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1
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Tanisaka Y, Ryozawa S, Mizuide M, Fujita A, Jinushi R, Watanabe R, Sato R, Tashima T, Mashimo Y. Prospective assessment of probe-based confocal laser endomicroscopy under direct cholangioscopic visualization for biliary strictures that could not be definitively diagnosed using endoscopic retrograde cholangiopancreatography (with video). DEN OPEN 2025; 5:e70007. [PMID: 39328351 PMCID: PMC11424493 DOI: 10.1002/deo2.70007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 08/08/2024] [Accepted: 08/20/2024] [Indexed: 09/28/2024]
Abstract
The definitive diagnosis of patients with indeterminate biliary strictures remains challenging. Probe-based confocal laser endomicroscopy (pCLE) provides real-time histological assessment of bile duct tissues. Since no previous studies have evaluated the efficacy of pCLE under direct cholangioscopic visualization for biliary strictures that cannot be definitively diagnosed through endoscopic retrograde cholangiopancreatography using fluoroscopy, we prospectively assessed the feasibility and safety of this procedure in three cases. pCLE findings were obtained in three cases, providing accurate diagnoses. Additionally, no adverse event was reported. pCLE under direct cholangioscopic visualization for indeterminate biliary strictures might be feasible and safe, even though these strictures were not previously diagnosed using endoscopic retrograde cholangiopancreatography. Further studies with more cases are warranted to clarify the effectiveness of pCLE under direct cholangioscopic visualization.
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Affiliation(s)
- Yuki Tanisaka
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Shomei Ryozawa
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Masafumi Mizuide
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Akashi Fujita
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Ryuhei Jinushi
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Ryuichi Watanabe
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Ryo Sato
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Tomoaki Tashima
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Yumi Mashimo
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
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2
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Papaefthymiou A, Landi R, Arvanitakis M, Tringali A, Gkolfakis P. Endoscopic retrograde cholangiopancreatography: A comprehensive review as a single diagnostic tool. Best Pract Res Clin Gastroenterol 2025; 74:101976. [PMID: 40210330 DOI: 10.1016/j.bpg.2025.101976] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/17/2024] [Accepted: 12/18/2024] [Indexed: 04/12/2025]
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) was initially introduced in clinical practice as diagnostic tool. However, the presence of adverse events and the development of non-invasive techniques, such as magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS), limited its role as a stand-alone diagnostic choice, modifying its role to the leader of therapeutic pancreatobiliary endoscopy. Despite technological advances, there are still conditions where non-invasive diagnostic modalities are inconclusive, such as indeterminate biliary and pancreatic duct strictures, primary sclerosing cholangitis functional stenoses, intraductal papillary mucinous neoplasms (IPMNs) and paediatric indications, such as congenital anatomical abnormalities. This narrative review aimed to identify and analyse indications of diagnostic ERCP, without the need for therapeutic manipulations.
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Affiliation(s)
| | - Rosario Landi
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy; Università Cattolica del Sacro Cuore, Centre for Endoscopic Research Therapeutics and Training (CERTT), Rome, Italy
| | - Marianna Arvanitakis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, ULB, Brussels, Belgium
| | - Andrea Tringali
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy; Università Cattolica del Sacro Cuore, Centre for Endoscopic Research Therapeutics and Training (CERTT), Rome, Italy
| | - Paraskevas Gkolfakis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, ULB, Brussels, Belgium; Department of Gastroenterology, General Hospital of Nea Ionia "Konstantopoulio-Patision", Athens, Greece.
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3
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Impellizzeri G, Grassini MV, Donato G, De Angelis CG, Pagano N. An Approach to and Treatment of Indeterminate Biliary Strictures: A Comprehensive Review of the Literature. J Clin Med 2024; 14:29. [PMID: 39797112 PMCID: PMC11721181 DOI: 10.3390/jcm14010029] [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: 11/08/2024] [Revised: 12/02/2024] [Accepted: 12/18/2024] [Indexed: 01/13/2025] Open
Abstract
This review aims to focus on what we know about the management of biliary strictures of unknown etiology, especially exploring our diagnostic armamentarium in the setting of indeterminate biliary strictures. Presently, this is a current issue that has a relevant impact both on patient prognosis, often delaying diagnosis, and on overall costs associated with repeating diagnostic procedures, sometimes performed with very expensive devices. We also focus on current biliary drainage approaches, providing an overview of therapeutic options, endoscopic or not.
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Affiliation(s)
- Giovanna Impellizzeri
- Gastroenterology Unit, Department of Oncological and Specialty Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy; (G.I.); (C.G.D.A.)
| | - Maria Vittoria Grassini
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy;
| | - Giulio Donato
- Gastroenterology Unit, Department of Oncological and Specialty Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy; (G.I.); (C.G.D.A.)
| | - Claudio Giovanni De Angelis
- Gastroenterology Unit, Department of Oncological and Specialty Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy; (G.I.); (C.G.D.A.)
| | - Nico Pagano
- Gastroenterology Unit, Department of Oncological and Specialty Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy; (G.I.); (C.G.D.A.)
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4
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Rushbrook SM, Kendall TJ, Zen Y, Albazaz R, Manoharan P, Pereira SP, Sturgess R, Davidson BR, Malik HZ, Manas D, Heaton N, Prasad KR, Bridgewater J, Valle JW, Goody R, Hawkins M, Prentice W, Morement H, Walmsley M, Khan SA. British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma. Gut 2023; 73:16-46. [PMID: 37770126 PMCID: PMC10715509 DOI: 10.1136/gutjnl-2023-330029] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 09/05/2023] [Indexed: 10/03/2023]
Abstract
These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations.
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Affiliation(s)
- Simon M Rushbrook
- Department of Hepatology, Norfolk and Norwich University Hospitals NHS Trust, Norwich, UK
| | - Timothy James Kendall
- Division of Pathology, University of Edinburgh, Edinburgh, UK
- University of Edinburgh MRC Centre for Inflammation Research, Edinburgh, UK
| | - Yoh Zen
- Department of Pathology, King's College London, London, UK
| | - Raneem Albazaz
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | | | - Richard Sturgess
- Digestive Diseases Unit, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Brian R Davidson
- Department of Surgery, Royal Free Campus, UCL Medical School, London, UK
| | - Hassan Z Malik
- Department of Surgery, University Hospital Aintree, Liverpool, UK
| | - Derek Manas
- Department of Surgery, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
| | - Nigel Heaton
- Department of Hepatobiliary and Pancreatic Surgery, King's College London, London, UK
| | - K Raj Prasad
- John Goligher Colorectal Unit, St. James University Hospital, Leeds, UK
| | - John Bridgewater
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK
| | - Rebecca Goody
- Department of Oncology, St James's University Hospital, Leeds, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | - Wendy Prentice
- King's College Hospital NHS Foundation Trust, London, UK
| | | | | | - Shahid A Khan
- Hepatology and Gastroenterology Section, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Imperial College Healthcare NHS Trust, London, UK
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5
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Takao M, Kawaguchi Y, Matsumura M, Kazami Y, Tanimoto M, Abe S, Maki H, Ishizawa T, Arita J, Akamatsu N, Kaneko J, Kokudo N, Hasegawa K. Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens. Hum Cell 2023; 36:2066-2073. [PMID: 37610678 PMCID: PMC10587259 DOI: 10.1007/s13577-023-00965-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 07/26/2023] [Indexed: 08/24/2023]
Abstract
Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins. Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software. Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6-110) vs. 48.3 (39.0-59.4), p = 0.002] and with chemotherapy [67.9 (54.6-89.2) vs. 48.6 (28.8-82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies. In summary, our study demonstrated real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.
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Affiliation(s)
- Mikiya Takao
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yoshikuni Kawaguchi
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Masaru Matsumura
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yusuke Kazami
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Meguri Tanimoto
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Satoru Abe
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Harufumi Maki
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Takeaki Ishizawa
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Junichi Kaneko
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
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6
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Fujii-Lau LL, Thosani NC, Al-Haddad M, Acoba J, Wray CJ, Zvavanjanja R, Amateau SK, Buxbaum JL, Calderwood AH, Chalhoub JM, Coelho-Prabhu N, Desai M, Elhanafi SE, Fishman DS, Forbes N, Jamil LH, Jue TL, Kohli DR, Kwon RS, Law JK, Lee JK, Machicado JD, Marya NB, Pawa S, Ruan W, Sawhney MS, Sheth SG, Storm A, Thiruvengadam NR, Qumseya BJ. American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: summary and recommendations. Gastrointest Endosc 2023; 98:685-693. [PMID: 37307900 DOI: 10.1016/j.gie.2023.06.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 06/14/2023]
Abstract
This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for the diagnosis of malignancy in patients with biliary strictures of undetermined etiology. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses the role of fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS in the diagnosis of malignancy in patients with biliary strictures. In the endoscopic workup of these patients, we suggest the use of fluoroscopic-guided biopsy sampling in addition to brush cytology over brush cytology alone, especially for hilar strictures. We suggest the use of cholangioscopic and EUS-guided biopsy sampling especially for patients who undergo nondiagnostic sampling, cholangioscopic biopsy sampling for nondistal strictures and EUS-guided biopsy sampling distal strictures or those with suspected spread to surrounding lymph nodes and other structures.
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Affiliation(s)
| | | | - Mohammad Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Jared Acoba
- Department of Hematology and Medical Oncology, University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | | | - Rodrick Zvavanjanja
- Department of Diagnostic and Interventional Imaging, UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Stuart K Amateau
- Division of Gastroenterology Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - James L Buxbaum
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Audrey H Calderwood
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
| | - Jean M Chalhoub
- Department of Gastroenterology and Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA
| | | | - Madhav Desai
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - Sherif E Elhanafi
- Division of Gastroenterology, Texas Tech University Health Sciences Center, El Paso, Texas, USA
| | - Douglas S Fishman
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Nauzer Forbes
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Laith H Jamil
- Section of Gastroenterology and Hepatology, Beaumont Health, Royal Oak, and Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA
| | - Terry L Jue
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Divyanshoo R Kohli
- Pancreas and Liver Clinic, Providence Sacred Heart Medical Center, Spokane, Washington, USA
| | - Richard S Kwon
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Joanna K Law
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA
| | - Jeffrey K Lee
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA
| | - Jorge D Machicado
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Neil B Marya
- Division of Gastroenterology and Hepatology, UMass Chan Medical School, Worcester, Massachusetts, USA
| | - Swati Pawa
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Wenly Ruan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Mandeep S Sawhney
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Sunil G Sheth
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew Storm
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Nikhil R Thiruvengadam
- Division of Gastroenterology and Hepatology, Loma Linda University, Loma Linda, California, USA
| | - Bashar J Qumseya
- Department of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
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7
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Yadlapati S, Mulki R, Sánchez-Luna SA, Ahmed AM, Kyanam Kabir Baig KR, Peter S. Clinical approach to indeterminate biliary strictures: Clinical presentation, diagnosis, and workup. World J Gastroenterol 2023; 29:5198-5210. [PMID: 37901449 PMCID: PMC10600956 DOI: 10.3748/wjg.v29.i36.5198] [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: 04/25/2023] [Revised: 07/23/2023] [Accepted: 08/21/2023] [Indexed: 09/20/2023] Open
Abstract
Despite advances in cross-sectional imaging and endoscopic technology, bile duct strictures remain a challenging clinical entity. It is crucial to make an early determination of benign or malignant nature of biliary strictures. Early diagnosis not only helps with further management but also minimizes mortality and morbidity associated with delayed diagnosis. Conventional imaging and endoscopic techniques, particularly endoscopic retrograde cholangiopancreatography (ERCP) and tissue sampling techniques play a key in establishing a diagnosis. Indeterminate biliary strictures (IDBSs) have no definite mass on imaging or absolute histopathological diagnosis and often warrant utilization of multiple diagnostics to ascertain an etiology. In this review, we discuss possible etiologies, clinical presentation, diagnosis, and management of IDBSs. Based on available data and expert opinion, we depict an evidence based diagnostic algorithm for management of IDBSs. Areas of focus include use of traditional tissue sampling techniques such as ERCP with brush cytology, intraductal biopsies, fluorescence in situ hybridization and flow cytometry. We also describe the role of endoscopic ultrasound (EUS)-guided fine needle aspiration and biopsies, cholangioscopy, confocal laser endomicroscopy, and intraductal EUS in management of IDBSs.
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Affiliation(s)
- Sujani Yadlapati
- Department of Gastroenterology and Hepatology, Indiana University Hospital, Indianapolis, IN 46202, USA
| | - Ramzi Mulki
- Department of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Sergio A Sánchez-Luna
- Department of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Ali M Ahmed
- Department of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | | | - Shajan Peter
- Department of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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8
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Chaves J, Fernandez Y Viesca M, Arvanitakis M. Using Endoscopy in the Diagnosis of Pancreato-Biliary Cancers. Cancers (Basel) 2023; 15:3385. [PMID: 37444495 DOI: 10.3390/cancers15133385] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
Pancreatic cancer and cholangiocarcinoma are life threatening oncological conditions with poor prognosis and outcome. Pancreatic cystic lesions are considered precursors of pancreatic cancer as some of them have the potential to progress to malignancy. Therefore, accurate identification and classification of these lesions is important to prevent the development of invasive cancer. In the biliary tract, the accurate characterization of biliary strictures is essential for providing appropriate management and avoiding unnecessary surgery. Techniques have been developed to improve the diagnosis, risk stratification, and management of pancreato-biliary lesions. Endoscopic ultrasound (EUS) and associated techniques, such as elastography, contrasted-enhanced EUS, and EUS-guided needle confocal laser endomicroscopy, may improve diagnostic accuracy. In addition, intraductal techniques applied during endoscopic retrograde cholangiopancreatography (ERCP), such as new generation cholangioscopy and in vivo cellular evaluation through probe-based confocal laser endomicroscopy, can increase the diagnostic yield in characterizing indeterminate biliary strictures. Both EUS-guided and intraductal approaches can provide the possibility for tissue sampling with new tools, such as needles, biopsies forceps, and brushes. At the molecular level, novel biomarkers have been explored that provide new insights into diagnosis, risk stratification, and management of these lesions.
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Affiliation(s)
- Julia Chaves
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - Michael Fernandez Y Viesca
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - Marianna Arvanitakis
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
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9
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Cadamuro M, Al-Taee A, Gonda TA. Advanced endoscopy meets molecular diagnosis of cholangiocarcinoma. J Hepatol 2023; 78:1063-1072. [PMID: 36740048 DOI: 10.1016/j.jhep.2023.01.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 12/22/2022] [Accepted: 01/18/2023] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma remains an aggressive and deadly malignancy that is often diagnosed late. Intrinsic tumour characteristics and the growth pattern of cancer cells contribute to the challenges of diagnosis and chemoresistance. However, establishing an early and accurate diagnosis, and in some instances identifying targetable changes, has the potential to impact survival. Primary sclerosing cholangitis, a chronic cholangiopathy prodromal to the development of a minority of cholangiocarcinomas, poses a particular diagnostic challenge. We present our diagnostic and theranostic approach to the initial evaluation of cholangiocarcinomas, focusing on extrahepatic cholangiocarcinoma. This involves a multipronged strategy incorporating advanced imaging, endoscopic methods, multiple approaches to tissue sampling, and molecular markers. We also provide an algorithm for the sequential use of these tools.
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Affiliation(s)
| | - Ahmad Al-Taee
- Carle Illinois College of Medicine, University of Illinois Urbaba-Champaign, Champaign County, IL, USA
| | - Tamas A Gonda
- Division of Gastroenterology and Hepatology, New York University, New York, NY, USA.
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10
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Abstract
PURPOSE OF REVIEW To summarize the current status and future perspectives of the endoscopic management of biliary strictures. RECENT FINDINGS In addition to conventional diagnostic modalities, such as cross-sectional imaging and endoscopic ultrasonography (EUS), per-oral cholangioscopy is helpful for indeterminate biliary strictures. It allows direct visualization of the biliary tract and targeted biopsy. For distal malignant biliary obstruction (MBO), a self-expandable metal stent (SEMS) via endoscopic retrograde cholangiopancreatography (ERCP) is a standard of care. EUS-guided biliary drainage (EUS-BD) is an emerging alternative to percutaneous transhepatic biliary drainage in cases with failed ERCP. EUS-BD is also an effective salvage option for perihilar MBO, which can not be managed via ERCP or percutaneous transhepatic biliary drainage. Preoperative drainage is necessary for most jaundiced patients as neoadjuvant chemotherapy is widely administered for resectable and borderline resectable pancreatic cancer, and a SEMS is preferred in this setting, too. For benign biliary strictures, a covered SEMS can improve stricture resolution and reduce the number of endoscopic sessions as compared to plastic stents. SUMMARY ERCP and EUS play a central role in the diagnosis and drainage for both malignant and benign biliary strictures.
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11
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Endoscopic Evaluation and Management of Cholangiocarcinoma. Gastroenterol Clin North Am 2022; 51:519-535. [PMID: 36153108 DOI: 10.1016/j.gtc.2022.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Cholangiocarcinoma is a rare malignancy of the biliary tract with a relatively poor prognosis. As a gastroenterologist, our main role is to differentiate between benign and malignant biliary disease, help achieve a diagnosis, and palliate jaundice related to biliary obstruction. This article focuses on summarizing the various tools currently available for endoscopic evaluation and management of cholangiocarcinoma.
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12
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Kawashima H, Ohno E, Ishikawa T, Mizutani Y, Iida T, Yamamura T, Kakushima N, Furukawa K, Nakamura M. Endoscopic management of perihilar cholangiocarcinoma. Dig Endosc 2022; 34:1147-1156. [PMID: 35377509 DOI: 10.1111/den.14317] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/25/2022] [Accepted: 04/01/2022] [Indexed: 02/08/2023]
Abstract
Endoscopic management for perihilar cholangiocarcinoma (PHCC) is evolving toward more accurate diagnosis and safer drainage. In imaging, it is important to diagnose the entire lesion using multidetector-row computed tomography to determine resectability and optimal surgical planning, followed by local diagnosis using endoscopic retrograde cholangiopancreatography. Video peroral cholangioscopy and probe-based confocal laser endomicroscopy have been newly introduced as diagnostic imaging methods and are being applied clinically. In transpapillary forceps biopsy for PHCC diagnosis, the location in the bile duct (for mapping biopsy) and the number of biopsy samples should be determined depending on resectability, the morphological type, and future surgical planning. Preoperative drainage has shifted from percutaneous transhepatic biliary drainage to endoscopic nasobiliary drainage given the possibility of seeding metastasis. In addition, considering potential patient discomfort from a nasal tube, the usefulness of the placement of a plastic stent above the papilla (inside stent) as a bridging therapy for surgery has been reported. For drainage of unresectable PHCC, the improved prognosis due to advances in chemotherapy has necessitated a strategy that accounts for reintervention. Thus, in addition to uncovered self-expandable metallic stents (SEMS), exchangeable slim fully covered SEMS and inside stents have started to be used. In addition to the conventional transpapillary approach, an endoscopic ultrasonography-guided approach has been introduced, and a combination of both methods has also been proposed. To improve the quality of life and prognosis of PHCC patients, endoscopists need to understand and be able to use the various methods of endoscopic management for PHCC.
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Affiliation(s)
- Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Yasuyuki Mizutani
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Naomi Kakushima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
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13
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Schepis T, Boškoski I, Tringali A, Costamagna G. Role of ERCP in Benign Biliary Strictures. Gastrointest Endosc Clin N Am 2022; 32:455-475. [PMID: 35691691 DOI: 10.1016/j.giec.2022.01.006] [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
Benign biliary strictures (BBS) can be associated with several causes, with postoperative and inflammatory strictures representing the most common ones. Endoscopy represents nowadays the first-line treatment in the management of BBS. Endoscopic balloon dilatation, plastic stents placement, fully covered metal stent placement, and magnetic compression anastomosis are the endoscopic techniques available for the treatment of BBS. The aim of this study is to perform a review of the literature to assess the role of endoscopy in the management of BBS and to evaluate the application of the different procedures in the different clinical settings.
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Affiliation(s)
- Tommaso Schepis
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Ivo Boškoski
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica Del Sacro Cuore di Roma, Italy.
| | - Andrea Tringali
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica Del Sacro Cuore di Roma, Italy
| | - Guido Costamagna
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica Del Sacro Cuore di Roma, Italy
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14
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Abstract
Biliary strictures that remain unclassified after cross-sectional imaging and endoscopic retrograde cholangiopancreatography-based tissue sampling are defined as indeterminate biliary strictures (IDBS). A substantial proportion of biliary strictures fall into this category due to low sensitivity of brush cytology and intraductal biopsy. Over last few decades, several modalities have emerged for the evaluation of IDBS. Of these, cholangioscopy and endosonography are the frontrunners and have cemented their place for the evaluation of IDBS. Both of these modalities are widely available, and therefore, biliary strictures that remain uncharacterized after their utilization represent IDBS in the current era.
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Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology & AIG Hospitals, Mind Space Road, Gachibowli, Hyderabad 500 032 India
| | - D Nageshwar Reddy
- Asian Institute of Gastroenterology & AIG Hospitals, Mind Space Road, Gachibowli, Hyderabad 500 032 India.
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15
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Mi J, Han X, Wang R, Ma R, Zhao D. Diagnostic accuracy of probe-based confocal laser endomicroscopy and tissue sampling by endoscopic retrograde cholangiopancreatography in indeterminate biliary strictures: a meta‑analysis. Sci Rep 2022; 12:7257. [PMID: 35508585 PMCID: PMC9068817 DOI: 10.1038/s41598-022-11385-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 04/22/2022] [Indexed: 11/18/2022] Open
Abstract
Probe-based confocal laser endomicroscopy (pCLE), also known as optical biopsy, is a new endoscopic technique that provides real-time magnification of 1000 × microscopic tissue information to diagnose indeterminate biliary strictures. Tissue sampling by endoscopic retrograde cholangiopancreatography (ERCP) is routinely performed to evaluate indeterminate biliary strictures. To evaluate the accuracy of pCLE and tissue sampling by ERCP in the diagnosis of indeterminate biliary strictures, 18 articles were included from 2008 to 2021 through Embase, PubMed, Web of Science, and Cochrane library databases. The summary estimates for the pCLE diagnosis of indeterminate biliary strictures were: sensitivity 0.88 (95% confidence interval (CI), 0.84-0.91); specificity 0.79 (95% CI 0.74-0.83); and Diagnostic Odds Ratio (DOR) 24.63 (95% CI 15.76-38.48). The summary estimates for tissue sampling by ERCP diagnosis for indeterminate biliary strictures were: sensitivity 0.54 (95% CI 0.49-0.59); specificity 0.96 (95% CI 0.94-0.98); and DOR 11.31 (95% CI 3.90-32.82). The area under the sROC curve of pCLE diagnosis of indeterminate biliary strictures is 0.90 higher than 0.65 of tissue sampling by ERCP. The pCLE is a better approach than tissue sampling by ERCP for the diagnosis of indeterminate biliary strictures by providing real-time microscopic images of the bile ducts.
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Affiliation(s)
- Junjie Mi
- Digestive Endoscopy Center, Shanxi Provincial People's Hospital, No. 29, Shuang ta si Street, Taiyuan, China.
| | - Xiaofang Han
- Reproductive Medicine, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Rong Wang
- Digestive Endoscopy Center, Shanxi Provincial People's Hospital, No. 29, Shuang ta si Street, Taiyuan, China
| | - Ruijun Ma
- Digestive Endoscopy Center, Shanxi Provincial People's Hospital, No. 29, Shuang ta si Street, Taiyuan, China
| | - Danyu Zhao
- Digestive Endoscopy Center, Shanxi Provincial People's Hospital, No. 29, Shuang ta si Street, Taiyuan, China
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16
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Abstract
Despite advances in noninvasive techniques for imaging the pancreaticobiliary system, several disease processes including indeterminate biliary strictures as well as neuroendocrine tumors, inflammatory pseudotumors, and complex cysts of the pancreas remain difficult to characterize. New endoscopic imaging technologies have emerged to address these challenges. Cholangioscopy and intraductal ultrasound (IDUS) are powerful tools to characterize subtle biliary concretions and strictures. Confocal Laser Endomicroscopy (CLE) and Optical Coherence Tomography (OCT) are emerging approaches for the most difficult biliary lesions. Contrast harmonic endoscopic ultrasound (CH-EUS), elastography, and 3D-EUS are improving the approach to subtle pancreatic lesions, particularly in the context of indeterminate tissue sampling. Pancreatoscopy, pancreatic IDUS, and intracystic CLE hold promise to further improve the assessment of pancreatic cysts. We aim to comprehensively review the emerging clinical evidence for these innovative endoscopic imaging techniques.
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17
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Oleas R, Alcívar-Vasquez J, Robles-Medranda C. New technologies for indeterminate biliary strictures. Transl Gastroenterol Hepatol 2022; 7:22. [PMID: 35548472 PMCID: PMC9081913 DOI: 10.21037/tgh.2020.03.05] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 03/12/2020] [Indexed: 08/30/2023] Open
Abstract
An early and accurate diagnosis of biliary strictures yields optimal patient outcomes; however, endoscopic retrograde cholangiopancreatography (ERCP) with cytobrush/biopsy forceps has low sensitivity with a high number of false negatives. Various attempts to improve the accuracy of diagnosing indeterminate biliary strictures though ERCP-guided specimen acquisition have been proposed, such as with the use of fluorescence in situ hybridization, an endoscopic scraper, and the wire-grasping method, with modest to large improvements in sensitivity. Direct visualization of the biliary tree during peroral cholangioscopy has shown high sensitivity and specificity for the differentiation of neoplastic and non-neoplastic biliary lesions; however, there is no consensus on the visual characteristics of neoplastic lesions and moderate agreement between observers. Peroral cholangioscopy system (POCS)-guided specimen acquisition using forceps has shown inferior sensitivity compared to the visual characteristics; however, the specificity remains high. Optimal specimen processing with onsite evaluations and touch imprint cytology have been shown to improve the sensitivity and accurately diagnose nearly 90% of patients. In vivo evaluations of biliary strictures with probe-based confocal laser endomicroscopy have demonstrated high sensitivity with modest specificity for malignant biliary strictures. Optical computed tomography described reproductible criteria for malignancy detection in biliary strictures, increasing the sensitivity during ERCP evaluations. Differentiating benign causes from malignant causes of biliary strictures is a challenging task in clinical practice, with various concerns that still need to be addressed. Efforts should be made to define each diagnostic method's role in the evaluation of indeterminate biliary strictures.
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Affiliation(s)
- Roberto Oleas
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Juan Alcívar-Vasquez
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Carlos Robles-Medranda
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
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18
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Advanced Imaging Within the Bile Duct During Endoscopic Retrograde Cholangiopancreatography. Clin Gastroenterol Hepatol 2022; 20:737-739. [PMID: 34995501 DOI: 10.1016/j.cgh.2021.12.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/18/2021] [Accepted: 12/04/2021] [Indexed: 02/07/2023]
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19
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The development and clinical application of microscopic endoscopy for in vivo optical biopsies: Endocytoscopy and confocal laser endomicroscopy. Photodiagnosis Photodyn Ther 2022; 38:102826. [PMID: 35337998 DOI: 10.1016/j.pdpdt.2022.102826] [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] [Received: 02/19/2022] [Accepted: 03/21/2022] [Indexed: 12/20/2022]
Abstract
Endoscopies are crucial for detecting and diagnosing diseases in gastroenterology, pulmonology, urology, and other fields. To accurately diagnose diseases, sample biopsies are indispensable and are currently considered the gold standard. However, random 4-quadrant biopsies have sampling errors and time delays. To provide intraoperative real-time microscopic images of suspicious lesions, microscopic endoscopy for in vivo optical biopsy has been developed, including endocytoscopy and confocal laser endomicroscopy. This article reviews recent advances in technology and clinical applications, as well as their shortcomings and future directions.
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20
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Kim DH, Krishna SG, Coronel E, Kröner PT, Wolfsen HC, Wallace MB, Corral JE. Confocal Laser Endomicroscopy in the Diagnosis of Biliary and Pancreatic Disorders: A Systematic Analysis. Clin Endosc 2022; 55:197-207. [PMID: 34839621 PMCID: PMC8995979 DOI: 10.5946/ce.2021.079] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/15/2021] [Accepted: 05/10/2021] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND/AIMS Endoscopic visualization of the microscopic anatomy can facilitate the real-time diagnosis of pancreatobiliary disorders and provide guidance for treatment. This study aimed to review the technique, image classification, and diagnostic performance of confocal laser endomicroscopy (CLE). METHODS We conducted a systematic review of CLE in pancreatic and biliary ducts of humans, and have provided a narrative of the technique, image classification, diagnostic performance, ongoing research, and limitations. RESULTS Probe-based CLE differentiates malignant from benign biliary strictures (sensitivity, ≥89%; specificity, ≥61%). Needlebased CLE differentiates mucinous from non-mucinous pancreatic cysts (sensitivity, 59%; specificity, ≥94%) and identifies dysplasia. Pancreatitis may develop in 2-7% of pancreatic cyst cases. Needle-based CLE has potential applications in adenocarcinoma, neuroendocrine tumors, and pancreatitis (chronic or autoimmune). Costs, catheter lifespan, endoscopist training, and interobserver variability are challenges for routine utilization. CONCLUSION CLE reveals microscopic pancreatobiliary system anatomy with adequate specificity and sensitivity. Reducing costs and simplifying image interpretation will promote utilization by advanced endoscopists.
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Affiliation(s)
- Do Han Kim
- Universidad Francisco Marroquin, School of Medicine, Guatemala City, Guatemala
| | - Somashekar G. Krishna
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Emmanuel Coronel
- Division of Gastroenterology and Hepatology, MD Anderson Cancer Center, Houston, Texas, USA
| | - Paul T. Kröner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Herbert C. Wolfsen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Michael B. Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Juan E. Corral
- Division of Gastroenterology and Hepatology, Presbyterian Health Services, Albuquerque, New Mexico, USA
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21
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Pilonis ND, Januszewicz W, di Pietro M. Confocal laser endomicroscopy in gastro-intestinal endoscopy: technical aspects and clinical applications. Transl Gastroenterol Hepatol 2022; 7:7. [PMID: 35243116 PMCID: PMC8826043 DOI: 10.21037/tgh.2020.04.02] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Accepted: 03/30/2020] [Indexed: 08/24/2023] Open
Abstract
Confocal laser endomicroscopy (CLE) is an advanced endoscopic imaging technology that provides a magnified, cellular level view of gastrointestinal epithelia. In conjunction with topical or intravenous fluorescent dyes, CLE allows for an "optical biopsy" for real-time diagnosis. Two different CLE system have been used in clinical endoscopy, probe-based CLE (pCLE) and endoscope-based CLE (eCLE). Using pCLE, the device can be delivered: (I) into the luminal gastrointestinal tract through the working channel of standard endoscopes; (II) into extraluminal cystic and solid parenchymal lesions through an endoscopic ultrasound (EUS) needle; or (III) into the biliary system through an endoscopic retrograde cholangiopancreatography (ERCP) accessory channel. With eCLE, the probe is directly integrated into the tip of a conventional endoscope, however, these endoscopes are no longer commercially available. CLE has moderate to high diagnostic accuracy for neoplastic and inflammatory conditions through the gastrointestinal tract including: oesophageal, gastric and colonic neoplasia, pancreatic cysts and solid lesions, malignant pancreatobiliary strictures and inflammatory bowel disease. Some studies have demonstrated the diagnostic benefit of CLE imaging when combined with either conventional white light endoscopy or advanced imaging technologies. Therefore, optical biopsies using CLE can resolve diagnostic dilemmas in some cases where conventional imaging fails to achieve conclusive results. CLE could also reduce the requirement for extensive tissue sampling during surveillance procedures. In the future, CLE in combination with molecular probes, could allow for the molecular characterization of diseases and assess response to targeted therapy. However, the narrow field of view, high capital costs and specialized operator training requirements remain the main limitations. Future multi-center, randomized trials with a focus on conventional diagnostic applications, cost-effectiveness and standardized training will be required for definitive evidence. The objective of this review is to evaluate the technical aspects and current applications of CLE in patients with gastrointestinal and pancreatobiliary diseases and discuss future directions for this technique.
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Affiliation(s)
- Nastazja Dagny Pilonis
- MRC Cancer Unit at the University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre for Postgraduate Education, Warsaw, Poland
- Department of Gastroenterological Oncology, the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
| | - Wladyslaw Januszewicz
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre for Postgraduate Education, Warsaw, Poland
- Department of Gastroenterological Oncology, the Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
| | - Massimiliano di Pietro
- MRC Cancer Unit at the University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
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22
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Biliary Tree Diagnostics: Advances in Endoscopic Imaging and Tissue Sampling. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58010135. [PMID: 35056443 PMCID: PMC8781810 DOI: 10.3390/medicina58010135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/10/2022] [Accepted: 01/11/2022] [Indexed: 12/12/2022]
Abstract
The diagnostic approach to the biliary tree disorders can be challenging, especially for biliary strictures. Albeit the great diagnostic impact of endoscopic retrograde cholangiopancreatography (ERCP) which allows one to obtain fluoroscopic imaging and tissue sampling through brush cytology and/or forceps biopsy, a considerable proportion of cases remain indeterminate, leading to the risk of under/over treated patients. In the last two decades, several endoscopic techniques have been introduced in clinical practice, shrinking cases of uncertainties and improving diagnostic accuracy. The aim of this review is to discuss recent advances and emerging technologies applied to the management of biliary tree disorders through peroral endoscopy procedures.
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23
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Han S, Kahaleh M, Sharaiha RZ, Tarnasky PR, Kedia P, Slivka A, Chennat JS, Joshi V, Sejpal DV, Sethi A, Shah RJ. Probe-based confocal laser endomicroscopy in the evaluation of dominant strictures in patients with primary sclerosing cholangitis: results of a U.S. multicenter prospective trial. Gastrointest Endosc 2021; 94:569-576.e1. [PMID: 33798541 DOI: 10.1016/j.gie.2021.03.027] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/21/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Patients with primary sclerosing cholangitis (PSC) and dominant biliary strictures carry increased risk for the development of cholangiocarcinoma. Although ERCP-based techniques including brush cytology and intraductal biopsy sampling represent first-line tissue sampling methods for dominant strictures, sensitivity is low. Probe-based confocal laser endomicroscopy (pCLE) offers microscopic-level imaging of subepithelial biliary mucosa. Because data regarding the use of pCLE in PSC are limited, we aimed to investigate its diagnostic performance in dominant strictures. METHODS This was a multicenter prospective study involving PSC patients with dominant strictures. ERCP with pCLE was performed with use of the Miami classification (2+ criteria for malignant diagnosis) and Paris classification. Final malignant diagnoses required histopathologic confirmation, and benign diagnoses required a minimum of 1 year of follow-up without development of cancer. RESULTS Fifty-nine patients (mean age, 49 years; 59% men) with 63 strictures were included in the study. Stricture locations included the common bile duct (31.7%), bifurcation (22.2%), and common hepatic duct (19%). Seven patients (11.9%) were found to have cholangiocarcinoma. The sensitivity and specificity of pCLE was 85.7% (95% confidence interval [CI], 42.1-99.6) and 73.1% (95% CI, 58.9-84.4), respectively. Within specific stricture locations, the highest sensitivity was seen at the bifurcation (100%; 95% CI, 2.5-100) and the right hepatic duct (100%; 95% CI, 29.2-100). The lowest sensitivities were seen at the common bile duct (25%; 95% CI, 5.5-57.2) and the left hepatic duct (28.6%; 95% CI, 3.7-70.9). CONCLUSIONS In this prospective multicenter study, pCLE had a high sensitivity in detecting cholangiocarcinoma, but technical aspects of the probe may limit evaluation in the common bile duct and left hepatic duct. Further evaluation is needed to elucidate the role of pCLE in the algorithm of excluding neoplasia in biliary strictures associated with PSC. (Clinical trial registration number: NCT02736708.).
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Affiliation(s)
- Samuel Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Michel Kahaleh
- Division of Gastroenterology, Rutgers Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USA
| | - Reem Z Sharaiha
- Division of Gastroenterology, Weill Cornell Medical Center, New York, New York, USA
| | - Paul R Tarnasky
- Division of Gastroenterology, Dallas Methodist Medical Center, Dallas, Texas, USA
| | - Prashant Kedia
- Division of Gastroenterology, Dallas Methodist Medical Center, Dallas, Texas, USA
| | - Adam Slivka
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jennifer S Chennat
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Virendra Joshi
- Division of Gastroenterology, Louisiana State University Health Center, New Orleans, Louisiana, USA
| | - Divyesh V Sejpal
- Division of Gastroenterology, Northwell Health, Manhasset, New York, USA
| | - Amrita Sethi
- Division of Gastroenterology, Columbia University Medical Center, New York, New York, USA
| | - Raj J Shah
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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24
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Cha SW. Recent advances of diagnostic approaches for indeterminate biliary tract obstruction. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2021. [DOI: 10.18528/ijgii210037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Sang-Woo Cha
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Soon Chun Hyang University, Seoul, Korea
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25
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Huynh R, Owers C, Pinto C, Nguyen TM, Kwok T. Endoscopic Evaluation of Biliary Strictures: Current and Emerging Techniques. Clin Endosc 2021; 54:825-832. [PMID: 34038998 PMCID: PMC8652159 DOI: 10.5946/ce.2021.048] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 02/17/2021] [Indexed: 11/25/2022] Open
Abstract
The diagnosis of biliary strictures in clinical practice can be challenging. Discriminating between benign and malignant biliary strictures is important to prevent the morbidity and mortality associated with incorrect diagnoses. Missing a malignant biliary stricture may delay surgery, resulting in poor prognostic outcomes. Conversely, it has been demonstrated that approximately 20% of patients who undergo surgery for suspected biliary malignancies have a benign etiology on histopathology. Traditional tissue sampling using endoscopic retrograde cholangiography does not always produce a definitive diagnosis, with a considerable proportion of cases remaining as indeterminate biliary strictures. Recent advances in endoscopic techniques have the potential to improve the diagnostic and prognostic accuracy of biliary strictures.
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Affiliation(s)
- Roy Huynh
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Corinne Owers
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Christopher Pinto
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Thuy-My Nguyen
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Titus Kwok
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
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26
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Kamp EJCA, Dinjens WNM, Doukas M, Bruno MJ, de Jonge PJF, Peppelenbosch MP, de Vries AC. Optimal tissue sampling during ERCP and emerging molecular techniques for the differentiation of benign and malignant biliary strictures. Therap Adv Gastroenterol 2021; 14:17562848211002023. [PMID: 33948111 PMCID: PMC8053835 DOI: 10.1177/17562848211002023] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 02/15/2021] [Indexed: 02/04/2023] Open
Abstract
Patients with cholangiocarcinoma have poor survival since the majority of patients are diagnosed at a stage precluding surgical resection, due to locally irresectable tumors and/or metastases. Optimization of diagnostic strategies, with a principal role for tissue diagnosis, is essential to detect cancers at an earlier stage amenable to curative treatment. Current barriers for a tissue diagnosis include both insufficient tissue sampling and a difficult cyto- or histopathological assessment. During endoscopic retrograde cholangiopancreatography, optimal brush sampling includes obtaining more than one brush within an individual patient to increase its diagnostic value. Currently, no significant increase of the diagnostic accuracy for the new cytology brush devices aiming to enhance the cellularity of brushings versus standard biliary brush devices has been demonstrated. Peroral cholangioscopy with bile duct biopsies appears to be a valuable tool in the diagnostic work-up of indeterminate biliary strictures, and may overcome current technical difficulties of fluoroscopic-guided biopsies. Over the past years, molecular techniques to detect chromosomal instability, mutations and methylation profiling of tumors have revolutionized, and implementation of these techniques on biliary tissue during diagnostic work-up of biliary strictures may be awaited in the near future. Fluorescence in situ hybridization has already been implemented in routine diagnostic evaluation of biliary strictures in several centers. Next-generation sequencing is promising for standard diagnostic care in biliary strictures, and recent studies have shown adequate detection of prevalent genomic alterations in KRAS, TP53, CDKN2A, SMAD4, PIK3CA, and GNAS on biliary brush material. Detection of DNA methylation of tumor suppressor genes and microRNAs may evolve over the coming years to a valuable diagnostic tool for cholangiocarcinoma. This review summarizes optimal strategies for biliary tissue sampling during endoscopic retrograde cholangiopancreatography and focuses on the evolving molecular techniques on biliary tissue to improve the differentiation of benign and malignant biliary strictures.
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Affiliation(s)
- Eline J. C. A. Kamp
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Winand N. M. Dinjens
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Pieter Jan F. de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Maikel P. Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, Room Na-609, Rotterdam, 3015 GD, The Netherlands
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Koda H, Hara K, Nozomi O, Kuwahara T, Nobumasa M, Haba S, Akira M, Hajime I. High-Resolution Probe-Based Confocal Laser Endomicroscopy for Diagnosing Biliary Diseases. Clin Endosc 2021; 54:924-929. [PMID: 33721485 PMCID: PMC8652165 DOI: 10.5946/ce.2020.191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 11/23/2020] [Indexed: 11/14/2022] Open
Abstract
Probe-based confocal laser endomicroscopy is an endoscopic technique that enables in vivo histological evaluation using fluorescent pigment. The ability to diagnostically differentiate between benign and malignant biliary disease using the "CholangioFlexTM", a dedicated biliary device, has been reported. However, the Miami and Paris classifications, used as diagnostic criteria, mainly evaluate findings in the submucosa, and visualizing the epithelium as the main site of lesions remains difficult. To address this problem, we verified the imaging findings and diagnostic ability of three types of probes: CholangioFlexTM, GastroFlexTM, and AlveoFlexTM. With GastroFlexTM, the clear mucosal epithelium was observed, and differential diagnoses as benign/malignant could be made based on epithelial findings. GastroFlexTM may be a good first-choice probe for probe-based confocal laser endomicroscopy of biliary diseases, and a new diagnostic classification based on bile duct epithelial findings may provide useful criteria independent of the Miami or Paris classifications.
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Affiliation(s)
- Hiroki Koda
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Okuno Nozomi
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takamichi Kuwahara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Mizuno Nobumasa
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Shin Haba
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Miyano Akira
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Isomoto Hajime
- Department of Gastroenterology, Tottori University Hospital, Yonago, Japan
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Tanisaka Y, Mizuide M, Fujita A, Ogawa T, Suzuki M, Katsuda H, Saito Y, Miyaguchi K, Tashima T, Mashimo Y, Ryozawa S. Diagnostic Process Using Endoscopy for Biliary Strictures: A Narrative Review. J Clin Med 2021; 10:jcm10051048. [PMID: 33802525 PMCID: PMC7961606 DOI: 10.3390/jcm10051048] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/17/2021] [Accepted: 02/27/2021] [Indexed: 12/13/2022] Open
Abstract
The diagnostic process for biliary strictures remains challenging in some cases. A broad differential diagnosis exists for indeterminate biliary strictures, including benign or malignant lesions. The diagnosis of indeterminate biliary strictures requires a combination of physical examination, laboratory testing, imaging modalities, and endoscopic procedures. Despite the progress of less invasive imaging modalities such as transabdominal ultrasonography, computed tomography, and magnetic resonance imaging, endoscopy plays an essential role in the accurate diagnosis, including the histological diagnosis. Imaging findings and brush cytology and/or forceps biopsy under fluoroscopic guidance with endoscopic retrograde cholangiopancreatography (ERCP) are widely used as the gold standard for the diagnosis of biliary strictures. However, ERCP cannot provide an intraluminal view of the biliary lesion, and its outcomes are not satisfactory. Recently, peroral cholangioscopy, confocal laser endomicroscopy, endoscopic ultrasound (EUS), and EUS-guided fine-needle aspiration have been reported as useful for indeterminate biliary strictures. Appropriate endoscopic modalities need to be selected according to the patient's condition, the lesion, and the expertise of the endoscopist. The aim of this review article is to discuss the diagnostic process for indeterminate biliary strictures using endoscopy.
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Boškoski I, Schepis T, Tringali A, Familiari P, Bove V, Attili F, Landi R, Perri V, Costamagna G. Personalized Endoscopy in Complex Malignant Hilar Biliary Strictures. J Pers Med 2021; 11:jpm11020078. [PMID: 33572913 PMCID: PMC7911877 DOI: 10.3390/jpm11020078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/25/2021] [Accepted: 01/26/2021] [Indexed: 12/13/2022] Open
Abstract
Malignant hilar biliary obstruction (HBO) represents a complex clinical condition in terms of diagnosis, surgical and medical treatment, endoscopic approach, and palliation. The main etiology of malignant HBO is hilar cholangiocarcinoma that is considered an aggressive biliary tract's cancer and has still today a poor prognosis. Endoscopy plays a crucial role in malignant HBO from the diagnosis to the palliation. This technique allows the collection of cytological or histological samples, direct visualization of the suspect malignant tissue, and an echoendoscopic evaluation of the primary tumor and its locoregional staging. Because obstructive jaundice is the most common clinical presentation of malignant HBO, endoscopic biliary drainage, when indicated, is the preferred treatment over the percutaneous approach. Several endoscopic techniques are today available for both the diagnosis and the treatment of biliary obstruction. The choice among them can differ for each clinical scenario. In fact, a personalized endoscopic approach is mandatory in order to perform the proper procedure in the singular patient.
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Affiliation(s)
- Ivo Boškoski
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Correspondence:
| | - Tommaso Schepis
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Andrea Tringali
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Pietro Familiari
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
| | - Vincenzo Bove
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
| | - Fabia Attili
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
| | - Rosario Landi
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
| | - Vincenzo Perri
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
| | - Guido Costamagna
- Center for Endoscopic Research Therapeutics and training (CERTT), Università Cattolica del Sacro Cuore, 20123 Rome, Italy; (T.S.); (A.T.); (P.F.); (V.B.); (F.A.); (R.L.); (V.P.); (G.C.)
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
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Solonitsyn E, Dechêne A. Diagnostic Approach to Suspected Perihilar Malignancy. Visc Med 2021; 37:3-9. [PMID: 33718479 DOI: 10.1159/000513950] [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] [Received: 11/15/2020] [Accepted: 12/18/2020] [Indexed: 12/14/2022] Open
Abstract
Background Cholangiocarcinomas are relatively rare tumors most frequently arising from the epithelium of the hilar bile ducts. The diagnosis is often made in advanced (symptomatic) stages, which accounts for the infavorable prognosis with a 5-year survival of less than 10%. Identification of perihilar cholangiocarcinoma (pCCA) is often challenging because there is no single method offering sufficient diagnostic accuracy. Summary Most tumors arise in patients without specific risk factors. Clinical symptoms of pCCA are nonspecific and reliable biomarkers are lacking, with carbohydrate antigen 19-9 being the most commonly used tumor marker (but with a low accuracy). Cross-sectional imaging (CT and MRI) is used to identify and map hilar strictures and determine resectability by showing vascular involvement. Endoscopic ultrasound offers additional information on locoregional tumor spread and lymph node involvement. Endoscopic retrograde cholangiography in combination with cholangioscopy gives direct access to and imaging of hilar strictures but it does not always distinguish between pCCA and benign hilar strictures. Tissue acquisition for histological diagnosis is challenging, with frequent sampling errors regardless of the method of biopsy procurement because of the cellular paucity of tumor tissue. Key Messages In suspected perihilar malignancy, a mosaic of clinical data has to be taken into account. Histological evaluation of (endoscopically harvested) specimens is pivotal to differential diagnosis. Several new techniques to increase diagnostic accuracy are under investigation (biomarkers and genetic testing among others).
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Affiliation(s)
- Evgeny Solonitsyn
- Almasov National Medical Research Centre, Saint-Petersburg, Russian Federation
| | - Alexander Dechêne
- Department of Gastroenterology, Hepatology and Endocrinology, University Hospital, Paracelsus Medical University Nuremberg, Nuremberg, Germany
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Diagnosis of Biliary Strictures Using Probe-Based Confocal Laser Endomicroscopy under the Direct View of Peroral Cholangioscopy: Results of a Prospective Study (with Video). Gastroenterol Res Pract 2020; 2020:6342439. [PMID: 33488697 PMCID: PMC7790558 DOI: 10.1155/2020/6342439] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 12/19/2020] [Indexed: 12/12/2022] Open
Abstract
Background The accurate diagnosis of biliary strictures remains problematic. The aim of the present study was to prospectively evaluate the clinical utility of probe-based confocal laser endomicroscopy (pCLE) under the direct view of peroral cholangioscopy (POCS) for the diagnosis of biliary strictures. Methods Consecutive patients with biliary strictures were included. We investigated sensitivity, specificity, and accuracy to diagnose malignancy for (1) ERCP alone, (2) POCS, (3) pCLE under the direct view of POCS, and (4) tissue sampling under the direct view of POCS. Results A total of 30 patients (17 with malignant lesions) were prospectively enrolled. (1) ERCP alone showed 88.2% sensitivity, 46.2% specificity, and 70% (95% confidence interval (CI), 52.1%–83.3%) accuracy. (2) POCS showed 100% sensitivity, 76.9% specificity, and 90% (95% CI, 74.4%–96.5%) accuracy. (3) pCLE under the direct view of POCS showed 94.1% sensitivity, 92.3% specificity, and 93.3% (95% CI, 78.7%–98.8%) accuracy. (4) Tissue sampling under the direct view of POCS showed 82.4% sensitivity, 100% specificity, and 90% (95% CI, 74.4%–96.5%) accuracy. Conclusions pCLE under the direct view of POCS provided highly accurate and sensitive characterization of biliary strictures and showed the potential for more diagnostic reliability and reduction of delays in diagnosis. This trial was registered at UMIN (registration number: UMIN000033801).
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Ungureanu BS, Pirici D, Dima SO, Popescu I, Hundorfean G, Surlin V, Saftoiu A. Morphometric Assessment of Confocal Laser Endomicroscopy for Pancreatic Ductal Adenocarcinoma, an Ex-Vivo Pilot Study. Diagnostics (Basel) 2020; 10:923. [PMID: 33182544 PMCID: PMC7696051 DOI: 10.3390/diagnostics10110923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/02/2020] [Accepted: 11/07/2020] [Indexed: 01/26/2023] Open
Abstract
UNLABELLED Ex-vivo freshly surgical removed pancreatic ductal adenocarcinoma (PDAC) specimens were assessed using pCLE and then processed for paraffin embeding and histopathological diagnostic in an endeavour to find putative image analysis algorithms that might recognise adenocarcinoma. METHODS Twelve patients diagnosed with PDAC on endoscopic ultrasound and FNA confirmation underwent surgery. Removed samples were sprayed with acriflavine as contrast agent, underwent pCLE with an experimental probe and compared with previous recordings of normal pancreatic tissue. Subsequently, all samples were subjected to cross-sectional histopathology, including surgical resection margins for controls. pCLE records, as well as corespondant cytokeratin-targeted immunohistochemistry images were processed using the same morphological classifiers in the Image ProPlus AMS image analysis software. Specific morphometric classifiers were automatically generated on all images: Area, Hole Area (HA), Perimeter, Roundness, Integrated Optical Density (IOD), Fractal Dimension (FD), Ferret max (Fmax), Ferret mean (Fmean), Heterogeneity and Clumpiness. RESULTS After histopathological confirmation of adenocarcinoma areas, we have found that the same morphological classifiers could clearly differentiate between tumor and non-tumor areas on both pathology and correspondand pCLE (area, roundness, IOD, ferret and heterogeneity (p < 0.001), perimeter and hole area (p < 0.05). CONCLUSIONS This pilot study proves that classical morphometrical classifiers can clearly differentiate adenocarcimoma on pCLE data, and the implementation in a live image-analysis algorithm might help in improving the specificity of pCLE in vivo diagnostic.
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Affiliation(s)
- Bogdan Silviu Ungureanu
- Gastroenterology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Daniel Pirici
- Histology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Simona Olimpia Dima
- Surgical Department, Fundeni Clinical Institute, 925200 Bucharest, Romania; (S.O.D.); (I.P.)
| | - Irinel Popescu
- Surgical Department, Fundeni Clinical Institute, 925200 Bucharest, Romania; (S.O.D.); (I.P.)
| | - Gheorghe Hundorfean
- Medical Clinic 1, Department of Medicine, University Hospital Erlangen, University Erlangen-Nuremberg, 91052 Erlangen, Germany;
| | - Valeriu Surlin
- Surgical Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Adrian Saftoiu
- Gastroenterology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
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SAGES TAVAC safety and efficacy analysis confocal laser endomicroscopy. Surg Endosc 2020; 35:2091-2103. [PMID: 32405892 DOI: 10.1007/s00464-020-07607-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 04/28/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Confocal laser endomicroscopy (CLE) is a novel endoscopic adjunct that allows real-time in vivo histological examination of mucosal surfaces. By using intravenous or topical fluorescent agents, CLE highlights certain mucosal elements that facilitate an optical biopsy in real time. CLE technology has been used in different organ systems including the gastrointestinal tract. There has been numerous studies evaluating this technology in gastrointestinal endoscopy, our aim was to evaluate the safety, value, and efficacy of this technology in the gastrointestinal tract. METHODS The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Technology and Value Assessment Committee (TAVAC) performed a PubMed/Medline database search of clinical studies involving CLE in May of 2018. The literature search used combinations of the keywords: confocal laser endomicroscopy, pCLE, Cellvizio, in vivo microscopy, optical histology, advanced endoscopic imaging, and optical diagnosis. Bibliographies of key references were searched for relevant studies not covered by the PubMed search. Case reports and small case series were excluded. The manufacturer's website was also used to identify key references. The United States Food and Drug Administration (U.S. FDA) Manufacturer And User facility and Device Experience (MAUDE) database was searched for reports regarding the device malfunction or injuries. RESULTS The technology offers an excellent safety profile with rare adverse events related to the use of fluorescent agents. It has been shown to increase the detection of dysplastic Barrett's esophagus, gastric intraepithelial neoplasia/early gastric cancer, and dysplasia associated with inflammatory bowel disease when compared to standard screening protocols. It also aids in the differentiation and classification of colorectal polyps, indeterminate biliary strictures, and pancreatic cystic lesions. CONCLUSIONS CLE has an excellent safety profile. CLE can increase the diagnostic accuracy in a number of gastrointestinal pathologies.
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Endoscopic Perspective in Cholangiocarcinoma Diagnostic Process. Gastroenterol Res Pract 2020; 2019:9704870. [PMID: 31933635 PMCID: PMC6942804 DOI: 10.1155/2019/9704870] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 11/23/2019] [Indexed: 12/13/2022] Open
Abstract
Cholangiocarcinoma is a malignancy arising from the epithelial lining of the intrahepatic or extrahepatic biliary tract. Timely diagnosis is challenging due to its silent clinical course. As reliable laboratory markers are lacking, diagnostic imaging plays a pivotal role. While cross-sectional imaging studies are usually conclusive for intrahepatic lesions, endoscopy plays an essential role in cases of extrahepatic tumors. Rational utilization of different diagnostic methods based on available evidence is needed. This article focuses on the diagnostic role of advanced biliary endoscopy, including endoscopic retrograde cholangiopancreatography, cholangioscopy, endoscopic ultrasonography, and intraductal sonography.
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Chascsa DM, Lindor KD. Cancer risk, screening and surveillance in primary sclerosing cholangitis. MINERVA GASTROENTERO 2019; 65:214-228. [PMID: 31220911 DOI: 10.23736/s1121-421x.19.02586-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory condition mainly of the large bile ducts, affecting predominantly young men, and is associated with the presence of inflammatory bowel disease. There is no known cure for PSC, which progresses to cirrhosis or death over 10-20 years. Hepatobiliary malignancy, especially cholangiocarcinoma, is a feared complication associated with poor overall survival. Screening and surveillance appear to improve overall outcomes. To capture as many relevant studies, broad search criteria were employed within the PubMed database. Given the high prevalence of IBD and its own associations with the development of malignancy two separate search strategies were employed. Results were filtered by English language. The first search identified the risks, epidemiological factors and surveillance strategies for patients with PSC at risk for developing malignancy. MeSH terms included: cholangitis, sclerosing, digestive system neoplasms, liver neoplasms, biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms, colonic neoplasms, rectal neoplasms, or pancreatic neoplasms, risk factors, risk, surveillance, epidemiology and screen. The second included inflammatory bowel diseases, Crohn's, or colitis, and assessed for additional malignancies such as lymphoma and skin neoplasms. A total of 288 results returned with 21 duplicates; 267 remaining abstracts were assessed for relevance for inclusion by the authors. Patients with PSC show significantly higher than average risk for the development of hepatobiliary and colonic malignancies including cholangiocarcinoma, gallbladder carcinoma and colorectal carcinoma. Yearly ultrasound surveillance followed with more definitive cross-sectional imaging is prudent to arrive in a timely diagnosis of carcinoma, reducing morbidity and mortality.
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Affiliation(s)
- David M Chascsa
- Departments of Gastroenterology and Hepatology and Transplant Center, Mayo Clinic, Phoenix, AZ, USA -
| | - Keith D Lindor
- Office of University Provost, Arizona State University, Phoenix, AZ, USA
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Fung BM, Tabibian JH. Biliary endoscopy in the management of primary sclerosing cholangitis and its complications. LIVER RESEARCH (BEIJING, CHINA) 2019; 3:106-117. [PMID: 31341699 PMCID: PMC6656407 DOI: 10.1016/j.livres.2019.03.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, idiopathic, cholestatic liver disease characterized by inflammation and fibrosis of the intrahepatic and/or extrahepatic bile ducts. It can affect individuals of all age groups and gender, has no established pharmacotherapy, and is associated with a variety of neoplastic (e.g. cholangiocarcinoma) and non-neoplastic (e.g. dominant strictures) hepatobiliary complications. Given these considerations, endoscopy plays a major role in the care of patients with PSC. In this review, we discuss and provide updates regarding endoscopic considerations in the management of hepatobiliary manifestations and complications of PSC. Where evidence is limited, we suggest pragmatic approaches based on currently available data and expert opinion.
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Affiliation(s)
- Brian M. Fung
- University of California Los Angeles-Olive View Internal Medicine Residency Program, Sylmar, CA, USA
| | - James H. Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-University of California Los Angeles Medical Center, Sylmar, CA, USA
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Dubow M, Tatman PD, Shah RJ. Individual probe based confocal laser endomicroscopy criteria in the analysis of indeterminate biliary strictures. Scand J Gastroenterol 2019; 53:1358-1363. [PMID: 30394137 DOI: 10.1080/00365521.2018.1512151] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Evaluation of indeterminate biliary strictures remains challenging due to limited sensitivity of endoscopic tissue sampling. Biliary probe-based confocal laser endomicroscopy (pCLE) has shown promise to detect and exclude neoplasia. However, knowledge of whether individual inflammatory criteria are more prevalent in neoplasia compared to benign strictures is limited. The objective of this work is to improve diagnosis of neoplastic and inflammatory conditions using pCLE. MATERIALS AND METHODS The charts of all patients who underwent pCLE at a single referral center between 2009 and 2015 were reviewed. ERCP reports were reviewed for eleven Miami and Paris criteria. Primary outcome was the identification of neoplasia by histopathology (defined as high-grade dysplasia and/or adenocarcinoma). To model predictors of neoplasia, we fit a binary regression model incorporating data from pCLE operating criteria, pCLE impression, and PSC status. RESULTS 97 patients were identified. In the 27 patients with neoplasia, there was increasing number of Miami malignant criteria (Pearson r = 0.512, p < .001) while inflammatory criteria were less prevalent. 10% (5/51, p < .001) of patients with benign pCLE impression developed neoplasia, while 48% (22/46, p < .001) with suspicious pCLE impressions developed neoplasia. The binary regression model to predict neoplasia had a sensitivity of 83.3%, specificity of 92.5%, and overall accuracy 89.7%. CONCLUSIONS Presence of malignant criteria and absence of certain inflammatory criteria are more prevalent in patients with neoplasia. Our model, which weights individual imaging components, shows impressive sensitivity and specificity over prior prognostic efforts. Prospective studies will be required to evaluate this model.
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Affiliation(s)
- Michael Dubow
- a Department of Medicine, Division of Gastroenterology , University of Colorado , Aurora , CO , USA
| | - Philip D Tatman
- a Department of Medicine, Division of Gastroenterology , University of Colorado , Aurora , CO , USA.,b Medical Scientist Training Program , University of Colorado , Aurora , CO , USA
| | - Raj J Shah
- a Department of Medicine, Division of Gastroenterology , University of Colorado , Aurora , CO , USA
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Mukewar S, Carr-Locke D. Advances in Endoscopic Imaging of the Biliary Tree. Gastrointest Endosc Clin N Am 2019; 29:187-204. [PMID: 30846148 DOI: 10.1016/j.giec.2018.12.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Direct endoscopic imaging of the biliary tree is increasingly performed by endoscopists since the introduction of digital single-operator cholangioscopy. In parallel, there have been several advances to overcome the challenges associated with direct peroral cholangioscopy with development of multibending cholangioscopes and new devices to enable direct placement of an endoscope into the biliary tree without a supporting duodenoscope. The indications for cholangioscopy are also evolving with newer indications, such as intraductal lithotripsy, foreign body (mostly stent) removal, guide wire cannulation of specific ducts, photodynamic therapy for cholangiocarcinoma, and performance of fluoroscopy-free cholangiography. There has also been progress in image enhancement during cholangioscopy and additional imaging techniques, such as intraductal ultrasound, confocal laser endomicroscopy, and optical coherence tomography.
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Affiliation(s)
- Saurabh Mukewar
- David H. Koch Medical Center, Department of Gastroenterology, Joan & Sanford I. Weill Medical, College of Cornell University, New York Presbyterian Hospital, 1278 York Avenue, 9th Floor, New York, NY 10065, USA.
| | - David Carr-Locke
- David H. Koch Medical Center, Department of Gastroenterology, Joan & Sanford I. Weill Medical, College of Cornell University, New York Presbyterian Hospital, 1278 York Avenue, 9th Floor, New York, NY 10065, USA
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Mascagni P, Longo F, Barberio M, Seeliger B, Agnus V, Saccomandi P, Hostettler A, Marescaux J, Diana M. New intraoperative imaging technologies: Innovating the surgeon's eye toward surgical precision. J Surg Oncol 2018; 118:265-282. [PMID: 30076724 DOI: 10.1002/jso.25148] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 06/04/2018] [Indexed: 04/13/2025]
Abstract
Imaging is one of the pillars for the ongoing evolution of surgical oncology toward a precision paradigm. In the present overview, some established or emerging intraoperative imaging technologies are described in light of the vision and experience of our group in image-guided surgery, focusing on digestive surgical oncology.
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Affiliation(s)
- Pietro Mascagni
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
| | - Fabio Longo
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
| | - Manuel Barberio
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
| | - Barbara Seeliger
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
| | - Vincent Agnus
- IRCAD, Research Institute against Digestive Cancer, Strasbourg, France
| | - Paola Saccomandi
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
| | | | - Jacques Marescaux
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
- IRCAD, Research Institute against Digestive Cancer, Strasbourg, France
| | - Michele Diana
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
- IRCAD, Research Institute against Digestive Cancer, Strasbourg, France
- Department of General, Digestive and Endocrine Surgery, University of Strasbourg, Strasbourg, France
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Sun B, Moon JH, Cai Q, Rerknimitr R, Ma S, Lakhtakia S, Ryozawa S, Kutsumi H, Yasuda I, Shiomi H, Li X, Li W, Zhang X, Itoi T, Wang HP, Qian D, Wong Lau JY, Yang Z, Ji M, Hu B. Review article: Asia-Pacific consensus recommendations on endoscopic tissue acquisition for biliary strictures. Aliment Pharmacol Ther 2018; 48:138-151. [PMID: 29876948 DOI: 10.1111/apt.14811] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Revised: 03/23/2018] [Accepted: 04/26/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Pre-operative tissue diagnosis for suspected malignant biliary strictures remains challenging. AIM To develop evidence-based consensus statements on endoscopic tissue acquisition for biliary strictures. METHODS The initial draft of statements was prepared following a systematic literature review. A committee of 20 experts from Asia-Pacific region then reviewed, discussed, and modified the statements. Two rounds of independent voting were conducted to reach a final version. Consensus was considered to be achieved when 80% or more of voting members voted "agree completely" or "agree with some reservation." RESULTS Eleven statements achieved consensus. The choice of tissue sampling modalities for biliary strictures depends on the clinical setting, the location of lesion, and availability of expertise. Detailed radiological and endoscopic evaluation is useful to guide the selection of appropriate tissue acquisition technique. Standard intraductal biliary brushing and/or forceps biopsy is the first option when endoscopic biliary drainage is required with an overall (range) sensitivity and specificity of 45% (26%-72%) and 99% (98%-100%), and 48% (15%-100%) and 99% (97%-100%), respectively, in diagnosing malignant biliary strictures. Probe-based confocal laser endomicroscopy and fluorescence in situ hybridisation using 4 fluorescent-labelled probes targeting chromosomes 3, 7, 17 and 9p21 locus may be added to improve the diagnostic yield. Cholangioscopy-guided biopsy and EUS-guided tissue acquisition can be considered after prior negative conventional tissue sampling with an overall (range) sensitivity and specificity of 60% (38%-88%) and 98% (83%-100%), and 80% (46%-100%) and 97% (92%-100%), respectively, in diagnosing malignant biliary strictures. CONCLUSION These consensus statements provide evidence-based recommendations for endoscopic tissue acquisition of biliary strictures.
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Taghavi SA, Eshraghian A, Niknam R, Sivandzadeh GR, Bagheri Lankarani K. Diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Expert Rev Gastroenterol Hepatol 2018; 12:575-584. [PMID: 29781738 DOI: 10.1080/17474124.2018.1473761] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 05/02/2018] [Indexed: 02/06/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the hepatobiliary system characterized by chronic inflammation, progressive fibrosis, stricture formation and destruction of extrahepatic and intrahepatic bile ducts. Areas covered: The increased incidence of cholangiocarcinoma (CCA) in PSC has been well documented and can be explained by the continuous inflammation in the biliary tree leading to an enhanced dysplasia-carcinoma sequence. Although PSC patients may progress to liver cirrhosis; CCA most commonly occurs between the ages of 30 and 45 years when cirrhosis has not yet developed. Therefore, CCA in patients with PSC occurs earlier than in patients without PSC. Expert commentary: Despite improvement in diagnostic methods and devices, the dilemma of diagnosing CCA in patients with PSC has not been solved yet and needs further investigation.
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Affiliation(s)
- Seyed Alireza Taghavi
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
| | - Ahad Eshraghian
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
| | - Ramin Niknam
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
| | - Gholam Reza Sivandzadeh
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
| | - Kamran Bagheri Lankarani
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
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Rizvi S, Eaton J, Yang JD, Chandrasekhara V, Gores GJ. Emerging Technologies for the Diagnosis of Perihilar Cholangiocarcinoma. Semin Liver Dis 2018; 38:160-169. [PMID: 29871021 PMCID: PMC6463495 DOI: 10.1055/s-0038-1655775] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The diagnosis of malignant biliary strictures remains problematic, especially in the perihilar region and in primary sclerosing cholangitis (PSC). Conventional cytology obtained during endoscopic retrograde cholangiography (ERC)-guided brushings of biliary strictures is suboptimal due to limited sensitivity, albeit it remains the gold standard with a high specificity. Emerging technologies are being developed and validated to address this pressing unmet patient need. Such technologies include enhanced visualization of the biliary tree by cholangioscopy, intraductal ultrasound, and confocal laser endomicroscopy. Conventional cytology can be aided by employing complementary and advanced cytologic techniques such as fluorescent in situ hybridization (FISH), and this technique should be widely adapted. Interrogation of bile and serum by examining extracellular vesicle number and cargo, and exploiting next-generation sequencing and proteomic technologies, is also being explored. Examination of circulating cell-free deoxyribonucleic acid (cfDNA) for differentially methylated regions is a promising test which is being rigorously validated. The special expertise required for these analyses has to date hampered their validation and adaptation. Herein, we will review these emerging technologies to inform the reader of the progress made and encourage further studies, as well as adaptation of validated approaches.
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Affiliation(s)
- Sumera Rizvi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John Eaton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Ju Dong Yang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Gao YD, Qu YW, Liu HF. Comparison of diagnostic efficacy between CLE, tissue sampling, and CLE combined with tissue sampling for undetermined pancreaticobiliary strictures: a meta-analysis. Scand J Gastroenterol 2018. [PMID: 29543078 DOI: 10.1080/00365521.2018.1448435] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The accurate diagnosis of undetermined pancreaticobiliary strictures remains challenging. Current ERCP-guided tissue sampling methods are of low sensitivity. Confocal laser endomicroscopy (CLE) is a new procedure and allows real optical biopsies that may improve the diagnosis of undetermined pancreaticobiliary strictures. The aim of this meta-analysis was to determine the diagnostic yield of CLE, tissue sampling, and CLE combined with tissue sampling for undetermined pancreaticobiliary strictures. METHOD Pubmed, Embase, and the Cochrane Library database were reviewed for relevant studies. Pooled estimates of sensitivity and specificity with 95% confidence intervals (CIs) were calculated using the random-effects meta-analysis model. The summary receiver-operating characteristic (SROC) curve was constructed, and the area under the receiver operating characteristic curve (AUC) was calculated. RESULTS Twelve studies involving 591 patients were enrolled in our analysis. The overall sensitivity and the specificity estimate of CLE for discriminating benign and malignant pancreaticobiliary strictures were 87% (95%CI, 83-91%) and 76% (95%CI, 70-81%), respectively. The AUC to assess the diagnostic efficacy was 0.8705. For tissue sampling, the overall sensitivity and the specificity estimate were 64% (95%CI, 57-70%) and 94% (95%CI, 90-97%), respectively. The AUC to assess the diagnostic efficacy was 0.8040. A combination of both methods increased the sensitivity (93%; 95%CI, 88-96%) with a specificity of 82% (95%CI, 74-89%). The AUC to assess the diagnostic efficacy was 0.9377. There was no publication bias by Deeks' Funnel Plot with p = .936. CONCLUSIONS Compared with tissue sampling, CLE may increase the sensitivity for the diagnosis of malignant pancreaticobiliary strictures. A combination of both can effectively diagnose malignant pancreaticobiliary strictures.
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Affiliation(s)
- Ya-Dong Gao
- a The Clinical College of the General Hospital of Chinese People's Armed Police Forces, Anhui Medical University , Hefei , China
| | - Ya-Wei Qu
- b Department of Gastroenterology , General Hospital of Chinese People's Armed Police Force , Beijing , China
| | - Hai-Feng Liu
- a The Clinical College of the General Hospital of Chinese People's Armed Police Forces, Anhui Medical University , Hefei , China
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Xie C, Aloreidi K, Patel B, Ridgway T, Thambi-Pillai T, Timmerman G, Khan A, Atiq M. Indeterminate biliary strictures: a simplified approach. Expert Rev Gastroenterol Hepatol 2018; 12:189-199. [PMID: 29034764 DOI: 10.1080/17474124.2018.1391090] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pre-operative evaluation of biliary strictures remains challenging. The dilemma that exists is how to balance the risk of failing to detect malignancy and the potential morbidity caused by unnecessary surgery in patients with benign etiologies. With emerging novel diagnostic modalities, this study aims to assess the efficacy of diagnostic techniques and facilitate a clinical approach to indeterminate biliary strictures. Areas covered: Conventional imaging modalities are crucial in identifying the location of a stricture and are helpful for choosing further diagnostic modalities. Utilization of endoscopic techniques, including endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), is key in establishing a diagnosis. The emergence of novel diagnostic modalities, such as fluorescence in-situ hybridization (FISH), peroral cholangioscopy (POC), intraductal endoscopic ultrasound (IDUS) and confocal laser endomicroscopy (CLE), enhance the diagnostic yield in the evaluation of indeterminate biliary strictures. Expert commentary: More reliable and validated visual criteria for differentiating malignancy from benign biliary conditions, utilizing advanced imaging modalities such as POC and CLE, need to be established. It is of significance to further evaluate these novel diagnostic modalities through ongoing trials and to develop a diagnostic algorithm that reconciles cost-effectiveness with diagnostic accuracy.
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Affiliation(s)
- Chencheng Xie
- a Internal Medicine , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Khalil Aloreidi
- a Internal Medicine , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Bhavesh Patel
- b Surgery , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Timothy Ridgway
- b Surgery , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Thavam Thambi-Pillai
- a Internal Medicine , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Gary Timmerman
- a Internal Medicine , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Adeel Khan
- c Surgery , Washington University in St. Louis , St. Louis , MO , USA
| | - Muslim Atiq
- b Surgery , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
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Bastos VR, Safatle-Ribeiro AV, Baba ER, da Costa Martins B, Maluf-Filho F. The impact of probe-based confocal endomicroscopy on the management of indeterminate bile duct strictures. VideoGIE 2018; 3:26-27. [PMID: 29905177 PMCID: PMC5965712 DOI: 10.1016/j.vgie.2017.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Taunk P, Singh S, Lichtenstein D, Joshi V, Gold J, Sharma A. Improved classification of indeterminate biliary strictures by probe-based confocal laser endomicroscopy using the Paris Criteria following biliary stenting. J Gastroenterol Hepatol 2017; 32:1778-1783. [PMID: 28294404 DOI: 10.1111/jgh.13782] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Revised: 02/26/2017] [Accepted: 03/03/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Probe-based confocal laser endomicroscopy (pCLE) using the Miami Criteria has improved classification of indeterminate biliary strictures. However, previous biliary stenting may result in their misclassification as malignant strictures. Inflammatory criteria were added to form the Paris Classification to prevent this misclassification and reduce false positives. The aim of this study was to assess if the Paris Classification was more accurate than the Miami Classification in classifying indeterminate biliary strictures after biliary stenting. METHODS This was a retrospective observational study involving 21 patients with indeterminate biliary strictures from whom 27 pCLE video sequences were obtained (20 benign and seven malignant). Patients with and without prior biliary stenting underwent pCLE. Two investigators classified the strictures as malignant or benign using the Miami and Paris Classifications. Diagnostic accuracy, sensitivity (Se), and specificity (Sp) of endoscopic retrograde-guided pCLE were compared with final histopathology. RESULTS In those without biliary stenting, the Miami Criteria resulted in Se 88%, Sp 75%, positive predictive value (PPV) 64%, negative predictive value (NPV) 92%, and accuracy 79%, while the Paris Classification resulted in Se 63%, Sp 88%, PPV 71%, NPV 82%, and accuracy 79%. In those with prior biliary stenting, the Miami Criteria resulted in Se 88%, Sp 36%, PPV 23%, NPV 93%, and accuracy 45%, while the Paris Classification resulted in Se 63%, Sp 73%, PPV 31%, NPV 91%, and accuracy 71%. The kappa statistic was 0.56. CONCLUSION The Paris Classification improved specificity and accuracy of biliary stricture classification in those who had been previously stented and decreased the rate of misclassification of benign strictures as malignant.
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Affiliation(s)
| | - Satish Singh
- Boston University Medical Center, Boston, Massachusetts, USA.,Boston VA Medical Center, Boston, Massachusetts, USA
| | | | | | - Jason Gold
- Boston VA Medical Center, Boston, Massachusetts, USA
| | - Ashish Sharma
- Kaiser Permanente Health System, Sacramento, California, USA
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Robles-Medranda C, Vargas M, Ospina J, Puga-Tejada M, Valero M, Soria M, Bravo G, Robles-Jara C, Lukashok HP. Clinical impact of confocal laser endomicroscopy in the management of gastrointestinal lesions with an uncertain diagnosis. World J Gastrointest Endosc 2017; 9:389-395. [PMID: 28874959 PMCID: PMC5565504 DOI: 10.4253/wjge.v9.i8.389] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 04/10/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate the clinical impact of confocal laser endomicroscopy (CLE) in the diagnosis and management of patients with an uncertain diagnosis.
METHODS A retrospective chart review was performed. Patients who underwent CLE between November 2013 and October 2015 and exhibited a poor correlation between endoscopic and histological findings were included. Baseline characteristics, indications, previous diagnostic studies, findings at the time of CLE, clinical management and histological results were analyzed. Interventions based on CLE findings were also analyzed. We compared the diagnostic accuracy of CLE and target biopsies of surgical specimens.
RESULTS A total of 144 patients were included. Of these, 51% (74/144) were female. The mean age was 51 years old. In all, 41/144 (28.4%) lesions were neoplastic (13 bile duct, 10 gastric, 8 esophageal, 6 colonic, 1 duodenal, 1 rectal, 1 ampulloma and 1 pancreatic). The sensitivity, specificity, positive predictive value, negative predictive value, and observed agreement when CLE was used to detect N-lesions were 85.37%, 87.38%, 72.92%, 93.75% and 86.81%, respectively. Cohen’s Kappa was 69.20%, thus indicating good agreement. Changes in management were observed in 54% of the cases.
CONCLUSION CLE is a new diagnostic tool that has a significant clinical impact on the diagnosis and treatment of patients with uncertain diagnosis.
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Papafragkakis C, Lee J. Comprehensive management of cholangiocarcinoma: Part I. Diagnosis. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2017. [DOI: 10.18528/gii1500341] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Charilaos Papafragkakis
- epartment of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey Lee
- epartment of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Bertani H, Palazzo L, Mirante VG, Pigò F. Confocal Laser Endomicroscopy in GI Tract. DIAGNOSIS AND ENDOSCOPIC MANAGEMENT OF DIGESTIVE DISEASES 2017:1-20. [DOI: 10.1007/978-3-319-42358-6_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Diana M, Robinet E, Liu YY, Legnèr A, Kong SH, Schiraldi L, Marchegiani F, Halvax P, Swanstrom L, Dallemagne B, Marescaux J. Confocal Imaging and Tissue-Specific Fluorescent Probes for Real-Time In Vivo Immunohistochemistry. Proof of the Concept in a Gastric Lymph Node Metastasis Model. Ann Surg Oncol 2016; 23:567-573. [PMID: 26511264 DOI: 10.1245/s10434-015-4928-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Indexed: 04/13/2025]
Abstract
BACKGROUND Tumor-specific fluorescent antibodies, which can be recognized at a cellular or tissue level using optical imaging such as confocal laser endomicroscopy (CLE), could provide a means for rapid and accurate tumor diagnosis and staging. The aim of this study was to evaluate the ability of CLE to detect the presence of tagged cells within lymph nodes in an original simulated metastatic model. MATERIALS AND METHODS A solution of indocyanine green containing a suspension of porcine hepatocytes, marked with carboxy-fluorescein-succinimidyl-ester (CFSE), was injected endoscopically in the gastric submucosa of 10 pigs. Fluorescence lymphography using a near-infrared laparoscope was used to identify sentinel and secondary drainage nodes. Additionally, a nonfluorescent gastric and a mesenteric node were identified. Every 5-10 min, those nodes were scanned using probe-based or needle-based CLE (pCLE or nCLE). Immunohistochemistry (IHC) using anti-cytokeratin 18 antibodies was subsequently performed to confirm the presence of hepatocytes in the lymph nodes. RESULTS A total of 36 lymph nodes were analyzed with both CLE probes. Hepatocyte penetration in lymph nodes, as assessed by repeated CLE scanning, took 10-40 min after submucosal injection. Concordance between CLE and IHC was 84 and 72 % for pCLE and nCLE, respectively. False negatives were partly due to incomplete CFSE labeling of hepatocytes, which could not be recognized by CLE, but were detected with IHC. CONCLUSIONS Real-time CLE analysis effectively recognized the presence in perigastric nodes of marked hepatic cells that had been injected endoscopically in the stomach. Validation studies on tumor-bearing animals using tumor-specific antibodies should be performed.
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Affiliation(s)
- Michele Diana
- Research Institute Against Cancer of the Digestive System, IRCAD, Strasbourg, France.
- Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France.
| | - Eric Robinet
- Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France
| | - Yu-Yin Liu
- Research Institute Against Cancer of the Digestive System, IRCAD, Strasbourg, France
- Department of General Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taoyuan, Taiwan
| | - Andras Legnèr
- Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France
| | - Seong-Ho Kong
- Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
| | - Luigi Schiraldi
- Research Institute Against Cancer of the Digestive System, IRCAD, Strasbourg, France
| | - Francesco Marchegiani
- Research Institute Against Cancer of the Digestive System, IRCAD, Strasbourg, France
| | - Peter Halvax
- Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France
| | - Lee Swanstrom
- Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France
| | - Bernard Dallemagne
- Research Institute Against Cancer of the Digestive System, IRCAD, Strasbourg, France
| | - Jacques Marescaux
- Research Institute Against Cancer of the Digestive System, IRCAD, Strasbourg, France
- Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France
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