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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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Authors, Collaborators. S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1786-1852. [PMID: 39389106 DOI: 10.1055/a-2344-6282] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
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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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Ebert MP, Fischbach W, Hollerbach S, Höppner J, Lorenz D, Stahl M, Stuschke M, Pech O, Vanhoefer U, Porschen R. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:535-642. [PMID: 38599580 DOI: 10.1055/a-2239-9802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Affiliation(s)
- Matthias P Ebert
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universitätsmedizin, Universität Heidelberg, Mannheim
- DKFZ-Hector Krebsinstitut an der Universitätsmedizin Mannheim, Mannheim
- Molecular Medicine Partnership Unit, EMBL, Heidelberg
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von Magen, Darm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro-Liga) e. V., Giessen
| | | | - Jens Höppner
- Klinik für Allgemeine Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
| | - Dietmar Lorenz
- Chirurgische Klinik I, Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Darmstadt, Darmstadt
| | - Michael Stahl
- Klinik für Internistische Onkologie und onkologische Palliativmedizin, Evang. Huyssensstiftung, Evang. Kliniken Essen-Mitte, Essen
| | - Martin Stuschke
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen
| | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle Endoskopie, Krankenhaus Barmherzige Brüder, Regensburg
| | - Udo Vanhoefer
- Klinik für Hämatologie und Onkologie, Katholisches Marienkrankenhaus, Hamburg
| | - Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus Osterholz, Osterholz-Scharmbeck
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Porschen R, Fischbach W, Gockel I, Hollerbach S, Hölscher A, Jansen PL, Miehlke S, Pech O, Stahl M, Vanhoefer U, Ebert MPA. Updated German guideline on diagnosis and treatment of squamous cell carcinoma and adenocarcinoma of the esophagus. United European Gastroenterol J 2024; 12:399-411. [PMID: 38284661 PMCID: PMC11017771 DOI: 10.1002/ueg2.12523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 11/21/2023] [Indexed: 01/30/2024] Open
Abstract
Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline "Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.
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Affiliation(s)
- Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus OsterholzOsterholz‐ScharmbeckGermany
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von MagenDarm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro‐Liga) e. V.GiessenGermany
| | - Ines Gockel
- Klinik für Viszeral‐, Transplantations‐, Thorax‐ und GefäßchirurgieLeipzigGermany
| | | | - Arnulf Hölscher
- Contilia Zentrum für SpeiseröhrenerkrankungenElisabeth Krankenhaus EssenEssenGermany
| | - Petra Lynen Jansen
- Deutsche Gesellschaft für GastroenterologieVerdauungs‐ und StoffwechselkrankheitenBerlinGermany
| | | | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle EndoskopieKrankenhaus Barmherzige BrüderRegensburgGermany
| | - Michael Stahl
- Klinik für Internistische Onkologie & Onkologische PalliativmedizinEvang. Kliniken Essen‐MitteEssenGermany
| | - Udo Vanhoefer
- Klinik für Hämatologie und OnkologieKath. MarienkrankenhausHamburgGermany
| | - Matthias P. A. Ebert
- Medizinische Fakultät MannheimII. Medizinische KlinikUniversitätsmedizinUniversität HeidelbergMannheimGermany
- DKFZ‐Hector Krebsinstitut an der Universitätsmedizin MannheimMannheimGermany
- Molecular Medicine Partnership UnitEMBLHeidelbergGermany
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Nguyen CL, Tovmassian D, Zhou M, Seyfi D, Gooley S, Falk GL. Durability of radiofrequency ablation for long-segment and ultralong-segment Barrett's esophagus over 10 years. Surg Endosc 2024; 38:1239-1248. [PMID: 38092973 DOI: 10.1007/s00464-023-10608-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 11/17/2023] [Indexed: 02/23/2024]
Abstract
BACKGROUND Long-term durability data for radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in long-segment (LSBE) and ultralong-segment Barrett's esophagus (ULSBE) is lacking. This study aimed to determine 10-year cancer progression, eradication, and complication rates in LSBE and ULSBE patients treated with RFA. METHODS Single-surgeon prospective database of patients with LSBE (≥ 3 to < 8 cm) and ULSBE (≥ 8 cm) who underwent RFA (2001-2021) were retrospectively analyzed. Ten-year cancer progression calculated with Kaplan-Meier analysis. Eradication rates, including complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM), and rates of recurrence and complications, compared between LSBE and ULSBE groups. RESULTS Ten years after starting treatment, the cancer rate was 14.3% in 56 patients. CR-D and CR-IM rates were 87.5% and 67.9%, respectively. Relapse rates from CR-D were 1.8% and 3.6% from CR-IM. Eradication rates for dysplasia in LSBE and ULSBE patients (90.6% versus 83.3%) and IM (71.9% versus 62.5%) were not significantly different. ULSBE patients required higher mean number of ablation sessions for IM eradication (4.7 versus 3.7, p = 0.032), while complication rates including strictures (4.2% versus 6.2%), perforation (0 versus 0), and bleeding (4.2% versus 3.1%), were similar between ULSBE and LSBE patients, respectively. On multivariate analysis, shorter Barrett's segment and baseline low-grade dysplasia were associated with increased likelihood for eradication of IM and dysplasia. A total number of ablation sessions or endoscopic resections ≥ 3 was associated with reduced likelihood for eradication. CONCLUSION RFA was durable in maintaining dysplasia and IM eradication in both LSBE and ULSBE over 10 years, and with low complication rates. IM eradication was more difficult to achieve in ULSBE. Late development of cancer occurred in 14.3%.
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Affiliation(s)
- Chu Luan Nguyen
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, 2139, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, 2050, Australia
| | - David Tovmassian
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, 2139, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, 2050, Australia
| | - Michael Zhou
- Department of Surgery, The University of Sydney, Camperdown, NSW, 2050, Australia
| | - Doruk Seyfi
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, 2139, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, 2050, Australia
| | - Suzanna Gooley
- Sydney Heartburn Clinic, Lindfield, NSW, 2070, Australia
| | - Gregory L Falk
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, 2139, Australia.
- Department of Surgery, The University of Sydney, Camperdown, NSW, 2050, Australia.
- Sydney Heartburn Clinic, Lindfield, NSW, 2070, Australia.
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Hilton CB, Lander S, Gibson MK. An Ailment with Which I Will Contend: A Narrative Review of 5000 Years of Esophagogastric Cancers and Their Treatments, with Special Emphasis on Recent Advances in Immunotherapeutics. Cancers (Basel) 2024; 16:618. [PMID: 38339368 PMCID: PMC10854527 DOI: 10.3390/cancers16030618] [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: 11/22/2023] [Revised: 01/24/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
Esophagogastric cancers are among the most common and deadly cancers worldwide. This review traces their chronology from 3000 BCE to the present. The first several thousand years were devoted to palliation, before advances in operative technique and technology led to the first curative surgery in 1913. Systemic therapies were introduced in 1910, and radiotherapy shortly thereafter. Operative technique improved massively over the 20th century, with operative mortality rates reducing from over 50% in 1933 to less than 5% by 1981. In addition to important roles in palliation, endoscopy became a key nonsurgical curative option for patients with limited-stage disease by the 1990s. The first nonrandomized studies on combination therapies (chemotherapy ± radiation ± surgery) were reported in the early 1980s, with survival benefit only for subsets of patients. Randomized trials over the next decades had similar overall results, with increasing nuance. Disparate conclusions led to regional variation in global practice. Starting with the first FDA approval in 2017, multiple immunotherapies now encompass more indications and earlier lines of therapy. As standards of care incorporate these effective yet expensive therapies, care must be given to disparities and methods for increasing access.
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Affiliation(s)
- C. Beau Hilton
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Ave, Nashville, TN 37232, USA
| | - Steven Lander
- Internal Medicine Residency Program, University of Tennessee Health Sciences Center, 920 Madison Ave, Suite 531, Memphis, TN 38163, USA;
| | - Michael K. Gibson
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Ave, Nashville, TN 37232, USA
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Knabe M, Wetzka J, Welsch L, Richl J, Michael F, Blößer S, Heilani M, Kronsbein H, May A. Radiofrequency ablation versus hybrid argon plasma coagulation in Barrett's esophagus: a prospective randomised trial. Surg Endosc 2023; 37:7803-7811. [PMID: 37605011 PMCID: PMC10520130 DOI: 10.1007/s00464-023-10313-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 07/15/2023] [Indexed: 08/23/2023]
Abstract
INTRODUCTION Radiofrequency ablation (RFA) and hybrid argon plasma coagulation (H-APC) are established thermal ablation techniques for eradicating Barrett's esophagus after endoscopic resection. This study aimed to compare RFA with H-APC in relation to safety, effectiveness and eradication rates. METHODS After endoscopic resection, patients were randomly assigned to H-APC or RFA. A simplified H-APC technique was applied at 60 W. RFA was used with a 90° focal catheter and a simplified protocol of 12 J/cm2 × 3 or with a Halo 360° balloon and 10 J/cm2/cleaning/10 J/cm2. Eradication rates and adverse events were recorded. Patients received follow-up examinations after 3, 6, 12 and 24 months. RESULTS One hundred and one patients were finally included in the study (RFA N = 47, H-APC N = 54). The median follow-up period for short-term was 6.0 (CI 5.4-6.9) months and for long term 21 (CI 19.2.5-22.7) months. In total 211 ablations were performed. The eradication rates after long-term follow-up were 74.2% in the RFA group and 82.9% in the H-APC group. Post-interventional pain was significantly greater in the RFA group, with a mean score of 4.56/10 and duration of 7.54 days, in comparison with a mean score of 2.07/10 over 3.59 days in the H-APC group. Stenoses requiring intervention were noted in 3.7% of patients in the H-APC arm and 14.9% of those in the RFA arm. CONCLUSIONS Both ablation techniques have good results in relation to the eradication rate, with a slightly better outcome in the H-APC group. The severity and duration of pain were significantly greater in the RFA group.
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Affiliation(s)
- Mate Knabe
- Department of Gastroenterology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
| | - Jens Wetzka
- Department of Medicine I, Asklepios Paulinen Klinik Wiesbaden, Wiesbaden, Germany
| | - Lukas Welsch
- Department of Gastroenterology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Johannes Richl
- Department of Gastroenterology, Sana Klinikum GmbH Offenbach, Offenbach, Germany
| | - Florian Michael
- Department of Gastroenterology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Sandra Blößer
- Department of Medicine I, Asklepios Paulinen Klinik Wiesbaden, Wiesbaden, Germany
| | - Myriam Heilani
- Department of Gastroenterology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Holger Kronsbein
- Department of Gastroenterology, Facility Bielefeld-Bethel, University Hospital Ostwestfalen-Lippe, Bielefeld, Germany
| | - Andrea May
- Department of Medicine I, Asklepios Paulinen Klinik Wiesbaden, Wiesbaden, Germany
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Autorinnen/Autoren, Collaborators:. S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:862-933. [PMID: 37494073 DOI: 10.1055/a-2060-1069] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
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Authors, und die Mitarbeiter der Leitlinienkommission, Collaborators:. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e209-e307. [PMID: 37285869 DOI: 10.1055/a-1771-6953] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
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Endoscopic therapy replaces surgery for clinical T1 oesophageal cancer in the Netherlands: a nationwide population-based study. Surg Endosc 2023:10.1007/s00464-023-09914-x. [PMID: 36849563 DOI: 10.1007/s00464-023-09914-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 01/28/2023] [Indexed: 03/01/2023]
Abstract
BACKGROUND Endoscopic resection for early oesophageal cancer was introduced around 2000 in the Netherlands. The scientific question was how the treatment and survival of early oesophageal and gastro-oesophageal junction cancer has changed over time in the Netherlands. METHODS Data were obtained from the nationwide population-based Netherlands Cancer Registry. All patients diagnosed with clinical in situ or T1 oesophageal or GOJ cancer without lymph node or distance metastasis during the study period (2000-2014) were extracted. Primary outcome parameters were the trends in treatment modalities over time and relative survival of each treatment regime. RESULTS A total of 1020 patients were diagnosed with a clinical in situ or T1 oesophageal or gastro-oesophageal junction cancer without lymph node or distance metastasis. The proportion of patients who received endoscopic treatment increased from 2.5% in 2000 to 58.1% in 2014. During the same period the proportion of patients who received surgery decreased from 57.5 to 23.1%. Five-year relative survival of all patients was 69%. Five-year relative survival after endoscopic therapy was 83% and after surgery 80%. Relative excess risk analyses showed no significant difference in survival between patients in the endoscopic therapy group and patients in the surgery group after adjustment for age, sex, clinical TNM classification, morphology and tumour location (RER 1.15; CI 0.76-1.75; p 0.76). CONCLUSION Our results demonstrate an increase in endoscopic treatment and a decrease of surgical treatment for in situ and T1 oesophageal/GOJ cancer between 2000-2014 in the Netherlands. The relative 5-year survival after endoscopic treatment is high (83%) and comparable with surgery (80%).
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Cotton CC, Eluri S, Shaheen NJ. Management of Dysplastic Barrett's Esophagus and Early Esophageal Adenocarcinoma. Gastroenterol Clin North Am 2022; 51:485-500. [PMID: 36153106 PMCID: PMC10173367 DOI: 10.1016/j.gtc.2022.06.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
While patients with Barrett's esophagus without dysplasia may benefit from endoscopic surveillance, those with low-grade dysplasia may be managed with either endoscopic surveillance or endoscopic eradication. Patients with Barrett's esophagus with high-grade dysplasia and/or intramucosal adenocarcinoma will generally require endoscopic eradication therapy. The management of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma is predominantly endoscopic, with multiple effective methods available for the resection of raised neoplasia and ablation of flat neoplasia. High-dose proton-pump inhibitor therapy is advised during the treatment of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma. After the endoscopic eradication of Barrett's esophagus and associated neoplasia, surveillance is required for the diagnosis and retreatment of recurrence or progression.
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Affiliation(s)
- Cary C Cotton
- Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, CB#7080, 130 Mason Farm Road, Suite 4153, Chapel Hill, NC 27599-7080, USA
| | - Swathi Eluri
- Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, CB#7080, 130 Mason Farm Road, Suite 4142, Chapel Hill, NC 27599-7080, USA
| | - Nicholas J Shaheen
- Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, CB#7080, 130 Mason Farm Road, Suite 4150, Chapel Hill, NC 27599-7080, USA.
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Maione F, Chini A, Maione R, Manigrasso M, Marello A, Cassese G, Gennarelli N, Milone M, De Palma GD. Endoscopic Diagnosis and Management of Barrett's Esophagus with Low-Grade Dysplasia. Diagnostics (Basel) 2022; 12:1295. [PMID: 35626450 PMCID: PMC9141542 DOI: 10.3390/diagnostics12051295] [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: 02/27/2022] [Revised: 05/17/2022] [Accepted: 05/19/2022] [Indexed: 02/05/2023] Open
Abstract
Barrett's Esophagus is a common condition associated with chronic gastroesophageal reflux disease. It is well known that it has an association with a higher incidence of esophageal adenocarcinoma, but this neoplastic transformation is first preceded by the onset of low and high-grade dysplasia. The evaluation of low grade dysplastic esophageal mucosa is still controversial; although endoscopic surveillance is preferred, several minimally invasive endoscopic therapeutic approaches are available. Endoscopic mucosal resection and radiofrequency ablation are the most used endoscopic treatments for the eradication of low-grade dysplasia, respectively, for nodular and flat dysplasia. Novel endoscopic treatments are cryotherapy ablation and argon plasma coagulation, that have good rates of eradication with less complications and post-procedural pain.
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Affiliation(s)
- Francesco Maione
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Alessia Chini
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Rosa Maione
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Michele Manigrasso
- Department of Advanced Biomedical Sciences, University of Naples “Federico II”, 80131 Naples, Italy;
| | - Alessandra Marello
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Gianluca Cassese
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Nicola Gennarelli
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Marco Milone
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Giovanni Domenico De Palma
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
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14
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Choi KKH, Sanagapalli S. Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies. World J Gastrointest Oncol 2022; 14:568-586. [PMID: 35321279 PMCID: PMC8919017 DOI: 10.4251/wjgo.v14.i3.568] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 11/12/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.
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Affiliation(s)
- Kevin Kyung Ho Choi
- AW Morrow Gastroenterology Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, NSW, Australia
| | - Santosh Sanagapalli
- Department of Gastroenterology, St Vincent’s Hospital, Darlinghurst 2010, NSW, Australia
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15
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van Munster SN, Frederiks CN, Nieuwenhuis EA, Alvarez Herrero L, Bogte A, Alkhalaf A, Schenk BE, Schoon EJ, Curvers WL, Koch AD, van de Ven SEM, de Jonge PJF, Tang TJ, Nagengast WB, Peters FTM, Westerhof J, Houben MHMG, Bergman JJGHM, Pouw RE, Weusten BLAM. Incidence and outcomes of poor healing and poor squamous regeneration after radiofrequency ablation therapy for early Barrett's neoplasia. Endoscopy 2022; 54:229-240. [PMID: 34062597 DOI: 10.1055/a-1521-6318] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Endoscopic eradication therapy with radiofrequency ablation (RFA) is effective in most patients with Barrett's esophagus (BE). However, some patients experience poor healing and/or poor squamous regeneration. We evaluated incidence and treatment outcomes of poor healing and poor squamous regeneration. METHODS We included all patients treated with RFA for early BE neoplasia from a nationwide Dutch registry based on a joint treatment protocol. Poor healing (active inflammatory changes or visible ulcerations ≥ 3 months post-RFA), poor squamous regeneration (< 50 % squamous regeneration), and treatment success (complete eradication of BE [CE-BE]) were evaluated. RESULTS 1386 patients (median BE C2M5) underwent RFA with baseline low grade dysplasia (27 %), high grade dysplasia (30 %), or early cancer (43 %). In 134 patients with poor healing (10 %), additional time and acid suppression resulted in complete esophageal healing, and 67/134 (50 %) had normal squamous regeneration with 97 % CE-BE. Overall, 74 patients had poor squamous regeneration (5 %). Compared with patients with normal regeneration, patients with poor squamous regeneration had a higher risk for treatment failure (64 % vs. 2 %, relative risk [RR] 27 [95 % confidence interval [CI] 18-40]) and progression to advanced disease (15 % vs. < 1 %, RR 30 [95 %CI 12-81]). Higher body mass index, longer BE segment, reflux esophagitis, and < 50 % squamous regeneration after baseline endoscopic resection were independently associated with poor squamous regeneration in multivariable logistic regression. CONCLUSIONS In half of the patients with poor healing, additional time and acid suppression led to normal squamous regeneration and excellent treatment outcomes. In patients with poor squamous regeneration, however, the risk for treatment failure and progression to advanced disease was significantly increased.
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Affiliation(s)
- Sanne N van Munster
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Charlotte N Frederiks
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands.,Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Esther A Nieuwenhuis
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Lorenza Alvarez Herrero
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Auke Bogte
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Alaa Alkhalaf
- Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, the Netherlands
| | - Boudewijn E Schenk
- Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, the Netherlands
| | - Erik J Schoon
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands
| | - Wouter L Curvers
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands
| | - Arjun D Koch
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Steffi E M van de Ven
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Pieter J F de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Thjon J Tang
- Department of Gastroenterology and Hepatology, IJsselland Hospital, Cappelle a/d IJssel, the Netherlands
| | - Wouter B Nagengast
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen University, Groningen, the Netherlands
| | - Frans T M Peters
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen University, Groningen, the Netherlands
| | - Jessie Westerhof
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen University, Groningen, the Netherlands
| | - Martin H M G Houben
- Department of Gastroenterology and Hepatology, Haga Hospital, Den Haag, the Netherlands
| | - Jacques J G H M Bergman
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Roos E Pouw
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Bas L A M Weusten
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands.,Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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16
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Comparative outcomes of radiofrequency ablation and cryoballoon ablation in dysplastic Barrett's esophagus: a propensity score-matched cohort study. Gastrointest Endosc 2022; 95:422-431.e2. [PMID: 34624303 DOI: 10.1016/j.gie.2021.09.037] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 09/27/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Strong evidence supports the use of radiofrequency ablation (RFA) in the management of dysplastic/neoplastic Barrett's esophagus (BE). Recently, the efficacy of the cryoballoon ablation (CBA) system was demonstrated in multicenter cohort studies. We aimed to assess the comparative effectiveness and safety of these 2 ablation modalities for endoscopic eradication therapy (EET) in a cohort study. METHODS Data were abstracted on patients with dysplastic BE or intramucosal carcinoma undergoing EET using RFA or CBA as the primary ablation modality at 2 referral centers. The primary outcome was the rate of complete remission intestinal metaplasia (CRIM). Secondary outcomes were rates of complete remission of dysplasia (CRD) and adverse events. Cox proportional hazards models and propensity scored-matched analyses were conducted to compare outcomes. RESULTS Three hundred eleven patients (CBA, 85 patients; RFA, 226 patients) with a median follow-up of 1.5 years (interquartile range, .8, 2.5) in the RFA group and 2.0 years (interquartile range, 1.3, 2.5) in the CBA group were studied. On multivariable analyses, the chances of reaching CRD and CRIM were not influenced by ablation modality. Propensity score-matched analysis revealed a comparable chance of achieving CRIM (CBA vs RFA: hazard ratio, 1.24; 95% confidence interval, .79-1.96; P = .35) and CRD (CBA vs RFA: hazard ratio, 1.19; 95% confidence interval, .82-1.73; P = .36). The CBA group had a higher stricture rate compared with the RFA group (10.4% vs 4.4%, P = .04). CONCLUSIONS Histologic outcomes of EET using CBA and RFA for dysplastic BE appear to be comparable. A randomized trial is needed to definitively compare outcomes between these 2 modalities.
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17
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Choi WT, Lauwers GY, Montgomery EA. Utility of ancillary studies in the diagnosis and risk assessment of Barrett's esophagus and dysplasia. Mod Pathol 2022; 35:1000-1012. [PMID: 35260826 PMCID: PMC9314252 DOI: 10.1038/s41379-022-01056-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/09/2022] [Accepted: 02/13/2022] [Indexed: 12/12/2022]
Abstract
Barrett's esophagus (BE) is a major risk factor for the development of esophageal adenocarcinoma (EAC). BE patients undergo periodic endoscopic surveillance with biopsies to detect dysplasia and EAC, but this strategy is imperfect owing to sampling error and inconsistencies in the diagnosis and grading of dysplasia, which may result in an inaccurate diagnosis or risk assessment for progression to EAC. The desire for more accurate diagnosis and better risk stratification has prompted the investigation and development of potential biomarkers that might assist pathologists and clinicians in the management of BE patients, allowing more aggressive endoscopic surveillance and treatment options to be targeted to high-risk individuals, while avoiding frequent surveillance or unnecessary interventions in those at lower risk. It is known that progression of BE to dysplasia and EAC is accompanied by a host of genetic alterations, and that exploration of these markers could be potentially useful to diagnose/grade dysplasia and/or to risk stratify BE patients. Several biomarkers have shown promise in identifying early neoplastic transformation and thus may be useful adjuncts to histologic evaluation. This review provides an overview of some of the currently available biomarkers and assays, including p53 immunostaining, Wide Area Transepithelial Sampling with Three-Dimensional Computer-Assisted Analysis (WATS3D), TissueCypher, mutational load analysis (BarreGen), fluorescence in situ hybridization, and DNA content abnormalities as detected by DNA flow cytometry.
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Affiliation(s)
- Won-Tak Choi
- University of California at San Francisco, Department of Pathology, San Francisco, CA, 94143, USA.
| | - Gregory Y. Lauwers
- grid.468198.a0000 0000 9891 5233H. Lee Moffitt Cancer Center and Research Institute, Department of Pathology, Tampa, FL 33612 USA
| | - Elizabeth A. Montgomery
- grid.26790.3a0000 0004 1936 8606University of Miami Miller School of Medicine, Department of Pathology and Laboratory Medicine, Miami, FL 33136 USA
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18
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Persistent or recurrent Barrett's neoplasia after an endoscopic therapy session is associated with DNA content abnormality and can be detected by DNA flow cytometric analysis of paraffin-embedded tissue. Mod Pathol 2021; 34:1889-1900. [PMID: 34108638 PMCID: PMC8443444 DOI: 10.1038/s41379-021-00832-8] [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: 03/27/2021] [Revised: 05/03/2021] [Accepted: 05/04/2021] [Indexed: 12/16/2022]
Abstract
Endoscopic therapy is currently the standard of care for the treatment of high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) in patients with Barrett's esophagus (BE). Visible lesions are treated with endoscopic mucosal resection (EMR), which is often coupled with radiofrequency ablation (RFA). However, endoscopic therapy may require multiple sessions (one session every 2-3 months) and does not always assure complete eradication of neoplasia. Furthermore, despite complete eradication, recurrences are not uncommon. This study assesses which potential risk factors can predict a poor response after endoscopic sessions. Forty-five BE patients who underwent at least one endoscopic session (EMR alone or ablation with or without preceding EMR) for the treatment of HGD/IMC, low-grade dysplasia (LGD), or indefinite for dysplasia (IND) were analyzed. DNA flow cytometry was performed on 82 formalin-fixed paraffin-embedded samples from the 45 patients, including 78 HGD/IMC, 2 LGD, and 2 IND. Eight non-dysplastic BE samples were used as controls. Three to four 60-micron thick sections were cut from each tissue block, and the area of HGD/IMC, LGD, or IND was manually dissected. Potential associations between clinicopathologic risk factors and persistent/recurrent HGD/IMC following each endoscopic session were examined using univariate and multivariate Cox models with frailty terms. Sixty (73%) of the 82 specimens showed abnormal DNA content (aneuploidy or elevated 4N fraction). These were all specimens with HGD/IMC (representing 77% of that group). Of these 60 HGD/IMC samples with abnormal DNA content, 42 (70%) were associated with subsequent development of persistent/recurrent HGD/IMC (n = 41) or esophageal adenocarcinoma (EAC; n = 1) within a mean follow-up time of 16 months (range: 1 month to 9.4 years). In contrast, only 6 (27%, all HGD/IMC) of the 22 remaining samples (all with normal DNA content) were associated with persistent/recurrent HGD/IMC. For outcome analysis per patient, 11 (24%) of the 45 patients developed persistent/recurrent HGD/IMC or EAC, despite multiple endoscopic sessions (mean: 3.6, range: 1-11). In a univariate Cox model, the presence of abnormal DNA content (hazard ratio [HR] = 3.8, p = 0.007), long BE segment ≥ 3 cm (HR = 3.4, p = 0.002), endoscopic nodularity (HR = 2.5, p = 0.042), and treatment with EMR alone (HR = 2.9, p = 0.006) were significantly associated with an increased risk for persistent/recurrent HGD/IMC or EAC. However, only abnormal DNA content (HR = 6.0, p = 0.003) and treatment with EMR alone (HR = 2.7, p = 0.047) remained as significant risk factors in a multivariate analysis. Age ≥ 60 years, gender, ethnicity, body mass index (BMI) ≥ 30 kg/m2, presence of hiatal hernia, and positive EMR lateral margin for neoplasia were not significant risk factors for persistent/recurrent HGD/IMC or EAC (p > 0.05). Three-month, 6-month, 1-year, 3-year, and 6-year adjusted probabilities of persistent/recurrent HGD/IMC or EAC in the setting of abnormal DNA content were 31%, 56%, 67%, 79%, and 83%, respectively. The corresponding probabilities in the setting of normal DNA content were 10%, 21%, 28%, 38%, and 43%, respectively. In conclusion, in BE patients with baseline HGD/IMC, both DNA content abnormality and treatment with EMR alone were significantly associated with persistent/recurrent HGD/IMC or EAC following each endoscopic session. DNA content abnormality as detected by DNA flow cytometry identifies HGD/IMC patients at highest risk for persistent/recurrent HGD/IMC or EAC, and it also serves as a diagnostic marker of HGD/IMC with an estimated sensitivity of 77%. The diagnosis of HGD/IMC in the setting of abnormal DNA content may warrant alternative treatment strategies as well as long-term follow-up with shorter surveillance intervals.
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19
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Optimizing Outcomes with Radiofrequency Ablation of Barrett's Esophagus: Candidates, Efficacy and Durability. Gastrointest Endosc Clin N Am 2021; 31:131-154. [PMID: 33213792 DOI: 10.1016/j.giec.2020.09.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The treatment of early Barrett's esophagus (BE) has undergone a paradigm shift from surgical subtotal esophagectomy to organ-saving endoluminal treatment. Over the past 15 years, several high-quality studies were conducted to assess safe oncological outcome of endoscopic resection of mucosal adenocarcinoma and high-grade dysplasia. It became clear that add-on ablative therapy with radiofrequency ablation (RFA) significantly reduces recurrence risk of neoplasia after resection. In this review, we highlight the most essential elements to optimize outcomes of RFA of BE, addressing the correct indication and patient selection in combination with the most efficient and safest treatment protocols to obtain long-term durability.
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20
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Canto MI, Trindade AJ, Abrams J, Rosenblum M, Dumot J, Chak A, Iyer P, Diehl D, Khara HS, Corbett FS, McKinley M, Shin EJ, Waxman I, Infantolino A, Tofani C, Samarasena J, Chang K, Wang B, Goldblum J, Voltaggio L, Montgomery E, Lightdale CJ, Shaheen NJ. Multifocal Cryoballoon Ablation for Eradication of Barrett's Esophagus-Related Neoplasia: A Prospective Multicenter Clinical Trial. Am J Gastroenterol 2020; 115:1879-1890. [PMID: 33009064 DOI: 10.14309/ajg.0000000000000822] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION:
Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE.
METHODS:
In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1–6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year.
RESULTS:
One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR.
DISCUSSION:
In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).
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Affiliation(s)
- Marcia Irene Canto
- Department of Medicine (Gastroenterology), Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Arvind J. Trindade
- Division of Gastroenterology at the Zucker School of Medicine of Hofstra/Northwell, Long Island Jewish Medical Center, Northwell Health System, New Hyde Park, New York, USA
| | - Julian Abrams
- Department of Medicine, Columbia University Medical Center, New York, New York, USA
| | - Michael Rosenblum
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, USA
| | - John Dumot
- Division of Gastroenterology at University Hospitals of Cleveland Medical Center, Cleveland, Ohio, USA
| | - Amitabh Chak
- Division of Gastroenterology at University Hospitals of Cleveland Medical Center, Cleveland, Ohio, USA
| | - Prasad Iyer
- Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA
| | - David Diehl
- Division of Gastroenterology, Geisinger Medical Center, Danby Pennsylvania, USA
| | - Harshit S. Khara
- Division of Gastroenterology, Geisinger Medical Center, Danby Pennsylvania, USA
| | | | - Matthew McKinley
- Division of Gastroenterology at the Zucker School of Medicine of Hofstra/Northwell, Long Island Jewish Medical Center, Northwell Health System, New Hyde Park, New York, USA
| | - Eun Ji Shin
- Department of Medicine (Gastroenterology), Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Irving Waxman
- Division of Gastroenterology, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Anthony Infantolino
- Division of Gastroenterology, Jefferson Medical Center, Philadelphia, Pennsylvania, USA
| | - Christina Tofani
- Division of Gastroenterology, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Jason Samarasena
- Division of Gastroenterology, University of California Irvine Medical Center, Irvine, California, USA
| | - Kenneth Chang
- Division of Gastroenterology, University of California Irvine Medical Center, Irvine, California, USA
| | - Bingkai Wang
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, USA
| | - John Goldblum
- Department of Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Lysandra Voltaggio
- Department ofPathology, Johns Hopkins Medical Institutions Baltimore Maryland, USA
| | - Elizabeth Montgomery
- Department ofPathology, Johns Hopkins Medical Institutions Baltimore Maryland, USA
| | - Charles J. Lightdale
- Division of Gastroenterology at the Zucker School of Medicine of Hofstra/Northwell, Long Island Jewish Medical Center, Northwell Health System, New Hyde Park, New York, USA
| | - Nicholas J. Shaheen
- Division of Gastroenterology, University of North Carolina, Chapel Hill, North Carolina, USA
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21
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Pouw RE, Klaver E, Phoa KN, van Vilsteren FG, Weusten BL, Bisschops R, Schoon EJ, Pech O, Manner H, Ragunath K, Fernández-Sordo JO, Fullarton G, Di Pietro M, Januszewicz W, O'Toole D, Bergman JJ. Radiofrequency ablation for low-grade dysplasia in Barrett's esophagus: long-term outcome of a randomized trial. Gastrointest Endosc 2020; 92:569-574. [PMID: 32217112 DOI: 10.1016/j.gie.2020.03.3756] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 03/12/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS A prior randomized study (Surveillance versus Radiofrequency Ablation study [SURF study]) demonstrated that radiofrequency ablation (RFA) of Barrett's esophagus (BE) with confirmed low-grade dysplasia (LGD) significantly reduces the risk of esophageal adenocarcinoma. Our aim was to report the long-term outcomes of this study. METHODS The SURF study randomized BE patients with confirmed LGD to RFA or surveillance. For this retrospective cohort study, all endoscopic and histologic data acquired at the end of the SURF study in May 2013 until December 2017 were collected. The primary outcome was rate of progression to high-grade dysplasia (HGD)/cancer. All 136 patients randomized to RFA (n = 68) or surveillance (n = 68) in the SURF study were included. After closure of the SURF study, 15 surveillance patients underwent RFA based on patient preference and study outcomes. RESULTS With 40 additional months (interquartile range, 12-51), the total median follow-up from randomization to last endoscopy was 73 months (interquartile range, 46-85). HGD/cancer was diagnosed in 1 patient in the RFA group (1.5%) and in 23 in the surveillance group (33.8%) (P = .000), resulting in an absolute risk reduction of 32.4% (95% confidence interval [CI], 22.4%-44.2%) with a number needed to treat of 3.1 (95% CI, 2.3-4.5). Seventy-five of 83 patients (90%; 95% CI, 82.1%-95.0%) treated with RFA for BE reached complete clearance of BE and dysplasia. BE recurred in 7 of 75 patients (9%; 95% CI, 4.6%-18.0%), mostly minute islands or tongues, and LGD in 3 of 75 (4%; 95% CI, 1.4%-11.1%). CONCLUSIONS RFA of BE with confirmed LGD significantly reduces the risk of malignant progression, with sustained clearance of BE in 91% and LGD in 96% of patients, after a median follow-up of 73 months. (Clinical trial registration number: NTR1198.).
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Affiliation(s)
- Roos E Pouw
- Department of Gastroenterology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Esther Klaver
- Department of Gastroenterology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - K Nadine Phoa
- Department of Gastroenterology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | | | - Bas L Weusten
- Department of Gastroenterology, St Antonius Hospital, Nieuwegein, the Netherlands
| | - Raf Bisschops
- Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium
| | - Erik J Schoon
- Department of Gastroenterology, Catharina Hospital, Eindhoven, the Netherlands
| | - Oliver Pech
- Department of Gastroenterology, Helios dr. Horst Schmidt Clinics Wiesbaden, Germany
| | - Hendrik Manner
- Department of Gastroenterology, Frankfurt Hoechst Hospital, Frankfurt, Germany
| | - Krish Ragunath
- Department of Gastroenterology, Queens Medical Center, Nottingham, UK
| | | | - Grant Fullarton
- Department of Surgical Gastroenterology, Glasgow Royal Infirmary, Glasgow, Scotland
| | | | | | - Dermot O'Toole
- Department of Clinical Medicine and Gastroenterology, St James's Hospital, Dublin, Ireland
| | - Jacques J Bergman
- Department of Gastroenterology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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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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Tan WK, Ragunath K, White JR, Santiago J, Fernandez-Sordo JO, Pana M, Alias B, Hadjinicolaou AV, Sujendran V, di Pietro M. Standard versus simplified radiofrequency ablation protocol for Barrett's esophagus: comparative analysis of the whole treatment pathway. Endosc Int Open 2020; 8:E189-E195. [PMID: 32010753 PMCID: PMC6976319 DOI: 10.1055/a-1005-6331] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 04/24/2019] [Indexed: 12/20/2022] Open
Abstract
Background and study aims The standard radiofrequency ablation (RFA) protocol for Barrett's esophagus (BE) encompasses an intermediary cleaning phase between two ablation sessions. A simplified protocol omitting the cleaning phase is less labor-intensive but equally effective in studies based on single ablation procedures. The aim of this study was to compare efficacy and safety of the standard and simplified RFA protocols for the whole treatment pathway for BE, including both circumferential and focal devices. Patients and methods We performed a retrospective analysis of prospectively collected data on patients receiving RFA between January 2007 and August 2017 at two institutions. Outcomes assessed were: 1) complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM) at 18 months; and 2) rate of esophageal strictures. Results One hundred forty-five patients were included of whom 73 patients received the standard and 72 patients received the simplified protocol. CR-D was achieved in 94.5 % and 95.8 % of patients receiving the standard and simplified protocol, respectively ( P = 0.71). CR-IM was achieved in 84.9 % and 77.8 % of patients treated with the standard and simplified protocol, respectively ( P = 0.27). Strictures were significantly more common among patients who received the simplified protocol (12.5 %) compared to the standard protocol (1.4 %; P = 0.008). The median number of esophageal dilations was one. Conclusion The simplified RFA protocol is as effective as the standard protocol in eradicating BE but carries a higher risk of strictures. This needs to be taken into account, particularly in patients with higher pretreatment risk of strictures, such as those with esophageal narrowing from previous endoscopic mucosal resection (EMR).
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Affiliation(s)
- Wei Keith Tan
- MRC Cancer unit, University of Cambridge, Cambridge, UK,Department of Gastroenterology, Addenbrookes Hospital, Cambridge, UK
| | - Krish Ragunath
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK,Nottingham Digestive Diseases Centre, The University of Nottingham, Nottingham, UK
| | - Jonathan R. White
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK,Nottingham Digestive Diseases Centre, The University of Nottingham, Nottingham, UK
| | - Jose Santiago
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK,Nottingham Digestive Diseases Centre, The University of Nottingham, Nottingham, UK
| | - Jacobo Ortiz Fernandez-Sordo
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK,Nottingham Digestive Diseases Centre, The University of Nottingham, Nottingham, UK
| | - Mirela Pana
- Nottingham Digestive Diseases Centre, The University of Nottingham, Nottingham, UK
| | - Bincy Alias
- MRC Cancer unit, University of Cambridge, Cambridge, UK
| | - Andreas V. Hadjinicolaou
- MRC Cancer unit, University of Cambridge, Cambridge, UK,Department of Gastroenterology, Addenbrookes Hospital, Cambridge, UK
| | - Vijay Sujendran
- Department of Surgery, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
| | - Massimiliano di Pietro
- MRC Cancer unit, University of Cambridge, Cambridge, UK,Corresponding author Massimiliano di Pietro MRC Cancer UnitUniversity of CambridgeCambridgeUK+01223 763241
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Dugalic P, Djuranovic S, Pavlovic-Markovic A, Dugalic V, Tomasevic R, Gluvic Z, Obradovic M, Bajic V, Isenovic ER. Proton Pump Inhibitors and Radiofrequency Ablation for Treatment of Barrett's Esophagus. Mini Rev Med Chem 2020; 20:975-987. [PMID: 31644405 DOI: 10.2174/1389557519666191015203636] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 06/04/2019] [Accepted: 06/25/2019] [Indexed: 02/07/2023]
Abstract
Gastroesophageal Reflux Disease (GERD) is characterized by acid and bile reflux in the distal oesophagus, and this may cause the development of reflux esophagitis and Barrett's oesophagus (BE). The natural histological course of untreated BE is non-dysplastic or benign BE (ND), then lowgrade (LGD) and High-Grade Dysplastic (HGD) BE, with the expected increase in malignancy transfer to oesophagal adenocarcinoma (EAC). The gold standard for BE diagnostics involves high-resolution white-light endoscopy, followed by uniform endoscopy findings description (Prague classification) with biopsy performance according to Seattle protocol. The medical treatment of GERD and BE includes the use of proton pump inhibitors (PPIs) regarding symptoms control. It is noteworthy that long-term use of PPIs increases gastrin level, which can contribute to transfer from BE to EAC, as a result of its effects on the proliferation of BE epithelium. Endoscopy treatment includes a wide range of resection and ablative techniques, such as radio-frequency ablation (RFA), often concomitantly used in everyday endoscopy practice (multimodal therapy). RFA promotes mucosal necrosis of treated oesophagal region via high-frequency energy. Laparoscopic surgery, partial or total fundoplication, is reserved for PPIs and endoscopy indolent patients or in those with progressive disease. This review aims to explain distinct effects of PPIs and RFA modalities, illuminate certain aspects of molecular mechanisms involved, as well as the effects of their concomitant use regarding the treatment of BE and prevention of its transfer to EAC.
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Affiliation(s)
- Predrag Dugalic
- Department of Gastroenterology and Hepatology, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Srdjan Djuranovic
- Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Pavlovic-Markovic
- Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vladimir Dugalic
- Clinical Centre of Serbia, Clinic for Surgery, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ratko Tomasevic
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Zoran Gluvic
- Department of Endocrinology and Diabetes, Faculty of Medicine, University of Belgrade, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
| | - Vladan Bajic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
| | - Esma R Isenovic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
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25
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Hao J, Critchley-Thorne R, Diehl DL, Snyder SR. A Cost-Effectiveness Analysis Of An Adenocarcinoma Risk Prediction Multi-Biomarker Assay For Patients With Barrett's Esophagus. CLINICOECONOMICS AND OUTCOMES RESEARCH 2019; 11:623-635. [PMID: 31749626 PMCID: PMC6818671 DOI: 10.2147/ceor.s221741] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 10/02/2019] [Indexed: 12/18/2022] Open
Abstract
PURPOSE This study evaluates the cost-effectiveness of a quantitative multi-biomarker assay (the Assay) that stratifies patients with Barrett's Esophagus (BE) by risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and can be used to guide clinical decisions, versus the current guidelines (standard of care [SOC]) for surveillance and treatment of BE. PATIENTS AND METHODS Markov decision modeling and simulation were used to compare cost and quality-adjusted life-years (QALYs) from the perspective of a US health insurer with care delivered by an integrated health system. Model assumptions and disease progression probabilities were derived from the literature. Performance metrics for the Assay were from an independent clinical validation study. Cost of the Assay was based on reimbursement rates from multiple payers. Other costs were derived from Geisinger payment data. RESULTS Base-case model results for a 5-year period comparing the Assay-directed care to the SOC estimated an incremental cost-effectiveness ratio (ICER) of $52,483/QALY in 2012 US dollars. Assay-directed care increased the use of endoscopic treatments by 58.4%, which reduced the progression to HGD, EAC and reduced EAC-related deaths by 51.7%, 47.1%, and 37.6%, respectively, over the 5-year period. Sensitivity analysis indicated that the probability of the Assay being cost-effective compared to the SOC was 57.3% at the $100,000/QALY acceptability threshold. CONCLUSION Given the model assumptions, the new Assay would be cost-effective after 5 years and improves patient outcomes due to improvement in the effectiveness of surveillance and treatment protocols resulting in fewer patients progressing to HGD and EAC and fewer EAC-related deaths.
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Affiliation(s)
- Jing Hao
- Department of Epidemiology and Health Services Research, Geisinger, Danville, PA, USA
| | | | - David L Diehl
- Department of Gastroenterology, Geisinger, Danville, PA, USA
| | - Susan R Snyder
- Department of Epidemiology and Health Services Research, Geisinger, Danville, PA, USA
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Ahmed O, Ajani JA, Lee JH. Endoscopic management of esophageal cancer. World J Gastrointest Oncol 2019; 11:830-841. [PMID: 31662822 PMCID: PMC6815921 DOI: 10.4251/wjgo.v11.i10.830] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Revised: 05/29/2019] [Accepted: 08/28/2019] [Indexed: 02/05/2023] Open
Abstract
Esophageal cancer (EC) generally consists of squamous cell carcinoma (which arise from squamous epithelium) and adenocarcinoma (which arise from columnar epithelium). Due to the increased recognition of risk factors associated with EC and the development of screening programs, there has been an increase in the diagnosis of early EC. Early EC is amenable to curative therapy by endoscopy, which can be performed by either endoscopic resection or endoscopic ablation. Endoscopic resection consists of either endoscopic mucosal resection (preferred in cases of adenocarcinoma) or endoscopic submucosal dissection (preferred in cases of squamous cell carcinoma). Endoscopic ablation can be performed by either radiofrequency ablation, cryotherapy, argon plasma coagulation or photodynamic therapy, amongst others. Endoscopy can also assist in the management of complications post-esophageal surgery, such as anastomotic leaks and perforations. Finally, there is a growing role for endoscopy to manage end-of-life palliative symptoms, especially dysphagia. The growing use of esophageal stents, debulking therapy and dilation can assist in improving a patient’s quality of life. In this review, we examine the multiple roles of endoscopy in the management of patients with EC.
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Affiliation(s)
- Osman Ahmed
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jaffer A Ajani
- Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jeffrey H Lee
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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27
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Self-sizing radiofrequency ablation balloon for eradication of Barrett's esophagus: results of an international multicenter randomized trial comparing 3 different treatment regimens. Gastrointest Endosc 2019; 90:415-423. [PMID: 31108093 DOI: 10.1016/j.gie.2019.05.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 05/12/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Recently, the 360 Express radiofrequency ablation balloon catheter (360 Express, Medtronic, Minneapolis, Minn, USA) has replaced the traditional system for circumferential radiofrequency ablation (RFA) of Barrett's esophagus (BE). The aim was to compare 3 different ablation regimens for the 360 Express. METHODS An international multicenter noninferiority randomized controlled trial was conducted in which patients with a BE (2-15 cm) with dysplasia or early cancer were randomly assigned to the standard (1 × 10 J/cm2-clean-1 × 10 J/cm2), simple-double (2 × 10 J/cm2-no clean), or simple-single ablation regimen (1 × 10 J/cm2-no clean). The primary outcome was the percentage endoscopically visual BE regression at 3 months. Secondary outcomes were procedure time, adverse events, and patient discomfort. RESULTS Between September 2015 and October 2017, 104 patients were enrolled. The simple-double ablation arm was closed prematurely because of a 21% stenosis rate. The trial continued with the standard (n = 37) and simple-single arm (n = 38). Both arms were comparable at baseline. Noninferiority of the simple-single arm could not be demonstrated: BE regression was 73% in the simple-single arm versus 85% in the standard arm; the median difference was 13% (95% confidence interval, 5%-23%). The procedure time was significantly longer in the standard arm (31 vs 17 minutes, P < .001). Both groups were comparable with regard to adverse events and patient discomfort. CONCLUSIONS This randomized trial shows that circumferential RFA with the 360 Express using the simple-double ablation regimen results in an unacceptable high risk of stenosis. Furthermore, the results suggest that a single ablation at 10 J/cm2 results in inferior BE regression at 3 months. We therefore advise using the standard ablation regimen (1 × 10 J/cm2-clean-1 × 10 J/cm2) for treatment of BE using the 360 Express. (Clinical trial registration number: NTR5191.).
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28
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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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29
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Peerally MF, Bhandari P, Ragunath K, Barr H, Stokes C, Haidry R, Lovat L, Smart H, Harrison R, Smith K, Morris T, de Caestecker JS. Radiofrequency ablation compared with argon plasma coagulation after endoscopic resection of high-grade dysplasia or stage T1 adenocarcinoma in Barrett's esophagus: a randomized pilot study (BRIDE). Gastrointest Endosc 2019; 89:680-689. [PMID: 30076843 DOI: 10.1016/j.gie.2018.07.031] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 07/25/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Endoscopic resection (ER) is safe and effective for Barrett's esophagus (BE) containing high-grade dysplasia (HGD) or mucosal adenocarcinoma (T1A). The risk of metachronous neoplasia is reduced by ablation of residual BE by using radiofrequency ablation (RFA) or argon plasma coagulation (APC). These have not been compared directly. We aimed to recruit up to 100 patients with BE and HGD or T1A confirmed by ER over 1 year in 6 centers in a randomized pilot study. METHODS Randomization was 1:1 to RFA or APC (4 treatments allowed at 2-month intervals). Recruitment, retention, dysplasia clearance, clearance of benign BE, adverse events, healthcare costs, and quality of life by using EQ-5D, EORTC QLQ-C30, or OES18 were assessed up to the end of the trial at 12 months. RESULTS Of 171 patients screened, 76 were randomized to RFA (n = 36) or APC (n = 40). The mean age was 69.7 years, and 82% were male. BE was <5 cm (n = 27), 5 to 10 cm (n = 45), and >10 cm (n = 4). Sixty-five patients completed the trial. At 12 months, dysplasia clearance was RFA 79.4% and APC 83.8% (odds ratio [OR] 0.7; 95% confidence interval [CI], 0.2-2.6); BE clearance was RFA 55.8%, and APC 48.3% (OR 1.4; 95% CI, 0.5-3.6). A total of 6.1% (RFA) and 13.3% (APC) had buried BE glands. Adverse events (including stricture rate after starting RFA 3/36 [8.3%] and APC 3/37 [8.1%]) and quality of life scores were similar, but RFA cost $27491 more per case than APC. CONCLUSION This pilot study suggests similar efficacy and safety but a cost difference favoring APC. A fully powered non-inferiority trial is appropriate to confirm these findings. (Clinical trial registration number: NCT01733719.).
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Affiliation(s)
- Mohammad Farhad Peerally
- Digestive Diseases Centre, University Hospitals of Leicester NHS Trust, UK and Leicester Cancer Research Centre, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, United Kingdom
| | | | - Krish Ragunath
- Nottingham Digestive Diseases Centre, University of Nottingham and NIHR Nottingham BRC, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| | - Hugh Barr
- Gloucester Royal Hospital, Gloucester, United Kingdom
| | - Clive Stokes
- Gloucester Royal Hospital, Gloucester, United Kingdom
| | - Rehan Haidry
- University College Hospital, London, United Kingdom
| | | | - Howard Smart
- Royal Liverpool Hospital, Liverpool, United Kingdom
| | - Rebecca Harrison
- Department of Pathology, University Hospitals of Leicester NHS trust, Leicester, United Kingdom
| | - Karen Smith
- Department of Health Sciences, University of Leicester, Leicester, United Kingdom
| | - Tom Morris
- Leicester Clinical Trials Unit, University of Leicester, Leicester, United Kingdom
| | - John S de Caestecker
- Digestive Diseases Centre, University Hospitals of Leicester NHS Trust, UK and Leicester Cancer Research Centre, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, United Kingdom
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30
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Abstract
Endoscopic resection for early esophageal cancer is a very precise endoscopic surgical technique and having experience in endoscopic resection is mandatory to perform these kinds of procedures safely. In case of adequate resection and favorable histological outcome, long-term prognosis of the patient is excellent. The basic principle for endoscopic treatment of early adenocarcinoma is based on the fact that the risk of lymph node metastasis gradually increases with the depth of invasion. Inspection and evaluation of all mucosal and submucosal lesions need to be done carefully before endoscopic resection. Endoscopic resection of mucosal (T1m1-3) and superficial submucosal (T1sm1) adenocarcinoma can be curative as well as for superficial mucosal (T1m1-m2) squamous cell carcinoma. In Paris type I lesions in Barrett's esophagus and for early squamous cell carcinoma endoscopic submucosal dissection (ESD) is the preferred option. The risk of severe adverse events associated with endoscopic resection are low. Most adverse events are managed endoscopically and can be treated conservatively. Endoscopic radiofrequency ablation is the most widely used ablation technique for Barrett's epithelium and highly effective to achieve full remission of dysplasia and intestinal metaplasia. The role of radiofrequency ablation in the treatment armamentarium in squamous cell carcinoma of the esophagus has still to be determined.
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Affiliation(s)
- Irma C Noordzij
- Department of Gastroenterology and Hepatology, Catharina Cancer Institute, Catharina Hospital, Eindhoven, The Netherlands
| | - Wouter L Curvers
- Department of Gastroenterology and Hepatology, Catharina Cancer Institute, Catharina Hospital, Eindhoven, The Netherlands
| | - Erik J Schoon
- Department of Gastroenterology and Hepatology, Catharina Cancer Institute, Catharina Hospital, Eindhoven, The Netherlands
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31
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Christman EM, Chandrakesan P, Weygant N, Maple JT, Tierney WM, Vega KJ, Houchen CW. Elevated doublecortin-like kinase 1 serum levels revert to baseline after therapy in early stage esophageal adenocarcinoma. Biomark Res 2019; 7:5. [PMID: 30899515 PMCID: PMC6408757 DOI: 10.1186/s40364-019-0157-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 02/27/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) incidence has been increasing in the United States for greater than 30 years. For the majority of EAC patients, treatment is limited and prognosis poor. Doublecortin like kinase-1 (DCLK1) is a cancer stem cell marker with elevated expression in BE patients with high grade dysplasia and/or EAC. This prospective cohort study was designed to compare serum DCLK1 levels before and after EAC treatment with endoscopic mucosal resection (EMR) and/or radio-frequency ablation (RFA). METHODS Barrett's esophagus patients with low or high-grade dysplasia (n = 9) and EAC patients (Stage I/II) eligible for treatment were enrolled (n = 14). Serum was obtained at enrollment and at end of treatment (EoT) where possible (n = 6). Normal control samples (n = 5) were obtained from patients with normal upper endoscopies. Serum was analyzed for DCLK1 protein content by ELISA. Kruskal-Wallis, Mann Whitney U, Pearson correlation, and Receiver Operating Characteristic tests were used to analyze the data. RESULTS Serum DCLK1 levels were increased by > 50% in Barrett's Esophagus (n = 9) and EAC patients (n = 14) vs controls (n = 5, p = 0.0007). These levels were reduced > 50% at EoT compared to EAC (p = 0.033). Although age was significantly lower in controls, this factor was not statistically related to DCLK1 serum levels (p = 0.66). CONCLUSIONS EAC treatment results in significantly decreased serum DCLK1 levels, suggesting that DCLK1 may be useful as a non-invasive disease regression biomarker following treatment. IMPACT Biomarkers for EAC therapeutic response have been poorly studied and no reliable marker has been discovered thus far. These results demonstrate that DCLK1 may have potential as a circulating biomarker of the response to therapy in EAC, which could be used to improve patient outcomes.
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Affiliation(s)
- Emily M. Christman
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK USA
| | - Parthasarathy Chandrakesan
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK USA
- Peggy and Charles Stephenson Cancer Center, Oklahoma City, OK USA
| | - Nathaniel Weygant
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK USA
| | - John T. Maple
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK USA
| | - William M. Tierney
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK USA
| | - Kenneth J. Vega
- Department of Medicine, Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, 1120 15th Street, AD 2226, Augusta, GA 30912 USA
| | - Courtney W. Houchen
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK USA
- Peggy and Charles Stephenson Cancer Center, Oklahoma City, OK USA
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32
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Alzoubaidi D, Graham D, Bassett P, Magee C, Everson M, Banks M, Novelli M, Jansen M, Lovat LB, Haidry R. Comparison of two multiband mucosectomy devices for endoscopic resection of Barrett's esophagus-related neoplasia. Surg Endosc 2019; 33:3665-3672. [PMID: 30671663 PMCID: PMC6795619 DOI: 10.1007/s00464-018-06655-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 12/24/2018] [Indexed: 02/07/2023]
Abstract
Background Esophageal adenocarcinoma carries a poor prognosis and therefore treatment of early neoplasia arising in the precursor condition Barrett’s esophagus (BE) is desirable. Visible lesions arising in BE need endoscopic mucosal resection for accurate staging and removal. Resection modalities include a cap-based system with snare and custom-made multiband mucosectomy (MBM) devices (Duette, Cook Medical Ltd). A new MBM device has recently become available (Captivator, Boston Scientific Ltd). Objectives A retrospective pilot study to compare the efficacy, safety, specimen size and histology of endoscopic mucosal resection (EMR) specimens resected with two MBM devices (Cook Duette and Boston Captivator) in treatment naive patients undergoing endoscopic therapy for BE neoplasia. Methods Consecutive EMR procedures carried out by a single experienced endoscopist were analysed. All visible lesions were marked and resected using one of the two MBM devices. All resected specimens were analysed by the same two experienced pathologists. The resected specimens in both groups were analysed for maximum diameter, minimum diameter, surface area and depth. Results Twenty consecutive patients were analysed (18M + 2F; mean age 74) in the Duette group and 20 (17M + 3F; mean age 72) in the Captivator group. A total of 58 specimens were resected in the Duette and 63 in the Captivator group. Min diameter, max diameter, surface area and depth of the ER specimens resected by the Captivator device were significantly larger than that by the Duette device [min diameter 9.89 mm vs 9.07 mm (p = 0.019); max diameter: 13.54 mm vs 12.38 mm (p = 0.024); surface area: 135.40 mm2 vs 113.89 mm2 (p = 0.005); depth 3.71 mm vs 2.89 (p = 0.001)]. Conclusions These two MBM devices showed equivalent efficacy and safety outcomes, but the EMR Captivator device resected specimens with a larger area in the esophagus when compared with the Duette device. A possible advantage of this is in situations where en bloc resections with fewer EMRs are desirable for larger lesions.
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Affiliation(s)
- Durayd Alzoubaidi
- Division of Surgery & Interventional Science, University College London (UCL), Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK.
| | - David Graham
- Department of Gastroenterology, University College London Hospital NHS Foundation Trust, London, UK
| | - Paul Bassett
- Statsconsultancy Ltd, 40 Longwood Lane, Amersham, HP7 9EN, UK
| | - Cormac Magee
- Department of Gastroenterology, University College London Hospital NHS Foundation Trust, London, UK
| | - Martin Everson
- Department of Gastroenterology, University College London Hospital NHS Foundation Trust, London, UK
| | - Matthew Banks
- Department of Gastroenterology, University College London Hospital NHS Foundation Trust, London, UK
| | - Marco Novelli
- Department of Pathology, University College London Hospital NHS Foundation Trust, London, UK
| | - Marnix Jansen
- Department of Pathology, University College London Hospital NHS Foundation Trust, London, UK
| | - Laurence B Lovat
- Division of Surgery & Interventional Science, University College London (UCL), Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK
| | - Rehan Haidry
- Division of Surgery & Interventional Science, University College London (UCL), Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK
- Department of Gastroenterology, University College London Hospital NHS Foundation Trust, London, UK
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33
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van Munster SN, Overwater A, Haidry R, Bisschops R, Bergman JJGHM, Weusten BLAM. Focal cryoballoon versus radiofrequency ablation of dysplastic Barrett's esophagus: impact on treatment response and postprocedural pain. Gastrointest Endosc 2018; 88:795-803.e2. [PMID: 29928869 DOI: 10.1016/j.gie.2018.06.015] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 06/05/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Radiofrequency ablation (RFA) is safe and effective for eradicating Barrett's esophagus (BE) but is associated with significant postprocedural pain. Alternatively, balloon-based focal cryoablation (CRYO) has recently been developed, which preserves the extracellular matrix and might therefore be less painful. Although data for CRYO are still limited, uncontrolled studies suggest comparable safety and efficacy to RFA in eradicating limited BE areas. Therefore, secondary endpoints such as pain might become decisive for treatment selection. We aimed to compare efficacy and tolerability between focal CRYO and RFA. METHODS We identified BE patients undergoing focal ablation (either RFA or CRYO) of all visible BE from our prospective cohort in 2 Dutch referral centers. After ablation, patients completed a 14-day digital diary to assess chest pain (0-10), dysphagia (0-4), and analgesics use. A follow-up endoscopy was scheduled after 3 months to assess the BE surface regression (blindly scored by 2 independent BE expert endoscopists). Outcomes were BE surface regression; 14-day cumulative scores (area under the curves [AUCs]) for pain, dysphagia, analgesics, and peak pain. RESULTS We identified 46 patients (20 CRYO, 26 RFA) with similar baseline characteristics. The BE regression was comparable (88% vs 90%, P = .62). AUCs for pain, dysphagia, and analgesics were significantly smaller after CRYO versus RFA (all P < .01). Peak pain was lower after CRYO (visual analog scale 2 vs 4, P < .01), and the duration of pain was also shorter after CRYO (2 vs 4 days, P < .01). CRYO patients used analgesics for 2 days versus 4 days for RFA (P < .01). CONCLUSIONS In this multicenter, nonrandomized cohort study, we found no differences in efficacy after a single treatment with CRYO and RFA for short-segment BE. Patients reported less pain after CRYO as compared with RFA. Moreover, CRYO patients used fewer analgesics. Our results suggest a different pain course favoring CRYO over RFA, but a randomized trial is needed for definitive conclusions. (Clinical trial registration number: NCT02249975.).
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Affiliation(s)
- Sanne N van Munster
- Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, the Netherlands; Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - Anouk Overwater
- Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, the Netherlands; Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Rehan Haidry
- Department of Gastroenterology, University College London Hospital, London, United Kingdom
| | - Raf Bisschops
- Department Of Gastroenterology, University Hospital Leuven, Leuven, Belgium
| | - Jacques J G H M Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - Bas L A M Weusten
- Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, the Netherlands; Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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Bar N, Schwartz N, Nissim M, Fliss-Isacov N, Zelber-Sagi S, Kariv R. Barrett’s esophagus with high grade dysplasia is associated with non-esophageal cancer. World J Gastroenterol 2018; 24:4472-4481. [PMID: 30356981 PMCID: PMC6196339 DOI: 10.3748/wjg.v24.i39.4472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 09/03/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To study factors associated with esophageal and non-esophageal cancer morbidity among Barrett’s esophagus (BE) patients.
METHODS A cohort study within a single tertiary center included 386 consecutive patients with biopsy proven BE, who were recruited between 2004-2014. Endoscopic and histologic data were prospectively recorded. Cancer morbidity was obtained from the national cancer registry. Main outcomes were BE related (defined as esophagus and cardia) and non-BE related cancers (all other cancers). Cancer incidence and all-cause mortality were compared between patients with high-grade dysplasia (HGD) and with low-grade or no dysplasia (non-HGD) using Kaplan-Meier curves and cox regression models.
RESULTS Of the 386 patients, 12 had HGD, 7 had a BE related cancer. There were 75 (19.4%) patients with 86 cases of lifetime cancers, 76 of these cases were non-BE cancers. Seven (1.8%) and 18 (4.7%) patients had BE and non-BE incident cancers, respectively. Twelve (3.1%) patients had HGD as worst histologic result. Two (16.7%) and 16 (4.4%) incident non-BE cancers occurred in the HGD and non-HGD group, respectively. Ten-year any cancer and non-BE cancer free survival was 63% and 82% in the HGD group compared to 93% and 95% at the non-HGD group, respectively. Log-rank test for patients with more than one endoscopy, assuring longer follow up, showed a significant difference (P < 0.001 and P = 0.017 respectively). All-cause mortality was not significantly associated with BE HGD.
CONCLUSION Patients with BE and HGD, may have a higher risk for all-cause cancer morbidity. The implications on cancer prevention recommendations should be further studied.
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Affiliation(s)
- Nir Bar
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Naama Schwartz
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Michal Nissim
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Naomi Fliss-Isacov
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Shira Zelber-Sagi
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- School for Public Health, University of Haifa, Haifa 31905, Israel
| | - Revital Kariv
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
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Chilukuri P, Gromski MA, Johnson CS, Ceppa DKP, Kesler KA, Birdas TJ, Rieger KM, Fatima H, Kessler WR, Rex DK, Al-Haddad M, DeWitt JM. Impact of the development of an endoscopic eradication program for Barrett's esophagus with high grade dysplasia or early adenocarcinoma on the frequency of surgery. Endosc Int Open 2018; 6:E1085-E1092. [PMID: 30211296 PMCID: PMC6133650 DOI: 10.1055/a-0640-3030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 03/12/2018] [Indexed: 11/20/2022] Open
Abstract
Background and aims The impact of the advent of an institutional endoscopic eradication therapy (EET) program on surgical practice for Barrett's esophagus (BE)-associated high grade dysplasia (HGD) or suspected T1a esophageal adenocarcinoma (EAC) is unknown. The aims of this study are to evaluate the different endoscopic modalities used during development of our EET program and factors associated with the use of EET or surgery for these patients after its development. Methods Patients who underwent primary endoscopic or surgical treatment for BE-HGD or early EAC at our hospital between January 1992 and December 2014 were retrospectively identified. They were categorized by their initial modality of treatment during the first year, and the impact over time for choice of therapy was assessed by multivariable logistic regression. Results We identified 386 patients and 80 patients who underwent EET and surgery, respectively. EET included single modality therapy in 254 (66 %) patients and multimodal therapy in 132 (34 %) patients. Multivariable logistic regression showed that, for each subsequent study year, EET was more likely to be performed in patients who were older ( P = 0.0009), with shorter BE lengths ( P < 0.0001), and with a pretreatment diagnosis of HGD ( P = 0.0054) compared to surgical patients. The diagnosis of EAC did not increase the utilization of EET compared to surgery as time progressed ( P = 0.8165). Conclusion The introduction of an EET program at our hospital increased the odds of utilizing EET versus surgery over time for initial treatment of patients who were older, had shorter BE lengths or the diagnosis of BE-HGD, but not in patients with EAC.
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Affiliation(s)
- Prianka Chilukuri
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark A. Gromski
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | | | - Duy Khanh P. Ceppa
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Kenneth A. Kesler
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Thomas J. Birdas
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Karen M. Rieger
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Hala Fatima
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - William R. Kessler
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Douglas K. Rex
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mohammad Al-Haddad
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - John M. DeWitt
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA,Corresponding author John M. DeWitt, MD Indiana University School of Medicine550 University BlvdSuite 4100IndianapolisIN 46202-5250USA+1-317-948-8144
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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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Abstract
The incidence of esophageal adenocarcinoma (EAC) and its precursor lesion Barrett's esophagus (BE) has been increasing steadily in the western world in recent decades. Understanding the cellular origins of BE and the conditions responsible for their malignant transformation would greatly facilitate risk assessment and identification of patients at risk of progression, but this topic remains a source of debate. Here, we review recent findings that have provided support for the gastroesophageal junction (GEJ) as the main source of stem cells that give rise to BE and EAC. These include both gastric cardia cells and transitional basal cells. Furthermore, we discuss the role of chronic injury and inflammation in a tumor microenvironment as a major factor in promoting stem cell expansion and proliferation as well as transformation of the GEJ-derived stem cells and progression to EAC. We conclude that there exists a large amount of empirical support for the GEJ as the likely source of BE stem cells. While BE seems to resemble a successful adaptation to esophageal damage, carcinogenesis appears as a consequence of natural selection at the level of GEJ stem cells, and later glands, that expand into the esophagus wherein the local ecology creates the selective landscape for cancer progression.
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Pouw RE, Künzli HT, Bisschops R, Sondermeijer CM, Koch AD, Didden P, Gotink AW, Schoon EJ, Curvers WL, Bergman JJGHM, Weusten BLAM. Simplified versus standard regimen for focal radiofrequency ablation of dysplastic Barrett's oesophagus: a multicentre randomised controlled trial. Lancet Gastroenterol Hepatol 2018; 3:566-574. [PMID: 29934224 DOI: 10.1016/s2468-1253(18)30157-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 04/19/2018] [Accepted: 04/23/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND For focal radiofrequency ablation of Barrett's oesophagus, a simplified regimen (3 × 15 J/cm2, without cleaning) has proven to be as effective as the standard regimen (2 × 15 J/cm2, followed by cleaning, followed by 2 × 15 J/cm2). However, this simplified regimen seemed to be associated with a higher stenosis rate. Therefore, we lowered the radiofrequency energy and hypothesised that this new simplified regimen would be as effective and safe as the standard regimen. METHODS This randomised non-inferiority trial included patients with dysplastic Barrett's oesophagus or residual Barrett's oesophagus after endoscopic resection or circumferential radiofrequency ablation, in five European tertiary referral centres. Patients were randomly assigned (1:1) to the new simplified regimen (3 × 12 J/cm2, without cleaning) or the standard regimen, with variable block sizes of four, six, and eight patients, stratified by participating hospital. Focal radiofrequency ablation was done every 3 months, up to a maximum of three treatments, until all Barrett's oesophagus was eradicated. The primary outcome was complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments, assessed in the intention-to-treat population. Non-inferiority was assessed on the basis of the difference between groups in the median percentage of Barrett's oesophagus surface regression, with a non-inferiority margin of -15%. This study is registered with www.trialregister.nl, number NTR4994, and is completed. FINDINGS Between March 25, 2015, and July 25, 2016, 84 patients were randomly assigned to treatment: 44 to receive the simplified regimen and 40 to receive the standard regimen. One patient assigned to the simplified regimen and four assigned to the standard regimen were excluded because they weree found not to be eligible; therefore the final intention-to-treat population consisted of 43 patients in the simplified ablation group and 36 in the standard ablation group. Complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments was achieved in 32 (74%, 95% CI 59-87) patients treated with the simplified protocol, versus 30 (83%, 95% CI 67-94) patients treated with the standard protocol (p=0·34). Median Barrett's oesophagus surface regression after two focal radiofrequency ablation sessions was 98% (IQR 95-100) in the simplified regimen group and 100% (97-100) in the standard regimen group. The difference between medians was 2% (95% CI -0·562 to 3·162); thus the simplified regimen was deemed non-inferior to the standard regimen. Stenoses requiring dilatation were observed in four (9%) of 43 patients in the simplified regimen group and four (11%) of 36 in the standard regimen group. Post-procedural bleeding requiring repeat endoscopy occurred in one (2%) patient in the simplified ablation group and three (8%) patients in the standard ablation group. One patient (2%) in the simplified treatment group died 36 days after the second radiofrequency ablation procedure, due to an unknown cause. INTERPRETATION Based on the results of this study, we conclude that the simplified regimen is the preferred regimen for focal radiofrequency ablation of Barrett's oesophagus. FUNDING None.
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Affiliation(s)
- Roos E Pouw
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands
| | - Hannah T Künzli
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands; Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands
| | - Raf Bisschops
- Department of Gastroenterology and Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Carine M Sondermeijer
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands
| | - Arjun D Koch
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Paul Didden
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Anniek W Gotink
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Erik J Schoon
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, Netherlands
| | - Wouter L Curvers
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, Netherlands
| | - Jacques J G H M Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands
| | - Bas L A M Weusten
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands; Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands.
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Bourke MJ, Neuhaus H, Bergman JJ. Endoscopic Submucosal Dissection: Indications and Application in Western Endoscopy Practice. Gastroenterology 2018; 154:1887-1900.e5. [PMID: 29486200 DOI: 10.1053/j.gastro.2018.01.068] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 01/11/2018] [Accepted: 01/11/2018] [Indexed: 12/11/2022]
Abstract
Endoscopic submucosal dissection was developed in Japan, early in this century, to provide a minimally invasive yet curative treatment for the large numbers of patients with early gastric cancer identified by the national screening program. Previously, the majority of these patients were treated surgically at substantial cost and with significant risk of short- and long-term morbidity. En-bloc excision of these early cancers, most with a limited risk of nodal metastasis, allowed complete staging of the tumor, stratification of the subsequent therapeutic approach, and potential cure. This transformative innovation changed the nature of endoscopic treatment for superficial mucosal neoplasia and, ultimately, for the first time allowed endoscopists to assert that the early cancer had been definitively cured. Subsequently, Western endoscopists have increasingly embraced the therapeutic possibilities offered by endoscopic submucosal dissection, but with some justifiable scientific caution. Here we provide an evidence-based critical appraisal of the role of endoscopic submucosal dissection in advanced endoscopic tissue resection.
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Affiliation(s)
- Michael J Bourke
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, New South Wales, Australia; Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia.
| | - Horst Neuhaus
- Department of Internal Medicine, Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Germany
| | - Jacques J Bergman
- Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, Netherlands
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40
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Belghazi K, Pouw RE, Sondermeijer C, Meijer SL, Schoon EJ, Koch AD, Weusten B, Bergman J. A single-step sizing and radiofrequency ablation catheter for circumferential ablation of Barrett's esophagus: Results of a pilot study. United European Gastroenterol J 2018; 6:990-999. [PMID: 30228886 PMCID: PMC6137598 DOI: 10.1177/2050640618768919] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 02/26/2018] [Indexed: 11/21/2022] Open
Abstract
Background The 360 Express balloon catheter (360 Express) has the ability to self-adjust to the esophageal lumen, ensuring optimal tissue contact. Objective The objective of this article is to evaluate the efficacy and safety of the 360 Express for radiofrequency ablation (RFA) treatment of Barrett's esophagus (BE). Methods BE patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD) or early cancer (EC) were included. Visible lesions were removed by endoscopic resection (ER) prior to RFA. RFA was performed with the 360 Express using the standard ablation regimen (12J/cm2–clean–12J/cm2). Primary outcome: BE regression percentage at three months. Secondary outcomes: procedure time, adverse events, complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM). Results Thirty patients (median BE C4M6) were included. Eight patients underwent ER prior to RFA. Median BE regression: 90%. Median procedure time: 31 minutes. Adverse events (13%): laceration (n = 1); atrial fibrillation (n = 1); vomiting and dysphagia (n = 1); dysregulated diabetes (n = 1). After subsequent treatment CE-D and CE-IM was achieved in 97% and 87%, respectively. In 10% a stenosis developed during additional treatment requiring a median of one dilation. Conclusion This study shows that circumferential RFA using the 360 Express may shorten procedure time, while maintaining efficacy compared to standard circumferential RFA.
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Affiliation(s)
- K Belghazi
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - R E Pouw
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - Cmt Sondermeijer
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - S L Meijer
- Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands
| | - E J Schoon
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands
| | - A D Koch
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Blam Weusten
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Jjghm Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
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Costamagna G, Battaglia G, Repici A, Fiocca R, Rugge M, Spada C, Villanacci V. Diagnosis and Endoscopic Management of Barrett's Esophagus: an Italian Experts' Opinion based document. Dig Liver Dis 2017; 49:1306-1313. [PMID: 28969923 DOI: 10.1016/j.dld.2017.08.034] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 08/14/2017] [Accepted: 08/15/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Barrett's esophagus (BE) is recognized as a risk factor for esophageal adenocarcinoma. An expert panel was organized in Italy with the aim of drafting a series of statements on BE to guide diagnosis and management of patients with BE. METHODS The working Group Coordinators worked on a literature search to identify key topics regarding critical steps of the endoscopic approach to BE. Based on the search and their expert opinion, a list of most meaningful questions was prepared and emailed to all members who were asked to vote the questions. When the survey was completed a consensus meeting was organized. According to the survey results, Group Coordinators proposed a draft statement that was voted. By definition, the statement was formulated when there was an agreement of ≥50% among participants. RESULTS Twenty nine participants deliberated 18 questions. The agreement was reached for 16 questions for which a recommendation was formulated. CONCLUSION The generated statements highlight the Italian contribution to the European Position Statement of the European Society of Gastrointestinal Endoscopy. The Italian statements preserve peculiarities when dealing with the endoscopic management of BE and wishes to be considered as a contribution for the care of BE patients even with a low risk of progression to esophageal neoplasia.
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Affiliation(s)
- Guido Costamagna
- Digestive Endoscopy Unit, Catholic University, Rome, Italy; IHU, Strasbourg, USIAS, University of Strasbourg, France.
| | - Giorgio Battaglia
- Digestive Endoscopy Unit, Veneto Institute of Oncology, Padova, Italy
| | - Alessandro Repici
- Department of Gastroenterology Istituto Clinico Humanitas, Milan, Italy
| | - Roberto Fiocca
- Department of Surgical and Morphological Sciences, Anatomic Pathology Division, University of Genoa and IRCCS San Martino/IST, Genoa, Italy
| | - Massimo Rugge
- Department of Medicine, DIMED, Pathology Unit, University of Padova, Padova, Italy
| | - Cristiano Spada
- Digestive Endoscopy Unit, Catholic University, Rome, Italy; Digestive Endoscopy Unit, Fondazione Poliambulanza, Brescia, Italy
| | - Vincenzo Villanacci
- Pathology Section, Department of Molecular and Translational Medicine, Spedali Civili and University of Brescia, Brescia, Italy
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Wani S, Muthusamy VR, Shaheen NJ, Yadlapati R, Wilson R, Abrams JA, Bergman J, Chak A, Chang K, Das A, Dumot J, Edmundowicz SA, Eisen G, Falk GW, Fennerty MB, Gerson L, Ginsberg GG, Grande D, Hall M, Harnke B, Inadomi J, Jankowski J, Lightdale CJ, Makker J, Odze RD, Pech O, Sampliner RE, Spechler S, Triadafilopoulos G, Wallace MB, Wang K, Waxman I, Komanduri S. Development of Quality Indicators for Endoscopic Eradication Therapies in Barrett's Esophagus: The TREAT-BE (Treatment With Resection and Endoscopic Ablation Techniques for Barrett's Esophagus) Consortium. Am J Gastroenterol 2017; 112:1032-1048. [PMID: 28570552 DOI: 10.1038/ajg.2017.166] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Sachin Wani
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | - V Raman Muthusamy
- University of California in Los Angeles, Los Angeles, California, USA
| | | | | | - Robert Wilson
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | | | | | | | - Kenneth Chang
- University of California in Irvine, Irvine, California, USA
| | - Ananya Das
- Arizona Center for Digestive Health, Gilbert, Arizona, USA
| | - John Dumot
- University Hospitals, Cleveland, Ohio, USA
| | | | | | - Gary W Falk
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | | | - Lauren Gerson
- California Pacific Medical Center, San Francisco, California, USA
| | - Gregory G Ginsberg
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | | | - Matt Hall
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | - Ben Harnke
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | - John Inadomi
- University of Washington, Seattle, Washington, USA
| | | | | | - Jitin Makker
- University of California in Los Angeles, Los Angeles, California, USA
| | - Robert D Odze
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Oliver Pech
- St. John of God Hospital, Regensburg, Germany
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Wani S, Muthusamy VR, Shaheen NJ, Yadlapati R, Wilson R, Abrams JA, Bergman J, Chak A, Chang K, Das A, Dumot J, Edmundowicz SA, Eisen G, Falk GW, Fennerty MB, Gerson L, Ginsberg GG, Grande D, Hall M, Harnke B, Inadomi J, Jankowski J, Lightdale CJ, Makker J, Odze RD, Pech O, Sampliner RE, Spechler S, Triadafilopoulos G, Wallace MB, Wang K, Waxman I, Komanduri S. Development of quality indicators for endoscopic eradication therapies in Barrett's esophagus: the TREAT-BE (Treatment with Resection and Endoscopic Ablation Techniques for Barrett's Esophagus) Consortium. Gastrointest Endosc 2017; 86:1-17.e3. [PMID: 28576294 DOI: 10.1016/j.gie.2017.03.010] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 03/06/2017] [Indexed: 12/11/2022]
Affiliation(s)
- Sachin Wani
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA.
| | - V Raman Muthusamy
- University of California in Los Angeles, Los Angeles, California, USA
| | | | | | - Robert Wilson
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | | | | | | | - Kenneth Chang
- University of California in Irvine, Irvine, California, USA
| | - Ananya Das
- Arizona Center for Digestive Health, Gilbert, Arizona, USA
| | - John Dumot
- University Hospitals, Cleveland, Ohio, USA
| | | | | | - Gary W Falk
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | | | - Lauren Gerson
- California Pacific Medical Center, San Francisco, California, USA
| | - Gregory G Ginsberg
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | | | - Matt Hall
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | - Ben Harnke
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | - John Inadomi
- University of Washington, Seattle, Washington, USA
| | | | | | - Jitin Makker
- University of California in Los Angeles, Los Angeles, California, USA
| | - Robert D Odze
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Oliver Pech
- St. John of God Hospital, Regensburg, Germany
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Visrodia K, Zakko L, Wang KK. Radiofrequency Ablation of Barrett's Esophagus: Efficacy, Complications, and Durability. Gastrointest Endosc Clin N Am 2017; 27:491-501. [PMID: 28577770 DOI: 10.1016/j.giec.2017.03.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
In the last decade, radiofrequency ablation in combination with endoscopic mucosal resection has simplified and improved the treatment of Barrett's esophagus. These treatments not only reduced the progression of dysplastic Barrett's esophagus to esophageal adenocarcinoma but also decreased treatment-related complications. More recent data from larger series with extended follow-up periods are emerging to refine expectations in patients treated with radiofrequency ablation. Although most patients achieve eradication of neoplasia and intestinal metaplasia, in the long-term a substantial portion of patients develop recurrent disease. This article provides an updated review of radiofrequency ablation efficacy, complications, and durability.
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Affiliation(s)
- Kavel Visrodia
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, 200 First Avenue, Southwest, Rochester, MN 55905, USA
| | - Liam Zakko
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, 200 First Avenue, Southwest, Rochester, MN 55905, USA
| | - Kenneth K Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, 200 First Avenue, Southwest, Rochester, MN 55905, USA.
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45
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Phoa KN, Rosmolen WD, Weusten BLAM, Bisschops R, Schoon EJ, Das S, Ragunath K, Fullarton G, DiPietro M, Ravi N, Tijssen JGP, Dijkgraaf MGW, Bergman JJGHM. The cost-effectiveness of radiofrequency ablation for Barrett's esophagus with low-grade dysplasia: results from a randomized controlled trial (SURF trial). Gastrointest Endosc 2017; 86:120-129.e2. [PMID: 27956164 DOI: 10.1016/j.gie.2016.12.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 12/01/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS The Surveillance versus Radiofrequency Ablation (SURF) trial randomized 136 patients with Barrett's esophagus (BE) containing low-grade dysplasia (LGD), to receive radiofrequency ablation (ablation, n = 68) or endoscopic surveillance (control, n = 68). Ablation reduced the risk of neoplastic progression to high-grade dysplasia and esophageal adenocarcinoma (EAC) by 25% over 3 years (1.5% for ablation vs 26.5% for control). We performed a cost-effectiveness analysis from a provider perspective alongside this trial. METHODS Patients were followed for 3 years to quantify their use of health care services, including therapeutic and surveillance endoscopies, treatment of adverse events, and medication. Costs for treatment of progression were analyzed separately. Incremental cost-effectiveness ratios (ICER) were calculated by dividing the difference in costs (excluding and including the downstream costs for treatment of progression) by the difference in prevented events of progression. Bootstrap analysis (1000 samples) was used to construct 95% confidence intervals (CIs). RESULTS Patients who underwent ablation generated mean costs of U.S.$13,503 during the trial versus $2236 for controls (difference $11,267; 95% CI, $9996-$12,378), with an ICER per prevented event of progression of $45,066. Including the costs for treatment of progression, ablation patients generated mean costs of $13,523 versus $4,930 for controls (difference $8593; 95% CI, $6881-$10,153) with an ICER of $34,373. Based on the various ICER estimates derived from the bootstrap analysis, one can be reasonably certain (>75%) that ablation is efficient at a willingness to pay of $51,664 per prevented event of progression or $40,915 including downstream costs of progression. CONCLUSIONS Ablation for patients with confirmed BE-LGD is more effective and more expensive than endoscopic surveillance in reducing the risk of progression to high-grade dysplasia/EAC. The increase in costs of ablation can be justified to avoid a serious event such as neoplastic progression. At a willingness to pay of $40,915 per prevented event of progression, one can be reasonably certain that ablation is efficient. (www.trialregister.nl number: NTR 1198.).
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Affiliation(s)
- K Nadine Phoa
- Department of Gastroenterology, Academic Medical Centre-University of Amsterdam, Amsterdam, the Netherlands
| | - Wilda D Rosmolen
- Department of Gastroenterology, Academic Medical Centre-University of Amsterdam, Amsterdam, the Netherlands
| | - Bas L A M Weusten
- Department of Gastroenterology, Academic Medical Centre-University of Amsterdam, Amsterdam, the Netherlands; Department of Gastroenterology, St Antonius Hospital, Nieuwegein, the Netherlands
| | - Raf Bisschops
- Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium
| | - Erik J Schoon
- Department of Gastroenterology, Catharina Hospital, Eindhoven, the Netherlands
| | - Shefali Das
- Department of Gastroenterology, Academic Medical Centre-University of Amsterdam, Amsterdam, the Netherlands
| | - Krish Ragunath
- Department of Gastroenterology, Queens Medical Centre, Nottingham, United Kingdom
| | - G Fullarton
- Department of Surgical Gastroenterology, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Massimiliano DiPietro
- Medical Research Council, Cancer Unit, Addenbrookes Hospital, Cambridge, United Kingdom
| | - Narayanasamy Ravi
- Department of Clinical Medicine & Gastroenterology, St James's Hospital, Dublin, Ireland
| | - Jan G P Tijssen
- Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
| | - Marcel G W Dijkgraaf
- Clinical Research Unit, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
| | - Jacques J G H M Bergman
- Department of Gastroenterology, Academic Medical Centre-University of Amsterdam, Amsterdam, the Netherlands
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Lee HC, Ahsen OO, Liu JJ, Tsai TH, Huang Q, Mashimo H, Fujimoto JG. Assessment of the radiofrequency ablation dynamics of esophageal tissue with optical coherence tomography. JOURNAL OF BIOMEDICAL OPTICS 2017; 22:76001. [PMID: 28687822 PMCID: PMC5499807 DOI: 10.1117/1.jbo.22.7.076001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 06/08/2017] [Indexed: 05/08/2023]
Abstract
Radiofrequency ablation (RFA) is widely used for the eradication of dysplasia and the treatment of early stage esophageal carcinoma in patients with Barrett’s esophagus (BE). However, there are several factors, such as variation of BE epithelium (EP) thickness among individual patients and varying RFA catheter-tissue contact, which may compromise RFA efficacy. We used a high-speed optical coherence tomography (OCT) system to identify and monitor changes in the esophageal tissue architecture from RFA. Two different OCT imaging/RFA application protocols were performed using an <italic<ex vivo</italic< swine esophagus model: (1) post-RFA volumetric OCT imaging for quantitative analysis of the coagulum formation using RFA applications with different energy settings, and (2) M-mode OCT imaging for monitoring the dynamics of tissue architectural changes in real time during RFA application. Post-RFA volumetric OCT measurements showed an increase in the coagulum thickness with respect to the increasing RFA energies. Using a subset of the specimens, OCT measurements of coagulum and coagulum + residual EP thickness were shown to agree with histology, which accounted for specimen shrinkage during histological processing. In addition, we demonstrated the feasibility of OCT for real-time visualization of the architectural changes during RFA application with different energy settings. Results suggest feasibility of using OCT for RFA treatment planning and guidance.
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Affiliation(s)
- Hsiang-Chieh Lee
- Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Cambridge, Massachusetts, United States
| | - Osman O. Ahsen
- Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Cambridge, Massachusetts, United States
| | - Jonathan J. Liu
- Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Cambridge, Massachusetts, United States
| | - Tsung-Han Tsai
- Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Cambridge, Massachusetts, United States
| | - Qin Huang
- Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States
- Harvard Medical School, Boston, Massachusetts, United States
| | - Hiroshi Mashimo
- Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States
- Harvard Medical School, Boston, Massachusetts, United States
| | - James G. Fujimoto
- Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Cambridge, Massachusetts, United States
- Address all correspondence to: James G. Fujimoto, E-mail:
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47
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Terheggen G, Horn EM, Vieth M, Gabbert H, Enderle M, Neugebauer A, Schumacher B, Neuhaus H. A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett's neoplasia. Gut 2017; 66:783-793. [PMID: 26801885 PMCID: PMC5531224 DOI: 10.1136/gutjnl-2015-310126] [Citation(s) in RCA: 159] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 12/06/2015] [Accepted: 12/23/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND For endoscopic resection of early GI neoplasia, endoscopic submucosal dissection (ESD) achieves higher rates of complete resection (R0) than endoscopic mucosal resection (EMR). However, ESD is technically more difficult and evidence from randomised trial is missing. OBJECTIVE We compared the efficacy and safety of ESD and EMR in patients with neoplastic Barrett's oesophagus (BO). DESIGN BO patients with a focal lesion of high-grade intraepithelial neoplasia (HGIN) or early adenocarcinoma (EAC) ≤3 cm were randomised to either ESD or EMR. Primary outcome was R0 resection; secondary outcomes were complete remission from neoplasia, recurrences and adverse events (AEs). RESULTS There were no significant differences in patient and lesion characteristics between the groups randomised to ESD (n=20) or EMR (n=20). Histology of the resected specimen showed HGIN or EAC in all but six cases. Although R0 resection defined as margins free of HGIN/EAC was achieved more frequently with ESD (10/17 vs 2/17, p=0.01), there was no difference in complete remission from neoplasia at 3 months (ESD 15/16 vs EMR 16/17, p=1.0). During a mean follow-up period of 23.1±6.4 months, recurrent EAC was observed in one case in the ESD group. Elective surgery was performed in four and three cases after ESD and EMR, respectively (p=1.0). Two severe AEs were recorded for ESD and none for EMR (p=0.49). CONCLUSIONS In terms of need for surgery, neoplasia remission and recurrence, ESD and EMR are both highly effective for endoscopic resection of early BO neoplasia. ESD achieves a higher R0 resection rate, but for most BO patients this bears little clinical relevance. ESD is, however, more time consuming and may cause severe AE. TRIAL REGISTRATION NUMBER NCT1871636.
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Affiliation(s)
- Grischa Terheggen
- GastroPraxis Köln-Nord, Schwerpunktpraxis für Gastroenterologie und Hepatologie Köln, Cologne, Germany
| | - Eva Maria Horn
- Department of Gastroenterology, Evangelisches Krankenhaus Düsseldorf, Düssseldorf, Germany
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | - Helmut Gabbert
- Institute of Pathology, University of Düsseldorf, Düssseldorf, Germany
| | | | | | - Brigitte Schumacher
- Klinik für Innere Medizin und Gastroenterologie, Elisabeth Krankenhaus Essen, Essen, Germany
| | - Horst Neuhaus
- Department of Gastroenterology, Evangelisches Krankenhaus Düsseldorf, Düssseldorf, Germany
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48
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Han S, Wani S. Quality Indicators in Endoscopic Ablation for Barrett's Esophagus. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2017; 15:241-255. [PMID: 28421454 DOI: 10.1007/s11938-017-0136-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OPINION STATEMENT Barrett's esophagus (BE) is a well-established premalignant condition for esophageal adenocarcinoma (EAC); a cancer that is associated with a poor 5-year survival rate. Several strategies have been explored in the context of reducing the burden of EAC. Endoscopic eradication therapy (EET) is considered the standard of care for the management of patients with BE with dysplasia and early neoplasia; a practice that has been endorsed by all gastroenterology societal guidelines. The effectiveness of EET has been demonstrated in multiple studies and contemporary management includes a combination of endoscopic mucosal resection (EMR) of all visible lesions followed by eradication of the remaining BE using ablative techniques of which radiofrequency ablation (RFA) has the best evidence supporting effectiveness and safety. These techniques are being used increasingly at academic tertiary care centers and community practices. In this era of value-based health care, there is increased focus on the establishment, documentation, and reporting of quality indicators; indicators that are important to physicians, patients, and payers. The purpose of this review is to highlight the current status of quality indicators in EET for the management of patients with BE-related neoplasia and discuss the future steps required to ensure that these quality indicators are uniformly incorporated into practice.
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Affiliation(s)
- Samuel Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, 1635 Aurora Court, Rm 2.031, Aurora, CO, 80045, USA
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, 1635 Aurora Court, Rm 2.031, Aurora, CO, 80045, USA.
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Komanduri S, Kahrilas PJ, Krishnan K, McGorisk T, Bidari K, Grande D, Keefer L, Pandolfino J. Recurrence of Barrett's Esophagus is Rare Following Endoscopic Eradication Therapy Coupled With Effective Reflux Control. Am J Gastroenterol 2017; 112:556-566. [PMID: 28195178 DOI: 10.1038/ajg.2017.13] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Accepted: 01/06/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Recent data suggest that effective control of gastroesophageal reflux improves outcomes associated with endoscopic eradication therapy (EET) for Barrett's esophagus (BE). However, the impact of reflux control on preventing recurrent intestinal metaplasia and/or dysplasia is unclear. The aims of the study were: (a) to determine the effectiveness and durability of EET under a structured reflux management protocol and (b) to determine the impact of optimizing anti-reflux therapy on achieving complete eradication of intestinal metaplasia (CE-IM). METHODS Consecutive BE patients referred for EET were enrolled and managed with a standardized reflux management protocol including twice-daily PPI therapy during eradication. Primary outcomes were rates of CE-IM and IM or dysplasia recurrence. RESULTS Out of 221 patients enrolled (46.0% with high-grade dysplasia/intramucosal carcinoma, 34.0% with low-grade dysplasia, and 20.0% with non-dysplastic BE) an overall CE-IM of 93% was achieved within 11.6±10.2 months. Forty-eight patients did not achieve CE-IM in 3 sessions. After modification of their reflux management, 45 (93.7%) achieved CE-IM in a mean of 1.1 RFA sessions. Recurrence occurred in 13 patients (IM in 10(4.8%), dysplasia in 3 (1.5%)) during a mean follow-up of 44±18.5 months. The only significant predictor of recurrence was the presence of a hiatal hernia. Recurrence of IM was significantly lower than historical controls (10.9 vs. 4.8%, P=0.04). CONCLUSIONS The current study highlights the importance of reflux control in patients with BE undergoing EET. In this setting, EET has long-term durability with low recurrence rates providing early evidence for extending endoscopic surveillance intervals after EET.
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Affiliation(s)
- Srinadh Komanduri
- Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Kumar Krishnan
- Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Tim McGorisk
- Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Kiran Bidari
- Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - David Grande
- Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Laurie Keefer
- Ichan School of Medicine at Mount Sinai, New York, New York, USA
| | - John Pandolfino
- Division of Gastroenterology and Hepatology, Department of Medicine and Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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50
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Desai M, Saligram S, Gupta N, Vennalaganti P, Bansal A, Choudhary A, Vennelaganti S, He J, Titi M, Maselli R, Qumseya B, Olyaee M, Waxman I, Repici A, Hassan C, Sharma P. Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett's esophagus-related neoplasia: a systematic review and pooled analysis. Gastrointest Endosc 2017; 85:482-495.e4. [PMID: 27670227 DOI: 10.1016/j.gie.2016.09.022] [Citation(s) in RCA: 109] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 09/12/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Focal EMR followed by radiofrequency ablation (f-EMR + RFA) and stepwise or complete EMR (s-EMR) are established strategies for eradication of Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC)/intramucosal carcinoma (IMC). The objective of this study was to derive pooled rates of efficacy and safety of individual methods in a large cohort of patients with BE and to indirectly compare the 2 methods. METHODS PubMed, Embase, Web of Science, Cochrane, and major conference proceedings were searched. A systematic review and pooled analysis were carried out to determine the following outcomes in patients with BE undergoing either f-EMR + RFA or s-EMR: (1) complete eradication rates of neoplasia (CE-N) and intestinal metaplasia (CE-IM); (2) recurrence rates of cancer (EAC), dysplasia, and IM; (3) incidence rates of adverse events. Mixed logistic regression was performed as an exploratory analysis to examine differences in outcomes between the 2 methods. RESULTS Nine studies (774 patients) of f-EMR + RFA and 11 studies (751 patients) of s-EMR were included. Patients undergoing f-EMR + RFA had high BE eradication rates (CE-N, 93.4%; CE-IM, 73.1%), whereas strictures occurred in 10.2%, bleeding in 1.1%, and perforations in 0.2% of patients. Recurrence of EAC, dysplasia, and IM was 1.4%, 2.6%, and 16.1%, respectively, in this group. Patients undergoing s-EMR also showed high BE eradication rates (CE-N, 94.9%; CE-IM, 79.6%) but a higher rate of adverse events (strictures in 33.5%, bleeding in 7.5%, and perforation in 1.3%). Recurrence of EAC, dysplasia, and IM was 0.7%, 3.3%, and 12.1%, respectively, in the s-EMR group. Mixed logistic regression showed that patients undergoing s-EMR might be more likely to develop esophageal strictures (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.61-13.85; P = .005), perforation (OR, 7.00; 95% CI, 1.56-31.33; P = .01), and bleeding (OR, 6.88; 95% CI, 2.19-21.62; P = 0.001) compared with f-EMR + RFA. CONCLUSIONS In patients with HGD/EAC, f-EMR followed by RFA seems to be equally effective as and safer than s-EMR.
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Affiliation(s)
- Madhav Desai
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Shreyas Saligram
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Neil Gupta
- Gastroenterology and Hepatology, Loyola University Medical Center, Chicago, Illinois, USA
| | - Prashanth Vennalaganti
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Ajay Bansal
- Department of Gastroenterology, Veteran Affairs Medical Center, Kansas City, Missouri, USA
| | - Abhishek Choudhary
- Department of Gastroenterology, Veteran Affairs Medical Center, Kansas City, Missouri, USA
| | - Sreekar Vennelaganti
- Department of Gastroenterology, Veteran Affairs Medical Center, Kansas City, Missouri, USA
| | - Jianghua He
- Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Mohammad Titi
- Department of Gastroenterology, Veteran Affairs Medical Center, Kansas City, Missouri, USA
| | - Roberta Maselli
- Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy
| | - Bashar Qumseya
- Division of Gastroenterology and Hepatology, Archbold Medical Group/Florida State University, Thomasville, Georgia, USA
| | - Mojtaba Olyaee
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Irwing Waxman
- Department of Gastroenterology and Hepatology, University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA
| | - Alessandro Repici
- Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy
| | - Cesare Hassan
- Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy
| | - Prateek Sharma
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA; Department of Gastroenterology, Veteran Affairs Medical Center, Kansas City, Missouri, USA
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