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S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1786-1852. [PMID: 39389106 DOI: 10.1055/a-2344-6282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
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S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:862-933. [PMID: 37494073 DOI: 10.1055/a-2060-1069] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
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Hartgerink C, Nimri FM, Zuchelli T, Jafri SM, Piraka C. Band Ligation Can Be Used to Treat Barrett's Esophagus and Concurrent Esophageal Varices: A Case Series. Dig Dis Sci 2023; 68:1381-1385. [PMID: 36131048 DOI: 10.1007/s10620-022-07696-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 09/05/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Patients with Barrett's esophagus (BE) and esophageal varices present a unique management dilemma. Endoscopic ablation and endoscopic resection are not suitable treatment options due to bleeding risk. Data are limited on successful eradication of BE and esophageal varices utilizing band ligation. AIMS To assess the outcomes of patients with BE and esophageal varices treated with banding. METHODS Retrospective analysis of patients with BE and esophageal varices who were treated with band ligation. RESULTS A total of eight patients were included in the case series. In all eight cases, BE and esophageal varices were successfully treated with band ligation alone. There were no bleeding, perforation or infectious complications in any patients undergoing banding for treatment of BE. Four patients had biopsy-proven dysplasia prior to treatment with band ligation. After band ligation, the 2 of 4 dysplastic cases that had repeat biopsies showed histologic resolution of the dysplasia. All patients who received banding for BE were followed at least yearly except for one patient lost to follow up. No interval esophageal cancers were reported in any patients with BE that were banded. CONCLUSIONS Band ligation was used to treat BE pathology in eight patients with esophageal varices. Treatment of dysplasia through this method yielded negative biopsies both for dysplasia and BE on repeat endoscopy. This case series highlights the value of utilizing band ligation to address the management dilemma of BE in the context of esophageal varices.
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Affiliation(s)
- Colin Hartgerink
- Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI, 48201, USA.
| | - Faisal M Nimri
- Department of Gastroenterology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA
| | - Tobias Zuchelli
- Department of Gastroenterology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA
| | - Syed-Mohammed Jafri
- Department of Gastroenterology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA
| | - Cyrus Piraka
- Department of Gastroenterology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA
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Jajosky A, Fels Elliott DR. Esophageal Cancer Genetics and Clinical Translation. Thorac Surg Clin 2022; 32:425-435. [DOI: 10.1016/j.thorsurg.2022.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Wong MT, Singhi AD, Larson BK, Huynh CAT, Balzer BL, Burch M, Dhall D, Gangi A, Gong J, Guindi M, Hendifar AE, Kim SA, de Peralta-Venturina M, Waters KM. Claudin-18: Patterns of Expression in the Upper Gastrointestinal Tract and Utility as a Marker of Gastric Origin in Neuroendocrine Tumors. Arch Pathol Lab Med 2022; 147:559-567. [PMID: 35976638 DOI: 10.5858/arpa.2021-0428-oa] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2022] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Claudin-18 is expressed in some gastric cancers. Clinical trials are evaluating it as a therapeutic target. OBJECTIVES.— To evaluate claudin-18 expression in intestinal metaplasia, dysplasia, and adenocarcinoma of the distal esophagus/gastroesophageal junction and stomach and to evaluate claudin-18 expression in gastric and nongastric neuroendocrine tumors as a marker of gastric origin. DESIGN.— Samples included gastroesophageal junction with intestinal metaplasia (n = 40), dysplasia (n = 54), and adenocarcinoma (n = 20) and stomach with intestinal metaplasia (n = 79), dysplasia (n = 43), and adenocarcinoma (n = 25). Additionally, gastric (n = 40) and nongastric (n = 322) neuroendocrine tumors were included. Claudin-18 expression was evaluated for any staining as positive and by meeting clinical trial inclusion criteria (≥2+ intensity in ≥50% of tumor). RESULTS.— Claudin-18 staining was not significantly different across dysplasia categories in the gastroesophageal junction (P = .11) or stomach (P = .12). The rate of positive staining was higher in gastroesophageal junction than stomach for intestinal metaplasia (37 of 40 [92.5%] versus 37 of 79 [46.8%]; P < .001) and high-grade dysplasia (33 of 38 [86.8%] versus 9 of 16 [56.3%]; P = .03). Intestinal metaplasia showed staining in 7 of 37 autoimmune gastritis samples (18.9%) compared with 30 of 42 samples without autoimmune gastritis (71.4%) (P < .001). Adenocarcinoma showed similar staining in gastroesophageal junction (15 of 20; 75.0%) and stomach (17 of 25; 68.0%) (P = .85). Eighty percent (32 of 40) of gastric neuroendocrine tumors were positive for claudin-18 expression, with 57.5% (23 of 40) meeting clinical trial inclusion criteria. Comparatively, 0.62% (2 of 322) of nongastric neuroendocrine tumors showed staining (P < .001). CONCLUSIONS.— Claudin-18 staining was similar in intestinal metaplasia, dysplasia, and adenocarcinoma. Claudin-18 was negative in most cases of intestinal metaplasia in autoimmune gastritis, indicating that intestinal metaplasia in this setting may differ from other forms. Claudin-18 was sensitive and specific for gastric origin in neuroendocrine tumors.
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Affiliation(s)
- Mary T Wong
- From the Department of Pathology, Oregon Health & Science University, Portland (Wong)
| | - Aatur D Singhi
- From the Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (Singhi)
| | - Brent K Larson
- From the Department of Pathology and Laboratory Medicine (Larson, Huynh, Balzer, Guindi, Kim, de Peralta-Venturina, Waters)
| | - Carissa A T Huynh
- From the Department of Pathology and Laboratory Medicine (Larson, Huynh, Balzer, Guindi, Kim, de Peralta-Venturina, Waters)
| | - Bonnie L Balzer
- From the Department of Pathology and Laboratory Medicine (Larson, Huynh, Balzer, Guindi, Kim, de Peralta-Venturina, Waters)
| | - Miguel Burch
- From the Division of Surgical Oncology, Department of Surgery (Burch, Gangi), Samuel Oschin Comprehensive Cancer Institute
| | - Deepti Dhall
- From Cedars-Sinai Medical Center, Los Angeles, California; and the Department of Pathology, University of Alabama at Birmingham (Dhall)
| | - Alexandra Gangi
- From the Division of Surgical Oncology, Department of Surgery (Burch, Gangi), Samuel Oschin Comprehensive Cancer Institute
| | - Jun Gong
- From the Department of Medicine, Division of Hematology and Oncology (Gong, Hendifar), Samuel Oschin Comprehensive Cancer Institute
| | - Maha Guindi
- From the Department of Pathology and Laboratory Medicine (Larson, Huynh, Balzer, Guindi, Kim, de Peralta-Venturina, Waters)
| | - Andrew E Hendifar
- From the Department of Medicine, Division of Hematology and Oncology (Gong, Hendifar), Samuel Oschin Comprehensive Cancer Institute
| | - Stacey A Kim
- From the Department of Pathology and Laboratory Medicine (Larson, Huynh, Balzer, Guindi, Kim, de Peralta-Venturina, Waters)
| | - Mariza de Peralta-Venturina
- From the Department of Pathology and Laboratory Medicine (Larson, Huynh, Balzer, Guindi, Kim, de Peralta-Venturina, Waters)
| | - Kevin M Waters
- From the Department of Pathology and Laboratory Medicine (Larson, Huynh, Balzer, Guindi, Kim, de Peralta-Venturina, Waters)
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Choi KKH, Sanagapalli S. Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies. World J Gastrointest Oncol 2022; 14:568-586. [PMID: 35321279 PMCID: PMC8919017 DOI: 10.4251/wjgo.v14.i3.568] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 11/12/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.
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Affiliation(s)
- Kevin Kyung Ho Choi
- AW Morrow Gastroenterology Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, NSW, Australia
| | - Santosh Sanagapalli
- Department of Gastroenterology, St Vincent’s Hospital, Darlinghurst 2010, NSW, Australia
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Chueca E, Valero A, Hördnler C, Puertas A, Carrera P, García-González MA, Strunk M, Lanas A, Piazuelo E. Quantitative analysis of p16 methylation in Barrett's carcinogenesis. Ann Diagn Pathol 2020; 47:151554. [PMID: 32570024 DOI: 10.1016/j.anndiagpath.2020.151554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 05/12/2020] [Accepted: 06/15/2020] [Indexed: 11/19/2022]
Abstract
p16 hypermethylation in Barrett's carcinogenesis has been evaluated in studies which did not take into account sample heterogeneity and yielded qualitative (methylated/unmethylated) instead of accurate quantitative (percentage of CpG methylation) data. We aimed to measure the degree of p16 methylation in pure samples representing all the steps of Barrett's tumorogenesis and to evaluate the influence of sample heterogeneity in methylation analysis. METHODS 77 paraffin-embedded human esophageal samples were analyzed. Histological grading was established by two pathologists in: negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Areas of interest were selected by laser-capture microdissection. p16 methylation was quantified by pyrosequencing. An adjacent section of the whole sample was also analyzed to compare methylation data. RESULTS After microdissection, we obtained 15 samples of squamous epithelium, 36 non-dysplastic Barrett's esophagus, 3 indefinite for dysplasia, 24 low-grade dysplasia, 4 high-grade dysplasia and 12 adenocarcinoma. Squamous epithelium showed the lowest methylation rates: 6% (IQR 5-11) vs. 11%(7-39.50) in negative/indefinite for dysplasia, p<0.01; 10.60%(6-24) in low-grade dysplasia, p<0.05; and 44.50%(9-66.75) in high-grade dysplasia/adenocarcinoma, p<0.01. This latter group also exhibited higher methylation rates than Barrett's epithelium with and without low-grade dysplasia (p<0.05). p16 methylation rates of microdissected and non-microdissected samples did not correlate unless the considered histological alteration comprised >71% of the sample. CONCLUSIONS p16 methylation is an early event in Barrett's carcinogenesis which increases with the severity of histological alteration. p16 methylation rates are profoundly influenced by sample heterogeneity, so selection of samples is crucial in order to detect differences.
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Affiliation(s)
- E Chueca
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain; IIS Aragón, Instituto de Investigación Sanitaria Aragón, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain
| | - A Valero
- Service of Pathology, University Hospital Miguel Servet, Paseo Isabel la Católica 1-3, 50009 Zaragoza, Spain
| | - C Hördnler
- Service of Pathology, University Hospital Miguel Servet, Paseo Isabel la Católica 1-3, 50009 Zaragoza, Spain
| | - A Puertas
- Service of Pathology, University Hospital Miguel Servet, Paseo Isabel la Católica 1-3, 50009 Zaragoza, Spain
| | - P Carrera
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain
| | - M A García-González
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain; IIS Aragón, Instituto de Investigación Sanitaria Aragón, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain; IACS Aragón, Instituto Aragonés de Ciencias de la Salud, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain
| | - M Strunk
- IACS Aragón, Instituto Aragonés de Ciencias de la Salud, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain
| | - A Lanas
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain; IIS Aragón, Instituto de Investigación Sanitaria Aragón, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain; University of Zaragoza, Calle de Pedro Cerbuna 12, 50009, Zaragoza, Spain
| | - E Piazuelo
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain; IIS Aragón, Instituto de Investigación Sanitaria Aragón, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain; IACS Aragón, Instituto Aragonés de Ciencias de la Salud, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain.
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Thiruvengadam SK, Tieu AH, Luber B, Wang H, Meltzer SJ. Risk Factors for Progression of Barrett's Esophagus to High Grade Dysplasia and Esophageal Adenocarcinoma. Sci Rep 2020; 10:4899. [PMID: 32184470 PMCID: PMC7078316 DOI: 10.1038/s41598-020-61874-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 03/01/2020] [Indexed: 12/17/2022] Open
Abstract
Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Methods of identifying BE patients at high risk for progression to high-grade dysplasia (HGD) or EAC are needed to improve outcomes and identify who will benefit most from intensive surveillance or ablative therapy. Clinical predictors of BE progression to HGD or EAC are poorly understood, with multiple contradictory studies. We performed a retrospective study which included 460 patients at Johns Hopkins Hospital who underwent at least 2 upper endoscopies 6 months apart showing biopsy-documented BE between 1992 and 2013. Patients with EAC or HGD at the initial endoscopy were excluded. Demographic, clinicopathological, and endoscopic data were collected. Univariate and multivariate Cox proportional hazards analyses with time to progression to HGD and EAC were performed. Among 460 patients included in the study, 132 BE patients developed HGD and 62 developed EAC. Significant EAC risk factors included age, abdominal obesity, caffeine intake, and the presence of HGD. Risk factors for HGD or EAC included age, caffeine intake, and low-grade dysplasia while colonic adenomas trended towards significance. Notably, a history of statin or SSRI usage reduced the risk of EAC or HGD by 49% or 61%, respectively. Our study validated several known and identified several novel risk factors, including a history of colonic adenomas or caffeine usage. Low-grade dysplasia was a risk factor for progression but various endoscopic characteristics were not, suggesting that screening strategies should focus on histology instead. We identified SSRIs as a new potentially chemoprotective medication.
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Affiliation(s)
| | - Alan H Tieu
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Division of Gastroenterology and Hepatology, Department of Medicine, Eastern Virginia Medical School, Norfolk, VA, United States
| | - Brandon Luber
- Division of Bioinformatics and Biostatistics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Hao Wang
- Division of Bioinformatics and Biostatistics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Stephen J Meltzer
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
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Cotton CC, Wolf WA, Overholt BF, Li N, Lightdale CJ, Wolfsen HC, Pasricha S, Wang KK, Shaheen NJ. Late Recurrence of Barrett's Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial. Gastroenterology 2017; 153:681-688.e2. [PMID: 28579538 PMCID: PMC5581683 DOI: 10.1053/j.gastro.2017.05.044] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 05/15/2017] [Accepted: 05/17/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS The goal of treatment for Barrett's esophagus (BE) with dysplasia is complete eradication of intestinal metaplasia (CEIM). The long-term durability of CEIM has not been well characterized, so the frequency and duration of surveillance are unclear. We report results from a 5-year follow-up analysis of patients with BE and dysplasia treated by radiofrequency ablation (RFA) in the randomized controlled Ablation of Intestinal Metaplasia Containing Dysplasia (AIM) trial. METHODS Participants for the AIM Dysplasia trial (18-80 years old) were recruited from 19 sites in the United States and had endoscopic evidence of non-nodular dysplastic BE ≤8 cm in length. Subjects (n = 127) were randomly assigned (2:1 ratio) to receive either RFA (entire BE segment ablated circumferentially) or a sham endoscopic procedure; patients in the sham group were offered RFA treatment 1 year later, and all patients were followed for 5 years. We collected data on BE recurrence (defined as intestinal metaplasia in the tubular esophagus) and dysplastic BE recurrence among patients who achieved CEIM. We constructed Kaplan-Meier estimates and applied parametric survival analysis to examine proportions of patients without any recurrence and without dysplastic recurrence. RESULTS Of 127 patients in the AIM Dysplasia trial, 119 received RFA and met inclusion criteria. Of those 119, 110 (92%) achieved CEIM. Over 401 person-years of follow-up (mean, 3.6 years per patient; range, 0.2-5.8 years), 35 of 110 (32%) patients had recurrence of BE or dysplasia, and 19 (17%) had dysplasia recurrence. The incidence rate of BE recurrence was 10.8 per 100 person-years overall (95% CI, 7.8-15.0); 8.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI, 4.9-14.0), and 13.5 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 8.8-20.7). The incidence rate of dysplasia recurrence was 5.2 per 100 person-years overall (95% CI 3.3-8.2); 3.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI 1.5-7.2), and 7.3 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 4.2-12.5). Neither BE nor dysplasia recurred at a constant rate. There was a greater probability of recurrence in the first year following CEIM than in the following 4 years combined. CONCLUSIONS In this analysis of prospective cohort data from the AIM Dysplasia trial, we found BE to recur after CEIM by RFA in almost one third of patients with baseline dysplastic disease; most recurrences occurred during the first year after CEIM. However, patients who achieved CEIM and remained BE free at 1 year after RFA had a low risk of BE recurrence. Studies are needed to determine when surveillance can be decreased or discontinued; our study did not identify any BE or dysplasia recurrence after 4 years of surveillance.
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Affiliation(s)
- Cary C Cotton
- From the University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina
| | - W Asher Wolf
- From the University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina
| | | | - Nan Li
- From the University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina
| | - Charles J Lightdale
- Division of Digestive and Liver Diseases, Columbia University, New York, New York
| | | | - Sarina Pasricha
- From the University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina
| | - Kenneth K Wang
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Nicholas J Shaheen
- From the University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina.
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Yamashita DT, Li C, Bethune D, Henteleff H, Ellsmere J. Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma: a Canadian experience. Can J Surg 2017; 60:129-133. [PMID: 28338468 DOI: 10.1503/cjs.013515] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Endoscopic mucosal resection (EMR) is increasingly being used as a first-line treatment for Barrett esophagus (BE) with high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC). We reviewed our experience with endoscopic treatment of BE with HGD and IMC at our institution with respect to eradication rates, complications and long-term recurrence. METHODS We performed a single-centre retrospective review of all patients referred between October 2010 and August 2014 for EMR with dysplastic BE or IMC. We performed EMR using a cap-fitted endoscope, and the procedure was repeated every 3 months until eradication or progression of disease. RESULTS A total of 28 patients were identified: 16 with dysplastic BE (14 HGD, 1 low-grade dysplasia, 1 intermediate dysplasia) and 12 with IMC. Complete eradication of HGD was achieved in 11 of 14 (79%) patients. Three of 12 (25%) patients initially referred with suspected IMC were found to have invasive adenocarcinoma on EMR. Eradication was successful in 8 of 9 (89%) patients with true IMC, with 1 patient progressing to salvage esophagectomy. Complications occurred in 2 of 28 (7%) patients; both had esophageal strictures managed with dilatation. Median duration of follow-up was 371 days. CONCLUSION Our experience supports the safety of EMR as a first-line treatment for patients with BE with dysplasia and IMC in early short-term follow-up.
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Affiliation(s)
- Denise Tami Yamashita
- From the Division of General, Surgery, Dalhousie University, Halifax, NS (Yamashita, Li, Ellsmere); and the Division of Thoracic Surgery, Dalhousie University, Halifax, NS (Bethune, Henteleff)
| | - Chao Li
- From the Division of General, Surgery, Dalhousie University, Halifax, NS (Yamashita, Li, Ellsmere); and the Division of Thoracic Surgery, Dalhousie University, Halifax, NS (Bethune, Henteleff)
| | - Drew Bethune
- From the Division of General, Surgery, Dalhousie University, Halifax, NS (Yamashita, Li, Ellsmere); and the Division of Thoracic Surgery, Dalhousie University, Halifax, NS (Bethune, Henteleff)
| | - Harry Henteleff
- From the Division of General, Surgery, Dalhousie University, Halifax, NS (Yamashita, Li, Ellsmere); and the Division of Thoracic Surgery, Dalhousie University, Halifax, NS (Bethune, Henteleff)
| | - James Ellsmere
- From the Division of General, Surgery, Dalhousie University, Halifax, NS (Yamashita, Li, Ellsmere); and the Division of Thoracic Surgery, Dalhousie University, Halifax, NS (Bethune, Henteleff)
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Lipman G, Haidry RJ. Endoscopic management of Barrett's and early oesophageal neoplasia. Frontline Gastroenterol 2017; 8:138-142. [PMID: 28839898 PMCID: PMC5369449 DOI: 10.1136/flgastro-2016-100763] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Revised: 12/19/2016] [Accepted: 12/26/2016] [Indexed: 02/04/2023] Open
Abstract
Barrett's oesophagus (BO) is the only known precursor to oesophageal adenocarcinoma (OAC). Dysplasia and intramucosal cancer arising in BO can safely be treated with endoscopic eradication therapy (EET) due to the low risk of subsequent lymph node metastasis. Treatment at an early stage is paramount due to the ongoing poor prognosis and outcomes of patients with advanced OAC. The mainstay of treatment is endoscopic resection of visible lesions for accurate staging followed by ablation therapy to all remaining columnar-lined epithelium, most commonly with radiofrequency ablation. Successful eradication of dysplasia can be achieved in >95% of patients with this EET combined approach.
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Affiliation(s)
- G Lipman
- Department of Gastroenterology, University College Hospital NHS Foundation Trust, London, UK
- Division of Surgery & Interventional Science, University College London, London, UK
| | - RJ Haidry
- Department of Gastroenterology, University College Hospital NHS Foundation Trust, London, UK
- Division of Surgery & Interventional Science, University College London, London, UK
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Abstract
This review provides a summary of our current understanding of, and the controversies surrounding, the diagnosis, pathogenesis, histopathology, and molecular biology of Barrett's esophagus (BE) and associated neoplasia. BE is defined as columnar metaplasia of the esophagus. There is worldwide controversy regarding the diagnostic criteria of BE, mainly with regard to the requirement to histologically identify goblet cells in biopsies. Patients with BE are at increased risk for adenocarcinoma, which develops in a metaplasia-dysplasia-carcinoma sequence. Surveillance of patients with BE relies heavily on the presence and grade of dysplasia. However, there are significant pathologic limitations and diagnostic variability in evaluating dysplasia, particularly with regard to the more recently recognized unconventional variants. Identification of non-morphology-based biomarkers may help risk stratification of BE patients, and this is a subject of ongoing research. Because of recent achievements in endoscopic therapy, there has been a major shift in the treatment of BE patients with dysplasia or intramucosal cancer away from esophagectomy and toward endoscopic mucosal resection and ablation. The pathologic issues related to treatment and its complications are also discussed in this review article.
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Abstract
The article by Banerjee and colleagues published in this issue of the journal involving a randomized control prevention trial of ursodeoxycholic acid (UDCA) in Barrett esophagus reported a null outcome despite being well designed and executed. Possible reasons for this null outcome are discussed focusing on use of surrogate endpoints in the trial. The trial is especially topical because it comes at a time when there are calls for a Pre-Cancer Genome Atlas (PCGA) for "understanding the earliest molecular and cellular events associated with cancer initiation…" This commentary discusses current concepts in prevention research including branched evolution that leads to therapeutic resistance. Length bias sampling postulates underdiagnosis is due to rapidly progressing disease that is difficult to detect by screening because it progresses to cancer too rapidly and that overdiagnosis is the result of very slowly or nonprogressing disease that is easy to detect by screening because it persists for a lifetime and the patient dies of unrelated causes. Finally, it also explores study designs, including surrogate endpoints in Barrett esophagus trials, and opportunities and pitfalls for a PCGA in the context of high levels of over and underdiagnosis of Barrett esophagus as well as many other cancers and their precursors. Cancer Prev Res; 9(7); 512-7. ©2016 AACRSee related article by Banerjee, et al., p. 528.
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Affiliation(s)
- Brian J Reid
- Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Departments of Genome Sciences and Medicine, University of Washington, Seattle, Washington.
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Das A, Callenberg KM, Styn MA, Jackson SA. Endoscopic ablation is a cost-effective cancer preventative therapy in patients with Barrett's esophagus who have elevated genomic instability. Endosc Int Open 2016; 4:E549-59. [PMID: 27227114 PMCID: PMC4874803 DOI: 10.1055/s-0042-103415] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 02/08/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The surveillance of patients with nondysplastic Barrett's esophagus (NDBE) has a high cost and is of limited effectiveness in preventing esophageal adenocarcinoma (EAC). Ablation for NDBE remains expensive and controversial. Biomarkers of genomic instability have shown promise in identifying patients with NDBE at high risk for progression to EAC. Here, we evaluate the cost-effectiveness of using such biomarkers to stratify patients with NDBE by risk for EAC and, subsequently, the cost-effectiveness of ablative therapy. METHODS A Markov decision tree was used to evaluate four strategies in a hypothetical cohort of 50-year old patients with NDBE over their lifetime: strategy I, natural history without surveillance; strategy II, surveillance per current guidelines; strategy III, ablation for all patients; strategy IV, risk stratification with use of a biomarker panel to assess genomic instability (i. e., mutational load [ML]). Patients with no ML underwent minimal surveillance, patients with low ML underwent standard surveillance, and patients with high ML underwent ablation. The incremental cost-effectiveness ratio (ICER) and incremental net health benefit (INHB) were assessed. RESULTS Strategy IV provided the best values for quality-adjusted life years (QALYs), ICER, and INHB in comparison with strategies II and III. RESULTS were robust in sensitivity analysis. In a Monte Carlo analysis, the relative risk for the development of cancer in the patients managed with strategy IV was decreased. Critical determinants of strategy IV cost-effectiveness were the complete response rate, cost of ablation, and surveillance interval in patients with no ML. CONCLUSION The use of ML to stratify patients with NDBE by risk was the most cost-effective strategy for preventive EAC treatment. Targeting ablation toward patients with high ML presents an opportunity for a paradigm shift in the management of NDBE.
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Affiliation(s)
- Ananya Das
- Arizona Center for Digestive Health, Gilbert, Arizona, USA,Corresponding author Ananya Das, MDF Arizona Center for Digestive Health2680 South Valvista Drive, Suite #116Gilbert, AZ 85295USA+1-412-224-6110
| | - Keith M. Callenberg
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA,Interpace Diagnostics Corporation (formerly RedPath Integrated Pathology), Pittsburgh, Pennsylvania, USA
| | - Mindi A. Styn
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA,Interpace Diagnostics Corporation (formerly RedPath Integrated Pathology), Pittsburgh, Pennsylvania, USA
| | - Sara A. Jackson
- Interpace Diagnostics Corporation (formerly RedPath Integrated Pathology), Pittsburgh, Pennsylvania, USA
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15
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Abstract
BACKGROUND Patients with Barrett esophagus (BE) are predisposed to developing dysplasia and cancer. Adenocarcinoma, which is associated with BE, is the most common type of esophageal tumor and, typically, it has an aggressive clinical course and a high rate of mortality. METHODS The English-language literature relating to tumor epidemiology, etiology, and the pathogenesis of BE was reviewed and summarized. RESULTS The role of pathologists in the diagnosis and pitfalls associated with grading Barrett dysplasia is addressed. Current molecular testing for Barrett neoplasia, as well as testing methods currently in development, is discussed, focusing on relevant tests for diagnosing tumor types, determining prognosis, and assessing therapeutic response. CONCLUSIONS Grading is essential for developing appropriate treatment plans, follow-up visits, and therapeutic interventions for each patient. Familiarity with current molecular testing methods will help physicians correctly diagnose the disease and select the most appropriate therapy for each of their patients.
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Affiliation(s)
- Sherma Zibadi
- Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL 33612, USA.
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16
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Ortiz-Fernández-Sordo J, Sami S, Mansilla-Vivar R, De Caestecker J, Cole A, Ragunath K. Incidence of metachronous visible lesions in patients referred for radiofrequency ablation (RFA) therapy for early Barrett's neoplasia: a single-centre experience. Frontline Gastroenterol 2016; 7:24-29. [PMID: 26834956 PMCID: PMC4717434 DOI: 10.1136/flgastro-2015-100561] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Revised: 02/05/2015] [Accepted: 02/09/2015] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE Evaluate the incidence of metachronous visible lesions (VLs) in patients referred for radiofrequency ablation (RFA) for early Barrett's neoplasia. DESIGN This study was conducted as part of the service evaluation audit. SETTING Tertiary referral centre. PATIENTS All patients with dysplastic Barrett's oesophagus referred for RFA were included for analysis. White light high-resolution endoscopy (HRE), autofluorescence imaging and narrow band imaging were sequentially performed. Endoscopic mucosal resection (EMR) was performed for all VL. Three to six months after EMR, all patients underwent initial RFA and then repeat RFA procedures at three monthly intervals. INTERVENTIONS All endoscopy reports and final staging by EMR/surgery were evaluated and included for analysis. RESULTS Fifty patients were analysed; median age 73 years, 84% men. 38/50 patients (76%) had a previous EMR due to the presence of VL before referred for ablation; twelve patients had no previous treatment. In total, 151 ablation procedures were performed, median per patient 2.68. Twenty metachronous VL were identified in 14 patients before the first ablation or during the RFA protocol; incidence was 28%. All metachronous lesions were successfully resected by EMR. Upstaging after rescue EMR compared with the initial histology was observed in four patients (28%). CONCLUSIONS In total, 28% of patients enrolled in the RFA programme were diagnosed to have metachronous lesions. This high-incidence rate highlights the importance of a meticulous examination to identify and resect any VL before every ablation session. RFA treatment for early Barrett's neoplasia should be performed in tertiary referral centres with HRE and EMR facilities and expertise.
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Affiliation(s)
- J Ortiz-Fernández-Sordo
- Nottingham Digestive Diseases Centre and NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham , Nottingham , UK
| | - S Sami
- Nottingham Digestive Diseases Centre and NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham , Nottingham , UK
| | - R Mansilla-Vivar
- Nottingham Digestive Diseases Centre and NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham , Nottingham , UK
| | - J De Caestecker
- Digestive Diseases Centre, University Hospitals of Leicester NHS Trust , Leicester , UK
| | - A Cole
- Gastroenterology and Hepatology Department , Derby Hospitals NHS Foundation Trust , Derby , UK
| | - K Ragunath
- Nottingham Digestive Diseases Centre and NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham , Nottingham , UK
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Paulson TG. Studying Cancer Evolution in Barrett’s Esophagus and Esophageal Adenocarcinoma. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 908:213-36. [DOI: 10.1007/978-3-319-41388-4_11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
Beginning in the 1980s, an alarming rise in the incidence of esophageal adenocarcinoma (EA) led to screening of patients with reflux to detect Barrett's esophagus (BE) and surveillance of BE to detect early EA. This strategy, based on linear progression disease models, resulted in selective detection of BE that does not progress to EA over a lifetime (overdiagnosis) and missed BE that rapidly progresses to EA (underdiagnosis). Here we review the historical thought processes that resulted in this undesired outcome and the transformation in our understanding of genetic and evolutionary principles governing neoplastic progression that has come from application of modern genomic technologies to cancers and their precursors. This new synthesis provides improved strategies for prevention and early detection of EA by addressing the environmental and mutational processes that can determine "windows of opportunity" in time to detect rapidly progressing BE and distinguish it from slowly or nonprogressing BE.
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Affiliation(s)
- Brian J. Reid
- Division of Human Biology, FredHutch, Seattle WA,Division of Public Health Sciences, FredHutch, Seattle WA,Department of Genome Sciences, University of Washington,Department of Medicine, University of Washington,Corresponding author Brian J. Reid, M.D., Ph.D. 1100 Fairview Ave N., C1-157 P.O. Box 19024 Seattle, WA 98109-1024 206-667-4073 (phone) 206-667-6192 (FAX)
| | | | - Xiaohong Li
- Division of Human Biology, FredHutch, Seattle WA
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19
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Stachler MD, Taylor-Weiner A, Peng S, McKenna A, Agoston AT, Odze RD, Davison JM, Nason KS, Loda M, Leshchiner I, Stewart C, Stojanov P, Seepo S, Lawrence MS, Ferrer-Torres D, Lin J, Chang AC, Gabriel SB, Lander ES, Beer DG, Getz G, Carter SL, Bass AJ. Paired exome analysis of Barrett's esophagus and adenocarcinoma. Nat Genet 2015; 47:1047-55. [PMID: 26192918 PMCID: PMC4552571 DOI: 10.1038/ng.3343] [Citation(s) in RCA: 268] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 05/29/2015] [Indexed: 12/14/2022]
Abstract
Barrett's esophagus is thought to progress to esophageal adenocarcinoma (EAC) through a stepwise progression with loss of CDKN2A followed by TP53 inactivation and aneuploidy. Here we present whole-exome sequencing from 25 pairs of EAC and Barrett's esophagus and from 5 patients whose Barrett's esophagus and tumor were extensively sampled. Our analysis showed that oncogene amplification typically occurred as a late event and that TP53 mutations often occurred early in Barrett's esophagus progression, including in non-dysplastic epithelium. Reanalysis of additional EAC exome data showed that the majority (62.5%) of EACs emerged following genome doubling and that tumors with genomic doubling had different patterns of genomic alterations, with more frequent oncogenic amplification and less frequent inactivation of tumor suppressors, including CDKN2A. These data suggest that many EACs emerge not through the gradual accumulation of tumor-suppressor alterations but rather through a more direct path whereby a TP53-mutant cell undergoes genome doubling, followed by the acquisition of oncogenic amplifications.
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Affiliation(s)
- Matthew D Stachler
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | | | - Shouyong Peng
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | | | - Agoston T Agoston
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Robert D Odze
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Jon M Davison
- University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Katie S Nason
- University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Massimo Loda
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | | | - Chip Stewart
- Eli and Edythe L. Broad Institute, Cambridge, Massachusetts, USA
| | - Petar Stojanov
- Eli and Edythe L. Broad Institute, Cambridge, Massachusetts, USA
| | - Sara Seepo
- Eli and Edythe L. Broad Institute, Cambridge, Massachusetts, USA
| | | | | | - Jules Lin
- Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Andrew C Chang
- Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Stacey B Gabriel
- Eli and Edythe L. Broad Institute, Cambridge, Massachusetts, USA
| | - Eric S Lander
- Eli and Edythe L. Broad Institute, Cambridge, Massachusetts, USA
- Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - David G Beer
- Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Gad Getz
- Eli and Edythe L. Broad Institute, Cambridge, Massachusetts, USA
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Scott L Carter
- Eli and Edythe L. Broad Institute, Cambridge, Massachusetts, USA
- Joint Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Broad Institute of Harvard and MIT, Harvard Medical School, Boston, Massachusetts, USA
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
| | - Adam J Bass
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Eli and Edythe L. Broad Institute, Cambridge, Massachusetts, USA
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20
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Eluri S, Brugge WR, Daglilar ES, Jackson SA, Styn MA, Callenberg KM, Welch DC, Barr TM, Duits LC, Bergman JJ, Shaheen NJ. The Presence of Genetic Mutations at Key Loci Predicts Progression to Esophageal Adenocarcinoma in Barrett's Esophagus. Am J Gastroenterol 2015; 110:828-34. [PMID: 26010308 PMCID: PMC4471888 DOI: 10.1038/ajg.2015.152] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Revised: 03/02/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Risk stratification in Barrett's esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS In this case-control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC. Cases had nondysplastic BE or low-grade dysplasia (LGD) at baseline and developed HGD/EAC ≥1 year later. Controls were matched 2:1, had nondysplastic BE or LGD, and no progression at follow-up. Formalin-fixed, paraffin-embedded tissue was microdissected for the epithelium. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed. ML was calculated from derangements in 10 genomic loci. High-clonality LOH mutations were assigned a value of 1, low-clonality mutations were assigned a value of 0.5, and MSI 0.75 at the first loci, and 0.5 for additional loci. These values were summed to the ML. Receiver operator characteristic (ROC) curves were created. RESULTS There were 69 patients (46 controls and 23 cases). Groups were similar in age, follow-up time, baseline histology, and the number of microdissected targets. Mean ML in pre-progression biopsies was higher in cases (2.21) than in controls (0.42; P<0.0001). Sensitivity was 100% at ML ≥0.5 and specificity was 96% at ML ≥1.5. Accuracy was highest at 89.9% for ML ≥1. ROC curves for ML ≥1 demonstrated an area under the curve (AUC) of 0.95. CONCLUSIONS ML in pre-progression BE tissue predicts progression to HGD or EAC. Although further validation is necessary, ML may have utility as a biomarker in endoscopic surveillance of BE.
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Affiliation(s)
- Swathi Eluri
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA
| | - William R Brugge
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Ebubekir S Daglilar
- Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Sara A Jackson
- Interpace Diagnostics Corporation, Pittsburgh, Pennsylvania, USA
| | - Mindi A Styn
- Interpace Diagnostics Corporation, Pittsburgh, Pennsylvania, USA
| | | | | | - Todd M Barr
- Department of Pathology and Laboratory Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA
| | - Lucas C Duits
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Jacques J Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Nicholas J Shaheen
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA,Medicine and Epidemiology, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, 130 Mason Farm Road CB# 7080, Chapel Hill, North Carolina 27599, USA. E-mail:
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21
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Endoscopic Mucosal Resection and Endoscopic Submucosal Dissection for Endoscopic Therapy of Barrett's Esophagus-related Neoplasia. Gastroenterol Clin North Am 2015; 44:317-35. [PMID: 26021197 DOI: 10.1016/j.gtc.2015.02.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
A major paradigm shift has occurred in the management of dysplastic Barrett's esophagus (BE) and early esophageal carcinoma. Endoscopic therapy has now emerged as the standard of care for this disease entity. Endoscopic resection techniques like endoscopic mucosal resection and endoscopic submucosal dissection combined with ablation techniques help achieve long-term curative success comparable with surgical outcomes, in this subgroup of patients. This article is an in-depth review of these endoscopic resection techniques, highlighting their role and value in the overall management of BE-related dysplasia and neoplasia.
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22
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Uno G, Ishimura N, Tada Y, Tamagawa Y, Yuki T, Matsushita T, Ishihara S, Amano Y, Maruyama R, Kinoshita Y. Simplified classification of capillary pattern in Barrett esophagus using magnifying endoscopy with narrow band imaging: implications for malignant potential and interobserver agreement. Medicine (Baltimore) 2015; 94:e405. [PMID: 25621687 PMCID: PMC4602634 DOI: 10.1097/md.0000000000000405] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The classification of Barrett esophagus (BE) using magnifying endoscopy with narrow band imaging (ME-NBI) is not widely used in clinical settings because of its complexity. To establish a new simplified available classification using ME-NBI.We conducted a cross-sectional study in a single-referral center. One hundred eight consecutive patients with BE using ME-NBI and crystal violet (CV) chromoendoscopy, and histological findings were enrolled. BE areas observed by ME-NBI were classified as type I or II on the basis of capillary pattern (CP), and as closed or open type on the basis of a mucosal pit pattern using CV chromoendoscopy; then, biopsy samples were obtained. We evaluated the relation between CP and pit pattern, expression of the factors with malignant potential, percentage of microvascular density, and interobserver agreement.One hundred thirty lesions from 91 patients were analyzed. Type II CP had more open type pit pattern areas and significantly greater microvascular density than type I. The presence of dysplasia, specialized intestinal metaplasia, expressions of COX-2, CDX2, and CD34, and PCNA index were significantly higher in type II, whereas the multivariate analysis showed that type II was the best predictor for the presence of dysplasia (OR 11.14), CD34 expression (OR 3.60), and PCNA (OR 3.29). Interobserver agreement for this classification was substantial (κ = 0.66).A simplified CP classification based on observation with ME-NBI is presented. Our results indicate that the classification may be useful for surveillance of BE with high malignant potential.
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Affiliation(s)
- Goichi Uno
- From the Department of Gastroenterology and Hepatology (GU, NI, Y. Tada, Y. Tamagawa, SI, YK), Shimane University School of Medicine; Division of Endoscopy (TY), Shimane University Hospital; Department of Pathology (TM, RM), Shimane University School of Medicine, Izumo; Division of Endoscopy (YA), Kaken Hospital, International University of Health and Welfare, Ichikawa, Japan; and Department of Internal Medicine (Y. Tamagawa), University of Texas Southwestern Medical Center, Dallas, TX
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23
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Abdalla M, Dhanekula R, Greenspan M, Mobarhan S, Patil A, Jakate S, Giusto D, Silva R, Li H, Melson J. Dysplasia detection rate of confirmatory EGD in nondysplastic Barrett's esophagus. Dis Esophagus 2014; 27:505-10. [PMID: 23020509 DOI: 10.1111/j.1442-2050.2012.01431.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Current guidelines for endoscopic surveillance of Barrett's esophagus (BE) recommend that patients with newly diagnosed BE undergo confirmatory esophagogastroduodenoscopy (EGD) to exclude the presence of dysplasia. The extent to which confirmatory endoscopy alters management and detects missed dysplasia in newly diagnosed BE has not been reported. The frequency with which confirmatory endoscopy changed surveillance management in patients with newly diagnosed BE was assessed. A two center cohort analysis was conducted on patients newly diagnosed with BE. The rate of dysplasia on confirmatory endoscopy for patients who had nondysplastic BE was obtained. Demographic and endoscopic variables were assessed for association with dysplasia detection using Firth logistic regression model. Out of the 146 patients newly diagnosed with BE and initially determined to be without dysplasia, 12 had dysplasia on the confirmatory second EGD (8.2%). Eleven of 12 cases with dysplasia on confirmatory endoscopy had long-segment BE (LSBE). Among all the LSBE cases in our cohort, 11 had newly diagnosed dysplasia on confirmatory EGD, 29.7% (11/37). The average number of biopsies obtained from the 11 LSBE cases with dysplasia was comparable with the rest of the LSBE cases without dysplasia (6.73 and 5.42, respectively, P-value 0.205). The rate of dysplasia detection in short-segment BE (SSBE) was much lower, 0.95% (1 out of 105). There were no cases of high-grade dysplasia (HGD) or cancer detected in any SSBE case. HGD was detected on confirmatory EGD in two cases, both were LSBE. Segment length was the only statistically significant factor to predict the presence of dysplasia on confirmatory endoscopy (odds ratio 9.158, P. 0.008). Confirmatory EGD in newly diagnosed LSBE had significant rate of dysplasia detection (29.7%) in this cohort. Among patients with SSBE, there was a low rate of dysplasia detection with confirmatory EGD, less than 1% of cases. No additional cases of HGD or esophageal carcinoma in SSBE cases were detected. This suggests that the yield of confirmatory EGD is greater in patients with LSBE.
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Affiliation(s)
- M Abdalla
- Advocate Christ Medical Center, Oak Lawn, USA
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24
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Khara HS, Jackson SA, Nair S, Deftereos G, Patel S, Silverman JF, Ellsworth E, Sumner C, Corcoran B, Smith DM, Finkelstein S, Gross SA. Assessment of mutational load in biopsy tissue provides additional information about genomic instability to histological classifications of Barrett's esophagus. J Gastrointest Cancer 2014; 45:137-145. [PMID: 24402860 PMCID: PMC4024388 DOI: 10.1007/s12029-013-9570-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE Progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is associated with accumulated genomic instability. Current risk stratification of BE for EAC relies on histological classification and grade of dysplasia. However, histology alone cannot assess the risk of patients with inconsistent or non-dysplastic BE histology. We, therefore, examined the presence and extent of genomic instability in advanced and less advanced BE histology using mutational load (ML). METHODS ML summarized the presence and clonality of loss of heterozygosity (LOH) mutations and the emergence of new alleles, manifested as microsatellite instability (MSI) mutations, in ten genomic loci around tumor suppressor genes associated with EAC. The ML of 877 microdissected targets from BE biopsies was correlated to their histology. Histological targets were categorized into three levels: no ML, low ML, and high ML. RESULTS Increasing ML correlated with increasingly severe histology. By contrast, proportions of targets that lacked mutations decreased with increasingly severe histology. A portion of targets with non-dysplastic and low-grade histology shared a similar ML as those with higher risk and EAC disease. The addition of MSI characterization to ML helped to differentiate the ML between advanced and less advanced histology. CONCLUSIONS Given that EAC is associated with accumulated genomic instability, high ML in less severe histology may identify BE disease at greater risk of progression to EAC. ML may help to better manage BE in early histological stages and when histology alone provides insufficient information.
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Affiliation(s)
| | | | | | - Georgios Deftereos
- Allegheny General Hospital, West Penn Allegheny Health System, Pittsburgh, PA USA
| | - Shweta Patel
- Allegheny General Hospital, West Penn Allegheny Health System, Pittsburgh, PA USA
| | - Jan F. Silverman
- Allegheny General Hospital, West Penn Allegheny Health System, Pittsburgh, PA USA
| | | | | | | | | | - Sydney Finkelstein
- RedPath Integrated Pathology, Pittsburgh, PA USA
- RedPath Integrated Pathology, Inc., 2515 Liberty Avenue, Pittsburgh, PA 15222 USA
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25
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Qumseya B, David W, McCrum M, Dong Y, Raimondo M, Woodward TA, Wallace MB, Wolfsen HC. Gender differences in remission of esophageal intestinal metaplasia after radiofrequency ablation. Am J Gastroenterol 2014; 109:369-74. [PMID: 24394753 DOI: 10.1038/ajg.2013.454] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 11/19/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Few studies have assessed the effect of gender on remission rates after radiofrequency ablation (RFA) of Barrett's esophagus (BE). We aim to assess the effect of gender on the time to achieve complete remission of intestinal metaplasia (CRIM) among patients with BE, who underwent RFA. METHODS This was a retrospective, observational study using a large RFA database in a tertiary referral center. The primary outcome was time to CRIM compared between males and females. Covariates included age, race, smoking history, use of endoscopic mucosal resection (EMR), histology before RFA, and the number of RFA sessions. Time to CRIM (in months) was calculated using the Kaplan-Meier method and compared using the log-rank test. Multivariable Cox-proportional hazard models were used to assess for any association between time to CRIM and gender. RESULTS Two hundred and fifty-seven patients, 11% (n=23) female, underwent RFA for BE between May 2005 and June 2012. Males and females were similar in mean age, race, smoking history, median BE length, history of EMR, and baseline histology. Median time to CRIM for females was longer than males (24 months (95% confidence interval (CI): 10.3-60.2) vs. 11.7 months (95% CI: 10-15), P=0.03). Using Cox-regression analysis, controlling for age, use of EMR, BE segment length, and the number of RFA sessions, female gender was associated with a 55% decrease in the rate of CRIM compared with that in males (hazard ratio=0.45 (95% CI: 0.25-0.82), P=0.009). CONCLUSIONS Females take longer time to achieve CRIM when treated with RFA when compared with males of similar age and BE length.
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Affiliation(s)
- Bashar Qumseya
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Waseem David
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Marta McCrum
- Harvard School of Public Health and the Center for Surgery and Public Health (Brigham and Women's Hospital), Boston, Massachusetts, USA
| | - Yan Dong
- Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts,USA
| | - Massimo Raimondo
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Timothy A Woodward
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Michael B Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Herbert C Wolfsen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
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Li X, Galipeau PC, Paulson TG, Sanchez CA, Arnaudo J, Liu K, Sather CL, Kostadinov RL, Odze RD, Kuhner MK, Maley CC, Self SG, Vaughan TL, Blount PL, Reid BJ. Temporal and spatial evolution of somatic chromosomal alterations: a case-cohort study of Barrett's esophagus. Cancer Prev Res (Phila) 2013; 7:114-27. [PMID: 24253313 DOI: 10.1158/1940-6207.capr-13-0289] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
All cancers are believed to arise by dynamic, stochastic somatic genomic evolution with genome instability, generation of diversity, and selection of genomic alterations that underlie multistage progression to cancer. Advanced esophageal adenocarcinomas have high levels of somatic copy number alterations. Barrett's esophagus is a risk factor for developing esophageal adenocarcinoma, and somatic chromosomal alterations (SCA) are known to occur in Barrett's esophagus. The vast majority (∼95%) of individuals with Barrett's esophagus do not progress to esophageal adenocarcinoma during their lifetimes, but a small subset develop esophageal adenocarcinoma, many of which arise rapidly even in carefully monitored patients without visible endoscopic abnormalities at the index endoscopy. Using a well-designed, longitudinal case-cohort study, we characterized SCA as assessed by single-nucleotide polymorphism arrays over space and time in 79 "progressors" with Barrett's esophagus as they approach the diagnosis of cancer and 169 "nonprogressors" with Barrett's esophagus who did not progress to esophageal adenocarcinoma over more than 20,425 person-months of follow-up. The genomes of nonprogressors typically had small localized deletions involving fragile sites and 9p loss/copy neutral LOH that generate little genetic diversity and remained relatively stable over prolonged follow-up. As progressors approach the diagnosis of cancer, their genomes developed chromosome instability with initial gains and losses, genomic diversity, and selection of SCAs followed by catastrophic genome doublings. Our results support a model of differential disease dynamics in which nonprogressor genomes largely remain stable over prolonged periods, whereas progressor genomes evolve significantly increased SCA and diversity within four years of esophageal adenocarcinoma diagnosis, suggesting a window of opportunity for early detection.
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Affiliation(s)
- Xiaohong Li
- Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024.
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Kurian AA, Swanström LL. Radiofrequency ablation in the management of Barrett's esophagus: present role and future perspective. Expert Rev Med Devices 2013; 10:509-17. [PMID: 23895078 DOI: 10.1586/17434440.2013.811863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Esophageal adenocarcinoma is the most rapidly increasing gastrointestinal cancer. Barrett's esophagus has been identified as a precancerous condition and major risk factor for esophageal cancer. Radiofrequency ablation has been shown to be a highly efficient in promoting remission of intestinal metaplasia. This technology has seen widespread clinical use since 2005. Radiofrequency ablation is common with all other ablative techniques; the concern that sound oncological principles are not being adhered to, that is, appropriate pathological staging, followed by appropriate definitive therapy. Endoscopic mucosal excision techniques are technically demanding; however, they are more attractive from an oncological perspective. Future research endeavors focusing on facilitation of large population screening, the identification of high risk phenotypes, endoscopic mucosal resection techniques will combat the esophageal adenocarcinoma epidemic.
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Affiliation(s)
- Ashwin A Kurian
- Providence Portland Cancer Center, 4805 NE Glisan Street, 6N60, Providence Cancer Center, Portland, OR 97213, USA
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Abstract
PURPOSE OF REVIEW There is a clinical need for biomarkers that can improve diagnostic accuracy and risk stratification of esophageal lesions. Here we review the current literature and highlight the most important, recent advancements in biomarkers as a supplement to histopathology for management of patients with Barrett's esophagus. RECENT FINDINGS A prospective cohort study in Northern Ireland shows that a small panel of biomarkers (low-grade dysplasia, abnormal DNA ploidy and Aspergillus oryzae lectin) can identify patients at high risk for developing high-grade dysplasia or cancer. Recent research in molecular imaging shows promise for molecular probes in endoscopy, using fluorescently labeled peptides or lectins to identify dysplastic areas of Barrett's epithelium. Based on the current literature, p53 immunostaining is starting to be adopted by some centers as an adjunct to histopathology diagnosis for dysplasia. SUMMARY The evidence base for the use of biomarkers is increasing and it appears that panels may have superior diagnostic and predictive power over single, candidate biomarkers. Prior to clinical implementation, biomarkers must overcome significant barriers including the need for large-scale prospective validation trials, and the limited ability of clinical laboratories to process and analyze complex biomarker assays.
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Koike T, Nakagawa K, Iijima K, Shimosegawa T. Endoscopic resection (endoscopic submucosal dissection/endoscopic mucosal resection) for superficial Barrett's esophageal cancer. Dig Endosc 2013; 25 Suppl 1:20-8. [PMID: 23480400 DOI: 10.1111/den.12047] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2012] [Accepted: 01/08/2013] [Indexed: 12/16/2022]
Abstract
Recently developed endoscopic resection (endoscopic submucosal dissection [ESD]/ endoscopic mucosal resection) has dramatically changed the therapeutic approach for Barrett's esophageal cancer. The rationale for endoscopic resection is that lesions confined to the mucosal layer have negligible risk for developing lymph node metastasis and can be successfully eradicated by endoscopic treatment as a curative treatment with minimal invasiveness. According to some reports that analyzed the rate of lymph-node involvement relative to the depth of mucosal or submucosal tumor infiltration, endoscopic resection is clearly indicated for intramucosal carcinoma and might be extended to lesions with invasion into the submucosa (<200 μm, sm1) because of the low risk for lymph node metastasis. Most Japanese experts recommend ESD for Barrett's esophageal cancer after accurate diagnosis of the margin of cancer using narrow band imaging with magnifying endoscopy because of its high curative rate. However, few studies have evaluated the long-term outcomes of endoscopic resection for Barrett's esophageal cancer in Japan. Further investigations should be conducted to establish endoscopic resection for Barrett's esophageal cancer.
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Affiliation(s)
- Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
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Ellsworth E, Jackson SA, Thakkar SJ, Smith DM, Finkelstein S. Correlation of the presence and extent of loss of heterozygosity mutations with histological classifications of Barrett's esophagus. BMC Gastroenterol 2012; 12:181. [PMID: 23270334 PMCID: PMC3553041 DOI: 10.1186/1471-230x-12-181] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Accepted: 12/18/2012] [Indexed: 02/06/2023] Open
Abstract
Background Recent advances in the management of Barrett’s Esophagus (BE) have placed greater emphasis on accurate diagnosis of BE as well as better prediction of risk for progression to esophageal adenocarcinoma (EAC). Histological evaluation of BE is particularly challenging with significant inter-observer variability. We explored the presence and extent of genomic instability in BE biopsy specimens as a means to add supplementary information to the histological classification and clinical decision-making related to early disease. Methods We reviewed histology slides from 271 patients known to have BE. Using histological features as a guide, we microdissected target cell populations with various histological classifications of BE (intestinal metaplasia, “indefinite for dysplasia”, low grade dysplasia, or high grade dysplasia). DNA was extracted from microdissected targets and analyzed for loss of heterozygosity (LOH) using a panel of 16 LOH mutational markers associated with tumor suppressor genes at chromosomal loci 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, 22q. The presence or absence of mutations and the clonality of each mutation were determined for each marker. Results The presence and clonal expansion of LOH mutations was formulated into mutational load (ML) for each microdissected target analyzed. ML correlated with the histological classification of microdissected targets, with increasingly severe histology having higher ML. Three levels of mutation load (no ML, low ML, and high ML) were defined based on the population of microdissected targets histologically classified as intestinal metaplasia. All microdissected targets with dysplasia had mutations, with a high ML consistently present in high grade dysplasia targets. Microdissected targets histologically classified as intestinal metaplasia or “indefinite for dysplasia” spanned a range of no, low, and high ML. Conclusions The results of this study reinforce the association of genomic instability with disease progression in BE. The presence and extent (clonality) of genomic instability, as assessed by mutational load, may assist histology in defining early stages of BE that are potentially at greater risk for disease progression. Assessment of mutational load using our panel of LOH mutational markers may be a useful adjunct to microscopic inspection of biopsy specimens, and thereby, improve patient management.
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Affiliation(s)
- Eric Ellsworth
- RedPath Integrated Pathology, Inc, 2515 Liberty Ave, Pittsburgh, PA 15222, USA
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Palma GDD. Management strategies of Barrett's esophagus. World J Gastroenterol 2012; 18:6216-6225. [PMID: 23180941 PMCID: PMC3501769 DOI: 10.3748/wjg.v18.i43.6216] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2012] [Revised: 07/02/2012] [Accepted: 07/09/2012] [Indexed: 02/06/2023] Open
Abstract
Barrett's esophagus is a condition resulting from chronic gastro-esophageal reflux disease with a documented risk of esophageal adenocarcinoma. Current strategies for improved survival in patients with Barrett's adenocarcinoma focus on detection of dysplasia. This can be obtained by screening programs in high-risk cohorts of patients and/or endoscopic biopsy surveillance of patients with known Barrett's esophagus (BE). Several therapies have been developed in attempts to reverse BE and reduce cancer risk. Aggressive medical management of acid reflux, lifestyle modifications, antireflux surgery, and endoscopic treatments have been recommended for many patients with BE. Whether these interventions are cost-effective or reduce mortality from esophageal cancer remains controversial. Current treatment requires combinations of endoscopic mucosal resection techniques to eliminate visible lesions followed by ablation of residual metaplastic tissue. Esophagectomy is currently indicated in multifocal high-grade neoplasia or mucosal Barrett's carcinoma which cannot be managed by endoscopic approach.
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Rajendra S, Sharma P. Management of Barrett's oesophagus and intramucosal oesophageal cancer: a review of recent development. Therap Adv Gastroenterol 2012; 5:285-99. [PMID: 22973415 PMCID: PMC3437535 DOI: 10.1177/1756283x12446668] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Barrett's oesophagus is the most important and recognizable precursor lesion for oesophageal adenocarcinoma, which is the one of the fastest growing cancers in the Western World. The incidence of oesophageal adenocarcinoma has increased 600% in the United States between 1975 and 2001 and is thought to represent a real increase in burden rather than a result of histologic or anatomical misclassification or overdiagnosis. Thus, the cancer risk in Barrett's oesophagus has to be managed and involves prevention (surveillance endoscopy), treating underlying gastroesophageal reflux disease (medically and or surgically) and endoscopic therapy to remove diseased epithelium in appropriate patient subgroups. In the last decade, new developments in imaging and molecular markers as well as an armamentarium of novel and effective endoscopic eradication therapy has become available to the endoscopist to combat this exponential rise in oesophageal adenocarcinoma. Paradoxically, the cancer risk in Barrett's oesophagus gets progressively downgraded which raises fundamental questions about our understanding of the known and unknown risk factors and molecular aberrations that are involved in the Barrett's metaplasia-dysplasia-carcinoma sequence. Future research has to be directed at these areas to fine tune our screening and surveillance programs to identify more accurately the high-risk group of progressors to oesophageal adenocarcinoma who would benefit most from endoscopic therapy.
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Affiliation(s)
- Shanmugarajah Rajendra
- Department of Gastroenterology & Hepatology, Bankstown-Lidcombe Hospital and South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Prateek Sharma
- Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center and University of Kansas School of Medicine, Kansas City, MO, USA
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Bennett C, Vakil N, Bergman J, Harrison R, Odze R, Vieth M, Sanders S, Gay L, Pech O, Longcroft-Wheaton G, Romero Y, Inadomi J, Tack J, Corley DA, Manner H, Green S, Al Dulaimi D, Ali H, Allum B, Anderson M, Curtis H, Falk G, Fennerty MB, Fullarton G, Krishnadath K, Meltzer SJ, Armstrong D, Ganz R, Cengia G, Going JJ, Goldblum J, Gordon C, Grabsch H, Haigh C, Hongo M, Johnston D, Forbes-Young R, Kay E, Kaye P, Lerut T, Lovat LB, Lundell L, Mairs P, Shimoda T, Spechler S, Sontag S, Malfertheiner P, Murray I, Nanji M, Poller D, Ragunath K, Regula J, Cestari R, Shepherd N, Singh R, Stein HJ, Talley NJ, Galmiche JP, Tham TCK, Watson P, Yerian L, Rugge M, Rice TW, Hart J, Gittens S, Hewin D, Hochberger J, Kahrilas P, Preston S, Sampliner R, Sharma P, Stuart R, Wang K, Waxman I, Abley C, Loft D, Penman I, Shaheen NJ, Chak A, Davies G, Dunn L, Falck-Ytter Y, Decaestecker J, Bhandari P, Ell C, Griffin SM, Attwood S, Barr H, Allen J, Ferguson MK, Moayyedi P, Jankowski JAZ. Consensus statements for management of Barrett's dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process. Gastroenterology 2012; 143:336-346. [PMID: 22537613 PMCID: PMC5538857 DOI: 10.1053/j.gastro.2012.04.032] [Citation(s) in RCA: 284] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2011] [Revised: 03/26/2012] [Accepted: 04/06/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.
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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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Barrett's Esophagus: Emerging Knowledge and Management Strategies. PATHOLOGY RESEARCH INTERNATIONAL 2012; 2012:814146. [PMID: 22701199 PMCID: PMC3369502 DOI: 10.1155/2012/814146] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2011] [Revised: 03/08/2012] [Accepted: 03/26/2012] [Indexed: 12/14/2022]
Abstract
The incidence of esophageal adenocarcinoma (EAC) has increased exponentially in the last 3 decades. Barrett's esophagus (BE) is the only known precursor of EAC. Patients with BE have a greater than 40 folds higher risk of EAC compared with the general population. Recent years have witnessed a revolution in the clinical and molecular research related to BE. However, several aspects of this condition remain controversial. Data regarding the true prevalence of BE have varied widely. Recent studies have suggested a lower incidence of EAC in nondysplastic BE (NDBE) than previously reported. There is paucity of prospective data showing a survival benefit of screening or surveillance for BE. Furthermore, the ever-increasing emphasis on healthcare cost containment has called for reexamination of the screening and surveillance strategies for BE. There is a need for identification of reliable clinical predictors or molecular biomarkers to risk-stratify patients who might benefit the most from screening or surveillance for BE. Finally, new therapies have emerged for the management of dysplastic BE. In this paper, we highlight the key areas of controversy and uncertainty surrounding BE. The paper discusses, in detail, the current literature about the molecular pathogenesis, biomarkers, histopathological diagnosis, and management strategies for BE.
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Williamson JML, Almond LM, Shepherd NA, Barr H. Current management of Barrett's oesophagus. Br J Hosp Med (Lond) 2012; 73:271-7. [DOI: 10.12968/hmed.2012.73.5.271] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- JML Williamson
- Department of Surgery, Bristol Royal Infirmary, Bristol BS2 8HW
| | - LM Almond
- Department of Oesophagogastric Surgery, Gloucestershire Royal Hospital, Gloucester
| | - NA Shepherd
- Histopathology, Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, Gloucestershire
| | - H Barr
- Surgery in the Department of Oesophagogastric Surgery, Gloucestershire Royal Hospital, Gloucester
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Surveillance and follow-up strategies in patients with high-grade dysplasia in Barrett's esophagus: a Dutch population-based study. Am J Gastroenterol 2012; 107:534-42. [PMID: 22270082 DOI: 10.1038/ajg.2011.459] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES In patients with high-grade dysplasia (HGD) in Barrett's esophagus (BE), it is incompletely known which factors are associated with developing esophageal adenocarcinoma (EAC). We analyzed prior biopsy and follow-up strategies in a large nationwide population-based cohort of patients with HGD in BE, and identified predictors of EAC progression. METHODS Prior biopsy records and follow-up evaluations were studied in patients with HGD in BE diagnosed between 1999 and 2008, using PALGA, a nationwide network and registry of histopathology and cytopathology in the Netherlands. Multivariate Cox proportional hazards regression analysis was performed to identify predictors for prevalent (≤ 6 months) and incident (> 6 months) EAC. RESULTS In total, 827 patients with HGD in BE were included. Follow-up data after HGD diagnosis were available in 699 (85%) patients. In 249 (36%) of these patients, an EAC was detected (14.1 EACs per 100 person-years). The risk of prevalent EAC (n=177) was lower with previous surveillance (hazards ratio 0.7; 95% confidence interval 0.5-0.9), unifocal HGD (0.3;0.2-0.6), diagnosis in a university hospital (0.5;0.3-0.9), endoscopic resection (0.5;0.3-0.7), or ablation (0.0;0.0-0.3); and higher when patients were 65-75 years (1.5;1.04-2.04). After exclusion of prevalent EACs, the progression rate was 4.2 EACs per 100 person-years. The risk of progression to incident EAC (n = 72) was lower with previous surveillance (0.6;0.3-0.9) and ablation (0.2;0.0-0.8), and higher when > 75 years (3.8;2.0-7.2) or with an interval > 6 months between HGD diagnosis and first follow-up (e.g., 7-12 months 2.9;1.3-6.3). CONCLUSIONS In this cohort of patients with HGD in BE, the EAC detection rate was 14.1 per 100 person-years and 4.2 per 100 person-years after excluding prevalent cases. The risk of both prevalent and incident EAC was reduced with previous surveillance and endoscopic treatment, while it was increased with older age.
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Varghese S, Lao-Sirieix P, Fitzgerald RC. Identification and clinical implementation of biomarkers for Barrett's esophagus. Gastroenterology 2012; 142:435-441.e2. [PMID: 22266150 DOI: 10.1053/j.gastro.2012.01.013] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
- Sibu Varghese
- MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Cambridge, UK
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Rice TW, Goldblum JR. Management of Barrett esophagus with high-grade dysplasia. Thorac Surg Clin 2011; 22:101-7, vii. [PMID: 22108694 DOI: 10.1016/j.thorsurg.2011.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
High-grade dysplasia in Barrett esophagus is a marker for future development of cancer and for the existence of synchronous cancer. A significant problem in management is intraobserver and interobserver variation in the diagnosis of high-grade dysplasia in Barrett esophagus, the natural history of which is poorly understood; thus, treatment decisions are problematic. The ability to preserve the esophagus with endoscopic mucosal ablation or resection and reduce morbidity of treatment has made endoscopic treatment the mainstay of therapy. Esophagectomy is reserved for treatment failures and for high-grade dysplasia not amenable to less aggressive therapies. This article outlines the data supporting current management strategies.
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Affiliation(s)
- Thomas W Rice
- Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, 9500 Euclid Avenue/Desk J4-1, Cleveland, OH 44195, USA.
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41
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Hoppo T, Rachit SD, Jobe BA. Esophageal Preservation in Esophageal High-Grade Dysplasia and Intramucosal Adenocarcinoma. Thorac Surg Clin 2011; 21:527-40. [DOI: 10.1016/j.thorsurg.2011.08.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Lekakos L, Karidis NP, Dimitroulis D, Tsigris C, Kouraklis G, Nikiteas N. Barrett's esophagus with high-grade dysplasia: focus on current treatment options. World J Gastroenterol 2011; 17:4174-4183. [PMID: 22072848 PMCID: PMC3208361 DOI: 10.3748/wjg.v17.i37.4174] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2010] [Revised: 04/21/2011] [Accepted: 04/28/2011] [Indexed: 02/06/2023] Open
Abstract
High-grade dysplasia (HGD) in Barrett's esophagus (BE) is the critical step before invasive esophageal adenocarcinoma. Although its natural history remains unclear, an aggressive therapeutic approach is usually indicated. Esophagectomy represents the only treatment able to reliably eradicate the neoplastic epithelium. In healthy patients with reasonable life expectancy, vagal-sparing esophagectomy, with associated low mortality and low early and late postoperative morbidity, is considered the treatment of choice for BE with HGD. Patients unfit for surgery should be managed in a less aggressive manner, using endoscopic ablation or endoscopic mucosal resection of the entire BE segment, followed by lifelong surveillance. Patients eligible for surgery who present with a long BE segment, multifocal dysplastic lesions, severe reflux symptoms, a large fixed hiatal hernia or dysphagia comprise a challenging group with regard to the appropriate treatment, either surgical or endoscopic.
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Abstract
The importance of Barrett's esophagus (BE) lies in its potential to give rise to esophageal adenocarcinoma (EAC), postulated to be through a series of progressive degrees of dysplasia; from intestinal metaplasia to low-grade dysplasia, high-grade dysplasia, and subsequently, to cancer. The management strategies for the detection and treatment of dysplasia and early esophageal cancer on a background of BE have changed significantly in the last few decades, with the emergence of newer and less invasive non-operative alternatives. This review aims to outline BE and its relation to EAC, the rationale and cost-effectiveness of both screening and surveillance programs, methods of diagnosing and identifying dysplasia and early cancer in Barrett's, and approaches to individualizing their endoscopic and surgical management based on best-available staging techniques.
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Affiliation(s)
- Alyisha Tan
- School of Medicine, the University of Melbourne, Melbourne, Victoria, Australia
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Ortiz-Fernández-Sordo J, Parra-Blanco A, García-Varona A, Rodríguez-Peláez M, Madrigal-Hoyos E, Waxman I, Rodrigo L. Endoscopic resection techniques and ablative therapies for Barrett's neoplasia. World J Gastrointest Endosc 2011; 3:171-182. [PMID: 21954414 PMCID: PMC3180609 DOI: 10.4253/wjge.v3.i9.171] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2010] [Revised: 07/04/2011] [Accepted: 08/15/2011] [Indexed: 02/05/2023] Open
Abstract
Esophageal adenocarcinoma is the most rapidly increasing cancer in western countries. High-grade dysplasia (HGD) arising from Barrett's esophagus (BE) is the most important risk factor for its development, and when it is present the reported incidence is up to 10% per patient-year. Adenocarcinoma in the setting of BE develops through a well known histological sequence, from non-dysplastic Barrett's to low grade dysplasia and then HGD and cancer. Endoscopic surveillance programs have been established to detect the presence of neoplasia at a potentially curative stage. Newly developed endoscopic treatments have dramatically changed the therapeutic approach of BE. When neoplasia is confined to the mucosal layer the risk for developing lymph node metastasis is negligible and can be successfully eradicated by an endoscopic approach, offering a curative intention treatment with minimal invasiveness. Endoscopic therapies include resection techniques, also known as tissue-acquiring modalities, and ablation therapies or non-tissue acquiring modalities. The aim of endoscopic treatment is to eradicate the whole Barrett's segment, since the risk of developing synchronous and metachronous lesions due to the persistence of molecular aberrations in the residual epithelium is well established.
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Affiliation(s)
- Jacobo Ortiz-Fernández-Sordo
- Jacobo Ortiz-Fernández-Sordo, Adolfo Parra-Blanco, Endoscopy Unit, Department of Gastroenterology, Central University Hospital of Asturias, Celestino Villamil S/N, Oviedo 33006, Asturias, Spain
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Schouten LJ, Steevens J, Huysentruyt CJR, Coffeng CE, Keulemans YCA, van Leeuwen FE, Driessen ALC, van den Brandt PA. Total cancer incidence and overall mortality are not increased among patients with Barrett's esophagus. Clin Gastroenterol Hepatol 2011; 9:754-61. [PMID: 21570484 DOI: 10.1016/j.cgh.2011.04.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2011] [Revised: 03/30/2011] [Accepted: 04/05/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Barrett's esophagus (BE) increases risk for esophageal adenocarcinoma, but it is not clear how it affects risk for other cancers or overall mortality. We analyzed data from a population-based cohort of subjects with BE. METHODS The Netherlands Cohort Study was initiated in 1986 and included 120,852 participants (55-69 years old at baseline). Until December 2002, 626 incident cases of BE (excluding nonintestinal metaplasia) were identified by record linkage with the nationwide Pathology Registry. This cohort was followed for a median period of 5.7 years; data on cancer and mortality were obtained from record linkage to the Netherlands Cancer Registry and Statistics Netherlands. The expected number of cases was calculated using national cancer incidence and mortality data. RESULTS In the BE cohort, 13 individuals developed esophageal cancer and 5 developed gastric cancer. The ratio of observed:expected (O:E) incidence of esophageal and gastric cancer was 10.0 (95% confidence interval [CI], 5.3-17.1) and 1.8 (95% CI, 0.6-4.2), respectively. Total cancer incidence (excluding esophageal and gastric cancer) increased in the BE cohort, although not by a statistically significant amount (O:E, 1.3; 95% CI, 1.0-1.6). Of cancer subtypes, incidences of small intestinal and pancreatic cancer increased in subjects with BE, but not by a statistically significant amount, after exclusion of data from the first 6 months of follow-up. During the follow-up period, 225 individuals with BE died. Mortality from all causes (excluding esophageal and gastric cancer) was not increased among subjects with BE (O:E, 1.0; 95% CI, 0.9-1.2), nor was mortality from specific causes of death. CONCLUSIONS The incidence of esophageal cancer was increased in a population-based cohort of subjects with BE. However, when esophageal and gastric cancers were excluded, total cancer incidence and overall mortality were not increased among subjects with BE.
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Affiliation(s)
- Leo J Schouten
- Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
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Endoscopy for upper GI cancer screening in the general population: a cost-utility analysis. Gastrointest Endosc 2011; 74:610-624.e2. [PMID: 21741639 DOI: 10.1016/j.gie.2011.05.001] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2011] [Accepted: 05/02/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND Colon cancer screening with colonoscopy is an accepted strategy; however, there are limited data regarding the cost-effectiveness of screening for upper GI cancers (esophageal adenocarcinoma with its premalignant precursor Barrett's esophagus, esophageal squamous cell cancer, gastric adenocarcinoma) in the United States. OBJECTIVE To evaluate the cost-effectiveness of screening the general population for upper GI cancers by performing an upper endoscopy at the time of screening colonoscopy. DESIGN Decision analysis. SETTING Third-party-payer perspective with a time horizon of 30 years or until death. PATIENTS This study involved 50-year-old patients already undergoing screening colonoscopy. INTERVENTION Comparison of two strategies: performing and not performing a screening upper endoscopy at the time of screening colonoscopy. MAIN OUTCOME MEASUREMENTS Incremental cost-effectiveness ratio (ICER). RESULTS One-time screening for the general population at the age of 50 for upper GI cancers required $115,664 per quality-adjusted life year (QALY) compared with no screening or surveillance. A strategy of screening and surveillance for Barrett's esophagus required only $95,559 per QALY saved. In 1-way sensitivity analyses, the prevalence rates of esophageal adenocarcinoma, esophageal squamous cell cancer, or gastric adenocarcinoma would have to increase by 654%, 1948%, and 337%, respectively, to generate an ICER of less than $50,000 per QALY. LIMITATIONS Omission of premalignant conditions for squamous cell cancer and gastric adenocarcinoma. CONCLUSION The ICER for screening the general population for upper GI cancers with endoscopy remains high, despite accounting for reduced endoscopy costs and the combined benefits of detecting early esophageal adenocarcinoma, esophageal squamous cell cancer, and gastric adenocarcinoma. However, the ICER compares favorably with commonly performed screening strategies for other cancers.
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Barthel JS, Kucera S, Harris C, Canchi D, Hoffe S, Meredith K. Cryoablation of persistent Barrett's epithelium after definitive chemoradiation therapy for esophageal adenocarcinoma. Gastrointest Endosc 2011; 74:51-7. [PMID: 21549371 DOI: 10.1016/j.gie.2011.03.1121] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2010] [Accepted: 03/07/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND Dysplastic Barrett's epithelium (BE) persists after chemoradiation therapy for esophageal adenocarcinoma (EAC) arising in Barrett's esophagus. This phenomenon may present a significant risk for development of metachronous adenocarcinoma. OBJECTIVE To analyze the safety and efficacy of endoscopic cryoablation therapy for persistent dysplastic BE in patients with complete clinical response after definitive chemoradiation therapy for EAC. DESIGN Retrospective cohort study. SETTING Single National Cancer Institute Comprehensive Cancer Center experience. PATIENTS Radiation and endoscopic oncology treatment records were reviewed between January 2004 and September 2009. Fourteen patients with EAC who had been treated with definitive chemoradiation therapy followed by cryoablation were identified. INTERVENTION Cryoablation therapy. MAIN OUTCOME MEASUREMENTS Reduction in Prague Classification and dysplasia status following cryoablation therapy. Complications reported at 24 hour after the procedure telephone survey and at subsequent endoscopy. RESULTS After complete clinical response of EAC to chemoradiation therapy, the median length of persistent BE was Prague classification C1M4 (C = circumferential extent, M = maximal extent). Cryoablation reduced the median length of persistent BE to Prague classification C0M1 (P = .009 with respect to circumferential extent and P = .004 with respect to maximal extent of BE). All 14 patients had dysplastic BE. Cryoablation resulted in histological downgrading in all 14 patients. Among patients with high-grade dysplasia, 20% (2/10) were reduced to low-grade dysplasia, 60% (6/10) to BE with no dysplasia, and 20% (2/10) to no BE. Among patients with low-grade dysplasia, 75% (3/4) were reduced to BE with no dysplasia, and 25% (1/4) to no BE. The median number of cryoablation treatments administered to the 14 patients evaluated was 1 (mean 1.5, range 1-5). Eighty-six percent (12/14) of patients reported no complaints during the 24 hours after cryoablation. No occurrences of perforation and no esophageal strictures were reported at surveillance endoscopy. LIMITATIONS Single-center, retrospective design involving a small number of patients. CONCLUSION Our observations suggest that cryoablation therapy is safe and effective for the treatment of persistent BE after definitive chemoradiation.
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Affiliation(s)
- James S Barthel
- Division of Gastrointestinal Oncology, University of South Florida, Tampa, FL, USA.
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van de Winkel A, van Zoest KPM, van Dekken H, Moons LMG, Kuipers EJ, van der Laan LJW. Differential expression of the nuclear receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR) for grading dysplasia in patients with Barrett's oesophagus. Histopathology 2011; 58:246-53. [PMID: 21323950 DOI: 10.1111/j.1365-2559.2011.03743.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
AIMS To investigate expression of nuclear receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR) as a diagnostic tool to improve grading of dysplasia in Barrett's oesophagus patients. METHODS AND RESULTS Immunostaining was analysed on a total of 192 biopsy samples of 22 Barrett's patients with no dysplasia (ND), 17 with low-grade dysplasia (LGD), 20 high-grade dysplasia (HGD) and 24 with adenocarcinoma (AC). Nuclear FXR expression was observed in 15 of 22 (68%) ND cases versus none of 19 HGD; 3 of 17 (18%); LGD; 5 of 60 (8%) patients with AC (P<0.001). FXR expression was highly specific for non-dysplastic tissue. Nuclear PXR was expressed in 16 of 20 (80%) HGD cases versus two of 16 (13%) LGD cases (PPV 89%). Upon examining adjacent tissue taken from HGD and AC patients, PXR expression was high in samples of all tissue types. CONCLUSIONS Nuclear receptors are expressed differentially during neoplastic progression, with FXR positivity being useful to distinguish ND from dysplasia and AC. PXR nuclear expression is able to separate HGD from LGD and ND. The combination of FXR and PXR also appears to have diagnostic and possibly prognostic value, but future prospective studies are required to investigate their predictive power for neoplastic progression in Barret's oesophagus.
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Affiliation(s)
- Anouk van de Winkel
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands.
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Yentz S, Wang TD. Molecular imaging for guiding oncologic prognosis and therapy in esophageal adenocarcinoma. Hosp Pract (1995) 2011; 39:97-106. [PMID: 21576902 PMCID: PMC3227392 DOI: 10.3810/hp.2011.04.399] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In the past 30 years, the incidence of esophageal adenocarcinoma (ACA) has increased significantly. Sadly, advances in treatment have not followed the same trend, and the prognosis for patients with esophageal ACA remains poor, with a 5-year survival rate of only 15%. Like most cancers, early detection is the key to improving prognosis, but this outcome has proven difficult in the esophagus for several reasons: 1) patients present with advanced disease because "alarm symptoms," such as dysphagia, occur at a late stage, and 2) high-grade dysplasia (HGD) and early ACA are not visible on routine surveillance endoscopy. Currently, the recommended surveillance strategy involves collection of random biopsies, an imperfect technique that is limited by sampling error and is infrequently used because of the considerable time and cost it requires. Even in patients with biopsy-proven dysplasia, adequate guidance for clinical management decisions is still lacking. Dysplasia alone is not an entirely reliable biomarker for the risk of progression to ACA because the natural history of this condition is extremely variable. Clearly, there is a need for additional biomarkers that can better characterize this disease and thus improve our ability to treat patients on an individual basis. As we better understand the molecular changes that lead to the development of this cancer, new molecular biomarkers are needed to allow for more personalized diagnoses, surveillance, and treatment. Targeted agents against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor (VEGF) are currently being evaluated for their role in combination chemotherapy for metastatic esophageal ACA. As these studies progress, a reliable approach for determining receptor status in individual patients is essential. Molecular imaging uses fluorescent probes that target specific cell-surface receptors, and has the potential to evaluate an individual patient's gene expression profile. By topically applying fluorescent probes to dysplastic epithelium during endoscopy, a variety of receptors can be visualized, and the response to treatment can be monitored in real time. This technique can mitigate the limitations of current surveillance protocols, allow for improved cancer detection, and be used for personalized treatment in the future.
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Affiliation(s)
- Sarah Yentz
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
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Feo CV, Patti MG. Importance of a multidisciplinary approach for the treatment of Barrett's esophagus. Updates Surg 2011; 63:5-9. [PMID: 21308492 DOI: 10.1007/s13304-011-0049-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2011] [Accepted: 01/21/2011] [Indexed: 12/12/2022]
Abstract
Barrett's esophagus is a consequence of gastroesophageal reflux disease. Today, it is the most common cause of esophageal adenocarcinoma. Cancer is usually the end results of a cascade of events whereby metaplasia changes into low- and high-grade dysplasia and eventually cancer. Today, we have the unique opportunity to block this cascade and avoid the development of esophageal cancer. A multidisciplinary approach with a team composed of radiologists, gastroenterologists, pathologists, and surgeons allows individualization of care and the best results.
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Affiliation(s)
- Carlo V Feo
- Department of Surgery, Institute of Clinical Surgery, University of Ferrara and University Hospital of Ferrara, Italy
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