1
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Anakha J, Prasad YR, Pande AH. Endostatin in disease modulation: From cancer to beyond. Vascul Pharmacol 2025; 158:107459. [PMID: 39708990 DOI: 10.1016/j.vph.2024.107459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/04/2024] [Accepted: 12/16/2024] [Indexed: 12/23/2024]
Abstract
Angiogenesis plays a pivotal role in various pathological conditions, making it a key target in therapeutic development. Anti-angiogenic therapies are gaining traction for their potential in treating a range of angiogenesis-dependent diseases. Among these, endogenous angiogenesis inhibitors, particularly endostatin, have garnered significant attention for their therapeutic potential. While extensively studied for its anti-angiogenic effects in cancer, endostatin also exhibits anti-atherosclerotic and anti-fibrotic properties, broadening its therapeutic scope. Despite the successful clinical use of recombinant human endostatin in China for nearly two decades, its broader therapeutic potential remains underexplored. Thus, this review delves into the multifaceted applications of endostatin, examining its role in ocular diseases, inflammation, reproductive disorders, and tumor angiogenesis. Furthermore, it provides a comprehensive overview of its emerging roles beyond angiogenesis, particularly in the context of atherosclerosis and fibroproliferative conditions.
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Affiliation(s)
- J Anakha
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India.
| | - Yenisetti Rajendra Prasad
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India
| | - Abhay H Pande
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India.
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2
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Worix A, Keswani RN. Advanced Techniques in Therapeutic and Inflammatory Bowel Disease Colonoscopy. Gastroenterol Clin North Am 2024; 53:587-602. [PMID: 39489577 DOI: 10.1016/j.gtc.2024.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2024]
Abstract
Colonoscopy is an essential diagnostic and therapeutic tool in the management of colorectal disease. This review explores the recent advances of colonoscopy that have revolutionized patient care in the era of minimally invasive medicine. Key areas of focus include innovations in imaging, advanced endoscopic resection techniques, and nonsurgical management of strictures. Advances in therapeutic endoscopy are especially evident in inflammatory bowel disease. As the landscape of colonoscopy continues to evolve, it will continue to play a central role in modern medicine, shaping the future of patient care, and therapeutic interventions.
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Affiliation(s)
- Alexander Worix
- Hospital Medicine, Northwestern Feinberg School of Medicine, Chicago, IL, USA
| | - Rajesh N Keswani
- Division of Gastroenterology, Northwestern Feinberg School of Medicine, Chicago, IL, USA.
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3
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Santacroce G, Zammarchi I, Tan CK, Coppola G, Varley R, Ghosh S, Iacucci M. Present and future of endoscopy precision for inflammatory bowel disease. Dig Endosc 2024; 36:292-304. [PMID: 37643635 DOI: 10.1111/den.14672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 08/28/2023] [Indexed: 08/31/2023]
Abstract
Several advanced imaging techniques are now available for endoscopists managing inflammatory bowel disease (IBD) patients. These tools, including dye-based and virtual chromoendoscopy, probe-based confocal laser endomicroscopy and endocytoscopy, are increasingly innovative applications in clinical practice. They allow for a more in-depth and refined evaluation of the mucosal and vascular bowel surface, getting closer to histology. They have demonstrated a remarkable ability in assessing intestinal inflammation, histologic remission, and predicting relapse and favorable long-term outcomes. In addition, the future application of molecular endoscopy to predict biological drug responses has yielded preliminary but encouraging results. Furthermore, these techniques are crucial in detecting and characterizing IBD-related dysplasia, assisting endoscopic mucosal resection and submucosal dissection towards a surgery-sparing approach. Artificial intelligence (AI) holds great potential in this promising landscape, as it can provide an objective and reproducible assessment of inflammation and dysplasia. Moreover, it can improve the prediction of outcomes and aid in subsequent therapeutic decision-making. This review aims to summarize the promising role of state-of-the-art advanced endoscopic techniques and related AI-enabled models for managing IBD, paving the way for precision medicine.
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Affiliation(s)
- Giovanni Santacroce
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Irene Zammarchi
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Chin Kimg Tan
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
- Gastroenterology and Hepatology, Changi General Hospital, Singapore City, Singapore
| | - Gaetano Coppola
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
- Internal Medicine and Gastroenterology - Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Rachel Varley
- Department of Gastroenterology, Mercy University Hospital, Cork, Ireland
| | - Subrata Ghosh
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
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4
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Zammarchi I, Santacroce G, Iacucci M. Next-Generation Endoscopy in Inflammatory Bowel Disease. Diagnostics (Basel) 2023; 13:2547. [PMID: 37568910 PMCID: PMC10417286 DOI: 10.3390/diagnostics13152547] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/28/2023] [Accepted: 07/29/2023] [Indexed: 08/13/2023] Open
Abstract
Endoscopic healing is recognized as a primary treatment goal in Inflammatory Bowel Disease (IBD). However, endoscopic remission may not reflect histological remission, which is crucial to achieving favorable long-term outcomes. The development of new advanced techniques has revolutionized the field of IBD assessment and management. These tools can accurately assess vascular and mucosal features, drawing endoscopy closer to histology. Moreover, they can enhance the detection and characterization of IBD-related dysplasia. Given the persistent challenge of interobserver variability, a more standardized approach to endoscopy is warranted, and the integration of artificial intelligence (AI) holds promise for addressing this limitation. Additionally, although molecular endoscopy is still in its infancy, it is a promising tool to forecast response to therapy. This review provides an overview of advanced endoscopic techniques, including dye-based and dye-less chromoendoscopy, and in vivo histological examinations with probe-based confocal laser endomicroscopy and endocytoscopy. The remarkable contribution of these tools to IBD management, especially when integrated with AI, is discussed. Specific attention is given to their role in improving disease assessment, detection, and characterization of IBD-associated lesions, and predicting disease-related outcomes.
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Affiliation(s)
| | | | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, T12 R229 Cork, Ireland; (I.Z.); (G.S.)
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5
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Vitali F, Morgenstern N, Eckstein M, Atreya R, Waldner M, Hartmann A, Neurath MF, Rath T. Endocytoscopy for assessing histologic inflammation in ulcerative colitis: development and prospective validation of the ELECT (ErLangen Endocytoscopy in ColiTis) score (with videos). Gastrointest Endosc 2023; 97:100-111.e1. [PMID: 36058265 DOI: 10.1016/j.gie.2022.08.023] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 08/11/2022] [Accepted: 08/19/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND AND AIMS Apart from endoscopic healing as an established treatment goal in patients with inflammatory bowel disease (IBD), histologic remission is an emerging endpoint that might even better predict disease outcome, especially in ulcerative colitis (UC). Within this study, we aimed to evaluate whether endocytoscopy (EC) as an in vivo contact microscopy technology can accurately assess histologic inflammation and predict the further course of disease in UC patients. METHODS Initially, a new and intuitive EC score reflecting the entire spectrum of microscopic disease activity in UC was consensually developed. Subsequently, this score was independently validated in 46 patients with UC who underwent close-meshed follow-up during which major adverse outcomes (MAOs; defined as disease flare, IBD-related hospitalization, IBD-related surgery, necessity for initiation or escalation therapy) were recorded. Results of EC grading of inflammatory activity were compared against 2 validated histologic scores in UC. Diagnostic performance of endoscopic remission under white-light endoscopy (Mayo Endoscopic Score and Ulcerative Colitis Endoscopic Index of Severity), EC, and histology were compared for the prediction of MAOs. RESULTS Endocytoscopic assessment of inflammatory activity in UC based on the newly developed ErLangen Endocytoscopy in ColiTis score showed strong correlation with histopathologic scoring (Robarts Histopathology Index, r = .70; Nancy Histologic Index, r = .73) and was superior to white-light endoscopy for grading of microscopic disease activity, with a sensitivity of 88%, specificity of 95.2%, and area under the curve of .916. Furthermore, EC exhibited a high interobserver agreement for in vivo grading of microscopic inflammation and was comparably accurate as histopathology for forecasting the occurrence of MAOs in UC. CONCLUSIONS Endocytoscopic grading of inflammatory activity along a newly developed scoring system enabled real-time histology in UC patients and better predicted clinical outcome in UC patients than endoscopic remission.
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Affiliation(s)
- Francesco Vitali
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Erlangen, Germany
| | - Nadine Morgenstern
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Erlangen, Germany
| | - Markus Eckstein
- Institute of Pathology, University Hospital of Erlangen, University Erlangen-Nürnberg, Erlangen, Germany
| | - Raja Atreya
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Erlangen, Germany
| | - Maximilian Waldner
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Erlangen, Germany
| | - Arndt Hartmann
- Institute of Pathology, University Hospital of Erlangen, University Erlangen-Nürnberg, Erlangen, Germany
| | - Markus F Neurath
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Erlangen, Germany
| | - Timo Rath
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Erlangen, Germany
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6
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Harold KM, MacCuaig WM, Holter-Charkabarty J, Williams K, Hill K, Arreola AX, Sekhri M, Carter S, Gomez-Gutierrez J, Salem G, Mishra G, McNally LR. Advances in Imaging of Inflammation, Fibrosis, and Cancer in the Gastrointestinal Tract. Int J Mol Sci 2022; 23:16109. [PMID: 36555749 PMCID: PMC9781634 DOI: 10.3390/ijms232416109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/14/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022] Open
Abstract
Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohn's disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes.
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Affiliation(s)
- Kylene M. Harold
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | | | | | | | - Kaitlyn Hill
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Alex X. Arreola
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Malika Sekhri
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Steven Carter
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Jorge Gomez-Gutierrez
- Department of Child Health, School of Medicine, University of Missouri, Columbia, MO 65211, USA
| | - George Salem
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Girish Mishra
- Wake Forest Baptist Health, Winston-Salem, NC 27157, USA
| | - Lacey R. McNally
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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7
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Pal P, Singh AP, Kanuri ND, Banerjee R. Electronic chromo-endoscopy: technical details and a clinical perspective. Transl Gastroenterol Hepatol 2022; 7:6. [PMID: 35243115 PMCID: PMC8826039 DOI: 10.21037/tgh-19-373] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 05/12/2020] [Indexed: 08/13/2023] Open
Abstract
Precise endoscopic assessment is necessary to detect neoplastic changes in an early stage. Electronic or virtual chromo-endoscopy (ECE) is an alternative to conventional dye-based chromo-endoscopy which markedly improves capillary pattern and hence can detect micro-vessel morphological changes of early neoplasia to target biopsies and aid in diagnosis. The clinical significance increased after the advent of endoscopic treatment modalities like ESD/EMR which requires precise delineation of extent and depth of lesion. Most of the studies have used narrow-band imaging (NBI) (Olympus Medical Systems Tokyo, Japan), although data from i-SCAN (PENTAX Endoscopy, Tokyo, Japan) and flexible spectral imaging color enhancement (FICE) (Fujinon, Fujifilm Medical Co, Saitama, Japan) are emerging. Electronic chromo-endoscopy is convenient compared to dye-based chromo-endoscopy in the sense that it is available at the push of a button in endoscope and reduces procedure time substantially with comparable efficacy. Scope of this review is to discuss available electronic chromo-endoscopy modalities and their role in the diagnosis, surveillance, and management of early GI neoplasia.
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Affiliation(s)
- Partha Pal
- Department of Medical Gastroenterology, AIG hospitals, Hyderabad, India
| | | | - Navya D Kanuri
- Department of Medical Gastroenterology, AIG hospitals, Hyderabad, India
| | - Rupa Banerjee
- Department of Medical Gastroenterology, AIG hospitals, Hyderabad, India
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8
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Moriichi K, Fujiya M, Okumura T. The endoscopic diagnosis of mucosal healing and deep remission in inflammatory bowel disease. Dig Endosc 2021; 33:1008-1023. [PMID: 33020947 DOI: 10.1111/den.13863] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 09/24/2020] [Accepted: 09/28/2020] [Indexed: 12/13/2022]
Abstract
The therapeutic goal in inflammatory bowel disease (IBD) patients has shifted from controlling the clinical activity alone to managing other associated problems. The concept of mucosal healing (MH) and deep remission (DR) are advocated and regarded as new therapeutic goals in IBD. However, the definition of MH still remains controversial. It is unclear whether or not the histological structures or functional factors should be included in the definition of DR in addition to clinical remission and MH. The classifications of white-light imaging (e.g. Mayo endoscopic subscore, UCEIS, CD Endoscopic Index of Severity, simple Endoscopic Score-CD) have been proposed and are now widely used to assess the severity as well as the MH of inflammation in IBD. In ulcerative colitis, magnifying chromoendoscopy has been shown to be useful to assess the MH of inflammation while other types of image-enhanced endoscopy, such as narrow-band imaging, have not. Endocytoscopy and confocal laser endomicroscopy (CLE) are also applied to assess the activity in IBD. These endoscopic procedures can estimate MH with more precision through observing the details of superficial structures, such as crypt openings. In addition, CLE can partially assess the mucosal function by detecting fluorescence leakage. Molecular imaging can possibly detect the molecules associated with inflammation, intestinal regeneration and differentiation, and various functions including the intestinal barrier and mucus secretion. These novel procedures may improve the diagnosis strategy of DR through the assessment of DR-associated factors such as the histological structures and functional factors in the near future.
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Affiliation(s)
- Kentaro Moriichi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
| | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
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9
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Solitano V, D’Amico F, Allocca M, Fiorino G, Zilli A, Loy L, Gilardi D, Radice S, Correale C, Danese S, Peyrin-Biroulet L, Furfaro F. Rediscovering histology: what is new in endoscopy for inflammatory bowel disease? Therap Adv Gastroenterol 2021; 14:17562848211005692. [PMID: 33948114 PMCID: PMC8053840 DOI: 10.1177/17562848211005692] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 03/08/2021] [Indexed: 02/04/2023] Open
Abstract
The potential of endoscopic evaluation in the management of inflammatory bowel diseases (IBD) has undoubtedly grown over the last few years. When dealing with IBD patients, histological remission (HR) is now considered a desirable target along with symptomatic and endoscopic remission, due to its association with better long-term outcomes. Consequently, the ability of endoscopic techniques to reflect microscopic findings in vivo without having to collect biopsies has become of upmost importance. In this context, a more accurate evaluation of inflammatory disease activity and the detection of dysplasia represent two mainstay targets for IBD endoscopists. New diagnostic technologies have been developed, such as dye-less chromoendoscopy, endomicroscopy, and molecular imaging, but their real incorporation in daily practice is not yet well defined. Although dye-chromoendoscopy is still recommended as the gold standard approach in dysplasia surveillance, recent research questioned the superiority of this technique over new advanced dye-less modalities [narrow band imaging (NBI), Fuji intelligent color enhancement (FICE), i-scan, blue light imaging (BLI) and linked color imaging (LCI)]. The endoscopic armamentarium might also be enriched by new video capsule endoscopy for monitoring disease activity, and high expectations are placed on the application of artificial intelligence (AI) systems to reduce operator-subjectivity and inter-observer variability. The goal of this review is to provide an updated insight on contemporary knowledge regarding new endoscopic techniques and devices, with special focus on their role in the assessment of disease activity and colorectal cancer surveillance.
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Affiliation(s)
- Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Ferdinando D’Amico
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy,IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Mariangela Allocca
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy,IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Gionata Fiorino
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy,IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Alessandra Zilli
- IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Laura Loy
- IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Daniela Gilardi
- IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Simona Radice
- IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Carmen Correale
- IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy,IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
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10
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van der Laan JJH, van der Waaij AM, Gabriëls RY, Festen EAM, Dijkstra G, Nagengast WB. Endoscopic imaging in inflammatory bowel disease: current developments and emerging strategies. Expert Rev Gastroenterol Hepatol 2021; 15:115-126. [PMID: 33094654 DOI: 10.1080/17474124.2021.1840352] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Developments in enhanced and magnified endoscopy have signified major advances in endoscopic imaging of ileocolonic pathology in inflammatory bowel disease (IBD). Artificial intelligence is increasingly being used to augment the benefits of these advanced techniques. Nevertheless, treatment of IBD patients is frustrated by high rates of non-response to therapy, while delayed detection and failures to detect neoplastic lesions impede successful surveillance. A possible solution is offered by molecular imaging, which adds functional imaging data to mucosal morphology assessment through visualizing biological parameters. Other label-free modalities enable visualization beyond the mucosal surface without the need of tracers. AREAS COVERED A literature search up to May 2020 was conducted in PubMed/MEDLINE in order to find relevant articles that involve the (pre-)clinical application of high-definition white light endoscopy, chromoendoscopy, artificial intelligence, confocal laser endomicroscopy, endocytoscopy, molecular imaging, optical coherence tomography, and Raman spectroscopy in IBD. EXPERT OPINION Enhanced and magnified endoscopy have enabled an improved assessment of the ileocolonic mucosa. Implementing molecular imaging in endoscopy could overcome the remaining clinical challenges by giving practitioners a real-time in vivo view of targeted biomarkers. Label-free modalities could help optimize the endoscopic assessment of mucosal healing and dysplasia detection in IBD patients.
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Affiliation(s)
- Jouke J H van der Laan
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen , Groningen, The Netherlands
| | - Anne M van der Waaij
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen , Groningen, The Netherlands
| | - Ruben Y Gabriëls
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen , Groningen, The Netherlands
| | - Eleonora A M Festen
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen , Groningen, The Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen , Groningen, The Netherlands
| | - Wouter B Nagengast
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen , Groningen, The Netherlands
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11
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Salavati M, Pérez-Accino J, Tan YL, Liuti T, Smith S, Morrison L, Salavati Schmitz S. Correlation of minimally invasive imaging techniques to assess intestinal mucosal perfusion with established markers of chronic inflammatory enteropathy in dogs. J Vet Intern Med 2020; 35:162-171. [PMID: 33314285 PMCID: PMC7848335 DOI: 10.1111/jvim.15997] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 11/24/2020] [Accepted: 12/01/2020] [Indexed: 02/06/2023] Open
Abstract
Background Minimally invasive diagnostic imaging techniques to detect intestinal inflammation in dogs are lacking. Contrast‐enhanced ultrasound (CEUS) and endoscopic narrow band imaging‐like endoscopy (Storz Professional Image Enhancement System [SPIES]) might allow quantification of intestinal mucosal perfusion and microvessel density in chronic inflammatory enteropathy (CIE) of dogs. Hypothesis/Objectives Markers of mucosal perfusion as determined by CEUS and SPIES endoscopy are potentially useful diagnostic markers to help characterize CIE and correlate with histological inflammation type and severity. Animals Thirty client‐owned dogs diagnosed with CIE at a referral hospital were prospectively enrolled. Materials and Methods Data from CEUS, SPIES, and white light (WL) endoscopy were correlated with World Small Animal Veterinary Association (WSAVA) endoscopy and histology scores and vessel density as determined by immunohistochemistry for von Willebrand factor (vWF). Automated linear modeling was used to determine predictors of endoscopic and histologic severity. Results Duodenal histology correlated with SPIES data (area percentage value, rho = 0.424, P = .04). White light endoscopy parameters correlated with SPIES parameters in the duodenum. Colonic histology correlated positively with CEUS, whereas colonic CEUS parameters correlated inversely with vWF expression. Several duodenal parameters combined predicted duodenal histology scores to a level of 73.4%. For the colon, 2 parameters contributed more than others to 73.1%. Conclusion and Clinical Importance Minimally invasive CEUS and SPIES appear feasible to assess intestinal perfusion in CIE. Use of SPIES endoscopy may be promising for assessing small intestinal inflammation, whereas CEUS could be used to assess colonic perfusion and inflammation. Both techniques need to be investigated further for their clinical utility.
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Affiliation(s)
- Mazdak Salavati
- Genetics and Genomics Department, The Roslin Institute, University of Edinburgh, Easter Bush, United Kingdom
| | - Jorge Pérez-Accino
- The Royal (Dick) School of Veterinary Studies, Hospital for Small Animals, University of Edinburgh, Easter Bush, United Kingdom
| | - Yi Lin Tan
- The Royal (Dick) School of Veterinary Studies, Hospital for Small Animals, University of Edinburgh, Easter Bush, United Kingdom
| | - Tiziana Liuti
- The Royal (Dick) School of Veterinary Studies, Hospital for Small Animals, University of Edinburgh, Easter Bush, United Kingdom
| | - Sionagh Smith
- Easter Bush Pathology, The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom
| | - Linda Morrison
- Easter Bush Pathology, The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom
| | - Silke Salavati Schmitz
- The Royal (Dick) School of Veterinary Studies, Hospital for Small Animals, University of Edinburgh, Easter Bush, United Kingdom
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12
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Dickson K, Malitan H, Lehmann C. Imaging of the Intestinal Microcirculation during Acute and Chronic Inflammation. BIOLOGY 2020; 9:E418. [PMID: 33255906 PMCID: PMC7760140 DOI: 10.3390/biology9120418] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 11/18/2020] [Indexed: 12/12/2022]
Abstract
Because of its unique microvascular anatomy, the intestine is particularly vulnerable to microcirculatory disturbances. During inflammation, pathological changes in blood flow, vessel integrity and capillary density result in impaired tissue oxygenation. In severe cases, these changes can progress to multiorgan failure and possibly death. Microcirculation may be evaluated in superficial tissues in patients using video microscopy devices, but these techniques do not allow the assessment of intestinal microcirculation. The gold standard for the experimental evaluation of intestinal microcirculation is intravital microscopy, a technique that allows for the in vivo examination of many pathophysiological processes including leukocyte-endothelial interactions and capillary blood flow. This review provides an overview of changes in the intestinal microcirculation in various acute and chronic inflammatory conditions. Acute conditions discussed include local infections, severe acute pancreatitis, necrotizing enterocolitis and sepsis. Inflammatory bowel disease and irritable bowel syndrome are included as examples of chronic conditions of the intestine.
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Affiliation(s)
- Kayle Dickson
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada;
| | - Hajer Malitan
- Department of Anesthesia, Pain and Perioperative Management, Dalhousie University, Halifax, NS B3H 4R2, Canada;
| | - Christian Lehmann
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada;
- Department of Anesthesia, Pain and Perioperative Management, Dalhousie University, Halifax, NS B3H 4R2, Canada;
- Department of Physiology and Biophysics, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
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Wang L, Wang S, Xue A, Shi J, Zheng C, Huang Y. Thalidomide Inhibits Angiogenesis via Downregulation of VEGF and Angiopoietin-2 in Crohn's Disease. Inflammation 2020; 44:795-807. [PMID: 33206273 DOI: 10.1007/s10753-020-01378-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/20/2020] [Accepted: 10/25/2020] [Indexed: 12/14/2022]
Abstract
Immune-mediated angiogenesis is important in the pathogenesis of inflammatory bowel disease and targeted treatment could alleviate the disease. Thalidomide is an effective drug in inflammatory bowel disease, which might be related to its multiple role in anti-inflammatory, immunoregulatory, and anti-angiogenesis. This study is to investigate the effect of thalidomide on angiogenesis in tissues from patients and in vitro cells. Angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), VEGF, and CD31 expressions in intestinal mucosa from pediatric CD patients before and after thalidomide treatment were measured by immunohistochemistry. Western blotting and polymerase chain reaction were performed to characterize the change of angiogenic factors before and after treatment in remission. Human umbilical vein endothelial cells (HUVECs) treated by thalidomide were used to examine its effect on endothelial cell proliferation and migration and capillary-like structures. Results showed that VEGF and Ang-2 levels were significantly greater in CD patients over controls. Thalidomide produced a significant reduction in protein expression of Ang-2 and VEGF, along with a decrease in mRNA expression of Ang-2. While, Ang-1 level did not show a statistically significant change. Thalidomide significantly inhibited cell proliferation in a dose-dependent manner. It also suppressed VEGF- and Ang-2-induced cell migration and capillary-like tube formation in HUVECs. Therefore, our study suggests that VEGF and Ang-2 levels are up-regulated in pediatric CD patients. It also indicated that thalidomide can be able to deactivate endothelium by the downregulation effect on angiogenic factors by targeting VEGF and Ang-2.
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Affiliation(s)
- Lin Wang
- Department of Gastroenterology, Children's Hospital of Fudan University/National Children's Medical Center, Shanghai, China
| | - Shengnan Wang
- Department of Gastroenterology, Children's Hospital of Fudan University/National Children's Medical Center, Shanghai, China
| | - Aijuan Xue
- Department of Gastroenterology, Children's Hospital of Fudan University/National Children's Medical Center, Shanghai, China
| | - Jieru Shi
- Department of Gastroenterology, Children's Hospital of Fudan University/National Children's Medical Center, Shanghai, China
| | - Cuifang Zheng
- Department of Gastroenterology, Children's Hospital of Fudan University/National Children's Medical Center, Shanghai, China
| | - Ying Huang
- Department of Gastroenterology, Children's Hospital of Fudan University/National Children's Medical Center, Shanghai, China.
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14
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Hasan B, Senada PA, Wallace MB, Iacucci M, Shen B. Chromoendoscopy in inflammatory bowel disease. ATLAS OF ENDOSCOPY IMAGING IN INFLAMMATORY BOWEL DISEASE 2020:265-309. [DOI: 10.1016/b978-0-12-814811-2.00019-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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15
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Klenske E, Atreya R, Hartmann A, Fischer S, Hirschmann S, Zundler S, Iaccuci M, Neurath MF, Rath T. Magnification endoscopy with optical chromoendoscopy shows strong correlation with histologic inflammation in patients with inflammatory bowel disease. Endosc Int Open 2019; 7:E1018-E1026. [PMID: 31404439 PMCID: PMC6687476 DOI: 10.1055/a-0953-1334] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 04/24/2019] [Indexed: 12/15/2022] Open
Abstract
Background and study aims Apart from mucosal healing as an established treatment goal in inflammatory bowel diseases (IBD), recent evidence suggests that histologic healing may become another key prognostic parameter in IBD patients. We aimed to evaluate whether magnification endoscopy with optical chromoendoscopy can accurately assess histologic inflammation in IBD patients. Patients and methods In this prospective study, 82 patients with IBD (30 UC, 52 CD) were included. In all patients, magnification endoscopy in conjunction with optical chromoendoscopy was performed and rated on a novel magnification endoscopy score by three independent endoscopists. Targeted biopsies of the imaged areas were obtained and results were compared against two histological scores in UC (Robarts Histopathology Index, RHI; Nancy Histology Index, NHI) and one score in CD (modified Riley index, mRI). Moreover, interobserver agreement was calculated. Results Magnification endoscopy showed strong correlation with histopathologic scoring in both UC (RHI: r = 0.83, NHI: r = 0.78, P < 0.05) and CD (mRI: r = 0.74, P < 0.05) with high accuracy, sensitivity, and specificity. Further, 25 % of patients with mucosal healing on standard endoscopy showed signs of microinflammation on magnification endoscopy with optical chromoendoscopy, while none of the patients with mucosal and vascular healing under magnification endoscopy with optical chromoendoscopy exhibited microscopic inflammation. Interobserver agreement for grading intestinal inflammation by magnification endoscopy with optical chromoendoscopy was substantial (κ > 0.7). Conclusion Magnification endoscopy in combination with optical chromoendoscopy shows strong correlation with histologic inflammation in patients with IBD. This approach has potential to reduce physical biopsies for monitoring of inflammatory activity in patients with IBD during colonoscopy.
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Affiliation(s)
- Entcho Klenske
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Germany
| | - Raja Atreya
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Germany
| | - Arndt Hartmann
- Institute of Pathology, University Hospital of Erlangen, University Erlangen-Nürnberg, Germany
| | - Sarah Fischer
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Germany
| | - Simon Hirschmann
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Germany
| | - Sebastian Zundler
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Germany
| | - Marietta Iaccuci
- Institute of Translational Medicine, University of Birmingham, United Kingdom
| | - Markus F. Neurath
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Germany
| | - Timo Rath
- Department of Medicine I, Division of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital of Erlangen, University Erlangen-Nürnberg, Germany
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Nardone OM, Cannatelli R, Zardo D, Ghosh S, Iacucci M. Can advanced endoscopic techniques for assessment of mucosal inflammation and healing approximate histology in inflammatory bowel disease? Therap Adv Gastroenterol 2019; 12:1756284819863015. [PMID: 31360224 PMCID: PMC6640057 DOI: 10.1177/1756284819863015] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 06/14/2019] [Indexed: 02/04/2023] Open
Abstract
The targets of therapy in inflammatory bowel disease have transformed in the last few years. The standard definition of mucosal healing assessed using white light standard definition endoscopy is being challenged because even when endoscopy suggests mucosal healing, the presence of histological activity can often still be observed. Of note, microscopic signs of inflammation correlate with clinical outcomes such as risk of relapse, hospitalization and colorectal cancer. Therefore, histological healing has increasingly become an important target to achieve. Advanced endoscopic technologies have been developed and many are starting to be adopted in daily clinical practice. They can provide a more detailed view of the mucosal and vascular architecture almost at the histology level, including crypt, vessel architecture and cellular infiltration. So, these can provide a more accurate definition of mucosal and histological healing. In this review we focus on new advanced endoscopic techniques, and how these have the potential to reduce the gap between histological and mucosal healing.
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Affiliation(s)
- Olga Maria Nardone
- Institute of Translational Medicine and
Institute of Immunology and Immunotherapy, University of Birmingham,
Heritage Building, Mindelsohn Way, Birmingham, B15 2TH, UK
| | - Rosanna Cannatelli
- Institute of Translational Medicine and
Institute of Immunology and Immunotherapy, University of Birmingham,
Birmingham, UK
| | - Davide Zardo
- University Hospitals Birmingham NHS Foundation
Trust, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Subrata Ghosh
- Institute of Translational Medicine and
Institute of Immunology and Immunotherapy, University of Birmingham,
Birmingham, UK
- University Hospitals Birmingham NHS Foundation
Trust, Queen Elizabeth Hospital Birmingham, Birmingham, UK
- NIHR Biomedical Research Centre, University of
Birmingham and University Hospitals NHS Foundation Trust Birmingham,
UK
| | - Marietta Iacucci
- Institute of Translational Medicine and
Institute of Immunology and Immunotherapy, University of Birmingham,
Birmingham, UK
- University Hospitals Birmingham NHS Foundation
Trust, Queen Elizabeth Hospital Birmingham, Birmingham, UK
- NIHR Biomedical Research Centre, University of
Birmingham and University Hospitals NHS Foundation Trust Birmingham,
UK
- University of Calgary, Calgary, Canada
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17
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Imbalanced mucosal microcirculation in the remission stage of ulcerative colitis using probe-based confocal laser endomicroscopy. BMC Gastroenterol 2019; 19:114. [PMID: 31262270 PMCID: PMC6604483 DOI: 10.1186/s12876-019-1037-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 06/24/2019] [Indexed: 12/31/2022] Open
Abstract
Background Microcirculatory disturbance is an important factor in the pathogenesis of Inflammatory Bowel Disease (IBD) but there have been few studies in this field. Confocal Laser Endomicroscopy (CLE) has been used over the last 10 years and has made it possible to explore the changes in microcirculation of the colonic mucosa. Methods We retrospectively selected patients who underwent probe-based Confocal Laser Endomicroscopy (pCLE) between 2014 and 2016. There were 7 patients with ulcerative colitis (UC) in clinical remission and 7 healthy subjects included in this study; all the UC patients’ medical data were reviewed. For each patient, three segments of the colon were examined using pCLE including the ascending, transverse/descending and sigmoid colon. In each segment, the representative pCLE images of the three sites were selected for analysis. Four indicators, including Mean Vessel Diameter (MVD), Diameter Standard Deviation (DSD), Functional Capillary Density-long (FCDL) and Functional Capillary Density-area (FCDA), were measured with a specially designed detection software algorithm. The four indicators were compared between UC patients and healthy subjects. According to the different blood flow patterns, three types of distribution were established: the Around (A), Cobweb (C) and Deficiency (D) type. The relationships between the recurrence and blood flow patterns of UC patients were analyzed. Results MVD, DSD, FCDL and FCDA were 10.62 ± 0.56 μm, 2.23 ± 0.26, 0.030 ± 0.019 μm and 0.289 ± 0.030 for the healthy subjects and 11.06 ± 1.10 μm, 2.68 ± 0.29, 0.026 ± 0.005 μm and 0.272 ± 0.034 for the UC patients, respectively. Compared with healthy subjects, DSD was significantly increased and FCDA was significantly decreased (P < 0.01 for both). There was no difference in MVD and FCDL between UC patients and healthy subjects. The type A and type C blood flows were observed in healthy subjects (66.67 and 33.33%, respectively) while type C appears more in UC patients (71.3%) and type D blood flow could only be found in UC patients (14.29%) P < 0.01. UC patients who showed Type D blood flow had a shorter recurrence interval. Conclusions Some local mucosal capillary density in UC patients was decreased, particularly in the inflammation-affected segment. The three mucosal blood flow patterns can be used as an indicator of mucosal healing.
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18
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Tian Y, Zheng Y, Dong J, Zhang J, Wang H. Papaverine adjuvant therapy for microcirculatory disturbance in severe ulcerative colitis complicated with CMV infection: a case report. Clin J Gastroenterol 2019; 12:407-413. [PMID: 30945123 PMCID: PMC6763508 DOI: 10.1007/s12328-019-00974-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 03/26/2019] [Indexed: 12/21/2022]
Abstract
Ulcerative colitis has hypercoagulable state and high risk of thrombosis; so mucosal disturbance of microcirculation may be mediate and amplify the inflammation of ulcerative colitis. A 56-year-old female patient was admitted in hospital for discontinuously mucous bloody stool for more than 1 year. Ulcerative colitis was determined after colonoscopy and pathologic examination. Mesalazine was effective during the year, but her symptoms recurred three times due to her bad compliance. One month before admission, the patient had severe recurrence after mesalazine withdrawal. At this time, the result of quantitative fluorescence PCR of colonic histic CMV-DNA was 1.6 × 104 copies/mL positive, CMV colitis was accompanied. After 4 weeks of ganciclovir and 6 weeks of mesalazine usage and nutrition support, the symptoms of diarrhea and abdominal cramp did not improve; stool frequency was more than twenty times a day. Probe-based confocal laser endomicroscopy revealed local microcirculation disturbance. Papaverine 90-mg slow drip for at least 10 h a day was added. The symptoms dramatically disappeared after 3 days of papaverine treatment. The patient had yellow mushy stool 2–3 times a day. Pathological findings showed diffuse submucosal hemorrhage and transparent thrombosis in capillaries. Treatment of microcirculatory disturbance in severe UC is a promising adjuvant therapy. Confocal laser endomicroscopy may be an effective method for microcirculation judgment.
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Affiliation(s)
- Yu Tian
- Gastroenterology Department of Peking, University First Hospital, Beijing, China
| | - Yue Zheng
- Gastroenterology Department of Peking, University First Hospital, Beijing, China
| | - Jinpei Dong
- Gastroenterology Department of Peking, University First Hospital, Beijing, China
| | - Jixin Zhang
- Pathology Department of Peking, University First Hospital, Beijing, China
| | - Huahong Wang
- Gastroenterology Department of Peking, University First Hospital, Beijing, China.
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19
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Mucosal healing in inflammatory bowel disease: Expanding horizon. Indian J Gastroenterol 2019; 38:98-109. [PMID: 31037509 DOI: 10.1007/s12664-019-00950-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 02/27/2019] [Indexed: 02/06/2023]
Abstract
Management of inflammatory bowel diseases has witnessed paradigm shift from 5-aminosalicylic acid and glucocorticoids to various immunosuppressant and biological agents. Targets of therapy have also been changed drastically from symptomatic improvement to mucosal, histological healing, and recently transmural healing. Mucosal healing is associated with reduced need of steroid therapy, hospitalization, and surgery. However, whether mucosal healing alters the natural history of disease remains to be proven. Though assessment of mucosal healing is traditionally done by endoscopic examination, newer tests like fecal calprotectin, capsule endoscopy, and magnetic resonance enterography have also shown promising results. Various immunosuppressants and biologicals are the main therapy being used to achieve mucosal healing. This review focuses on the need for achieving mucosal healing, its long-term benefits, various methods and algorithm for diagnosis, and achievement of mucosal healing.
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20
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Narrow-Band Imaging Colonoscopy to Assess Mucosal Angiogenesis in Ulcerative Colitis. Gastroenterol Res Pract 2019; 2019:8312624. [PMID: 30918516 PMCID: PMC6409060 DOI: 10.1155/2019/8312624] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 12/15/2018] [Accepted: 01/30/2019] [Indexed: 01/17/2023] Open
Abstract
Background and Aim It has been documented that angiogenesis is a largely unstudied component of the pathogenesis of ulcerative colitis (UC). Under narrow-band imaging (NBI) colonoscopy, the mucosal vascular pattern (MVP) can be visualized without the use of dyes. The aim of this study was to assess the grade of mucosal angiogenesis based on the MVP in UC. Methods A total of 119 colorectal segments taken from 42 patients with UC were observed using NBI colonoscopy. The MVP was classified as follows: clear, obscure, or absent. Quantification of the degree of inflammation was performed using histological colitis scoring. Potent angiogenic activity was assessed by immunohistochemical staining for vascular endothelial growth factor (VEGF). Microvascular density was assessed using vessel counts as revealed by CD31 staining. The correlation between the MVP and histological grades of inflammation and angiogenesis was evaluated. Results The MVP correlated well with the histological severity of inflammation. We also demonstrated an increasing level of microvascular density and VEGF staining along with the ordered types of MVPs. In addition, a statistically strong association existed between microvascular density and VEGF staining. Conclusions NBI colonoscopy might be a useful tool for the in vivo assessment of the grade of mucosal angiogenesis in UC.
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21
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Lu C, Merrill C, Medellin A, Novak K, Wilson SR. Bowel Ultrasound State of the Art: Grayscale and Doppler Ultrasound, Contrast Enhancement, and Elastography in Crohn Disease. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:271-288. [PMID: 30604884 DOI: 10.1002/jum.14920] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 11/08/2018] [Accepted: 11/22/2018] [Indexed: 06/09/2023]
Abstract
Bowel ultrasound (US) is accurate for assessing bowel inflammation and complications in Crohn disease. Additionally, contrast-enhanced US provides a quantitative, objective measurement of inflammatory activity in inflammatory bowel disease, and shear wave elastography predicts the stiffness of bowel, an increase of which suggests less response to medical therapy, often necessitating surgery. Overall, bowel US is an excellent, safe, and repeatable choice for routine surveillance and for urgent imaging. We describe an approach to evaluating inflammatory bowel disease and review its features on standard grayscale US with Doppler imaging and show how contrast-enhanced US and shear wave elastography can distinguish between inflammatory and fibrostenotic bowel.
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Affiliation(s)
- Cathy Lu
- Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Christina Merrill
- Department of Radiology, University of Calgary, Calgary, Alberta, Canada
| | - Alexandra Medellin
- Department of Radiology, University of Calgary, Calgary, Alberta, Canada
| | - Kerri Novak
- Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Stephanie R Wilson
- Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
- Department of Radiology, University of Calgary, Calgary, Alberta, Canada
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22
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Modern Endoscopic Imaging in Diagnosis and Surveillance of Inflammatory Bowel Disease Patients. Gastroenterol Res Pract 2018; 2018:5738068. [PMID: 29955228 PMCID: PMC6000858 DOI: 10.1155/2018/5738068] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 04/24/2018] [Indexed: 12/18/2022] Open
Abstract
Endoscopy remains the most important diagnostic and monitoring modality in the management of inflammatory bowel disease. Advances in imaging have progressively added new tools into the armamentarium of endoscopists with the goal of more accurate, sensitive, and accessible visual diagnoses for the benefit of patients with gastrointestinal diseases. Here, we review the relevant literature regarding commonly used endoscopic techniques (dye-based and digital chromoendoscopy, high-definition endoscopy, capsule endoscopy, and endosonography), as well as advanced and experimental technologies (full-spectrum endoscopy, endocytoscopy, autofluorescence, laser endoscopy, and endomicroscopy, including molecular imaging), applicable to inflammatory bowel diseases and emerging for implementation into everyday practice. Additionally, we discuss future directions and techniques as candidates for a superior inflammation imaging in the diagnosis and prediction of therapeutic response.
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23
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Sasanuma S, Ohtsuka K, Kudo SE, Ogata N, Maeda Y, Misawa M, Mori Y, Kudo T, Hisayuki T, Wakamura K, Hayashi T, Katagiri A, Miyachi H, Baba T, Ishida F. Narrow band imaging efficiency in evaluation of mucosal healing/relapse of ulcerative colitis. Endosc Int Open 2018; 6:E518-E523. [PMID: 29713677 PMCID: PMC5906109 DOI: 10.1055/s-0044-102297] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 01/10/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND AND STUDY AIMS Mucosal healing is a current treatment target in ulcerative colitis (UC), while histological remission is another target. The aim of this study was to evaluate the efficiency of magnified narrow band imaging (NBI) findings of mucosal healing and their relationship with histological activity and prognosis. PATIENTS AND METHODS Patients with UC who underwent total colonoscopy between January 2010 and December 2012 with left-sided or total-colitis type UC and achieved clinical remission with an endoscopic Mayo score of 0 or 1 were included. Each colon section was observed with white light and magnified NBI, with the colonoscopy being repeated at 1-year follow-up. We assessed the relationships of magnified NBI with histological disease activity and prognosis. Magnified NBI findings were divided into three categories; honeycomb-like blood vessels (BV-H), blood vessels shaped like bare branches (BV-BB), and blood vessels shaped like vines (BV-V). RESULTS Fifty-two patients were included. The percentage of remitted mucosa with BV-BB was 37 %, while that of mucosa with scars with BV-H was 35 %. BV-H and BV-BB did not show pathological activity (12/292 and 8/299, respectively), while BV-V showed high pathological activity (27/33, 81 %). There was a correlation between magnified NBI findings and pathological findings ( P < 0.01). The odds ratio for inflammation activity at 1-year follow-up was 14.2 for BV-BB (95 % CI, 3.3 - 60.9). CONCLUSION Magnified NBI findings showed a good relationship with histological activity. This suggests that we could estimate histological activity without biopsy, and also the possibility of predicting relapse over the following year.
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Affiliation(s)
- Seiko Sasanuma
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan,Corresponding author Seiko Sasanuma (Hayashi) Showa University Northern Yokohama Hospital – Digestive Disease Center35-1 Chigasaki-chuo TsuzukiYokohama Kanagawa 224-8503Japan+81-45-949-7263
| | - Kazuo Ohtsuka
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan,Department of Endoscopy, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shin-ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Noriyuki Ogata
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Yasuharu Maeda
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Toyoki Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Tomokauzu Hisayuki
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Kunihiko Wakamura
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Takemasa Hayashi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Atsushi Katagiri
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Hideyuki Miyachi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Toshiyuki Baba
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Fumio Ishida
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
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Mechanisms of angiogenesis in microbe-regulated inflammatory and neoplastic conditions. Angiogenesis 2017; 21:1-14. [PMID: 29110215 DOI: 10.1007/s10456-017-9583-4] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Accepted: 10/24/2017] [Indexed: 12/19/2022]
Abstract
Commensal microbiota inhabit all the mucosal surfaces of the human body. It plays significant roles during homeostatic conditions, and perturbations in numbers and/or products are associated with several pathological disorders. Angiogenesis, the process of new vessel formation, promotes embryonic development and critically modulates several biological processes during adulthood. Indeed, deregulated angiogenesis can induce or augment several pathological conditions. Accumulating evidence has implicated the angiogenic process in various microbiota-associated human diseases. Herein, we critically review diseases that are regulated by microbiota and are affected by angiogenesis, aiming to provide a broad understanding of how angiogenesis is involved and how microbiota regulate angiogenesis in microbiota-associated human conditions.
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Adham M, Musa Z, Lisnawati, Suryati I. Sensitivity and specificity of narrow-band imaging nasoendoscopy compared to histopathology results in patients with suspected nasopharyngeal carcinoma. ACTA ACUST UNITED AC 2017. [DOI: 10.1088/1742-6596/884/1/012114] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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26
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Nisa K, Lim SY, Shinohara M, Nagata N, Sasaoka K, Dermlim A, Leela-Arporn R, Morita T, Yokoyama N, Osuga T, Sasaki N, Morishita K, Nakamura K, Ohta H, Takiguchi M. Repeatability and reproducibility of quantitative contrast-enhanced ultrasonography for assessing duodenal perfusion in healthy dogs. J Vet Med Sci 2017; 79:1585-1590. [PMID: 28781327 PMCID: PMC5627333 DOI: 10.1292/jvms.17-0174] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Contrast-enhanced ultrasonography (CEUS) with microbubbles as a contrast agent allows the visualization and quantification of tissue perfusion. The assessment of canine intestinal perfusion by quantitative CEUS may provide
valuable information for diagnosing and monitoring chronic intestinal disorders. This study aimed to assess the repeatability (intraday variability) and reproducibility (interday variability) of quantitative duodenal CEUS in
healthy dogs. Six healthy beagles underwent CEUS three times within one day (4-hr intervals) and on two different days (1-week interval). All dogs were sedated with a combination of butorphanol (0.2 mg/kg) and midazolam (0.1
mg/kg) prior to CEUS. The contrast agent (Sonazoid®) was administered using the intravenous bolus method (0.01 ml/kg) for imaging of the duodenum. Time-intensity curves (TIC) were created by drawing
multiple regions of interest (ROIs) in the duodenal mucosa, and perfusion parameters, including the time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), and wash-in and wash-out rates (WiR and WoR, respectively),
were generated. Intraday and interday coefficients of variation (CVs) for TTP, PI, AUC, WiR and WoR were <25% (range, 2.27–23.41%), which indicated that CEUS was feasible for assessing duodenal perfusion in healthy sedated
dogs. A further study of CEUS in dogs with chronic intestinal disorders is necessary to evaluate its clinical applicability.
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Affiliation(s)
- Khoirun Nisa
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Sue Yee Lim
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Masayoshi Shinohara
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Noriyuki Nagata
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Kazuyoshi Sasaoka
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Angkhana Dermlim
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Rommaneeya Leela-Arporn
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Tomoya Morita
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Nozomu Yokoyama
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Tatsuyuki Osuga
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Noboru Sasaki
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Keitaro Morishita
- Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Kensuke Nakamura
- Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Hiroshi Ohta
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Mitsuyoshi Takiguchi
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
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Ultrasound Shear Wave Elastography and Contrast Enhancement: Effective Biomarkers in Crohn's Disease Strictures. Inflamm Bowel Dis 2017; 23:421-430. [PMID: 28129289 DOI: 10.1097/mib.0000000000001020] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Inflammation, fibrosis, and muscular hypertrophy lead to thickened bowel in Crohn's disease forming strictures. Ultrasound shear wave elastography (SWE) measures bowel wall stiffness. Contrast-enhanced ultrasound (CEUS) uniquely detects bowel wall inflammation. We aim to correlate SWE of ileal Crohn's disease in vivo to CEUS peak enhancement and pathology grades of inflammation, fibrosis, and muscular hypertrophy. METHODS In a prospective institutional review board-approved study, 105 consecutive ileal patients with Crohn's disease received ultrasound. At maximal bowel wall thickness (>4 mm), SWE and CEUS were performed. Fifteen patients had ileal resection within a mean time interval of 71.0 ± 66.9 days. Pathology scores for inflammation, fibrosis, and muscular hypertrophy were compared with SWE and CEUS measurements. RESULTS Mean in vivo SWE velocity for patients with and without surgery was 2.8 ± 0.7 and 2.2 ± 0.8 m/s (P < 0.01), respectively. In all ileal specimens, chronic exceeded active inflammatory change (P < 0.001). There was an inverse relationship between CEUS peak enhancement and both fibrosis, r = -0.59, P = 0.02, and SWE velocity measurements, r = -0.61, P = 0.03. Strictured bowel specimens had more smooth muscle hypertrophy than fibrosis, P < 0.001. There was moderate correlation between SWE and muscular hypertrophy, r = 0.59, P = 0.02 and no significant relationship between SWE and fibrosis scores (P > 0.05). CONCLUSIONS Stiffer bowel from smooth muscle hypertrophy increases SWE measurements. We report a novel relation of high SWE with muscle hypertrophy, and inverse relationship with CEUS peak enhancement; providing differentiation between active and chronic bowel wall inflammation to improve selection between medical therapy and surgery.
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Kiesslich R, Neurath MF. Advanced endoscopy imaging in inflammatory bowel diseases. Gastrointest Endosc 2017; 85:496-508. [PMID: 27816496 DOI: 10.1016/j.gie.2016.10.034] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 10/24/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Rapid assessment of mucosal inflammation is of crucial importance for the initial diagnosis and the assessment of mucosal healing in inflammatory bowel disease (IBD). Moreover, the identification of intraepithelial neoplasias in IBD is of key relevance for clinical management. Here, we systematically analyzed the utility of advanced endoscopic imaging techniques for optimized diagnosis in IBD. METHODS PubMed/Medline, Web of Knowledge, and Cochrane library were searched twice for diagnostic studies on advanced endoscopic imaging in IBD. Clinical and technical information was retrieved and subsequently analyzed. Main outcome parameters consisted of the quality of the results, adverse events, and diagnostic yield. RESULTS Fifty-six clinical studies with a total of 3296 patients were selected for final analysis. Filter technologies permitted a more detailed analysis of mucosal inflammation in IBD. In spite of substantial heterogeneity across studies, dye-based chromoendoscopy with targeted biopsy sampling yielded higher detection rates of intraepithelial neoplasias in ulcerative colitis as compared with white-light endoscopy with random biopsy sampling. Moreover, endocytoscopy and endomicroscopy allowed subsurface imaging of inflamed or neoplastic mucosa in IBD at subcellular resolution. Finally, endomicroscopy-aided molecular imaging enabled the identification of membrane-bound tumor necrosis factor on mucosal cells as a potential driver of disease activity in Crohn's disease. No relevant adverse events were reported. CONCLUSIONS Advanced endoscopic imaging technologies are feasible, safe, and partially effective tools for detailed diagnosis of mucosal inflammation and detection of neoplasias in IBD. Results obtained from these advanced techniques may provide a rational basis for individualized, optimized therapy for IBD patients.
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Affiliation(s)
- Ralf Kiesslich
- Department of Medicine II, HELIOS Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
| | - Markus F Neurath
- Medical Clinic 1, Department of Medicine, University Hospital Erlangen, University of Erlangen-Nürnberg, Nürnberg, Germany; Ludwig Demling Endoscopy Center of Excellence, Erlangen, Germany
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Li Y, Zhu W, Zuo L, Shen B. The Role of the Mesentery in Crohn's Disease: The Contributions of Nerves, Vessels, Lymphatics, and Fat to the Pathogenesis and Disease Course. Inflamm Bowel Dis 2016; 22:1483-95. [PMID: 27167572 DOI: 10.1097/mib.0000000000000791] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Crohn's disease (CD) is a complex gastrointestinal disorder involving multiple levels of cross talk between the immunological, neural, vascular, and endocrine systems. The current dominant theory in CD is based on the unidirectional axis of dysbiosis-innate immunity-adaptive immunity-mesentery-body system. Emerging clinical evidence strongly suggests that the axis be bidirectional. The morphologic and/or functional abnormalities in the mesenteric structures likely contribute to the disease progression of CD, to a less extent the disease initiation. In addition to adipocytes, mesentery contains nerves, blood vessels, lymphatics, stromal cells, and fibroblasts. By the secretion of adipokines that have endocrine functions, the mesenteric fat tissue exerts its activity in immunomodulation mainly through response to afferent signals, neuropeptides, and functional cytokines. Mesenteric nerves are involved in the pathogenesis and prognosis of CD mainly through neuropeptides. In addition to angiogenesis observed in CD, lymphatic obstruction, remodeling, and impaired contraction maybe a cause and consequence of CD. Lymphangiogenesis and angiogenesis play a concomitant role in the progress of chronic intestinal inflammation. Finally, the interaction between neuropeptides, adipokines, and vascular and lymphatic endothelia leads to adipose tissue remodeling, which makes the mesentery an active participator, not a bystander, in the disease initiation and precipitation CD. The identification of the role of mesentery, including the structure and function of mesenteric nerves, vessels, lymphatics, and fat, in the intestinal inflammation in CD has important implications in understanding its pathogenesis and clinical management.
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Affiliation(s)
- Yi Li
- *Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; and †Center for Inflammatory Bowel Disease, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
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Knod JL, Crawford K, Dusing M, Collins MH, Chernoguz A, Frischer JS. Angiogenesis and Vascular Endothelial Growth Factor-A Expression Associated with Inflammation in Pediatric Crohn's Disease. J Gastrointest Surg 2016; 20:624-30. [PMID: 26530519 DOI: 10.1007/s11605-015-3002-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 10/18/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIMS Angiogenesis is a component of chronic inflammatory diseases including inflammatory bowel disease. Some studies describe increased angiogenesis associated with acute disease in adult Crohn's disease and ulcerative colitis, while animal models aid investigations of mechanism and pathophysiology of angiogenesis. We aim to explore the role of angiogenesis and its pathways in pediatric Crohn's disease. METHODS Surgical specimens were obtained from pediatric Crohn's disease (both inflamed and non-inflamed regions of ileum) and control patients. Samples were examined for inflammation, microvessel density, and molecular expression of vascular endothelial growth factor-A, platelet-derived growth factor-β, angiopoietin-1, and angiopoietin-2. RESULTS Angiogenesis and inflammation were increased in parallel in Crohn's disease compared to controls. We also discovered increased angiogenesis in Crohn's disease tissue that was relatively free of inflammatory disease. Vascular endothelial growth factor-A gene expression (P = 0.034) was elevated in Crohn's disease over controls, while gene expression of platelet-derived growth factor-β (P = 0.069), angiopoietin-1 (P = 0.206), and angiopoietin-2 (P = 0.082) was not significantly elevated. CONCLUSIONS We confirm that inflammation-associated angiogenesis is upregulated in pediatric Crohn's disease. This population also exhibits elevated mucosal angiogenesis at the surgical margin with limited inflammation. This suggests that angiogenesis is an additional pathologic characteristic to potentially identify normal mucosa and margins of surgical resection that are uninvolved with disease and, furthermore, may have implications for monitoring complete disease remission. We further identify the vascular endothelial growth factor-A pathway involvement in the disease process, which may serve as a future molecular target for anti-angiogenic therapy in inflammatory bowel disease.
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Affiliation(s)
- J Leslie Knod
- Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Kelly Crawford
- Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Mary Dusing
- Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Margaret H Collins
- Division of Pediatric Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Artur Chernoguz
- Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jason S Frischer
- Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. .,Director, Colorectal Center for Children, Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnett Avenue, MLC-2023, Cincinnati, OH, 45229, USA.
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Tontini GE, Rath T, Neumann H. Advanced gastrointestinal endoscopic imaging for inflammatory bowel diseases. World J Gastroenterol 2016; 22:1246-1259. [PMID: 26811662 PMCID: PMC4716035 DOI: 10.3748/wjg.v22.i3.1246] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Revised: 10/15/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn's disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection.
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Angiogenesis in Inflammatory Bowel Disease. Int J Inflam 2015; 2015:970890. [PMID: 26839731 PMCID: PMC4709626 DOI: 10.1155/2015/970890] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 12/07/2015] [Accepted: 12/08/2015] [Indexed: 12/24/2022] Open
Abstract
Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature.
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Dulai PS, Levesque BG, Feagan BG, D’Haens G, Sandborn WJ. Assessment of mucosal healing in inflammatory bowel disease: review. Gastrointest Endosc 2015; 82:246-55. [PMID: 26005012 PMCID: PMC6709676 DOI: 10.1016/j.gie.2015.03.1974] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 03/20/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Mucosal healing is an important treatment end-point in inflammatory bowel disease, and achieving mucosal healing has been demonstrated to improve disease-related outcomes. Considerable uncertainty exists, however, regarding the optimal approach for the assessment of mucosal healing. AIMS To compare currently available diagnostic tools for the assessment of mucosal healing and outline the ideal approach to integrating these tools into clinical trials and clinical practice. METHODS Review article. RESULTS Endoscopy represents the criterion standard for the assessment of mucosal healing, and frequent endoscopic assessment is associated with a higher rate of achieving mucosal healing. The use of mucosal biopsy allows for the identification of persistent histologic disease activity, but the incremental clinical benefit of achieving histologic healing is yet to be determined. Magnetic resonance enterography has a high sensitivity for ulcer healing in endoscopically inaccessible disease activity. However, the presence of mucosal lesions cannot be reliably excluded based on this modality alone, and further small-bowel endoscopy should be considered in symptomatic patients. Video capsule endoscopy or device-assisted enteroscopy can be used, with device-assisted enteroscopy being preferred in stricturing Crohn's disease because of the risk of capsule retention or in patients in whom small-bowel malignancy is a possibility. CONCLUSIONS Endoscopy remains the criterion standard for the assessment of mucosal healing. Several alternative diagnostic modalities have become available that can be of value in specific clinical circumstances, particularly in patients with small-bowel involvement.
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Affiliation(s)
- Parambir S. Dulai
- University of California San Diego, San Diego, CA
- Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada
| | - Barrett G. Levesque
- University of California San Diego, San Diego, CA
- Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada
| | - Brian G. Feagan
- Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada
- Department of Medicine, Western University, London, Ontario, Canada
| | - Geert D’Haens
- Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada
- Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands
| | - William J. Sandborn
- University of California San Diego, San Diego, CA
- Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada
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Tontini GE, Vecchi M, Neurath MF, Neumann H. Advanced endoscopic imaging techniques in Crohn's disease. J Crohns Colitis 2014; 8:261-9. [PMID: 24080247 DOI: 10.1016/j.crohns.2013.09.004] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2013] [Revised: 09/05/2013] [Accepted: 09/05/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Endoscopy is of pivotal importance in Crohn's disease (CD) patients for diagnosis, surveillance and assessment of disease activity and extent. Device-assisted enteroscopy (DAE) and small-bowel capsule endoscopy (SBCE) have recently changed our endoscopic approach to small-bowel imaging. Furthermore, new advanced endoscopic imaging techniques have been implemented into clinical practice to improve both characterization of mucosal inflammation and detection of dysplastic lesions. AIM To provide readers with a review about the concept of advanced endoscopic imaging for the diagnosis and characterization of CD. METHODS A literature search on the use of advanced endoscopy techniques in IBD patients was performed. RESULTS DAE and SBCE allow for deep enteroscopy with high diagnostic yields and low complication's rate but their collocation in the diagnostic algorithm is still not clearly defined. Dye-based chromoendoscopy (DBC) and magnification chromoendoscopy improved dysplasia's detection in long standing colitis and prediction of inflammatory activity and extent. Dye-less chromoendoscopy (DLC) might offer the potential to replace conventional DBC for surveillance. However, both narrow band imaging and i-scan have already shown to significantly improve activity and extent assessment in comparison to white-light endoscopy. Confocal laser endomicroscopy (CLE) can detect more dysplastic lesions in surveillance colonoscopy and predict neoplastic and inflammatory changes with high accuracy compared to histology. Moreover, CLE-based molecular imaging may anticipate the therapeutic responses to biological therapy. Endocytoscopy can identify in vivo inflammatory mucosal cells harboring a new method to assess the mucosal activity. CONCLUSIONS Recent progresses in small-bowel enteroscopy offer several potential benefits to improve both diagnosis and characterization of CD. New advanced endoscopic imaging techniques can improve detection of dysplasia and refine mucosal healing assessment, even looking beyond the morphological parameters revealed by conventional endoscopic imaging.
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Affiliation(s)
- Gian Eugenio Tontini
- Department of Medicine I, University of Erlangen-Nuremberg, Germany; Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
| | - Maurizio Vecchi
- Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy; Department of Medical Science for Health, University of Milan, Italy
| | - Markus F Neurath
- Department of Medicine I, University of Erlangen-Nuremberg, Germany
| | - Helmut Neumann
- Department of Medicine I, University of Erlangen-Nuremberg, Germany.
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Tontini GE, Vecchi M, Neurath MF, Neumann H. Review article: newer optical and digital chromoendoscopy techniques vs. dye-based chromoendoscopy for diagnosis and surveillance in inflammatory bowel disease. Aliment Pharmacol Ther 2013; 38:1198-208. [PMID: 24117471 DOI: 10.1111/apt.12508] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2013] [Revised: 07/16/2013] [Accepted: 09/05/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recent innovations in gastrointestinal endoscopy have changed our traditional approach to diagnosis and therapy in patients with inflammatory bowel diseases (IBD). While traditionally used dye-based chromoendoscopy (DBC) techniques suffer from several limitations that reduce their utility in daily routine practice, newer 'dye-less' chromoendoscopy (DLC) techniques offer a great potential to overcome most of these limitations. AIM To review available optical and digital chromoendoscopy techniques, by critically discussing their potential for diagnostic and surveillance colonoscopy in patients with IBD. METHODS A literature search on the use of dye-less and dye-based chromoendoscopy in IBD patients was performed. RESULTS In long-standing IBD, DBC improves detection of dysplasia (diagnostic odds ratio = 17.5, 95% CI = 1.2-247.1) as well as prediction of inflammatory disease activity and extent of disease compared with standard video-colonoscopy. Narrow band imaging (NBI) shows no improvement in dysplasia detection rates compared with white-light endoscopy and DBC (P = 0.6). Moreover, NBI results in a suboptimal differentiation of dysplastic from nondysplastic lesions. No data regarding digital DLC techniques (i.e. FICE, i-scan) for dysplasia detection in IBD are yet available. Both NBI and i-scan are superior to white-light endoscopy in assessing the activity and extent of colorectal IBD. CONCLUSIONS Although the potential benefits of newer optical and digital dye-less chromoendoscopy techniques over traditionally used DBC are substantial, only DBC can currently be recommended to improve dysplasia detection in long-standing IBD. In contrast, DLC has the potential to quantify disease activity and mucosal healing in IBD.
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Affiliation(s)
- G E Tontini
- Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany; Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
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Neumann H, Vieth M, Günther C, Neufert C, Kiesslich R, Grauer M, Atreya R, Neurath MF. Virtual chromoendoscopy for prediction of severity and disease extent in patients with inflammatory bowel disease: a randomized controlled study. Inflamm Bowel Dis 2013; 19:1935-42. [PMID: 23839228 DOI: 10.1097/mib.0b013e318290550e] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Increased vascular permeability and angiogenesis play a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Aim was to determine whether computed virtual chromoendoscopy has the potential to enhance assessment of disease severity and extent in patients with mild or inactive IBD in comparison to high-definition white-light endoscopy. METHODS Consecutive patients with IBD were randomly assigned at a 1:1 ratio to undergo colonoscopy with high-definition white light (group A) or computed virtual chromoendoscopy (group B). The mucosal vascular pattern and any mucosal abnormalities were recorded. Subsequent to endoscopic characterization targeted, biopsies were obtained from every segment for subsequent histopathological analysis of disease activity. RESULTS Overall, 100 patients were screened to participate in this study of whom 78 patients (high-definition white light, n = 39; computed virtual chromoendoscopy, n = 39) completed the study protocol thereby matching the previously calculated sample size. Average duration of the examination was 18 minutes in group A and 20.5 minutes in group B that was not statistically significant. When comparing the endoscopic prediction of inflammatory extent and activity with the histological results, an overall agreement of 48.71% and 53.85% (group A) and 92.31% and 89.74% (group B) was found, respectively. These differences were statistically significant (P = 0.0009 and P = 0.066). CONCLUSIONS This study indicates that computed virtual chromoendoscopy significantly improves the diagnosis of the severity and extent of mucosal inflammation in patients with IBD. This newly developed imaging technique may therefore have important implications for therapeutic interventions in patients with IBD.
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Affiliation(s)
- Helmut Neumann
- Department of Medicine I, University of Erlangen-Nuremberg, Germany.
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Kong WX, Gao Q. Progress in the diagnosis of ileocecal lesions. Shijie Huaren Xiaohua Zazhi 2012; 20:2382-2387. [DOI: 10.11569/wcjd.v20.i25.2382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The ileocecal area includes the ileocecal valve, terminal ileum, cecum, appendix, and top ascending colon. Since this area may be affected by pathologic conditions that are either common throughout the gastrointestinal system or exclusive to this area, a great variety of intestinal diseases may arise in this region, making the diagnosis of ileocecal lesions difficult. In clinic, the diagnosis of ileocecal lesions depends on the combination of disease history, clinical features, imaging and endoscopic findings. The development of advanced imaging and endoscopy technology has greatly increased the detection rate of ileocecal lesions. In this review, we discuss the use of imaging and endoscopic examinations for evaluation of ileocecal area to help ensure accurate diagnosis and appropriate treatment.
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Advanced endoscopic imaging for diagnosis of Crohn's disease. Gastroenterol Res Pract 2011; 2012:301541. [PMID: 22144998 PMCID: PMC3226328 DOI: 10.1155/2012/301541] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2011] [Accepted: 09/12/2011] [Indexed: 02/07/2023] Open
Abstract
Endoscopy in IBD has tremendous importance to diagnose inflammatory activity, to evaluate therapeutic success and for the surveillance of colitis associated cancer. Thus it becomes obvious that there is a need for new and more advanced endoscopic imaging techniques for better characterization of mucosal inflammation and early neoplasia detection in IBD. This paper describes the concept of advanced endoscopic imaging for the diagnosis and characterization of Crohn's disease, including magnification endoscopy, chromoendoscopy, balloon-assisted enteroscopy, capsule endoscopy, confocal laser endomicroscopy, and endocytoscopy.
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Confocal laser endomicroscopy and narrow-band imaging-aided endoscopy for in vivo imaging of colitis and colon cancer in mice. Nat Protoc 2011; 6:1471-81. [PMID: 21886109 DOI: 10.1038/nprot.2011.377] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
New endoscopic techniques such as narrow-band imaging (NBI) and confocal laser endomicroscopy (CLE) have improved the in vivo diagnosis of human gastrointestinal diseases in the colon. Whereas NBI may facilitate the identification of neoplastic lesions, CLE permits real-time histology of the inflamed or neoplastic colonic mucosa through the use of fluorescent dyes. These techniques have been recently adopted for use during ongoing endoscopy in mice. This protocol, which can be completed in 2 h, provides a detailed description of NBI and CLE in the mouse colon. In contrast to other techniques, this approach does not require laparotomy, and it allows direct CLE analysis of lesions identified by NBI. Mice exposed to models of colitis or colorectal cancer are anesthetized and examined with a miniaturized NBI endoscope, which provides an increased contrast of the vasculature. Upon identification of suspicious areas by NBI and the administration of fluorescent dyes, a confocal laser probe can be directed to the area of interest through the endoscope and confocal images can be obtained. Through the use of various fluorescent dyes, different aspects of the mucosa can be assessed. In addition, fluorescence-labeled antibodies can be used for molecular imaging of mice in vivo. Mouse NBI endoscopy and CLE represent reliable and fast high-quality techniques for the endoscopic characterization and molecular imaging of the mucosa in colitis and colon cancer.
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Meier J, Sturm A. Current treatment of ulcerative colitis. World J Gastroenterol 2011; 17:3204-12. [PMID: 21912469 PMCID: PMC3158396 DOI: 10.3748/wjg.v17.i27.3204] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2011] [Revised: 06/20/2011] [Accepted: 06/27/2010] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic disease featuring recurrent inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complications of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice-orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.
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Esaki M, Kubokura N, Kudo T, Matsumoto T. Endoscopic findings under narrow band imaging colonoscopy in ulcerative colitis. Dig Endosc 2011; 23 Suppl 1:140-2. [PMID: 21535220 DOI: 10.1111/j.1443-1661.2011.01110.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Narrow band imaging (NBI) depicts distinct intramucosal vascular network and pit pattern without any use of dye technique. It is thus suggested that NBI can be used for the assessment of severity in inflammatory bowel diseases, especially in ulcerative colitis (UC). In the active UC, NBI colonoscopy depicts friability as a black area. In the inflamed granular mucosa, crypt openings and villous structure become evident through the procedure. In the inactive UC, there are two types of mucosal vascular pattern; one being composed of deep, green vessels and superficial, black vessels, and the other lacking in superficial vessels. With used of a magnifying instrument, the mildly active mucosa can be classified into the mucosa with obvious crypt openings and that with villous structure. Mucosal vascular pattern in the inactive mucosa is shown as a honeycomb-like structure or irregular, tortuous structure under magnifying NBI observation. Furthermore, such NBI findings show close correlations with histologic findings including crypt distortion, goblet cell depletion and basal plasmacytosis. Therefore, NBI colonoscopy might be of value for the precise assessment of histologic severity in mildly active and inactive UC.
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Affiliation(s)
- Motohiro Esaki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
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