C, Monk D, Davies G, Wajed S, Johnston D, Gibbons M, Cullen S, Church N, Langley R, Griffin M, Alderson D, Deloukas P, Hunt SE, Gray E, Dronov S, Potter SC, Tashakkori-Ghanbaria A, Anderson M, Brooks C, Blackwell JM, Bramon E, et alSu Z, Gay LJ, Strange A, Palles C, Band G, Whiteman DC, Lescai F, Langford C, Nanji M, Edkins S, van der Winkel A, Levine D, Sasieni P, Bellenguez C, Howarth K, Freeman C, Trudgill N, Tucker AT, Pirinen M, Peppelenbosch MP, van der Laan LJW, Kuipers EJ, Drenth JPH, Peters WH, Reynolds JV, Kelleher DP, McManus R, Grabsch H, Prenen H, Bisschops R, Krishnadath K, Siersema PD, van Baal JWPM, Middleton M, Petty R, Gillies R, Burch N, Bhandari P, Paterson S, Edwards C, Penman I, Vaidya K, Ang Y, Murray I, Patel P, Ye W, Mullins P, Wu AH, Bird NC, Dallal H, Shaheen NJ, Murray LJ, Koss K, Bernstein L, Romero Y, Hardie LJ, Zhang R, Winter H, Corley DA, Panter S, Risch HA, Reid BJ, Sargeant I, Gammon MD, Smart H, Dhar A, McMurtry H, Ali H, Liu G, Casson AG, Chow WH, Rutter M, Tawil A, Morris D, Nwokolo C, Isaacs P, Rodgers C, Ragunath K, MacDonald C, Haigh C, Monk D, Davies G, Wajed S, Johnston D, Gibbons M, Cullen S, Church N, Langley R, Griffin M, Alderson D, Deloukas P, Hunt SE, Gray E, Dronov S, Potter SC, Tashakkori-Ghanbaria A, Anderson M, Brooks C, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Duncanson A, Markus HS, Mathew CG, Palmer CNA, Plomin R, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Wood N, Trynka G, Wijmenga C, Cazier JB, Atherfold P, Nicholson AM, Gellatly NL, Glancy D, Cooper SC, Cunningham D, Lind T, Hapeshi J, Ferry D, Rathbone B, Brown J, Love S, Attwood S, MacGregor S, Watson P, Sanders S, Ek W, Harrison RF, Moayyedi P, de Caestecker J, Barr H, Stupka E, Vaughan TL, Peltonen L, Spencer CCA, Tomlinson I, Donnelly P, Jankowski JAZ. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus. Nat Genet 2012; 44:1131-1136. [PMID: 22961001 PMCID: PMC3459818 DOI: 10.1038/ng.2408] [Show More Authors] [Citation(s) in RCA: 131] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Accepted: 08/15/2012] [Indexed: 02/07/2023]
Abstract
Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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Affiliation(s)
- Zhan Su
- Wellcome Trust Centre for Human Genetics, Oxford, UK
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Abstract
Barrett's esophagus (BE) is a common lesion that predisposes to a highly fatal esophageal adenocarcinoma (EA). There is evidence that BE or parts of its phenotype are genetically predisposed. Several single-nucleotide polymorphisms (SNPs) have been validated as predisposing to BE but the inherent flaws in the trial sizes, presence of controls and statistical power need circumspect analysis. The current paper links the interleukin 18 cytokine with BE and perhaps EA. Setting aside the issues above there are other issues such as the functional relevance of these SNPs for the association BE. There have been several case control series published indicating other genes. Furthermore, there are some sibling pairs study results with another set of genes identified. Invariably as useful as these studies are the size, scale to answer complex questions (complexity) and potential clinical significance are proportional in genomic studies. The new era of large-scale genome-wide studies in Barrett's and EA is needed. Shortly the first will be published showing two SNPs of significance in 7,838 Barrett's patients.
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Moyes LH, McEwan H, Radulescu S, Pawlikowski J, Lamm CG, Nixon C, Sansom OJ, Going JJ, Fullarton GM, Adams PD. Activation of Wnt signalling promotes development of dysplasia in Barrett's oesophagus. J Pathol 2012; 228:99-112. [PMID: 22653845 DOI: 10.1002/path.4058] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2012] [Revised: 04/24/2012] [Accepted: 05/21/2012] [Indexed: 02/06/2023]
Abstract
Barrett's oesophagus is a precursor of oesophageal adenocarcinoma, via intestinal metaplasia and dysplasia. Risk of cancer increases substantially with dysplasia, particularly high-grade dysplasia. Thus, there is a clinical need to identify and treat patients with early-stage disease (metaplasia and low-grade dysplasia) that are at high risk of cancer. Activated Wnt signalling is critical for normal intestinal development and homeostasis, but less so for oesophageal development. Therefore, we asked whether abnormally increased Wnt signalling contributes to the development of Barrett's oesophagus (intestinal metaplasia) and/or dysplasia. Forty patients with Barrett's metaplasia, dysplasia or adenocarcinoma underwent endoscopy and biopsy. Mice with tamoxifen- and β-naphthoflavone-induced expression of activated β-catenin were used to up-regulate Wnt signalling in mouse oesophagus. Immunohistochemistry of β-catenin, Ki67, a panel of Wnt target genes, and markers of intestinal metaplasia was performed on human and mouse tissues. In human tissues, expression of nuclear activated β-catenin was found in dysplasia, particularly high grade. Barrett's metaplasia did not show high levels of activated β-catenin. Up-regulation of Ki67 and Wnt target genes was also mostly associated with high-grade dysplasia. Aberrant activation of Wnt signalling in mouse oesophagus caused marked tissue disorganization with features of dysplasia, but only selected molecular indicators of metaplasia. Based on these results in human tissues and a mouse model, we conclude that abnormal activation of Wnt signalling likely plays only a minor role in initiation of Barrett's metaplasia but a more critical role in progression to dysplasia.
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Affiliation(s)
- Lisa H Moyes
- University Department of Surgery, Royal Infirmary, Glasgow, UK.
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Shutt JD, Boger P, Neale JR, Patel P, Sampson AP. Activity of the leukotriene pathway in Barrett's metaplasia and oesophageal adenocarcinoma. Inflamm Res 2012; 61:1379-84. [PMID: 22851204 DOI: 10.1007/s00011-012-0539-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2012] [Revised: 07/17/2012] [Accepted: 07/19/2012] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE Leukotriene (LT) B(4) is a lipid inflammatory mediator implicated in tumorigenesis in animal models of Barrett's oesophagitis, but little is known about the cysteinyl-leukotrienes (LTC(4), LTD(4), LTE(4)), which have distinct inflammatory and tumorigenic actions in other tissues. We recently showed that the terminal enzymes for the synthesis of both LT families are highly expressed in human oesophageal adenocarcinoma (OA) tissues. This study therefore examined the capacity of Barrett's metaplasia (BM) and OA tissues to synthesise LTs in vitro. SUBJECTS AND METHODS Oesophageal biopsies from patients with BM (n = 14), high-grade dysplasia (n = 2), OA (n = 11), and squamous control tissues (n = 11) were cultured with calcium ionophore A32187 (2 μM) for 60 min. LTB(4) and cysteinyl-leukotrienes were extracted and measured by specific enzyme immunoassays. RESULTS Levels of LTB(4) and cysteinyl-leukotrienes were 8.6-fold (P < 0.01) and 2.4-fold (P < 0.02) higher, respectively, in OA tissues than in squamous control tissues, but levels in BM tissues (n = 14) were not altered. Production of the two LT families correlated across all tissue types (r = 0.62, p < 0.00005). CONCLUSIONS Increased synthesis of LTB(4) and cysteinyl-leukotrienes has not previously been shown in human OA tissue and our results may indicate a role of these lipids in Barrett's disease progression.
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Affiliation(s)
- James David Shutt
- Department of Luminal Gastroenterology, University Hospitals Southampton NHS Foundation Trust, Southampton General Hospital, Southampton, UK
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Milind R, Attwood SE. Natural history of Barrett's esophagus. World J Gastroenterol 2012; 18:3483-91. [PMID: 22826612 PMCID: PMC3400849 DOI: 10.3748/wjg.v18.i27.3483] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2010] [Revised: 03/27/2012] [Accepted: 05/12/2012] [Indexed: 02/06/2023] Open
Abstract
The natural history of Barrett’s esophagus (BE) is difficult to quantify because, by definition, it should describe the course of the condition if left untreated. Pragmatically, we assume that patients with BE will receive symptomatic treatment with acid suppression, usually a proton pump inhibitor, to treat their heartburn. This paper describes the development of complications of stricture, ulcer, dysplasia and adenocarcinoma from this standpoint. Controversies over the definition of BE and its implications in clinical practice are presented. The presence of intestinal metaplasia and its relevance to cancer risk is discussed, and the need to measure the extent of the Barrett’s epithelium (long and short segments) using the Prague guidelines is emphasized. Guidelines and international consensus over the diagnosis and management of BE are being regularly updated. The need for expert consensus is important due to the lack of randomized trials in this area. After searching the literature, we have tried to collate the important studies regarding progression of Barrett’s to dysplasia and adenocarcinoma. No therapeutic studies yet reported show a clear reduction in the development of cancer in BE. The effect of pharmacological and surgical intervention on the natural history of Barrett’s is a subject of ongoing research, including the Barrett’s Oesophagus Surveillance Study and the aspirin and esomeprazole cancer chemoprevention trial with interesting results. The geographical variation and the wide range of outcomes highlight the difficulty of providing an individualized risk profile to patients with BE. Future studies on the interaction of genome wide abnormalities in Barrett’s and their interaction with environmental factors may allow individualization of the risk of cancer developing in BE.
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Detection of asymptomatic adenocarcinoma at endoscopy prior to gastric banding justifies routine endoscopy. Obes Surg 2012; 22:594-6. [PMID: 21887608 DOI: 10.1007/s11695-011-0506-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Pre-operative upper gastrointestinal (GI) endoscopy prior to gastric banding surgery remains controversial. We report the finding of asymptomatic oesophageal adenocarcinomas detected at pre-operative endoscopy in our unit. METHODS Data from a prospectively maintained database concerning the period May 2003 to October 2010 were reviewed. We identified 371 patients who had undergone upper GI endoscopy prior to gastric banding. Endoscopy reports were reviewed to identify any pathology detected. RESULTS Endoscopy revealed abnormalities in 207 (56%) patients. A range of abnormalities were detected, the most significant of which were two asymptomatic oesophageal adenocarcinomas. CONCLUSIONS The detection of two early, asymptomatic oesophageal adenocarcinomas in a high risk patient group justifies our policy of routine upper GI endoscopy prior to gastric banding surgery.
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Lee S, Han MJ, Lee KS, Back SC, Hwang D, Kim HY, Shin JH, Suh SP, Ryang DW, Kim HR, Shin MG. Frequent occurrence of mitochondrial DNA mutations in Barrett's metaplasia without the presence of dysplasia. PLoS One 2012; 7:e37571. [PMID: 22629421 PMCID: PMC3358277 DOI: 10.1371/journal.pone.0037571] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2012] [Accepted: 04/20/2012] [Indexed: 01/31/2023] Open
Abstract
Background Barrett's esophagus (BE) is one of the most common premalignant lesions and can progress to esophageal adenocarcinoma (EA). The numerous molecular events may play a role in the neoplastic transformation of Barrett’s mucosa such as the change of DNA ploidy, p53 mutation and alteration of adhesion molecules. However, the molecular mechanism of the progression of BE to EA remains unclear and most studies of mitochondrial DNA (mtDNA) mutations in BE have performed on BE with the presence of dysplasia. Methods/Findings Thus, the current study is to investigate new molecular events (Barrett’s esophageal tissue-specific-mtDNA alterations/instabilities) in mitochondrial genome and causative factors for their alterations using the corresponding adjacent normal mucosal tissue (NT) and tissue (BT) from 34 patients having Barrett’s metaplasia without the presence of dysplasia. Eighteen patients (53%) exhibited mtDNA mutations which were not found in adjacent NT. mtDNA copy number was about 3 times higher in BT than in adjacent NT. The activity of the mitochondrial respiratory chain enzyme complexes in tissues from Barrett’s metaplasia without the presence of dysplasia was impaired. Reactive oxygen species (ROS) level in BT was significantly higher than those in corresponding samples. Conclusion/Significance High ROS level in BT may contribute to the development of mtDNA mutations, which may play a crucial role in disease progression and tumorigenesis in BE.
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Affiliation(s)
- Soong Lee
- Department of Internal Medicine, College of Medicine, Seonam University, Namwon, Korea
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Dettmar PW, Strugala V, Tselepis C, Jankowski JA. The effect of alginates on deoxycholic-acid-induced changes in oesophageal mucosal biology at pH 4. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2012; 18:317-33. [PMID: 17471768 DOI: 10.1163/156856207779996922] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Long-standing gastro-oesophageal reflux disease (GORD) can give rise to Barrett's oesophagus (BM), a metaplastic condition and precursor to oesophageal adenocarcinoma (AC). Oesophageal cancer was once rare but is now the 5th biggest cancer killer in the U.K. Reflux of bile acids into the oesophagus is implicated in the progression to BM as bile acids at pH 4 have been shown to induce c-myc expression, an oncogene upregulated in BM and AC. In the present study we investigated the role of the biopolymer alginate on bile acid induced molecular changes in oesophageal cell lines. OE21, OE33 and TE-7 oesophageal cell lines were exposed to 100 microM deoxycholic acid at pH 4 in the presence or absence of alginates. Levels of c-myc, E-cadherin, beta-catenin and Tcf signalling were determined by Real-Time PCR, Western blotting, immunofluoresence and reporter assays. All alginates tested were able to prevent the induction of c-myc by acidified deoxycholic acid in vitro. The upstream effects of acidified deoxycholic acid on E-cadherin, beta-catenin and Tcf signalling were also suppressed by alginate. Therefore, we have demonstrated that reflux of bile acids into the oesophagus initiates a potentially damaging molecular cascade of events using an in vitro model and that a biopolymer, alginate, can protect against these effects.
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Affiliation(s)
- Peter W Dettmar
- Technostics, The Deep Business Centre, Kingston Upon Hull, East Yorkshire, HU1 4BG, UK
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Winberg H, Lindblad M, Lagergren J, Dahlstrand H. Risk factors and chemoprevention in Barrett's esophagus--an update. Scand J Gastroenterol 2012; 47:397-406. [PMID: 22428928 DOI: 10.3109/00365521.2012.667145] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Barrett's esophagus (BO) is a precursor of esophageal adenocarcinoma (OAC), a cancer with a poor prognosis and an increasing incidence. Hence there is an interest in mapping causal factors underlying BO and finding strategies to reduce the risk of dysplasia progression in patients with BO. Here we review current knowledge on established as well as less risk factors for the development of BO. Additionally, we summarize today's status on the use of chemoprevention aiming to reduce the risk of cancer progression in BO patients. METHODS We searched Medline and the Cochrane Library using the MeSH terms "Barrett's esophagus" and "Barrett esophagus," both alone and combined with the terms "risk factor," "aetiology," "diet," or "prevention." Focus was on original contributions, systematic reviews, and meta-analyses. RESULTS Established risk factors for the development of BO include gastro-esophageal reflux, obesity, male gender, Caucasian ethnicity, and increasing age. Smoking might increase the risk of BO, while aspirin/NSAIDs, Helicobacter pylori infection, and specific "healthy" dietary factors may lower the risk. The potential value of using chemoprevention with proton pump inhibitors, aspirin/NSAIDs, or statins is still uncertain. CONCLUSIONS There is today a substantial knowledge of risk factors of BO. Certain diet may be protective of BO, albeit yet to be proven. The efficiency of chemoprevention in BO is currently addressed further in randomized clinical trials.
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Affiliation(s)
- Hanna Winberg
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Upper Gastrointestinal Research (UGIR), Stockholm, Sweden
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Malfertheiner P, Nocon M, Vieth M, Stolte M, Jaspersen D, Koelz HR, Labenz J, Leodolter A, Lind T, Richter K, Willich SN. Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care--the ProGERD study. Aliment Pharmacol Ther 2012; 35:154-64. [PMID: 22070159 DOI: 10.1111/j.1365-2036.2011.04901.x] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The evolution of gastro-oesophageal reflux disease (GERD) under current management options remains uncertain. AIM To examine whether, depending on the initial presentation, non-erosive (NERD) and erosive reflux disease (ERD) without Barrett's oesophagus will progress to more severe disease under current routine care following the resolution of the initial condition. METHODS Patients with the primary symptom of heartburn were included at baseline, and stratified into non-erosive (NERD) and erosive reflux disease (ERD), LA grades A-D (Los Angeles classification). After a 2- to 8-week course with esomeprazole therapy to achieve endoscopic healing in ERD and symptom relief in NERD, patients were treated routinely at the discretion of their physician. We report oesophagitis status and the presence of endoscopic and confirmed Barrett's oesophagus after 5 years. RESULTS A total of 6215 patients were enrolled in the study of whom 2721 patients completed the 5-year follow-up. Progression, regression and stability of GERD severity were followed from baseline to 5 years. Only a few patients with NERD and mild/moderate ERD progressed to severe forms of ERD and even Barrett's oesophagus. Most patients remained stable or showed improvement in their oesophagitis; 5.9% of the NERD patients, 12.1% of LA grade A/B patients and 19.7% of LA grade C/D patients in whom no Barrett's oesophagus was recorded at baseline progressed to endoscopic or confirmed Barrett's oesophagus at 5 years. CONCLUSION Most GERD patients remain stable or improve over a 5-year observation period under current routine clinical care.
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Affiliation(s)
- P Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
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Abstract
Gastroesophageal reflux disease (GERD) affects 20-30% of the population in Western countries, and is one of the most common clinical problems in daily practice. GERD-associated functional and structural abnormalities are caused by recurrent exposure of the esophagus to acidic and nonacidic refluxate of gastric contents (containing duodenal and intestinal proteases as well as acid and gastric pepsin) from the stomach. Major progress has been made in the understanding of the molecular pathogenesis of GERD-associated mucosal inflammation, suggesting a complex and multifactorial pathogenesis and immune-mediated effects. This Review summarizes the complexity of mucosal pathogenesis, including microscopic changes, mucosal inflammation and GERD-specific molecular mediators, in the context of the clinical features and pathophysiological characteristics of GERD. The abnormal exposure of the esophagus to luminal contents leads to chronic mucosal inflammation that is characterized by the release of IL-8 specifically, as well as other proinflammatory mediators, from the esophageal mucosa. Evidence from animal studies indicates a stepwise inflammatory response by the epithelium, which attracts immune effector cells to infiltrate the mucosa. From bench to bedside, these novel molecular findings might provide new treatment options beyond current acid-suppressive therapy and the principle of inhibition of transient lower esophageal sphincter relaxation.
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Wiseman EF, Ang YS. Risk factors for neoplastic progression in Barrett’s esophagus. World J Gastroenterol 2011; 17:3672-83. [PMID: 21990948 PMCID: PMC3181452 DOI: 10.3748/wjg.v17.i32.3672] [Citation(s) in RCA: 17] [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: 07/21/2010] [Revised: 10/11/2010] [Accepted: 10/18/2010] [Indexed: 02/06/2023] Open
Abstract
Barrett’s esophagus (BE) confers a significant increased risk for development of esophageal adenocarcinoma (EAC), with the pathogenesis appearing to progress through a “metaplasia-dysplasia-carcinoma” (MDC) sequence. Many of the genetic insults driving this MDC sequence have recently been characterized, providing targets for candidate biomarkers with potential clinical utility to stratify risk in individual patients. Many clinical risk factors have been investigated, and associations with a variety of genetic, specific gastrointestinal and other modifiable factors have been proposed in the literature. This review summarizes the current understanding of the mechanisms involved in neoplastic progression of BE to EAC and critically appraises the relative roles and contributions of these putative risk factors from the published evidence currently available.
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Chemoprevention in Barrett's oesophagus. Best Pract Res Clin Gastroenterol 2011; 25:569-79. [PMID: 22122772 DOI: 10.1016/j.bpg.2011.10.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2011] [Revised: 10/12/2011] [Accepted: 10/27/2011] [Indexed: 02/07/2023]
Abstract
Barrett's oesophagus normally affects the distal oesophagus when metaplastic columnar lined epithelium replaces stratified squamous epithelium which predisposes to cancer development. This develops as a consequence of chronic gastroesophageal reflux (GORD). Those with Barrett's have a 40 fold increased risk of oesophageal adenocarcinoma [1]. There are is still a lack of understanding of the natural history of the cell of origin. This does hamper research into this area. We accept that there is a limitation in testing of the pathogenesis of Barrett's oesophagus due to a lack of a universally accepted animal model. The major questions surrounding Barrett's oesophagus include validity of surveillance strategies, the optimal treatment and more importantly an agent that can prevent progression to cancer without unacceptable side effects. The main chemopreventative agents that show promise are aspirin and proton pump inhibitors (PPIs). There are other agents such as green tea, berries and antioxidants and diet that have been suggested; we discuss the evidence available for these strategies. We hope for continued improvement in the clinical trial infrastructure to facilitate testing of new pharmacological and endoscopic interventions for Barrett's oesophagus.
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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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Affiliation(s)
- Janusz A Jankowski
- Digestive Diseases Centre, Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, UK.
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Kendall C, Day J, Hutchings J, Smith B, Shepherd N, Barr H, Stone N. Evaluation of Raman probe for oesophageal cancer diagnostics. Analyst 2010; 135:3038-41. [PMID: 20949209 DOI: 10.1039/c0an00536c] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Early detection of (pre-)cancerous changes improves prognosis, therefore in the UK patients at high risk of developing gastrointestinal cancers are enrolled on endoscopic surveillance programmes or the Bowel Cancer Screening Programme. The current gold standard technique for the detection of pre-cancerous changes in the gastrointestinal tract is histopathological analysis of biopsy tissue collected at endoscopy. This relies upon subjective assessment of morphological changes within the excised tissue samples and poor targeting of pre-malignant lesions. Raman spectroscopy offers a number of potential advantages for in vivo assessment of tissue at endoscopy. The performance of a custom built Raman probe as a biopsy targeting tool has been evaluated using excised biopsy material. Multivariate classification models have been used to demonstrate the likely ability of a miniature, confocal, fibre optic Raman probe to be used as an optical biopsy tool at endoscopy to provide spectral information in clinically practicable timescales. This technique could facilitate improved targeting of excisional biopsy with associated clinical benefits.
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Affiliation(s)
- Catherine Kendall
- Biophotonics Research Group, Leadon House, Gloucestershire Hospitals NHS Foundation Trust, Great Western Road, Gloucester, GL1 3NN, UK
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Boger PC, Turner D, Roderick P, Patel P. A UK-based cost-utility analysis of radiofrequency ablation or oesophagectomy for the management of high-grade dysplasia in Barrett's oesophagus. Aliment Pharmacol Ther 2010; 32:1332-42. [PMID: 21050235 DOI: 10.1111/j.1365-2036.2010.04450.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND In the UK, oesophagectomy is the current recommendation for patients with persistent high-grade dysplasia in Barrett's oesophagus. Radiofrequency ablation is an alternative new technology with promising early trial results. AIM To undertake a cost-utility analysis comparing these two strategies. METHODS We constructed a Markov model to simulate the natural history of a cohort of patients with high-grade dysplasia in Barrett's oesophagus undergoing one of two treatment options: (i) oesophagectomy or (ii) radiofrequency ablation followed by endoscopic surveillance with oesophagectomy for high-grade dysplasia recurrence or persistence. RESULTS In the base case analysis, radiofrequency ablation dominated as it generated 0.4 extra quality of life years at a cost saving of £1902. For oesophagectomy to be the most cost-effective option, it required a radiofrequency ablation treatment failure rate (high-grade dysplasia persistence or progression to cancer) of >44%, or an annual risk of high-grade dysplasia recurrence or progression to cancer in the ablated oesophagus of >15% per annum. There was an 85% probability that radiofrequency ablation remained cost-effective at the NICE willingness to pay threshold range of £20 000-30 000. CONCLUSION Radiofrequency ablation is likely to be a cost-effective option for high-grade dysplasia in Barrett's oesophagus in the UK.
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Affiliation(s)
- P C Boger
- Department of Luminal Gastroenterology, Southampton General Hospital, UK.
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36
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A systematic review of the evidence for radiofrequency ablation for Barrett's esophagus. Surg Endosc 2010. [PMID: 20464420 DOI: 10.1007/s00464-010-1087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Radiofrequency ablation with the HALO system is a new option for the treatment of patients with Barrett's esophagus. This systematic review summarizes the results of all relevant publications on this topic to answer patient-relevant clinical questions and to evaluate the potential benefit and harm of this new therapy. METHODS A systematic literature search of MEDLINE and CENTRAL up to May 2009 was performed. To identify the relevant literature, references were evaluated by two reviewers independently. The inclusion criteria for the review required that studies investigated patients with Barrett's esophagus, used radiofrequency ablation as the intervention, and had a minimum follow-up period of 12 months. RESULTS A total of nine relevant observational studies (involving 429 patients) were identified. Complete eradication of Barrett's esophagus dysplasia and metaplasia was achieved respectively for 71-100% and for 46-100% of the patients. Only six cases of stenosis and one case of buried intestinal metaplasia were reported among all the patients. Only a few mild adverse events were reported. CONCLUSIONS Based on the evidence of observational studies, the summary of the current data suggests that radiofrequency ablation with the HALO system could be a promising method associated with a low complication rate, low risk of stricture formations, and a minor probability of buried glands. To evaluate the potential benefit at a higher level of evidence, randomized controlled trials (RCTs) involving a direct comparison with other more established endoscopic methods such as photodynamic therapy are necessary.
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A systematic review of the evidence for radiofrequency ablation for Barrett's esophagus. Surg Endosc 2010; 24:2935-43. [PMID: 20464420 DOI: 10.1007/s00464-010-1087-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2009] [Accepted: 03/11/2010] [Indexed: 12/28/2022]
Abstract
BACKGROUND Radiofrequency ablation with the HALO system is a new option for the treatment of patients with Barrett's esophagus. This systematic review summarizes the results of all relevant publications on this topic to answer patient-relevant clinical questions and to evaluate the potential benefit and harm of this new therapy. METHODS A systematic literature search of MEDLINE and CENTRAL up to May 2009 was performed. To identify the relevant literature, references were evaluated by two reviewers independently. The inclusion criteria for the review required that studies investigated patients with Barrett's esophagus, used radiofrequency ablation as the intervention, and had a minimum follow-up period of 12 months. RESULTS A total of nine relevant observational studies (involving 429 patients) were identified. Complete eradication of Barrett's esophagus dysplasia and metaplasia was achieved respectively for 71-100% and for 46-100% of the patients. Only six cases of stenosis and one case of buried intestinal metaplasia were reported among all the patients. Only a few mild adverse events were reported. CONCLUSIONS Based on the evidence of observational studies, the summary of the current data suggests that radiofrequency ablation with the HALO system could be a promising method associated with a low complication rate, low risk of stricture formations, and a minor probability of buried glands. To evaluate the potential benefit at a higher level of evidence, randomized controlled trials (RCTs) involving a direct comparison with other more established endoscopic methods such as photodynamic therapy are necessary.
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Abstract
Metaplasia (or transdifferentiation) is defined as the transformation of one tissue type to another. Clues to the molecular mechanisms that control the development of metaplasia are implied from knowledge of the transcription factors that specify tissue identity during normal embryonic development. Barrett's metaplasia describes the development of a columnar/intestinal phenotype in the squamous oesophageal epithelium and is the major risk factor for oesophageal adenocarcinoma. This particular type of cancer has a rapidly rising incidence and a dismal prognosis. The homoeotic transcription factor Cdx2 (Caudal-type homeobox 2) has been implicated as a master switch gene for intestine and therefore for Barrett's metaplasia. Normally, Cdx2 expression is restricted to the epithelium of the small and large intestine. Loss of Cdx2 function, or conditional deletion in the intestine, results in replacement of intestinal cells with a stratified squamous phenotype. In addition, Cdx2 is sufficient to provoke intestinal metaplasia in the stomach. In the present paper, we review the evidence for the role of Cdx2 in the development of Barrett's metaplasia.
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Affiliation(s)
- Benjamin J Colleypriest
- Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
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Ingravallo G, Dall'Olmo L, Segat D, Fassan M, Mescoli C, Dazzo E, Castoro C, Polimeno L, Rizzetto C, Baroni MD, Zaninotto G, Ancona E, Rugge M. CDX2 hox gene product in a rat model of esophageal cancer. J Exp Clin Cancer Res 2009; 28:108. [PMID: 19664209 PMCID: PMC3225830 DOI: 10.1186/1756-9966-28-108] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2009] [Accepted: 08/07/2009] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis. METHODS The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: <10 weeks; Group B: 10-30 weeks; Group C: >30 weeks). RESULTS No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001). CONCLUSION De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.
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Affiliation(s)
- Giuseppe Ingravallo
- Department of Medical Diagnostic Sciences & Special Therapies, Pathology Unit, University of Padova, Padova, Italy
- Department of Pathological Anatomy, University of Bari, Bari, Italy
| | | | - Daniela Segat
- Department of Mathematics, Physics, and Natural Sciences, University of Padova, Padova, Italy
| | - Matteo Fassan
- Department of Medical Diagnostic Sciences & Special Therapies, Pathology Unit, University of Padova, Padova, Italy
| | - Claudia Mescoli
- Department of Medical Diagnostic Sciences & Special Therapies, Pathology Unit, University of Padova, Padova, Italy
| | - Emanuela Dazzo
- Department of Mathematics, Physics, and Natural Sciences, University of Padova, Padova, Italy
| | - Carlo Castoro
- Istituto Oncologico Veneto (IOV-IRCCS), Padova, Italy
| | - Lorenzo Polimeno
- Department of Emergency & Organ Transplantation, University of Bari, Bari, Italy
| | - Christian Rizzetto
- Department of Gastrointestinal & Surgical Sciences, Clinica Chirurgica III, University of Padova, Padova, Italy
| | - Maurizio David Baroni
- Department of Mathematics, Physics, and Natural Sciences, University of Padova, Padova, Italy
| | - Giovanni Zaninotto
- Department of Gastrointestinal & Surgical Sciences, Clinica Chirurgica III, University of Padova, Padova, Italy
- Department of General Surgery, Sts Giovanni & Paolo Hospital, Venezia, Italy
| | - Ermanno Ancona
- Istituto Oncologico Veneto (IOV-IRCCS), Padova, Italy
- Department of Gastrointestinal & Surgical Sciences, Clinica Chirurgica III, University of Padova, Padova, Italy
| | - Massimo Rugge
- Department of Medical Diagnostic Sciences & Special Therapies, Pathology Unit, University of Padova, Padova, Italy
- Istituto Oncologico Veneto (IOV-IRCCS), Padova, Italy
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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: 40] [Impact Index Per Article: 2.5] [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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Abstract
This article reviews the environmental risk factors and predisposing conditions for the two main histologic types of esophageal cancer. Tobacco smoking, excessive alcohol consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of esophageal squamous cell carcinoma. Results of investigations on other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and, probably, absence of H pylori in the stomach increase the risk of esophageal adenocarcinoma. Results of studies investigating other factors are also discussed.
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Affiliation(s)
- Farin Kamangar
- Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 3034, Bethesda, MD 20892-7232, Phone: (301) 594-2936,
| | - Wong-Ho Chow
- Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 8100, Bethesda, MD 20892-7240, Phone: (301) 435-4708,
| | - Christian Abnet
- Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 3042, Bethesda, MD 20892-7232, Phone: (301) 594-1511,
| | - Sanford Dawsey
- Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 3024, Bethesda, MD 20892-7232, Phone: (301) 594-2930,
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Das D, Chilton AP, Jankowski JA. Chemoprevention of oesophageal cancer and the AspECT trial. Recent Results Cancer Res 2009; 181:161-9. [PMID: 19213566 DOI: 10.1007/978-3-540-69297-3_15] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2025]
Abstract
Oesophageal cancer is on the rise and often present in an advanced state. Advances in surgical techniques, chemotherapy and radiotherapy have not changed the prognosis of oesophageal cancer over the last 20 years. With the unravelling of molecular biology of carcinogenesis in the oesophagus, there is a need for a paradigm shift from cancer treatment to prevention. Barrett's oesophagus is the commonest pre-malignant condition for development of oesophageal adenocarcinomas and is eminently suitable for the study of chemoprevention strategies. Now in its third year, the AspECT trial is the biggest, multicentre, randomised controlled clinical trial looking at the long-term chemoprevention effect of esomeprazole with or without aspirin. More than 85% of the participants tolerated the medications at the initial intended doses, and the drop-out rate has been 7%; the interim analysis is due in 2011.
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Affiliation(s)
- Debasish Das
- Digestive Disease Centre, Leicester Royal Infirmary, UK
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The application of Prague C and M criteria in the diagnosis of Barrett's esophagus in an ethnic Chinese population. Am J Gastroenterol 2009; 104:13-20. [PMID: 19098843 DOI: 10.1038/ajg.2008.43] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To investigate the prevalence of endoscopically suspected esophageal metaplasia (ESEM) in an ethnic Chinese population by endoscopic and pathologic evaluation and to assess the utility of Prague C and M criteria. METHODS Consecutive patients who received esophagogastroduodenoscopy either as a part of therapy for various upper abdominal symptoms or as an annual health check-up were evaluated for the existence of ESEM and Barrett's esophagus (BE). Biopsy with standardized random four pieces every 2 cm from the four quarters of esophagus with ESEM lesion was performed. BE was defined by histological verification of specialized intestinal metaplasia and gastric metaplasia and was categorized according to the Prague C and M criteria. RESULTS A total of 5,179 subjects were screened from Jan. 2007 to Dec. 2007. This study enrolled 4,797, including 3,386 for referral endoscopy and 1,411 for screening endoscopy. Prevalence of BE among the referral endoscopy, screening endoscopy, and overall was 1.06%, 0.35%, and 0.85%, respectively. A total of 41 subjects with BE were detected among 93 ESEM subjects. Short segment BE (75.6%, n=31) was more prevalent than long segment BE (24.4%, n=10). The proportions of BE from subjects with ESEM by Prague C and M criteria were C< or =1M1 38.9% (19/50), C< or =1M2 40% (12/30), and CxM> or =3 76.9% (10/13). CONCLUSIONS On the basis of the standardized protocol with random four-quadrate endoscopic biopsy, we have demonstrated the utility of Prague C and M criteria to characterize the BE in an ethnic Chinese population.
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Hölscher AH, Vallböhmer D, Gutschow C, Bollschweiler E. Reflux esophagitis, high-grade neoplasia, and early Barrett's carcinoma-what is the place of the Merendino procedure? Langenbecks Arch Surg 2008; 394:417-24. [PMID: 18989696 DOI: 10.1007/s00423-008-0429-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2008] [Accepted: 09/25/2008] [Indexed: 01/02/2023]
Abstract
INTRODUCTION Because of the increasing frequency of Barrett's cancer in Western industrialized countries, the management of reflux disease with the potential development of Barrett's esophagus, neoplasia, and early carcinoma is very important. In case of established Barrett's esophagus, the malignant degeneration of the specialized epithelium cannot definitely be prevented by antireflux surgery or continuous medication. Mucosal adenocarcinomas nearly never develop lymph node metastasis and can mostly be treated by endoscopic mucosectomy. The deeper the submucosa is infiltrated, the higher is the rate of lymph node metastasis which is, on the average, 30% for submucosal carcinoma. CONCLUSIONS Therefore, radical subtotal esophagectomy is the treatment of choice for submucosal carcinoma, whereas distal esophageal resection with limited lymph node dissection is only indicated in mucosal carcinoma which cannot be completely removed by interventional endoscopy.
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Affiliation(s)
- A H Hölscher
- Department of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
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von Rahden BHA, Stein HJ, Weber A, Vieth M, Stolte M, Rösch T, Schmid RM, Sarbia M, Meining A. Critical reappraisal of current surveillance strategies for Barrett's esophagus: analysis of a large German Barrett's database. Dis Esophagus 2008; 21:685-9. [PMID: 18847456 DOI: 10.1111/j.1442-2050.2008.00857.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE). Based on a large database, gathered from predominantly community-based practices in Germany, we aimed to investigate the time-course of malignant progression and apply these findings to current clinical practice. Data of 1438 patients with BE from a large German BE database were analyzed. Patients with at least one follow-up endoscopy/biopsy were included. Detection of 'malignant Barrett' (either high-grade intra-epithelial neoplasia or invasive adenocarcinoma) was considered as study end-point. Of 1438 patients with BE, 57 patients had low-grade intra-epithelial neoplasia (LG-IN) on initial biopsy and 1381 exhibited non-neoplastic BE. 'Malignant Barrett' was detected in 28 cases (1.9%) during a median follow-up period of 24 months (1-255), accounting for an incidence of 0.95% per patient year of follow-up. The frequency of 'malignant Barrett' was significantly higher (P < 0.001, chi(2)-test) in the LG-IN group (n = 11, 19.3%) compared with the non-neoplastic BE group (n = 17, 1.2%). In the non-neoplastic BE group, 'malignant Barrett' was predominantly found during re-endoscopy within the first year of follow-up (12 of 17; 70.6%), in contrast to the LG-IN group, in which 'malignant Barrett' was observed predominantly after a time exceeding 12 months (8 of 11, 72.7%; P = 0.05, Fisher's exact test). Initial endoscopic evaluations seem to play the most crucial role in managing BE. After 1 year of follow-up, endoscopic surveillance should be focused on patients with LG-IN. In patients with repeatedly proven non-neoplastic BE, elongation of the follow-up intervals to the upper limit of current guidelines, that is, 5 years, might be justified.
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Affiliation(s)
- B H A von Rahden
- Department of Surgery, Technical University Munich, Munich, Germany
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Tseng PH, Lee YC, Chiu HM, Huang SP, Liao WC, Chen CC, Wang HP, Wu MS, Lin JT. Prevalence and clinical characteristics of Barrett's esophagus in a Chinese general population. J Clin Gastroenterol 2008; 42:1074-1079. [PMID: 18360296 DOI: 10.1097/mcg.0b013e31809e7126] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The prevalence of Barrett esophagus (BE) remains elusive in the general populations. GOALS The purpose of this study was to identify the prevalence and clinical characteristics of BE in a Chinese general population. STUDY Between June 2003 and December 2006, consecutive subjects were evaluated via upper gastrointestinal endoscopy during a routine health examination. Patients were evaluated for any abnormalities, including endoscopically suspected esophageal metaplasia (ESEM) and erosive esophagitis (EE). Biopsies were attained from patients with ESEM to confirm a diagnosis of BE. The demographic data and endoscopic findings were retrospectively analyzed. RESULTS Of the 19,812 endoscopies performed, 56 patients (0.28%) were diagnosed with ESEM and 3129 patients (15.7%) with EE. Twelve of the 56 patients diagnosed with ESEM (0.06% of the total number of patients who underwent endoscopy) were confirmed to have BE after histologic analysis of the biopsies. Patients with BE were older than patients without BE (61.6 vs. 51.7 y), and only one of the 12 patients diagnosed with BE (8.3%) reported typical gastroesophageal reflux symptoms. A majority of the BE patients were categorized as short-segment BE (91.7%) and concomitant EE was found in 4 (33.3%). Smoking, alcohol, and metabolic disorders seemed to be associated with the presence of BE and EE. CONCLUSIONS The prevalence of BE in a Chinese general population was lower than that in other reported studies, particularly in comparison with the studies originating from Western countries. Patients with advanced age and metabolic disorders are risk factors for developing BE.
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Affiliation(s)
- Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin County, Taipei, Taiwan
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Tischoff I, Tannapfel A. Barrett's esophagus: can biomarkers predict progression to malignancy? Expert Rev Gastroenterol Hepatol 2008; 2:653-63. [PMID: 19072343 DOI: 10.1586/17474124.2.5.653] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Barrett's esophagus (BE) is one of the most common premalignant lesions and can progress to esophageal adenocarcinoma. It is characterized histologically by a specialized intestinal metaplasia that replaces the squamous epithelium of the distal esophagus, and is associated with chronic gastroesophageal reflux disease and obesity. Similar to the adenoma-carcinoma sequence of colorectal carcinomas, esophageal adenocarcinoma develops through progression from BE to low- and high-grade dysplasia, then to adenocarcinoma with accumulation of genetic and epigenetic abnormalities. The exact malignancy potential of BE is uncertain. Dysplasia is the most predictive marker for risk of esophageal adenocarcinoma, whereas endoscopic and histological diagnoses are still the gold standard for surveillance of patients with BE. However, both are limited, either by sampling errors in biopsies or by differences in histological interpretation. Several studies have identified candidate biomarkers that may have predictive value and may serve as additional factors for the risk assessment of esophageal adenocarcinoma. This review discusses the role of biomarkers in the progression from BE to adenocarcinoma, focusing on clinical and molecular markers.
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Affiliation(s)
- Iris Tischoff
- Institute of Pathology, Ruhr-University of Bochum, Bürkle-de-la-Camp-Platz, Bochum 44789, Germany.
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Abstract
The incidence of esophageal adenocarcinoma continues to increase at a rate greater than that of any other cancer in the western world. Current strategies to deal with this situation are problematic, and the time has come for new approaches to this problem. Chemoprevention is one such approach. In this issue of the American Journal of Gastroenterology, Hur et al. examined Barrett's esophagus patient preferences for cancer chemoprevention with either aspirin or celecoxib. They found that 93% of their patients were willing to take one of these two drugs, but that nearly five times as many patients preferred aspirin to celecoxib (76%vs 15%). The most important reason for willingness to use celecoxib or aspirin was cancer prevention, while the most important reason for not using celecoxib was risk of myocardial infarction and for aspirin gastrointestinal adverse events. While this study indicates that there is a strong interest among Barrett's esophagus patients for chemoprevention, it is still premature for our patients to embark on such an approach. The role of chemoprevention in Barrett's esophagus still awaits the results of ongoing clinical trials in the United Kingdom and North America.
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Rai N, Jenkins GJS, McAdam E, Hibbitts SJ, Fiander AN, Powell NG. Human papillomavirus infection in Barrett's oesophagus in the UK: an infrequent event. J Clin Virol 2008; 43:250-2. [PMID: 18718811 DOI: 10.1016/j.jcv.2008.07.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2008] [Revised: 06/26/2008] [Accepted: 07/02/2008] [Indexed: 02/07/2023]
Abstract
BACKGROUND Human papillomavirus (HPV) infection has been reported in squamous cell carcinomas of the oesophagus and has been recently described in Barrett's oesophagus, a premalignant condition which may give rise to oesophageal adenocarcinoma. OBJECTIVES To investigate HPV infection in Barrett's oesophagus in a UK population. STUDY DESIGN DNA was extracted from 73 Barrett's oesophagus biopsies and examined for the presence of DNA for 14 high risk (HR) and 6 low risk (LR) HPV types. RESULTS HPV DNA was present in only 1 of 73 samples; genotyping indicated this was a high risk type 51 infection. CONCLUSIONS HPV infection appears unlikely to be a significant factor in the aetiology of Barrett's oesophagus in the UK.
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Affiliation(s)
- N Rai
- Department of Obstetrics and Gynaecology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom
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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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