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Boer LS, Nierkens S, Weusten BLAM. Applications of cryotherapy in premalignant and malignant esophageal disease: Preventing, treating, palliating disease and enhancing immunogenicity? World J Gastrointest Oncol 2025; 17:103746. [DOI: 10.4251/wjgo.v17.i5.103746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 02/21/2025] [Accepted: 04/11/2025] [Indexed: 05/15/2025] Open
Abstract
Cryotherapy is a treatment modality that uses extreme cold to destroy unwanted tissue through both immediate and delayed cellular injury. This therapy is increasingly being adopted across various medical specialties due to its minimally invasive nature and technological advancements that have been made. In the esophagus, cryotherapy is particularly utilized for the management of Barrett esophagus. It has been demonstrated to be effective and safe with potential benefits, such as a reduction in pain, over radiofrequency ablation. Additionally, it might offer a valuable alternative for patients unresponsive to radiofrequency ablation. Cryotherapy is applied for other conditions as well, including esophageal squamous cell neoplasia and malignant dysphagia. More research is needed to gain understanding of the utility in these conditions. Interestingly, cryotherapy has shown the ability to enhance the host’s immune response in reaction to antigens left in situ after treatment. While preclinical data have demonstrated promising results, the immune response is often insufficient to induce tumor regression in the clinical setting. Therefore, there is growing interest in the combination of cryotherapy and immunotherapy where ablation creates an antigen depot, and the immune system is subsequently stimulated. This combination holds promise for the future and potentially opens new doors for a breakthrough in cancer treatment.
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Affiliation(s)
- Laura Sophie Boer
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht 3584 CX, Utrecht, Netherlands
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein 3435 CM, Utrecht, Netherlands
| | - Stefan Nierkens
- Department of Translational Immunology, University Medical Center Utrecht, Utrecht 3584 CX, Utrecht, Netherlands
| | - Bas L A M Weusten
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht 3584 CX, Utrecht, Netherlands
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein 3435 CM, Utrecht, Netherlands
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Skrobic O, Simic A, Pesko P, Kravic-Stevovic T, Martinovic T, Bumbasirevic V. Impact of post RFA treatment on neosquamous epithelium microstructure. Sci Rep 2024; 14:28895. [PMID: 39572749 PMCID: PMC11582558 DOI: 10.1038/s41598-024-80081-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Accepted: 11/14/2024] [Indexed: 11/24/2024] Open
Abstract
Radiofrequency ablation (RFA) is effective treatment for Barrett's esophagus (BE). Product of successful RFA is neosquamous epithelium (NSE), which resembles native squamous epithelium and has lower risk for neoplastic transformation. Dilated intercellular spaces (IS) are common microscopic feature of reflux induced injury of esophagus. The aim of this study was to analyze the ultrastructure of NSE by transmission electron microscopy (TEM), depending on the post RFA treatment modalities and to asses impact of these findings on BE recurrence. Prospective observational clinical study based on TEM analysis of biopsy of specimens obtained from patients in whom CE of BE was achieved minimum 6 months after the last RFA session. In each patient biopsies were taken from NSE and proximal esophagus. Two groups of patients were defined according to the post RFA treatment: proton pump inhibitors (PPI's) or laparoscopic Nissen fundoplication (LNF). Comparative analysis of IS length was made between two groups. Endoscopic surveillance with biopsies was conducted for 5 years. Overall 22 patients with CE of BE after RFA underwent complete study protocol, out of whom in 10 LNF was performed, while 12 were treated with PPI's. The mean values of IS length in the proximal esophagus and NSE in LNF group were 0.378 ± 0.116 µm and 0.878 ± 0.354, while in PPI's group 0.724 ± 0.325 µm and 1.228 ± 0.226 µm, respectively. Mean lenghts of IS were statistically significantly higher in PPI's group both in NSE (p = 0.032) and proximal esophagus (p = 0.009). There were 5 BE recurrences after 5 years surveillance, 4 in PPI group and 1 in LNF group, without statistical significance (p = 0.084). Dilated IS are commonly presented in NSE of patients with CE of BE with RFA who are treated with PPI's. LNF provides may offer better reflux protection of NSE than PPI's and may reduce the rates of recurrence after successful RFA treatment.
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Affiliation(s)
- Ognjan Skrobic
- Department of Esophagogastric Surgery, Hospital for Digestive Surgery, School of Medicine, University Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia.
| | - Aleksandar Simic
- Department of Esophagogastric Surgery, Hospital for Digestive Surgery, School of Medicine, University Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia
| | - Predrag Pesko
- Department of Esophagogastric Surgery, Hospital for Digestive Surgery, School of Medicine, University Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia
- Serbian Academy of Sciences and Arts, Beograd, Serbia
| | - Tamara Kravic-Stevovic
- Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Tamara Martinovic
- Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vladimir Bumbasirevic
- Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia
- Serbian Academy of Sciences and Arts, Beograd, Serbia
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Rubenstein JH, Sawas T, Wani S, Eluri S, Singh S, Chandar AK, Perumpail RB, Inadomi JM, Thrift AP, Piscoya A, Sultan S, Singh S, Katzka D, Davitkov P. AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia. Gastroenterology 2024; 166:1020-1055. [PMID: 38763697 PMCID: PMC11345740 DOI: 10.1053/j.gastro.2024.03.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/21/2024]
Abstract
BACKGROUND & AIMS Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.
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Affiliation(s)
- Joel H Rubenstein
- Center for Clinical Management Research, Lieutenant Colonel Charles S. Kettles Veterans Affairs Medical Center, Ann Arbor, Michigan; Barrett's Esophagus Program, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan; Cancer Control and Population Sciences Program, Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan.
| | - Tarek Sawas
- Division of Digestive and Liver Disease, University of Texas Southwestern, Dallas, Texas
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Swathi Eluri
- Division of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, Florida
| | - Shailendra Singh
- Division of Gastroenterology, West Virginia University, Morgantown, West Virginia; Advanced Center for Endoscopy, West Virginia University Medicine, Morgantown, West Virginia
| | - Apoorva K Chandar
- Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | | | - John M Inadomi
- Department of Internal Medicine, The University of Utah School of Medicine, Salt Lake City, Utah
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | | | - Shahnaz Sultan
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota; Veterans Affairs Healthcare System, Minneapolis, Minnesota
| | - Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - David Katzka
- Division of Gastroenterology and Hepatology, Columbia University, New York, New York
| | - Perica Davitkov
- Department of Medicine, Case Western Reserve University, Cleveland, Ohio; Division of Gastroenterology, Veterans Affairs Northeast Ohio Healthcare System, Cleveland, Ohio
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Weusten BLAM, Bisschops R, Dinis-Ribeiro M, di Pietro M, Pech O, Spaander MCW, Baldaque-Silva F, Barret M, Coron E, Fernández-Esparrach G, Fitzgerald RC, Jansen M, Jovani M, Marques-de-Sa I, Rattan A, Tan WK, Verheij EPD, Zellenrath PA, Triantafyllou K, Pouw RE. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2023; 55:1124-1146. [PMID: 37813356 DOI: 10.1055/a-2176-2440] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
MR1 : ESGE recommends the following standards for Barrett esophagus (BE) surveillance:- a minimum of 1-minute inspection time per cm of BE length during a surveillance endoscopy- photodocumentation of landmarks, the BE segment including one picture per cm of BE length, and the esophagogastric junction in retroflexed position, and any visible lesions- use of the Prague and (for visible lesions) Paris classification- collection of biopsies from all visible abnormalities (if present), followed by random four-quadrant biopsies for every 2-cm BE length.Strong recommendation, weak quality of evidence. MR2: ESGE suggests varying surveillance intervals for different BE lengths. For BE with a maximum extent of ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE with a maximum extent of ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent of ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies. For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance are advised.Weak recommendation, low quality of evidence. MR3: ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient's life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered. Weak recommendation, very low quality of evidence. MR4: ESGE recommends offering endoscopic eradication therapy using ablation to patients with BE and low grade dysplasia (LGD) on at least two separate endoscopies, both confirmed by a second experienced pathologist.Strong recommendation, high level of evidence. MR5: ESGE recommends endoscopic ablation treatment for BE with confirmed high grade dysplasia (HGD) without visible lesions, to prevent progression to invasive cancer.Strong recommendation, high level of evidence. MR6: ESGE recommends offering complete eradication of all remaining Barrett epithelium by ablation after endoscopic resection of visible abnormalities containing any degree of dysplasia or esophageal adenocarcinoma (EAC).Strong recommendation, moderate quality of evidence. MR7: ESGE recommends endoscopic resection as curative treatment for T1a Barrett's cancer with well/moderate differentiation and no signs of lymphovascular invasion.Strong recommendation, high level of evidence. MR8: ESGE suggests that low risk submucosal (T1b) EAC (i. e. submucosal invasion depth ≤ 500 µm AND no [lympho]vascular invasion AND no poor tumor differentiation) can be treated by endoscopic resection, provided that adequate follow-up with gastroscopy, endoscopic ultrasound (EUS), and computed tomography (CT)/positrion emission tomography-computed tomography (PET-CT) is performed in expert centers.Weak recommendation, low quality of evidence. MR9: ESGE suggests that submucosal (T1b) esophageal adenocarcinoma with deep submucosal invasion (tumor invasion > 500 µm into the submucosa), and/or (lympho)vascular invasion, and/or a poor tumor differentiation should be considered high risk. Complete staging and consideration of additional treatments (chemotherapy and/or radiotherapy and/or surgery) or strict endoscopic follow-up should be undertaken on an individual basis in a multidisciplinary discussion.Strong recommendation, low quality of evidence. MR10 A: ESGE recommends that the first endoscopic follow-up after successful endoscopic eradication therapy (EET) of BE is performed in an expert center.Strong recommendation, very low quality of evidence. B: ESGE recommends careful inspection of the neo-squamocolumnar junction and neo-squamous epithelium with high definition white-light endoscopy and virtual chromoendoscopy during post-EET surveillance, to detect recurrent dysplasia.Strong recommendation, very low level of evidence. C: ESGE recommends against routine four-quadrant biopsies of neo-squamous epithelium after successful EET of BE.Strong recommendation, low level of evidence. D: ESGE suggests, after successful EET, obtaining four-quadrant random biopsies just distal to a normal-appearing neo-squamocolumnar junction to detect dysplasia in the absence of visible lesions.Weak recommendation, low level of evidence. E: ESGE recommends targeted biopsies are obtained where there is a suspicion of recurrent BE in the tubular esophagus, or where there are visible lesions suspicious for dysplasia.Strong recommendation, very low level of evidence. MR11: After successful EET, ESGE recommends the following surveillance intervals:- For patients with a baseline diagnosis of HGD or EAC:at 1, 2, 3, 4, 5, 7, and 10 years after last treatment, after which surveillance may be stopped.- For patients with a baseline diagnosis of LGD:at 1, 3, and 5 years after last treatment, after which surveillance may be stopped.Strong recommendation, low quality of evidence.
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Affiliation(s)
- Bas L A M Weusten
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Department of Gastroenterology and Hepatology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
| | - Raf Bisschops
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, TARGID, Leuven, Belgium
| | - Mario Dinis-Ribeiro
- Department of Gastroenterology, Porto Comprehensive Cancer Center, and RISE@CI-IPOP (Health Research Network), Porto Portugal
| | - Massimiliano di Pietro
- Early Cancer Institute, University of Cambridge and Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Oliver Pech
- Department of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Germany
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Francisco Baldaque-Silva
- Advanced Endoscopy Center Carlos Moreira da Silva, Department of Gastroenterology, Pedro Hispano Hospital, Matosinhos, Portugal
- Division of Medicine, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
| | - Maximilien Barret
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital and University of Paris, Paris, France
| | - Emmanuel Coron
- Institut des Maladies de l'Appareil Digestif, IMAD, Centre hospitalier universitaire Hôtel-Dieu, Nantes, Nantes, France
- Department of Gastroenterology and Hepatology, University Hospital of Geneva (HUG), Geneva, Switzerland
| | - Glòria Fernández-Esparrach
- Endoscopy Unit, Department of Gastroenterology, Hospital Clínic of Barcelona, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Biomedical Research Network on Hepatic and Digestive Diseases (CIBEREHD), Barcelona, Spain
| | - Rebecca C Fitzgerald
- Early Cancer Institute, University of Cambridge and Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Marnix Jansen
- Department of Histopathology, University College London Hospital NHS Trust, London, UK
| | - Manol Jovani
- Division of Gastroenterology, Maimonides Medical Center, New York, New York, USA
| | - Ines Marques-de-Sa
- Department of Gastroenterology, Porto Comprehensive Cancer Center, and RISE@CI-IPOP (Health Research Network), Porto Portugal
| | - Arti Rattan
- Department of Gastroenterology, Wollongong Hospital, Wollongong, New South Wales, Australia
| | - W Keith Tan
- Early Cancer Institute, University of Cambridge and Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Eva P D Verheij
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Pauline A Zellenrath
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, Second Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece
| | - Roos E Pouw
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Cancer Center Amsterdam, Amsterdam, The Netherlands
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5
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Shaheen NJ. Top tips for endoscopic management of refractory Barrett's esophagus. Gastrointest Endosc 2023:S0016-5107(23)03035-3. [PMID: 37925108 DOI: 10.1016/j.gie.2023.10.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 10/18/2023] [Accepted: 10/26/2023] [Indexed: 11/06/2023]
Affiliation(s)
- Nicholas J Shaheen
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
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6
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Samaddar S, Buckles D, Saha S, Zhang Q, Bansal A. Translating Molecular Biology Discoveries to Develop Targeted Cancer Interception in Barrett's Esophagus. Int J Mol Sci 2023; 24:11318. [PMID: 37511077 PMCID: PMC10379200 DOI: 10.3390/ijms241411318] [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: 06/24/2023] [Revised: 07/05/2023] [Accepted: 07/07/2023] [Indexed: 07/30/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates the at-risk population. Ample research has elucidated the pathogenesis of BE and its progression from metaplasia to invasive carcinoma; and multiple molecular pathways have been implicated in this process, presenting several points of cancer interception. Here, we explore the mechanisms of action of various agents, including proton pump inhibitors, non-steroidal anti-inflammatory drugs, metformin, and statins, and explain their roles in cancer interception. Data from the recent AspECT trial are discussed to determine how viable a multipronged approach to cancer chemoprevention would be. Further, novel concepts, such as the repurposing of chemotherapeutic drugs like dasatinib and the prevention of post-ablation BE recurrence using itraconazole, are discussed.
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Affiliation(s)
- Sohini Samaddar
- Department of Internal Medicine, University of Kansas Health System, Kansas City, KS 66160, USA
| | - Daniel Buckles
- Department of Gastroenterology and Hepatology, University of Kansas Health System, Kansas City, KS 66160, USA
| | - Souvik Saha
- Department of Internal Medicine, University of Kansas Health System, Kansas City, KS 66160, USA
| | - Qiuyang Zhang
- Center for Esophageal Diseases, Department of Medicine, Baylor University Medical Center, Dallas, TX 75246, USA
- Center for Esophageal Research, Baylor Scott & White Research Institute, Dallas, TX 75246, USA
| | - Ajay Bansal
- Department of Gastroenterology and Hepatology, University of Kansas Health System, Kansas City, KS 66160, USA
- University of Kansas Cancer Center, Kansas City, KS 66160, USA
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Reiter AJ, Farina DA, Fronza JS, Komanduri S. Magnetic sphincter augmentation: considerations for use in Barrett's esophagus. Dis Esophagus 2023; 36:doac096. [PMID: 36575922 PMCID: PMC10267686 DOI: 10.1093/dote/doac096] [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: 09/08/2022] [Revised: 11/11/2022] [Accepted: 11/23/2022] [Indexed: 12/29/2022]
Abstract
Barrett's esophagus (BE) occurs in 5-15% of patients with gastroesophageal reflux disease (GERD). While acid suppressive therapy is a critical component of BE management to minimize the risk of progression to esophageal adenocarcinoma, surgical control of mechanical reflux is sometimes necessary. Magnetic sphincter augmentation (MSA) is an increasingly utilized anti-reflux surgical therapy for GERD. While the use of MSA is listed as a precaution by the United States Food and Drug Administration, there are limited data showing effective BE regression with MSA. MSA offers several advantages in BE including effective reflux control, anti-reflux barrier restoration and reduced hiatal hernia recurrence. However, careful patient selection for MSA is necessary.
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Affiliation(s)
- Audra J Reiter
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Domenico A Farina
- Department of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jeffrey S Fronza
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Srinadh Komanduri
- Department of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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8
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Triggs JR, Krogh K, Simon V, Krause A, Kaplan JB, Yang GY, Wani S, Kahrilas PJ, Pandolfino J, Komanduri S. Novel histologic score predicts recurrent intestinal metaplasia after successful endoscopic eradication therapy. Dis Esophagus 2023; 36:doac078. [PMID: 36446594 PMCID: PMC10150172 DOI: 10.1093/dote/doac078] [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: 03/23/2022] [Revised: 09/17/2022] [Accepted: 10/08/2022] [Indexed: 12/02/2022]
Abstract
Endoscopic eradication therapy (EET) is an effective treatment for Barrett's esophagus (BE); however, disease recurrence remains problematic requiring surveillance post-treatment. While data regarding predictors of recurrence are limited, uncontrolled reflux may play a significant role. Our aim was to develop a scoring system based on histopathologic reflux in surveillance biopsies following EET to identify patients at high risk for recurrence of BE. Patients were identified from two centers in the treatment with resection and endoscopic ablation techniques for BE consortium. Hematoxylin and eosin-stained slides of surveillance biopsies post-EET were assessed for histologic changes associated with reflux from a cohort of patients who also underwent pH-metry (derivation cohort). We developed a novel scoring system (Recurrent Epithelial Changes from Uncontrolled Reflux [RECUR]) composed of dilated intercellular spaces, epithelial ballooning, basal cell hyperplasia, and parakeratosis, to identify patients with abnormal esophageal acid exposure. This scoring system was then used to grade surveillance biopsies from patients with or without recurrence of BE following EET (validation cohort). Of 41 patients in the derivation cohort, 19.5% had abnormal acid exposure times (AET) while on proton pump inhibitor therapy. The mean (SD) RECUR score for patients with AET <4% was 4.0 (1.6), compared with 5.5 (0.9) for AET ≥4% (P = 0.015). In the validation cohort consisting of 72 patients without recurrence and 64 patients with recurrence following EET, the RECUR score was the only significant predictor of recurrence (odds ratio: 1.36, 95% confidence interval: 1.10-1.69, P = 0.005). Histologic grading of surveillance biopsies using the RECUR scoring system correlates with BE recurrence following EET.
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Affiliation(s)
- Joseph R Triggs
- Division of Gastroenterology, Department of Medicine, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Katrina Krogh
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Violette Simon
- Division of Gastroenterology, Department of Medicine, University of Colorado, Denver, CO, USA
| | - Amanda Krause
- Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jeffrey B Kaplan
- Department of Pathology, University of Colorado, Denver, CO, USA
| | - Guang-Yu Yang
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Sachin Wani
- Division of Gastroenterology, Department of Medicine, University of Colorado, Denver, CO, USA
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - John Pandolfino
- Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Srinadh Komanduri
- Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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Spadaccini M, Alfarone L, Chandrasekar VT, Maselli R, Capogreco A, Franchellucci G, Massimi D, Fugazza A, Colombo M, Carrara S, Facciorusso A, Bhandari P, Sharma P, Hassan C, Repici A. What Is "Cold" and What Is "Hot" in Mucosal Ablation for Barrett's Oesophagus-Related Dysplasia: A Practical Guide. Life (Basel) 2023; 13:1023. [PMID: 37109552 PMCID: PMC10142767 DOI: 10.3390/life13041023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/31/2023] [Accepted: 04/12/2023] [Indexed: 04/29/2023] Open
Abstract
Over the last two decades, endoscopic eradication therapy has been established as the therapeutic strategy of choice for patients with Barrett's oesophagus-related dysplasia and early oesophageal adenocarcinoma. With a multimodal approach, ablative therapies have been highly effective in achieving remarkable eradication rates of metaplastic epithelium with an acceptable adverse event rate. Among ablative techniques, radiofrequency ablation is currently considered as the first-line option as its efficacy and safety are strongly supported by relevant data. Nevertheless, radiofrequency ablation is costly, and not universally available, or applicable to every situation. Moreover, primary failure and recurrence rates are not negligible. In the last few years, cryotherapy techniques and hybrid argon plasma coagulation have been increasingly assessed as potential novel ablative therapies. Preliminary data have been promising and suggest that they may even have a role as first-line options, alternatively to radiofrequency ablation. The aim of this review is to provide a practical guide for the ablation of Barrett's oesophagus, with emphasis on the different ablative options.
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Affiliation(s)
- Marco Spadaccini
- Department of Biomedical Sciences, Humanitas University, 20089 Rozzano, Italy
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Ludovico Alfarone
- Department of Biomedical Sciences, Humanitas University, 20089 Rozzano, Italy
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | | | - Roberta Maselli
- Department of Biomedical Sciences, Humanitas University, 20089 Rozzano, Italy
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Antonio Capogreco
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Gianluca Franchellucci
- Department of Biomedical Sciences, Humanitas University, 20089 Rozzano, Italy
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Davide Massimi
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Alessandro Fugazza
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Matteo Colombo
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Silvia Carrara
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Pradeep Bhandari
- Department of Gastroenterology, Portsmouth Hospitals University NHS Trust, Portsmouth PO6 3LY, UK
| | - Prateek Sharma
- Department of Gastroenterology and Hepatology, Kansas City VA Medical Center, Kansas City, MO 66045, USA
| | - Cesare Hassan
- Department of Biomedical Sciences, Humanitas University, 20089 Rozzano, Italy
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, 20089 Rozzano, Italy
- Digestive Endoscopy Unit, Department of Endoscopy, Humanitas Research Hospital, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
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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] [Download PDF] [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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11
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Weiss S, Pellat A, Corre F, Abou Ali E, Belle A, Terris B, Leconte M, Dohan A, Chaussade S, Coriat R, Barret M. Predictive factors of radiofrequency ablation failure in the treatment of dysplastic Barrett's esophagus. Clin Res Hepatol Gastroenterol 2023; 47:102065. [PMID: 36494071 DOI: 10.1016/j.clinre.2022.102065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 11/29/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Radiofrequency ablation (RFA) has become the recommended endoscopic treatment for flat dysplastic Barrett's esophagus. However, the outcomes of this treatment are variable across European countries. Our aim was to report the results of a French high-volume center, and to investigate factors associated with treatment failure. METHODS We conducted a single-center retrospective study from a prospectively collected database from 2011 to 2020, including all consecutive patients treated with RFA for flat dysplastic Barrett's esophagus. The primary endpoint was the failure rate of esophageal radiofrequency treatment, defined as either persistence of intestinal metaplasia at the end of treatment, or neoplastic progression during RFA. RESULTS 96 patients treated with a median of four RFA sessions for a mean C5M6 Barrett's esophagus were included in the analysis. Complete eradication of intestinal metaplasia and dysplasia were achieved in 59% and 79% of patients, respectively, resulting in a treatment failure rate of 41%. Ten patients experienced neoplastic progression during treatment. We recorded 14% of post-RFA esophageal strictures, all successfully treated by endoscopic dilatation. Univariate analysis identified the length of Barrett's esophagus and the absence of hiatal hernia as predictive factors for treatment failure, however not confirmed in multivariate analysis. CONCLUSION In our experience, RFA of flat dysplastic Barrett's esophagus had a 41% treatment failure rate. The length of the Barrett's segment might be associated with treatment failure. Although our results confirm a role for RFA in the management of dysplastic Barrett's esophagus, the treatment failure rate was higher than expected. This suggest that endoscopists, even in high-volume centers, should receive specific training in RFA.
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Affiliation(s)
- Simon Weiss
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France
| | - Anna Pellat
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France
| | - Felix Corre
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France
| | - Einas Abou Ali
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France
| | - Arthur Belle
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France
| | - Benoit Terris
- Department of Pathology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France
| | - Mahaut Leconte
- Department of Digestive Surgery, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France
| | - Anthony Dohan
- Department of Abdominal and Interventional Imaging, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France
| | - Stanislas Chaussade
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France
| | - Romain Coriat
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France
| | - Maximilien Barret
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France; Université de Paris Cité, France.
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12
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Vantanasiri K, Iyer PG. State-of-the-art management of dysplastic Barrett's esophagus. Gastroenterol Rep (Oxf) 2022; 10:goac068. [PMID: 36381221 PMCID: PMC9651477 DOI: 10.1093/gastro/goac068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 10/19/2022] [Accepted: 10/24/2022] [Indexed: 08/15/2023] Open
Abstract
Endoscopic eradication therapy (EET) has become a standard of care for treatment of dysplastic Barrett's esophagus (BE) and early Barrett's neoplasia. EET mainly consists of removal of any visible lesions via endoscopic resection and eradication of all remaining Barrett's mucosa using endoscopic ablation. Endoscopic mucosal resection and endoscopic submucosal dissection are the two available resection techniques. After complete resection of all visible lesions, it is crucial to perform endoscopic ablation to ensure complete eradication of the remaining Barrett's segment. Endoscopic ablation can be done either with thermal techniques, including radiofrequency ablation and argon plasma coagulation, or cryotherapy techniques. The primary end point of EET is achieving complete remission of intestinal metaplasia (CRIM) to decrease the risk of dysplastic recurrence after successful EET. After CRIM is achieved, a standardized endoscopic surveillance protocol needs to be implemented for early detection of BE recurrence.
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Affiliation(s)
- Kornpong Vantanasiri
- Barrett’s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Prasad G Iyer
- Barrett’s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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13
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An Endoscopic and Histologic Study on Healing of Radiofrequency Ablation Wounds in Patients With Barrett's Esophagus. Am J Gastroenterol 2022; 117:1583-1592. [PMID: 35970814 DOI: 10.14309/ajg.0000000000001940] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 07/29/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Radiofrequency ablation (RFA) of Barrett's esophagus (BE) inflicts a wound spanning 3 epithelial types (stratified squamous, Barrett's metaplasia, gastric epithelium), yet the esophageal injury heals almost completely with squamous epithelium. Knowledge of how this unique wound heals might elucidate mechanisms underlying esophageal metaplasia. We aimed to prospectively and systematically characterize the early endoscopic and histologic features of RFA wound healing. METHODS Patients with nondysplastic BE had endoscopy with systematic esophageal photographic mapping, biopsy, and volumetric laser endomicroscopy performed before and at 1, 2, and 4 weeks after RFA. RESULTS Seven patients (6 men; mean age 56.1 ± 10.9 years) completed this study. Squamous re-epithelialization of RFA wounds did not only progress exclusively through squamous cells extending from the proximal wound edge but also progressed through islands of squamous epithelium sprouting throughout the ablated segment. Volumetric laser endomicroscopy revealed significant post-RFA increases in subepithelial glandular structures associated with the squamous islands. In 2 patients, biopsies of such islands revealed newly forming squamous epithelium contiguous with immature-appearing squamous cells arising from esophageal submucosal gland ducts. Subsquamous intestinal metaplasia (SSIM) was found in biopsies at 2 and/or 4 weeks after RFA in 6 of 7 patients. DISCUSSION RFA wounds in BE are re-epithelialized, not just by squamous cells from the proximal wound margin but by scattered squamous islands in which esophageal submucosal gland duct cells seem to redifferentiate into the squamous progenitors that fuel squamous re-epithelialization. SSIM can be found in most patients during the healing process. We speculate that this SSIM might underlie Barrett's recurrences after apparently successful eradication.
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Mittal C, Muthusamy VR, Simon VC, Brauer BC, Mullady DK, Hollander T, Sloan I, Kushnir V, Early D, Rastogi A, Hammad HT, Edmundowicz SA, Han S, Thaker AM, Ezekwe E, Wani S, Kwasny MJ, Komanduri S. Threshold evaluation for optimal number of endoscopic treatment sessions to achieve complete eradication of Barrett's metaplasia. Endoscopy 2022; 54:927-933. [PMID: 35135015 DOI: 10.1055/a-1765-7197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Endoscopic eradication therapy (EET) is the standard of care for Barrett's esophagus (BE)-associated neoplasia. Previous data suggest the mean number of EET sessions required to achieve complete eradication of intestinal metaplasia (CE-IM) is 3. This study aimed to define the threshold of EET sessions required to achieve CE-IM. METHODS The TREAT-BE Consortium is a multicenter outcomes cohort including prospectively enrolled patients with BE undergoing EET. All patients achieving CE-IM were included. Demographic, endoscopic, and histologic data were recorded at treatment onset along with treatment details and surveillance data. Kaplan-Meier analysis was performed to define a threshold of EET sessions, with 95 %CI, required to achieve CE-IM. A secondary analysis examined predictors of incomplete response to EET using multiple logistic regression and recurrence rates. RESULTS 623 patients (mean age 65.2 [SD 11.6], 79.6 % male, 86.5 % Caucasian) achieved CE-IM in a mean of 2.9 (SD 1.7) EET sessions (median 2) and a median total observation period of 2.7 years (interquartile range 1.4-5.0). After three sessions, 73 % of patients achieved CE-IM (95 %CI 70 %-77 %). Age (odds ratio [OR] 1.25, 95 %CI 1.05-1.50) and length of BE (OR 1.24, 95 %CI 1.17-1.31) were significant predictors of incomplete response. CONCLUSION The current study found that a threshold of three EET sessions would achieve CE-IM in the majority of patients. Alternative therapies and further diagnostic testing should be considered for patients who do not have significant response to EET after three sessions.
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Affiliation(s)
- Chetan Mittal
- Interventional Oncology and Surgical Endoscopy, Parkview Health, Fort Wayne, Indiana, United States
| | - V Raman Muthusamy
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California, United States
| | - Violette C Simon
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Brian C Brauer
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Daniel K Mullady
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, United States
| | - Thomas Hollander
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, United States
| | - Ian Sloan
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, United States
| | - Vladimir Kushnir
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, United States
| | - Dayna Early
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, United States
| | - Amit Rastogi
- Division of Gastroenterology, Kansas University, Kansas City, Kansas, United States
| | - Hazem T Hammad
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Steven A Edmundowicz
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Samuel Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Adarsh M Thaker
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California, United States
| | - Ezenwanyi Ezekwe
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Mary J Kwasny
- Interventional Oncology and Surgical Endoscopy, Parkview Health, Fort Wayne, Indiana, United States
| | - Srinadh Komanduri
- Interventional Oncology and Surgical Endoscopy, Parkview Health, Fort Wayne, Indiana, United States
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Wani S, Souza RF, Durkalski VL, Serrano J, Hamilton F, Shaheen NJ. Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett's Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications. Gastroenterology 2022; 163:556-562.e4. [PMID: 35679951 PMCID: PMC9398991 DOI: 10.1053/j.gastro.2022.05.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 05/17/2022] [Accepted: 05/30/2022] [Indexed: 12/02/2022]
Affiliation(s)
- Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Rhonda F. Souza
- Department of Medicine, Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott & White Research Institute, Dallas, Texas
| | - Valerie L. Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Jose Serrano
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive Kidney Diseases, National Institute of Health, Bethesda, Maryland
| | - Frank Hamilton
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive Kidney Diseases, National Institute of Health, Bethesda, Maryland
| | - Nicholas J. Shaheen
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina
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Surveillance After Treatment of Barrett's Esophagus Benefits Those With High-Grade Dysplasia or Intramucosal Cancer Most. Am J Gastroenterol 2022; 117:1056-1062. [PMID: 35435856 PMCID: PMC9246923 DOI: 10.14309/ajg.0000000000001784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 04/12/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Endoscopic eradication therapy with radiofrequency ablation (RFA) and endoscopic mucosal resection is a safe and effective treatment for Barrett's esophagus. Although the outcomes of surveillance endoscopy after successful endoscopic eradication therapy have been described, no previous studies have modeled the natural history or the effect of surveillance endoscopy after successful ablation to prevent progression to invasive esophageal adenocarcinoma. METHODS The US RFA Registry is a multicenter registry consisting of patients treated with RFA for Barrett's esophagus at 148 institutions (113 community-based and 35 academic-affiliated). The authors fit models to impute the natural history of recurrence and neoplastic progression after any recurrence or retreatment. Natural history estimates of invasive adenocarcinoma after ablation therapy were compared with as-treated estimates at 5 years to derive the preventive risk difference for surveillance. RESULTS Natural history estimates for the postablation progression of high-grade dysplasia (HGD) or intramucosal adenocarcinoma to invasive adenocarcinoma after treatment were 6.3% at 5 years compared with 1.3% for low-grade dysplasia (LGD). The natural history model found a much higher preventative risk difference for surveillance for HGD/intramucosal adenocarcinoma (-4.8%), compared with LGD (-1.1%). The numbers needed to surveil at 5 years were 21 and 90 for these groups, respectively, to prevent one case of invasive esophageal adenocarcinoma, making surveillance after successful ablation of baseline HGD more than 4 times as effective at preventing invasive cancer than after successful ablation of baseline LGD. DISCUSSION Endoscopic surveillance after successful ablation of baseline HGD or intramucosal cancer is much more effective than surveillance after successful treatment of baseline LGD in averting invasive adenocarcinoma. Although the modest benefits of surveillance for treated LGD may be greater than the risks for patients at average risk for adverse effects of endoscopy, clinicians should concentrate on retaining patients with baseline HGD or cancer in endoscopic surveillance programs.
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17
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Adherence to Surveillance Endoscopies Posteradication of Barrett's Esophagus With High-grade Dysplasia or Carcinoma In Situ. J Clin Gastroenterol 2022; 57:459-465. [PMID: 35389913 DOI: 10.1097/mcg.0000000000001701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 03/08/2022] [Indexed: 12/10/2022]
Abstract
GOALS We aimed to evaluate factors associated with patient adherence to recommended surveillance guidelines during the first 3 years after endoscopic eradication of Barrett's esophagus (BE) with high-grade dysplasia (HGD) or T1a carcinoma in situ (CIS) and the relationship between adherence and detection of recurrence. BACKGROUND While surveillance endoscopies after treatment of BE with HGD or T1a CIS are an important component of therapy, it is unclear whether these high-risk patients are adhering to recommended surveillance guidelines. MATERIALS AND METHODS A total of 123 BE patients who underwent radiofrequency ablation±endoscopic mucosal resection for biopsy-proven HGD, or CIS between January 2010 and November 2018 underwent retrospective review for adherence to surveillance guidelines, patient factors related to adherence, and recurrence of dysplasia or CIS at 12, 24, and 36 months. RESULTS Of 123 BE patients (89 HGD and 34 CIS), adherence during the first year following treatment was 26.97% for HGD patients and 41.18% for CIS patients, with increasing adherence rates in subsequent years. Patients who received 3 to 4 surveillance endoscopies in the first year posttreatment had significantly higher rates of recurrence detection than patients who received 0 to 2 surveillance endoscopies over this interval (P=0.01). No patient factors were found to impact adherence significantly. CONCLUSIONS Adherence to recommended surveillance intervals after endoscopic treatment of BE with HGD or CIS is low, with poor adherence during the first year associated with decreased detection of recurrence. Future studies are needed to evaluate risk factors and develop a potential intervention for poor adherence in this high-risk population.
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18
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Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol 2022; 117:559-587. [PMID: 35354777 DOI: 10.14309/ajg.0000000000001680] [Citation(s) in RCA: 229] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 02/04/2022] [Indexed: 02/07/2023]
Abstract
Barrett's esophagus (BE) is a common condition associated with chronic gastroesophageal reflux disease. BE is the only known precursor to esophageal adenocarcinoma, a highly lethal cancer with an increasing incidence over the last 5 decades. These revised guidelines implement Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the definition and diagnosis of BE, screening for BE and esophageal adenocarcinoma, surveillance of patients with known BE, and the medical and endoscopic treatment of BE and its associated early neoplasia. Important changes since the previous iteration of this guideline include a broadening of acceptable screening modalities for BE to include nonendoscopic methods, liberalized intervals for surveillance of short-segment BE, and volume criteria for endoscopic therapy centers for BE. We recommend endoscopic eradication therapy for patients with BE and high-grade dysplasia and those with BE and low-grade dysplasia. We propose structured surveillance intervals for patients with dysplastic BE after successful ablation based on the baseline degree of dysplasia. We could not make recommendations regarding chemoprevention or use of biomarkers in routine practice due to insufficient data.
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Hybrid APC in Combination With Resection for the Endoscopic Treatment of Neoplastic Barrett's Esophagus: A Prospective, Multicenter Study. Am J Gastroenterol 2022; 117:110-119. [PMID: 34845994 PMCID: PMC8715998 DOI: 10.14309/ajg.0000000000001539] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 09/27/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The current therapy of neoplastic Barrett's esophagus (BE) consists of endoscopic resection plus ablation, with radiofrequency ablation as the best studied technique. This prospective trial assesses a potential alternative, namely hybrid argon plasma ablation. METHODS Consecutive patients with neoplastic BE undergoing ablation after curative endoscopic resection (89.6%) or primarily were included into this prospective trial in 9 European centers. Up to 5 ablation sessions were allowed for complete eradication of BE (initial complete eradication of intestinal metaplasia [CE-IM]), by definition including BE-associated neoplasia, documented by 1 negative endoscopy with biopsies. The main outcome was the rate of initial CE-IM in intention-to-treat (ITT) and per-protocol (PP) samples at 2 years. The secondary end points were the rate of recurrence-free cases (sustained CE-IM) documented by negative follow-up endoscopies with biopsies and immediate/delayed adverse events. RESULTS One hundred fifty-four patients (133 men and 21 women, mean age 64 years) received a mean of 1.2 resection and 2.7 ablation sessions (range 1-5). Initial CE-IM was achieved in 87.2% of 148 cases in the PP analysis (ITT 88.4%); initial BE-associated neoplasia was 98.0%. On 2-year follow-up of the 129 successfully treated cases, 70.8% (PP) or 65.9% (ITT) showed sustained CE-IM; recurrences were mostly endoscopy-negative biopsy-proven BE epithelium and neoplasia in 3 cases. Adverse events were seen in 6.1%. DISCUSSION Eradication and recurrence rates of Barrett's intestinal metaplasia and neoplasia by means of hybrid argon plasma coagulation at 2 years seem to be within expected ranges. Final evidence in comparison to radiofrequency ablation can only be provided by a randomized comparative trial.
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20
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Zhang LY, Kalloo AN, Ngamruengphong S. Therapeutic Endoscopy and the Esophagus: State of the Art and Future Directions. Gastroenterol Clin North Am 2021; 50:935-958. [PMID: 34717880 DOI: 10.1016/j.gtc.2021.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Therapeutic gastrointestinal endoscopy is rapidly evolving, and this evolution is quite apparent for esophageal diseases. Minimally invasive endoluminal therapy now allows outpatient treatment of many esophageal diseases that were traditionally managed surgically. In this review article, we explore the most exciting new developments. We discuss the use of peroral endoscopic myotomy for treatment of achalasia and other related diseases, as well as the modifications that have allowed its use in treatment of Zenker diverticulum. We cover endoscopic treatment of gastroesophageal reflux disease and Barrett's esophagus. Further, we explore advanced endoscopic resection techniques.
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Affiliation(s)
- Linda Y Zhang
- Division of Gastroenterology & Hepatology, Johns Hopkins Medicine, 1800 Orleans St, Sheikh Zayed Tower, Suite M2058, Baltimore, MD 21287, USA
| | - Anthony N Kalloo
- Department of Medicine, Maimonides Medical Center, 4802 Tenth Avenue, Brooklyn, NY 11219, USA; Department of Medicine, Johns Hopkins Medicine, 1800 Orleans St, Sheikh Zayed Tower, Baltimore, MD 21287, USA
| | - Saowanee Ngamruengphong
- Division of Gastroenterology & Hepatology, Johns Hopkins Medicine, 4940 Eastern Avenue, A Building, 5th Floor, A-501, Baltimore, MD 21224, USA.
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21
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Pan L, Liu X, Wang W, Zhu L, Yu W, Lv W, Hu J. The Influence of Different Treatment Strategies on the Long-Term Prognosis of T1 Stage Esophageal Cancer Patients. Front Oncol 2021; 11:700088. [PMID: 34722247 PMCID: PMC8551622 DOI: 10.3389/fonc.2021.700088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 08/31/2021] [Indexed: 12/02/2022] Open
Abstract
Objective To compare the long-term prognosis effects of non-esophagectomy and esophagectomy on patients with T1 stage esophageal cancer. Methods All esophageal cancer patients in the study were included from the National Surveillance Epidemiology and End Results (SEER) database between 2005-2015. These patients were classified into non-esophagectomy group and esophagectomy group according to therapy methods and were compared in terms of esophagus cancer specific survival (ECSS) and overall survival (OS) rates. Results A total of 591 patients with T1 stage esophageal cancer were enrolled in this study, including 212 non-esophagectomy patients and 111 esophagectomy patients in the T1a subgroup and 37 non-esophagectomy patients and 140 esophagectomy patients in the T1b subgroup. In all T1 stage esophageal cancer patients, there was no difference in the effect of non-esophagectomy and esophagectomy on postoperative OS, but postoperative ECSS in patients treated with non-esophagectomy was significantly better than those treated with esophagectomy. Cox proportional hazards regression model analysis showed that the risk factors affecting ECSS included race, primary site, tumor size, grade, and AJCC stage but factors affecting OS only include tumor size, grade, and AJCC stage in T1 stage patients. In the subgroup analysis, there was no difference in either ECSS or OS between the non-esophagectomy group and the esophagectomy group in T1a patients. However, in T1b patients, the OS after esophagectomy was considerably better than that of non-esophagectomy. Conclusions Non-esophagectomy, including a variety of non-invasive procedures, is a safe and available option for patients with T1a stage esophageal cancer. For some T1b esophageal cancer patients, esophagectomy cannot be replaced at present due to its diagnostic and therapeutic effect on lymph node metastasis.
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Affiliation(s)
- Liang Pan
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xingyu Liu
- Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Weidong Wang
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Linhai Zhu
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wenfeng Yu
- Department of Thoracic Surgery, The Hangzhou Chest Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wang Lv
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jian Hu
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Condon A, Muthusamy VR. The evolution of endoscopic therapy for Barrett's esophagus. Ther Adv Gastrointest Endosc 2021; 14:26317745211051834. [PMID: 34708204 PMCID: PMC8543722 DOI: 10.1177/26317745211051834] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 09/21/2021] [Indexed: 12/20/2022] Open
Abstract
Barrett’s esophagus is the condition in which a metaplastic columnar epithelium
replaces the stratified squamous epithelium that normally lines the distal
esophagus. The condition develops as a consequence of chronic gastroesophageal
reflux disease and predisposes the patient to the development of esophageal
adenocarcinoma. The diagnosis and management of Barrett’s esophagus have
undergone dramatic changes over the years and continue to evolve today.
Endoscopic eradication therapy has revolutionized the management of dysplastic
Barrett’s esophagus and early esophageal adenocarcinoma by significantly
reducing the morbidity and mortality associated with the prior gold standard of
therapy, esophagectomy. The purpose of this review is to highlight current
principles in the management and endoscopic treatment of this disease.
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Affiliation(s)
- Ashwinee Condon
- Vatche & Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - V Raman Muthusamy
- Vatche & Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, UCLA, 200 UCLA Medical Plaza, Room 330-37, Los Angeles, CA 90095, USA
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23
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Desai M, Rösch T, Sundaram S, Chandrasekar VT, Kohli D, Spadaccini M, Hassan C, Repici A, Sharma P. Systematic review with meta-analysis: the long-term efficacy of Barrett's endoscopic therapy-stringent selection criteria and a proposal for definitions. Aliment Pharmacol Ther 2021; 54:222-233. [PMID: 34165205 DOI: 10.1111/apt.16473] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/16/2021] [Accepted: 05/25/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Barrett's endoscopic therapy (BET) is well established for neoplasia in Barrett's oesophagus using a concept of complete eradication of all Barrett's. However, long-term efficacy is not known. AIMS To perform a systematic review and meta-analysis to examine long-term efficacy of BET for Barrett's neoplasia. METHODS Electronic databases were searched for studies meeting stringent criteria: (a) subjects with high-grade dysplasia and/or superficial adenocarcinoma who underwent BET (ablation ± endoscopic mucosal resection); (b) BET completion by confirmation of complete eradication of neoplasia (CE-N) and intestinal metaplasia (CE-IM) with systematic sampling and (c) clearly defined follow-up (endoscopy and biopsy) protocol of ≥2 years thereafter for detection of recurrence. Pooled estimates of CE-N and CE-IM after BET completion and follow-up were analysed. RESULTS Eight studies met the stringent criteria (n = 794, males 89%, age 64.6 years). Despite high efficacy of BET at therapy completion (CE-N: 95.9 [91.7-98.7]%; CE-IM: 90.9 [83-96.6]%), this declined (CE-N: 89 [73.4-98.2]%; CE-IM: 77.8 [65.6-88]%) over 3.4 years of follow-up. There was considerable heterogeneity. Only two studies reported a post-BET follow-up of >5 years (CE-IM 50 [41.5%-58.5]%). Higher person years of follow-up seem to correlate with decrease in BET efficacy. CONCLUSION Using stringent criteria for appropriate study selection with sufficient follow-up, a lack of high-quality controlled intervention trials becomes evident for assessment of long-term durable remission rates of BET despite initial high success rates. We plea for a uniform documentation of study details which could be used in future trials.
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Affiliation(s)
- Madhav Desai
- Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, MO, USA.,Department of Gastroenterology and Hepatology, University of Kansas School of Medicine, Kansas City, KS, USA
| | - Thomas Rösch
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Suneha Sundaram
- Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, MO, USA
| | | | - Divyanshoo Kohli
- Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, MO, USA
| | - Marco Spadaccini
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy
| | - Cesare Hassan
- Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy
| | - Alessandro Repici
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy
| | - Prateek Sharma
- Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, MO, USA.,Department of Gastroenterology and Hepatology, University of Kansas School of Medicine, Kansas City, KS, USA
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24
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Barret M, Pioche M, Terris B, Ponchon T, Cholet F, Zerbib F, Chabrun E, Le Rhun M, Coron E, Giovannini M, Caillol F, Laugier R, Jacques J, Legros R, Boustiere C, Rahmi G, Metivier-Cesbron E, Vanbiervliet G, Bauret P, Escourrou J, Branche J, Jilet L, Abdoul H, Kaddour N, Leblanc S, Bensoussan M, Prat F, Chaussade S. Endoscopic radiofrequency ablation or surveillance in patients with Barrett's oesophagus with confirmed low-grade dysplasia: a multicentre randomised trial. Gut 2021; 70:1014-1022. [PMID: 33685969 DOI: 10.1136/gutjnl-2020-322082] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 02/25/2021] [Accepted: 02/27/2021] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Due to an annual progression rate of Barrett's oesophagus (BO) with low-grade dysplasia (LGD) between 9% and 13% per year endoscopic ablation therapy is preferred to surveillance. Since this recommendation is based on only one randomised trial, we aimed at checking these results by another multicentre randomised trial with a similar design. DESIGN A prospective randomised study was performed in 14 centres comparing radiofrequency ablation (RFA) (maximum of 4 sessions) to annual endoscopic surveillance, including patients with a confirmed diagnosis of BO with LGD. Primary outcome was the prevalence of LGD at 3 years. Secondary outcomes were the prevalence of LGD at 1 year, the complete eradication of intestinal metaplasia (CE-IM) at 3 years, the rate of neoplastic progression at 3 years and the treatment-related morbidity. RESULTS 125 patients were initially included, of whom 82 with confirmed LGD (76 men, mean age 62.3 years) were finally randomised, 40 patients in the RFA and 42 in the surveillance group. At 3 years, CE-IM rates were 35% vs 0% in the RFA and surveillance groups, respectively (p<0.001). At the same time, the prevalence LGD was 34.3% (95% CI 18.6 to 50.0) in the RFA group vs 58.1% (95% CI 40.7 to 75.4) in the surveillance group (OR=0.38 (95% CI 0.14 to 1.02), p=0.05). Neoplastic progression was found in 12.5% (RFA) vs 26.2% (surveillance; p=0.15). The complication rate was maximal after the first RFA treatment (16.9%). CONCLUSION RFA modestly reduced the prevalence of LGD as well as progression risk at 3 years. The risk-benefit balance of endoscopic ablation therapy should therefore be carefully weighted against surveillance in patients with BO with confirmed LGD. TRIAL REGISTRATION NUMBER NCT01360541.
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Affiliation(s)
- Maximilien Barret
- Gastroenterology and Digestive Oncology, Hopital Cochin, Paris, Île-de-France, France
| | - Mathieu Pioche
- Gastroenterology and Endoscopy, Groupement Hospitalier Edouard Herriot, Lyon, Rhône-Alpes, France
| | - Benoit Terris
- Pathology, Hopital Cochin, Paris, Île-de-France, France
| | - Thierry Ponchon
- Gastroenterology, Groupement Hospitalier Edouard Herriot, Lyon, Rhône-Alpes, France
| | - Franck Cholet
- Digestive Endoscopy, CHRU de Brest, Brest, Bretagne, France
| | - Frank Zerbib
- Gastroenterology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France
| | - Edouard Chabrun
- Gastroenterology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France
| | - Marc Le Rhun
- Gastroenterology, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France
| | - Emmanuel Coron
- Gastroenterology, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France
| | - Marc Giovannini
- Gastroenterology, Institut Paoli-Calmettes, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Fabrice Caillol
- Gastroenterology, Institut Paoli-Calmettes, Marseille, Provence-Alpes-Côte d'Azur, France
| | - René Laugier
- Gastroenterology, Hospital Timone, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Jeremie Jacques
- Gastroenterology, Centre Hospitalier Universitaire de Limoges, Limoges, Limousin, France
| | - Romain Legros
- Gastroenterology, Centre Hospitalier Universitaire de Limoges, Limoges, Limousin, France
| | - Christian Boustiere
- Gastroenterology, Hopital Saint Joseph, Marseille, Provence-Alpes-Côte d'Azu, France
| | - Gabriel Rahmi
- Gastroenterology and Digestive Endoscopy, Hopital Europeen Georges Pompidou, Paris, France
| | - Elodie Metivier-Cesbron
- Digestive Endoscopy Unit, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
| | - Geoffroy Vanbiervliet
- Gastroenterology, Centre Hospitalier Universitaire de Nice, Nice, Provence-Alpes-Côte d'Azur, France
| | - Paul Bauret
- Gastroenterology, Centre Hospitalier Universitaire de Montpellier, Montpellier, Languedoc-Roussillon, France
| | - Jean Escourrou
- Gastroenterology, Centre Hospitalier Universitaire de Toulouse, Toulouse, Midi-Pyrénées, France
| | - Julien Branche
- Gastroenterology, Centre Hospitalier Universitaire de Lille, Lille, Hauts-de-France, France
| | - Lea Jilet
- Clinical Research Unit, Hospital Cochin, Paris, Île-de-France, France
| | - Hendy Abdoul
- Clinical Research Unit, Hospital Cochin, Paris, Île-de-France, France
| | - Nadira Kaddour
- Clinical Research Unit, Hospital Cochin, Paris, Île-de-France, France
| | - Sarah Leblanc
- Gastroenterology and Digestive Oncology, Hopital Cochin, Paris, Île-de-France, France
| | - Michael Bensoussan
- Gastroenterology, Centre intégré de santé et de services sociaux de la Montérégie-Centre du Québec territoire Champlain-Charles-Le Moyne, Saint-Hubert, Quebec, Canada
| | - Frederic Prat
- Gastroenterology and Digestive Oncology, Hopital Cochin, Paris, Île-de-France, France
| | - Stanislas Chaussade
- Gastroenterology and Digestive Oncology, Hopital Cochin, Paris, Île-de-France, France
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25
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Zerbib F, Bredenoord AJ, Fass R, Kahrilas PJ, Roman S, Savarino E, Sifrim D, Vaezi M, Yadlapati R, Gyawali CP. ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro-esophageal reflux disease. Neurogastroenterol Motil 2021; 33:e14075. [PMID: 33368919 DOI: 10.1111/nmo.14075] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/11/2020] [Accepted: 12/13/2020] [Indexed: 02/08/2023]
Abstract
Up to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term "refractory GERD" has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD-related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term "refractory GERD symptoms" only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.
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Affiliation(s)
- Frank Zerbib
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | | | - Ronnie Fass
- Digestive Health Center, MetroHealth System, Cleveland, OH, USA
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL, USA
| | - Sabine Roman
- Hospices Civils de Lyon, Hôpital E Herriot, Digestive Physiology, Université de Lyon, Inserm U1032, LabTAU, Lyon, France
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy
| | - Daniel Sifrim
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael Vaezi
- Division of Gastroenterology, Vanderbilt University, Nashville, TN, USA
| | - Rena Yadlapati
- Division of Gastroenterology, University of California San Diego School of Medicine, La Jolla, CA, USA
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
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26
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Mittal SK, Baboli KM, Bremner RM. Reflux Control After Barrett’s Esophagus Ablation. FOREGUT: THE JOURNAL OF THE AMERICAN FOREGUT SOCIETY 2021; 1:78-85. [DOI: 10.1177/2634516121997233] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Esophageal adenocarcinoma (EAC) is difficult to treat and carries a poor prognosis. Barrett’s esophagus, which develops from long-standing gastroesophageal reflux disease, is the only known precursor to EAC. Endoscopic eradication therapy is a major advancement in the treatment of dysplastic Barrett’s esophagus and early EAC; however, failure to eradicate disease and a high rate of recurrence with risk of progression currently remain unacceptably high with the use of acid suppressive medication for reflux. Herein, we describe the physiology of gastroesophageal reflux and review the current literature on endoscopic eradication therapy for Barrett’s esophagus. We summarize that antireflux surgery for reflux control as an adjunct to endoscopic eradication therapy may decrease the need for multiple endoscopic sessions (to achieve eradication), decrease the risk for recurrence/progression, and potentially decrease the need for surveillance.
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Affiliation(s)
- Sumeet K. Mittal
- Norton Thoracic Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
- Creighton University School of Medicine, Phoenix, AZ, USA
| | - Komeil Mirzaei Baboli
- Norton Thoracic Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
| | - Ross M. Bremner
- Norton Thoracic Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
- Creighton University School of Medicine, Phoenix, AZ, USA
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27
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Farina DA, Condon A, Komanduri S, Muthusamy VR. A Practical Approach to Refractory and Recurrent Barrett's Esophagus. Gastrointest Endosc Clin N Am 2021; 31:183-203. [PMID: 33213795 DOI: 10.1016/j.giec.2020.09.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Endoscopic eradication therapy (EET) is recommended for patients with Barrett's esophagus (BE)-associated neoplasia and is effective in achieving complete eradication of intestinal metaplasia (CE-IM). However, BE that is refractory to EET, defined as partial or no improvement in dysplasia after less than or equal to 3 ablative sessions, and the development of recurrence post-EET is not uncommon. Identification of refractory BE or recurrent intestinal metaplasia should prompt esophageal physiologic testing and modification of antireflux strategy, as appropriate. In patients who ultimately fail standard EET despite optimization of reflux control, salvage EET with alternate modalities may need to be considered.
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Affiliation(s)
- Domenico A Farina
- Department of Gastroenterology and Hepatology, Northwestern University, 676 North St. Clair Street, Arkes Pavilion Suite 1400, Chicago, IL 60611, USA
| | - Ashwinee Condon
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Room 330-37, Los Angeles, CA 90095, USA
| | - Srinadh Komanduri
- Department of Gastroenterology and Hepatology, Northwestern University, 676 North St. Clair Street, Arkes Pavilion Suite 1400, Chicago, IL 60611, USA
| | - V Raman Muthusamy
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Room 330-37, Los Angeles, CA 90095, USA.
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28
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Demkowicz R, Thota PN, Benjamin T, Lopez R, Lu H, Patil DT, Downs-Kelly E, Jeung JA, Lai KK, Lapinski J, Savage EC, Goldblum JR, Gordon IO. Allaying uncertainty in diagnosing buried Barrett's esophagus. Ann Diagn Pathol 2020; 51:151672. [PMID: 33418428 DOI: 10.1016/j.anndiagpath.2020.151672] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 11/17/2020] [Accepted: 11/19/2020] [Indexed: 02/06/2023]
Abstract
Subsquamous intestinal metaplasia (SSIM) in the setting of Barrett's esophagus (BE) is a technically challenging diagnosis. While the risk for progression of BE involving the surface mucosa is well documented, the potential risk for development of advanced neoplasia associated with SSIM has been controversial. This study aimed to determine the effects of specimen adequacy, presence of dysplasia, and interobserver agreement for SSIM interpretation. Adult patients (n = 28) who underwent endoscopic therapy for BE with high-grade dysplasia or intramucosal carcinoma (HGD/IMC) between October 2005 and June 2013 were included. Initial evaluation (n = 140 slides) by an experienced gastrointestinal pathologist was followed by an interobserver study by 8 pathologists. Forty-seven (34%) slides had insufficient subsquamous tissue to assess for SSIM. SSIM was found in 19% of all slides and 29% of slides with sufficient subsquamous tissue. At least one slide had SSIM in 54% to 64% of patients. Subsquamous low grade dysplasia (LGD) was found in 4 (15%) slides with SSIM and subsquamous HGD/IMC was found in 5 (19%) slides with SSIM. At the patient level, 8 (53%) had no dysplasia, 4 (27%) had LGD and 3 (20%) had HGD/IMC. Overall agreement for SSIM by slide was 92% to 94% (κ = 0.73 to κ = 0.82, moderate to strong agreement), and by patient was 82% to 94% (κ = 0.65 to κ = 0.87, moderate to strong agreement). This study confirms the need for assessing specimen adequacy and assessing the prevalence of SSIM and is the first to assess interobserver agreement for SSIM and dysplasia within SSIM.
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Affiliation(s)
- Ryan Demkowicz
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Prashanthi N Thota
- Department of Gastroenterology, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Tanmayee Benjamin
- Department of Gastroenterology, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, OH, United States of America; Marshfield Clinic, Marshfield, WI, United States of America
| | - Rocio Lopez
- Department of Quantitative Health Sciences and Center for Populations Health Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Haiyan Lu
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Deepa T Patil
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Erinn Downs-Kelly
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Jennifer A Jeung
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Keith K Lai
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - James Lapinski
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Erica C Savage
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - John R Goldblum
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America
| | - Ilyssa O Gordon
- Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America.
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29
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Abstract
Gastroesophageal reflux disease (GERD) is a multifaceted disorder encompassing a family of syndromes attributable to, or exacerbated by, gastroesophageal reflux that impart morbidity, mainly through troublesome symptoms. Major GERD phenotypes are non-erosive reflux disease, GERD hypersensitivity, low or high grade esophagitis, Barrett's esophagus, reflux chest pain, laryngopharyngeal reflux, and regurgitation dominant reflux. GERD is common throughout the world, and its epidemiology is linked to the Western lifestyle, obesity, and the demise of Helicobacter pylori. Because of its prevalence and chronicity, GERD is a substantial economic burden measured in physician visits, diagnostics, cancer surveillance protocols, and therapeutics. An individual with typical symptoms has a fivefold risk of developing esophageal adenocarcinoma, but mortality from GERD is otherwise rare. The principles of management are to provide symptomatic relief and to minimize potential health risks through some combination of lifestyle modifications, diagnostic testing, pharmaceuticals (mainly to suppress or counteract gastric acid secretion), and surgery. However, it is usually a chronic recurring condition and management needs to be personalized to each case. While escalating proton pump inhibitor therapy may be pertinent to healing high grade esophagitis, its applicability to other GERD phenotypes wherein the modulating effects of anxiety, motility, hypersensitivity, and non-esophageal factors may dominate is highly questionable.
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Affiliation(s)
- David A Katzka
- Mayo Clinic, Division of Gastroenterology and Hepatology, Rochester, MN, USA
| | - Peter J Kahrilas
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Chicago, IL USA
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30
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Wani S, Han S, Kushnir V, Early D, Mullady D, Hammad H, Brauer B, Thaker A, Simon V, Ezekwe E, Hollander T, Wood M, Rastogi A, Edmundowicz S, Muthusamy VR, Komanduri S. Recurrence Is Rare Following Complete Eradication of Intestinal Metaplasia in Patients With Barrett's Esophagus and Peaks at 18 Months. Clin Gastroenterol Hepatol 2020; 18:2609-2617.e2. [PMID: 31982610 DOI: 10.1016/j.cgh.2020.01.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 12/12/2019] [Accepted: 01/11/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There have been few studies describing the long-term durability of complete eradication of intestinal metaplasia (CE-IM) in patients with Barrett's esophagus (BE)-related neoplasia who received endoscopic eradication therapy (EET). Data are needed to guide surveillance interval protocols and identify patients at risk for recurrence. We assessed the rate of recurrence of intestinal metaplasia and dysplasia, histologic features, and outcomes after recurrence of CE-IM, and identified factors associated with recurrence. METHODS We performed a prospective study of 807 patients with BE who underwent EET, which produced CE-IM, at 4 tertiary-care referral centers, from January 2013 to October 2018. Kaplan-Meier estimates of cumulative incidence rates (IR) of recurrence were calculated for up to 5 years following CE-IM and were stratified by baseline level of histology. Density estimates of recurrence were used to determine the change in the rate of recurrence over time. We conducted logistic regression analysis to identify factors associated with recurrence. RESULTS Intestinal metaplasia recurred in 121 patients (15%; IR, 5.2/100 person-years), and dysplasia recurred in 41 patients (5.1%; IR, 1.8/100 person-years), after a median follow-up time of 2317 person-years. The rate of recurrence was not constant and the time to any recurrence converged to a normal distribution; recurrences peaked at 1.6 y after patients had CE-IM. Baseline high-grade dysplasia or intramucosal cancer (adjusted odds ratio [aOR], 4.19), presence of reflux symptoms (aOR, 12.1) or hiatal hernia (aOR, 13.8), and number of sessions required to achieve CE-IM (aOR, 1.8) were associated with recurrence. CONCLUSIONS In a prospective study of a large cohort of patients with BE undergoing EET, we found a low rate of recurrence after CE-IM. The rate of recurrence peaked at 1-2 y after CE-IM. These findings indicate that aggressive surveillance might not be necessary more than 1 y after CE-IM and should be considered in surveillance guidelines. Clinicaltrials.gov no: NCT02634645.
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Affiliation(s)
- Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
| | - Samuel Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Vladimir Kushnir
- Division of Gastroenterology and Hepatology, Washington University School of Medicine, St Louis, Missouri
| | - Dayna Early
- Division of Gastroenterology and Hepatology, Washington University School of Medicine, St Louis, Missouri
| | - Daniel Mullady
- Division of Gastroenterology and Hepatology, Washington University School of Medicine, St Louis, Missouri
| | - Hazem Hammad
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Brian Brauer
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Adarsh Thaker
- Vatche and Tamar Maoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Violette Simon
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Eze Ezekwe
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Thomas Hollander
- Division of Gastroenterology and Hepatology, Washington University School of Medicine, St Louis, Missouri
| | - Mariah Wood
- Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Amit Rastogi
- Division of Gastroenterology and Hepatology, University of Kansas School of Medicine, Kansas City, Kansas
| | - Steven Edmundowicz
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - V Raman Muthusamy
- Vatche and Tamar Maoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Srinadh Komanduri
- Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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31
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Shimamura Y, Iwaya Y, Kobayashi R, Rodriguez de Santiago E, Muwanwella N, Raftopoulos S, Mosko JD, May GR, Kandel G, Kortan P, Marcon N, Teshima CW. Clinical and pathological predictors of failure of endoscopic therapy for Barrett's related high-grade dysplasia and early esophageal adenocarcinoma. Surg Endosc 2020; 35:5468-5479. [PMID: 32989547 DOI: 10.1007/s00464-020-08037-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 09/16/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND AIMS Multimodal endoscopic treatment for Barrett's esophagus (BE) related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) is safe and effective. However, there is a paucity of data to predict the response to endoscopic treatment. This study aimed to identify predictors of failure to achieve complete eradication of neoplasia (CE-N) and complete eradication of intestinal metaplasia (CE-IM). METHODS We performed a retrospective analysis of prospectively collected data of all HGD/EAC cases treated endoscopically at a tertiary referral center. Only patients with confirmed HGD/EAC from initial endoscopic mucosal resection (EMR) were included. Potential predictive variables including clinical characteristics, endoscopic features, and index histologic parameters of the EMR specimens were evaluated using multivariate Cox regression. RESULTS A total of 457 patients were diagnosed with HGD/EAC by initial EMR from January 2008 to January 2019. Of these, 366 patients who underwent subsequent endoscopic treatment with or without RFA were included. Cumulative incidence rates at 3 years for CE-N and CE-IM were 91.4% (95% CI 87.8-94.2%) and 66.8% (95% CI 61.2-72.3%), respectively during a median follow-up period of 35 months. BE segment of 3-10 cm (HR 0.45; 95% CI 0.36-0.57) and > 10 cm (HR 0.25; 95% CI 0.15-0.40) were independent clinical predictors associated with failure to achieve CE-N. With respect to CE-IM, increasing age (HR 0.88; 95% CI 0.78-1.00) was another predictor along with BE segment of 3-10 cm (HR 0.37; 95% CI 0.28-0.49) and > 10 cm (HR 0.15; 95% CI 0.07-0.30). Lymphovascular invasion increased the risk of CE-N and CE-IM failure in EAC cases. CONCLUSION Failure to achieve CE-N and CE-IM is associated with long-segment BE and other clinical variables. Patients with these predictors should be considered for a more intensive endoscopic treatment approach at expert centers.
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Affiliation(s)
- Yuto Shimamura
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada.
| | - Yugo Iwaya
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Ryosuke Kobayashi
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Enrique Rodriguez de Santiago
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramon Y Cajal, IRYCIS, Universidad de Alcala, Madrid, Spain
| | - Niroshan Muwanwella
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
| | - Spiro Raftopoulos
- Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Jeffrey D Mosko
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Gary R May
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Gabor Kandel
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Paul Kortan
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Norman Marcon
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Christopher W Teshima
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
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Alzoubaidi D, Hussein M, Sehgal V, Makahamadze C, Magee CG, Everson M, Graham D, Sweis R, Banks M, Sami SS, Novelli M, Lovat L, Haidry R. Cryoballoon ablation for treatment of patients with refractory esophageal neoplasia after first line endoscopic eradication therapy. Endosc Int Open 2020; 8:E891-E899. [PMID: 32665972 PMCID: PMC7340530 DOI: 10.1055/a-1149-1414] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 02/12/2020] [Indexed: 12/18/2022] Open
Abstract
Background and study aims Cryoablation with the Cryoballoon device is a novel ablative therapy that uses cycles of freezing and thawing to induce cell death. This single-center prospective study evaluated the feasibility of the focal cryoablation device for the treatment of areas of refractory esophageal neoplasia in patients who had undergone first line endoscopic eradication therapy (EET). Complete remission of dysplasia (CR-D) and complete remission of intestinal metaplasia (CR-IM) at first follow-up endoscopy, durability of disease reversal, rates of stenosis and adverse events were studied. Patients and methods Eighteen cases were treated. At baseline, nine patients had low-grade dysplasia (LGD), six had high-grade dysplasia (HGD) and three had intramucosal carcinoma (IMC). Median length of dysplastic Barrett's esophagus (BE) treated was 3 cm. The median number of ablations per patient was 11. Each selected area of visible dysplasia received 10 seconds of ablation. One session of cryoablation was performed per patient. Biopsies were performed at around 3 months post-ablation. Results CR-D was achieved in 78 % and CR-IM in 39 % of patients. There were no device malfunction or adverse events. Stenosis was noted in 11 % of cases. At a median follow up of 19-months, CR-D was maintained in 72 % of patients and CR-IM in 33 %. Conclusions Cryoablation appears to be a viable rescue strategy in patients with refractory neoplasia. It is well tolerated and successful in obtaining CR-D and CR-IM in patients with treatment-refractory BE. Further trials of dosimetry, efficacy and safety in treatment-naïve patients are underway.
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Affiliation(s)
- Durayd Alzoubaidi
- Division of Surgery and interventional science, University College London (UCL), London, UK
| | - Mohamed Hussein
- Division of Surgery and interventional science, University College London (UCL), London, UK
| | - Vinay Sehgal
- Department of Gastroenterology, University College London Hospital (UCLH), London, UK
| | | | - Cormac G. Magee
- Department of Gastroenterology, University College London Hospital (UCLH), London, UK
| | - Martin Everson
- Department of Gastroenterology, University College London Hospital (UCLH), London, UK
| | - David Graham
- Department of Gastroenterology, University College London Hospital (UCLH), London, UK
| | - Rami Sweis
- Department of Gastroenterology, University College London Hospital (UCLH), London, UK
| | - Matthew Banks
- Department of Gastroenterology, University College London Hospital (UCLH), London, UK
| | - Sarmed S. Sami
- Division of Surgery and interventional science, University College London (UCL), London, UK
| | - Marco Novelli
- Department of Histopathology, University College London Hospital (UCLH), London, UK
| | - Laurence Lovat
- Division of Surgery and interventional science, University College London (UCL), London, UK
| | - Rehan Haidry
- Division of Surgery and interventional science, University College London (UCL), London, UK
- Department of Gastroenterology, University College London Hospital (UCLH), London, UK
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Abstract
Because of the rising incidence and lethality of esophageal adenocarcinoma, Barrett's esophagus (BE) is an increasingly important premalignant target for cancer prevention. BE-associated neoplasia can be safely and effectively treated with endoscopic eradication therapy (EET), incorporating tissue resection and ablation. Because EET has proliferated, managing patients after complete eradication of intestinal metaplasia has taken on increasing importance. Recurrence after complete eradication of intestinal metaplasia occurs in 8%-10% of the patients yearly, and the incidence may remain constant over time. Most recurrences occur at the gastroesophageal junction, whereas those in the tubular esophagus are endoscopically visible and distally located. A simplified biopsy protocol limited to the distal aspect of the BE segment, in addition to gastroesophageal junction sampling, may enhance efficiency and cost without significantly reducing recurrence detection. Similarly, research suggests that current surveillance intervals may be excessively frequent, failing to reflect the cancer risk reduction of EET. If validated, longer surveillance intervals could reduce the burden of resource-intensive endoscopic surveillance. Several important questions in post-EET management remain unanswered, including surveillance duration, the significance of gastric cardia intestinal metaplasia, and the role of advanced imaging and nonendoscopic sampling techniques in detecting recurrence. These merit further research to enhance quality of care and promote a more evidence-based approach.
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Rouphael C, Anil Kumar M, Sanaka MR, Thota PN. Indications, contraindications and limitations of endoscopic therapy for Barrett's esophagus and early esophageal adenocarcinoma. Therap Adv Gastroenterol 2020; 13:1756284820924209. [PMID: 32523628 PMCID: PMC7257851 DOI: 10.1177/1756284820924209] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 04/15/2020] [Indexed: 02/04/2023] Open
Abstract
Endoscopic eradication therapy (EET) has revolutionized management of Barrett's esophagus (BE)-associated neoplasia, traditionally treated by esophagectomy, which carries very high mortality and morbidity. EET, usually performed in the outpatient setting, has a safe risk profile. It is indicated in patients with BE with high-grade dysplasia and intramucosal cancer, confirmed, and persistent low-grade dysplasia, and in highly selected cases of non-dysplastic BE and submucosal cancers. Multiple EET modalities are available and can be categorized into two groups: ablation therapies and resection techniques with resection techniques usually reserved for nodular/raised lesions or lesions with suspected neoplasia. Patients usually require multiple ablation sessions with a goal of achieving complete eradication of metaplasia. Despite very good results, EET has its limitations and is not 100% effective: it targets a small subset of patients along the spectrum of BE and esophageal adenocarcinoma, as most patients with esophageal adenocarcinoma remain asymptomatic until the disease has progressed to advanced stages. Post-ablation surveillance is mandatory, as recurrences are common. An area of concern is buried metaplasia reported to occur following ablation therapy and thought to be from de novo growth of metaplastic tissue underneath the neosquamous epithelium, following ablation. The focus of this review article is to present the indications, contraindications and limitations of EET.
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Affiliation(s)
- Carol Rouphael
- Department of Gastroenterology and Hepatology,
Cleveland Clinic, Cleveland, OH, USA
| | - Mythri Anil Kumar
- Department of Gastroenterology and Hepatology,
Cleveland Clinic, Cleveland, OH, USA
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Raphael KL, Trindade AJ. Management of Barrett’s esophagus with dysplasia refractory to radiofrequency ablation. World J Gastroenterol 2020; 26:2030-2039. [PMID: 32536772 PMCID: PMC7267696 DOI: 10.3748/wjg.v26.i17.2030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 04/08/2020] [Accepted: 04/24/2020] [Indexed: 02/06/2023] Open
Abstract
Radiofrequency ablation (RFA) is very effective for eradication of flat Barrett’s mucosa in dysplastic Barrett’s esophagus after endoscopic resection of raised lesions. However, in a minority of the time, RFA may be ineffective at eradication of the Barrett’s mucosa. Achieving complete eradication of intestinal metaplasia can be challenging in these patients. This review article focuses on the management of patients with dysplastic Barrett’s esophagus refractory to RFA therapy. Management strategies discussed in this review include optimizing the RFA procedure, optimizing acid suppression (with medical, endoscopic, and surgical management), cryotherapy, hybrid argon plasma coagulation, and EndoRotor resection.
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Affiliation(s)
- Kara L Raphael
- Division of Gastroenterology, Long Island Jewish Medical Center, Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, New Hyde Park, NY 11040, United States
| | - Arvind J Trindade
- Division of Gastroenterology, Long Island Jewish Medical Center, Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, New Hyde Park, NY 11040, United States
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Putra J, Arva NC, Tan SY, Melin-Aldana H, Bass LM, Mitchell PD, Fox VL, Goldsmith JD. Barrett Esophagus and Intestinal Metaplasia of the Gastroesophageal Junction in Children: A Clinicopathologic Study. J Pediatr Gastroenterol Nutr 2020; 70:562-567. [PMID: 31977949 DOI: 10.1097/mpg.0000000000002640] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Barrett esophagus (BE) and intestinal metaplasia of gastroesophageal junction (IMGEJ) are rare in the pediatric population. This multi-institutional retrospective study evaluated the clinicopathologic characteristics and natural history of BE and IMGEJ in children. METHODS Data from 20 BE patients (70% boys, mean age: 14.9 years) and 17 IMGEJ patients (71% boys, mean age: 14 years) were retrospectively obtained from chart review. Endoscopic and pathologic findings from index and follow-up endoscopies were analyzed. RESULTS Most patients (70% BE and 59% IMGEJ) had underlying conditions which put them at risk for gastroesophageal reflux disease. Increased body mass index (BMI) was observed in patients without underlying conditions (BE: 30.1 ± 9.8; IMGEJ: 23.9 ± 6.3) compared with those with underlying conditions (BE: 19.6 ± 7.8; IMGEJ: 16.4 ± 2.1) (BE, P = 0.02; IMGEJ, P = 0.01). Incomplete intestinal metaplasia (IM) was the predominant histology seen in BE (80%) and IMGEJ patients (75%). Dysplasia and malignancy were not identified in the initial and follow-up biopsies. Concurrent gastric biopsies showed various findings (79% BE and 40% IMGEJ were normal), with 1 IMGEJ patient showing coexisting gastric IM (7%). Follow-up in 12 BE patients (mean follow-up time 51.6 months) showed 100% persistent endoscopic disease and 58% persistent IM histologically. Three of 6 IMGEJ patients (mean follow-up time 24 months) demonstrated endoscopic and histologic features consistent with BE on subsequent procedures. Moreover, a subset of BE (57%) and IMGEJ patients (67%) who underwent endoscopy before initial diagnosis showed nongoblet columnar mucosa above the anatomic gastroesophageal junction. CONCLUSIONS Increased BMI may be a risk factor for BE and IMGEJ in pediatric patients without underlying conditions. Nongoblet columnar metaplasia and IMGEJ might represent incomplete forms of BE. Our data suggest that these patients should be closely monitored.
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Affiliation(s)
- Juan Putra
- Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
| | | | | | | | - Lee M Bass
- Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Paul D Mitchell
- Institutional Centers for Clinical and Translational Research
| | - Victor L Fox
- Division of Gastroenterology, Hepatology, and Nutrition
| | - Jeffrey D Goldsmith
- Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, MA
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Sharma P, Shaheen NJ, Katzka D, Bergman JJGHM. AGA Clinical Practice Update on Endoscopic Treatment of Barrett's Esophagus With Dysplasia and/or Early Cancer: Expert Review. Gastroenterology 2020; 158:760-769. [PMID: 31730766 DOI: 10.1053/j.gastro.2019.09.051] [Citation(s) in RCA: 132] [Impact Index Per Article: 26.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 09/12/2019] [Accepted: 09/16/2019] [Indexed: 12/15/2022]
Abstract
DESCRIPTION The purpose of this best practice advice article is to describe the role of Barrett's endoscopic therapy (BET) in patients with Barrett's esophagus (BE) with dysplasia and/or early cancer and appropriate follow-up of these patients. METHODS The best practice advice provided in this document is based on evidence and relevant publications reviewed by the committee. BEST PRACTICE ADVICE 1: In BE patients with confirmed low-grade dysplasia, a repeat examination with high-definition white-light endoscopy should be performed within 3-6 months to rule out the presence of a visible lesion, which should prompt endoscopic resection. BEST PRACTICE ADVICE 2: Both BET and continued surveillance are reasonable options for the management of BE patients with confirmed and persistent low-grade dysplasia. BEST PRACTICE ADVICE 3: BET is the preferred treatment for BE patients with high-grade dysplasia (HGD). BEST PRACTICE ADVICE 4: BET should be preferred over esophagectomy for BE patients with intramucosal esophageal adenocarcinoma (T1a). BEST PRACTICE ADVICE 5: BET is a reasonable alternative to esophagectomy in patients with submucosal esophageal adenocarcinoma (T1b) with low-risk features (<500-μm invasion in the submucosa [sm1], good to moderate differentiation, and no lymphatic invasion) especially in those who are poor surgical candidates. BEST PRACTICE ADVICE 6: In all patients undergoing BET, mucosal ablation should be applied to 1) all visible esophageal columnar mucosa; 2) 5-10 mm proximal to the squamocolumnar junction and 3) 5-10 mm distal to the gastroesophageal junction, as demarcated by the top of the gastric folds (ie, gastric cardia) using focal ablation in a circumferential fashion. BEST PRACTICE ADVICE 7: Mucosal ablation therapy should only be performed in the presence of flat BE without signs of inflammation and in the absence of visible abnormalities. BEST PRACTICE ADVICE 8: BET should be performed by experts in high-volume centers that perform a minimum of 10 new cases annually. BEST PRACTICE ADVICE 9: BET should be continued until there is an absence of columnar epithelium in the tubular esophagus on high-definition white-light endoscopy and preferably optical chromoendoscopy. In case of complete endoscopic eradication, the neosquamous mucosa and the gastric cardia are sampled by 4-quadrant biopsies. BEST PRACTICE ADVICE 10: If random biopsies obtained from the neosquamous epithelium demonstrate intestinal metaplasia/dysplasia or subsquamous intestinal metaplasia, a repeat endoscopy should be performed and visible islands or tongues should undergo targeted focal ablation. BEST PRACTICE ADVICE 11: Intestinal metaplasia of the gastric cardia (without residual columnar epithelium in the tubular esophagus) should not warrant additional ablation therapy. BEST PRACTICE ADVICE 12: When consenting patients for BET, the most common complication of therapy to be quoted is post-procedural stricture formation, occurring in about 6% of cases. Bleeding and perforation occur at rates <1%. BEST PRACTICE ADVICE 13: After complete eradication (endoscopic and histologic) of intestinal metaplasia has been achieved with BET, surveillance endoscopy with biopsies should be performed at the following intervals: for baseline diagnosis of HGD/esophageal adenocarcinoma: at 3, 6, and 12 months and annually thereafter; and baseline diagnosis of low-grade dysplasia: at 1 and 3 years. BEST PRACTICE ADVICE 14: Endoscopic surveillance post therapy should be performed with high-definition white-light endoscopy, including careful inspection of the neosquamous mucosal and retroflexed inspection of the gastric cardia. BEST PRACTICE ADVICE 15: The approach to recurrent disease is similar to that of the initial therapy; visible recurrent nodular lesions require endoscopic resection, whereas flat areas of columnar mucosa in the tubular esophagus can be treated with mucosal ablation. BEST PRACTICE ADVICE 16: Patients should be counseled on cancer risk in the absence of BET, as well as after BET, to allow for informed decision-making between the patient and the physician.
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Affiliation(s)
- Prateek Sharma
- University of Kansas School of Medicine Center, Kansas City, Kansas; Veterans Affairs Medical Center, Kansas City, Kansas.
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Endoscopic GERD therapy: a primer for the transoral incisionless fundoplication procedure. Gastrointest Endosc 2019; 90:370-383. [PMID: 31108091 DOI: 10.1016/j.gie.2019.05.028] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 05/11/2019] [Indexed: 02/06/2023]
Abstract
Patients with medically refractory GERD have the option of surgery but may opt for effective minimally invasive interventions, when available. However, the primary GERD pharmacologic therapy, proton pump inhibitors, does not satisfactorily address the pathophysiology of the disease. Moreover, a therapeutic gap exists in those severely symptomatic patients who fail medical management and who are poor candidates for surgical fundoplication. Recently, a revival of minimally invasive endoscopic interventions aiming to correct the antireflux barrier has followed existing device modifications, enhancing their safety and efficacy profile. Of these technologies, the trans-oral incisionless fundoplication (TIF) technique, in its current 2.0 iteration, has been studied in several randomized controlled trials with favorable outcomes and a low rate of adverse events. In this review, we discuss the landscape of endoscopic GERD therapy, focusing on recent updates in the TIF 2.0 procedure with the EsophyX-Z device (EndoGastricSolutions, Redmond, Wash, USA). We discuss the evolution, differences, and improvements in this technique across different generations of the EsophyX device. We also present a framework for candidate selection, based on medical and anatomic considerations. When streamlined within a milieu of comprehensive multidisciplinary programs, these improved endoscopic interventions can provide viable avenues for a carefully selected patients population, bridging therapy gaps, and selectively targeting the primary pathophysiology of the disease.
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Soroush A, Poneros JM, Lightdale CJ, Abrams JA. Shorter time to achieve endoscopic eradication is not associated with improved long-term outcomes in Barrett's esophagus. Dis Esophagus 2019; 32:5475051. [PMID: 30997483 DOI: 10.1093/dote/doz026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Quality indicators have been proposed for endoscopic eradication therapy of Barrett's esophagus (BE). One such measure suggests that complete eradication of intestinal metaplasia (CE-IM) should be achieved within 18 months of starting treatment. The aim of this study was to assess whether achievement of CE-IM within 18 months is associated with improved long-term clinical outcomes. This was a retrospective cohort study of BE patients who underwent endoscopic eradication. Time to CE-IM was recorded and categorized as ≤ or > 18 months. The main outcome measures were recurrence of IM and of dysplasia after CE-IM, defined as a single endoscopy without endoscopic evidence of BE or histologic evidence of intestinal metaplasia. Recurrence was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards modeling. A total of 290 patients were included in the analyses. The baseline histology was high-grade dysplasia or intramucosal carcinoma in 74.2% of patients. CE-IM was achieved in 85.5% of patients, and 54.1% of the cohort achieved CE-IM within 18 months. Achieving CE-IM within 18 months was not associated with reduced risk of recurrence of IM or dysplasia in both unadjusted and adjusted analyses. In this cohort, older age and increased BE length were associated with IM recurrence, and increased hiatal hernia size was associated with dysplasia recurrence. Compared to longer times, achieving CE-IM within 18 months was not associated with a reduced risk of recurrence of IM or dysplasia. Alternative evidence-based quality metrics for endoscopic eradication therapy should be identified.
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Affiliation(s)
- Ali Soroush
- Department of Medicine, Columbia University Medical Center, New York, USA
| | - John M Poneros
- Department of Medicine, Columbia University Medical Center, New York, USA
| | | | - Julian A Abrams
- Department of Medicine, Columbia University Medical Center, New York, USA
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Sami SS, Ravindran A, Kahn A, Snyder D, Santiago J, Ortiz-Fernandez-Sordo J, Tan WK, Dierkhising RA, Crook JE, Heckman MG, Johnson ML, Lansing R, Ragunath K, di Pietro M, Wolfsen H, Ramirez F, Fleischer D, Wang KK, Leggett CL, Katzka DA, Iyer PG. Timeline and location of recurrence following successful ablation in Barrett's oesophagus: an international multicentre study. Gut 2019; 68:1379-1385. [PMID: 30635408 DOI: 10.1136/gutjnl-2018-317513] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 11/19/2018] [Accepted: 12/17/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett's oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines. DESIGN Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies. RESULTS 594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4-4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI -7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia). CONCLUSIONS BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.
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Affiliation(s)
- Sarmed S Sami
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Adharsh Ravindran
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Allon Kahn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Diana Snyder
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Jose Santiago
- National Institute for Health Research (NIHR) Biomedical Research Centre in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust, The University of Nottingham, Queen's Medical Centre Campus, Nottingham, UK
| | - Jacobo Ortiz-Fernandez-Sordo
- National Institute for Health Research (NIHR) Biomedical Research Centre in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust, The University of Nottingham, Queen's Medical Centre Campus, Nottingham, UK
| | - Wei Keith Tan
- Hutchison/MRC Research Centre, Cambridge University Hospitals NHS Trust and MRC Cancer Unit, University of Cambridge, Cambridge, UK
| | - Ross A Dierkhising
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | - Julia E Crook
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida, USA
| | - Michael G Heckman
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida, USA
| | - Michele L Johnson
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ramona Lansing
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Krish Ragunath
- National Institute for Health Research (NIHR) Biomedical Research Centre in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust, The University of Nottingham, Queen's Medical Centre Campus, Nottingham, UK
| | - Massimiliano di Pietro
- Hutchison/MRC Research Centre, Cambridge University Hospitals NHS Trust and MRC Cancer Unit, University of Cambridge, Cambridge, UK
| | - Herbert Wolfsen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Francisco Ramirez
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - David Fleischer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Kenneth K Wang
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Cadman L Leggett
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - David A Katzka
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Prasad G Iyer
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Reed CC, Shaheen NJ. Durability of Endoscopic Treatment for Dysplastic Barrett’s Esophagus. ACTA ACUST UNITED AC 2019; 17:171-186. [DOI: 10.1007/s11938-019-00226-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Shaheen NJ. Where is the finish line for endoscopic eradication therapy in Barrett's esophagus? Gastrointest Endosc 2019; 89:926-928. [PMID: 31005132 DOI: 10.1016/j.gie.2019.01.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 01/15/2019] [Indexed: 02/08/2023]
Affiliation(s)
- Nicholas J Shaheen
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
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Persistent intestinal metaplasia after endoscopic eradication therapy of neoplastic Barrett's esophagus increases the risk of dysplasia recurrence: meta-analysis. Gastrointest Endosc 2019; 89:913-925.e6. [PMID: 30529044 DOI: 10.1016/j.gie.2018.11.035] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Accepted: 11/28/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Endoscopic eradication therapy (EET) is the main treatment for dysplastic Barrett's esophagus and intramucosal adenocarcinoma. Although the goal of EET is to achieve complete remission of intestinal metaplasia (CRIM), treatment might achieve complete remission of dysplasia (CR-D) only, without achieving CRIM. Persistent intestinal metaplasia after eradication of dysplasia might carry a higher risk for progression into advanced neoplasia. METHODS We performed a systematic review and meta-analysis after searching multiple databases to identify studies that evaluated dysplasia recurrence risk after successful eradication of neoplasia with EET. We calculated the pooled cumulative incidence of dysplasia and advanced neoplasia recurrence after CRIM and CR-D only and then compared the two using risk ratios. RESULTS Forty studies were included (4410 patients with total follow-up of 12,976 patient-years). A total of 4061 achieved CRIM and 349 achieved CR-D only. The cumulative incidence of CR-D only was 14% (95% confidence interval [CI], 10%-19%). The pooled cumulative incidence of any dysplasia recurrence after achieving CRIM was 5% (95% CI, 3%-7%) and 12% (95% CI, 4%-23%) after achieving CR-D only. Comparing dysplasia detection after achieving CR-D only with CRIM, there was a significantly higher risk for detection after CR-D (risk ratio [RR], 2.8; 95% CI, 1.7-4.6). The pooled cumulative incidence rate of high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) recurrence was 3% (95% CI, 2%-4%) after achieving CRIM and 6% (95% CI, 0%-16%) after achieving CR-D only. Comparing HGD/EAC recurrence after achieving CR-D only with CRIM, there was a significantly higher risk for recurrence after CR-D (RR, 3.6; 95% CI, 1.45-9). When excluding patients who underwent ablation for non-dysplastic Barrett's esophagus only, these differences persisted with dysplasia recurrence after achieving CR-D only compared with CRIM showing a significantly higher risk for recurrence after CR-D (RR, 2.9; 95% CI, 1.66-5). CONCLUSIONS CRIM was associated with a lower risk of dysplasia and advanced neoplasia recurrence compared with CR-D only. Achieving CRIM should remain the goal of EET in dysplastic Barrett's esophagus.
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Siddiki HA, Lam-Himlin DM, Kahn A, Bandres MV, Burdick GE, Crowell MD, Pannala R, Ramirez FC, Vela MF, Fleischer DE. Intestinal metaplasia of the gastric cardia: findings in patients with versus without Barrett's esophagus. Gastrointest Endosc 2019; 89:759-768. [PMID: 30447215 DOI: 10.1016/j.gie.2018.10.048] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 10/31/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS There is controversy about finding intestinal metaplasia (IM) of the gastric cardia on biopsy. The most recent American College of Gastroenterology guideline comments that IM cardia is not more common in patients with Barrett's esophagus (BE). It provides limited guidance on whether the cardia should be treated when patients with BE undergo endoscopic eradication therapy (EET) and whether the cardia should undergo biopsy after ablation. The aims of our study were to determine the frequency in the proximal stomach of (1) histologic gastric cardia mucosa and (2) IM cardia. A third aim was to explore the frequency of advanced pathology (dysplasia and adenocarcinoma) in the cardia after patients with BE have undergone EET. METHODS Consecutive patients undergoing esophagogastroduodenoscopy between January 2008 and December 2014 who had proximal stomach biopsies were included. Patients who had histologically confirmed BE were compared with those without BE. RESULTS Four hundred sixty-two patients, 289 with BE and 173 without BE, were included. Histologically confirmed cardiac mucosa was found in 81.6% of all patients. This was more frequent in those with versus without BE (86% vs 75%; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.28-3.32; P = .003). IM cardia was more common in the BE group (17% vs 7%; OR, 2.67; 95% CI, 1.38-5.19; P = .004). Advanced pathology was more likely in the patients with BE who had undergone EET. CONCLUSIONS Cardiac mucosa is present in most patients who undergo endoscopy for upper GI symptoms. IM cardia is more common in patients with BE than those without. Advanced histologic changes in the cardia were seen only in the subgroup of patients with BE who had undergone EET.
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Affiliation(s)
- Hassan A Siddiki
- Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Dora M Lam-Himlin
- Department of Pathology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Allon Kahn
- Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - M Veronica Bandres
- Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA
| | - George E Burdick
- Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Michael D Crowell
- Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Rahul Pannala
- Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | | | - Marcelo F Vela
- Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - David E Fleischer
- Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
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Cholapranee A, Trindade AJ. Challenges in Endoscopic Therapy of Dysplastic Barrett's Esophagus. ACTA ACUST UNITED AC 2019; 17:32-47. [PMID: 30663018 DOI: 10.1007/s11938-019-00215-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE OF REVIEW Barrett's esophagus (BE) is the only known measurable factor associated with esophageal adenocarcinoma. The development of endoscopic eradication therapy (EET) has transformed the way BE is managed. Given the fairly recent development of EET, its role in BE is still evolving. RECENT FINDINGS This paper discusses the challenges that endoscopists face at the preprocedural, intraprocedural, and postprocedural stages of BE management. These include challenges in risk stratification, dysplasia detection, ablation methods and dosimetry, choice of resection technique, and management of refractory disease. Despite the advances in EET in BE, there remain challenges that this review focuses on. Future research into these challenges will optimize ablation techniques and strategies in the future.
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Affiliation(s)
- Aurada Cholapranee
- Division of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Long Island Jewish Medical Center, 270-05 76th Avenue, New Hyde Park, NY, 11040, USA
| | - Arvind J Trindade
- Division of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, Long Island Jewish Medical Center, 270-05 76th Avenue, New Hyde Park, NY, 11040, USA.
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Feczko AF, Louie BE. Endoscopic Resection in the Esophagus. Thorac Surg Clin 2018; 28:481-497. [PMID: 30268294 DOI: 10.1016/j.thorsurg.2018.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The article is a review of the principles behind endoscopic resection of esophageal dysplasia and early cancers. The techniques of endoscopic mucosal resection and endoscopic submucosal dissection are reviewed, and the supporting literature compared. Endoscopic resection is compared with esophagectomy for the management of these lesions and current areas of controversy with regard to T1b lesions and gastroesophageal reflux following resection are addressed.
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Affiliation(s)
- Andrew F Feczko
- Division of Thoracic Surgery, Swedish Cancer Institute, 1101 Madison Avenue, Seattle, WA 98104, USA
| | - Brian E Louie
- Division of Thoracic Surgery, Swedish Cancer Institute, 1101 Madison Avenue, Seattle, WA 98104, USA.
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Singh T, Sanaka MR, Thota PN. Endoscopic therapy for Barrett’s esophagus and early esophageal cancer: Where do we go from here? World J Gastrointest Endosc 2018; 10:165-174. [PMID: 30283599 PMCID: PMC6162248 DOI: 10.4253/wjge.v10.i9.165] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 06/13/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
Since Barrett’s esophagus is a precancerous condition, efforts have been made for its eradication by various ablative techniques. Initially, laser ablation was attempted in non-dysplastic Barrett’s esophagus and subsequently, endoscopic ablation using photodynamic therapy was used in Barrett’s patients with high-grade dysplasia who were poor surgical candidates. Since then, various ablative therapies have been developed with radiofrequency ablation having the best quality of evidence. Resection of dysplastic areas only without complete removal of entire Barrett’s segment is associated with high risk of developing metachronous neoplasia. Hence, the current standard of management for Barrett’s esophagus includes endoscopic mucosal resection of visible abnormalities followed by ablation to eradicate remaining Barrett’s epithelium. Although endoscopic therapy cannot address regional lymph node metastases, such nodal involvement is present in only 1% to 2% of patients with intramucosal adenocarcinoma in Barrett esophagus and therefore is useful in intramucosal cancers. Post ablation surveillance is recommended as recurrence of intestinal metaplasia and dysplasia have been reported. This review includes a discussion of the technique, efficacy and complication rate of currently available ablation techniques such as radiofrequency ablation, cryotherapy, argon plasma coagulation and photodynamic therapy as well as endoscopic mucosal resection. A brief discussion of the emerging technique, endoscopic submucosal dissection is also included.
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Affiliation(s)
- Tavankit Singh
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Madhusudhan R Sanaka
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Prashanthi N Thota
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
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Han S, Yadlapati R, Simon V, Ezekwe E, Early DS, Kushnir V, Hollander T, Brauer BC, Hammad H, Edmundowicz SA, Wood M, Shaheen NJ, Muthusamy RV, Komanduri S, Wani S. Dysplasia severity is associated with poor quality of life in patients with Barrett's esophagus referred for endoscopic eradication therapy. Dis Esophagus 2018; 32:5085984. [PMID: 30169612 PMCID: PMC6303730 DOI: 10.1093/dote/doy086] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Limited data exist regarding patient-reported outcomes and quality of life (QOL) experienced by patients with Barrett's esophagus (BE) referred for endoscopic eradication therapy (EET). Specifically, the impact of grade of dysplasia has not been explored. The purpose of this study is to measure patient-reported symptoms and QOL and identify factors associated with poor QOL in BE patients referred for EET. This was a prospective multicenter study conducted from January 2015 to October 2017, which included patients with BE referred for EET. Participants completed a set of validated questionnaires to measure QOL, symptom severity, and psychosocial factors. The primary outcome was poor QOL defined by a PROMIS score >12. Multivariable logistic regression analysis was performed to identify factors associated with poor QOL. In total, 193 patients participated (mean age 64.6 years, BE length 5.5 cm, 82% males, 92% Caucasians) with poor QOL reported in 104 (53.9%) participants. On univariate analysis, patients with poor QOL had lower use of twice daily proton pump inhibitor use (61.5% vs. 86.5%, P = 0.03), shorter disease duration (4.9 vs. 5.9 years, P = 0.04) and progressive increase in grade of dysplasia (high-grade dysplasia: 68.8% vs. 31.3%, esophageal adenocarcinoma: 75.5% vs. 24.5%, P < 0.001). Multivariate analysis demonstrated that high-grade dysplasia was independently associated with poor QOL (OR: 5.57, 95% CI: 1.05, 29.5, P = 0.04). In summary, poor QOL is experienced by the majority of patients with BE referred for EET and the degree of dysplasia was independently associated with poor QOL, which emphasizes the need to incorporate patient-centered outcomes when studying treatment of BE-related dysplasia.
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Affiliation(s)
- S Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado
| | - R Yadlapati
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado
| | - V Simon
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado
| | - E Ezekwe
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado
| | - D S Early
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, Missouri
| | - V Kushnir
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, Missouri
| | - T Hollander
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, Missouri
| | - B C Brauer
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado
| | - H Hammad
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado
| | - S A Edmundowicz
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado
| | - M Wood
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois
| | - N J Shaheen
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina
| | - R V Muthusamy
- Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California, USA
| | - S Komanduri
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois
| | - S Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado,Address correspondence to: Sachin Wani, Associate Professor of Medicine, Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, 1635 Aurora Court, Rm 2.031, Aurora, CO 80045, USA.
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Abstract
The management of Barrett's esophagus and early esophageal adenocarcinoma has shifted away from esophagectomy and toward endoscopic techniques, including endoscopic resection and ablative therapies. The most commonly used ablative therapies are radiofrequency ablation and cryotherapy. Radiofrequency ablation has risen to the top of the management algorithm due to its favorable safety profile and established track record of efficacy in patients with dysplastic Barrett's. Cryotherapy offers early promise as an alternatively safe and effective ablative modality. We review radiofrequency ablation and cryotherapy techniques, and updated data regarding their efficacy and safety as well as their roles in the management of Barrett's esophagus.
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Abstract
Endoscopic ablative therapy including radiofrequency ablation (RFA) represents the preferred management strategy for dysplastic Barrett's esophagus (BE) and appears to diminish the risk of developing esophageal adenocarcinoma (EAC). Limited data describe the natural history of the post-ablation esophagus. Recent findings demonstrate that recurrent intestinal metaplasia (IM) following RFA is relatively frequent. However, dysplastic BE and EAC subsequent to the complete eradication of intestinal metaplasia (CEIM) are uncommon. Moreover, data suggest that the risk of recurrent disease is probably highest in the first year following CEIM. Recurrent IM and dysplasia are usually successfully eradicated with repeat RFA. Future studies may refine surveillance intervals and inform the length of time surveillance should be conducted following RFA with CEIM. Further data will also be necessary to understand the utility of chemopreventive strategies, including NSAIDs, in reducing the risk of recurrent disease.
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Affiliation(s)
- Craig C Reed
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, 101 Manning Drive, Chapel Hill, NC, 27514, USA
| | - Nicholas J Shaheen
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
- University of North Carolina School of Medicine, CB#7080, Chapel Hill, NC, 27599-7080, USA.
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