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Sparrelid E, Valls-Duran C, Danielsson O, Sun W, Engstrand J, Gilg S, Ghorbani P, Sturesson C, Jansson A. Ciliated hepatic foregut cysts: a large retrospective single-centre series. Scand J Gastroenterol 2025; 60:355-360. [PMID: 39950493 DOI: 10.1080/00365521.2025.2465622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 02/01/2025] [Accepted: 02/05/2025] [Indexed: 04/02/2025]
Abstract
OBJECTIVE This study aimed to provide insight about clinical management of ciliated hepatic foregut cysts (CHFC) at a tertiary centre. BACKGROUND CHFC is a rare cystic lesion of the liver with malignant potential according to previous reports. However, the current recommendation to resect all cysts in fit patients is based on limited evidence. METHODS Retrospective observational single-centre study including all patients with radiological suspicion of CHFC at Karolinska University Hospital during the years 2015-2022. Patients were characterised, mainly descriptively, regarding baseline characteristics, radiological and histopathological data, as well as data on follow-up. RESULTS A total of 41 patients with suspected CHFC were identified. Of these, 23 were operated and 18 only diagnosed radiologically. Of the operated, 19 patients (83%) had a histopathological examination confirming CHCF diagnosis. No patient had dysplasia or cancer in the specimen, and no patient developed cancer during a follow-up length (from first radiology) of 82 months (3-215). CONCLUSIONS CHFC can be diagnosed radiologically with acceptable accuracy. No patient in this study had malignant transformation, neither in the specimens nor during follow-up. Surgical treatment of CHCF for all patients fit for surgery should probably be challenged, but further studies supporting this change of management are needed.
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Affiliation(s)
- Ernesto Sparrelid
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Carlos Valls-Duran
- Division of Radiology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Olof Danielsson
- Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Wenwen Sun
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden
| | - Jennie Engstrand
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Stefan Gilg
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Poya Ghorbani
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Christian Sturesson
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Anders Jansson
- Department of Clinical Sciences, Karolinska Institutet, Danderyds Hospital, Stockholm, Sweden
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Umar N, Alleyne L, Cheung D, Rees J, Trudgill C, Zanetto U, Muzaffar S, Trudgill N. Variation in proliferative and cell cycle markers in Barrett's esophagus in relation to circumferential and axial location in the esophagus. Eur J Gastroenterol Hepatol 2024; 36:306-312. [PMID: 38251437 DOI: 10.1097/meg.0000000000002700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
BACKGROUND Adenocarcinoma in Barrett's esophagus (BE) occurs more frequently between 12 and 3 o'clock at the gastroesophageal junction (GEJ). METHODS BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined. RESULTS 110 patients: median age 64 (IQR, 56-71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6-5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o'clock, and overall was 49.6% higher in the 12-6 o'clock position compared to 6-12 o'clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00-2.12)]. A similar pattern was found with p21 [1.82 (1.00-3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29-2.34)]; Cyclo-oxygenase 2 [2.03 (1.48-2.78]) and p21 [2.06 (1.16-3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43-0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma. CONCLUSION Increased cellular proliferation was seen at 12-6 o'clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE.
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Affiliation(s)
- Nosheen Umar
- Sandwell and West Birmingham NHS Trust, West Bromwich, UK
| | - Lance Alleyne
- Sandwell and West Birmingham NHS Trust, West Bromwich, UK
| | - Danny Cheung
- Worcestershire Acute Hospitals NHS Trust, Worcester, UK
| | - James Rees
- Worcestershire Acute Hospitals NHS Trust, Worcester, UK
| | | | | | | | - Nigel Trudgill
- Sandwell and West Birmingham NHS Trust, West Bromwich, UK
- Institute of Cancer and Genomic Sciences, University of Birmingham, UK
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Gounella R, Granado TC, Hideo Ando Junior O, Luporini DL, Gazziro M, Carmo JP. Endoscope Capsules: The Present Situation and Future Outlooks. Bioengineering (Basel) 2023; 10:1347. [PMID: 38135938 PMCID: PMC10741108 DOI: 10.3390/bioengineering10121347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/04/2023] [Accepted: 11/20/2023] [Indexed: 12/24/2023] Open
Abstract
This paper presents new perspectives on photonic technologies for capsule endoscopy. It first presents a review of conventional endoscopy (upper endoscopy and colonoscopy), followed by capsule endoscopy (CE), as well as their techniques, advantages, and drawbacks. The technologies for CEs presented in this paper include integration with the existing endoscopic systems that are commercially available. Such technologies include narrow-band imaging (NBI), photodynamic therapy (PDT), confocal laser endomicroscopy (CLE), optical coherence tomography (OCT), and spectroscopy in order to improve the performance of the gastrointestinal (GI) tract examination. In the context of NBI, two optical filters were designed and fabricated for integration into endoscopic capsules, allowing for the visualization of light centered at the 415 nm and 540 nm wavelengths. These optical filters are based on the principle of Fabry-Perot and were made of thin films of titanium dioxide (TiO2) and silicon dioxide (SiO2). Moreover, strategies and solutions for the adaptation of ECs for PDT are also discussed.
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Affiliation(s)
- Rodrigo Gounella
- Group of Metamaterials Microwaves and Optics (GMeta), Department of Electrical Engineering (SEL), University of São Paulo (USP), Avenida Trabalhador São-Carlense, Nr. 400, Parque Industrial Arnold Schimidt, São Carlos 13566-590, Brazil; (T.C.G.); (J.P.C.)
| | - Talita Conte Granado
- Group of Metamaterials Microwaves and Optics (GMeta), Department of Electrical Engineering (SEL), University of São Paulo (USP), Avenida Trabalhador São-Carlense, Nr. 400, Parque Industrial Arnold Schimidt, São Carlos 13566-590, Brazil; (T.C.G.); (J.P.C.)
| | - Oswaldo Hideo Ando Junior
- Academic Unit of Cabo de Santo Agostinho (UACSA), Federal Rural University of Pernambuco (UFRPE), Cabo de Santo Agostinho 54518-430, Brazil;
| | - Daniel Luís Luporini
- Clinica Endoscopia São Carlos, Rua Paulino Botelho de Abreu Sampaio, 958, Centro, São Carlos 13561-060, Brazil;
| | - Mario Gazziro
- Information Engineering Group, Department of Engineering and Social Sciences (CECS), Federal University of ABC (UFABC), Av. dos Estados, 5001, Santo André 09210-580, Brazil;
| | - João Paulo Carmo
- Group of Metamaterials Microwaves and Optics (GMeta), Department of Electrical Engineering (SEL), University of São Paulo (USP), Avenida Trabalhador São-Carlense, Nr. 400, Parque Industrial Arnold Schimidt, São Carlos 13566-590, Brazil; (T.C.G.); (J.P.C.)
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Mejza M, Małecka-Wojciesko E. Diagnosis and Management of Barrett's Esophagus. J Clin Med 2023; 12:jcm12062141. [PMID: 36983142 PMCID: PMC10057256 DOI: 10.3390/jcm12062141] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/07/2023] [Accepted: 03/07/2023] [Indexed: 03/30/2023] Open
Abstract
Barrett's esophagus is a metaplastic change of esophageal mucosa, which can be characterized by its salmon-colored lining and the presence of columnar epithelium with goblet cells. It is a well-established precancerous state of esophageal adenocarcinoma, a tumor with very poor survival rates, which incidence is rapidly growing. Despite numerous research, the debate about its diagnosis and management is still ongoing. This article aims to provide an overview of the current recommendations and new discoveries regarding the subject.
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Affiliation(s)
- Maja Mejza
- Department of Digestive Tract Diseases, Medical University, 90-153 Lodz, Poland
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Rajendra S, Sharma P. Causal Link of Human Papillomavirus in Barrett Esophagus and Adenocarcinoma: Are We There Yet? Cancers (Basel) 2023; 15:cancers15030873. [PMID: 36765833 PMCID: PMC9913573 DOI: 10.3390/cancers15030873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/07/2023] [Accepted: 01/26/2023] [Indexed: 02/04/2023] Open
Abstract
Esophageal cancer is a relatively common malignancy worldwide with a high mortality (5-year survival of <15%). Despite screening, surveillance, improved imaging and treatment, the exponential rise in OAC continues. The strongest risk factors for OAC are chronic heartburn and metaplastic transformation of the lower third of the esophagus (Barrett's esophagus). The risk profile includes Caucasian race, male gender older age, obesity and smoking. Although the tumor risk in BO has been progressively revised downwards, the exponential rise in OAC remains unchecked. This paradox points to an unidentified missing link. Relatively recently, we provided the world's initial data for a strong association of biologically relevant hr-HPV with BD and OAC. Since then, systematic reviews and meta-analysis have documented HPV DNA prevalence rates in OAC of between 13 to 35%. In this review, we provide some evidence for a probable causal relationship between hr-HPV and OAC. This is challenging given the multifactorial etiology and long latency. Increasingly, high-risk HPV (hr-HPV) is regarded as a risk factor for OAC. This discovery will aid identification of a sub-group of high-risk progressors to esophageal cancer by surveillance and the development of effective preventive strategies including vaccination.
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Affiliation(s)
- Shanmugarajah Rajendra
- Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, NSW 2170, Australia
- South Western Sydney Clinical School, University of New South Wales, Kensington, Sydney, NSW 2052, Australia
- Department of Gastroenterology & Hepatology, Bankstown-Lidcombe Hospital, South-Western Sydney Local Health Network, Bankstown, Sydney, NSW 2200, Australia
- Correspondence: ; Tel.: +61-(0)-2-9722-8814; Fax: +61-(0)-9722-8570
| | - Prateek Sharma
- Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, MO 64128, USA
- School of Medicine, University of Kansas, Kansas City, MO 66160, USA
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Choi KKH, Sanagapalli S. Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies. World J Gastrointest Oncol 2022; 14:568-586. [PMID: 35321279 PMCID: PMC8919017 DOI: 10.4251/wjgo.v14.i3.568] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 11/12/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.
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Affiliation(s)
- Kevin Kyung Ho Choi
- AW Morrow Gastroenterology Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, NSW, Australia
| | - Santosh Sanagapalli
- Department of Gastroenterology, St Vincent’s Hospital, Darlinghurst 2010, NSW, Australia
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Fang HY, Stangl S, Marcazzan S, Carvalho MJB, Baumeister T, Anand A, Strangmann J, Huspenina JS, Wang TC, Schmid RM, Feith M, Friess H, Ntziachristos V, Multhoff G, Gorpas D, Quante M. Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett's esophagus. Eur J Nucl Med Mol Imaging 2022; 49:2049-2063. [PMID: 34882260 PMCID: PMC9016004 DOI: 10.1007/s00259-021-05582-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 10/03/2021] [Indexed: 01/21/2023]
Abstract
PURPOSE The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett's esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy. METHODS Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy. RESULTS Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized by human BE dysplastic patient-derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations. CONCLUSION In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients.
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Affiliation(s)
- Hsin-Yu Fang
- II Medizinische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany
| | - Stefan Stangl
- Department of Radiation Oncology and Central Institute for Translational Cancer Research, (TranslaTUM), Technische Universität München, Munich, Germany
| | - Sabrina Marcazzan
- II Medizinische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany ,Chair of Biological Imaging, School of Medicine, Technische Universität München, Munich, Germany; Helmholtz Zentrum München, Institute of Biological and Medical Imaging, Neuherberg, Germany
| | - Marcos J. Braz Carvalho
- II Medizinische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany
| | - Theresa Baumeister
- II Medizinische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany
| | - Akanksha Anand
- II Medizinische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany
| | - Julia Strangmann
- II Medizinische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany ,Innere Medizin II, Universitätsklinik Freiburg, Universität Freiburg, Freiburg im Breisgau, Germany
| | | | - Timothy C. Wang
- Department of Medicine, Columbia University Irving Medical Center, New York, NY USA
| | - Roland M. Schmid
- II Medizinische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany
| | - Marcus Feith
- Chirurgische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany
| | - Helmut Friess
- Chirurgische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany
| | - Vasilis Ntziachristos
- Chair of Biological Imaging, School of Medicine, Technische Universität München, Munich, Germany; Helmholtz Zentrum München, Institute of Biological and Medical Imaging, Neuherberg, Germany
| | - Gabriele Multhoff
- Department of Radiation Oncology and Central Institute for Translational Cancer Research, (TranslaTUM), Technische Universität München, Munich, Germany
| | - Dimitris Gorpas
- Chair of Biological Imaging, School of Medicine, Technische Universität München, Munich, Germany; Helmholtz Zentrum München, Institute of Biological and Medical Imaging, Neuherberg, Germany
| | - Michael Quante
- II Medizinische Klinik, Klinikum Rechts Der Isar, Technische Universität München, Munich, Germany ,Innere Medizin II, Universitätsklinik Freiburg, Universität Freiburg, Freiburg im Breisgau, Germany
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8
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Fang Y, Li W, Chen X. P63 Deficiency and CDX2 Overexpression Lead to Barrett's-Like Metaplasia in Mouse Esophageal Epithelium. Dig Dis Sci 2021; 66:4263-4273. [PMID: 33469811 PMCID: PMC8286978 DOI: 10.1007/s10620-020-06756-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 12/01/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND The cellular origin and molecular mechanisms of Barrett's esophagus (BE) are still controversial. Trans-differentiation is a mechanism characterized by activation of the intestinal differentiation program and inactivation of the squamous differentiation program. AIMS Renal capsule grafting (RCG) was used to elucidate whether CDX2 overexpression on the basis of P63 deficiency in the esophageal epithelium may generate intestinal metaplasia. METHODS P63-/-;Villin-Cdx2 embryos were generated by crossing P63+/- mice with Villin-Cdx2 mice. E18.5 esophagus was xenografted in a renal capsule grafting (RCG) model. At 1, 2, or 4 weeks after RCG, the mouse esophagus was immunostained for a proliferation marker (BrdU), squamous transcription factors (SOX2, PAX9), squamous differentiation markers (CK5, CK4, and CK1), intestinal transcription factors (CDX1, HNF1α, HNF4α, GATA4, and GATA6), intestinal columnar epithelial cell markers (A33, CK8), goblet cell marker (MUC2, TFF3), Paneth cell markers (LYZ and SOX9), enteroendocrine cell marker (CHA), and Tuft cell marker (DCAMKL1). RESULTS The P63-/-;Villin-Cdx2 RCG esophagus was lined with proliferating PAS/AB+ cuboidal cells and formed an intestinal crypt-like structure. The goblet cell markers (TFF3 and MUC2) and intestinal transcription factors (CDX1, HNF1α, HNF4α, GATA4, and GATA6) were expressed although no typical morphology of goblet cells was observed. Other intestinal cell markers including enteroendocrine cell marker (CHA), Paneth cell markers (LYZ and Sox9), and intestinal secretory cell marker (UEA/WGA) were also expressed in the P63-/-;Villin-Cdx2 RCG esophagus. Squamous cell markers (PAX9 and SOX2) were also expressed, suggesting a transitional phenotype. CONCLUSION CDX2 overexpression on the basis of P63 deficiency in esophageal epithelial cells induces Barrett's-like metaplasia in vivo. Additional factors may be needed to drive this transitional phenotype into full-blown BE.
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Affiliation(s)
- Yu Fang
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400045, China,Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George St., Durham, NC 27707. USA
| | - Wenbo Li
- Department of Gastroenterology, 960 Hospital, Clinical Teaching Hospital of JinZhou Medical University, Jinan 250031, China,Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George St., Durham, NC 27707. USA
| | - Xiaoxin Chen
- Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George St., Durham, NC 27707. USA
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Norita K, Koike T, Saito M, Shinkai H, Ami R, Abe Y, Dairaku N, Inomata Y, Kayaba S, Ishiyama F, Oikawa T, Ohyauchi M, Ito H, Asonuma S, Hoshi T, Kato K, Ohara S, Shimodaira Y, Watanabe K, Shimosegawa T, Masamune A, Iijima K. Long-term endoscopic surveillance for Barrett's esophagus in Japan: Multicenter prospective cohort study. Dig Endosc 2021; 33:1085-1092. [PMID: 33277694 DOI: 10.1111/den.13910] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 12/01/2020] [Accepted: 12/01/2020] [Indexed: 01/07/2023]
Abstract
OBJECTS Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient-years in Japan, the long-term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort. METHODS A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010-2012 and received at least one follow-up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma (EAC) were calculated as the number of events divided by patient-years of follow-up and were expressed as %/year. RESULTS Overall, the median endoscopic follow-up period was 59.9 (first and third quartiles, 48.5-60.8) months, constituting a total of 427 patient-years of observation. Since two EAC cases developed, the cancer incidence was 0.47% (0.01%-1.81%)/year. The cancer incidence was 0.39% (-0.16% to 2.44%) in 232 patient-years and 0.31% (-0.13% to 1.95%)/year in 318 patient-years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow-up, 12 of 92 patients (13.0%) died, but none died from EAC. CONCLUSION This is the largest prospective follow-up study with endoscopy to investigate the incidence of EAC in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large-scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs 1.2%/year).
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Affiliation(s)
- Kazuaki Norita
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Masahiro Saito
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Hirohiko Shinkai
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Reiko Ami
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Yasuhiko Abe
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Naohiro Dairaku
- Department of Gastroenterology, Iwaki Kyoritsu General Hospital, Fukushima, Japan
| | | | - Shoichi Kayaba
- Department of Gastroenterology, Iwate Prefectural Isawa Hospital, Iwate, Japan
| | - Fumitake Ishiyama
- Department of Gastroenterology, Iwate Prefectural Isawa Hospital, Iwate, Japan
| | - Tomoyuki Oikawa
- Department of Gastroenterology, Hachinohe City Hospital, Aomori, Japan
| | - Motoki Ohyauchi
- Department of Gastroenterology, Osaki Citizen Hospital, Miyagi, Japan
| | - Hirotaka Ito
- Department of Gastroenterology, Osaki Citizen Hospital, Miyagi, Japan
| | - Sho Asonuma
- Department of Gastroenterology, South Miyagi Medical Center, Miyagi, Japan
| | - Tatsuya Hoshi
- Department of Gastroenterology, Kesennuma City Hospital, Miyagi, Japan
| | - Katsuaki Kato
- Cancer Detection Center, Miyagi Cancer Society, Miyagi, Japan
| | - Shuichi Ohara
- Department of Gastroenterology, Tohoku Rosai Hospital, Miyagi, Japan
| | - Yosuke Shimodaira
- Department of Gastroenterology, Akita University School of Medicine, Akita, Japan
| | - Kenta Watanabe
- Department of Gastroenterology, Akita University School of Medicine, Akita, Japan
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan.,Department of Gastroenterology, South Miyagi Medical Center, Miyagi, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Katsunori Iijima
- Department of Gastroenterology, Akita University School of Medicine, Akita, Japan
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Westra WM, Straub D, Milano F, Buttar NS, Wang KK, Krishnadath KK. Inhibition of the BMP pathway prevents development of Barrett's-associated adenocarcinoma in a surgical rat model. Dis Esophagus 2021; 35:6412930. [PMID: 34718471 PMCID: PMC9113020 DOI: 10.1093/dote/doab072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/30/2021] [Accepted: 09/19/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Esophageal adenocarcinoma (EAC) is an aggressive cancer, associated with reflux esophagitis and intestinal metaplasia (IM). One underlying biological mechanism, which possibly drives the development of EAC, is the dysregulated expression of Bone Morphogenetic Proteins (BMPs). AIM To investigate if local delivery of Noggin, a BMP antagonist, reduced EAC. METHODS After obtaining proof of principal on local delivery of a Noggin/Sucralfate substance, a randomized controlled trial to test the effects of Noggin on EAC development was performed in a surgical rat model. In the model, an esophago-jejunostomy leads to development of reflux-esophagitis, IM and eventually EAC. Rats were treated by Noggin/Sucralfate or Sucralfate alone. Treatment was administered from 26 to 29 weeks after the operation. RESULTS Of the 112 operated rats, 52 survived beyond 26 weeks. Finally, 25 rats treated with Noggin/Sucralfate and 21 with Sucralfate, were evaluated. At the end, 39 (85%) of the animals had IM while 28 (61%) developed cancer. There were significantly more cancers in the Noggin/Sucralfate arm (50%) versus the Sucralfate group (73%) (Chi square, P < 0.05). Most cancers were mucous producing T3 adenocarcinomas. There were no significant differences in the amount of IM, size or grade of the cancers, or expression of columnar and squamous markers between the two groups. CONCLUSION In this study, we demonstrated that inhibition of BMPs by Noggin reduced development of EAC in a surgical esophagitis-IM-EAC rat model. In future, effective targeting of the BMP pathway with selective BMP-inhibitors could become an important asset to improve EAC patient outcome.
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Affiliation(s)
- Wytske M Westra
- Center for Experimental and Molecular Medicine (CEMM), AUMC, Amsterdam, The Netherlands,Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, The Netherlands,Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Danielle Straub
- Center for Experimental and Molecular Medicine (CEMM), AUMC, Amsterdam, The Netherlands
| | - Francesca Milano
- Center for Experimental and Molecular Medicine (CEMM), AUMC, Amsterdam, The Netherlands
| | - Navtej S Buttar
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kenneth K Wang
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kausilia K Krishnadath
- Address correspondence to: Professor Kausilia K. Krishnadath, Department of Gastroenterology, University of Amsterdam Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Tel: +31 20 5666703; Fax: +31 20 6917033;
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11
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Risk of Progression of Gastric Intestinal Metaplasia Is Significantly Greater When Detected in Both Antrum and Body. Dig Dis Sci 2021; 66:3470-3475. [PMID: 33094451 DOI: 10.1007/s10620-020-06659-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 10/06/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide. GC is usually preceded by a cascade of well-defined precursor lesions, set in place by an environmental trigger (H. pylori) including intestinal metaplasia (GIM) and dysplasia. AIMS To investigate the rates of progression of GIM to dysplasia and GC in a region of low gastric cancer incidence. METHODS We identified all patients diagnosed with GIM between January 1, 2008, and June 30, 2012. Any repeat upper endoscopy more than 1 year after index diagnosis and before December 31, 2018, was considered follow-up. Carcinomas the bulk of which were macroscopically located below the OGJ were considered primary gastric cancer. RESULTS Progression to more advanced lesions was observed in six patients (0.6%). Four patients (three male) developed GC at median age 74 years (SD 6). Two patients progressed to dysplasia (one male) at median age 71 years (SD 4). Patients with GIM in both gastric antrum and body were significantly more likely to progress than those with GIM in only one location (3.1% vs. 0.4%) (p value 0.017). Fifty-eight patients who had H. pylori eradicated were followed up. No progression to dysplasia or GC was noted in this group, with 28 patients having persistent GIM at follow-up. CONCLUSION Patients with GIM in both antrum and body had a significantly increased risk of progression and warrant close attention. This is comparable to routinely followed premalignant conditions such as Barrett's esophagus and Colonic Polyps, and appropriate surveillance protocols should be followed in this group.
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12
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Bornschein J, Quante M, Jansen M. The complexity of cancer origins at the gastro-oesophageal junction. Best Pract Res Clin Gastroenterol 2021; 50-51:101729. [PMID: 33975686 DOI: 10.1016/j.bpg.2021.101729] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 02/08/2021] [Indexed: 01/31/2023]
Abstract
Chronic acid-biliary reflux and Helicobacter pylori infection are instrumental environmental drivers of cancer initiation and progression in the upper gastrointestinal tract. Remarkably, although these environmental carcinogens are quite dissimilar, the tumour progression cascade these carcinogens engender is highly comparable. For this reason, studies of malignant progression occurring at the anatomic borderland between the oesophagus and the stomach have traditionally lumped junctional adenocarcinomas with either oesophageal adenocarcinoma or gastric adenocarcinoma. Whilst studies have revealed remarkable epidemiological and genetic similarities of these cancers and their associated premalignant conditions, these works have also revealed some key differences. This highlights that further scientific effort demands a dedicated focus on the understanding of the cell-cell interaction between the epithelium and the local microenvironment in this anatomic region. We here review available evidence with regards to tumour progression occurring at the gastro-oesophageal junction and contrast it with available data on cancer evolution in the metaplastic oesophagus and distal stomach.
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Affiliation(s)
- Jan Bornschein
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom and NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
| | - Michael Quante
- Klinik für Innere Medizin II, Universitätsklinikum Freiburg, Germany
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13
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Optimizing Outcomes with Radiofrequency Ablation of Barrett's Esophagus: Candidates, Efficacy and Durability. Gastrointest Endosc Clin N Am 2021; 31:131-154. [PMID: 33213792 DOI: 10.1016/j.giec.2020.09.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The treatment of early Barrett's esophagus (BE) has undergone a paradigm shift from surgical subtotal esophagectomy to organ-saving endoluminal treatment. Over the past 15 years, several high-quality studies were conducted to assess safe oncological outcome of endoscopic resection of mucosal adenocarcinoma and high-grade dysplasia. It became clear that add-on ablative therapy with radiofrequency ablation (RFA) significantly reduces recurrence risk of neoplasia after resection. In this review, we highlight the most essential elements to optimize outcomes of RFA of BE, addressing the correct indication and patient selection in combination with the most efficient and safest treatment protocols to obtain long-term durability.
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14
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Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases. Int J Mol Sci 2020; 21:ijms21218042. [PMID: 33126685 PMCID: PMC7672620 DOI: 10.3390/ijms21218042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 10/27/2020] [Indexed: 12/29/2022] Open
Abstract
Bile acids (BAs) have been implicated in the development of oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma (OAC). However, whether BAs promote cancer invasiveness has not been elucidated. We evaluated the role of BAs, in particular deoxycholic acid (DCA), in OAC invasion. Migration and invasiveness in untreated and BA-treated oesophageal SKGT-4 cancer cells were evaluated. Activity and expression of different matrix metalloproteinases (MMPs) were determined by zymography, ELISA, PCR and Western blot. Finally, human OAC tissues were stained for MMP-10 by immunohistochemistry. It was found that SKGT-4 cells incubated with low concentrations of DCA had a significant increase in invasion. In addition, MMP-10 mRNA and protein expression were also increased in the presence of DCA. MMP-10 was found to be highly expressed both in-vitro and in-vivo in neoplastic OAC cells relative to non-neoplastic squamous epithelial cells. Our results show that DCA promotes OAC invasion and MMP-10 overexpression. This study will advance our understanding of the pathophysiological mechanisms involved in human OAC and shows promise for the development of new therapeutic strategies.
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15
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Magnet-assist endoscopic augmentation of the lower esophageal sphincter for treatment of gastroesophageal reflux disease: cadaveric and survival studies in a porcine model (with video). Surg Endosc 2020; 35:4478-4484. [DOI: 10.1007/s00464-020-07954-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 08/27/2020] [Indexed: 02/07/2023]
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Loomans-Kropp HA, Chaloux M, Richmond E, Umar A. Association of Common Use Pharmaceuticals in Reducing Risk of Esophageal Adenocarcinoma: A SEER-Medicare Analysis. Cancer Prev Res (Phila) 2020; 14:195-204. [PMID: 32998939 DOI: 10.1158/1940-6207.capr-20-0274] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 08/15/2020] [Accepted: 09/17/2020] [Indexed: 12/24/2022]
Abstract
Barrett's esophagus (BE), a recognized risk factor for esophageal adenocarcinoma (EAC), is routinely managed with proton pump inhibitors (PPIs) when symptomatic. Several lines of evidence suggest that PPIs may prevent malignant transformation. Chronic use of other common drugs, namely, statins nonsteroidal anti-inflammatory drugs (NSAIDs) and metformin, may also interfere with BE carcinogenesis, but confirmatory evidence is lacking. We identified 1,943 EAC cases and 19,430 controls (matched 10:1) between 2007 and 2013 that met our specified inclusion criteria in the SEER-Medicare database. Conditional logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (95% CI). Wald χ2 tests were used to assess significance of covariates. Compared with controls, EAC cases had a higher prevalence of BE (26.2%). Use of PPIs, NSAIDs, statins, or metformin reduced the odds of EAC (PPIs: 0.10; 95% CI, 0.09-0.12; NSAIDs: 0.62; 95% CI, 0.51-0.74; statins: 0.15; 95% CI, 0.13-0.17; metformin: 0.76; 95% CI, 0.62-0.93). When stratified by BE, these associations persisted, though no association was found between NSAID use and EAC risk for participants with BE. Dual use of PPIs with NSAIDs or statins, and NSAID, statin, or metformin use alone also showed significant EAC risk reduction among all participants and those without BE. Use of PPIs alone and with NSAIDs, statins, or metformin was associated with reduced risk of EAC; however, a history of BE may diminish drug efficacy. These results indicate that common pharmacologic agents alone or in combination may decrease EAC development.Prevention Relevance: The use of common drugs, such as proton pump inhibitors, statins, non-steroidal anti-inflammatory drugs, or metformin, may reduce one's risk of developing esophageal adenocarcinoma. These results suggest that repurposing agents often used for common chronic conditions may be a new strategy for cancer prevention efforts.
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Affiliation(s)
- Holli A Loomans-Kropp
- Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI, Bethesda, Maryland. .,Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, NCI, Bethesda, Maryland
| | | | - Ellen Richmond
- Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, NCI, Bethesda, Maryland
| | - Asad Umar
- Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, NCI, Bethesda, Maryland
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17
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Chueca E, Valero A, Hördnler C, Puertas A, Carrera P, García-González MA, Strunk M, Lanas A, Piazuelo E. Quantitative analysis of p16 methylation in Barrett's carcinogenesis. Ann Diagn Pathol 2020; 47:151554. [PMID: 32570024 DOI: 10.1016/j.anndiagpath.2020.151554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 05/12/2020] [Accepted: 06/15/2020] [Indexed: 11/19/2022]
Abstract
p16 hypermethylation in Barrett's carcinogenesis has been evaluated in studies which did not take into account sample heterogeneity and yielded qualitative (methylated/unmethylated) instead of accurate quantitative (percentage of CpG methylation) data. We aimed to measure the degree of p16 methylation in pure samples representing all the steps of Barrett's tumorogenesis and to evaluate the influence of sample heterogeneity in methylation analysis. METHODS 77 paraffin-embedded human esophageal samples were analyzed. Histological grading was established by two pathologists in: negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Areas of interest were selected by laser-capture microdissection. p16 methylation was quantified by pyrosequencing. An adjacent section of the whole sample was also analyzed to compare methylation data. RESULTS After microdissection, we obtained 15 samples of squamous epithelium, 36 non-dysplastic Barrett's esophagus, 3 indefinite for dysplasia, 24 low-grade dysplasia, 4 high-grade dysplasia and 12 adenocarcinoma. Squamous epithelium showed the lowest methylation rates: 6% (IQR 5-11) vs. 11%(7-39.50) in negative/indefinite for dysplasia, p<0.01; 10.60%(6-24) in low-grade dysplasia, p<0.05; and 44.50%(9-66.75) in high-grade dysplasia/adenocarcinoma, p<0.01. This latter group also exhibited higher methylation rates than Barrett's epithelium with and without low-grade dysplasia (p<0.05). p16 methylation rates of microdissected and non-microdissected samples did not correlate unless the considered histological alteration comprised >71% of the sample. CONCLUSIONS p16 methylation is an early event in Barrett's carcinogenesis which increases with the severity of histological alteration. p16 methylation rates are profoundly influenced by sample heterogeneity, so selection of samples is crucial in order to detect differences.
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Affiliation(s)
- E Chueca
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain; IIS Aragón, Instituto de Investigación Sanitaria Aragón, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain
| | - A Valero
- Service of Pathology, University Hospital Miguel Servet, Paseo Isabel la Católica 1-3, 50009 Zaragoza, Spain
| | - C Hördnler
- Service of Pathology, University Hospital Miguel Servet, Paseo Isabel la Católica 1-3, 50009 Zaragoza, Spain
| | - A Puertas
- Service of Pathology, University Hospital Miguel Servet, Paseo Isabel la Católica 1-3, 50009 Zaragoza, Spain
| | - P Carrera
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain
| | - M A García-González
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain; IIS Aragón, Instituto de Investigación Sanitaria Aragón, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain; IACS Aragón, Instituto Aragonés de Ciencias de la Salud, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain
| | - M Strunk
- IACS Aragón, Instituto Aragonés de Ciencias de la Salud, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain
| | - A Lanas
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain; IIS Aragón, Instituto de Investigación Sanitaria Aragón, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain; University of Zaragoza, Calle de Pedro Cerbuna 12, 50009, Zaragoza, Spain
| | - E Piazuelo
- CIBERehd, Instituto de Salud Carlos III, Calle Monforte de Lemos 3-5, 28029 Madrid, Spain; IIS Aragón, Instituto de Investigación Sanitaria Aragón, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain; IACS Aragón, Instituto Aragonés de Ciencias de la Salud, Avenida San Juan Bosco 13, 50009 Zaragoza, Spain.
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18
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Koretz RL. JPEN
Journal Club 50. Trial Sequential Analysis. JPEN J Parenter Enteral Nutr 2020; 44:729-732. [DOI: 10.1002/jpen.1753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 11/11/2019] [Indexed: 11/08/2022]
Affiliation(s)
- Ronald L. Koretz
- Olive View‐UCLA Medical Center David Geffen‐UCLA School of Medicine Sylmar and Los Angeles California USA
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Abstract
Background: Obesity is a known independent risk factor for both Barrett esophagus and esophageal adenocarcinoma. However, data about the effect of obesity on the risk of progression from nondysplastic Barrett esophagus to dysplasia or esophageal adenocarcinoma are lacking. The aim of this study was to evaluate whether obese patients with nondysplastic Barrett esophagus had a higher incidence of dysplasia development during routine surveillance than nonobese patients. Methods: In a retrospective review, 1,999 patients who had a first diagnosis of nondysplastic Barrett esophagus made by esophagogastroduodenoscopy (EGD) at a single community hospital were tracked to their surveillance EGD 3 to 5 years later to evaluate for dysplasia (low grade, high grade, or adenocarcinoma). We compared the incidence of dysplasia development in obese patients (body mass index [BMI] ≥30 kg/m2) with nonobese patients (BMI <30 kg/m2). Results: The sample population included 1,019 obese patients (51.0%) and 980 nonobese patients (49.0%) with nondysplastic Barrett esophagus. Their mean age was 56.5 ± 11.6 years, 1,228 (61.4%) were male, and 1,853 (92.7%) were Caucasian. At surveillance endoscopy performed at a mean follow-up of 3.7 years after their first EGD, 51 obese patients (incidence of 15.3 cases per 1,000 person-years, 95% confidence interval [CI], 11.5-19.9) and 15 nonobese patients (incidence of 4.6 cases per 1,000 person-years, 95% CI, 2.7-7.4) had developed dysplasia (P=0.0001). Conclusion: We found a significant increase in the incidence of dysplasia development in obese patients with nondysplastic Barrett esophagus at 3- to 5-year follow-up compared to nonobese patients. This finding suggests that more frequent surveillance in obese patients with nondysplastic Barrett esophagus may be warranted for early detection of dysplasia.
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20
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Karamchandani DM, Zhang Q, Liao XY, Xu JH, Liu XL. Inflammatory bowel disease- and Barrett's esophagus-associated neoplasia: the old, the new, and the persistent struggles. Gastroenterol Rep (Oxf) 2019; 7:379-395. [PMID: 31857901 PMCID: PMC6911999 DOI: 10.1093/gastro/goz032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 04/30/2019] [Accepted: 06/04/2019] [Indexed: 12/30/2022] Open
Abstract
Early diagnosis of and adequate therapy for premalignant lesions in patients with inflammatory bowel disease (IBD) and Barrett's esophagus (BE) has been shown to decrease mortality. Endoscopic examination with histologic evaluation of random and targeted biopsies remains the gold standard for early detection and adequate treatment of neoplasia in both these diseases. Although eventual patient management (including surveillance and treatment) depends upon a precise histologic assessment of the initial biopsy, accurately diagnosing and grading IBD- and BE-associated dysplasia is still considered challenging by many general as well as subspecialized pathologists. Additionally, there are continuing updates in the literature regarding the diagnosis, surveillance, and treatment of these disease entities. This comprehensive review discusses the cancer risk, detailed histopathological features, diagnostic challenges, and updates as well as the latest surveillance and treatment recommendations in IBD- and BE-associated dysplasia.
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Affiliation(s)
- Dipti M Karamchandani
- Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Qin Zhang
- Department of Pathology, The Third Central Hospital of Tianjin, Tianjin, China
| | - Xiao-Yan Liao
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Jing-Hong Xu
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiu-Li Liu
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA
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Hao J, Critchley-Thorne R, Diehl DL, Snyder SR. A Cost-Effectiveness Analysis Of An Adenocarcinoma Risk Prediction Multi-Biomarker Assay For Patients With Barrett's Esophagus. CLINICOECONOMICS AND OUTCOMES RESEARCH 2019; 11:623-635. [PMID: 31749626 PMCID: PMC6818671 DOI: 10.2147/ceor.s221741] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 10/02/2019] [Indexed: 12/18/2022] Open
Abstract
PURPOSE This study evaluates the cost-effectiveness of a quantitative multi-biomarker assay (the Assay) that stratifies patients with Barrett's Esophagus (BE) by risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and can be used to guide clinical decisions, versus the current guidelines (standard of care [SOC]) for surveillance and treatment of BE. PATIENTS AND METHODS Markov decision modeling and simulation were used to compare cost and quality-adjusted life-years (QALYs) from the perspective of a US health insurer with care delivered by an integrated health system. Model assumptions and disease progression probabilities were derived from the literature. Performance metrics for the Assay were from an independent clinical validation study. Cost of the Assay was based on reimbursement rates from multiple payers. Other costs were derived from Geisinger payment data. RESULTS Base-case model results for a 5-year period comparing the Assay-directed care to the SOC estimated an incremental cost-effectiveness ratio (ICER) of $52,483/QALY in 2012 US dollars. Assay-directed care increased the use of endoscopic treatments by 58.4%, which reduced the progression to HGD, EAC and reduced EAC-related deaths by 51.7%, 47.1%, and 37.6%, respectively, over the 5-year period. Sensitivity analysis indicated that the probability of the Assay being cost-effective compared to the SOC was 57.3% at the $100,000/QALY acceptability threshold. CONCLUSION Given the model assumptions, the new Assay would be cost-effective after 5 years and improves patient outcomes due to improvement in the effectiveness of surveillance and treatment protocols resulting in fewer patients progressing to HGD and EAC and fewer EAC-related deaths.
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Affiliation(s)
- Jing Hao
- Department of Epidemiology and Health Services Research, Geisinger, Danville, PA, USA
| | | | - David L Diehl
- Department of Gastroenterology, Geisinger, Danville, PA, USA
| | - Susan R Snyder
- Department of Epidemiology and Health Services Research, Geisinger, Danville, PA, USA
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Peters Y, Al-Kaabi A, Shaheen NJ, Chak A, Blum A, Souza RF, Di Pietro M, Iyer PG, Pech O, Fitzgerald RC, Siersema PD. Barrett oesophagus. Nat Rev Dis Primers 2019; 5:35. [PMID: 31123267 DOI: 10.1038/s41572-019-0086-z] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Barrett oesophagus (BE), the only known histological precursor of oesophageal adenocarcinoma (EAC), is a condition in which the squamous epithelium of the oesophagus is replaced by columnar epithelium as an adaptive response to gastro-oesophageal reflux. EAC has one of the fastest rising incidences of cancers in Western countries and has a dismal prognosis. BE is usually detected during endoscopic examination, and diagnosis is confirmed by the histological presence of intestinal metaplasia. Advances in genomics and transcriptomics have improved our understanding of the pathogenesis and malignant progression of intestinal metaplasia. As the majority of EAC cases are diagnosed in individuals without a known history of BE, screening for BE could potentially decrease disease-related mortality. Owing to the pre-malignant nature of BE, endoscopic surveillance of patients with BE is imperative for early detection and treatment of dysplasia to prevent further progression to invasive EAC. Developments in endoscopic therapy have resulted in a major shift in the treatment of patients with BE who have dysplasia or early EAC, from surgical resection to endoscopic resection and ablation. In addition to symptom control by optimization of lifestyle and pharmacological therapy with proton pump inhibitors, chemopreventive strategies based on NSAIDs and statins are currently being investigated for BE management.
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Affiliation(s)
- Yonne Peters
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Ali Al-Kaabi
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Nicholas J Shaheen
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Amitabh Chak
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University, Cleveland, OH, USA
| | - Andrew Blum
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University, Cleveland, OH, USA
| | - Rhonda F Souza
- Department of Medicine and the Center for Esophageal Diseases, Baylor University Medical Center at Dallas and the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, TX, USA
| | | | - Prasad G Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Oliver Pech
- Department of Gastroenterology, St John of God Hospital, Regensburg, Germany
| | | | - Peter D Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands.
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Alkaddour A, McGaw C, Hritani R, Palacio C, Munoz JC, Vega KJ. Protective Propensity of Race or Environmental Features in the Development of Barrett's Esophagus in African Americans - A Single Center Pilot Study. J Natl Med Assoc 2019; 111:198-201. [PMID: 30366610 DOI: 10.1016/j.jnma.2018.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 08/25/2018] [Accepted: 09/24/2018] [Indexed: 11/24/2022]
Abstract
BACKGROUND AND STUDY AIMS Barrett's Esophagus (BE) is a well-recognized pre-malignant condition. Previous data indicate histologically confirmed BE frequency varies by ethnicity in the United States. However, clinical factor assessment to explain this has only occurred in a veteran population to date. The study aim was to determine which clinical factors may be associated with the ethnic variation seen in histologically confirmed BE among a general population. PATIENTS AND METHODS The University of Florida-Jacksonville endoscopy database was searched for all cases of endoscopic BE from September 2002 to October 2012. Histologic BE was diagnosed only if salmon colored, columnar-appearing esophageal mucosa was seen at endoscopy and biopsy revealed intestinal metaplasia with Alcian blue-stained goblet cells. Data collected included: age/BMI at diagnosis, ethnicity, sex, GERD history, atypical manifestations, endoscopic BE length, presence of esophageal stricture/ulcer/hiatal hernia, presence/absence of dysplasia and medication use (aspirin/NSAIDs/statin/PPI). RESULTS Salmon colored esophageal mucosa was observed in 1105 of 15,564 patients (7.1%) with BE histologically confirmed in 249 of 1105 patients (23%). Ethnic distribution of histologic BE patients: 83% non-Hispanic white (nHw), 13% African American (AA) and 4% other. No difference was seen between groups with regard to BMI, GERD symptom/complications, BE length, and cigarette, alcohol or medication use. CONCLUSION BE occurs primarily in nHw in north Florida. This occurs despite similarities in GERD history, cigarette/alcohol use, medications prescribed and BMI. Molecular level investigation is necessary to explain this observed disparity between nHw and AA.
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Affiliation(s)
- Ahmad Alkaddour
- Department of Medicine, University of Florida/Jacksonville, Jacksonville, FL, USA
| | - Camille McGaw
- Division of Gastroenterology, University of Florida/Jacksonville, Jacksonville, FL, USA
| | - Rama Hritani
- Division of Gastroenterology, University of Florida/Jacksonville, Jacksonville, FL, USA
| | - Carlos Palacio
- Department of Medicine, University of Florida/Jacksonville, Jacksonville, FL, USA
| | - Juan Carlos Munoz
- Division of Gastroenterology, University of Florida/Jacksonville, Jacksonville, FL, USA
| | - Kenneth J Vega
- Division of Gastroenterology, University of Florida/Jacksonville, Jacksonville, FL, USA; Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, GA.
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Abstract
Evidence-based medicine (EBM) has become a fixture in today's medical practice. Evidence consists of memorialized observations and should be contrasted with dogmatic pronouncements and/or hypotheses. Evidence has varying degrees of reliability. The randomized clinical trial (RCT) or a systematic review of RCTs is accorded the highest level of credibility and expert opinion the lowest. This ranking reflects the internal validity (degree to which factors in the study interfere with the gathering or interpretation of the observations) of the study design; more valid designs are more credible. The provision of healthcare requires an almost constant assessment of evidence. In so doing, there are a number of principles of EBM that need to be kept in mind: Association can never prove causation. Various methodologic biases can influence conclusions made in both RCTs and observational studies. The strength of RCTs is in the elimination of confounding bias. Surrogate outcomes must be validated in RCTs assessing how they are changed compared with the clinical outcomes. Subgroup analyses cannot prove hypotheses although they can generate them. P < 0.05 is not the same as truth. Type I errors are more likely to occur when multiple analyses are performed, when trials are prematurely stopped for perceived benefit when there was no a priori plan to do so, or in small papers with dramatic results that are selectively published. The failure to find a difference does not mean that no difference exists (type II error).
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Affiliation(s)
- Ronald L Koretz
- David Geffen UCLA School of Medicine, Los Angeles, California, USA.,Olive View UCLA Medical Center, Sylmar, California, USA
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Biswas Roy S, Banks P, Kunz M, Ipsen TR, Masuda T, Mittal SK, Smith MA, Bremner RM. Prevalence and Natural History of Barrett's Esophagus in Lung Transplant: A Single-Center Experience. Ann Thorac Surg 2018; 107:1017-1023. [PMID: 30481513 DOI: 10.1016/j.athoracsur.2018.10.041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 09/27/2018] [Accepted: 10/10/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Barrett's esophagus (BE)-intestinal metaplasia in the esophagus-may progress to low-grade dysplasia (LGD), high-grade dysplasia (HGD), and ultimately, invasive esophageal adenocarcinoma (EAC). The course of BE in immunosuppressed lung transplant recipients is unknown. METHODS This study retrospectively reviewed the records of patients who underwent lung transplant at a single center, Norton Thoracic Institute in Phoenix, Arizona, between January 1, 2010 and October 31, 2016. Pretransplant esophagram, esophagogastroduodenoscopy, 24-hour pH monitoring, high-resolution manometry, and gastric emptying studies were analyzed. RESULTS Of the 466 patients who underwent lung transplant during the study period, 54 (11.59%) had BE on pretransplant esophagogastroduodenoscopy. Of these, 1 patient had HGD before lung transplant. The median age of patients was 64 years (interquartile range, 58.25 to 68.75 years); 66.7% were men. Median follow-up duration was 29.48 months (interquartile range, 19.69 to 37.98 months). Sixteen of 54 patients (29.62%) underwent antireflux surgery after lung transplant. LGD or EAC developed in 3 patients during posttransplant surveillance. One patient had a diagnosis of HGD 24 months after retransplant. She underwent complete endoscopic ablation and was dysplasia-free for 5 months, but ultimately the condition recurred, and she underwent esophagectomy for invasive cancer. Two patients had a diagnosis of LGD 7 and 13 months after lung transplant and were successfully treated with radiofrequency ablation. The rate of progression to dysplasia or EAC was 2.3% per patient-year. CONCLUSIONS BE seems to be more prevalent in lung transplant recipients than in the general population. The study findings suggest that patients with BE have a higher risk of BE-to-EAC progression after lung transplant and that HGD may progress rapidly in immunosuppressed patients. More intensive surveillance endoscopy may be required in patients with BE after lung transplant.
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Affiliation(s)
- Sreeja Biswas Roy
- Department of Internal Medicine, St. Joseph's Hospital and Medical Center, Phoenix, Arizona
| | - Paul Banks
- Midwestern University, Glendale, Arizona
| | | | | | - Takahiro Masuda
- Division of Thoracic Surgery, Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona
| | - Sumeet K Mittal
- Division of Thoracic Surgery, Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona
| | - Michael A Smith
- Division of Thoracic Surgery, Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona
| | - Ross M Bremner
- Division of Thoracic Surgery, Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
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Davison JM, Shah MB, Deitrick C, Chennat J, Fasanella KE, McGrath K. Low-grade dysplasia diagnosis ratio and progression metrics identify variable Barrett's esophagus risk stratification proficiency in independent pathology practices. Gastrointest Endosc 2018; 88:807-815.e2. [PMID: 29944863 DOI: 10.1016/j.gie.2018.06.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Accepted: 06/05/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The diagnosis of low-grade dysplasia (LGD) in Barrett's esophagus (BE) is subject to substantial interobserver variation. Our central aim in this study is to compare independent pathology practices using objective measures of BE risk stratification proficiency, including frequency of diagnosis and rate of progression, with high-grade dysplasia (HGD) or adenocarcinoma (EAC) after the first diagnosis of LGD. METHODS We retrospectively evaluated over 29,000 endoscopic biopsy cases to identify 4734 patients under endoscopic biopsy surveillance for BE in a healthcare system with multiple independent pathology practices: a subspecialized GI pathology group (SSGI; 162 BE cases per pathologist annually), 3 high BE volume general surgical pathology practices (GSPs; >50 BE cases per pathologist annually), and multiple low BE volume GSPs (10.6 BE cases per pathologist annually). We measured LGD diagnosis frequencies and rates of diagnostic progression to HGD or EAC in patients diagnosed with LGD. RESULTS The proportion of all BE cases diagnosed as LGD (LGD/BE diagnosis ratio) ranged from 1.1% to 6.8% in the different hospital settings (P < .001). The cumulative proportion of patients with HGD or EAC within 2 years of the first diagnosis of LGD was 35.3% in the SSGI and ranged from 1.4% to 14.3% in the GSPs (P < .001). LGD diagnosed by the GSP with the lowest LGD/BE diagnosis ratio had an adjusted risk of progression similar to LGD diagnosed by subspecialists (hazard ratio, .42; 95% CI, .06-3.03). However, when LGD was diagnosed by other generalists, the adjusted risk of progression was 79% to 91% lower than subspecialists (P < .001). When LGD was diagnosed in a low-volume GSP practice, the risk of progression was not significantly increased relative to patients with nondysplastic BE (hazard ratio, 1.3; 95% CI, .4-3.9). CONCLUSIONS General surgical pathologists and subspecialists show highly significant differences with respect to LGD/BE ratio, risk of progression relative to nondysplastic BE, crude annual progression rates, and the cumulative 2-year progression rate after LGD. These metrics can be used to assess proficiency in BE risk stratification in historical cases. Some general practitioners were able to achieve results similar to subspecialists. General surgical pathologists with little annual experience evaluating BE biopsy specimens did not successfully risk stratify patients with BE.
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Affiliation(s)
- Jon M Davison
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Maulin B Shah
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Christopher Deitrick
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Jennifer Chennat
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Ken E Fasanella
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Kevin McGrath
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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Meyer C, Fuller K, Scott J, Vassar M. Is publication bias present in gastroenterological research? An analysis of abstracts presented at an annual congress. PeerJ 2018; 6:e4995. [PMID: 29942685 PMCID: PMC6016530 DOI: 10.7717/peerj.4995] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 05/28/2018] [Indexed: 01/07/2023] Open
Abstract
Background Publication bias is the tendency of investigators, reviewers, and editors to submit or accept manuscripts for publication based on their direction or strength of findings. In this study, we investigated if publication bias was present in gastroenterological research by evaluating abstracts at Americas Hepato-Pancreato-Biliary Congresses from 2011 to 2013. Methods We searched Google, Google Scholar, and PubMed to locate the published reports of research described in these abstracts. If a publication was not found, a second investigator searched to verify nonpublication. If abstract publication status remained undetermined, authors were contacted regarding reasons for nonpublication. For articles reaching publication, the P value, study design, time to publication, citation count, and journals in which the published report appeared were recorded. Results Our study found that of 569 abstracts presented, 297 (52.2%) reported a P value. Of these, 254 (85.5%) contained P values supporting statistical significance. The abstracts reporting a statistically significant outcome were twice as likely to reach publication than abstracts with no significant findings (OR 2.10, 95% CI [1.06–4.14]). Overall, 243 (42.7%) abstracts reached publication. The mean time to publication was 14 months and a median time of nine months. Conclusion In conclusion, we found evidence for publication bias in gastroenterological research. Abstracts with significant P values had a higher probability of reaching publication. More than half of abstracts presented from 2011 to 2013 failed to reach publication. Readers should take these findings into consideration when reviewing medical literature.
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Affiliation(s)
- Chase Meyer
- Oklahoma State University College of Osteopathic Medicine, Tulsa, OK, United States of America
| | - Kaleb Fuller
- Oklahoma State University College of Osteopathic Medicine, Tulsa, OK, United States of America
| | - Jared Scott
- Oklahoma State University College of Osteopathic Medicine, Tulsa, OK, United States of America
| | - Matt Vassar
- Oklahoma State University College of Osteopathic Medicine, Tulsa, OK, United States of America
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Shaheen NJ, Fennerty MB, Bergman JJ. Less Is More: A Minimalist Approach to Endoscopy. Gastroenterology 2018; 154:1993-2003. [PMID: 29454789 DOI: 10.1053/j.gastro.2017.12.044] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 11/08/2017] [Accepted: 12/04/2017] [Indexed: 12/20/2022]
Abstract
A substantial literature documents inappropriate usage of gastrointestinal endoscopy in a variety of clinical settings. Overusage of endoscopy appears to be common, and 30% or more of procedures performed in some clinical settings have questionable indications. The potential reasons for overuse of endoscopy are multiple, and include cancer phobia, fear of medical malpractice litigation, profit motive, the investigation of "incidentalomas" found on other imaging, and underappreciation of the delayed harms of endoscopy, among other reasons. Clinical guidelines, which should limit overuse of endoscopy, may instead serve to promote it, if authors opt to be "conservative," recommending endoscopy in situations of unclear utility. Several strategies may decrease overuse of endoscopy, including careful attention to risk stratification when choosing patients to screen, adherence to guidelines for surveillance intervals for colonoscopy, the use of quality indicators to identify outliers in endoscopy utilization, and education on appropriate indications and the risks of overuse at the medical student, residency, and fellowship levels.
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Affiliation(s)
- Nicholas J Shaheen
- University of North Carolina at Chapel Hill, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina.
| | - M Brian Fennerty
- Division of Gastroenterology and Hepatology, Oregon Health and Sciences University, Portland, Oregon
| | - Jacques J Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
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Souza RF, Rubenstein JH, Kao JY, Hirano I. Contributions From Gastroenterology: Acid Peptic Disorders, Barrett's Esophagus and Eosinophilic Esophagitis. Gastroenterology 2018. [PMID: 29524399 DOI: 10.1053/j.gastro.2017.12.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Affiliation(s)
- Rhonda F Souza
- Department of Medicine, Division of Gastroenterology, Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, Texas
| | - Joel H Rubenstein
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan; Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan
| | - John Y Kao
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan
| | - Ikuo Hirano
- Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
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Endoscopic eradication therapy for Barrett’s esophagus: Adverse outcomes, patient values, and cost-effectiveness. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2018. [DOI: 10.1016/j.tgie.2018.02.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Parasa S, Vennalaganti S, Gaddam S, Vennalaganti P, Young P, Gupta N, Thota P, Cash B, Mathur S, Sampliner R, Moawad F, Lieberman D, Bansal A, Kennedy KF, Vargo J, Falk G, Spaander M, Bruno M, Sharma P. Development and Validation of a Model to Determine Risk of Progression of Barrett's Esophagus to Neoplasia. Gastroenterology 2018; 154:1282-1289.e2. [PMID: 29273452 DOI: 10.1053/j.gastro.2017.12.009] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 12/11/2017] [Accepted: 12/13/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS A system is needed to determine the risk of patients with Barrett's esophagus for progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). We developed and validated a model to determine of progression to HGD or EAC in patients with BE, based on demographic data and endoscopic and histologic findings at the time of index endoscopy. METHODS We performed a longitudinal study of patients with BE at 5 centers in United States and 1 center in Netherlands enrolled in the Barrett's Esophagus Study database from 1985 through 2014. Patients were excluded from the analysis if they had less than 1 year of follow-up, were diagnosed with HGD or EAC within the past year, were missing baseline histologic data, or had no intestinal metaplasia. Seventy percent of the patients were used to derive the model and 30% were used for the validation study. The primary outcome was development of HGD or EAC during the follow-up period (median, 5.9 years). Survival analysis was performed using the Kaplan-Meier method. We assigned a specific number of points to each BE risk factor, and point totals (scores) were used to create categories of low, intermediate, and high risk. We used Cox regression to compute hazard ratios and 95% confidence intervals to determine associations between risk of progression and scores. RESULTS Of 4584 patients in the database, 2697 were included in our analysis (84.1% men; 87.6% Caucasian; mean age, 55.4 ± 20.1 years; mean body mass index, 27.9 ± 5.5 kg/m2; mean length of BE, 3.7 ± 3.2 cm). During the follow-up period, 154 patients (5.7%) developed HGD or EAC, with an annual rate of progression of 0.95%. Male sex, smoking, length of BE, and baseline-confirmed low-grade dysplasia were significantly associated with progression. Scores assigned identified patients with BE that progressed to HGD or EAC with a c-statistic of 0.76 (95% confidence interval, 0.72-0.80; P < .001). The calibration slope was 0.9966 (P = .99), determined from the validation cohort. CONCLUSIONS We developed a scoring system (Progression in Barrett's Esophagus score) based on male sex, smoking, length of BE, and baseline low-grade dysplasia that identified patients with BE at low, intermediate, and high risk for HGD or EAC. This scoring system might be used in management of patients.
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Affiliation(s)
- Sravanthi Parasa
- Division of Gastroenterology, Swedish Medical Group, Seattle, Washington
| | - Sreekar Vennalaganti
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri
| | - Srinivas Gaddam
- Division of Gastroenterology, Cedar-Sinai Medical Center, Los Angeles, California
| | - Prashanth Vennalaganti
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri; Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas
| | - Patrick Young
- Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Neil Gupta
- Division of Gastroenterology, Loyola University Medical Center, Maywood, Illinois
| | - Prashanthi Thota
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio
| | - Brooks Cash
- University of South Alabama, Mobile, Alabama; American Gastroenterological Association
| | - Sharad Mathur
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri
| | - Richard Sampliner
- Department of Gastroenterology and Hepatology, University of Arizona, Tucson, Arizona
| | - Fouad Moawad
- Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - David Lieberman
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon
| | - Ajay Bansal
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri; Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas
| | - Kevin F Kennedy
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri
| | - John Vargo
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio
| | - Gary Falk
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Manon Spaander
- Department of Gastroenterology, Erasmus Medical Centre, Rotterdam, Netherlands
| | - Marco Bruno
- Department of Gastroenterology, Erasmus Medical Centre, Rotterdam, Netherlands
| | - Prateek Sharma
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri; Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas.
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Abstract
OBJECTIVES The aim of this study was to evaluate adherence to Barrett's esophagus (BE) surveillance guidelines in Denmark. METHODS The Danish Pathology Registry was used to identify 3692 patients. A total of 300 patients were included by drawing a simple random sample. Description of the BE segment, biopsy protocol, communication with the pathologist and planned follow-up endoscopy, was evaluated. RESULTS Thirty-one patients were excluded due to missing reports and 83 patients (28%) due to no endoscopic evidence of BE. Endoscopists suspected BE in 186 patients (62%) and these patients were included. Prague C&M classification was used in 34% of the endoscopy reports. The median number of biopsies was 4 (interquartile range (IQR), 3-6). The BE segment was stratified by lengths of 1-5, 6-10 and 11-15 cm and endoscopists obtained a sufficient number of biopsies in 12, 8 and 0% of cases, respectively. 28% of endoscopists described the exact location of the biopsy site in the pathology requisition. Patients with nondysplastic BE had endoscopic surveillance performed after a median of 24 months (IQR, 6-24). CONCLUSIONS Adherence to the Danish guidelines was poor. This may be associated with insufficient quality of BE surveillance. Lack of endoscopic evidence of BE in the Danish Pathology Registry may have underestimated the incidence of adenocarcinoma in BE patients in previous studies.
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Affiliation(s)
- Jes Sefland Vogt
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark
| | - Anders Christian Larsen
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark.,b Department of Surgery , Region Hospital Randers , Randers , Denmark
| | - Thorbjørn Sommer
- b Department of Surgery , Region Hospital Randers , Randers , Denmark
| | - Per Ejstrud
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark
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Maddalo G, Fassan M, Cardin R, Piciocchi M, Marafatto F, Rugge M, Zaninotto G, Pozzan C, Castoro C, Ruol A, Biasiolo A, Farinati F. Squamous Cellular Carcinoma Antigen Serum Determination as a Biomarker of Barrett Esophagus and Esophageal Cancer: A Phase III Study. J Clin Gastroenterol 2018; 52:401-406. [PMID: 28422774 DOI: 10.1097/mcg.0000000000000790] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
GOAL To evaluate the potential role of the determination of the immunocomplexed form of squamous cell carcinoma antigen [SCCA-immunoglobulin (Ig)M] for the screening of Barrett esophagus (BE) and esophageal adenocarcinoma (EAC). BACKGROUND The cost-effectiveness of surveillance in BE is still debated and the use of biomarkers in screening and surveillance still not recommended. No information is available regarding SCCA-IgM determination in BE. STUDY SCCA-IgM levels were determined (enzyme-linked immunosorbent assay) in 231 patients prospectively recruited, 71 with BE, 53 with EAC, and 107 controls, including 42 blood donors and 65 patients with gastroesophageal reflux. SCCA-IgM cutoffs between BE/EAC and controls and for BE "at risk" versus short nondysplastic BE were calculated by receiver operating characteristic curves. Immunostaining for SCCA-IgM was obtained in a subgroup of patients. RESULTS Median SCCA-IgM values were significantly higher in BE and EAC than in controls (P=0.0001). Patients with SCCA-IgM levels above the cutoff had a 33 times higher relative risk of harboring BE or EAC (P=0.0001). Patients "at risk," with long or dysplastic BE had SCCA-IgM levels significantly higher than those with short nondysplastic BE (P=0.035) and patients with SCCA-IgM above the cutoff had a 8 times higher relative risk of having BE "at risk." SCCA was expressed in Barrett mucosa but not in cardiac metaplasia. CONCLUSIONS Serum SCCA-IgM determination allows the identification of patients at risk for BE/EAC and the stratification of BE patients in subgroups with different cancer risk. Because of the still limited number of controls, large, prospective studies are required to confirm this evidence.
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Affiliation(s)
- Gemma Maddalo
- Departments of Surgery, Oncology and Gastroenterology
| | | | | | | | | | | | - Giovanni Zaninotto
- Department of Surgery and Cancer, Imperial College, St Mary's Hospital, London, UK
| | | | - Carlo Castoro
- Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, Italy
| | - Alberto Ruol
- Departments of Surgery, Oncology and Gastroenterology
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Upchurch E, Griffiths S, Lloyd GR, Isabelle M, Kendall C, Barr H. Developments in optical imaging for gastrointestinal surgery. Future Oncol 2017; 13:2363-2382. [PMID: 29121775 DOI: 10.2217/fon-2017-0181] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
To improve outcomes for patients with cancer, in terms of both survival and a reduction in the morbidity and mortality that results from surgical resection and treatment, there are two main areas that require improvement. Accurate early diagnosis of the cancer, at a stage where curative and, ideally, minimally invasive treatment is achievable, is desired as well as identification of tumor margins, lymphatic and distant disease, enabling complete, but not unnecessarily extensive, resection. Optical imaging is making progress in achieving these aims. This review discusses the principles of optical imaging, focusing on fluorescence and spectroscopy, and the current research that is underway in GI tract carcinomas.
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Affiliation(s)
- Emma Upchurch
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Great Western Road, Gloucester, UK, GL1 3NN.,Department of Upper GI Surgery, Gloucestershire Royal Hospital, Great Western Road, Gloucester, UK, GL1 3NN
| | - Shelly Griffiths
- Department of Upper GI Surgery, Gloucestershire Royal Hospital, Great Western Road, Gloucester, UK, GL1 3NN
| | - Gavin-Rhys Lloyd
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Great Western Road, Gloucester, UK, GL1 3NN
| | - Martin Isabelle
- Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK, GL12 8JR
| | - Catherine Kendall
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Great Western Road, Gloucester, UK, GL1 3NN
| | - Hugh Barr
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Great Western Road, Gloucester, UK, GL1 3NN.,Department of Upper GI Surgery, Gloucestershire Royal Hospital, Great Western Road, Gloucester, UK, GL1 3NN
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Alkaddour A, Palacio C, Vega KJ. Risk of histologic Barrett's esophagus between African Americans and non-Hispanic whites: A meta-analysis. United European Gastroenterol J 2017; 6:22-28. [PMID: 29435310 DOI: 10.1177/2050640617707862] [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: 01/20/2017] [Accepted: 03/29/2017] [Indexed: 12/16/2022] Open
Abstract
Background Barrett's esophagus (BE) is rare in African Americans (AA). However, the risk difference magnitude in histologic BE prevalence between AA and non-Hispanic whites (nHw) has not been quantified to date. Objective The objective of this article is to determine the degree of histologic BE risk difference between AA and nHw. Methods PubMed, Web of Science and EMBASE were searched for studies reporting histologic BE in AA/nHw for inclusion. Pooled odds ratios (ORs) with risk estimates of histologic BE occurrence between AA/nHw were calculated along with 95% confidence intervals (CIs). Forest plots were used to quantify heterogeneity. Funnel plots and the Cochrane Collaboration Risk of Bias tool were used to assess bias risk. Results Eight studies reported BE histologic confirmation in AA/nHw. Analysis demonstrated a nearly 400% increased histologic BE risk in nHw patients compared to AA (OR 3.949, 95% CI 3.069-5.082). In the model without the case-control study, histologic BE risk remained elevated at approximately 360% in nHw compared to AA (OR 3.618, 95% CI 2.769-4.726). Heterogeneity was not present in either model. Risk of bias was significant. Conclusions Histologic BE risk is elevated in nHw by 3.6-4 times compared to AA. Investigation into understanding any clinical, molecular or genetic mechanisms underlying this risk disparity is warranted.
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Affiliation(s)
- Ahmad Alkaddour
- Department of Medicine, University of Florida/Jacksonville, Jacksonville, FL, USA
| | - Carlos Palacio
- Department of Medicine, University of Florida/Jacksonville, Jacksonville, FL, USA
| | - Kenneth J Vega
- Division of Gastroenterology, National Jewish Health, Denver, CO, USA
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Powell AGMT, Hughes DL, Brown J, Larsen M, Witherspoon J, Lewis WG. Esophageal cancer's 100 most influential manuscripts: a bibliometric analysis. Dis Esophagus 2017; 30:1-8. [PMID: 28375483 DOI: 10.1093/dote/dow039] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Indexed: 12/11/2022]
Abstract
Bibliometric analysis highlights key topics and publications that have shaped the understanding and management of esophageal cancer (EC). Here, the 100 most cited manuscripts in the field of EC are analyzed. The Thomson Reuters Web of Science database with the search terms 'esophageal cancer' or 'esophageal carcinoma' or 'oesophageal cancer' or 'oesophageal carcinoma' or 'gastroscopy' was used to identify all English language full manuscripts for the study. The 100 most cited papers were further analyzed by topic, journal, author, year, and institution. A total of 121,556 eligible papers were returned and the median (range) citation number was 406.5 (1833 to 293). The most cited paper focused on the role of perioperative chemotherpy in EC (1833 citations). Gastroenterology published the highest number of papers (n = 15, 6362 citations) and The New England Journal of Medicine received the most citations (n = 12, 12125 citations). The country and year with the greatest number of publications were the USA (n = 50), and 1998, 1999, and 2000 (n = 7). The most ubiquitous topic was the pathology of EC (n = 66) followed by management of EC (n = 54), and studies related to EC prognosis (n = 44). The most cited manuscripts highlighted the pathology, management, and prognosis of EC and this bibliometirc review provides the most influential references serving as a guide to popular research themes.
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Affiliation(s)
- A G M T Powell
- Division of Cancer and Genetics, Cardiff University, University Hospital of Wales, Cardiff, UK.,Department of Surgery, University Hospital of Wales, Cardiff, UK
| | - D L Hughes
- Department of Surgery, University Hospital of Wales, Cardiff, UK
| | - J Brown
- Department of Surgery, University Hospital of Wales, Cardiff, UK
| | - M Larsen
- Department of Surgery, University Hospital of Wales, Cardiff, UK
| | - J Witherspoon
- Department of Surgery, University Hospital of Wales, Cardiff, UK
| | - W G Lewis
- Department of Surgery, University Hospital of Wales, Cardiff, UK
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37
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Abstract
Barrett esophagus (BE) is a precursor lesion for esophageal adenocarcinoma (EAC). Developments in imaging and molecular markers, and endoscopic eradication therapy, are available to curb the increase of EAC. Endoscopic surveillance is recommended, despite lack of data. The cancer risk gets progressively downgraded, raising questions about the understanding of risk factors and molecular biology involved. Recent data point to at least 2 carcinogenic pathways operating in EAC. The use of p53 overexpression and high-risk human papillomavirus may represent the best chance to detect progressors. Genome-wide technology may provide molecular signatures to aid diagnosis and risk stratification in BE.
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38
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Kojima K, Yamashita K, Ushiku H, Katoh H, Ishii S, Tanaka T, Yokoi K, Suzuki M, Ooizumi Y, Igarashi K, Hosoda K, Moriya H, Mieno H, Katada N, Tanabe S, Watanabe M. The clinical significance of cysteine dioxygenase type 1 methylation in Barrett esophagus adenocarcinoma. Dis Esophagus 2017; 30:1-9. [PMID: 28184414 DOI: 10.1093/dote/dow001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Methylation of cysteine dioxygenase type 1 (CDO1) gene, a tumor suppressor gene, has been studied in various cancers; however, there is no information regarding Barrett esophagus cancer. In this study, the clinical significance of CDO1 methylation in Barrett esophagus adenocarcinoma (BEA) was clarified. CDO1 gene promoter methylation was analyzed for DNA from the patient's specimens using quantitative methylation-specific polymerase chain reaction. Thirty-eight BEA patients who underwent resection were identified between 2000 and 2014. Hypermethylation of CDO1 gene was demonstrated to be frequently recognized even at early stage in BEA by quantitative methylation-specific polymerase chain reaction. In BEA, there is a robust prognostic difference between stage I and stage II/III/IV with regard to 5-year relapse-free survival (P = 0.0016) and 5-year overall survival (P = 0.0024), and the tumor size separated by 7 cm was also a prognostic factor. There was significant difference in CDO1 gene methylation according to the tumor size (P = 0.036). BEA patients with CDO1 gene methylation were shown marginally significantly poorer prognosis (P = 0.054) than otherwise patients. In conclusion, higher CDO1 gene methylation was seen in BEA at earlier stage than in squamous cell carcinoma, and it may account for aggressive phenotype of BEA.
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Affiliation(s)
- K Kojima
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - K Yamashita
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - H Ushiku
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - H Katoh
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - S Ishii
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - T Tanaka
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - K Yokoi
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - M Suzuki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Y Ooizumi
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - K Igarashi
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - K Hosoda
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - H Moriya
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - H Mieno
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - N Katada
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - S Tanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - M Watanabe
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
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39
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Savarino E, de Bortoli N, De Cassan C, Della Coletta M, Bartolo O, Furnari M, Ottonello A, Marabotto E, Bodini G, Savarino V. The natural history of gastro-esophageal reflux disease: a comprehensive review. Dis Esophagus 2017; 30:1-9. [PMID: 27862680 DOI: 10.1111/dote.12511] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastroesophageal reflux disease (GERD) is a common disorder of the upper gastrointestinal tract which is typically characterized by heartburn and acid regurgitation. These symptoms are widespread in the community and range from 2.5% to more than 25%. Economic analyses showed an increase in direct and indirect costs related to the diagnosis, treatment and surveillance of GERD and its complications. The aim of this review is to provide current information regarding the natural history of GERD, taking into account the evolution of its definition and the worldwide gradual change of its epidemiology. Present knowledge shows that there are two main forms of GERD, that is erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter comprises the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, which is considered as a pre-cancerous lesion. Although data from medical literature on the natural history of this disease are limited and mainly retrospective, they seem to indicate that both NERD and mild esophagitis tend to remain as such with time and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur in a small proportion of patients, ranging from 0 to 30%, 10 to 22% and 1 to 13% of cases, respectively. It is necessary to stress that these data are strongly influenced by the use of powerful antisecretory drugs (PPIs). Further studies are needed to better elucidate this matter and overcome the present limitations represented by the lack of large prospective longitudinal investigations, absence of homogeneous definitions of the various forms of GERD, influence of different treatments, clear exclusion of patients with functional disorders of the esophagus.
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Affiliation(s)
- E Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - N de Bortoli
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - C De Cassan
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - M Della Coletta
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - O Bartolo
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - M Furnari
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - A Ottonello
- Department of Surgical Medical Sciences and Integrated Diagnostic, University of Genoa, Genoa, Italy
| | - E Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - G Bodini
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - V Savarino
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
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40
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Januszewicz W, Kaminski MF, Wieszczy P, Wronska E, Bielasik A, Wojciechowska U, Didkowska J, Orlowska J, Regula J. Adenocarcinoma risk in patients registered with Polish Barrett's Oesophagus Registry. Dis Esophagus 2017; 30:1-6. [PMID: 27377059 DOI: 10.1111/dote.12483] [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] [Indexed: 12/11/2022]
Abstract
Barrett's Oesophagus (BO) is a complication of chronic gastro-oesophageal reflux disease (GORD) and is a major risk factor for oesophageal adenocarcinoma. Current guidelines are based on data showing a 0.5% annual malignancy progression rate. The Polish Barrett's Oesophagus Registry (POBOR) was established to characterize Polish patients with BO and estimate the risk of malignant progression. POBOR was established in 1999 after a dedicated training of endoscopists and histopathologists. Physicians registered patients using a dedicated registry form. After excluding patients known to have endoscopic treatment for BO, follow-up <1 year and adenocarcinoma found at index endoscopy we have linked patients personal identification numbers (PESEL) with the National Cancer Registry to identify those with a diagnosis of oesophageal or gastric cardia adenocarcinoma. In total, 843 patients were registered [609 men (72.2%), male to female ratio 2.6:1] with median age at diagnosis of 56 years (IQR:47-67). Long segment BE was found at index endoscopy in 294 patients (39.4%) whereas low grade dysplasia in 147 (17.4%). 112 patients (13.3%) fulfilled the exclusion criteria and the remaining 731 were followed for a median of 9.8 years (IQR: 9.3-10.0). After 6779 patient-years, 6 adenocarcinomas were diagnosed yielding an incidence rate of 0.89 per 1000 patients-years (95% confidence interval [CI 0.40-1.97]) which corresponds to annual malignancy progression rate of less than 0.1%. The malignancy rate in patients with low grade dysplasia was 3.70 per 1000 patient-years (95% CI 1.39-9.85). In Polish BO patients the risk of malignant progression was lower than previously reported. It was notably higher in patients with low grade dysplasia than in those with no dysplasia at index endoscopy, which may warrant strict surveillance in these patients.
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Affiliation(s)
- Wladyslaw Januszewicz
- Department of Gastroenterological Oncology, the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.,Department of Gastroenterology and Hepatology, Medical Centre for Postgraduate Education, Warsaw, Poland
| | - Michal F Kaminski
- Department of Gastroenterological Oncology, the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.,Department of Gastroenterology and Hepatology, Medical Centre for Postgraduate Education, Warsaw, Poland.,Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Paulina Wieszczy
- Department of Gastroenterology and Hepatology, Medical Centre for Postgraduate Education, Warsaw, Poland
| | - Ewa Wronska
- Department of Gastroenterological Oncology, the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.,Department of Gastroenterology and Hepatology, Medical Centre for Postgraduate Education, Warsaw, Poland
| | - Andrzej Bielasik
- Department of Gastroenterological Oncology, the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.,Department of Gastroenterology and Hepatology, Medical Centre for Postgraduate Education, Warsaw, Poland
| | - Urszula Wojciechowska
- The National Cancer Registry of Poland, the Maria-Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Joanna Didkowska
- The National Cancer Registry of Poland, the Maria-Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Janina Orlowska
- Department of Pathology and Diagnostic Laboratory, the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
| | - Jaroslaw Regula
- Department of Gastroenterological Oncology, the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.,Department of Gastroenterology and Hepatology, Medical Centre for Postgraduate Education, Warsaw, Poland
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41
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Evans RPT, Mourad MM, Fisher SG, Bramhall SR. Evolving management of metaplasia and dysplasia in Barrett's epithelium. World J Gastroenterol 2016; 22:10316-10324. [PMID: 28058012 PMCID: PMC5175244 DOI: 10.3748/wjg.v22.i47.10316] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 10/30/2016] [Accepted: 12/02/2016] [Indexed: 02/06/2023] Open
Abstract
Oesophageal cancer affects more than 450000 people worldwide and despite continued medical advancements the incidence of oesophageal cancer is increasing. Oesophageal cancer has a 5 year survival of 15%-25% and now globally attempts are made to more aggressively diagnose and treat Barrett's oesophagus the known precursor to invasive disease. Currently diagnosis the of Barrett's oesophagus is predominantly made after endoscopic visualisation and histopathological confirmation. Minimally invasive techniques are being developed to improve the viability of screening programs. The management of Barrett's oesophagus can vary greatly dependent on the presence and severity of dysplasia. There is no consensus between the major international medical societies to determine and agreed surveillance and intervention pathway. In this review we analysed the current literature to demonstrate the evolving management of metaplasia and dysplasia in Barrett's epithelium.
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42
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The evolution and outcome of surveillance of Barrett's oesophagus over four decades in a UK District General Hospital. Eur J Gastroenterol Hepatol 2016; 28:1365-1373. [PMID: 27571366 DOI: 10.1097/meg.0000000000000730] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION We present the long-term outcome of Barrett's oesophagus (BO) at a District General Hospital set against the increasing numbers of patients with gastro-oesophageal reflux disease (GORD). METHODS Data were collected prospectively over 37 years. Comparison of GORD without Barrett's (NoBO) versus BO was performed from 1/1/1977 to 31/12/2001 when the NoBO database closed and outcomes of all cases of BO diagnosed until 31/12/2011 and followed up until 31/12/2013 have been reported. RESULTS During the period 1977-2001 the number of GORD NoBO cases was 11 610, and that of BO cases was 764 (6.2% of all GORD); total number of BO cases in 1977-2011 was 1468. NoBO patients were younger than BO patients: 52.2 versus 61.6 years. There was a male predominance in both groups: NoBO 55% and BO 62% (P<0.0001). The prevalence of oesophageal adenocarcinoma (OAC) was 87/1468 (5.9%) BO cases. Its incidence was 54/1381 (3.9%); the mean interval between the diagnosis of BO and incident OAC was 9 years (range 13 months-25.4 years); there was one OAC per 192 patient-years of follow-up (0.52% per year). Mortality was significantly lower in 37 patients under endoscopic surveillance at the time OAC was diagnosed (51 vs. 88% P=0.0141) partly because of older age and comorbidity of the other 17, in whom serial endoscopy was contraindicated. A proportional hazards model to allow for age estimated that the hazard rate ratio was lower in the surveillance group; however, this difference did not reach statistical significance (0.64, 95% confidence interval 0.30-1.48, P=0.08). Excluding prevalent cancers from both groups, mortality in BO was double that in NoBO (47 vs. 24%). CONCLUSION These 37 years of observation suggest, but do not confirm, that endoscopic surveillance may reduce the risk of death from OAC. Modern technology is likely to yield better results, but larger prospective studies are needed to confirm the benefits.
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43
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Schoofs N, Bisschops R, Prenen H. Progression of Barrett's esophagus toward esophageal adenocarcinoma: an overview. Ann Gastroenterol 2016; 30:1-6. [PMID: 28042232 PMCID: PMC5198232 DOI: 10.20524/aog.2016.0091] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 09/12/2016] [Indexed: 12/11/2022] Open
Abstract
In Barrett's esophagus, normal squamous epithelium is replaced by a metaplastic columnar epithelium as a consequence of chronic gastroesophageal reflux disease. There is a strong association with esophageal adenocarcinoma. In view of the increasing incidence of esophageal adenocarcinoma in the western world, it is important that more attention be paid to the progression of Barrett's esophagus toward esophageal adenocarcinoma. Recently, several molecular factors have been identified that contribute to the sequence towards adenocarcinoma. This might help identify patients at risk and detect new targets for the prevention and treatment of esophageal adenocarcinoma in the future.
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Affiliation(s)
- Nele Schoofs
- Department of Gastroenterology, University Hospitals Leuven and Department of Oncology, KU Leuven, Belgium
| | - Raf Bisschops
- Department of Gastroenterology, University Hospitals Leuven and Department of Oncology, KU Leuven, Belgium
| | - Hans Prenen
- Department of Gastroenterology, University Hospitals Leuven and Department of Oncology, KU Leuven, Belgium
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44
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Voltaggio L, Cimino-Mathews A, Bishop JA, Argani P, Cuda JD, Epstein JI, Hruban RH, Netto GJ, Stoler MH, Taube JM, Vang R, Westra WH, Montgomery EA. Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system. CA Cancer J Clin 2016; 66:408-36. [PMID: 27270763 DOI: 10.3322/caac.21350] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Answer questions and earn CME/CNE In this report, a team of surgical pathologists has provided a review of intraepithelial neoplasia in a host of (but not all) anatomic sites of interest to colleagues in various medical specialties, namely, uterine cervix, ovary, breast, lung, head and neck, skin, prostate, bladder, pancreas, and esophagus. There is more experience with more readily accessible sites (such as the uterine cervix and skin) than with other anatomic sites, and the lack of uniform terminology, together with divergent biology in various sites, makes it difficult to paint a unifying, relevant portrait. The authors' aim was to provide a framework from which to move forward as we care for patients with such precancerous lesions. CA Cancer J Clin 2016;66:408-436. © 2016 American Cancer Society.
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Affiliation(s)
- Lysandra Voltaggio
- Assistant Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Ashley Cimino-Mathews
- Assistant Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Justin A Bishop
- Associate Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Pedram Argani
- Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Jonathan D Cuda
- Assistant Professor of Dermatology, Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Jonathan I Epstein
- Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
- Professor of Urology, Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD
| | - Ralph H Hruban
- Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - George J Netto
- Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Mark H Stoler
- Professor of Pathology, Department of Pathology, University of Virginia Health System, Charlottesville, VA
| | - Janis M Taube
- Associate Professor of Dermatology and Pathology, Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Russell Vang
- Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - William H Westra
- Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Elizabeth A Montgomery
- Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
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45
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Koretz RL, Lipman TO. Understanding Systematic Reviews and Meta-Analyses. JPEN J Parenter Enteral Nutr 2016; 41:316-323. [DOI: 10.1177/0148607116661841] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Ronald L. Koretz
- Olive View–UCLA Medical Center, David Geffen–UCLA School of Medicine, Sylmar and Los Angeles, California, USA
| | - Timothy O. Lipman
- Gastroenterology, Hepatology, and Nutrition Section, Veterans Affairs Medical Center, Washington, DC, USA
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46
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Otaki F, Shaheen NJ. Stratifying Risk in Barrett's Esophagus With Low-grade Dysplasia: Making the Best of a (Not So) Bad Situation. Clin Gastroenterol Hepatol 2016; 14:963-5. [PMID: 27001267 DOI: 10.1016/j.cgh.2016.03.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Revised: 03/09/2016] [Accepted: 03/11/2016] [Indexed: 02/07/2023]
Affiliation(s)
- Fouad Otaki
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, New York
| | - Nicholas J Shaheen
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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47
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Martinucci I, de Bortoli N, Russo S, Bertani L, Furnari M, Mokrowiecka A, Malecka-Panas E, Savarino V, Savarino E, Marchi S. Barrett’s esophagus in 2016: From pathophysiology to treatment. World J Gastrointest Pharmacol Ther 2016; 7:190-206. [PMID: 27158534 PMCID: PMC4848241 DOI: 10.4292/wjgpt.v7.i2.190] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 11/05/2015] [Accepted: 03/18/2016] [Indexed: 02/06/2023] Open
Abstract
Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett’s esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.
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48
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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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49
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Swager AF, Curvers WL, Bergman JJ. Diagnosis by Endoscopy and Advanced Imaging of Barrett's Neoplasia. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016; 908:81-98. [PMID: 27573768 DOI: 10.1007/978-3-319-41388-4_5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Evaluation of patients with Barrett's esophagus (BE) using dye-based chromoendoscopy, optical chromoendoscopy, autofluorescence imaging, or confocal laser endomicroscopy does not significantly increase the number of patients with a diagnosis of early neoplasia compared with high-definition white light endoscopy (HD-WLE) with random biopsy analysis. These newer imaging techniques are not more effective in standard surveillance of patients with BE because the prevalence of early neoplasia is low and HD-WLE with random biopsy analysis detects most cases of neoplasia. The evaluation and treatment of patients with BE and early stage neoplasia should be centralized in tertiary referral centers, where procedures are performed under optimal conditions, by expert endoscopists. Lesions that require resection are almost always detected by HD-WLE, although advanced imaging techniques can detect additional flat lesions. However, these are of limited clinical significance because they are effectively eradicated by ablation therapy. No endoscopic imaging technique can reliably assess submucosal or lymphangio invasion. Endoscopic resection of early stage neoplasia in patients with BE is important for staging and management. Optical chromoendoscopy can also be used to evaluate lesions before endoscopic resection and in follow-up after successful ablation therapy.
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Affiliation(s)
- Anne-Fré Swager
- Department of Gastroenterology and Hepatology, Academic Medical Center, Room B1-245, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands
| | - Wouter L Curvers
- Department of Gastroenterology and Hepatology, Catharina Hospital, Michelangelolaan 2, Eindhoven, 5623 EJ, The Netherlands
| | - Jacques J Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center, Room B1-245, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
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50
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Patel A, Gyawali CP. Definitions of Gastroesophageal Reflux Disease (GERD). DIAGNOSIS AND TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE 2016:1-17. [DOI: 10.1007/978-3-319-19524-7_1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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