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Sardelli L, Perottoni S, Tunesi M, Boeri L, Fusco F, Petrini P, Albani D, Giordano C. Technological tools and strategies for culturing human gut microbiota in engineered in vitro models. Biotechnol Bioeng 2021; 118:2886-2905. [PMID: 33990954 PMCID: PMC8361989 DOI: 10.1002/bit.27816] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 03/29/2021] [Accepted: 05/04/2021] [Indexed: 12/13/2022]
Abstract
The gut microbiota directly impacts the pathophysiology of different human body districts. Consequently, microbiota investigation is an hot topic of research and its in vitro culture has gained extreme interest in different fields. However, the high sensitivity of microbiota to external stimuli, such as sampling procedure, and the physicochemical complexity of the gut environment make its in vitro culture a challenging task. New engineered microfluidic gut-on-a-chip devices have the potential to model some important features of the intestinal structure, but they are usually unable to sustain culture of microbiota over an extended period of time. The integration of gut-on-a-chip devices with bioreactors for continuous bacterial culture would lead to fast advances in the study of microbiota-host crosstalk. In this review, we summarize the main technologies for the continuous culture of microbiota as upstream systems to be coupled with microfluidic devices to study bacteria-host cells communication. The engineering of integrated microfluidic platforms, capable of sustaining both anaerobic and aerobic cultures, would be the starting point to unveil complex biological phenomena proper of the microbiota-host crosstalks, paving to way to multiple research and technological applications.
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Affiliation(s)
- Lorenzo Sardelli
- Department of ChemistryMaterials and Chemical Engineering “Giulio Natta,” Politecnico di MilanoMilanItaly
| | - Simone Perottoni
- Department of ChemistryMaterials and Chemical Engineering “Giulio Natta,” Politecnico di MilanoMilanItaly
| | - Marta Tunesi
- Department of ChemistryMaterials and Chemical Engineering “Giulio Natta,” Politecnico di MilanoMilanItaly
| | - Lucia Boeri
- Department of ChemistryMaterials and Chemical Engineering “Giulio Natta,” Politecnico di MilanoMilanItaly
| | - Federica Fusco
- Department of ChemistryMaterials and Chemical Engineering “Giulio Natta,” Politecnico di MilanoMilanItaly
| | - Paola Petrini
- Department of ChemistryMaterials and Chemical Engineering “Giulio Natta,” Politecnico di MilanoMilanItaly
| | - Diego Albani
- Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly
| | - Carmen Giordano
- Department of ChemistryMaterials and Chemical Engineering “Giulio Natta,” Politecnico di MilanoMilanItaly
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Abstract
Inflammatory bowel disease (IBD) is frequently associated with a variety of problematic symptoms, including abdominal pain and bowel habit changes, which are associated with poor patient quality of life and significant healthcare expenditure. Interestingly, silent IBD, a condition where patients demonstrate reduced perception and/or reporting of symptoms in the setting of active inflammation, may be as clinically consequential. This condition has been associated with serious complications leading to more costly interventions. It is by its nature an under-recognized phenomenon that affects substantial portions of patients with either Crohn's disease or ulcerative colitis. At the present time, although there are a variety of theories relating to the underlying causes and contributors, little is known about why this phenomenon occurs. As a result, there is a lack of cost-effective, reliable diagnostic methods to identify and manage "at-risk" patients. However, it is significantly likely that further study and an improved understanding of this condition will lead to improved approaches for the diagnosis and treatment of patients with silent IBD as well as other gastrointestinal disorders associated with alterations in symptomatic perception. In this article, we critically review studies that have investigated silent IBD. Specifically, we discuss the following: (1) the methods for defining silent IBD, (2) the known epidemiology of silent IBD, (3) potential causes of and contributors to this clinical entity, (4) current diagnostic modalities available to identify it, and (5) gaps in our understanding as well as potential novel diagnostic and therapeutic applications that could be developed with further study of this condition.
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Affiliation(s)
- Matthew D Coates
- Department of Medicine, Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, Pennsylvania, USA
- Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - David G Binion
- Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
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Perperidis A, Dhaliwal K, McLaughlin S, Vercauteren T. Image computing for fibre-bundle endomicroscopy: A review. Med Image Anal 2020; 62:101620. [PMID: 32279053 PMCID: PMC7611433 DOI: 10.1016/j.media.2019.101620] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 11/18/2019] [Indexed: 12/12/2022]
Abstract
Endomicroscopy is an emerging imaging modality, that facilitates the acquisition of in vivo, in situ optical biopsies, assisting diagnostic and potentially therapeutic interventions. While there is a diverse and constantly expanding range of commercial and experimental optical biopsy platforms available, fibre-bundle endomicroscopy is currently the most widely used platform and is approved for clinical use in a range of clinical indications. Miniaturised, flexible fibre-bundles, guided through the working channel of endoscopes, needles and catheters, enable high-resolution imaging across a variety of organ systems. Yet, the nature of image acquisition though a fibre-bundle gives rise to several inherent characteristics and limitations necessitating novel and effective image pre- and post-processing algorithms, ranging from image formation, enhancement and mosaicing to pathology detection and quantification. This paper introduces the underlying technology and most prevalent clinical applications of fibre-bundle endomicroscopy, and provides a comprehensive, up-to-date, review of relevant image reconstruction, analysis and understanding/inference methodologies. Furthermore, current limitations as well as future challenges and opportunities in fibre-bundle endomicroscopy computing are identified and discussed.
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Affiliation(s)
- Antonios Perperidis
- Institute of Sensors, Signals and Systems (ISSS), Heriot Watt University, EH14 4AS, UK; EPSRC IRC "Hub" in Optical Molecular Sensing & Imaging, MRC Centre for Inflammation Research, Queen's Medical Research Institute (QMRI), University of Edinburgh, EH16 4TJ, UK.
| | - Kevin Dhaliwal
- EPSRC IRC "Hub" in Optical Molecular Sensing & Imaging, MRC Centre for Inflammation Research, Queen's Medical Research Institute (QMRI), University of Edinburgh, EH16 4TJ, UK.
| | - Stephen McLaughlin
- Institute of Sensors, Signals and Systems (ISSS), Heriot Watt University, EH14 4AS, UK.
| | - Tom Vercauteren
- School of Biomedical Engineering and Imaging Sciences, King's College London, WC2R 2LS, UK.
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Development of Dual-Scale Fluorescence Endoscopy for In Vivo Bacteria Imaging in an Orthotopic Mouse Colon Tumor Model. APPLIED SCIENCES-BASEL 2020. [DOI: 10.3390/app10030844] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Colorectal cancer is a representative cancer where early diagnosis and proper treatment monitoring are important. Recently, cancer treatment using bacteria has actively progressed and has been successfully monitored using fluorescence imaging techniques. However, because subcutaneous tumor models are limited in reflecting the actual colorectal cancer situation, new imaging approaches are needed to observe cancers growing in the colon. The fluorescence endoscopic approach is an optimal monitoring modality to evaluate the therapeutic response of bacteria in orthotopic colon cancer. In this study, we developed dual-scaled fluorescence endoscopy (DSFE) by combining wide-field fluorescence endoscopy (WFE) and confocal fluorescence endomicroscopy (CFEM) and demonstrated its usefulness for evaluating bacterial therapy. Firstly, the endoscopic probe of DSFE was developed by integrating the CFEM probe into the guide sheath of WFE. Secondly, colorectal cancer tumor growth and tumors infiltrating the fluorescent bacteria were successfully monitored at the multi-scale using DSFE. Finally, the bacterial distribution of the tumor and organs were imaged and quantitatively analyzed using CFEM. DSFE successfully exhibited fluorescent bacterial signals in an orthotopic mouse colon tumor model. Thus, it can be concluded that the DSFE system is a promising modality to monitor bacterial therapy in vivo.
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Passos MAT, Chaves FC, Chaves-Junior N. THE IMPORTANCE OF COLONOSCOPY IN INFLAMMATORY BOWEL DISEASES. ACTA ACUST UNITED AC 2018; 31:e1374. [PMID: 29972402 PMCID: PMC6044200 DOI: 10.1590/0102-672020180001e1374] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 03/29/2018] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Endoscopic evaluation, particularly the macroscopic mucosal and histological results of ileocolic biopsies, is essential for the management of inflammatory bowel disease. Endoscopic appearance is not always sufficient to differentiate Crohn's disease and ulcerative colitis, but there are some characteristics that favor one or another diagnosis. Both diseases have an increased incidence of colorectal carcinoma; so, surveillance colonoscopy is important for detecting early neoplastic lesions. OBJECTIVE To update the importance of endoscopy in the evaluation, diagnosis and prognosis of inflammatory bowel disease. METHOD Search was done in the scientific literature of the TRIP database, chosen from clinical questions (PICO) with the following descriptors: "inflammatory bowel disease", "endoscopy/colonoscopy", "Crohn's disease", "ulcerative colitis" and "diagnosis/treatment". RESULTS Endoscopic investigation in patients with chronic colitis is quite accurate for the differential diagnosis between ulcerative colitis and Crohn's disease. Endoscopy is indicated for ulcerative colitis during severe crisis due to its prognostic value. Another accepted indication for endoscopy in inflammatory bowel disease is its use in the screening for dysplastic lesion. CONCLUSION Ileocolonoscopy allows an accurate diagnosis of Crohn's disease or ulcerative colitis in up to 90% of cases. The healing of the mucosa assessed by endoscopy after treatments despite not being consensus is still the gold-standard in the evaluation of remission of the disease. Colonoscopy is essential for long-term cancer surveillance and in the future the implementation of Confocal Laser Endomicroscopy seems to be very promising in assessing the initial dysplasia.
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Affiliation(s)
| | - Fernanda Correa Chaves
- Hospital Universitário de Vassouras, Universidade Severino Sombra, Vassouras, RJ, Brazil
| | - Nilson Chaves-Junior
- Hospital Universitário de Vassouras, Universidade Severino Sombra, Vassouras, RJ, Brazil
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Ueda N, Isomoto H, Ikebuchi Y, Kurumi H, Kawaguchi K, Yashima K, Ueki M, Matsushima K, Akashi T, Uehara R, Takeshima F, Hayashi T, Nakao K. Endocytoscopic classification can be predictive for relapse in ulcerative colitis. Medicine (Baltimore) 2018; 97:e0107. [PMID: 29517688 PMCID: PMC5882457 DOI: 10.1097/md.0000000000010107] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The present study was conducted to explore the association of endocytoscopy (EC) classification with microscopic inflammatory features of ulcerative colitis (UC) and disease relapse.EC was performed for mild-to-moderate UC 32 cases from January 2010 to August 2016. EC appearance was stratified into 4 categories: EC-A, regular arrangement of round to oval pits; EC-B, irregular arrangement with/without enlarged spaces between regular pits; EC-C, deformed pits with distorted crypt lumen which are unordered in arrangement but not disrupted; and EC-D, disruptive or disappeared pits. We evaluated the association of EC classification with Mayo endoscopic subscores (MES) and the clinically active state. Microscopic features including the severity in mucosal inflammatory infiltrates the presence of crypt abscess and goblet cell depletion were assessed by an experienced pathologist who was blinded to clinical and endoscopic information. Clinical follow-up was provided for treating 22 UC patients more than 60 months after EC.There were 15 cases in EC-A, 8 in EC-B, 5 in EC-C, and 4 in EC-D. Interobserver agreement was excellent with κ value of 0.77. There were 13 patients in active disease stage, while 19 in remission. Each EC-A case was in clinically remission stage, while all the EC-C and EC-D cases were in the active stage. There were 4 and 4 EC-B cases in remission and active stage, respectively. The EC-A group consisted of 11 MES0 and 4 MES1 cases, whereas the EC-B group consisted of 2 MES0 and 6 MES1 cases. There were no cases of MES0 in the EC-C and -D groups. The EC stratification was significantly associated with pathognomonic microscopic features for UC. There were significant differences in the remission rate among the EC groups. None had relapse in the EC-A group during the follow-up period.EC stratification could be predictive for relapse in UC. Moreover, EC is reliable to assess UC specific microscopic features.
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Affiliation(s)
- Naoki Ueda
- Division of Medicine and Clinical Science, Tottori University Faculty of Medicine, Tottori
| | - Hajime Isomoto
- Division of Medicine and Clinical Science, Tottori University Faculty of Medicine, Tottori
| | - Yuichiro Ikebuchi
- Division of Medicine and Clinical Science, Tottori University Faculty of Medicine, Tottori
| | - Hiroki Kurumi
- Division of Medicine and Clinical Science, Tottori University Faculty of Medicine, Tottori
| | - Koichiro Kawaguchi
- Division of Medicine and Clinical Science, Tottori University Faculty of Medicine, Tottori
| | - Kazuo Yashima
- Division of Medicine and Clinical Science, Tottori University Faculty of Medicine, Tottori
| | - Masaru Ueki
- Division of Medicine and Clinical Science, Tottori University Faculty of Medicine, Tottori
| | | | - Taro Akashi
- Department of Gastroenterology and Hepatology
| | | | | | - Tomayoshi Hayashi
- Department of Pathology, Nagasaki University Hospital, Nagasakai, Japan
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Maione F, Giglio MC, Luglio G, Rispo A, D'Armiento M, Manzo B, Cassese G, Schettino P, Gennarelli N, Siciliano S, D'Armiento FP, De Palma GD. Confocal laser endomicroscopy in ulcerative colitis: beyond endoscopic assessment of disease activity. Tech Coloproctol 2017; 21:531-540. [PMID: 28674950 DOI: 10.1007/s10151-017-1654-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Accepted: 02/25/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this study was to investigate the role of confocal laser endomicroscopy (CLE) in the assessment of disease activity in ulcerative colitis (UC). METHODS Consecutive patients with UC referred to our inflammatory bowel disease unit for colonoscopy were enrolled. Patients without UC were used as controls. UC activity was evaluated by white light endoscopy and classified according to the Mayo Ulcerative Colitis Endoscopic Score of Severity. Endoscopic biopsies were also taken for histological assessment of disease activity and then assessed with CLE. Three parameters were evaluated; crypt architecture (crypt diameter, inter-crypt distance, presence of fused crypts, crypts regularity), microvascular pattern (regular, dilated, irregular and deformed), fluorescein leakage. RESULTS Fifty patients with UC and 10 controls were enrolled. At colonoscopy, 11 patients (22%), 19 patients (38%), 12 patients (24%) and 8 patients (16%) presented a Mayo score of 0, 1, 2 and 3, respectively. At CLE, fused crypts were present in all the patients with UC and absent in controls. Crypt diameter and inter-crypt distance showed a parallel increase with the Mayo score. Fluorescein leakage and irregular vessels were more frequently found in case of a high level of endoscopic severity, but were also identified in about 20% of UC patients with normal mucosa. Biopsies also demonstrated the presence of histological activity in 4 patients with endoscopically inactive colitis. CONCLUSIONS CLE might be a useful tool to determine inflammatory activity in UC. Fused crypts appeared to be a CLE marker of UC, while other abnormalities, like microvascular alteration and fluorescein leakage, have also been identified in patients with mucosal healing at endoscopy. Larger series are required to validate these results and the advantages of a CLE-based assessment of UC activity.
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Affiliation(s)
- F Maione
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - M C Giglio
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - G Luglio
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - A Rispo
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - M D'Armiento
- Department of Advanced Biomedical Sciences, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - B Manzo
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - G Cassese
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - P Schettino
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - N Gennarelli
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - S Siciliano
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - F P D'Armiento
- Department of Advanced Biomedical Sciences, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - G D De Palma
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
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Zhang S, Cao X, Huang H. Sampling Strategies for Three-Dimensional Spatial Community Structures in IBD Microbiota Research. Front Cell Infect Microbiol 2017; 7:51. [PMID: 28286741 PMCID: PMC5323387 DOI: 10.3389/fcimb.2017.00051] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Accepted: 02/10/2017] [Indexed: 12/12/2022] Open
Abstract
Identifying intestinal microbiota is arguably an important task that is performed to determine the pathogenesis of inflammatory bowel diseases (IBD); thus, it is crucial to collect and analyze intestinally-associated microbiota. Analyzing a single niche to categorize individuals does not enable researchers to comprehensively study the spatial variations of the microbiota. Therefore, characterizing the spatial community structures of the inflammatory bowel disease microbiome is critical for advancing our understanding of the inflammatory landscape of IBD. However, at present there is no universally accepted consensus regarding the use of specific sampling strategies in different biogeographic locations. In this review, we discuss the spatial distribution when screening sample collections in IBD microbiota research. Here, we propose a novel model, a three-dimensional spatial community structure, which encompasses the x-, y-, and z-axis distributions; it can be used in some sampling sites, such as feces, colonoscopic biopsy, the mucus gel layer, and oral cavity. On the basis of this spatial model, this article also summarizes various sampling and processing strategies prior to and after DNA extraction and recommends guidelines for practical application in future research.
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Affiliation(s)
- Shaocun Zhang
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin UniversityTianjin, China; Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin UniversityTianjin, China; Collaborative Innovation Center of Chemical Science and EngineeringTianjin, China
| | - Xiaocang Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital; Tianjin Medical University Tianjin, China
| | - He Huang
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin UniversityTianjin, China; Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin UniversityTianjin, China; Collaborative Innovation Center of Chemical Science and EngineeringTianjin, China
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Wei ZZ, Li N. Application of confocal laser endomicroscopy in ulcerative colitis. Shijie Huaren Xiaohua Zazhi 2015; 23:1924-1929. [DOI: 10.11569/wcjd.v23.i12.1924] [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 etiology of ulcerative colitis (UC) is not very clear. Most scholars believe that intestinal inflammation caused by immune system abnormalities plays an important role in the pathogenesis of UC. The clinical course of UC is characterized by episodes of exacerbation and remission alternately. Traditional electronic endoscopy with random biopsy plays an important role in the diagnosis, treatment and prognosis evaluation of UC. However, this method has some deficiencies, such as poor sensitivity, cumbersome procedures, bleeding caused by multiple biopsies and other complications. The advent of high resolution confocal laser endomicroscopy (CLE) can allow real-time, noninvasive histopathological examination in vivo, to achieve the goal of "virtual biopsy". This paper reviews the application of CLE in UC.
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Buda A, Hatem G, Neumann H, D'Incà R, Mescoli C, Piselli P, Jackson J, Bruno M, Sturniolo GC. Confocal laser endomicroscopy for prediction of disease relapse in ulcerative colitis: a pilot study. J Crohns Colitis 2014; 8:304-11. [PMID: 24094597 DOI: 10.1016/j.crohns.2013.09.005] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Revised: 09/02/2013] [Accepted: 09/04/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Neoangiogenesis and increased endothelial permeability are observed as results of chronic intestinal inflammation. However, limited data on microvascular and crypt architecture during remission phases is available. The aim of this prospective investigator blinded cohort study was to assess crypt and microvascular architecture and function in ulcerative colitis by probe based confocal laser endomicroscopy; we also evaluated whether these findings may have the potential to predict disease relapse. METHODS 19 ulcerative colitis patients in clinical and endoscopic remission and 19 controls were studied. A computer based image processing technique was applied to construct 20 mosaicing image sets from each subject. Remitting patients were sub-grouped into either inactive or quiescent disease according to histology. RESULTS Pericrypt fluorescence (p<0.01), crypt diameter (p<0.05) but not intercrypt distance (p=0.07) were significantly increased in ulcerative colitis patients compared to controls. Patients with inactive disease showed a significant increase in fluorescence leakage (median fluorescence (IQR), 3888 (3560-4240) vs. 2696 (2502-3390), p<0.01), crypt diameter (median diameter (IQR), 92.5 (85.5-101) vs. 73 (70-77), p<0.05) and intercrypt distance (median distance (IQR), 82.5 (70.5-91.2) vs. 66 (59.5-73.5), p<0.05) compared to those with quiescent disease. A composite outcome score combining fluorescence leakage and crypt diameter was able to predict a disease flare during a 12 month follow-up period (p<0.01). CONCLUSIONS In vivo intramucosal changes detected by confocal endomicroscopy in ulcerative colitis remittent patients can predict disease relapse. This observation may have further implications for disease management and medical treatment.
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Affiliation(s)
- Andrea Buda
- Department of Surgical, Gastroenterological and Oncological Sciences, University of Padova, Padova, Italy.
| | - Giorgia Hatem
- Department of Surgical, Gastroenterological and Oncological Sciences, University of Padova, Padova, Italy
| | - Helmut Neumann
- Department of Surgical, Gastroenterological and Oncological Sciences, Division of Gastroenterology, University of Padova, The Netherlands
| | - Renata D'Incà
- Department of Surgical, Gastroenterological and Oncological Sciences, University of Padova, Padova, Italy
| | - Claudia Mescoli
- Department of Medicine I Interdisciplinary Endoscopy, University of Erlangen, Germany
| | | | - John Jackson
- Department of Epidemiology and Pre-Clinical Sciences, IRCCS "L. Spallanzani", Roma, Italy
| | - Marco Bruno
- School of Clinical Sciences, University of Bristol, Bristol, UK
| | - Giacomo Carlo Sturniolo
- Department of Surgical, Gastroenterological and Oncological Sciences, University of Padova, Padova, Italy
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Tabatabaei N, Kang D, Wu T, Kim M, Carruth RW, Leung J, Sauk JS, Shreffler W, Yuan Q, Katz A, Nishioka NS, Tearney GJ. Tethered confocal endomicroscopy capsule for diagnosis and monitoring of eosinophilic esophagitis. BIOMEDICAL OPTICS EXPRESS 2013; 5:197-207. [PMID: 24466487 PMCID: PMC3891332 DOI: 10.1364/boe.5.000197] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Revised: 11/13/2013] [Accepted: 11/18/2013] [Indexed: 05/04/2023]
Abstract
Eosinophilic esophagitis (EoE) is an allergic condition that is characterized by eosinophils infiltrating the esophageal wall. The treatment of the disease may require multiple follow up sedated endoscopies and biopsies to confirm elimination of eosinophils. These procedures are expensive, time consuming, and may be difficult for patients to tolerate. Here we report on the development of a confocal microscopy capsule for diagnosis and monitoring of EoE. The swallowable capsule implements a high-speed fiber-based reflectance confocal microscopy technique termed Spectrally Encoded Confocal Microscopy (SECM). SECM scans the sample in one dimension without moving parts by using wavelength swept source illumination and a diffraction grating at the back plane of the objective lens. As the wavelength of the source is tuned, the SECM optics within the 7 x 30 mm capsule are rotated using a driveshaft enclosed in a 0.8 mm flexible tether. A single rotation of the optics covered a field of view of 22 mm x 223 µm. The lateral and axial resolutions of the device were measured to be 2.1 and 14 µm, respectively. Images of Acetic Acid stained swine esophagus obtained with the capsule ex vivo and in vivo clearly showed squamous epithelial nuclei, which are smaller and less reflective than eosinophils. Imaging of esophageal biopsies from EoE patients ex vivo demonstrated the capability of this technology to visualize individual eosinophils. Based on the results of this study, we believe that this capsule will be a simpler and more effective device for diagnosing EoE and monitoring the therapeutic response of this disease.
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Affiliation(s)
- Nima Tabatabaei
- Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
| | - DongKyun Kang
- Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
| | - Tao Wu
- Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
| | - Minkyu Kim
- Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
- School of Engineering, The University of Tokyo, Yayoi 2-11-16 Bunkyo, Tokyo 113-8656, Japan
| | - Robert W. Carruth
- Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
| | - John Leung
- Food Allergy Center and Pediatric Allergy & Immunology, Harvard Medical School/Massachusetts General Hospital, Boston, MA 02114, USA
| | - Jenny S Sauk
- Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Wayne Shreffler
- Food Allergy Center and Pediatric Allergy & Immunology, Harvard Medical School/Massachusetts General Hospital, Boston, MA 02114, USA
| | - Qian Yuan
- Department of Pediatrics, Harvard Medical School/Massachusetts General Hospital, Boston, MA 02114, USA
| | - Aubrey Katz
- Department of Pediatrics, Harvard Medical School/Massachusetts General Hospital, Boston, MA 02114, USA
| | - Norman S Nishioka
- Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Guillermo J. Tearney
- Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
- Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
- Department of Pathology, Harvard Medical School/Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
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Mazzuoli S, Guglielmi FW, Antonelli E, Salemme M, Bassotti G, Villanacci V. Definition and evaluation of mucosal healing in clinical practice. Dig Liver Dis 2013; 45:969-977. [PMID: 23932331 DOI: 10.1016/j.dld.2013.06.010] [Citation(s) in RCA: 105] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 05/21/2013] [Accepted: 06/26/2013] [Indexed: 12/11/2022]
Abstract
Since the introduction of biological therapy, endoscopic and histological remission, i.e. mucosal healing, has become an important therapeutic goal in Crohn's Disease and Ulcerative Colitis. Mucosal healing is associated with lower rates of hospitalization and surgery, although its role in preventing progression and changing the natural history of the disease has not been clearly demonstrated. A precise definition of mucosal healing has not yet been established, although the concept used in clinical trials is the "complete absence of all inflammatory and ulcerative lesions in all segments of gut" at endoscopy. This definition does not include mucosal improvement and does not distinguish among grades of mucosal healing. In both Crohn's Disease and Ulcerative Colitis trials, several qualitative and quantitative numeric endoscopic indices have been proposed to measure and distinguish endoscopic changes. In addition, the microscopic features associated with inflammatory bowel diseases are considerably modified by the course of the disease and the treatments adopted. However, it is not yet clear whether microscopic healing should be a primary endpoint in clinical trials. In this paper we discuss endoscopic and histological findings and the limitations of the endoscopic and histological indices as a basis for a standardised diagnosis of mucosal healing.
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Affiliation(s)
- Silvia Mazzuoli
- Gastroenterology and Artificial Nutrition Department, "San Nicola Pellegrino" Hospital Trani, BT, Italy
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Palma GDD, Rispo A. Confocal laser endomicroscopy in inflammatory bowel diseases: dream or reality? World J Gastroenterol 2013; 19:5593-5597. [PMID: 24039350 PMCID: PMC3769894 DOI: 10.3748/wjg.v19.i34.5593] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2013] [Revised: 06/27/2013] [Accepted: 08/04/2013] [Indexed: 02/06/2023] Open
Abstract
Confocal laser endomicroscopy (CLE) is a newly introduced procedure that provide real-time, high-resolution imaging of the gastrointestinal mucosa during endoscopy, allowing the visualization of the pathology of the mucosal epithelium with its cellular and subcellular structures. Recently, the use of CLE was reported in the study of colonic mucosa in patients with inflammatory bowel diseases and in particular in patients affected by ulcerative colitis. CLE has the potential to have an important role in management of inflammatory bowel diseases (IBD) patients as it can be used to assess the grading of colitis and in detection of microscopic colitis in endoscopically silent segments. Moreover, CLE can be used in surveillance programs especially in high-risk patients. Finally, CLE has been effectively used in diagnosing a biliary dysplasia/neoplasia in patients with primary sclerosing cholangitis, a pathological condition frequently associated with IBD, with a coexisting bile duct stricture.
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Chen YX, Qiao L. Adenoma-like and non-adenoma-like dysplasia-associated lesion or mass in ulcerative colitis. J Dig Dis 2013; 14:157-9. [PMID: 23374421 DOI: 10.1111/1751-2980.12043] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Ulcerative colitis (UC) patients have an increased risk of colorectal cancer. UC has two general patterns of dysplasia, which are commonly classified as adenoma-like dysplasia-associated lesion or mass (DALM) and non-adenoma-like DALM. The latter has a high risk of concurrent malignancy and often requires a colectomy. Unfortunately, non-adenoma-like DALMs sometimes have endoscopic features similar to those of adenoma-like DALMs. Therefore, new endoscopic techniques to distinguish between these two kinds of DALM have been proposed.
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Affiliation(s)
- Ying Xuan Chen
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China.
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