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Dhaliwal L, Kamboj AK, Williams JL, Chandar AK, Sachdeva K, Gibbons E, Lansing R, Passe M, Perez JA, Avenir KLR, Martin SA, Leggett CL, Chak A, Falk GW, Wani S, Shaheen NJ, Kisiel JB, Iyer PG. Prevalence and Predictors of Barrett's Esophagus After Negative Initial Endoscopy: Analysis From Two National Databases. Clin Gastroenterol Hepatol 2024; 22:523-531.e3. [PMID: 37716614 PMCID: PMC10922211 DOI: 10.1016/j.cgh.2023.08.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/17/2023] [Accepted: 08/22/2023] [Indexed: 09/18/2023]
Abstract
BACKGROUND & AIMS Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.
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Affiliation(s)
- Lovekirat Dhaliwal
- Department of Internal Medicine, Louisiana State University Health, Shreveport, Louisiana
| | - Amrit K Kamboj
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Apoorva K Chandar
- Department of Internal Medicine, Case Western Reserve University Hospitals, Cleveland, Ohio
| | - Karan Sachdeva
- Department of Internal Medicine, Louisiana State University Health, Shreveport, Louisiana
| | - Erin Gibbons
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Ramona Lansing
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Melissa Passe
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Jaime A Perez
- Clinical Research Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Katelin L R Avenir
- Clinical Research Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Scott A Martin
- Clinical Research Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Cadman L Leggett
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Amitabh Chak
- Division of Gastroenterology, Case Western Reserve University Hospitals, Cleveland, Ohio
| | - Gary W Falk
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Nicholas J Shaheen
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina
| | - John B Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Prasad G Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Gaber CE, Abdelaziz AI, Sarker J, Lund JL, Dellon ES, Cotton CC, Eluri S, Shaheen NJ. Adherence to prescription proton pump inhibitor therapy amongst individuals diagnosed with Barrett's esophagus. Pharmacoepidemiol Drug Saf 2024; 33:e5760. [PMID: 38362648 DOI: 10.1002/pds.5760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 12/21/2023] [Accepted: 01/18/2024] [Indexed: 02/17/2024]
Abstract
INTRODUCTION In the United States, clinical guidelines recommend daily use of proton pump inhibitors (PPIs) amongst individuals diagnosed with Barrett's esophagus to decrease the risk of progression to dysplasia and neoplasia. Prior studies documenting adherence to PPIs in this population have not characterized heterogeneity in adherence patterns. Factors that may relate to adherence are incompletely described. METHODS We used administrative claims data from the Merative MarketScan Commercial Claims and Encounters database to conduct a retrospective study of adherence to prescription PPIs. A cohort of individuals diagnosed with incident Barrett's esophagus between 2010 and 2019 was identified. Group-based trajectory models were generated to detect longitudinal adherence subgroups. RESULTS 79 701 individuals with a new diagnosis of Barrett's esophagus were identified. The best fitting model detected five distinct adherence trajectory groups: consistently high (44% of the population), moderate decline (18%), slow decline (12%), rapid decline (10%), and decline-then-increase (16%). Compared to individuals starting PPIs, those already using PPIs were less likely to have a declining adherence pattern. Other factors associated with membership in a declining adherence group included (but were not limited to): female sex, having a past diagnosis of anxiety or depression, and having one or more emergency department visits in the past year. DISCUSSION Using an exploratory method, we detected heterogeneity in adherence to prescription PPIs. Less than half of individuals were classified into the consistently high adherence group, suggesting that many individuals with Barrett's esophagus receive inadequate pharmacologic therapy.
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Affiliation(s)
- Charles E Gaber
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA
- Center for Pharmacoeconomics and Pharmacoepidemiology & Pharmacoeconomic Research, College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA
| | - Abdullah I Abdelaziz
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA
| | - Jyotirmoy Sarker
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA
| | - Jennifer L Lund
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Evan S Dellon
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Cary C Cotton
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Swathi Eluri
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Nicholas J Shaheen
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Bloomfield M, Cimini D. The fate of extra centrosomes in newly formed tetraploid cells: should I stay, or should I go? Front Cell Dev Biol 2023; 11:1210983. [PMID: 37576603 PMCID: PMC10413984 DOI: 10.3389/fcell.2023.1210983] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 07/17/2023] [Indexed: 08/15/2023] Open
Abstract
An increase in centrosome number is commonly observed in cancer cells, but the role centrosome amplification plays along with how and when it occurs during cancer development is unclear. One mechanism for generating cancer cells with extra centrosomes is whole genome doubling (WGD), an event that occurs in over 30% of human cancers and is associated with poor survival. Newly formed tetraploid cells can acquire extra centrosomes during WGD, and a generally accepted model proposes that centrosome amplification in tetraploid cells promotes cancer progression by generating aneuploidy and chromosomal instability. Recent findings, however, indicate that newly formed tetraploid cells in vitro lose their extra centrosomes to prevent multipolar cell divisions. Rather than persistent centrosome amplification, this evidence raises the possibility that it may be advantageous for tetraploid cells to initially restore centrosome number homeostasis and for a fraction of the population to reacquire additional centrosomes in the later stages of cancer evolution. In this review, we explore the different evolutionary paths available to newly formed tetraploid cells, their effects on centrosome and chromosome number distribution in daughter cells, and their probabilities of long-term survival. We then discuss the mechanisms that may alter centrosome and chromosome numbers in tetraploid cells and their relevance to cancer progression following WGD.
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Affiliation(s)
- Mathew Bloomfield
- Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA, United States
| | - Daniela Cimini
- Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA, United States
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Gurges P, Murray BJ, Boulos MI. Relationship between gastroesophageal reflux disease and objective sleep quality. J Clin Sleep Med 2022; 18:2731-2738. [PMID: 35934919 PMCID: PMC9713921 DOI: 10.5664/jcsm.10198] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 07/01/2022] [Accepted: 07/06/2022] [Indexed: 12/14/2022]
Abstract
STUDY OBJECTIVES To objectively characterize (1) the relationship between gastroesophageal reflux disease (GERD) and sleep quality, and (2) the influence of sleep position on this relationship, using in-laboratory polysomnography. METHODS We retrospectively analyzed first-night diagnostic in-laboratory polysomnography data for 3411 patients (median age 55 years; 48% male). Medication use and medical condition data were obtained through self-reported questionnaires. Associations between sleep quality and the presence of GERD, and the influence of sleep position on these associations, were analyzed using multivariable linear regression models. RESULTS After adjusting for age, sex, body mass index, and relevant comorbidities, GERD was associated with a 3.0% decrease in sleep efficiency, 8.8-minute increase in wake after sleep onset, 24.4-minute increase in rapid eye movement (REM) latency, 13.4-minute decrease in total sleep time, 1.4% decrease in %REM sleep, and 1.5% increase in %N3 sleep. Having both GERD and the majority of sleep on the right side was associated with an 8.6% decrease in sleep efficiency, 27.5-minute increase in wake after sleep onset, 35.6-minute decrease in total sleep time, 2.1% decrease in %REM sleep, and 3.5% increase in %N3 sleep. Having both GERD and the majority of sleep on the left side was associated with an 8.7-minute increase in sleep onset latency. CONCLUSIONS GERD is associated with an impairment in objective sleep quality. These associations were more pronounced in right-sided sleep and mostly ameliorated in left-sided sleep. Physicians should recognize the potential for poor sleep quality in patients with GERD and the effect of body position on this relationship. CITATION Gurges P, Murray BJ, Boulos MI. Relationship between gastroesophageal reflux disease and objective sleep quality. J Clin Sleep Med. 2022;18(12):2731-2738.
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Affiliation(s)
- Patrick Gurges
- Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Brian J. Murray
- Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
- Sleep Laboratory, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Mark I. Boulos
- Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
- Sleep Laboratory, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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The Use of Confocal Laser Endomicroscopy in Diagnosing Barrett’s Esophagus and Esophageal Adenocarcinoma. Diagnostics (Basel) 2022; 12:diagnostics12071616. [PMID: 35885521 PMCID: PMC9317308 DOI: 10.3390/diagnostics12071616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/26/2022] [Accepted: 06/29/2022] [Indexed: 11/17/2022] Open
Abstract
Confocal laser endomicroscopy (CLE) is a diagnostic technique that enables real-time microscopic imaging during microscopic examination and evaluation of epithelial structures with 1000-fold magnification. CLE can be used in the diagnosis of various pathologies, in pneumology, and in urology, and it is very widely utilized in gastroenterology, most importantly in the diagnosis of Barrett’s esophagus (BE), esophageal adenocarcinoma (EAC), biliary strictures, and cystic pancreatic lesions. A literature search was made in MEDLINE/PubMed and Google Scholar databases while focusing on diagnostics using CLE of BE and EAC. We then examined randomized and observational studies, systematic reviews, and meta-analyses relating to the utilization of CLE in BE and EAC diagnostics. Here, we discuss whether CLE can be a suitable diagnostic method for surveillance of BE. Even though many studies have proven that CLE increases diagnostic accuracy in detecting neoplastic transformation of BE, CLE is still not used as a standard diagnostic tool in BE surveillance due to a deficiency of scientific evidence. More studies and data are needed if CLE is to find a place as a new technique in BE surveillance.
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The Role of Microbiota in the Pathogenesis of Esophageal Adenocarcinoma. BIOLOGY 2021; 10:biology10080697. [PMID: 34439930 PMCID: PMC8389269 DOI: 10.3390/biology10080697] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/05/2021] [Accepted: 07/12/2021] [Indexed: 12/20/2022]
Abstract
Simple Summary Esophageal adenocarcinoma has a poor 5-year survival rate and is among the highest mortality cancers. Changes in the esophageal microbiome have been associated with cancer pathogenesis; however, the molecular mechanism remains obscure. This review article critically analyzes the molecular mechanisms through which microbiota may mediate the development and progression of esophageal adenocarcinoma and its precursors-gastroesophageal reflux disease and Barrett’s esophagus. It summarizes changes in esophageal microbiome composition in normal and pathologic states and subsequently discusses the role of altered microbiota in disease progression. The potential role of esophageal microbiota in protecting against the development of esophageal adenocarcinoma is also discussed. By doing so, this article highlights specific directions for future research developing microbiome-mediated therapeutics for esophageal adenocarcinoma. Abstract Esophageal adenocarcinoma (EAC) is associated with poor overall five-year survival. The incidence of esophageal cancer is on the rise, especially in Western societies, and the pathophysiologic mechanisms by which EAC develops are of extreme interest. Several studies have proposed that the esophageal microbiome may play an important role in the pathophysiology of EAC, as well as its precursors—gastroesophageal reflux disease (GERD) and Barrett’s esophagus (BE). Gastrointestinal microbiomes altered by inflammatory states have been shown to mediate tumorigenesis directly and are now being considered as novel targets for both cancer treatment and prevention. Elucidating molecular mechanisms through which the esophageal microbiome potentiates the development of GERD, BE, and EAC will provide a foundation on which new therapeutic targets can be developed. This review summarizes current findings that elucidate the molecular mechanisms by which microbiota promote the pathogenesis of GERD, BE, and EAC, revealing potential directions for additional research on the microbiome-mediated pathophysiology of EAC.
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Fedorova E, Watson TJ. Antireflux and Endoscopic Therapies for Barrett Esophagus and Superficial Esophageal Neoplasia. Surg Clin North Am 2021; 101:391-403. [PMID: 34048760 DOI: 10.1016/j.suc.2021.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Barrett esophagus (BE), defined as intestinal metaplasia of the distal esophageal mucosa, typically results from chronic gastroesophageal reflux disease and is the only known precursor of esophageal adenocarcinoma. The standard of care for the management of early esophageal neoplasia in the setting of BE has changed drastically over the past 15 years. Further investigation into diagnostic and therapeutic adjuncts will continue to improve our ability to control or cure BE before its advancement to a life-threatening malignancy.
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Affiliation(s)
- Ekaterina Fedorova
- MedStar Franklin Square Medical Center, 9000 Franklin Square Drive, Department of Surgery, Baltimore, MD 21237, USA
| | - Thomas J Watson
- MedStar Georgetown University Hospital, 3800 Reservoir Rd, NW, 4PHC Department of Surgery, Washington, DC 20007, USA.
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Kamboj AK, Katzka DA, Iyer PG. Endoscopic Screening for Barrett's Esophagus and Esophageal Adenocarcinoma: Rationale, Candidates, and Challenges. Gastrointest Endosc Clin N Am 2021; 31:27-41. [PMID: 33213798 PMCID: PMC8127641 DOI: 10.1016/j.giec.2020.08.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), a cancer with increasing incidence and poor survival. Risk of EAC in patients with BE is higher compared with the general population. Endoscopic screening for BE is performed to identify patients earlier in the metaplasia-dysplasia-carcinoma sequence from BE to EAC to enable eradication therapy. BE screening should be considered in individuals with multiple risk factors for BE and EAC. Challenges to BE screening include the absence of a cost-effective, widely applicable minimally invasive screening tool, gastroesophageal reflux disease centric screening recommendations, and limitations of current endoscopic surveillance practice.
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Abstract
OBJECTIVES: Barrett's esophagus (BE) is the precursor lesion and a major risk factor for esophageal adenocarcinoma (EAC). Although patients with BE undergo routine endoscopic surveillance, current screening methodologies have proven ineffective at identifying individuals at risk of EAC. Since microRNAs (miRNAs) have potential diagnostic and prognostic value as disease biomarkers, we sought to identify an miRNA signature of BE and EAC. METHODS: High-throughput sequencing of miRNAs was performed on serum and tissue biopsies from 31 patients identified either as normal, gastroesophageal reflux disease (GERD), BE, BE with low-grade dysplasia (LGD), or EAC. Logistic regression modeling of miRNA profiles with Lasso regularization was used to identify discriminating miRNA. Quantitative reverse transcription polymerase chain reaction was used to validate changes in miRNA expression using 46 formalin-fixed, paraffin-embedded specimens obtained from normal, GERD, BE, BE with LGD or HGD, and EAC subjects. RESULTS: A 3-class predictive model was able to classify tissue samples into normal, GERD/BE, or LGD/EAC classes with an accuracy of 80%. Sixteen miRNAs were identified that predicted 1 of the 3 classes. Our analysis confirmed previous reports indicating that miR-29c-3p and miR-193b-5p expressions are altered in BE and EAC and identified miR-4485-5p as a novel biomarker of esophageal dysplasia. Quantitative reverse transcription polymerase chain reaction validated 11 of 16 discriminating miRNAs. DISCUSSION: Our data provide an miRNA signature of normal, precancerous, and cancerous tissue that may stratify patients at risk of progressing to EAC. We found that serum miRNAs have a limited ability to distinguish between disease states, thus limiting their potential utility in early disease detection.
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10
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Petrakis IE, Sciacca V, Iascone C. Diagnosis and Treatment of Barrett’s Oesophagus. A General Survey. Acta Chir Belg 2020. [DOI: 10.1080/00015458.2001.12098586] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- I. E. Petrakis
- 1st Department of General Surgery, Policlinico Umberto I, Rome University La Sapienza, Rome, Italy
| | - V. Sciacca
- 1st Department of General Surgery, Policlinico Umberto I, Rome University La Sapienza, Rome, Italy
| | - C. Iascone
- 1st Department of General Surgery, Policlinico Umberto I, Rome University La Sapienza, Rome, Italy
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11
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Quach DT, Pham QT, Tran TL, Vu NT, Le QD, Nguyen DT, Dang NL, Le HM, Le NQ, Sharma P, Ho KY. Prevalence, clinical characteristics, and risk factors of Barrett esophagus in Vietnamese patients with upper gastrointestinal symptoms. Medicine (Baltimore) 2020; 99:e21791. [PMID: 32846811 PMCID: PMC7447484 DOI: 10.1097/md.0000000000021791] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 04/28/2020] [Accepted: 07/16/2020] [Indexed: 12/28/2022] Open
Abstract
The current barrier for investigation of Barrett esophagus (BE) in Asia is diagnostic standardization, which is a challenge to identify its true risk factors. This study aimed to investigate the prevalence, clinical characteristics and risk factors of BE in Vietnamese patients with upper gastrointestinal symptoms.A cross-sectional study was conducted on consecutive outpatients who underwent upper gastrointestinal endoscopy. Endoscopically suspected esophageal metaplasia (ESEM) which was clearly visible at least 1 cm above the gastroesophageal junction at endoscopy was taken biopsy. At least 1 biopsy per 2 cm in tongues of ESEM and 4 biopsies per 2 cm of circumferential ESEM were taken. The diagnostic criterion for BE was replacement of the normal squamous epithelial lining by columnar epithelium confirmed by histology.A total of 1947 patients were recruited. Forty-seven out of 58 patients with ESEM were histologically confirmed BE. The prevalences of BE and hiatal hernia (HH) were 2.4% (95% confidence interval [CI], 1.7-3.1%) and 2.3% (95% CI, 1.6-2.9%), respectively. Heartburn and/or regurgitation presented in only 61.7% (95% CI, 46.4-75.5%) of patients with BE. In multivariate analysis, the only 2 factors significantly associated with BE were HH (OR 7.53; 95% CI, 3.13-18.11; P < .001) and typical reflux symptom (OR 2.07; 95% CI, 1.12-3.83; P = .020).BE is not uncommon in Vietnamese patients with upper gastrointestinal symptoms. In addition, typical reflux symptoms and HH are the risk factors for BE in Vietnamese.
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Affiliation(s)
- Duc T. Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Hochiminh City
- Department of Endoscopy, University Medical Center at Hochiminh City
- Department of Gastroenterology, Gia-Dinh's People Hospital
| | | | - Truc L.T. Tran
- Department of Endoscopy, University Medical Center at Hochiminh City
| | - Nhu T.H. Vu
- Department of Internal Medicine, University of Medicine and Pharmacy at Hochiminh City
- Department of Endoscopy, University Medical Center at Hochiminh City
| | - Quang D. Le
- Department of Internal Medicine, University of Medicine and Pharmacy at Hochiminh City
- Department of Endoscopy, University Medical Center at Hochiminh City
- Department of Gastroenterology, Gia-Dinh's People Hospital
| | - Doan T.N. Nguyen
- Department of Internal Medicine, University of Medicine and Pharmacy at Hochiminh City
- Department of Endoscopy, University Medical Center at Hochiminh City
| | - Ngoc L.B. Dang
- Department of Endoscopy, University Medical Center at Hochiminh City
| | - Huy M. Le
- Department of Endoscopy, University Medical Center at Hochiminh City
- Department of Surgical Pathology, University of Medicine and Pharmacy at Hochiminh City, Hochiminh City, Vietnam
| | - Nhan Q. Le
- Department of Endoscopy, University Medical Center at Hochiminh City
| | - Prateek Sharma
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, MO
| | - Khek-Yu Ho
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore
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12
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Baudoin NC, Nicholson JM, Soto K, Martin O, Chen J, Cimini D. Asymmetric clustering of centrosomes defines the early evolution of tetraploid cells. eLife 2020; 9:54565. [PMID: 32347795 PMCID: PMC7250578 DOI: 10.7554/elife.54565] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 04/28/2020] [Indexed: 12/13/2022] Open
Abstract
Tetraploidy has long been of interest to both cell and cancer biologists, partly because of its documented role in tumorigenesis. A common model proposes that the extra centrosomes that are typically acquired during tetraploidization are responsible for driving tumorigenesis. However, tetraploid cells evolved in culture have been shown to lack extra centrosomes. This observation raises questions about how tetraploid cells evolve and more specifically about the mechanisms(s) underlying centrosome loss. Here, using a combination of fixed cell analysis, live cell imaging, and mathematical modeling, we show that populations of newly formed tetraploid cells rapidly evolve in vitro to retain a near-tetraploid chromosome number while losing the extra centrosomes gained at the time of tetraploidization. This appears to happen through a process of natural selection in which tetraploid cells that inherit a single centrosome during a bipolar division with asymmetric centrosome clustering are favored for long-term survival.
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Affiliation(s)
- Nicolaas C Baudoin
- Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, United States
| | - Joshua M Nicholson
- Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, United States
| | - Kimberly Soto
- Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, United States
| | - Olga Martin
- Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, United States
| | - Jing Chen
- Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, United States
| | - Daniela Cimini
- Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, United States
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13
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O'Farrell NJ, Phelan JJ, Feighery R, Doyle B, Picardo SL, Ravi N, O'Toole D, Reynolds JV, O'Sullivan J. Differential Expression Profiles of Oxidative Stress Levels, 8-oxo-dG and 4-HNE, in Barrett's Esophagus Compared to Esophageal Adenocarcinoma. Int J Mol Sci 2019; 20:ijms20184449. [PMID: 31509954 PMCID: PMC6770156 DOI: 10.3390/ijms20184449] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 09/03/2019] [Indexed: 12/22/2022] Open
Abstract
Barrett’s esophagus (BE), a chronic inflammatory condition, is the leading risk factor for esophageal adenocarcinoma (EAC). In inflammation to cancer pathways, oxidative stress profiles have been linked to cancer progression. However, the relevance of oxidative stress profiles along the BE-disease sequence remains to be elucidated. In this study, markers of oxidative stress; DNA adducts (8-oxo-dG) and lipoperoxidation (4-HNE), and markers of proliferation (Ki67) were measured in patient biopsies representing the BE-disease sequence. Differences in expression of these markers in Barrett’s patients with cancer-progression and non-progression were examined. Proliferation was reduced in Barrett’s specialized intestinal metaplasia (SIM) compared with EAC (p < 0.035). Correcting for cell proliferation levels, a confounding factor, linked to oxidative stress profiles, SIM demonstrated increased levels of 8-oxo-dG and 4-HNE (p < 0.05) compared with EAC. Longitudinal analysis of Barrett’s patients demonstrated decreased levels of 8-oxo-dG in SIM cancer progression (p < 0.05). BE is an environment of increased oxidative stress and inflammation. Patients with progressive disease demonstrated reduced oxidative stress levels in 8-oxo-dG. Perhaps these alterations facilitate Barrett’s progression, whereas in non-progressive disease, cells follow the rules of increased oxidative stress ultimately triggers cell apoptosis, thereby preventing propagation and survival.
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Affiliation(s)
- Naoimh J O'Farrell
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James' Hospital, Dublin 8, Ireland
| | - James J Phelan
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James' Hospital, Dublin 8, Ireland
| | - Ronan Feighery
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James' Hospital, Dublin 8, Ireland
| | - Brendan Doyle
- Department of Histopathology, St. James' Hospital, Dublin 8, Ireland
| | - Sarah L Picardo
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James' Hospital, Dublin 8, Ireland
| | - Narayanasamy Ravi
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James' Hospital, Dublin 8, Ireland
| | - Dermot O'Toole
- Department of Clinical Medicine, Trinity Translational Medicine Institute, St. James' Hospital, Dublin 8, Ireland
| | - John V Reynolds
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James' Hospital, Dublin 8, Ireland
| | - Jacintha O'Sullivan
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James' Hospital, Dublin 8, Ireland.
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14
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Vasavi M, Ponnala S, Gujjari K, Boddu P, Bharatula RS, Prasad R, Ahuja YR, Hasan Q. Dna Methylation in Esophageal Diseases Including Cancer: Special Reference to hMLH1 Gene Promoter Status. TUMORI JOURNAL 2019; 92:155-62. [PMID: 16724696 DOI: 10.1177/030089160609200212] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Aims and Background Chronic inflammation leading to malignancy in the esophagus may be due to errors in mismatch repair (MMR) genes such as hMLH1. Promoter hypermethylation has been suggested as the main cause of hMLH1 silencing. In this study we assessed hMLH1 promoter hypermethylation in a range of esophageal diseases. Further, we evaluated the role of factors affecting the methylation cycle: (1) methyt-enetetrahydrofolate reductase (MTHFR) C677T mutation and (2) serum homocysteine levels. Methods We endoscopically and histologically categorized 124 paired tissue and blood samples from patients into cancer, precancer, reflux esophagitis, other inflammatory esophagitis and controls (endoscopically normal). Restriction enzyme-based methylation analysis was carried out to assess hMLH1 promoter hypermethylation. Results and Conclusions hMLH1 promoter hypermethylation in tissue was seen in 63.5% of patients with cancer and 53.8% of those with precancer, which was significantly increased when compared with controls (P <0.001). There appears to be an increasing degree of hMLH1 hypermethylation with disease progression. Patients with gastroesophageal reflux disease (GERD) showed a high degree of hMLH1 hypermethylation (88.8%), indicating that local environment due to reflux may be promoting hypermethylation. We suggest that GERD is a progressive condition with an increased risk for developing into cancer. Only 14.5% of cases exhibited hypermethylation both in tissue and blood. Hence, we conclude that hMLH1 promoter hypermethylation is a tissue-specific change in the esophagus and blood testing cannot be used as a noninvasive tool to assess it. DNA methylation is dependent on the methylation cycle; MTHFR is a major enzyme in this pathway. MTHFR mutations did not correlate with hypermethylation or clinical pathology (P >0.5). Elevated homocysteine levels, independent of MTHFR mutation, correlated significantly with hMLH1 hypermethylation in tissue (P <0.005). Our study shows that hMLH1 hypermethylation in tissue may be the primary event caused by endogenous/exogenous factors in esophageal diseases, aiding disease progression.
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Affiliation(s)
- Mohan Vasavi
- Department of Genetics and Molecular Medicine, Gastroenterology and Biochemistry, Kamineni Hospitals, Hyderabad, India
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15
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Furneri G, Klausnitzer R, Haycock L, Ihara Z. Economic value of narrow-band imaging versus white light endoscopy for the diagnosis and surveillance of Barrett's esophagus: Cost-consequence model. PLoS One 2019; 14:e0212916. [PMID: 30865673 PMCID: PMC6415878 DOI: 10.1371/journal.pone.0212916] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 02/12/2019] [Indexed: 12/26/2022] Open
Abstract
Barrett’s esophagus (BE) is an abnormality arising from gastroesophageal reflux disease that can progressively evolve into a sequence of dysplasia and adenocarcinoma. Progression of Barrett’s esophagus into dysplasia is monitored with endoscopic surveillance. The current surveillance standard requests random biopsies plus targeted biopsies of suspicious lesions under white-light endoscopy, known as the Seattle protocol. Recently, published evidence has shown that narrow-band imaging (NBI) can guide targeted biopsies to identify dysplasia and reduce the need for random biopsies. We aimed to assess the health economic implications of adopting NBI-guided targeted biopsy vs. the Seattle protocol from a National Health Service England perspective. A decision tree model was developed to undertake a cost-consequence analysis. The model estimated total costs (i.e. staff and overheads; histopathology; adverse events; capital equipment) and clinical implications of monitoring a cohort of patients with known/suspected BE, on an annual basis. In the simulation, BE patients (N = 161,657 at Year 1; estimated annual increase: +20%) entered the model every year and underwent esophageal endoscopy. After 7 years, the adoption of NBI with targeted biopsies resulted in cost reduction of £458.0 mln vs. HD-WLE with random biopsies (overall costs: £1,966.2 mln and £2,424.2 mln, respectively). The incremental investment on capital equipment to upgrade hospitals with NBI (+£68.3 mln) was offset by savings due to the reduction of histological examinations (-£505.2 mln). Reduction of biopsies also determined savings for avoided adverse events (-£21.1 mln). In the base-case analysis, the two techniques had the same accuracy (number of correctly identified cases: 1.934 mln), but NBI was safer than HD-WLE. Budget impact analysis and cost-effectiveness analyses confirmed the findings of the cost-consequence analysis. In conclusion, NBI-guided targeted biopsies was a cost-saving strategy for NHS England, compared to current practice for detection of dysplasia in patients with BE, whilst maintaining at least comparable health outcomes for patients.
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Affiliation(s)
| | | | - Laura Haycock
- Value, Access and Pricing, CBPartners, London, United Kingdom
| | - Zenichi Ihara
- Medical Systems Division, Olympus Europa, Hamburg, Germany
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16
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Shrestha P, Penninkilampi R, Eslick GD. The Esophageal Microbiome. GASTROINTESTINAL DISEASES AND THEIR ASSOCIATED INFECTIONS 2019:1-16. [DOI: 10.1016/b978-0-323-54843-4.00001-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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17
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Abstract
In Western countries, the incidence of esophageal adenocarcinoma has increased rapidly in parallel with its premalignant condition, Barrett esophagus (BE). Unlike colonoscopy, endoscopic screening for BE is not currently recommended for all patients; however, surveillance endoscopy is advocated for patients with established BE. Novel imaging and sampling techniques have been developed and investigated for the purpose of improving the detection of Barrett esophagus, dysplasia, and neoplasia. This article discusses several screening and surveillance techniques, including Seattle protocol, chromoendoscopy, electronic chromoendoscopy, wide area transepithelial sampling with 3-dimensional analysis, nonendoscopic sampling devices, and transnasal endoscopy.
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Affiliation(s)
- Yoshihiro Komatsu
- Esophageal and Lung Institute, Allegheny Health Network, Western Pennsylvania Hospital, Suite 158, Mellon Pavilion, 4815 Liberty Avenue, Pittsburgh, PA 15224, USA
| | - Kirsten M Newhams
- Esophageal and Lung Institute, Allegheny Health Network, Western Pennsylvania Hospital, Suite 158, Mellon Pavilion, 4815 Liberty Avenue, Pittsburgh, PA 15224, USA
| | - Blair A Jobe
- Esophageal and Lung Institute, Allegheny Health Network, Western Pennsylvania Hospital, Suite 158, Mellon Pavilion, 4815 Liberty Avenue, Pittsburgh, PA 15224, USA.
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18
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Zeki SS, Bergman JJ, Dunn JM. Endoscopic management of dysplasia and early oesophageal cancer. Best Pract Res Clin Gastroenterol 2018; 36-37:27-36. [PMID: 30551853 DOI: 10.1016/j.bpg.2018.11.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 11/19/2018] [Indexed: 01/31/2023]
Abstract
In the past decade there have been technological advances in Endoscopic Eradication Therapy (EET) for the management of patients with oesophageal neoplasia and early cancer. Multiple endoscopic techniques now exist for both squamous and Barrett's oesophagus associated neoplasia or early cancer. A fundamental aspect of endotherapy is removal of the target lesion by endoscopic mucosal resection, or endosopic submucosal dissection. Residual tissue is subsequently ablated to remove the risk of recurrence. The most validated technique for Barrett's oesophagus is radiofrequency ablation, but other techniques such as hybrid-APC and cryotherapy also show good results. This chapter will discuss the evolution of EET, and which patients are most likely to benefit. It will also explore the evidence behind the success of different techniques and provide practical advice on how to carry out the endoscopic techniques with a focus on radiofrequency ablation and endoscopic mucosal resection in particular.
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Affiliation(s)
- S S Zeki
- Dept of Gastroenterology, Guy's & St Thomas' Hospitals NHS Foundation Trust, Westminster Bridge Road, London, SE1 7EH, United Kingdom.
| | - J J Bergman
- Dep. of Gastroenterology, Academic Medical Center, Amsterdam, Netherlands
| | - J M Dunn
- Dept of Gastroenterology, Guy's & St Thomas' Hospitals NHS Foundation Trust, Westminster Bridge Road, London, SE1 7EH, United Kingdom
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19
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Helicobacter pylori Infection Is Associated With Reduced Risk of Barrett's Esophagus: An Analysis of the Barrett's and Esophageal Adenocarcinoma Consortium. Am J Gastroenterol 2018; 113:1148-1155. [PMID: 29880962 DOI: 10.1038/s41395-018-0070-3] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 03/13/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Epidemiological studies of Helicobacter pylori infection and risk of Barrett's esophagus (BE) have reported conflicting results. We examined the association between H. pylori infection and BE and sought to determine whether the association is mediated by gastroesophageal reflux disease (GERD) and to identify potential effect modifiers. METHODS We used individual level data from 1308 patients with BE (cases), 1388 population-based controls, and 1775 GERD controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). We estimated study-specific odds ratios (ORs) and 95% CIs using multivariable logistic regression models and obtained summary risk estimates using a random-effects meta-analytic approach. We examined potential effect modification by waist-to-hip ratio (WHR), body mass index (BMI), and smoking status by conducting stratified analyses. RESULTS For comparisons with population-based controls, H. pylori infection was inversely associated with the risk of BE (adjusted OR = 0.44, 95% CI = 0.36-0.55), with no evidence of between-study heterogeneity (I2 = 0%). A stronger inverse association between H. pylori and BE was observed among individuals with the CagA-positive strain (P for interaction = 0.017). We found no evidence of interaction between WHR, BMI, smoking status, and H. pylori infection on the risk of BE. There was no association between H. pylori infection and BE for comparisons with GERD controls (OR = 0.96, 95% CI = 0.67-1.37; I2 = 48%). CONCLUSIONS This study provides the strongest evidence yet that H. pylori infection is strongly inversely associated with BE. This effect is probably mediated by a decrease in GERD in infected patients, since the protective effect disappears in patients with GERD symptoms.
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20
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Krishnamoorthi R, Singh S, Ragunathan K, Visrodia K, Wang KK, Katzka DA, Iyer PG. Factors Associated With Progression of Barrett's Esophagus: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018; 16:1046-1055.e8. [PMID: 29199147 DOI: 10.1016/j.cgh.2017.11.044] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 09/21/2017] [Accepted: 11/15/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Endoscopic surveillance of patients with Barrett's esophagus (BE) is inefficient. Risk stratification of patients might improve the effectiveness of surveillance. We performed a systematic review and meta-analysis to identify factors associated with progression of BE without dysplasia or BE with low-grade dysplasia (LGD) to high-grade dysplasia or esophageal adenocarcinoma. METHODS We performed a systematic search of databases through May 2016 to identify cohort studies of patients with baseline BE without dysplasia or BE with LGD that reported predictors of progression. Pooled estimates (odds ratios) of associations of age, sex, smoking, alcohol use, obesity, baseline LGD, segment length, and medication use with progression were calculated. RESULTS We identified 20 studies, reporting 1231 events in 74943 patients. The studies associated BE progression with increasing age (12 studies; odds ratio [OR], 1.03; 95% CI, 1.01-1.05), male sex (11 studies; OR, 2.16; 95% CI, 1.84-2.53), ever smoking (current or past, 8 studies; OR, 1.47; 95% CI, 1.09-1.98), and increasing BE segment length (10 studies; OR, 1.25; 95% CI, 1.16-1.36), with a low degree of heterogeneity. LGD was associated with a 4-fold increase in risk of BE progression (11 studies; OR, 4.25; 95% CI, 2.58-7.0). Use of proton pump inhibitors (4 studies; OR, 0.55; 95% CI, 0.32-0.96) or statins (3 studies; OR, 0.48; 95% CI, 0.31-0.73) were associated with lower risk of BE progression. Alcohol use and obesity did not associate with risk of progression. CONCLUSIONS In a systematic review and meta-analysis, we associated older age, male sex, smoking, longer BE segment, and LGD with risk of progression of BE. Individuals with these features should undergo more intensive surveillance or endoscopic therapy. Smoking is a modifiable risk factor for cancer prevention in patients with BE.
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Affiliation(s)
- Rajesh Krishnamoorthi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Siddharth Singh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Karthik Ragunathan
- Department of Internal Medicine, University of Illinois College of Medicine, Peoria, Illinois
| | - Kavel Visrodia
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Kenneth K Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - David A Katzka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Prasad G Iyer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
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21
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Costamagna G, Battaglia G, Repici A, Fiocca R, Rugge M, Spada C, Villanacci V. Diagnosis and Endoscopic Management of Barrett's Esophagus: an Italian Experts' Opinion based document. Dig Liver Dis 2017; 49:1306-1313. [PMID: 28969923 DOI: 10.1016/j.dld.2017.08.034] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 08/14/2017] [Accepted: 08/15/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Barrett's esophagus (BE) is recognized as a risk factor for esophageal adenocarcinoma. An expert panel was organized in Italy with the aim of drafting a series of statements on BE to guide diagnosis and management of patients with BE. METHODS The working Group Coordinators worked on a literature search to identify key topics regarding critical steps of the endoscopic approach to BE. Based on the search and their expert opinion, a list of most meaningful questions was prepared and emailed to all members who were asked to vote the questions. When the survey was completed a consensus meeting was organized. According to the survey results, Group Coordinators proposed a draft statement that was voted. By definition, the statement was formulated when there was an agreement of ≥50% among participants. RESULTS Twenty nine participants deliberated 18 questions. The agreement was reached for 16 questions for which a recommendation was formulated. CONCLUSION The generated statements highlight the Italian contribution to the European Position Statement of the European Society of Gastrointestinal Endoscopy. The Italian statements preserve peculiarities when dealing with the endoscopic management of BE and wishes to be considered as a contribution for the care of BE patients even with a low risk of progression to esophageal neoplasia.
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Affiliation(s)
- Guido Costamagna
- Digestive Endoscopy Unit, Catholic University, Rome, Italy; IHU, Strasbourg, USIAS, University of Strasbourg, France.
| | - Giorgio Battaglia
- Digestive Endoscopy Unit, Veneto Institute of Oncology, Padova, Italy
| | - Alessandro Repici
- Department of Gastroenterology Istituto Clinico Humanitas, Milan, Italy
| | - Roberto Fiocca
- Department of Surgical and Morphological Sciences, Anatomic Pathology Division, University of Genoa and IRCCS San Martino/IST, Genoa, Italy
| | - Massimo Rugge
- Department of Medicine, DIMED, Pathology Unit, University of Padova, Padova, Italy
| | - Cristiano Spada
- Digestive Endoscopy Unit, Catholic University, Rome, Italy; Digestive Endoscopy Unit, Fondazione Poliambulanza, Brescia, Italy
| | - Vincenzo Villanacci
- Pathology Section, Department of Molecular and Translational Medicine, Spedali Civili and University of Brescia, Brescia, Italy
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22
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Trindade AJ, Inamdar S, Kothari S, Berkowitz J, McKinley M, Kaul V. Feasibility of liquid nitrogen cryotherapy after failed radiofrequency ablation for Barrett's esophagus. Dig Endosc 2017; 29:680-685. [PMID: 28303613 DOI: 10.1111/den.12869] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 03/13/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM Radiofrequency ablation (RFA) for dysplastic Barrett's esophagus (BE) is highly effective. RFA failures are infrequent but can be a challenging cohort to manage. There are limited data on the feasibility of liquid nitrogen cryospray ablation for complete eradication of dysplasia (CE-D) and/or intestinal metaplasia (CE-IM) after RFA has failed to achieve CE-IM in patients with dysplastic BE. METHODS This is a retrospective review from two medical centers of prospectively maintained databases looking at patients that underwent liquid nitrogen cryospray ablation for refractory intestinal metaplasia post failed RFA. RESULTS Eighteen patients were identified that met inclusion criteria. Eleven patients had persistent dysplasia and IM following RFA and seven had persistent non-dysplastic IM. More than 80% of patients were male with long-segment BE (median length 8 cm). Seventy two percent of patients with dysplasia achieved CE-D after cryotherapy. Fifty percent (9/18) of all RFA failures achieved CE-IM with cryotherapy. In comparison, RFA has a CE-IM of 78% in a less challenging treatment naïve cohort from a large-scale meta-analysis of 3802 patients. No adverse events occurred in our cohort. CONCLUSION Cryospray ablation is feasible and safe for achieving CE-D and CE-IM after RFA failure. The CE-D rates are high with cryotherapy in this population. CE-IM with cryotherapy is acceptable in this difficult-to-treat cohort when compared to CE-IM rates with RFA in dysplastic BE treatment naïve patients (50% vs 78%).
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Affiliation(s)
- Arvind J Trindade
- Division of Gastroenterology, Department of Medicine, Hofstra Northwell School of Medicine, Northwell Health System, Long Island Jewish Medical Center, New Hyde Park, USA
| | - Sumant Inamdar
- Division of Gastroenterology, Department of Medicine, Hofstra Northwell School of Medicine, Northwell Health System, Long Island Jewish Medical Center, New Hyde Park, USA
| | - Shivangi Kothari
- Strong Memorial Hospital, University of Rochester Medical Center, Rochester, USA
| | - Joshua Berkowitz
- Division of Gastroenterology, Department of Medicine, Hofstra Northwell School of Medicine, Northwell Health System, Long Island Jewish Medical Center, New Hyde Park, USA
| | - Matthew McKinley
- Division of Gastroenterology, Department of Medicine, Hofstra Northwell School of Medicine, Northwell Health System, Long Island Jewish Medical Center, New Hyde Park, USA
| | - Vivek Kaul
- Strong Memorial Hospital, University of Rochester Medical Center, Rochester, USA
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23
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Ichihara S, Uedo N, Gotoda T. Considering the esophagogastric junction as a 'zone'. Dig Endosc 2017; 29 Suppl 2:3-10. [PMID: 28425656 DOI: 10.1111/den.12792] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 12/21/2016] [Indexed: 02/08/2023]
Abstract
Siewert's classification of adenocarcinoma of the esophagogastric junction (EGJ) classifies tumors anatomically for determining the appropriate surgical technique. According to this classification, a type II tumor, true carcinoma of the cardia, is defined as a cancer within 1 cm proximal to 2 cm distal of the EGJ. Histological analysis indicates that the cardiac gland is present with a high degree of frequency between 1-2 cm to the gastric side and 1-2 cm to the esophageal side of the EGJ, which means that this zone can be considered as neither the stomach nor the esophagus but rather as a third zone known as the 'EGJ zone'. It has been suggested that there are multiple causes for development of adenocarcinoma in the EGJ zone. The TNM Classification of Malignant Tumours 7th Edition considers EGJ adenocarcinoma (EGJAC) occurring in the EGJ zone to be a part of esophageal adenocarcinoma (EAC). However, recent studies have indicated that EGJAC behaves differently from EAC and gastric carcinoma. Barrett's esophagus is now considered an important factor in the etiology of EGJAC, but, as yet, no studies have elucidated the differences between cancer arising from short-segment Barrett's esophagus and cancer of the gastric cardia. Thus, there is currently no clinical relevance to subdivision of adenocarcinoma in the EGJ zone into above or below the EGJ line.
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Affiliation(s)
- Shin Ichihara
- Department of Surgical Pathology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
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24
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Visrodia K, Singh S, Krishnamoorthi R, Ahlquist DA, Wang KK, Iyer PG, Katzka DA. Systematic review with meta-analysis: prevalent vs. incident oesophageal adenocarcinoma and high-grade dysplasia in Barrett's oesophagus. Aliment Pharmacol Ther 2016; 44:775-84. [PMID: 27562355 DOI: 10.1111/apt.13783] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Revised: 07/20/2016] [Accepted: 08/05/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND The proportion of oesophageal adenocarcinoma that is detected concurrently with initial Barrett's oesophagus diagnosis is not well studied. AIM To compare the proportion of prevalent adenocarcinoma vs. incident adenocarcinoma found during surveillance of Barrett's. METHODS We performed a systematic search of MEDLINE, EMBASE and Web of Science (from their inception to 31 May 2015) for cohort studies in adults with Barrett's (nondysplastic Barrett's ± Barrett's with low-grade dysplasia) with minimum average follow-up of 3 years, and providing numbers of prevalent adenocarcinoma detected (concurrently with Barrett's diagnosis and up to 1 year afterwards) vs. incident adenocarcinoma detected (greater than 1 year after Barrett's diagnosis). Pooled weighted proportions of prevalent and incident adenocarcinoma were calculated, using a random effects model. RESULTS On meta-analysis of 13 studies reporting on 603 adenocarcinomas in 9657 Barrett's patients, 85.1% of adenocarcinomas were classified as prevalent [95% confidence interval (CI), 78.1-90.2%) and 14.9% as incident (95% CI, 9.8-21.9%), with substantial heterogeneity (I(2) = 66%). Among nine studies reporting on 787 high-grade dysplasia and oesophageal adenocarcinomas in 8098 Barrett's patients, the proportion of prevalent high-grade dysplasia-oesophageal adenocarcinoma was similar at 80.5% (95% CI, 68.1-88.8%, I(2) = 87%). These results remained stable across multiple subgroup analyses including study quality, setting, duration of follow-up and presence of baseline dysplasia. CONCLUSIONS In our meta-analysis, four of five patients diagnosed with adenocarcinoma or high-grade dysplasia at index endoscopy or within 1 year of Barrett's follow-up were considered to be prevalent cases. Continued efforts are needed to identify patients with Barrett's before the development of adenocarcinoma.
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Affiliation(s)
- K Visrodia
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - S Singh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.,Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.,Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA
| | - R Krishnamoorthi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - D A Ahlquist
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - K K Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - P G Iyer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - D A Katzka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
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25
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Nomura K, Iizuka T, Inoshita N, Kuribayashi Y, Toba T, Yamada A, Yamashita S, Furuhata T, Kikuchi D, Matsui A, Mitani T, Ogawa O, Hoteya S, Ueno M, Udagawa H, Kaise M. Adenocarcinoma of the cervical esophagus arising from ectopic gastric mucosa: report of two cases and review of the literature. Clin J Gastroenterol 2016; 8:367-76. [PMID: 26476962 DOI: 10.1007/s12328-015-0610-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 09/12/2015] [Indexed: 12/28/2022]
Abstract
Esophageal adenocarcinoma arising from ectopic gastric mucosa (EGM) is extremely rare. We describe here two Japanese patients with adenocarcinoma of the cervical esophagus arising from EGM. Case 1 is a 62-year-old man who had slightly red EGM in the cervical esophagus on upper gastrointestinal endoscopy (UGE). Because the biopsy showed atypical glands that were suspicious for adenocarcinoma, endoscopic submucosal dissection was performed. Histopathological examination revealed that the lesion was a well-differentiated adenocarcinoma (pT1a MM). Lymphovascular invasion was absent, and the margins were free from carcinoma. Case 2 is a 57-year-old man who had an elevated lesion with a bleeding tendency in an area of EGM in the cervical esophagus on UGE. Adenocarcinoma was diagnosed in the biopsy. Because of the presence of enlarged lymph nodes (#106recL), preoperative chemoradiotherapy was performed to reduce the size of the adenocarcinoma and lymph nodes prior to resection of the cervical esophagus and reconstruction with free jejunal grafts. Histopathological examination revealed moderately differentiated adenocarcinoma (0-I, pT2N1M0, pStage II). In both cases, adenocarcinoma was surrounded by EGM, which led to the diagnosis of EGM-derived esophageal adenocarcinoma. Here, we report its immunohistochemical characteristics in the present cases and discuss the histogenesis.
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Abstract
There is a well-established association between Barrett's esophagus and esophageal adenocarcinoma. Primary esophageal neuroendocrine carcinoma is a rare tumor and has not previously been reported in association with Barrett's esophagus. We report such a case with immunohistochemical and electron microscopic findings. Int J Surg Pathol 2(1):43-46, 1994
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Affiliation(s)
- John Slavin
- Department of Anatomical Pathology, Royal Mel bourne Hospital, Parkville, Victoria, Australia, and Repatriation General Hospital, West Heidleberg, Victoria, Australia
| | - Graham Pitson
- Department of Anatomical Pathology, Royal Mel bourne Hospital, Parkville, Victoria, Australia, and Repatriation General Hospital, West Heidleberg, Victoria, Australia
| | - John P. Dowling
- Department of Anatomical Pathology, Royal Mel bourne Hospital, Parkville, Victoria, Australia, and Repatriation General Hospital, West Heidleberg, Victoria, Australia
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27
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Sun X, Elston RC, Barnholtz-Sloan JS, Falk GW, Grady WM, Faulx A, Mittal SK, Canto M, Shaheen NJ, Wang JS, Iyer PG, Abrams JA, Tian YD, Willis JE, Guda K, Markowitz SD, Chandar A, Warfe JM, Brock W, Chak A. Predicting Barrett's Esophagus in Families: An Esophagus Translational Research Network (BETRNet) Model Fitting Clinical Data to a Familial Paradigm. Cancer Epidemiol Biomarkers Prev 2016; 25:727-35. [PMID: 26929243 PMCID: PMC4873373 DOI: 10.1158/1055-9965.epi-15-0832] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 02/03/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Barrett's esophagus is often asymptomatic and only a small portion of Barrett's esophagus patients are currently diagnosed and under surveillance. Therefore, it is important to develop risk prediction models to identify high-risk individuals with Barrett's esophagus. Familial aggregation of Barrett's esophagus and esophageal adenocarcinoma, and the increased risk of esophageal adenocarcinoma for individuals with a family history, raise the necessity of including genetic factors in the prediction model. Methods to determine risk prediction models using both risk covariates and ascertained family data are not well developed. METHODS We developed a Barrett's Esophagus Translational Research Network (BETRNet) risk prediction model from 787 singly ascertained Barrett's esophagus pedigrees and 92 multiplex Barrett's esophagus pedigrees, fitting a multivariate logistic model that incorporates family history and clinical risk factors. The eight risk factors, age, sex, education level, parental status, smoking, heartburn frequency, regurgitation frequency, and use of acid suppressant, were included in the model. The prediction accuracy was evaluated on the training dataset and an independent validation dataset of 643 multiplex Barrett's esophagus pedigrees. RESULTS Our results indicate family information helps to predict Barrett's esophagus risk, and predicting in families improves both prediction calibration and discrimination accuracy. CONCLUSIONS Our model can predict Barrett's esophagus risk for anyone with family members known to have, or not have, had Barrett's esophagus. It can predict risk for unrelated individuals without knowing any relatives' information. IMPACT Our prediction model will shed light on effectively identifying high-risk individuals for Barrett's esophagus screening and surveillance, consequently allowing intervention at an early stage, and reducing mortality from esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 25(5); 727-35. ©2016 AACR.
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Affiliation(s)
- Xiangqing Sun
- Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio
| | - Robert C Elston
- Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Jill S Barnholtz-Sloan
- Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Gary W Falk
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - William M Grady
- Clinical Research Division, Fred Hutchinson Cancer Research Center and Gastroenterology Division, University of Washington School of Medicine, Seattle, Washington
| | - Ashley Faulx
- Division of Gastroenterology and Hepatology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio. Division of Gastroenterology and Hepatology, Louis Stokes Veterans Administration Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Sumeet K Mittal
- Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska
| | - Marcia Canto
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Nicholas J Shaheen
- Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
| | - Jean S Wang
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri
| | - Prasad G Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Julian A Abrams
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Ye D Tian
- Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio
| | - Joseph E Willis
- Department of Pathology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Kishore Guda
- Division of General Medical Sciences (Oncology), Case Comprehensive Cancer Center, Cleveland, Ohio
| | - Sanford D Markowitz
- Department of Medicine and Case Comprehensive Cancer Center, Case Medical Center, Case Western Reserve University, Cleveland, Ohio
| | - Apoorva Chandar
- Division of Gastroenterology and Hepatology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - James M Warfe
- Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio
| | - Wendy Brock
- Division of Gastroenterology and Hepatology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Amitabh Chak
- Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio. Division of Gastroenterology and Hepatology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
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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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Choe JW, Kim YC, Joo MK, Kim HJ, Lee BJ, Kim JH, Yeon JE, Park JJ, Kim JS, Byun KS, Bak YT. Application of the Prague C and M criteria for endoscopic description of columnar-lined esophagus in South Korea. World J Gastrointest Endosc 2016; 8:357-361. [PMID: 27114749 PMCID: PMC4835663 DOI: 10.4253/wjge.v8.i8.357] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 09/16/2015] [Accepted: 12/02/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To ascertain whether the Prague circumferential (C) length and maximal (M) length criteria for grading the extent of Barrett’s esophagus can be applied prior to its widespread application in South Korea.
METHODS: Two hundred and thirteen consecutive cases with endoscopic columnar-lined esophagus (CLE) were included and classified according to the Prague C and M criteria.
RESULTS: Of 213 cases with CLE, the distribution of maximum CLE lengths was: 0.5-0.9 cm in 99 cases (46.5%); 1.0-1.4 cm in 63 cases (29.6%); 1.5-1.9 cm in 15 cases (7.0%); 2.0-2.4 cm in 14 cases (6.6%); 2.5-2.9 cm in 1 case (0.5%); and 7.0 cm in 1 case (0.5%). Twenty cases (9.4%) had columnar islands alone. Two hundred and eight cases (97.7%) lacked the circumferential CLE component (C0Mx). Columnar islands were found in 70 cases (32.9%), of which 20 cases (9.4%) had columnar islands alone.
CONCLUSION: In regions where most CLE patients display short or ultrashort tongue-like appearance, more detailed descriptions of CLE’s in < 1.0 cm lengths and columnar islands, as well as avoidance of repeating the prefix “C0” need to be considered in parallel with the widespread application of the Prague system in South Korea.
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Thrift AP. Esophageal Adenocarcinoma: The Influence of Medications Used to Treat Comorbidities on Cancer Prognosis. Clin Gastroenterol Hepatol 2015; 13:2225-32. [PMID: 25835331 DOI: 10.1016/j.cgh.2015.03.028] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Revised: 03/23/2015] [Accepted: 03/25/2015] [Indexed: 02/07/2023]
Abstract
Esophageal adenocarcinoma has undergone a continuous rise in incidence since the early 1970s and is the fastest rising cancer among white men in the United States. Epidemiologic studies have demonstrated that medications commonly used to treat multiple chronic conditions (for example, aspirin, non-aspirin nonsteroidal anti-inflammatory drugs, and statins) as well as powerful acid suppressants such as proton pump inhibitors are associated with a reduced risk of esophageal adenocarcinoma. The chemopreventive potential of these classes of medications appears to be especially applicable to persons with Barrett's esophagus, the only known premalignant condition for esophageal adenocarcinoma. However, it is not known whether these medications also influence cancer recurrence and cancer-specific mortality in persons diagnosed with esophageal adenocarcinoma. This is an important question because most patients with esophageal adenocarcinoma have 1 or more comorbid conditions at the time of their cancer diagnosis and are receiving medication to treat these conditions. This article summarizes the evidence on the associations between 4 commonly used classes of medications and (1) risk of developing esophageal adenocarcinoma and Barrett's esophagus and (2) risk of cancer recurrence and cancer-specific mortality in patients with esophageal adenocarcinoma.
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Affiliation(s)
- Aaron P Thrift
- Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
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Runge TM, Abrams JA, Shaheen NJ. Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterol Clin North Am 2015; 44:203-31. [PMID: 26021191 PMCID: PMC4449458 DOI: 10.1016/j.gtc.2015.02.001] [Citation(s) in RCA: 154] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC), a disease with increasing burden in the Western world, especially in white men. Risk factors for BE include obesity, tobacco smoking, and gastroesophageal reflux disease (GERD). EAC is the most common form of esophageal cancer in the United States. Risk factors include GERD, tobacco smoking, and obesity, whereas nonsteroidal antiinflammatory drugs and statins may be protective. Factors predicting progression from nondysplastic BE to EAC include dysplastic changes on esophageal histology and length of the involved BE segment. Biomarkers have shown promise, but none are approved for clinical use.
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Affiliation(s)
- Thomas M. Runge
- University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, NC
| | - Julian A. Abrams
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY
| | - Nicholas J. Shaheen
- University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, NC
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Wang RH. From reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma. World J Gastroenterol 2015; 21:5210-5219. [PMID: 25954094 PMCID: PMC4419061 DOI: 10.3748/wjg.v21.i17.5210] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Revised: 01/19/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
The occurrence of gastroesophageal reflux disease is common in the human population. Almost all cases of esophageal adenocarcinoma are derived from Barrett’s esophagus, which is a complication of esophageal adenocarcinoma precancerous lesions. Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett’s esophagus. The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia, which is closely associated with the development of esophageal adenocarcinoma. However, the exact mechanism of injury is not completely understood. Various animal models of the developmental mechanisms of disease, and theoretical and clinical effects of drug treatment have been widely used in research. Recently, animal models employed in studies on gastroesophageal reflux injury have allowed significant progress. The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results. In this article, various modeling methods are reviewed, with discussion of the major findings on the developmental mechanism of Barrett’s esophagus, which should help to develop better prevention and treatment strategies for Barrett’s esophagus.
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Winzer BM, Paratz JD, Whitehead JP, Whiteman DC, Reeves MM. The feasibility of an exercise intervention in males at risk of oesophageal adenocarcinoma: a randomized controlled trial. PLoS One 2015; 10:e0117922. [PMID: 25706622 PMCID: PMC4338269 DOI: 10.1371/journal.pone.0117922] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Accepted: 01/02/2015] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE To investigate the feasibility and safety of a 24-week exercise intervention, compared to control, in males with Barrett's oesophagus, and to estimate the effect of the intervention, compared to control, on risk factors associated with oesophageal adenocarcinoma development. METHODS A randomized controlled trial of an exercise intervention (60 minutes moderate-intensity aerobic and resistance exercise five days/week over 24 weeks; one supervised and four unsupervised sessions) versus attention control (45 minutes stretching five days/week over 24 weeks; one supervised and four unsupervised sessions) in inactive, overweight/obese (25.0-34.9 kg/m2) males with Barrett's oesophagus, aged 18-70 years. Primary outcomes were obesity-associated hormones relevant to oesophageal adenocarcinoma risk (circulating concentrations of leptin, adiponectin, interleukin-6, tumour necrosis factor-alpha, C-reactive protein, and insulin resistance [HOMA]). Secondary outcomes included waist circumference, body composition, fitness, strength and gastro-oesophageal reflux symptoms. Outcomes were measured at baseline and 24-weeks. Intervention effects were analysed using generalised linear models, adjusting for baseline value. RESULTS Recruitment was difficult in this population with a total of 33 participants recruited (target sample size: n = 80); 97% retention at 24-weeks. Adherence to the exercise protocol was moderate. No serious adverse events were reported. A statistically significant intervention effect (exercise minus control) was observed for waist circumference (-4.5 [95% CI -7.5, -1.4] cm; p < 0.01). Effects on primary outcomes were not statistically significant. CONCLUSION This small, exploratory trial provides important information to inform future trial development including recruitment rates and estimates of effect sizes on outcomes related to oesophageal adenocarcinoma risk. Future trials should investigate a combined dietary and exercise intervention to achieve greater weight loss in this population and relax inclusion criteria to maximize recruitment. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000401257.
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Affiliation(s)
- Brooke M. Winzer
- Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Australia
| | - Jennifer D. Paratz
- Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Australia
| | - Jonathan P. Whitehead
- Metabolic Medicine Group, Mater Research Institute University of Queensland, Brisbane, Australia
| | - David C. Whiteman
- Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Marina M. Reeves
- Cancer Prevention Research Centre, School of Public Health, The University of Queensland, Brisbane, Australia
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Abdallah J, Maradey-Romero C, Lewis S, Perzynski A, Fass R. The relationship between length of Barrett's oesophagus mucosa and body mass index. Aliment Pharmacol Ther 2015; 41:137-44. [PMID: 25327893 DOI: 10.1111/apt.12991] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 09/11/2014] [Accepted: 09/26/2014] [Indexed: 01/12/2023]
Abstract
BACKGROUND Length of Barrett's oesophagus (BE) is a risk factor for oesophageal cancer. The underlying mechanisms that determine BE length are nor fully known. AIM To determine if there is a correlation between obesity and length of BE. METHODS Using a population-based study, 381 patients diagnosed with Barrett's oesophagus between 1999 and 2013 were included. Body mass index (BMI) at the time of BE diagnosis was calculated. Upper endoscopy reports were reviewed to obtain the length of BE. Spearman's correlation coefficient was performed to assess the strength of the relationship between Barrett's length and BMI. A multivariate logistic regression analysis was conducted to further examine the association between BMI and length of BE. RESULTS The adjusted odds ratio for each five-point increase in BMI was 1.5 (95% CI 1.24-1.81, P < 0.001). The mean BMI was significantly higher in patients with long segment BE as compared to patients with short segment BE (32.7 vs. 30.3, P = 0.001). There was also a positive trend in long segment BE as patients entered into higher BMI categories (Z = 4.25, P < 0.001). There was a significant correlation between BMI and length of BE (r = 0.25, P < 0.0001). CONCLUSION The study demonstrated a correlation between BMI and the length of Barrett's oesophagus mucosa. Thus, increased BMI is associated with longer segment of Barrett's oesophagus.
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Affiliation(s)
- J Abdallah
- Division of Gastroenterology and Hepatology, The Esophageal and Swallowing Center, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
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The incidence of esophageal adenocarcinoma in a national veterans cohort with Barrett's esophagus. Am J Gastroenterol 2014; 109:1862-8; quiz 1861, 1869. [PMID: 25331350 DOI: 10.1038/ajg.2014.324] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Revised: 09/08/2014] [Accepted: 09/09/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The increasing incidence of esophageal adenocarcinoma (EA) in the United States may have leveled off in recent years. The risk of EA among patients with Barrett's esophagus (BE) seems to be decreasing in several European cohorts, but these estimates are unknown in the United States. We aimed to determine the risk of developing EA in a national cohort of BE patients in the US Veterans Health Administration and to account for the use of endoscopic ablation and esophagectomy. METHODS This was a retrospective cohort study from a total of 121 facilities in the Veterans Health Administration. Veteran patients with BE diagnosed between 1 October 2003 and 30 September 2009 were included and followed until esophageal cancer diagnosis, death or 30 September 2011. All EA diagnoses were verified in detailed structured reviews of medical records. RESULTS We identified 29,536 patients with BE who met our eligibility criteria. Most were men (96.9%) and White (83.2%), with a mean age of 61.8 years. During 144,949 person-years of follow-up, 466 patients developed EA, yielding an incidence rate of 3.21 per 1,000 person-years (95% confidence interval (CI) 2.94-3.52). Excluding those who developed EA within 1 year of their index BE date lowered the incidence rate to 1.75 per 1,000 person-years. However, including additional patients who underwent endoscopic ablation or esophagectomy for HGD or EA increased the incidence rate to 4.79 (95% CI 4.44-5.16). CONCLUSIONS The incidence of EA in a US national cohort of mostly male veterans may be lower than previous estimates. Almost half of the EA cases were diagnosed within 1 year of their BE index date.
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The case for ablating nondysplastic Barrett's esophagus. Gastrointest Endosc 2014; 80:866-72. [PMID: 25436398 DOI: 10.1016/j.gie.2014.06.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 06/03/2014] [Indexed: 02/08/2023]
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Tolone S, Limongelli P, Romano M, Federico A, Docimo G, Ruggiero R, Brusciano L, Del Genio G, Docimo L. The patterns of reflux can affect regression of non-dysplastic and low-grade dysplastic Barrett's esophagus after medical and surgical treatment: a prospective case-control study. Surg Endosc 2014; 29:648-57. [PMID: 25030477 DOI: 10.1007/s00464-014-3713-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Accepted: 06/30/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND To date, therapeutic guidelines and pattern of reflux for patients with no-dysplasia (ND) or low-grade dysplasia (LGD) Barrett's esophagus (BE) remain unclear. We aimed to analyze pattern of reflux and regression of ND- or LGD-BE after medical and surgical treatment. METHODS We studied a cohort of ND- and LGD-BE patients who underwent laparoscopic total fundoplication and a cohort of ND- and LGD-BE patients managed medically. Patients were matched for age, sex, and disease duration. After 1 year of follow-up at least, all patients underwent upper endoscopy with esophageal biopsies to evaluate any histological changes, as well as manometry and impedance-pH-metry to re-assess reflux patterns. RESULTS Thirty-seven patients (20 LGD, 17 ND) undergoing laparoscopic fundoplication were enrolled and compared with 25 patients (13 LGD, 12 ND) managed with proton pump inhibitors (PPI). Laparoscopic fundoplication resulted in a better control of both acidic and weakly acidic reflux (P < 0.001) and was associated with a higher probability of reversion for LGD (P < 0.01). Esophageal motility did not differ between surgically and medically treated patients. CONCLUSIONS In patients with ND- or LGD-BE, laparoscopic fundoplication seems to warrant a better control of all kinds of refluxate and it is associated with a higher likelihood of reversion of both LGD- and ND-BE, compared with PPI therapy.
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Affiliation(s)
- Salvatore Tolone
- Division of General and Bariatric Surgery, Department of Surgery, Second University of Naples, Via Pansini, 5, 80131, Naples, NA, Italy,
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Abstract
GOALS To evaluate the incidence of extraesophageal malignancies among patients with Barrett esophagus (BE). BACKGROUND Gastroesophageal reflux disease has been reported to be associated with upper aerodigestive malignancies. BE is considered a consequence of long-standing gastroesophageal reflux disease; however, the association of BE with extraesophageal malignancies is controversial. STUDY The database of the largest health service provider in Israel was queried for all patients diagnosed with BE between 2000 and 2010. Data regarding medical background and diagnosis of malignancy were recorded. Malignancy rates were compared with subjects without BE or malignancy and matched for age, sex, and smoking status (1:4 ratio). Patients in whom a malignancy was diagnosed within 1 year of BE diagnosis were excluded. RESULTS A total of 3669 patients with BE and 14,676 controls were included. Several nonesophageal malignancies were significantly more prevalent among BE patients: colorectal cancer (relative risk 1.98, P<0.001) and prostate cancer (relative risk 1.99, P<0.001), but not cancer of the upper aerodigestive tract. Multivariate analysis revealed that Jewish origin and the presence of BE were associated with higher malignancy risk [hazard ratio (HR) 1.83, HR 1.41, respectively; P<0.001]; body mass index was inversely associated with malignancy risk (HR 0.98; P<0.005). CONCLUSIONS BE seems to be associated with colorectal and prostate cancer. Further research is necessary to determine whether this is a causative relationship and, consequently, whether a change in the screening policy for colorectal cancer in patients with BE is warranted.
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Watari J, Oshima T, Fukui H, Tomita T, Miwa H. Carcinogenesis of Barrett's esophagus: a review of the clinical literature. Clin J Gastroenterol 2013; 6:399-414. [PMID: 26182128 DOI: 10.1007/s12328-013-0412-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2013] [Accepted: 07/25/2013] [Indexed: 11/25/2022]
Abstract
Barrett's esophagus (BE) is a premalignant condition of esophageal adenocarcinoma (EAC). Although the incidence of BE has risen rapidly in the West, it is rare in Asia despite a recent increase in the prevalence of gastroesophageal reflux disease. Controversies over the definition of BE are presented because most cases show short-segment BE, especially ultra-short BE, in Asia. Here we review possible risk factors for the development of EAC, particularly possible roles of ethnicity, specialized intestinal metaplasia (SIM), BE length, and environmental factors, such as Helicobacter pylori infection and obesity. Additionally, we summarize recent studies on the effect of chemoprevention including proton pump inhibitors, nonsteroidal anti-inflammatory drugs or aspirin in order to reduce the risk of neoplastic progression in BE patients. Although substantial knowledge of risk factors of dysplasia/EAC in BE is shown, the risk for neoplastic development may be influenced by geographic variation, study population, the presence or absence of SIM or dysplasia at baseline, and the small number of BE patients investigated. Recently, the efficiency of surveillance for BE patients has been discussed from the standpoint of cost-effectiveness. It may be too difficult to draw conclusions because no randomized clinical trials of BE surveillance have been performed.
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Affiliation(s)
- Jiro Watari
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Tadayuki Oshima
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hirokazu Fukui
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Toshihiko Tomita
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hiroto Miwa
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
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A statistical study of esophageal lesions in Egypt when correlated with Ki-67 activity in GERD, Barrett’s esophagus, and carcinoma of the esophagus. ACTA ACUST UNITED AC 2013. [DOI: 10.1097/01.xej.0000436654.76150.18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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[Barrett's esophagus: analyses from human and experimental animal studies]. DER PATHOLOGE 2013; 34:138-47. [PMID: 23430135 DOI: 10.1007/s00292-012-1731-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Whereas attention in the past has been focused on goblet cells as the primary marker for Barrett's esophagus (BE), the recent change in the definition now includes the non-goblet cell columnar cell-lined esophagus. In the present study the histological features of neoplasia of the lower esophagus and esophago-gastric junction in a German cohort were examined using immunohistochemical staining for MUC, CD10, intestinal and gastric type major tight junction proteins (claudins). Experimental studies using rat duodenogastric content reflux models have also been performed and data show that most neoplastic lesions of the esophageal glands in humans express gastric mucin phenotypes. Cardiac type mucosa was the main histological type in the surrounding mucosa of neoplastic lesions; however, most cardiac type mucosa has intestinal type tight junction proteins. BE with goblet cells has been reported to originate from stem cells located in the basal layer of esophageal squamous cell epithelium in previous models. However, the cardiac type mucosa seems to develop from the site of the stomach and not from the basal layer of esophageal squamous cell epithelium according to our model.
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Duggan C, Onstad L, Hardikar S, Blount PL, Reid BJ, Vaughan TL. Association between markers of obesity and progression from Barrett's esophagus to esophageal adenocarcinoma. Clin Gastroenterol Hepatol 2013; 11:934-43. [PMID: 23466711 PMCID: PMC3722274 DOI: 10.1016/j.cgh.2013.02.017] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Accepted: 02/18/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Individuals with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EA). Obesity contributes to the development of BE and its progression to cancer. We investigated the roles of obesity-induced hyperinsulinemia and dysregulation of adipokines in these processes. METHODS We measured fasting levels of glucose, insulin, leptin, and adiponectin in 392 patients enrolled in the Seattle Barrett's Esophagus Study. We calculated homeostatic model assessment scores (a measure of insulin sensitivity) and identified subjects with metabolic syndrome. We evaluated the association between these measures and the risk of EA using Cox regression models adjusted for known risk factors. RESULTS Increasing homeostatic model assessment scores were associated with an increasing risk for EA; the strongest association was observed within the first 3 years after participants entered the study (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.43-4.1; P trend = .001). Leptin level also was associated significantly with an increased risk of EA within 3 years (HR, 2.51; 95% CI, 1.09-5.81; P trend = .03) and 6 years (HR, 2.07; 95% CI, 1.01-4.26; P trend = .048) of baseline. The level of high-molecular-weight adiponectin had a nonlinear inverse association with risk of EA; the strongest associations were observed in the second tertile (HR, 0.34; 95% CI, 0.14-0.82). Metabolic syndrome was not associated with risk of EA. CONCLUSIONS Among patients with BE, increased levels of leptin and insulin resistance are associated with increased risk for EA, whereas increased levels of high-molecular-weight adiponectin is associated inversely with EA. These biomarkers might be used to determine cancer risk among patients with BE.
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Affiliation(s)
- Catherine Duggan
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Lynn Onstad
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Sheetal Hardikar
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Patricia L Blount
- Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Department of Medicine, University of Washington, Seattle, WA, USA
| | - Brian J Reid
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Department of Medicine, University of Washington, Seattle, WA, USA,Department of Genome Sciences, University of Washington, Seattle, WA, USA
| | - Thomas L Vaughan
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Department of Epidemiology, University of Washington, Seattle, WA, USA
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43
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Solaymani-Dodaran M, Card TR, West J. Cause-specific mortality of people with Barrett's esophagus compared with the general population: a population-based cohort study. Gastroenterology 2013; 144:1375-83, 1383.e1. [PMID: 23583429 DOI: 10.1053/j.gastro.2013.02.050] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Revised: 01/29/2013] [Accepted: 02/05/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Understanding the causes of death in people with Barrett's esophagus (BE) could guide evidence-based practice in the follow-up of these patients. METHODS We identified individuals diagnosed with BE in the UK's Clinical Practice Research Datalink and linked their information with that from England's Hospital Episode Statistics database. Eligible patients (N = 8448) were matched with individuals without BE for age, sex, and general practice (controls, N = 155,212). Causes of death were obtained from the UK's Office for National Statistics. Cox proportional hazard regression, excluding data from the first year of follow-up, was used to estimate hazard ratios and cumulative mortality. Absolute excess risks were calculated by subtracting cause-specific mortality values of controls from those of patients with BE. RESULTS Compared with the control population, patients with BE had increased risks of death from neoplasms and from respiratory and digestive causes but not from circulatory disorders. The annual mortality rate from esophageal cancer among patients with BE was 0.14%; 4.5% of deaths among these patients resulted from this cancer, leading to a cumulative 10-year risk of almost 2%. Nonetheless, the largest single cause of death among patients with BE was ischemic heart disease (5.6 per 1000 patients); 168 patients with BE died of this cause, nearly 4-fold the number that died of esophageal cancer. CONCLUSIONS Among patients with BE, approximately 2% will die of esophageal cancer within 10 years. However, patients with BE died more frequently of other causes, such as ischemic heart disease. Evidence-based strategies are available to prevent this disease and might be more cost-effective for reducing mortality among patients with BE.
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Affiliation(s)
- Masoud Solaymani-Dodaran
- Minimally Invasive Surgery Research Center, Tehran University of Medical Sciences, Rasoul Akram Hospital, Tehran, Iran.
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Rubenstein JH, Morgenstern H, Appelman H, Scheiman J, Schoenfeld P, McMahon LF, Metko V, Near E, Kellenberg J, Kalish T, Inadomi JM. Prediction of Barrett's esophagus among men. Am J Gastroenterol 2013; 108:353-62. [PMID: 23318485 PMCID: PMC3903120 DOI: 10.1038/ajg.2012.446] [Citation(s) in RCA: 127] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Risk factors for Barrett's esophagus include gastroesophageal reflux disease (GERD) symptoms, age, abdominal obesity, and tobacco use. We aimed to develop a tool using these factors to predict the presence of Barrett's esophagus. METHODS Male colorectal cancer (CRC) screenees were recruited to undergo upper endoscopy, identifying newly diagnosed cases of Barrett's esophagus. Logistic regression models predicting Barrett's esophagus using GERD symptoms alone and together with abdominal obesity, tobacco use, and age were compared. RESULTS Barrett's esophagus was found in 70 (8.5%) of 822 CRC screenees. Mutually adjusting for other covariates, Barrett's esophagus was associated with weekly GERD (odds ratio (OR)=2.33, 95% confidence interval (CI)=1.34, 4.05), age (OR per 10 years=1.53, 95% CI=1.05, 2.25), waist-to-hip ratio (OR per 0.10=1.44, 95% CI=0.898, 2.32) and pack-years of cigarette use (OR per 10 pack-years=1.09, 95% CI=1.04, 1.14). A model including those four factors had a greater area under the receiver operating characteristics curve than did a model based on GERD frequency and duration alone (0.72 vs. 0.61, P<0.001), and it had a net reclassification improvement index of 19-25%. CONCLUSIONS The prevalence of Barrett's esophagus was substantial in our population of older overweight men. A model based on GERD, age, abdominal obesity, and cigarette use more accurately classified the presence of Barrett's esophagus than did a model based on GERD alone. Following validation of the tool in another population, its use in clinical practice might improve the efficiency of screening for Barrett's esophagus.
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Affiliation(s)
- Joel H. Rubenstein
- Center for Clinical Management Research, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan, USA,Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Hal Morgenstern
- Departments of Epidemiology and Environmental Health Sciences, School of Public Health, and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA
| | - Henry Appelman
- Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - James Scheiman
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Philip Schoenfeld
- Center for Clinical Management Research, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan, USA,Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Laurence F. McMahon
- Department of Internal Medicine, Division of General Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Valbona Metko
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Ellen Near
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Joan Kellenberg
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Tal Kalish
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - John M. Inadomi
- Department of Internal Medicine, Division of Gastroenterology, University of Washington Medical School, Seattle, Washington, USA
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Chan LW, Wang YN, Lin LY, Upton MP, Hwang JH, Pun SH. Synthesis and characterization of anti-EGFR fluorescent nanoparticles for optical molecular imaging. Bioconjug Chem 2013; 24:167-75. [PMID: 23273065 DOI: 10.1021/bc300355y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Molecular imaging, the visualization of molecular and cellular markers, is a promising method for detection of dysplasia and early cancer in the esophagus and can potentially be used to identify regions of interest for biopsy or tumor margins for resection. EGFR is a previously reported cell surface receptor with stepwise increases in expression during the progression from Barrett's metaplasia to adenocarcinoma. In this work, a 200 nm fluorescent nanoparticle contrast agent was synthesized for targeted imaging of EGFR through a series of surface modifications to dye-encapsulated polystyrene particles. Amino-functionalized polystyrene particles were PEGylated using a heterobifunctional PEG linker. Subsequently, thiolated M225 antibodies were conjugated to maleimide functional groups on attached PEGs for EGFR targeting. In vitro binding studies using flow cytometry demonstrated specific binding of M225-PEG-NP to EGFR-expressing cells with minimal nonspecific binding in EGFR(-) cells. Binding was shown to increase proportionally with the number of conjugated M225 antibodies. Adsorbed formulations with unmodified M225 antibodies, M225 + PEG-NP, were synthesized using the same antibody feeds used in M225-PEG-NP synthesis to determine the contribution of adsorbed antibodies to EGFR targeting. Adsorbed antibodies were less efficient at mediated nanoparticle targeting to EGFR than conjugated antibodies. Finally, M225-PEG-NP demonstrated binding to EGFR-expressing regions in human esophageal tissue sections.
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Affiliation(s)
- Leslie W Chan
- Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
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Effects of feeding on luminal pH and morphology of the gastroesophageal junction of snakes. ZOOLOGY 2012; 115:319-29. [DOI: 10.1016/j.zool.2012.04.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2011] [Revised: 04/02/2012] [Accepted: 04/12/2012] [Indexed: 11/23/2022]
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Frankel A, Nancarrow D, Wayte N, Barbour A. Clinical issues in oesophageal adenocarcinoma: could DNA copy number hold the key? ANZ J Surg 2012; 82:599-606. [PMID: 22856687 DOI: 10.1111/j.1445-2197.2012.06144.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2011] [Indexed: 01/10/2023]
Abstract
While not being considered a common cancer, since 1975 oesophageal adenocarcinoma (OAC) has had the fastest-rising incidence of any malignancy in Caucasian Western populations. In the absence of major improvements in treatment since this rise began, the number of deaths has also increased rapidly. In contrast, there have been significant advances in basic science in this period. One such advance is the discovery of DNA copy number aberrations (CNAs), and their potential role in carcinogenesis. The study of CNAs offers the potential to answer fundamental clinical questions in OAC, which in turn may lead to improved diagnosis, staging and treatment. This review outlines current clinical dilemmas in OAC, discusses the role that CNAs have been shown to play to date and highlights potential future applications.
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Affiliation(s)
- Adam Frankel
- School of Medicine, University of Queensland, Woolloongabba, Queensland, Australia.
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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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Ki-67 Antigen Overexpression Is Associated with the Metaplasia-Adenocarcinoma Sequence in Barrett's Esophagus. Gastroenterol Res Pract 2012; 2012:639748. [PMID: 22844273 PMCID: PMC3401558 DOI: 10.1155/2012/639748] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Accepted: 05/26/2012] [Indexed: 01/17/2023] Open
Abstract
Introduction. The objective of this study was to evaluate Ki-67 antigen expression in patients with Barrett's esophagus and esophageal adenocarcinoma and to assess its correlation with the metaplasia-esophageal adenocarcinoma progression. Methods. Using immunohistochemistry we evaluated the Ki-67 index in patients with Barrett's esophagus, esophageal adenocarcinoma, and controls. We included patients with endoscopically visible columnar mucosa of the distal esophagus (whose biopsies revealed specialized intestinal-type metaplasia), patients with esophageal and esophagogastric tumors types I and II, and patients with histologically normal gastric mucosa (control). Results. In the 57 patients studied there were no statistically significant differences between the groups with respect to age or race. Patients with cancer were predominantly men. The Ki-67 index averaged 10 ± 4
% in patients with normal gastric mucosa (n = 17), 21 ± 15
% in patients with Barrett's esophagus (n = 21), and 38 ± 16
% in patients with cancer (n = 19).
Ki-67 expression was significantly different between all groups (P < 0.05).
There was a strong linear correlation between Ki-67 expression and the metaplasia-adenocarcinoma sequence (P < 0.01).
In patients with cancer, Ki-67 was not associated with clinical or surgical staging. Conclusions. Ki-67 antigen has increased expression along the metaplasia-adenocarcinoma sequence. There is a strong linear correlation between Ki-67 proliferative activity and Barrett's carcinogenesis.
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Panjehpour M, Overholt BF, Vo-Dinh T, Coppola D. The effect of reactive atypia/inflammation on the laser-induced fluorescence diagnosis of non-dysplastic Barrett's esophagus. Lasers Surg Med 2012; 44:390-6. [PMID: 22535652 PMCID: PMC3371107 DOI: 10.1002/lsm.22033] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/03/2012] [Indexed: 11/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Differential Normalized Fluorescence (DNF) technique has been used to distinguish high-grade dysplasia from non-dysplastic Barrett's esophagus. This technology may assist gastroenterologists in targeting biopsies, reducing the number of biopsies using the standard protocol. In the presence of reactive atypia/inflammation, it becomes difficult for the pathologist to differentiate non-dysplastic Barrett's esophagus from Barrett's esophagus with low-grade dysplasia. Before DNF technique may be used to guide target biopsies, it is critical to know whether reactive atypia/inflammation in non-dysplastic Barrett's may result in false positives. This study was conducted to determine whether DNF technique is adversely affected by the presence of reactive atypia/inflammation in non-dysplastic Barrett's esophagus resulting in false positives. STUDY DESIGN/MATERIALS AND METHODS Four hundred ten-nanometer laser light was used to induce autofluorescence of Barrett's mucosa in 49 patients. The clinical study included 37 males and 12 females. This was a blinded retrospective data analysis study. A total of 303 spectra were collected and matched to non-dysplastic Barrett's biopsy results. One hundred seventy-five spectra were collected from areas with a pathology of non-dysplastic Barrett's esophagus with reactive atypia/inflammation. One hundred twenty-eight spectra were collected from areas with non-dysplastic Barrett's esophagus without reactive changes/inflammation. The spectra were analyzed using the DNF Index at 480 nm and classified as positive or negative using the threshold of -0.75 × 10(-3). RESULTS Using DNF technique, 92.6% of non-dysplastic samples with reactive atypia/inflammation were classified correctly (162/175). 92.2% of non-dysplastic samples without reactive atypia/inflammation were classified correctly (118/128). Comparing the ratios of false positives among the two sample groups, there was not a statistically significant difference between the two groups. CONCLUSION Using DNF technique for classification of non-dysplastic Barrett's mucosa does not result in false-positive readings due to reactive atypia/inflammation. Target biopsies guided by DNF technique may drastically reduce the number of pinch biopsies using the standard biopsy protocol.
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Affiliation(s)
- Masoud Panjehpour
- Laser Center, Thompson Cancer Survival Center, Knoxville, TN 37916, USA.
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