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ElFawal MH, Taha O, Abdelaal M, Mohamad D, El Haj II, Tamim H, ElFawal K, El Ansari W. Reflux-Related Abnormalities at Distal oesophagus, Gastric Pouch and Anastomotic Site 4 Years After OAGB: Diagnostic Accuracies of Endoscopy Compared to Biopsy and of Symptoms Compared to Both. Obes Surg 2025; 35:1273-1284. [PMID: 40087244 DOI: 10.1007/s11695-025-07700-3] [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: 11/10/2024] [Revised: 12/30/2024] [Accepted: 01/16/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND The purpose of the current study is to appraise the diagnostic accuracy of upper endoscopy (UE) vs histopathological assessment of patients after one-anastomosis gastric bypass (OAGB), and the presence/absence of symptoms vs these two diagnostic modalities. METHODS Retrospective study of 50 consecutive patients who underwent OAGB during April 2019-April 2020 and consented to participate. Symptoms (symptoms score questionnaire), macroscopic and microscopic data were collected 4 years later to assess distal oesophageal, gastric pouch and anastomotic site changes. Diagnostic accuracies (sensitivity, specificity, positive/negative predictive values) of UE vs biopsy and symptoms vs both were assessed. RESULTS Mean age was 48.6 ± 13.3 years; 66% were females. At 4 years, 54% had symptoms (symptom score ≥ 4). There were no dysplasia or cancer among this series. UE abnormalities included non-erosive gastritis (44%) and ulcer/s or erosive gastritis (16% each); histopathology abnormalities included chronic gastritis (80%) and Barrett's oesophagus (14%). For UE compared to biopsy, highest sensitivity (76.5%) was at the level of distal oesophagus and highest specificity (100%) at anastomotic site. Pertaining to symptoms compared to investigative modality, highest sensitivity (81.5%) was in relation to symptoms vs UE, while highest specificity (82.6%) was for symptoms vs biopsy. CONCLUSIONS It is generally not recommended that (a) UE be used to forecast biopsy abnormalities or lack thereof, except at the anastomotic site, and (b) symptoms or lack thereof be used to forecast the findings of investigative modalities, except with caution, to forecast UE findings in identifying healthy individuals, or to forecast biopsy findings in identifying diseased individuals. Long-term routine follow-up is needed post-OAGB regardless of whether patients are symptomatic or otherwise to rule in or out possible macroscopic/microscopic pathologies. Further research on UE and biopsy findings post-OAGB and their relationships with each other and with symptoms/lack thereof are required to strengthen the thin evidence base.
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Affiliation(s)
| | - Osama Taha
- Bariatric Unit, Plastic Surgery Department, Assiut University, Assiut, Egypt
| | - Mahmoud Abdelaal
- Bariatric Unit, Plastic Surgery Department, Assiut University, Assiut, Egypt
| | - Dyaa Mohamad
- Department of Surgery, American Academy of Cosmetic Surgery Hospital, Dubai, United Arab Emirates
| | - Ihab I El Haj
- Department of Gastroenterology, Faculty of Medicine, University of Saint Georges, Beirut, Lebanon
| | - Hani Tamim
- Department of Biostatistics, American University of Beirut, Beirut, Lebanon
| | - Karim ElFawal
- Mount Lebanon Hospital, University of Balamand, Beirut, Lebanon
| | - Walid El Ansari
- College of Medicine, Ajman University, Ajman, United Arab Emirates.
- Department of Surgery, Hamad Medical Corporation, Doha, Qatar.
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Chandan S, Khan SR, Deliwala SS, Dahiya DS, Mohan BP, Ramai D, Saghir SM, Dhindsa BS, Kassab LL, Facciorusso A, Nandipati K, Yang D, Adler DG. Risk of De Novo Barrett's Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol 2025; 23:33-44.e10. [PMID: 39059544 DOI: 10.1016/j.cgh.2024.06.041] [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: 02/16/2024] [Revised: 06/23/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND & AIMS Sleeve gastrectomy (SG) is one of the most commonly performed bariatric procedures worldwide. Gastroesophageal reflux disease (GERD) is a major concern in patients undergoing SG and is a risk factor for Barrett's esophagus (BE). We conducted a systematic review and meta-analysis to assess the incidence of and analyze predictive factors for post-SG BE. METHODS A comprehensive literature search was conducted in April 2024, for studies reporting on incidence of BE, erosive esophagitis (EE), and hiatal hernia (HH) post-SG. Primary outcomes were post-SG pooled rates of de novo BE, EE, GERD symptoms, proton pump inhibitor use, and HH. Meta-regression analysis was performed to assess if patient and post-SG factors influenced the rates of post-SG BE. RESULTS Nineteen studies with 2046 patients (79% females) were included. Mean age was 42.2 years (standard deviation, 11.1) and follow-up ranged from 2 to 11.4 years. The pooled rate of de novo BE post-SG was 5.6% (confidence interval, 3.5-8.8). Significantly higher pooled rates of EE (risk ratio [RR], 3.37], HH (RR, 2.09), GER/GERD symptoms (RR, 3.32), and proton pump inhibitor use (RR, 3.65) were found among patients post-SG. GER/GERD symptoms post-SG positively influenced the pooled BE rates, whereas age, sex, body mass index, post-SG EE, and HH did not. CONCLUSIONS Our analysis shows that SG results in a significantly increased risk of de novo BE and higher rates of EE, proton pump inhibitor use, and HH. Our findings suggest that clinicians should routinely screen patients with SG for BE and future surveillance intervals should be followed as per societal guidelines.
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Affiliation(s)
- Saurabh Chandan
- Center for Interventional Endoscopy, Advent Health, Orlando, Florida
| | - Shahab R Khan
- Department of Internal Medicine, Brigham's & Women Hospital, Boston, Massachusetts
| | - Smit S Deliwala
- Department of Gastroenterology, Emory University, Atlanta, Georgia
| | - Dushyant S Dahiya
- Division of Gastroenterology Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, Kansas
| | | | - Daryl Ramai
- Department of Gastroenterology, Hepatology & Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts
| | - Syed M Saghir
- Division of Gastroenterology and Hepatology, Creighton University School of Medicine, Omaha, Nebraska
| | - Banreet S Dhindsa
- Department of Gastroenterology, NYU Langone Medical Center, New York, New York
| | - Lena L Kassab
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy
| | - Kalyana Nandipati
- Division of Surgery, Gastroenterology, Creighton University School of Medicine, Omaha, Nebraska
| | - Dennis Yang
- Center for Interventional Endoscopy, Advent Health, Orlando, Florida
| | - Douglas G Adler
- Center for Advanced Therapeutic Endoscopy, Centura Health, Porter Adventist Hospital, Denver, Colorado.
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Rosmolen WD, Pouw RE, Bergman JJ, Sprangers MAG, Nieuwkerk PT. Reasons for fear of cancer recurrence after endoscopic treatment of T1 esophageal adenocarcinoma. A semi-structured interview study. Dis Esophagus 2024; 37:doae067. [PMID: 39169835 PMCID: PMC11605615 DOI: 10.1093/dote/doae067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 07/12/2024] [Accepted: 08/10/2024] [Indexed: 08/23/2024]
Abstract
Prior research has shown that patients with early Barrett's neoplasia treated endoscopically report at least the same level of fear for cancer recurrence as patients treated surgically for a more advanced disease stage. The aim of this qualitative study was to gain insight into the reasons why endoscopically treated patients fear or not fear cancer recurrence. Patients treated endoscopically for T1 esophageal adenocarcinoma participated in a semi-structured interview. Patients were asked open questions about their fear of cancer recurrence and presented an a priori list of possible reasons for experiencing or not experiencing fear of cancer recurrence. Data saturation was reached with 12 patients who added 7 new reasons. Reasons that induced fear of cancer recurrence were related to physical symptoms, if cancer was diagnosed as an accidental finding and experiences with cancer in close relations. Endoscopic surveillance was mentioned as a reason for not experiencing fear of cancer recurrence. Patients reduced their fear of cancer recurrence by talking to close relations and seeking distraction. Caregivers reduced patients fear of cancer recurrence by giving adequate information and by showing photo of the treatment and the results of the treatment. According to patients with early Barrett's neoplasia, receiving comprehensible information about the risk of recurrence and potential symptoms that may or may not be indicative of cancer recurrence, and continuing endoscopic surveillance, reduced fear of cancer recurrence. We recommend that healthcare providers discuss fear of cancer recurrence with their patients to enable tailoring information provision to their needs.
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Affiliation(s)
- Wilda D Rosmolen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Boelelaan 1117, 1118, 1081HV Amsterdam, The Netherlands
| | - Roos E Pouw
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Boelelaan 1117, 1118, 1081HV Amsterdam, The Netherlands
| | - Jacques J Bergman
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Boelelaan 1117, 1118, 1081HV Amsterdam, The Netherlands
| | - Mirjam A G Sprangers
- Department of Medical Psychology, Amsterdam UMC, University of Amsterdam, Boelelaan 1117, 1118, 1081HV Amsterdam, The Netherlands
| | - Pythia T Nieuwkerk
- Department of Medical Psychology, Amsterdam UMC, University of Amsterdam, Boelelaan 1117, 1118, 1081HV Amsterdam, The Netherlands
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Eltahir Z, Eisa AA, Keayta MH, Aljhani YA, Alfaroqui O, Jenkins GJ. Microenvironment and Biomarkers in Esophageal Cancers: An Approach for Early Detection and Identification. Cureus 2024; 16:e74242. [PMID: 39717344 PMCID: PMC11663622 DOI: 10.7759/cureus.74242] [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] [Accepted: 11/22/2024] [Indexed: 12/25/2024] Open
Abstract
Background Esophageal cancer is a prevalent and highly lethal malignancy worldwide, comprising two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While both subtypes are frequently encountered, ESCC has historically been more common globally. However, in recent decades, EAC has emerged as the predominant type in industrialized nations, often developing from Barrett's esophagus, a condition driven by chronic gastroesophageal reflux disease (GERD). ESCC typically occurs in the upper esophagus, whereas EAC arises near the lower gastroesophageal junction. The etiology of esophageal cancer is multifactorial, with diverse causes and clinical management strategies. Notably, diagnosing tumors located in the lower esophagus presents significant challenges. EAC is particularly prone to diagnostic errors, as it can be mistaken for ESCC. This study aims to investigate potential histological biomarkers for EAC to facilitate early and accurate identification of histological changes, especially in patients with GERD. Methods This cross-sectional study examined archival histological samples from patients with lower esophageal abnormalities. Immunohistochemistry was used to investigate the P63 marker, while Masson's trichrome stain was employed to evaluate cancer progression and associated microenvironmental changes. Results A total of 104 cases were analyzed, including 13 with known P63-positive staining and five P63-negative controls. The remaining cases consisted of both precancerous and cancerous tissues diagnosed as EAC. Among these, 86 cases showed negative P63 staining, confirming their origin from non-squamous cells and supporting their classification as true Barrett's-related epithelium. In contrast, five of the 13 SCC control cases exhibited P63 positivity, demonstrating a highly significant association (p < 0.00001). Additionally, Masson's trichrome staining revealed stromal collagen fibers infiltrating the malignant tissue areas. Conclusions This study highlights the significance of the P63 marker in distinguishing between ESCC and EAC. It also suggests a potential role for Masson's trichrome stain in identifying early microenvironmental changes associated with EAC progression.
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Affiliation(s)
- Zakaria Eltahir
- College of Applied Medical Sciences, Department of Clinical Laboratory Sciences, Taibah University, Medina, SAU
- College of Medicine, Translation Clinical Trials Unit, Taibah University, Medina, SAU
| | - Alaa A Eisa
- Department of Pathology and Laboratory Medicine, Taibah University, Medina, SAU
| | - Mohamed H Keayta
- College of Applied Medical Sciences, Department of Clinical Laboratory Sciences, Taibah University, Medina, SAU
| | - Yousif A Aljhani
- College of Applied Medical Sciences, Department of Clinical Laboratory Sciences, Taibah University, Medina, SAU
| | - Omar Alfaroqui
- Department of Histopathology, King Fahad Hospital, Medina, SAU
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Ma TT, Chang Z, Zhang N, Xu H. Application of electronic nose technology in the diagnosis of gastrointestinal diseases: a review. J Cancer Res Clin Oncol 2024; 150:401. [PMID: 39192027 PMCID: PMC11349790 DOI: 10.1007/s00432-024-05925-w] [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: 01/02/2024] [Accepted: 08/14/2024] [Indexed: 08/29/2024]
Abstract
Electronic noses (eNoses) are electronic bionic olfactory systems that use sensor arrays to produce response patterns to different odors, thereby enabling the identification of various scents. Gastrointestinal diseases have a high incidence rate and occur in 9 out of 10 people in China. Gastrointestinal diseases are characterized by a long course of symptoms and are associated with treatment difficulties and recurrence. This review offers a comprehensive overview of volatile organic compounds, with a specific emphasis on those detected via the eNose system. Furthermore, this review describes the application of bionic eNose technology in the diagnosis and screening of gastrointestinal diseases based on recent local and international research progress and advancements. Moreover, the prospects of bionic eNose technology in the field of gastrointestinal disease diagnostics are discussed.
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Affiliation(s)
- Tan-Tan Ma
- Department of Gastroenterology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China
| | - Zhiyong Chang
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, 130022, China
| | - Nan Zhang
- Department of Gastroenterology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China.
| | - Hong Xu
- Department of Gastroenterology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China.
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Vantanasiri K, Kamboj AK, Kisiel JB, Iyer PG. Advances in Screening for Barrett Esophagus and Esophageal Adenocarcinoma. Mayo Clin Proc 2024; 99:459-473. [PMID: 38276943 PMCID: PMC10922282 DOI: 10.1016/j.mayocp.2023.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/11/2023] [Accepted: 07/18/2023] [Indexed: 01/27/2024]
Abstract
Esophageal adenocarcinoma (EAC), the primary form of esophageal cancer in the United States, is a lethal cancer with exponentially increasing incidence. Screening for Barrett esophagus (BE), the only known precursor to EAC, followed by endoscopic surveillance to detect dysplasia and early-stage EAC and subsequent endoscopic treatment (to prevent progression of dysplasia to EAC and to treat early-stage EAC effectively) is recommended by several society guidelines. Sedated endoscopy (the primary current tool for BE screening) is both invasive and expensive, limiting its widespread use. In this review, we aim to provide a comprehensive review of recent innovations in the nonendoscopic detection of BE and EAC. These include swallowable cell sampling devices combined with protein and epigenetic biomarkers (which are now guideline endorsed as alternatives to sedated endoscopy), tethered capsule endomicroscopy, emerging peripheral blood-sampled molecular biomarkers, and exhaled volatile organic compounds. We also summarize progress and challenges in assessing BE and EAC risk, which is an important complementary component of the process for the clinical implementation of these innovative nonendoscopic tools, and propose a new paradigm for the strategy to reduce EAC incidence and mortality.
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Affiliation(s)
- Kornpong Vantanasiri
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Amrit K Kamboj
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - John B Kisiel
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Prasad G Iyer
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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Peabody JW, Cruz JD, Ganesan D, Paculdo D, Critchley-Thorne RJ, Wani S, Shaheen NJ. A Randomized Controlled Study on Clinical Adherence to Evidence-Based Guidelines in the Management of Simulated Patients With Barrett's Esophagus and the Clinical Utility of a Tissue Systems Pathology Test: Results From Q-TAB. Clin Transl Gastroenterol 2024; 15:e00644. [PMID: 37767993 PMCID: PMC10810603 DOI: 10.14309/ctg.0000000000000644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 09/19/2023] [Indexed: 09/29/2023] Open
Abstract
INTRODUCTION Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma. Physicians infrequently adhere to guidelines for managing BE, leading to either reduced detection of dysplasia or inappropriate re-evaluation. METHODS We conducted a three-arm randomized controlled trial with 2 intervention arms to determine the impact of a tissue systems pathology (TSP-9) test on the adherence to evidence-based guidelines for simulated patients with BE. Intervention 1 received TSP-9 results, and intervention 2 had the option to order TSP-9 results. We collected data from 259 practicing gastroenterologists and gastrointestinal surgeons who evaluated and made management decisions for 3 types of simulated patients with BE: nondysplastic BE, indefinite for dysplasia, and low-grade dysplasia. RESULTS Intervention 1 was significantly more likely to correctly assess risk of progression to high-grade dysplasia/esophageal adenocarcinoma and offer treatment in accordance with US society guidelines compared with the control group (+6.9%, 95% confidence interval +1.4% to +12.3%). There was no significant difference in ordering guideline-recommended endoscopic eradication therapy. However, for cases requiring annual endoscopic surveillance, we found significant improvement in adherence for intervention 1, with a difference-in-difference of +18.5% ( P = 0.019). Intervention 2 ordered the TSP-9 test in 21.9% of their cases. Those who ordered the test performed similarly to intervention 1; those who did not, performed similarly to the control group. DISCUSSION The TSP-9 test optimized adherence to clinical guidelines for surveillance and treatment of both patients with BE at high and low risk of disease progression. Use of the TSP-9 test can enable physicians to make risk-aligned management decisions, leading to improved patient health outcomes.
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Affiliation(s)
- John W. Peabody
- QURE Healthcare, San Francisco, California, USA
- University of California, San Francisco, California, USA
- University of California, Los Angeles, California, USA
| | | | | | | | | | - Sachin Wani
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | - Nicholas J. Shaheen
- University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Tang JC, Magalhães R, Wisniowiecki A, Razura D, Walker C, Applegate BE. Optical coherence tomography technology in clinical applications. BIOPHOTONICS AND BIOSENSING 2024:285-346. [DOI: 10.1016/b978-0-44-318840-4.00017-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
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Tsai MC, Yen HH, Tsai HY, Huang YK, Luo YS, Kornelius E, Sung WW, Lin CC, Tseng MH, Wang CC. Artificial intelligence system for the detection of Barrett's esophagus. World J Gastroenterol 2023; 29:6198-6207. [PMID: 38186865 PMCID: PMC10768395 DOI: 10.3748/wjg.v29.i48.6198] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 11/13/2023] [Accepted: 12/12/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Barrett's esophagus (BE), which has increased in prevalence worldwide, is a precursor for esophageal adenocarcinoma. Although there is a gap in the detection rates between endoscopic BE and histological BE in current research, we trained our artificial intelligence (AI) system with images of endoscopic BE and tested the system with images of histological BE. AIM To assess whether an AI system can aid in the detection of BE in our setting. METHODS Endoscopic narrow-band imaging (NBI) was collected from Chung Shan Medical University Hospital and Changhua Christian Hospital, resulting in 724 cases, with 86 patients having pathological results. Three senior endoscopists, who were instructing physicians of the Digestive Endoscopy Society of Taiwan, independently annotated the images in the development set to determine whether each image was classified as an endoscopic BE. The test set consisted of 160 endoscopic images of 86 cases with histological results. RESULTS Six pre-trained models were compared, and EfficientNetV2B2 (accuracy [ACC]: 0.8) was selected as the backbone architecture for further evaluation due to better ACC results. In the final test, the AI system correctly identified 66 of 70 cases of BE and 85 of 90 cases without BE, resulting in an ACC of 94.37%. CONCLUSION Our AI system, which was trained by NBI of endoscopic BE, can adequately predict endoscopic images of histological BE. The ACC, sensitivity, and specificity are 94.37%, 94.29%, and 94.44%, respectively.
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Affiliation(s)
- Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua 500, Taiwan
- Artificial Intelligence Development Center, Changhua Christian Hospital, Changhua 500, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 400, Taiwan
| | - Hui-Yu Tsai
- Department of Medical Informatics, Chung Shan Medical University, Taichung 402, Taiwan
| | - Yu-Kai Huang
- Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Yu-Sin Luo
- Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Edy Kornelius
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
- Department of Endocrinology and Metabolism, Chung-Shan Medical University Hospital, Taichung 402, Taiwan
| | - Wen-Wei Sung
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
- Department of Urology, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Chun-Che Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Ming-Hseng Tseng
- Department of Medical Informatics, Chung Shan Medical University, Taichung 402, Taiwan
- Information Technology Office, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Chi-Chih Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
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Giacometti C, Gusella A, Cassaro M. Gastro-Esophageal Junction Precancerosis: Histological Diagnostic Approach and Pathogenetic Insights. Cancers (Basel) 2023; 15:5725. [PMID: 38136271 PMCID: PMC10741421 DOI: 10.3390/cancers15245725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 11/23/2023] [Accepted: 12/05/2023] [Indexed: 12/24/2023] Open
Abstract
Barrett's esophagus (BE) was initially defined in the 1950s as the visualization of gastric-like mucosa in the esophagus. Over time, the definition has evolved to include the identification of goblet cells, which confirm the presence of intestinal metaplasia within the esophagus. Chronic gastro-esophageal reflux disease (GERD) is a significant risk factor for adenocarcinoma of the esophagus, as intestinal metaplasia can develop due to GERD. The development of adenocarcinomas related to BE progresses in sequence from inflammation to metaplasia, dysplasia, and ultimately carcinoma. In the presence of GERD, the squamous epithelium changes to columnar epithelium, which initially lacks goblet cells, but later develops goblet cell metaplasia and eventually dysplasia. The accumulation of multiple genetic and epigenetic alterations leads to the development and progression of dysplasia. The diagnosis of BE requires the identification of intestinal metaplasia on histologic examination, which has thus become an essential tool both in the diagnosis and in the assessment of dysplasia's presence and degree. The histologic diagnosis of BE dysplasia can be challenging due to sampling error, pathologists' experience, interobserver variation, and difficulty in histologic interpretation: all these problems complicate patient management. The development and progression of Barrett's esophagus (BE) depend on various molecular events that involve changes in cell-cycle regulatory genes, apoptosis, cell signaling, and adhesion pathways. In advanced stages, there are widespread genomic abnormalities with losses and gains in chromosome function, and DNA instability. This review aims to provide an updated and comprehensible diagnostic approach to BE based on the most recent guidelines available in the literature, and an overview of the pathogenetic and molecular mechanisms of its development.
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Affiliation(s)
- Cinzia Giacometti
- Pathology Unit, Department of Diagnostic Services, ULSS 6 Euganea, 35131 Padova, Italy; (A.G.); (M.C.)
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Swei E, Helmkamp L, Samuels J, Schoen J, Scott FI, Wani S, Sullivan S. Reflux and Barrett's esophagus after sleeve gastrectomy: analysis of a statewide database. Surg Obes Relat Dis 2023; 19:1023-1029. [PMID: 36948973 DOI: 10.1016/j.soard.2023.02.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 12/12/2022] [Accepted: 02/04/2023] [Indexed: 02/17/2023]
Abstract
BACKGROUND Recent studies have suggested that sleeve gastrectomy (SG) is associated with the development of Barrett esophagus (BE) even in the absence of gastroesophageal reflux disease (GERD) symptoms. OBJECTIVE The aim of this study was to assess the rates of upper endoscopy and incidence of new BE diagnoses in patients undergoing SG. SETTING This was a claims-data study of patients who underwent SG between 2012 and 2017 while enrolled in a U.S. statewide database. METHODS Diagnostic claims data were used to identify pre- and postoperative rates of upper endoscopy, GERD, reflux esophagitis, and BE. Time-to-event analysis using a Kaplan-Meier approach was performed to estimate the cumulative postoperative incidence of these conditions. RESULTS We identified 5562 patients who underwent SG between 2012 and 2017. Of these, 1972 patients (35.5%) had at least 1 diagnostic record of upper endoscopy. The preoperative incidences of a diagnosis of GERD, esophagitis, and BE were 54.9%, 14.6%, and .9%, respectively. The predicted postoperative incidences of GERD, esophagitis, and BE, respectively, were 18%, 25.4%, and 1.6% at 2 years and 32.1%, 85.0%, and 6.4% at 5 years. CONCLUSIONS In this large statewide database, rates of esophagogastroduodenoscopy remained low after SG, but the incidence of a new postoperative esophagitis or BE diagnosis in patients who underwent esophagogastroduodenoscopy was higher than in the general population. Patients undergoing SG may have a disproportionately high risk of developing reflux complications including BE after surgery.
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Affiliation(s)
- Eric Swei
- Division of Gastroenterology, University of Colorado School of Medicine, Aurora, Colorado
| | - Laura Helmkamp
- Adult and Child Center for Outcomes Research and Delivery Science (ACCORDS), University of Colorado School of Medicine, Aurora, Colorado
| | - Jason Samuels
- Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Jonathan Schoen
- Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Frank I Scott
- Division of Gastroenterology, University of Colorado School of Medicine, Aurora, Colorado
| | - Sachin Wani
- Division of Gastroenterology, University of Colorado School of Medicine, Aurora, Colorado
| | - Shelby Sullivan
- Division of Gastroenterology, University of Colorado School of Medicine, Aurora, Colorado.
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Samuels TL, Blaine-Sauer S, Yan K, Plehhova K, Coyle C, Johnston N. Topical Alginate Protection against Pepsin-Mediated Esophageal Damage: E-Cadherin Proteolysis and Matrix Metalloproteinase Induction. Int J Mol Sci 2023; 24:ijms24097932. [PMID: 37175640 PMCID: PMC10178445 DOI: 10.3390/ijms24097932] [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: 02/27/2023] [Revised: 04/18/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
Epithelial barrier dysfunction is a hallmark of gastroesophageal reflux disease (GERD) related to symptom origination, inflammatory remodeling and carcinogenesis. Alginate-based antireflux medications were previously shown to topically protect against peptic barrier disruption, yet the molecular mechanisms of injury and protection were unclear. Herein, Barrett's esophageal (BAR-T) cells were pretreated with buffered saline (HBSS; control), dilute alginate medications (Gaviscon Advance or Gaviscon Double Action, Reckitt Benckiser), a viscosity-matched placebo, or ADAM10 and matrix metalloproteinase (MMP) inhibitors before exposure to HBSS pH7.4 or pH4 ± 1 mg/mL pepsin for 10-60 min. Cell viability was assessed by ATP assay; mediators of epithelial integrity, E-cadherin, ADAM10, and MMPs were examined by Western blot and qPCR. Alginate rescued peptic reduction of cell viability (p < 0.0001). Pepsin-pH4 yielded E-cadherin fragments indicative of regulated intramembrane proteolysis (RIP) which was not rescued by inhibitors of known E-cadherin sheddases. Transcriptional targets of E-cadherin RIP fragments were elevated at 24 h (MMP-1,2,9,14; p < 0.01). Alginate rescued E-cadherin cleavage, ADAM10 maturation, and MMP induction (p < 0.01). Results support RIP as a novel mechanism of peptic injury during GERD. Alginate residue after wash-out to mimic physiologic esophageal clearance conferred lasting protection against pepsin-induced molecular mechanisms that may exacerbate GERD severity and promote carcinogenesis in the context of weakly acidic reflux.
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Affiliation(s)
- Tina L Samuels
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Simon Blaine-Sauer
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Ke Yan
- Department of Pediatrics Quantitative Health Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | | | | | - Nikki Johnston
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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13
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Hartgerink C, Nimri FM, Zuchelli T, Jafri SM, Piraka C. Band Ligation Can Be Used to Treat Barrett's Esophagus and Concurrent Esophageal Varices: A Case Series. Dig Dis Sci 2023; 68:1381-1385. [PMID: 36131048 DOI: 10.1007/s10620-022-07696-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 09/05/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Patients with Barrett's esophagus (BE) and esophageal varices present a unique management dilemma. Endoscopic ablation and endoscopic resection are not suitable treatment options due to bleeding risk. Data are limited on successful eradication of BE and esophageal varices utilizing band ligation. AIMS To assess the outcomes of patients with BE and esophageal varices treated with banding. METHODS Retrospective analysis of patients with BE and esophageal varices who were treated with band ligation. RESULTS A total of eight patients were included in the case series. In all eight cases, BE and esophageal varices were successfully treated with band ligation alone. There were no bleeding, perforation or infectious complications in any patients undergoing banding for treatment of BE. Four patients had biopsy-proven dysplasia prior to treatment with band ligation. After band ligation, the 2 of 4 dysplastic cases that had repeat biopsies showed histologic resolution of the dysplasia. All patients who received banding for BE were followed at least yearly except for one patient lost to follow up. No interval esophageal cancers were reported in any patients with BE that were banded. CONCLUSIONS Band ligation was used to treat BE pathology in eight patients with esophageal varices. Treatment of dysplasia through this method yielded negative biopsies both for dysplasia and BE on repeat endoscopy. This case series highlights the value of utilizing band ligation to address the management dilemma of BE in the context of esophageal varices.
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Affiliation(s)
- Colin Hartgerink
- Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI, 48201, USA.
| | - Faisal M Nimri
- Department of Gastroenterology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA
| | - Tobias Zuchelli
- Department of Gastroenterology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA
| | - Syed-Mohammed Jafri
- Department of Gastroenterology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA
| | - Cyrus Piraka
- Department of Gastroenterology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA
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14
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Stawinski PM, Dziadkowiec KN, Kuo LA, Echavarria J, Saligram S. Barrett's Esophagus: An Updated Review. Diagnostics (Basel) 2023; 13:diagnostics13020321. [PMID: 36673131 PMCID: PMC9858189 DOI: 10.3390/diagnostics13020321] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/05/2022] [Accepted: 11/09/2022] [Indexed: 01/18/2023] Open
Abstract
Barrett’s esophagus (BE) is a change in the distal esophageal mucosal lining, whereby metaplastic columnar epithelium replaces squamous epithelium of the esophagus. This change represents a pre-malignant mucosal transformation which has a known association with the development of esophageal adenocarcinoma. Gastroesophageal reflux disease is a risk factor for BE, other risk factors include patients who are Caucasian, age > 50 years, central obesity, tobacco use, history of peptic stricture and erosive gastritis. Screening for BE remains selective based on risk factors, a screening program in the general population is not routinely recommended. Diagnosis of BE is established with a combination of endoscopic recognition, targeted biopsies, and histologic confirmation of columnar metaplasia. We aim to provide a comprehensive review of the epidemiology, pathogenesis, screening and advanced techniques of detecting and eradicating Barrett’s esophagus.
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15
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High rate of missed Barrett's esophagus when screening with forceps biopsies. Esophagus 2023; 20:143-149. [PMID: 35864425 PMCID: PMC9813185 DOI: 10.1007/s10388-022-00943-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 07/11/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Screening for Barrett's esophagus (BE) with endoscopy plus forceps biopsy (FB) has poor compliance with the recommended Seattle protocol and fails to sample large areas of mucosa. This statistical modeling study estimates, for the first time, the actual frequency of missed BE cases by FB. METHODS Published, calibrated models in the literature were combined to calculate the age-specific prevalence of BE in white males with gastroesophageal reflux disease (GERD). We started with estimates of the prevalence of BE and GERD, and applied the relative risk for BE in patients with GERD based on the literature. This created estimates of the true prevalence of BE in white males with GERD by decade of life. The proportion of BE missed was calculated as the difference between the prevalence and the proportion with a positive screen. RESULTS The prevalence of BE in white males with GERD was 8.9%, 12.1%, 15.3%, 18.7% and 22.0% for the third through eighth decades of life. Even after assuming no false positives, missed cases of BE were about 50% when estimated for patients of ages 50 or 60 years, and over 60% for ages of 30, 40 or 70 years. Sensitivity analysis was done for all variables in the model calculations. For ages 50 and 60 years, this resulted in values from 30.3 to 57.3% and 36.4 to 60.9%. CONCLUSION Screening for BE with endoscopy and FB misses approximately 50% of BE cases. More sensitive methods of BE detection or better adherence to the Seattle protocol are needed.
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16
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Vedantam S, Katona BW, Sussman DA, Kumar S. Outcomes of upper endoscopy screening in Lynch syndrome: a meta-analysis. Gastrointest Endosc 2023; 97:2-10.e1. [PMID: 36084717 DOI: 10.1016/j.gie.2022.08.040] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/17/2022] [Accepted: 08/30/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Lynch syndrome (LS) predisposes affected individuals to a high lifetime risk of malignancies, including colorectal, endometrial, gastric, and duodenal cancers. The role of upper GI (UGI) cancer screening in LS has been uncertain, but recent studies have evaluated its utility. METHODS Databases were queried through December 2021 to identify studies that examined upper endoscopy screening in LS using EGD. Mantel-Haenszel pooled odds ratios and 95% confidence intervals (CIs) for outcomes were constructed using a random-effects model to identify pooled odds of endoscopic findings in persons with LS. Event rates for detection of gastric and duodenal cancers, high-risk lesions, and clinically actionable findings were calculated. Statistical heterogeneity was assessed using the I2 statistic. RESULTS Nine studies were identified with 2356 LS patients undergoing approximately 7838 EGDs. In total, 47 LS-associated UGI cancers (18 gastric and 29 duodenal cancers), 237 high-risk lesions, and 335 clinically actionable findings were identified. The pooled event rate for detection of any UGI cancer, high-risk lesions, and clinically actionable findings during screening were .9% (95% CI, .3-2.1; I2 = 89%), 4.2% (95% CI, 1.6-10.9; I2 = 98%), and 6.2% (95% CI, 2.2-16.5; I2 = 99%), respectively. There was no difference between LS-associated gene and gastric or duodenal cancer detection. CONCLUSIONS In LS, there is evidence that endoscopic screening detects UGI cancers, precancerous lesions, and other clinically actionable findings that favor its use as a part of cancer risk management in LS.
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Affiliation(s)
- Shyam Vedantam
- Department of Medicine, University of Miami, Miami, Florida, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Daniel A Sussman
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, Miami, Florida, USA
| | - Shria Kumar
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, Miami, Florida, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine at the University of Miami, Miami, Florida, USA.
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17
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Cruz JDC, Paculdo D, Ganesan D, Baker M, Critchley-Thorne RJ, Shaheen NJ, Wani S, Peabody JW. Clinical variation in surveillance and management of Barrett's esophagus: A cross-sectional study of gastroenterologists and gastrointestinal surgeons. Medicine (Baltimore) 2022; 101:e32187. [PMID: 36595793 PMCID: PMC9794215 DOI: 10.1097/md.0000000000032187] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Appropriate surveillance and treatment of Barrett's esophagus (BE) is vital to prevent disease progression and decrease esophageal adenocarcinoma (EAC)-related mortality. We sought to determine the variation in BE care and identify improvement opportunities. 275 physicians (113 general gastroenterologists, 128 interventional gastroenterologists, 34 gastrointestinal surgeons) cared for 3 simulated patients, one each from 3 BE clinical scenarios: non-dysplastic BE (NDBE), BE indefinite for dysplasia (IND), and BE with low grade dysplasia (LGD), and care scores were measured against societal guidelines. Overall quality-of-care scores ranged from 17% to 85% with mean of 47.9% ± 11.8% for NDBE, 50.8% ± 11.7% for IND, and 52.7% ± 12.2% for LGD. Participants appropriately determined risk of progression 20.3% of the time: 14.4% for NDBE cases, 19.9% for LGD cases, and 26.8% for IND cases (P = .001). Treatment and follow-up care scores averaged 12.9% ± 17.5% overall. For the LGD cases, guideline-recommended twice-daily PPI treatment was ordered only 24.7% of the time. Guideline-based follow-up endoscopic surveillance was done in only 27.7% of NDBE cases and 32.7% of IND cases. For the LGD cases, 45.4% ordered endoscopic eradication therapy while 25.1% chose annual endoscopic surveillance. Finally, participants provided counseling on lifestyle modifications in just 20% of cases. Overall care of patients diagnosed with BE varied widely and showed room for improvement. Specific opportunities for improvement were adherence to guideline recommended surveillance intervals, patient counseling, and treatment selection for LGD. Physicians would potentially benefit from additional BE education, endoscopic advances, and better methods for risk stratification.
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Affiliation(s)
| | | | | | | | | | | | - Sachin Wani
- University of Colorado Anschutz Medical Center, Aurora, CO
| | - John W Peabody
- QURE Healthcare, San Francisco, CA
- University of California, San Francisco, CA
- University of California, Los Angeles, CA
- *Correspondence: John W Peabody QURE Healthcare, 450 Pacific Avenue, Suite 200, San Francisco, CA 94133 (e-mail: )
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18
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Zhu M, Shi B, Li C, Xu S. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway. Open Med (Wars) 2022; 17:1883-1895. [PMID: 36518116 PMCID: PMC9719370 DOI: 10.1515/med-2022-0601] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 10/07/2022] [Accepted: 10/16/2022] [Indexed: 01/23/2025] Open
Abstract
Ten-eleven translocation 3 (TET3) participates in tumorigenesis and malignant transformation by mediating DNA demethylation and specific gene activation in malignances. This study aims to elucidate its molecular function and regulatory mechanism in esophageal squamous cell carcinoma (ESCC). Stable ESCC cells that infected with TET3 overexpression (OE) and knockdown lentiviral vector had been established. The biological behaviors and molecular mechanism of TET3 were demonstrated by cell biology experiments in vitro and in vivo. Tissues from patients with ESCC were used to demonstrate the clinical value of TET3. Our findings revealed that TET3 is highly expressed in ESCC tissues and related to poor prognosis of patients with ESCC. OE of TET3 presented a significant effect on proliferation, metastatic potential, and spheroid formation of ESCC cells by activating the PI3K/AKT/GSK3β/β-catenin axis. Knockdown of TET3 could remarkably reverse these malignant phenotypes. Patients with ESCC with high TET3 expression resulted in a shorter overall survival (OS) and disease-free survival. Based on the multivariate analysis, TET3 could be an independent favorable factor for predicting OS and recurrence. The high expression of TET3 not only aggravates malignant behaviors in vitro and in vivo but also becomes a novel biomarker for clinical monitoring and individualized precision treatment for patients with ESCC.
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Affiliation(s)
- Maoling Zhu
- Department of Gastroenterology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, P.R. China
| | - Bowen Shi
- Department of Thoracic Surgery, Changhai Hospital, Navy Military Medical University, Shanghai 200438, China
| | - Chunguang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Shuchang Xu
- Department of Gastroenterology, Tongji Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
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19
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Kolb JM, Fox C, Friedman C, Scott FI, Han S, Marsh M, McCarter M, Kaplan J, Lieu CH, Gleisner A, Katzka DA, Wani S. Prognostic Impact of the Presence of Barrett's Esophagus and Intestinal Metaplasia on Esophageal Adenocarcinoma Survival. FOREGUT (THOUSAND OAKS, CALIF.) 2022; 2:356-364. [PMID: 36578279 PMCID: PMC9793872 DOI: 10.1177/26345161211033277] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Background/Aims Barrett's esophagus (BE), defined by the presence of intestinal metaplasia (IM) on histology, is thought to be the only identifiable precursor lesion for esophageal adenocarcinoma (EAC). Recent studies have suggested the possibility of an alternate, non-IM associated EAC that is a more aggressive form of EAC with worse survival. Among EAC patients, we aimed to compare survival of patients with and without IM at the time of diagnosis. Methods This was a retrospective cohort study of all patients with histologic confirmed EAC evaluated at a tertiary care center from 2013 to 2019. Cases were categorized according to the presence or absence of IM on histologic specimens (Group I-IM-EAC and Group II-non-IM-EAC). We compared demographic characteristics, clinical stage, therapy, and survival between the 2 groups using the Chi-square and ANOVA tests (for categorical and continuous variables, respectively). We used Cox proportional hazards regression to determine the association of IM with overall survival, adjusting for sex, age at diagnosis, tumor location, histologic grade, and clinical stage. Results A total of 475 patients were included in this analysis (mean age 64.8 years [SD 10.8], 89% white) and 109 (23.0%) had no evidence of IM. Compared with IM-EAC (Group I), individuals in the non-IM-EAC group were younger (P = .01) and had a greater proportion of patients diagnosed with advanced disease (49.5 vs 20.2% for stage 4, P < .001). These patients were less likely to undergo endoscopic therapy alone (0.92% vs 29.78%, P < .001) or surgery alone (0 vs 9.84%, P = .001). On multivariable analysis, the presence of IM-EAC was associated with improved overall survival compared to non-IM-EAC (HR 0.69, 95% CI 0.49-0.96). Additional factors associated with poor survival was increasing stage of diagnosis (HR 6.49: 95% CI 3.77-11.15 for stage 4, HR 2.19: 95% CI 1.25-3.84 for stage 3, HR 2.04: 95% CI 0.98-4.25 for stage 2 compared to stage 1) and more advanced histologic stage (HR 2.00, 95% CI 1.26-3.19) for poorly/undifferentiated compared to well differentiated). Conclusions EAC without the presence of IM on histology was associated with worse survival compared to those with IM. Future prospective studies with detailed molecular sequencing are required to clarify if 2 separate phenotypes of EAC exist (IM-EAC and non-IM-EAC). If confirmed, this may have significant implications for screening and management strategies.
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Affiliation(s)
| | - Charlie Fox
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Chloe Friedman
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Frank I. Scott
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Samuel Han
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Megan Marsh
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Martin McCarter
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Jeffrey Kaplan
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | | | - Ana Gleisner
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | | | - Sachin Wani
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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20
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Kusano C, Singh R, Lee YY, Soh YSA, Sharma P, Ho KY, Gotoda T. Global variations in diagnostic guidelines for Barrett's esophagus. Dig Endosc 2022; 34:1320-1328. [PMID: 35475586 DOI: 10.1111/den.14342] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 04/25/2022] [Indexed: 02/08/2023]
Abstract
Endoscopic diagnosis of gastroesophageal junction and Barrett's esophagus is essential for surveillance and early detection of esophageal adenocarcinoma and esophagogastric junction cancer. Despite its small size, the gastroesophageal junction has many inherent problems, including marked differences in diagnostic methods for Barrett's esophagus in international guidelines. To define Barrett's esophagus, gastroesophageal junction location should be clarified. Although gastric folds and palisade vessels are landmarks for identifying this junction, they are sometimes difficult to observe due to air entry or reflux esophagitis. The possibility of diagnosing a malignancy associated with Barrett's esophagus <1 cm, identified using palisade vessels, should be re-examined. Nontargeted biopsies of Barrett's esophagus are commonly used to detect intestinal metaplasia, dysplasia, and cancer as described in the Seattle protocol. Barrett's esophagus with intestinal metaplasia has a high risk of becoming cancerous. Furthermore, the frequency of cancer in patients with Barrett's esophagus without intestinal metaplasia is high, and the guidelines differ on whether to include the presence of intestinal metaplasia in the diagnosis of Barrett's esophagus. Use of advanced imaging technologies, including narrow-band imaging with magnifying endoscopy and linked color imaging, is reportedly valid for diagnosing Barrett's esophagus. Furthermore, artificial intelligence has facilitated the diagnosis of Barrett's esophagus through its deep learning and image recognition capabilities. However, it is necessary to first use the endoscopic definition of the gastroesophageal junction, which is common in all countries, and then elucidate the characteristics of Barrett's esophagus in each region, for example, length differences in the risk of carcinogenesis with and without intestinal metaplasia.
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Affiliation(s)
- Chika Kusano
- Division of Gastroenterology and Hepatology, Department of Medicine, Kitasato University School of Medicine, Kanagawa, Japan
| | - Rajvinder Singh
- Department of Gastroenterology, The Lyell McEwin Hospital, Adelaide, Australia.,The University of Adelaide, Adelaide, Australia
| | - Yeong Yeh Lee
- GI Function and Motility Unit, Hospital Universiti Sains Malaysia, Kota Bharu, Malaysia.,School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Yu Sen Alex Soh
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Prateek Sharma
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, USA.,Gastroenterology, School of Medicine, University of Kansas, Kansas City, USA
| | - Khek-Yu Ho
- Department of Medicine, National University Hospital, Singapore
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
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21
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Patankar M, Li M, Khalatbari A, Castle JD, Hu L, Zhang C, Shaker A. Inflammatory and Proliferative Pathway Activation in Human Esophageal Myofibroblasts Treated with Acidic Bile Salts. Int J Mol Sci 2022; 23:ijms231810371. [PMID: 36142285 PMCID: PMC9498994 DOI: 10.3390/ijms231810371] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/01/2022] [Accepted: 09/04/2022] [Indexed: 11/16/2022] Open
Abstract
Subepithelial human esophageal myofibroblasts (HEMFs) in gastroesophageal reflux disease (GERD) are exposed to luminal contents via impaired squamous epithelium barrier integrity. The supernatant of HEMFs treated with acidic bile salts reflective of in vivo reflux increases squamous epithelial thickness. We aimed to identify the involved mechanisms using an unbiased approach. Acidic-bile-salt-treated primary HEMF cultures (n = 4) were submitted for RNA-Seq and analyzed with Partek Flow followed by Ingenuity Pathway Analysis (IPA). A total of 1165 molecules (579 downregulated, 586 upregulated) were differentially expressed, with most top regulated molecules either extracellular or in the plasma membrane. Increases in HEMF CXCL-8, IL-6, AREG, and EREG mRNA, and protein secretion were confirmed. Top identified canonical pathways were agranulocyte and granulocyte adhesion and diapedesis, PI3K/AKT signaling, CCR5 signaling in macrophages, and the STAT3 pathway. Top diseases and biological functions were cellular growth and development, hematopoiesis, immune cell trafficking, and cell-mediated response. The targets of the top upstream regulator ErbB2 included CXCL-8, IL-6, and AREG and the inhibition of CXCL-8 in the HEMF supernatant decreased squamous epithelial proliferation. Our work shows an inflammatory/immune cell and proliferative pathways activation in HEMFs in the GERD environment and identifies CXCL-8 as a HEMF-derived chemokine with paracrine proliferative effects on squamous epithelium.
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Affiliation(s)
- Madhura Patankar
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Meng Li
- USC Libraries Bioinformatics Services, University of Southern California, Los Angeles, CA 90007, USA
| | - Atousa Khalatbari
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Joshua D. Castle
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Liping Hu
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Chunying Zhang
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Anisa Shaker
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
- Correspondence: ; Tel.: +1-323-442-2084
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22
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Shahsavari D, Kudaravalli P, Yap JEL, Vega KJ. Expanding beyond endoscopy: A review of non-invasive modalities in Barrett’s esophagus screening and surveillance. World J Gastroenterol 2022; 28:4516-4526. [PMID: 36157931 PMCID: PMC9476875 DOI: 10.3748/wjg.v28.i32.4516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 05/14/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
Barrett’s esophagus (BE) is a condition that results from replacement of the damaged normal squamous esophageal mucosa to intestinal columnar mucosa and is the most significant predisposing factor for development of esophageal adenocarcinoma. Current guidelines recommend endoscopic evaluation for screening and surveillance based on various risk factors which has limitations such as invasiveness, availability of a trained specialist, patient logistics and cost. Trans-nasal endoscopy is a less invasive modality but still has similar limitations such as limited availability of trained specialist and costs. Non-endoscopic modalities, in comparison, require minimal intervention, can be done in an office visit and has the potential to be a more ideal choice for mass public screening and surveillance, particularly in patents at low risk for BE. These include newer generations of esophageal capsule endoscopy which provides direct visualization of BE, and tethered capsule endomicroscopy which can obtain high-resolution images of the esophagus. Various cell collection devices coupled with biomarkers have been used for BE screening. Cytosponge, in combination with TFF3, as well as EsophaCap and EsoCheck have shown promising results in various studies when used with various biomarkers. Other modalities including circulatory microRNAs and volatile organic compounds that have demonstrated favorable outcomes. Use of these cell collection methods for BE surveillance is a potential area of future research.
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Affiliation(s)
- Dariush Shahsavari
- Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, GA 30912, United States
| | - Praneeth Kudaravalli
- Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, GA 30912, United States
| | - John Erikson L Yap
- Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, GA 30912, United States
| | - Kenneth J Vega
- Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, GA 30912, United States
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23
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Fasullo M, Shah T, Patel M, Mutha P, Zfass A, Lippman R, Smallfield G. Outcomes of Radiofrequency Ablation Compared to Liquid Nitrogen Spray Cryotherapy for the Eradication of Dysplasia in Barrett's Esophagus. Dig Dis Sci 2022; 67:2320-2326. [PMID: 33954846 DOI: 10.1007/s10620-021-06991-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 04/05/2021] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Current guidelines recommend endoscopic eradication therapy (EET) for Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma using either radiofrequency ablation (RFA) or liquid nitrogen spray cryotherapy (LNSC). The aims of this multicenter study are to compare the rate and number of treatment sessions of RFA vs. LNSC to achieve CE-D and CE-IM and assess outcomes for those who switched therapy. METHODS This is a retrospective cohort study of patients with BE undergoing EET. Demographics, baseline variables, endoscopy details, and histology information were abstracted. RESULTS One hundred and sixty-two patients were included in this study with 100 patients in the RFA group and 62 patients in the LNSC group. The rate of CE-D and CE-IM did not differ between the RFA group and LNSC group (81% vs. 71.0%, p = 0.14) and (64% vs. 66%, p = 0.78), respectively. The number of sessions to achieve CE-D and CE-IM was higher with LNSC compared to RFA (4.2 vs. 3.2, p = 0.05) and (4.8 vs. 3.5, p = 0.04), respectively. The likelihood of developing recurrent dysplasia was higher among patients who did not achieve CE-IM (12%) compared to those who did achieve CE-IM (4%), p = 0.04. Similar findings were found in those who switched treatment modalities. DISCUSSION EET is highly effective in eradication of Barrett's associated dysplasia and neoplasia. Both RFA and LNSC achieved similar rates of CE-D and CE-IM although LNSC required more sessions. Also, achievement of CE-IM was associated with less recurrence rates of dysplasia.
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Affiliation(s)
- Matthew Fasullo
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Health System, 1200 E. Broad St, PO Box 980341, Richmond, VA, 23298, USA. .,Division of Gastroenterology and Hepatology, Hunter Holmes-McGuire VA Medical Center, Richmond, VA, 23249, USA.
| | - Tilak Shah
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Health System, 1200 E. Broad St, PO Box 980341, Richmond, VA, 23298, USA.,Division of Gastroenterology and Hepatology, Hunter Holmes-McGuire VA Medical Center, Richmond, VA, 23249, USA
| | - Milan Patel
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Health System, 1200 E. Broad St, PO Box 980341, Richmond, VA, 23298, USA.,Division of Gastroenterology and Hepatology, Hunter Holmes-McGuire VA Medical Center, Richmond, VA, 23249, USA
| | - Pritesh Mutha
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Health System, 1200 E. Broad St, PO Box 980341, Richmond, VA, 23298, USA.,Division of Gastroenterology and Hepatology, Hunter Holmes-McGuire VA Medical Center, Richmond, VA, 23249, USA
| | - Alvin Zfass
- Division of Gastroenterology and Hepatology, Hunter Holmes-McGuire VA Medical Center, Richmond, VA, 23249, USA
| | - Robert Lippman
- Department of Pathology, Hunter Holmes-McGuire VA Medical Center, Richmond, VA, 23249, USA
| | - George Smallfield
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Health System, 1200 E. Broad St, PO Box 980341, Richmond, VA, 23298, USA
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Wang H, Peng D, Gan M, He Z, Kuang Y. CPEB3 overexpression caused by miR-106b-5p inhibition inhibits esophageal carcinoma in-vitro progression and metastasis. Anticancer Drugs 2022; 33:335-351. [PMID: 35102025 DOI: 10.1097/cad.0000000000001265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This study investigates the role of CPEB3 in esophageal cancer (EC) progression. The prognosis of EC patients was shown by survival analysis. CPEB3-targeting microRNAs were predicted by bioinformatics tools and further validated by dual-luciferase assay and RNA immunoprecipitation. CPEB3 expression in EC cell lines and EC tissues was analyzed by quantitative reverse transcription PCR. The viabilities of KYSE150 and EC9706 cells were measured by MTT and Cell Counting Kit-8 assays. The migration, invasion and tube formation of KYSE150 and EC9706 cells were examined by wound healing, Transwell and tube formation assay, respectively. E-cadherin, N-cadherin, fibronectin, vimentin and vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) [and phosphorylation (p)] and STAT3 levels (and phosphorylation) in KYSE150 and EC9706 cells were determined by western blot analysis or quantitative reverse transcription PCR. In addition, a xenograft tumor model was established through subcutaneously implanting KYSE150 and EC9706 cells transfected with Lv-CPEB3 or Lv-control viruses. CPEB3 expression was downregulated in EC cells and tissues, and its overexpression inhibited viability, migration, invasion and the expressions of N-cadherin, fibronectin, vimentin and VEGF, EGFR, p-EGFR and p-STAT3 levels in KYSE150 cells, but promoted E-cadherin expression. Small interfering RNA (siRNA)-CPEB3 inversely affected these phenotypes and gene expressions in EC9706 cells. miR-106b-5p targeted CPEB3 and negatively regulated CPEB3 expression. miR-106b-5p mimics reversed the effect of CPEB3 overexpression on KYSE150 cells, and miR-106b-5p inhibitor reversed the effect of siRNA-CPEB3 on EC9706 cells. In mice, tumor volumes, weights and Ki-67 expression were lower in mice treated with Lv-CPEB3 than that with Lv-control. CPEB3 overexpressed by miR-106b-5p inhibition suppressed EC progression involved in EGFR and STAT3 signaling.
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Affiliation(s)
| | | | - Mei Gan
- Intensive Care Medicine, Jiangxi Cancer Hospital, Nanchang, China
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Progression of Barrett's esophagus, crypt dysplasia, and low-grade dysplasia diagnosed by wide-area transepithelial sampling with 3-dimensional computer-assisted analysis: a retrospective analysis. Gastrointest Endosc 2022; 95:410-418.e1. [PMID: 34537193 DOI: 10.1016/j.gie.2021.09.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 09/04/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS3D) is used as an adjunct to forceps biopsy sampling in Barrett's esophagus (BE). BE-associated crypt dysplasia (CD), which can be detected by WATS3D, involves crypts but not surface epithelium. The risk of neoplastic progression of CD has never been evaluated. The prognosis of WATS3D-diagnosed nondysplastic BE (NDBE) and low-grade dysplasia (LGD) is also unknown. We assessed the risk of progression of WATS3D-reported NDBE, CD, and LGD with high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS We analyzed patients who underwent WATS3D in routine care. Eligible patients had 2 WATS3D ≥12 months apart. Patients were categorized by the initial WATS3D finding as NDBE, CD, or LGD. Patient-years of observation were calculated by multiplying the mean follow-up by the number of patients. Progression, defined as a subsequent finding of HGD/EAC on forceps biopsy sampling, was assessed. The crude progression rate was calculated, and Kaplan-Meier analysis compared progression rates stratified by baseline histology. Bivariate analysis identified progression risk factors. RESULTS Of 151,224 WATS3D cases, 43,145 (29%) had BE. Of these, 4545 patients had 2 WATS3D separated by ≥12 months. The mean follow-up was 1.97 years (range, 1.0-6.42). In patients with baseline NDBE, progression was .08% per patient-year (95% confidence interval [CI], .02%-.14%). Progression of baseline CD was significantly higher, at 1.42% per patient-year (95% CI, 0%-3.01%). For baseline LGD, progression was 5.79% per patient-year (95% CI, 1.02%-10.55%). Other risk factors for progression were increasing age and BE segment length. CONCLUSIONS NDBE found on WATS3D has a very low risk of progression. CD reported on WATS3D appears to be a neoplastic precursor lesion, with a risk of progression in this study significantly higher than NDBE but lower than LGD. The clinical utility of CD requires further investigation.
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Upper Gastrointestinal Cancer Surveillance in Lynch Syndrome. Cancers (Basel) 2022; 14:cancers14041000. [PMID: 35205747 PMCID: PMC8869779 DOI: 10.3390/cancers14041000] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 01/31/2022] [Accepted: 02/09/2022] [Indexed: 01/27/2023] Open
Abstract
Simple Summary Lynch syndrome is the most common cause of hereditary colorectal cancer, but is also associated with increased extracolonic cancer risk, including upper gastrointestinal cancers. While there is agreement regarding the benefit of frequent colonoscopic surveillance in Lynch syndrome, there remains a lack of consensus on the use of upper gastrointestinal cancer surveillance. Here, we review the upper gastrointestinal cancer risks in Lynch syndrome, the varying guideline recommendations in this area, and the published outcomes of upper gastrointestinal cancer surveillance in this high-risk population. Finally, we highlight ongoing controversies in upper gastrointestinal cancer surveillance and opine on how upper gastrointestinal cancer surveillance can be incorporated into a Lynch syndrome risk management program. Upper gastrointestinal cancer surveillance is an increasingly studied area of risk management in Lynch syndrome, and continued research will be vital in determining how to best incorporate this surveillance in these high-risk patients. Abstract Lynch syndrome is a common hereditary cancer predisposition syndrome associated with increased digestive cancer risk including colorectal, gastric, and duodenal cancers. While colorectal cancer surveillance is widely accepted to be an important part of a comprehensive Lynch syndrome risk management plan, the use of upper gastrointestinal cancer surveillance in Lynch syndrome remains more controversial. Currently, upper gastrointestinal cancer surveillance guidelines for Lynch syndrome vary widely, and there is no consensus on who should undergo upper gastrointestinal cancer surveillance, how surveillance should be performed, the age at which to initiate surveillance, or how often individuals with Lynch syndrome should undergo upper gastrointestinal cancer surveillance. Fortunately, research groups around the world have been focusing on upper gastrointestinal cancer surveillance in Lynch syndrome, and recent evidence in this field has demonstrated that upper gastrointestinal cancer surveillance can be performed with identification of precancerous lesions as well as early-stage upper gastrointestinal cancers. In this manuscript, we review the upper gastrointestinal cancer risks in Lynch syndrome, differing guideline recommendations for surveillance, outcomes of upper gastrointestinal cancer surveillance, and controversies in the field, and we provide a framework based on our collective experience with which to incorporate upper gastrointestinal cancer surveillance into a risk management program for individuals with Lynch syndrome.
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Odze RD, Goldblum J, Kaul V. Role of Wide-Area Transepithelial Sampling With 3D Computer-Assisted Analysis in the Diagnosis and Management of Barrett's Esophagus. Clin Transl Gastroenterol 2021; 12:e00422. [PMID: 34874019 PMCID: PMC8751778 DOI: 10.14309/ctg.0000000000000422] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 09/07/2021] [Indexed: 12/15/2022] Open
Abstract
Barrett's esophagus (BE) is a premalignant condition in which cancer prevention is performed by endoscopic surveillance combined with Seattle protocol mucosal biopsies. The Seattle protocol has significant limitations, including a high rate of sampling error due to the focality of dysplasia/carcinoma, low endoscopist adherence to the protocol, and a high degree of variability in pathologic interpretation. These factors all contribute to a high incidence of cancers missed within 1 year of surveillance endoscopy. Wide-area transepithelial sampling with computer-assisted three-dimensional analysis (WATS3D) is a relatively new technique that minimizes sampling error by using a brush biopsy device that extensively samples "at risk" mucosa and helps pathologists diagnose dysplasia/neoplasia by generating three-dimensional images of whole crypts using a neural network-based software program. Several large prospective trials (involving both academic and community practices) have shown significantly increased rates of detection of dysplasia and intestinal metaplasia in both screening and surveillance in patients with BE when used as an adjunct to Seattle protocol-based forceps biopsies. The WATS3D diagnostic platform was included in the most recent American Society for Gastrointestinal Endoscopy Barrett's guideline as an adjunct to forceps biopsies (conditional recommendation and low quality of evidence). This review summarizes the scientific and pathologic basis of WATS3D technology, its potential impact on BE surveillance and management, and its limitations and future directions.
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Affiliation(s)
| | - John Goldblum
- Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Vivek Kaul
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, New York, USA
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Szymański M, Marek I, Wilczyński M, Janczy A, Bigda J, Kaska Ł, Proczko-Stepaniak M. Evaluation of esophageal pathology in a group of patients 2 years after one-anastomosis gastric bypass (OAGB) — Cohort study. Obes Res Clin Pract 2021; 16:82-86. [PMID: 34922847 DOI: 10.1016/j.orcp.2021.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 11/21/2021] [Accepted: 12/12/2021] [Indexed: 12/11/2022]
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Chang K, Jackson CS, Vega KJ. Barrett's Esophagus: Diagnosis, Management, and Key Updates. Gastroenterol Clin North Am 2021; 50:751-768. [PMID: 34717869 DOI: 10.1016/j.gtc.2021.08.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Barrett's esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC) development. Unfortunately, BE screening/surveillance has not provided the anticipated EAC reduction benefit. Noninvasive techniques are increasingly available or undergoing testing to screen for BE among those with/without known risk factors, and the use of artificial intelligence platforms to aid endoscopic screening and surveillance will likely become routine, minimizing missed cases or lesions. Management of high-grade dysplasia and intramucosal EAC is clear with endoscopic eradication therapy preferred to surgery. BE with low-grade dysplasia can be managed with removal of visible lesions combined with endoscopic eradication therapy or endoscopic surveillance at present.
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Affiliation(s)
- Karen Chang
- Department of Internal Medicine, University of California, Riverside School of Medicine, 900 University Avenue, Riverside, CA 92521, USA
| | - Christian S Jackson
- Section of Gastroenterology, Loma Linda VA Healthcare System, 11201 Benton Street, 2A-38, Loma Linda, CA 92357, USA
| | - Kenneth J Vega
- Division of Gastroenterology & Hepatology, Augusta University-Medical College of Georgia, 1120 15th Street, AD-2226, Augusta, GA 30912, USA.
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Fasullo M, Sreenivasen A, Holzwanger E, Lavender C, Patel M, Shah T, Mutha P, Yacavone RF, Sultan K, Trindade AJ, Smallfield G. Co-existing inflammatory bowel disease and Barrett's esophagus is associated with esophageal dysplasia: a propensity score-matched cohort. Endosc Int Open 2021; 9:E1524-E1529. [PMID: 34540545 PMCID: PMC8445678 DOI: 10.1055/a-1526-0507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 05/27/2021] [Indexed: 01/03/2023] Open
Abstract
Background and study aims Barrett's esophagus (BE) and inflammatory bowel disease (IBD) predispose to the development of dysplasia and cancer. It is unclear if the inflammatory cascade seen in IBD affects disease progression in BE. We aimed to determine if patients with BE who have co-existing IBD had a higher risk of dysplasia, nodular disease, or longer segments than BE patients without IBD. Patients and methods This was a multicenter, retrospective propensity score-matched cohort study. We compared rates of dysplasia, nodular disease, and segment length in patients with BE and IBD (cases) to patients with BE who did not have IBD (controls). Controls were 1:1 propensity score matched with controls for age, sex, body mass index (BMI), smoking, and hiatal hernia. Results A total of 132 patients were included in the IBD + BE group and 132 patients in the BE group. Patients with IBD + BE had higher rates of esophageal dysplasia compared to controls (15.9 % vs. 6.1 % [adjusted odds ratio [OR]: 2.9, 95 % CI: 1.2-6.9]) and more nodules (9.8 % vs. 3.0 % [adjusted OR: 3.5, 95 % CI: 1.1-11.0]). IBD + BE group was also associated with longer BE segments (43.9 % vs. 12.1 % [OR: 5.7, 95 % CI: 3.0-10.6]). Conclusions Co-existing IBD may increase the risk of dysplasia and esophageal nodules in patients with BE. Our findings may have implications for BE surveillance intervals in IBD patients. Prospective studies are needed to confirm our findings.
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Affiliation(s)
- Matthew Fasullo
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
| | - Aditya Sreenivasen
- Division of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Long Island Jewish Medical Center, New Hyde Park, New York, United States
| | - Erik Holzwanger
- Division of Gastroenterology & Hepatology, Tufts Medical Center, Boston, Massachusetts, United States
| | - Charles Lavender
- Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
| | - Milan Patel
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
| | - Tilak Shah
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
| | - Pritesh Mutha
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
| | - Robert F. Yacavone
- Division of Gastroenterology & Hepatology, Tufts Medical Center, Boston, Massachusetts, United States
| | - Keith Sultan
- Division of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Long Island Jewish Medical Center, New Hyde Park, New York, United States
| | - Arvind J. Trindade
- Division of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Long Island Jewish Medical Center, New Hyde Park, New York, United States
| | - George Smallfield
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
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Kelly RJ, Ansari AM, Miyashita T, Zahurak M, Lay F, Ahmed AK, Born LJ, Pezhouh MK, Salimian KJ, Ng C, Matsangos AE, Stricker-Krongrad AH, Mukaisho KI, Marti GP, Chung CH, Canto MI, Rudek MA, Meltzer SJ, Harmon JW. Targeting the Hedgehog Pathway Using Itraconazole to Prevent Progression of Barrett's Esophagus to Invasive Esophageal Adenocarcinoma. Ann Surg 2021; 273:e206-e213. [PMID: 31290765 PMCID: PMC8147663 DOI: 10.1097/sla.0000000000003455] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVE The aim of the study was to investigate whether inhibition of Sonic Hedgehog (SHH) pathway would prevent progression of Barrett's Esophagus (BE) to esophageal adenocarcinoma. BACKGROUND The hedgehog signaling pathway is a leading candidate as a molecular mediator of BE and esophageal adenocarcinoma (EAC). Repurposed use of existing off-patent, safe and tolerable drugs that can inhibit hedgehog, such as itraconazole, could prevent progression of BE to EAC. METHODS The efficacy of itraconazole was investigated using a surgical rat reflux model of Barrett's Metaplasia (BM). Weekly intraperitoneal injections of saline (control group) or itraconazole (treatment group; 200 mg/kg) were started at 24 weeks postsurgery. Esophageal tissue was harvested at 40 weeks. The role of the Hh pathway was also evaluated clinically. Esophageal tissue was harvested after 40 weeks for pathological examination and evaluation of the SHH pathway by immunohistochemistry. RESULTS BM was present in control animals 29 of 31 (93%) versus itraconazole 22 of 24 (91%). EAC was significantly lower in itraconazole 2 of 24 (8%) versus control 10 of 31 (32%), respectively (P = 0.033). Esophageal SHH levels were lower in itraconazole vs control (P = 0.12). In esophageal tissue from humans with recurrent or persistent dysplastic BE within 24 months of ablative treatment, strong SHH and Indian Hedgehog expression occurred in distal BE versus proximal squamous epithelium, odds ratio = 6.1 (95% confidence interval: 1.6, 23.4) and odds ratio = 6.4 (95% confidence interval: 1.2, 32.8), respectively. CONCLUSION Itraconazole significantly decreases EAC development and SHH expression in a preclinical animal model of BM. In humans, BE tissue expresses higher SHH, Indian Hedgehog, and bone morphogenic protein levels than normal squamous esophageal epithelium.
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Affiliation(s)
- Ronan J Kelly
- The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD
- Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX
| | - Amir M Ansari
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Tomoharu Miyashita
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Marianna Zahurak
- Department of Oncology, Division of Biostatistics and Bioinformatics, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD
| | - Frank Lay
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - A Karim Ahmed
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Louis J Born
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Maryam K Pezhouh
- Department of Pathology, Northwestern University School of Medicine, Chicago, IL
| | - Kevan J Salimian
- Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD
| | - Christopher Ng
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Aerielle E Matsangos
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Ken-Ichi Mukaisho
- Department of Pathology, Shiga University of Medical Science, Shiga, Japan
| | - Guy P Marti
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Christine H Chung
- Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, FL
| | - Marcia I Canto
- Department of Medicine, Division of gastroenterology, The Johns Hopkins University School of Medicine
| | - Michelle A Rudek
- Analytical Pharmacology Core, Department of Oncology, Department of Medicine/Division of Clinical Pharmacology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Stephen J Meltzer
- Department of Medicine, Division of gastroenterology, The Johns Hopkins University School of Medicine
| | - John W Harmon
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD
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Qumseya BJ, Qumsiyeh Y, Ponniah SA, Estores D, Yang D, Johnson-Mann CN, Friedman J, Ayzengart A, Draganov PV. Barrett's esophagus after sleeve gastrectomy: a systematic review and meta-analysis. Gastrointest Endosc 2021; 93:343-352.e2. [PMID: 32798535 DOI: 10.1016/j.gie.2020.08.008] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/04/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Sleeve gastrectomy (SG) has become significantly more common in recent years. Gastroesophageal reflux disease (GERD) is a major concern in patients undergoing SG and is the major risk factor for Barrett's esophagus (BE). We aimed to assess the prevalence of BE in patients who had undergone SG. METHODS We searched the major search engines ending in July 2020. We included studies on patients who had undergone esophagogastroduodenoscopy (EGD) after SG. The primary outcome was the prevalence of BE in patients who had undergone SG. We assessed heterogeneity using I2 and Q statistics. We used funnel plots and the classic fail-safe test to assess for publication bias. We used random-effects modeling to report effect estimates. RESULTS Our final analysis included 10 studies that included 680 patients who had undergone EGD 6 months to 10 years after SG. The pooled prevalence of BE was 11.6% (95% confidence interval [CI], 8.1%-16.4%; P < .001; I2 = 28.7%). On logistic meta-regression analysis, there was no significant association between BE and the prevalence of postoperative GERD (β = 3.5; 95% CI, -18 to 25; P = .75). There was a linear relationship between the time of postoperative EGD and the rate of esophagitis (β = 0.13; 95% CI, 0.06-0.20; P = .0005); the risk of esophagitis increased by 13% each year after SG. CONCLUSIONS The prevalence of BE in patients who had EGD after SG appears to be high. There was no correlation with GERD symptoms. Most cases were observed after 3 years of follow-up. Screening for BE should be considered in patients after SG even in the absence of GERD symptoms postoperatively.
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Affiliation(s)
- Bashar J Qumseya
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Yazan Qumsiyeh
- Department of Surgery, University of California-San Francisco, Fresno, California, USA
| | - Sandeep A Ponniah
- Department of Medicine, University of Florida, Gainesville, Florida, USA
| | - David Estores
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Dennis Yang
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Crystal N Johnson-Mann
- UF Health Bariatric Surgery Center, Department of Surgery, University of Florida, Gainesville, Florida, USA
| | - Jeffrey Friedman
- UF Health Bariatric Surgery Center, Department of Surgery, University of Florida, Gainesville, Florida, USA
| | - Alexander Ayzengart
- UF Health Bariatric Surgery Center, Department of Surgery, University of Florida, Gainesville, Florida, USA
| | - Peter V Draganov
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
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Kolb JM, Wani S. Barrett's esophagus: current standards in advanced imaging. Transl Gastroenterol Hepatol 2021; 6:14. [PMID: 33409408 DOI: 10.21037/tgh.2020.02.10] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 01/21/2020] [Indexed: 12/13/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) continues to be one of the fastest rising incident cancers in the Western population with the majority of patients presenting with late stage disease and associated with a dismal 5-year survival rate. Barrett's esophagus (BE) is the only identifiable precursor lesion to EAC. Strategies to screen for and survey BE are critical to detect earlier cancers and reduce morbidity and mortality related to EAC. A high-quality endoscopic examination with careful inspection of the Barrett's segment and adherence to the Seattle protocol for tissue sampling are critical. Advanced imaging modalities offer the potential to improve dysplasia detection, predict histopathology in real time and guide endoscopic eradication therapy (EET). Several technologies have been studied and although most are not yet recommended for routine clinical practice, high definition white light endoscopy (HD-WLE) as well as chromoendoscopy (including virtual chromoendoscopy) improved dysplasia detection in numerous studies supporting their use. Future studies should evaluate the role of artificial intelligence in optimizing detection of dysplasia in BE patients.
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Affiliation(s)
- Jennifer M Kolb
- Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Sachin Wani
- Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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Cook MB, Thrift AP. Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma: Implications for Screening and Surveillance. Gastrointest Endosc Clin N Am 2021; 31:1-26. [PMID: 33213789 PMCID: PMC7887893 DOI: 10.1016/j.giec.2020.08.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
In the United States, the incidence of esophageal adenocarcinoma increased markedly since the 1970s with a recent stabilization. Despite evolving screening and surveillance strategies to diagnose, risk triage, and intervene in Barrett's esophagus patients to prevent esophageal adenocarcinoma, most cases present with advanced disease and poor resultant survival. Epidemiologic studies have identified the main risk factors for these conditions, including increasing age, male sex, white race, gastroesophageal reflux disease, abdominal obesity, cigarette smoking, and lack of infection with Helicobacter pylori. This review summarizes the current epidemiologic evidence with implications for screening and surveillance in Barrett's esophagus and esophageal adenocarcinoma.
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Affiliation(s)
- Michael B Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E430, Rockville, MD 20850, USA.
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, MS: BCM307, Room 621D, Houston, TX 77030, USA
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Singer ME, Smith MS. Wide Area Transepithelial Sampling with Computer-Assisted Analysis (WATS 3D) Is Cost-Effective in Barrett's Esophagus Screening. Dig Dis Sci 2021; 66:1572-1579. [PMID: 32578042 PMCID: PMC8053177 DOI: 10.1007/s10620-020-06412-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 06/12/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance. AIMS To examine the cost-effectiveness of adding WATS3D to the Seattle protocol in screening patients for BE. METHODS A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS3D. The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year. RESULTS Between 320 and 337 people would need to be screened with WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY. CONCLUSIONS Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.
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Affiliation(s)
- Mendel E. Singer
- Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH USA
| | - Michael S. Smith
- Division of Gastroenterology and Hepatology, Mount Sinai West and Mount Sinai Morningside Hospitals, Icahn School of Medicine at Mount Sinai, Ambulatory Care Center, 13th Floor, 440 W 114th St., New York, NY 10025 USA
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Andalib A, Bouchard P, Demyttenaere S, Ferri LE, Court O. Esophageal cancer after sleeve gastrectomy: a population-based comparative cohort study. Surg Obes Relat Dis 2020; 17:879-887. [PMID: 33547014 DOI: 10.1016/j.soard.2020.12.011] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 12/11/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Sleeve gastrectomy (SG) is the most common bariatric surgery; however, this approach may induce gastroesophageal reflux disease (GERD). Both obesity and GERD are independent risk factors for esophageal cancer, however the impact of SG on risk of esophageal cancer remains unknown. OBJECTIVE To evaluate the risk of esophageal cancer after reflux-prone bariatric surgery. SETTING Population-level, provincial administrative healthcare database, Quebec, Canada. METHODS We identified a population-based cohort of all patients with obesity who underwent reflux-prone surgery (SG and duodenal switch [DS]) or reflux-protective Roux-en-Y gastric bypass (RYGB) during 01/2006-12/2012 in Quebec, Canada. For every surgical patient, 2-3 nonsurgical controls with obesity matched for age, sex, and geography were also identified. Crude incidence rate ratios (IRRs) for esophageal cancer were calculated using person-time analysis. Hazard ratios (HRs) were obtained using multivariate cox regression. RESULTS A total of 4121 patients had reflux-prone procedures and 852 underwent RYGB. At a mean follow-up of 7.6 years, 8 cases of esophageal cancer were identified after bariatric surgery. Compared with RYGB, IRR for esophageal cancer in reflux-prone group was 1.45 (95%CI: .19-65.5) and HR = .83 (95%CI: .10-7.27). The crude incidence rate of esophageal cancer in the reflux-prone group was higher than that of nonsurgical controls (n = 12,159; IRR = 3.46, 95%CI: 1.00-12.5), but after adjustment the difference disappeared (HR = 2.47, 95%CI: .82-7.45). CONCLUSIONS Long-term incidence of esophageal cancer after reflux-prone bariatric surgery is not greater than RYGB. While crude incidence of esophageal cancer after reflux-prone surgery is higher than in nonsurgical patients with obesity, such difference disappears after accounting for confounders. Given the low incidence of esophageal cancer and slow progression of dysplastic Barrett esophagus, studies with longer follow-up are needed.
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Affiliation(s)
- Amin Andalib
- Center for Bariatric Surgery, Department of Surgery, McGill University, Montreal, Canada.
| | - Philippe Bouchard
- Center for Bariatric Surgery, Department of Surgery, McGill University, Montreal, Canada
| | - Sebastian Demyttenaere
- Center for Bariatric Surgery, Department of Surgery, McGill University, Montreal, Canada
| | - Lorenzo E Ferri
- Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Canada
| | - Olivier Court
- Center for Bariatric Surgery, Department of Surgery, McGill University, Montreal, Canada
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Alzahrani MA, Hammadi EA, Alshehri MA, Belali RM, Tahtouh EI, Almanjahi IM, Hammad MS, Nebrawi KY, Alshehri AM, Elmalahy TM, Shehata SF. Clinical significance of endoscopy before bariatric surgery: An experience of a tertiary hospital. ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.obmed.2020.100289] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Maitra I, Date RS, Martin FL. Towards screening Barrett's oesophagus: current guidelines, imaging modalities and future developments. Clin J Gastroenterol 2020; 13:635-649. [PMID: 32495144 PMCID: PMC7519897 DOI: 10.1007/s12328-020-01135-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 05/21/2020] [Indexed: 02/07/2023]
Abstract
Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma (OAC). Although guidelines on the screening and surveillance exist in Barrett's oesophagus, the current strategies are inadequate. Oesophagogastroduodenoscopy (OGD) is the gold standard method in screening for Barrett's oesophagus. This invasive method is expensive with associated risks negating its use as a current screening tool for Barrett's oesophagus. This review explores current definitions, epidemiology, biomarkers, surveillance, and screening in Barrett's oesophagus. Imaging modalities applicable to this condition are discussed, in addition to future developments. There is an urgent need for an alternative non-invasive method of screening and/or surveillance which could be highly beneficial towards reducing waiting times, alleviating patient fears and reducing future costs in current healthcare services. Vibrational spectroscopy has been shown to be promising in categorising Barrett's oesophagus through to high-grade dysplasia (HGD) and OAC. These techniques need further validation through multicentre trials.
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Affiliation(s)
- Ishaan Maitra
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE UK
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Abstract
PURPOSE OF REVIEW Barrett's oesophagus is the only identifiable precursor lesion to oesophageal adenocarcinoma. The stepwise progression of Barrett's oesophagus to dysplasia and invasive carcinoma provides the opportunity to intervene and reduce the morbidity and mortality associated with this lethal cancer. Several studies have demonstrated the efficacy and safety of endoscopic eradication therapy (EET) for the management of Barrett's oesophagus related neoplasia. The primary goal of EET is to achieve complete eradication of intestinal metaplasia (CE-IM) followed by enrolment of patients in surveillance protocols to detect recurrence of Barrett's oesophagus and Barrett's oesophagus related neoplasia. RECENT FINDINGS EET depends on early and accurate detection and diagnosis of Barrett's oesophagus related neoplasia. All visible lesions should be resected followed by ablation of the remaining Barrett's epithelium. After treatment, patients should be enrolled in endoscopic surveillance programmes. For nondysplastic Barrett's oesophagus, surveillance alone is recommended. For low-grade dysplasia, both surveillance and ablation are reasonable options and should be decided on an individual basis according to patient risk factors and preferences. EET is preferred for high-grade dysplasia and intramucosal carcinoma. For T1b oesophageal adenocarcinoma, esophagectomy remains the standard of care, but endoscopic therapy can be considered in select cases. SUMMARY EET is now standard of care and endorsed by societal guidelines for the treatment of Barrett's oesophagus related neoplasia. Future studies should focus on risk stratification models using a combination of clinical data and biomarkers to identify ideal candidates for EET, and to predict recurrence. Optimal therapy for T1b cancer and surveillance strategy after CE-IM are topics that require further study.
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Steve M D, Lindsey B C, Byung Soo Y, Parth J P, David A J. Microbiome and Gastroesophageal Disease: Pathogenesis and Implications for Therapy. ACTA ACUST UNITED AC 2020. [DOI: 10.29328/journal.acgh.1001018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Houston T, Sharma P. Volumetric laser endomicroscopy in Barrett's esophagus: ready for primetime. Transl Gastroenterol Hepatol 2020; 5:27. [PMID: 32258531 DOI: 10.21037/tgh.2019.11.16] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 11/14/2019] [Indexed: 12/20/2022] Open
Abstract
Barrett's esophagus (BE) is the condition where intestinal metaplastic changes are found in the normal stratified squamous epithelium of the esophagus predisposing an individual to dysplasia and esophageal adenocarcinoma (EAC). It tends to affect males and is often the result of chronic gastroesophageal reflux disease (GERD). The current standard of therapy for diagnosing Barrett's is white light endoscopy (WLE) with biopsies obtained using the Seattle protocol. Multiple newer advanced modalities have been developed to improve diagnostic abilities, including volumetric laser endomicroscopy (VLE). This technique utilizes second generation optical coherence tomography (OCT) to provide an enhanced circumferential image to a depth of 3 mm with the potential for improved diagnostic yield for dysplasia, particularly submucosal lesions or lesions not seen by WLE. It has also been evaluated in guiding mapping of endotherapy as well as post therapy surveillance for recurrence. Although the results have been promising when used with current diagnostic standards, overall data are limited to support the routine use of VLE.
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Affiliation(s)
- Trevor Houston
- Department of Internal Medicine, University of Nevada, Las Vegas School of Medicine, Las Vegas, NV, USA
| | - Prateek Sharma
- Department of Gastroenterology, University of Kansas Medical Center, Kansas City, KS, USA
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Chang VC, Pan P, Shah SK, Srinivasan A, Haberl E, Wan C, Kajese TM, Primomo JA, Davis G. Routine preoperative endoscopy in patients undergoing bariatric surgery. Surg Obes Relat Dis 2020; 16:745-750. [PMID: 32192865 DOI: 10.1016/j.soard.2020.02.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 01/12/2020] [Accepted: 02/04/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND The role of routine preoperative endoscopy before primary weight loss surgery remains controversial. OBJECTIVE We reviewed our experience to determine the frequency of abnormal findings in patients undergoing routine preoperative endoscopy before bariatric surgery. SETTING A tertiary level, academic-affiliated bariatric surgery practice. METHODS A retrospective chart review was performed between July 2014 and June 2016 of patients undergoing routine preoperative endoscopy before primary bariatric surgery. Variables evaluated included preendoscopy symptoms, planned bariatric surgical procedure, abnormal findings on endoscopy, and changes in planned bariatric surgical procedure after endoscopy. RESULTS A total of 631 patients met inclusion criteria. Of patients, 72% (457) were female. The median age was 44 (interquartile range 36-55). The median body mass index was 46 (interquartile range 42-51). Most patients had no preendoscopy clinical symptoms (61.3%). The most frequent abnormal findings included esophagitis (26.5%), hiatal hernia (27.1%), gastric ulcer (4.9%), and biopsy-proven Barrett's esophagus (4.6%). Although patients with preoperative symptoms were more likely to have abnormal findings on endoscopy, there were no significant differences in rates of Barrett's esophagus in patients with (5.3%) or without (4.1%) symptoms. Of the total cohort, 18.4% had a change in their planned operation after endoscopy results. CONCLUSION The findings in our large series suggest selective screening in symptomatic patients only may lead to failure of discovery of foregut pathology that should prompt consideration for changes in the planned bariatric surgical procedure. Further study is necessary to see if our findings have broad applicability.
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Affiliation(s)
- Victoria C Chang
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas; UT Physicians, The Davis Clinic at Memorial Hermann-Memorial City Medical Center, Houston, Texas
| | - Ping Pan
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas; UT Physicians, The Davis Clinic at Memorial Hermann-Memorial City Medical Center, Houston, Texas
| | - Shinil K Shah
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas; Michael E. DeBakey Institute for Comparative Cardiovascular Science and Biomedical Devices, Texas A&M University, College Station, Texas
| | - Aditya Srinivasan
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas
| | - Elizabeth Haberl
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas
| | - Charlie Wan
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas
| | - Tanyaradzwa M Kajese
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas; UT Physicians, The Davis Clinic at Memorial Hermann-Memorial City Medical Center, Houston, Texas.
| | - John A Primomo
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas; UT Physicians, The Davis Clinic at Memorial Hermann-Memorial City Medical Center, Houston, Texas
| | - Garth Davis
- Division of Minimally Invasive and Elective General Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas; UT Physicians, The Davis Clinic at Memorial Hermann-Memorial City Medical Center, Houston, Texas
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Graham DY, Tan MC. No Barrett's-No Cancer: A Proposed New Paradigm for Prevention of Esophageal Adenocarcinoma. J Clin Gastroenterol 2020; 54:136-143. [PMID: 31851107 DOI: 10.1097/mcg.0000000000001298] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Esophageal adenocarcinoma is inflammation-associated cancer with a recognizable preneoplastic stage, Barrett's. Barrett's describes the metaplastic transformation of esophageal squamous mucosa into columnar epithelium that typically results secondary to mucosal damage caused by acidic gastroduodenal reflux. Continued acid reflux may then result in mucosal inflammation which results in progressive inflammation-induced genetic instability that may eventuate in esophageal adenocarcinoma. Barrett's is the only recognized precursor lesion to esophageal carcinoma. Barrett's mucosa is unique among preneoplastic lesions; ablation therapy results in restitution of a squamous epithelium reducing or eliminating accumulated genetic instabilities and resetting the biological clock progressing toward invasive cancer. However, recurrence of Barrett's after ablation is common. We propose that both Barrett's and recurrence of Barrett's after ablation can be prevented and discuss how current approaches to therapy for gastroesophageal reflux disease, for Barrett's screening, chemoprevention, and ablation therapy all might be reconsidered. We propose (1) improved approaches to Barrett's prevention, (2) universal Barrett's screening by linking Barrett's screening to colon cancer screening, (3) ablation of all Barrett's mucosa along with (4) acid-suppressive-antireflux therapy tailored to prevent development of Barrett's or the recurrence of Barrett's after ablation therapy. We propose that ultimately, treatment decisions for gastroesophageal reflux disease and prevention of Barrett's and esophageal carcinoma should be based on assessing and maintaining esophageal mucosal integrity. This will require development and verification of specific measurements that reliably correlate with prevention of Barrett's. We outline the new research and technical advances needed to cost-effectively achieve these goals.
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Affiliation(s)
- David Y Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX
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SHAHEEN NICHOLASJ. ENDOSCOPIC TREATMENT OF ESOPHAGEAL NEOPLASIA: A DECADE OF EVOLUTION. TRANSACTIONS OF THE AMERICAN CLINICAL AND CLIMATOLOGICAL ASSOCIATION 2020; 131:297-314. [PMID: 32675869 PMCID: PMC7358467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Traditional therapy for early esophageal neoplasia has been esophagectomy. In the past decade, the approach to these conditions has rapidly evolved, such that endoscopic therapy has become the primary modality to treat patients with esophageal dysplasia and superficial carcinoma. A variety of modalities are available, including thermal methods, such as radiofrequency ablation and argon plasma coagulation; cryotherapy, including spray liquid nitrogen cryotherapy and balloon-based nitrous oxide cryotherapy; and tissue resection methods, such as endoscopic mucosal resection and endoscopic submucosal dissection. Level 1 evidence substantiates that patients treated with these therapies have a low risk of developing invasive cancer. These treatments demonstrate an excellent safety profile. Future work in this area will define the best modalities of treatment, assess the utility of endoscopic therapy in combination with radiation therapy and chemotherapy, and improve current screening regimens to allow earlier detection of neoplasia.
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Affiliation(s)
- NICHOLAS J. SHAHEEN
- Correspondence and reprint requests: Nicholas Shaheen, MD, MPH, University of North Carolina School of Medicine, 130 Mason Farm Road, Suite 4150, Chapel Hill, NC 27599-7080919-966-7047
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McGoran J, Bennett A, Cooper J, De Caestecker J, Lovat LB, Guha N, Ragunath K, Sami SS. Acceptability to patients of screening disposable transnasal endoscopy: qualitative interview analysis. BMJ Open 2019; 9:e030467. [PMID: 31831531 PMCID: PMC6924752 DOI: 10.1136/bmjopen-2019-030467] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 10/27/2019] [Accepted: 11/01/2019] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES Screening in selected high risk populations for Barrett's oesophagus (BO) and oesophageal varices (OVs) has been proposed, but there are obstacles with conventional oesophagogastroduodenoscopy (C-OGD), including patient acceptability. Portable and disposable office-based transnasal endoscopy (TNE) is a feasible and accurate alternative to C-OGD that may have use in primary and secondary care. This article outlines a qualitative analysis of patient experiences of TNE and C-OGD in order to gain an insight into an acceptable delivery of an endoscopic screening service. DESIGN Purposeful sampling identified 23 participants who then underwent semi-structured interviews to determine their experiences of both procedures. Thematic analysis was conducted to derive meaning from their lived experiences. SETTING A secondary care endoscopy unit, clinic room and interview room. PARTICIPANTS Patients referred for BO or OV surveillance and for endoscopy to investigate dyspepsia underwent unsedated TNE using the EG Scan II device followed by C-OGD with or without sedation (patient choice), as part of a clinical trial. RESULTS The themes that arose from our analysis were: inclusivity in one's own healthcare, comfort level and convenience, validity of the procedure and application to a screening population and a sense of altruism and reciprocity. Positive aspects of TNE included participant empowerment, reduced discomfort and avoidance of conscious sedation. Participants felt that if TNE screening was of proven efficacy it would be welcomed, though views on use in a community setting were mixed. CONCLUSIONS Most patients preferred TNE to unsedated C-OGD and the reasons they gave featured strongly in the emerging themes. Preferences between TNE and sedated C-OGD were more subtle, with equivalent comfort scores but merits and drawbacks of both being discussed. This information identifies opportunities and challenges in establishing an endoscopic screening service. Trial registration number ISRCTNregistry identifier: 70595405; Pre-results.
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Affiliation(s)
- John McGoran
- Digestive Diseases Centre, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Andrea Bennett
- National Institute for Health Research (NIHR) Biomedical Research Center in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust, Nottingham, Nottingham, UK
| | - Joanne Cooper
- National Institute for Health Research (NIHR) Biomedical Research Center in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust, Nottingham, Nottingham, UK
| | - John De Caestecker
- Digestive Diseases Centre, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Laurence B Lovat
- Division of Surgery and Interventional Science, University College London, London, London, UK
| | - Neil Guha
- National Institute for Health Research (NIHR) Biomedical Research Center in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust, Nottingham, Nottingham, UK
| | - Krish Ragunath
- National Institute for Health Research (NIHR) Biomedical Research Center in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust, Nottingham, Nottingham, UK
| | - Sarmed S Sami
- Division of Surgery and Interventional Science, University College London, London, London, UK
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Preoperative Endoscopic Findings in Veterans Undergoing Bariatric Surgery: Prevalence and Predictors of Barrett’s Esophagus. Obes Surg 2019; 30:657-663. [DOI: 10.1007/s11695-019-04234-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Soh YSA, Lee YY, Gotoda T, Sharma P, Ho KY. Challenges to diagnostic standardization of Barrett's esophagus in Asia. Dig Endosc 2019; 31:609-618. [PMID: 30892742 DOI: 10.1111/den.13402] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 03/13/2019] [Indexed: 12/14/2022]
Abstract
Barrett's esophagus (BE), a premalignant condition of the lower esophagus, is increasingly prevalent in Asia. However, endoscopic and histopathological criteria vary widely between studies across Asia, making it challenging to assess comparability between geographical regions. Furthermore, guidelines from various societies worldwide provide differing viewpoints and definitions, leading to diagnostic challenges that affect prognostication of the condition. In this review, the authors discuss the controversies surrounding the diagnosis of BE, particularly in Asia. Differences between guidelines worldwide are summarized with further discussion regarding various classifications of BE used, different definitions of gastroesophageal junction used across geographical regions and the clinical implications of intestinal metaplasia in the setting of BE. Although many guidelines recommend the Seattle protocol as the preferred approach regarding dysplasia surveillance in BE, some limitations exist, leading to poor adherence. Newer technologies, such as acetic acid-enhanced magnification endoscopy, narrow band imaging, Raman spectroscopy, molecular approaches and the use of artificial intelligence appear promising in addressing these problems, but further studies are required before implementation into routine clinical practice. The Asian Barrett's Consortium also outlines its ongoing plans to tackle the challenge of standardizing the diagnosis of BE in Asia.
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Affiliation(s)
- Yu Sen Alex Soh
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Prateek Sharma
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, USA.,Gastroenterology, University of Kansas, School of Medicine, Kansas City, USA
| | - Khek-Yu Ho
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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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: 16] [Impact Index Per Article: 2.7] [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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Que J, Garman KS, Souza RF, Spechler SJ. Pathogenesis and Cells of Origin of Barrett's Esophagus. Gastroenterology 2019; 157:349-364.e1. [PMID: 31082367 PMCID: PMC6650338 DOI: 10.1053/j.gastro.2019.03.072] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 03/22/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023]
Abstract
In patients with Barrett's esophagus (BE), metaplastic columnar mucosa containing epithelial cells with gastric and intestinal features replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease. This condition is estimated to affect 5.6% of adults in the United States, and is a major risk factor for esophageal adenocarcinoma. Despite the prevalence and importance of BE, its pathogenesis is incompletely understood and there are disagreements over the cells of origin. We review mechanisms of BE pathogenesis, including transdifferentiation and transcommitment, and discuss potential cells of origin, including basal cells of the squamous epithelium, cells of esophageal submucosal glands and their ducts, cells of the proximal stomach, and specialized populations of cells at the esophagogastric junction (residual embryonic cells and transitional basal cells). We discuss the concept of metaplasia as a wound-healing response, and how cardiac mucosa might be the precursor of the intestinal metaplasia of BE. Finally, we discuss shortcomings in current diagnostic criteria for BE that have important clinical implications.
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Affiliation(s)
- Jianwen Que
- Division of Digestive and Liver Diseases and Center for Human Development, Department of Medicine, Columbia University, New York, New York.
| | - Katherine S. Garman
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine. Durham, NC
| | - Rhonda F. Souza
- Center for Esophageal Diseases, Department of Medicine, Baylor University Medical Center at Dallas, and Center for Esophageal Research, Department of Medicine, Baylor Scott & White Research Institute, Dallas, TX
| | - Stuart Jon Spechler
- Center for Esophageal Diseases, Department of Medicine, Baylor University Medical Center at Dallas, Dallas, Texas; Center for Esophageal Research, Department of Medicine, Baylor Scott & White Research Institute, Dallas, Texas.
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