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He Z, Wang P, Liang Y, Fu Z, Ye X. Clinically Available Optical Imaging Technologies in Endoscopic Lesion Detection: Current Status and Future Perspective. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:7594513. [PMID: 33628407 PMCID: PMC7886528 DOI: 10.1155/2021/7594513] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 01/13/2021] [Accepted: 01/27/2021] [Indexed: 01/02/2023]
Abstract
Endoscopic optical imaging technologies for the detection and evaluation of dysplasia and early cancer have made great strides in recent decades. With the capacity of in vivo early detection of subtle lesions, they allow modern endoscopists to provide accurate and effective optical diagnosis in real time. This review mainly analyzes the current status of clinically available endoscopic optical imaging techniques, with emphasis on the latest updates of existing techniques. We summarize current coverage of these technologies in major hospital departments such as gastroenterology, urology, gynecology, otolaryngology, pneumology, and laparoscopic surgery. In order to promote a broader understanding, we further cover the underlying principles of these technologies and analyze their performance. Moreover, we provide a brief overview of future perspectives in related technologies, such as computer-assisted diagnosis (CAD) algorithms dealing with exploring endoscopic video data. We believe all these efforts will benefit the healthcare of the community, help endoscopists improve the accuracy of diagnosis, and relieve patients' suffering.
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Affiliation(s)
- Zhongyu He
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, China
| | - Peng Wang
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, China
| | - Yuelong Liang
- Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Zuoming Fu
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, China
| | - Xuesong Ye
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, China
- State Key Laboratory of CAD and CG, Zhejiang University, Hangzhou 310058, China
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Buchner AM. Confocal Laser Endomicroscopy in the Evaluation of Inflammatory Bowel Disease. Inflamm Bowel Dis 2019; 25:1302-1312. [PMID: 30877772 DOI: 10.1093/ibd/izz021] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, can be effectively monitored with the use of endoscopy. The additional application of small field imaging technology such as confocal laser endomicroscopy CLE during ongoing endoscopic evaluation has led to real-time visualization of mucosal abnormalities and thus in vivo histology. The endomicroscopy (CLE) can improve IBD endoscopic evaluation by identifying seemingly normal-appearing mucosa, assessing the function of the intestinal barrier of the epithelium and vascular permeability, and by characterizing any mucosal lesions, including dysplastic lesions. CLE used during conventional endoscopy could especially facilitate the evaluation of mucosal healing in IBD. In addition, future developments in molecular imaging in IBD may optimize therapeutic approaches by identifying mucosal targets for therapy and determining the reasons for lack of response to specific therapy or subsequent loss of the response.
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Affiliation(s)
- Anna M Buchner
- Division of Gastroenterology at University of Pennsylvania, Philadelphia, Pennsylvania
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Koulaouzidis A, Toth E. Magnifying advanced endoscopy in collagenous colitis: now you see? Endosc Int Open 2017; 5:E1074-E1075. [PMID: 29250582 PMCID: PMC5659866 DOI: 10.1055/s-0043-118412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Anastasios Koulaouzidis
- Endoscopy Unit, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom,Corresponding author Anastasios Koulaouzidis, MD Endoscopy UnitThe Royal Infirmary of Edinburgh51 Little France CrescentEdinburgh EH164SAUnited Kingdom+44-131-2421619
| | - Ervin Toth
- Endoscopy Unit, Skåne University Hospital, Lund University, Malmö, Sweden
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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] [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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Buchner AM, Wallace MB. Endomicroscopy and Molecular Tools to Evaluate Inflammatory Bowel Disease. Gastrointest Endosc Clin N Am 2016; 26:657-68. [PMID: 27633594 DOI: 10.1016/j.giec.2016.06.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Endoscopy is an essential tool for effective care of patients with inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis. The newest endoscopic small-field imaging technologies with confocal endomicroscopy have allowed real-time imaging of gastrointestinal mucosal during ongoing endoscopic evaluation and in vivo histology. Thus, endomicroscopy has a potential to further enhance the endoscopic evaluation of IBD. Advances in molecular in vivo imaging in IBD may be used not only to better understand the pathophysiology of IBD but also to guide optimized therapy and thus to allow a personalized, new approach to the IBD management.
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Affiliation(s)
- Anna M Buchner
- Division of Gastroenterology, University of Pennsylvania, 3400 Civic Center PCAM 7 South, Philadelphia, PA 19104, USA
| | - Michael B Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
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Almadi MA, Neumann H. Probe based confocal laser endomicroscopy of the pancreatobiliary system. World J Gastroenterol 2015; 21:12696-708. [PMID: 26640347 PMCID: PMC4658625 DOI: 10.3748/wjg.v21.i44.12696] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Revised: 07/08/2015] [Accepted: 09/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To review applications of confocal laser endomicroscopy (CLE) in pancreatobiliary lesions and studies that assessed training and interpretation of images. METHODS A computerized literature search was performed using OVID MEDLINE, EMBASE, Cochrane library, and the ISI Web of Knowledge from 1980 to October 2014. We also searched abstracts from major meetings that included the Digestive Disease Week, Canadian Digestive Disease Week and the United European Gastroenterology Week using a combination of controlled vocabulary and text words related to pCLE, confocal, endomicroscopy, probe-based confocal laser endomicroscopy, and bile duct to identify reports of trials. In addition, recursive searches and cross-referencing was performed, and manual searches of articles identified after the initial search was also completed. We included fully published articles and those in abstract form. Given the relatively recent introduction of CLE we included randomized trials and cohort studies. RESULTS In the evaluation of indeterminate pancreatobiliary strictures CLE with ERCP compared to ERCP alone can increase the detection of cancerous strictures with a sensitivity of (98% vs 45%) and has a negative predictive value (97% vs 69%), but decreased the specificity (67% vs 100%) and the positive predictive value (71% vs 100%) when compared to index pathology. Modifications in the classification systems in indeterminate biliary strictures have increased the specificity of pCLE from 67% to 73%. In pancreatic cystic lesions there is a need to develop similar systems to interpret and characterize lesions based on CLE images obtained. The presence of superficial vascular network predicts serous cystadenomas accurately. Also training in acquiring and interpretation of images is feasible in those without any prior knowledge in CLE in a relatively simple manner and computer-aided diagnosis software is a promising innovation. CONCLUSION The role of pCLE in the evaluation of pancreatobiliary disorders might be better suited for those with an intermediate and low probability.
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Giataganas P, Hughes M, Yang GZ. Force adaptive robotically assisted endomicroscopy for intraoperative tumour identification. Int J Comput Assist Radiol Surg 2015; 10:825-32. [PMID: 25900339 DOI: 10.1007/s11548-015-1179-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Accepted: 03/13/2015] [Indexed: 02/02/2023]
Abstract
PURPOSE For effective tumour margin definition for cancer surgery, there is an increasing demand for the development of real-time intraoperative tissue biopsy techniques. Recent advances in miniaturized biophotonics probes have permitted the development of endomicroscopy techniques that are clinically attractive. With these approaches, cellular-level imaging can be achieved through millimetre-scale flexible probes and be performed in real-time, in vivo and in situ. Due to the limited field of view and flexibility of these probes, however, large area tissue coverage for acquiring histology-like images over complex three-dimensional surfaces is challenging. This is particularly the case because current surgical robots, such as the Da Vinci ®, lack haptic feedback, making it difficult to maintain optimum tissue contact when these probes are deployed in vivo. METHODS This paper proposes a simple force-controlled pick-up probe that can be integrated with the Da Vinci instruments for intraoperative endomicroscopy imaging. The device uses a new low-friction air bearing with adaptive axial force control to maintain constant contact between the tissue and the imaging probe, facilitating microscopy scans over complex surfaces. Detailed ex vivo user experiments have been conducted to demonstrate the effectiveness of the technique. RESULTS The adaptive probe mount could achieve consistent low-magnitude probe-sample contact forces compared with a rigid mount. In the user study, the adaptive probe combined with a high frame rate endomicroscopy system allowed larger mosaics to be generated over curved surfaces. CONCLUSIONS The device can improve the performance of large area mosaicking over complex 3D surfaces with improved handling and intraoperative control.
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Affiliation(s)
- Petros Giataganas
- Hamlyn Centre for Robotic Surgery, Institute of Global Health Innovation, Imperial College London, London, SW7 2AZ, UK,
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Hoffman A, Rey JW, Mueller L, Hansen T, Goetz M, Tresch A, Galle PR, Kiesslich R. Analysis of interobserver variability for endomicroscopy of the gastrointestinal tract. Dig Liver Dis 2014; 46:140-5. [PMID: 24210992 DOI: 10.1016/j.dld.2013.09.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Revised: 08/26/2013] [Accepted: 09/07/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Endomicroscopy allows in vivo microscopic investigation of enteral mucosa during endoscopic examinations. The aim of this study was to determine interobserver variability in the evaluation of endomicroscopic pictures of several organs by groups of investigators composed of confocal experts, pathologists and students. METHODS Twenty-five selected representative endomicroscopic pictures of the colon, stomach and oesophagus (total number, 75) were evaluated based on tissue, inflammatory and neoplastic changes (secondary endpoints). The endomicroscopic presence of neoplastic features was the primary endpoint and correlated with the final histological diagnosis. RESULTS The kappa values for experts examining colon, stomach, and oesophagus pictures were 0.80, 0.91, and 0.488, respectively; for students 0.74, 0.684, and 0.527 and for pathologists 0.749, 0.633, and 0.346, respectively. Neoplasia was accurately diagnosed in 67-97% of patients with no significant differences between the 3 groups. Tissue differentiation was determined best by pathologists, whereas the degree of inflammation was better diagnosed by experts and students. In all 3 groups the diagnosis of oesophageal diseases was the most difficult. CONCLUSIONS Endomicroscopic images can be interpreted with high concordance. In our study, the diagnostic reliability was not different between students, endomicroscopic experts, and pathologists. Thus, endomicroscopy could be an additional and reliable imaging modality for diagnosing mucosal neoplasia of the gut.
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Affiliation(s)
- Arthur Hoffman
- St. Mary's Hospital, Department of Medicine, Frankfurt, Germany; Medical Department, Johannes Gutenberg University of Mainz, Germany.
| | - Johannes Wilhelm Rey
- St. Mary's Hospital, Department of Medicine, Frankfurt, Germany; Medical Department, Johannes Gutenberg University of Mainz, Germany
| | - Lena Mueller
- Medical Department, Johannes Gutenberg University of Mainz, Germany
| | - Torsten Hansen
- Institute of Pathology, Johannes Gutenberg University Mainz, Germany
| | - Martin Goetz
- Medical Department, Johannes Gutenberg University of Mainz, Germany; Medical Department, University of Tübingen, Germany
| | | | | | - Ralf Kiesslich
- St. Mary's Hospital, Department of Medicine, Frankfurt, Germany; Medical Department, Johannes Gutenberg University of Mainz, Germany
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Chiew WM, Lin F, Qian K, Seah HS. A heterogeneous computing system for coupling 3D endomicroscopy with volume rendering in real-time image visualization. COMPUT IND 2014. [DOI: 10.1016/j.compind.2013.10.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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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: 7] [Impact Index Per Article: 0.6] [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] [Accepted: 08/06/2013] [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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Amin S, Dimaio CJ, Kim MK. Advanced EUS imaging for early detection of pancreatic cancer. Gastrointest Endosc Clin N Am 2013; 23:607-23. [PMID: 23735106 DOI: 10.1016/j.giec.2013.03.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Endoscopic ultrasound (EUS)-fine needle aspiration remains the gold standard for diagnosing pancreatic malignancy. However, in a subset of patients, limitations remain in regards to image quality and diagnostic yield of biopsies. Several new devices and processors have been developed that allow for enhancement of the EUS image. Initial studies of these modalities do show promise. However, cost, availability, and overall incremental benefit to EUS-fine needle aspiration have yet to be determined.
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Affiliation(s)
- Sunil Amin
- Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, 5 East 98th Street, 11th Floor, New York, NY 10029, USA
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Neumann H, Vieth M, Atreya R, Grauer M, Siebler J, Bernatik T, Neurath MF, Mudter J. Assessment of Crohn's disease activity by confocal laser endomicroscopy. Inflamm Bowel Dis 2012; 18:2261-9. [PMID: 22344873 DOI: 10.1002/ibd.22907] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2011] [Accepted: 01/16/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND Confocal laser endomicroscopy (CLE) allows microscopic imaging within the mucosal layer of the gut during ongoing endoscopy. Different studies have addressed the potential of CLE for in vivo diagnosis of ulcerative colitis and microscopic colitis. However, there are no data on the utility of CLE for in vivo diagnosis of Crohn's disease (CD). The aim was to assess the clinical utility of CLE in patients with CD and to determine whether disease activity can be graded using CLE. METHODS Consecutive patients with and without CD were enrolled. The colonic mucosa was examined by standard white-light endoscopy followed by CLE. The features seen on CLE were compared between CD patients and controls. RESULTS In all, 76 patients with CD were screened, of whom 54 patients were included in the present study. Eighteen patients without inflammatory bowel disease (IBD) served as controls. A significantly higher proportion of patients with active CD had increased colonic crypt tortuosity, enlarged crypt lumen, microerosions, augmented vascularization, and increased cellular infiltrates within the lamina propria. In quiescent CD, a significant increase in crypt and goblet cell number was detected compared with controls. Based on our findings, we propose a Crohn's Disease Endomicroscopic Activity Score (CDEAS) for assessing CD activity in vivo. CONCLUSIONS CLE has the potential to significantly improve diagnosis of CD compared with standard endoscopy. These findings should be evaluated in future prospective trials to assess the value of this newly developed CLE score for prediction of disease course and therapeutic responses.
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Affiliation(s)
- Helmut Neumann
- Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany.
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Hoetker MS, Kiesslich R, Diken M, Moehler M, Galle PR, Li Y, Goetz M. Molecular in vivo imaging of gastric cancer in a human-murine xenograft model: targeting epidermal growth factor receptor. Gastrointest Endosc 2012; 76:612-20. [PMID: 22771099 DOI: 10.1016/j.gie.2012.05.013] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Accepted: 05/09/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND The prognosis of gastric cancer depends on early diagnosis. Targeted therapies against epidermal growth factor receptors (EGFRs) are currently emerging for the treatment of gastric cancer. OBJECTIVE To specifically visualize gastric cancer by using monoclonal antibodies targeting EGFR1 as molecular probes for in vivo molecular confocal laser endomicroscopy (mCLE) in a human-murine xenograft model. DESIGN Prospective in vivo animal study. SETTING Animal laboratory. INTERVENTIONS Human gastric carcinoma xenografts were examined in 26 nude mice by using mCLE after injection of fluorescently labeled antibodies. Nine mice received low-dose anti-EGFR1 antibodies, 7 mice cetuximab, and 7 control mice isotype antibodies. Three mice were screened for autofluorescence without injection. Macroscopic fluorescence was evaluated in 2 additional mice. MAIN OUTCOME MEASUREMENTS Molecular imaging of gastric cancer with confocal laser endomicroscopy. RESULTS Fluorescence intensity in the anti-EGFR1 (P = .0145) and cetuximab group (P = .0047) was significantly higher than in isotype control mice. The same protocol allowed macroscopic fluorescence detection of tumor xenografts. LIMITATIONS Animal model. CONCLUSIONS In vivo microscopic and macroscopic molecular imaging of gastric cancer is feasible in a human-murine xenograft model with both diagnostic and therapeutic antibodies targeting EGFR1. In perspective, mCLE could help diagnose and molecularly characterize gastric cancer during ongoing gastroscopy and may even assist in the prediction of response to therapy.
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Affiliation(s)
- Michael S Hoetker
- 1st Department of Medicine, University Medical Center of Johannes Gutenberg University Mainz, Mainz, Germany
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Carignan CS, Yagi Y. Optical endomicroscopy and the road to real-time, in vivo pathology: present and future. Diagn Pathol 2012; 7:98. [PMID: 22889003 PMCID: PMC3502368 DOI: 10.1186/1746-1596-7-98] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2012] [Accepted: 07/19/2012] [Indexed: 02/07/2023] Open
Abstract
UNLABELLED Epithelial cancers account for substantial mortality and are an important public health concern. With the need for earlier detection and treatment of these malignancies, the ability to accurately detect precancerous lesions has an increasingly important role in controlling cancer incidence and mortality. New optical technologies are capable of identifying early pathology in tissues or organs in which cancer is known to develop through stages of dysplasia, including the esophagus, colon, pancreas, liver, bladder, and cervix. These diagnostic imaging advances, together as a field known as optical endomicroscopy, are based on confocal microscopy, spectroscopy-based imaging, and optical coherence tomography (OCT), and function as "optical biopsies," enabling tissue pathology to be imaged in situ and in real time without the need to excise and process specimens as in conventional biopsy and histopathology. Optical biopsy techniques can acquire high-resolution, cross-sectional images of tissue structure on the micron scale through the use of endoscopes, catheters, laparoscopes, and needles. Since the inception of these technologies, dramatic technological advances in accuracy, speed, and functionality have been realized. The current paradigm of optical biopsy, or single-area, point-based images, is slowly shifting to more comprehensive microscopy of larger tracts of mucosa. With the development of Fourier-domain OCT, also known as optical frequency domain imaging or, more recently, volumetric laser endomicroscopy, comprehensive surveillance of the entire distal esophagus is now achievable at speeds that were not possible with conventional OCT technologies. Optical diagnostic technologies are emerging as clinically useful tools with the potential to set a new standard for real-time diagnosis. New imaging techniques enable visualization of high-resolution, cross-sectional images and offer the opportunity to guide biopsy, allowing maximal diagnostic yields and appropriate staging without the limitations and risks inherent with current random biopsy protocols. However, the ability of these techniques to achieve widespread adoption in clinical practice depends on future research designed to improve accuracy and allow real-time data transmission and storage, thereby linking pathology to the treating physician. These imaging advances are expected to eventually offer a see-and-treat paradigm, leading to improved patient care and potential cost reduction. VIRTUAL SLIDES The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5372548637202968.
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Thong PSP, Tandjung SS, Movania MM, Chiew WM, Olivo M, Bhuvaneswari R, Seah HS, Lin F, Qian K, Soo KC. Toward real-time virtual biopsy of oral lesions using confocal laser endomicroscopy interfaced with embedded computing. JOURNAL OF BIOMEDICAL OPTICS 2012; 17:056009. [PMID: 22612132 DOI: 10.1117/1.jbo.17.5.056009] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Oral lesions are conventionally diagnosed using white light endoscopy and histopathology. This can pose a challenge because the lesions may be difficult to visualise under white light illumination. Confocal laser endomicroscopy can be used for confocal fluorescence imaging of surface and subsurface cellular and tissue structures. To move toward real-time "virtual" biopsy of oral lesions, we interfaced an embedded computing system to a confocal laser endomicroscope to achieve a prototype three-dimensional (3-D) fluorescence imaging system. A field-programmable gated array computing platform was programmed to enable synchronization of cross-sectional image grabbing and Z-depth scanning, automate the acquisition of confocal image stacks and perform volume rendering. Fluorescence imaging of the human and murine oral cavities was carried out using the fluorescent dyes fluorescein sodium and hypericin. Volume rendering of cellular and tissue structures from the oral cavity demonstrate the potential of the system for 3-D fluorescence visualization of the oral cavity in real-time. We aim toward achieving a real-time virtual biopsy technique that can complement current diagnostic techniques and aid in targeted biopsy for better clinical outcomes.
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Confocal Laser Endomicroscopy in the Study of Colonic Mucosa in IBD Patients: A Review. Gastroenterol Res Pract 2012; 2012:525098. [PMID: 22474440 PMCID: PMC3303710 DOI: 10.1155/2012/525098] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2011] [Accepted: 12/27/2011] [Indexed: 12/19/2022] Open
Abstract
Confocal laser endomicroscopy (CLE) is one of several novel methods that provide real-time, high-resolution imaging at a micronscale via endoscopes. CLE and related technologies are often termed “virtual biopsy” as they simulate the images seen in traditional histology. 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 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. This report aims to evaluate the current data on the application of confocal endomicroscopy in clinical gastroenterology and particularly in the study of colonic mucosa in UC patients.
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Li SZ, Wang Q. Feasibility of diagnosis of early gastric cancer assisted by confocal microscopy. Shijie Huaren Xiaohua Zazhi 2012; 20:205-209. [DOI: 10.11569/wcjd.v20.i3.205] [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
Gastric cancer has high incidence and mortality and does serious harm to the health of human beings. Early diagnosis and radical operation are crucial for prognosis in patients with gastric cancer. Worldwide efforts have been taken to search new methods and technologies that can enable early, accurate and efficient diagnosis of gastric cancer. The birth of the confocal microscope makes the dream come true. It perfectly combines the advantages of various kinds of technologies and allows early, rapid and accurate diagnosis of gastric cancer. In this paper, we discuss the possibility of using laser confocal microscopy for the early diagnosis of gastric cancer to improve patients' life quality and survival rate.
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Yoo H, Kang D, Katz AJ, Lauwers GY, Nishioka NS, Yagi Y, Tanpowpong P, Namati J, Bouma BE, Tearney GJ. Reflectance confocal microscopy for the diagnosis of eosinophilic esophagitis: a pilot study conducted on biopsy specimens. Gastrointest Endosc 2011; 74:992-1000. [PMID: 21944314 PMCID: PMC3425354 DOI: 10.1016/j.gie.2011.07.020] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Accepted: 07/14/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND Diagnosis of eosinophilic esophagitis (EoE) currently requires endoscopic biopsy and histopathologic analysis of the biopsy specimens to count intraepithelial eosinophils. Reflectance confocal microscopy (RCM) is an endomicroscopy technology that is capable of obtaining high-resolution, optically sectioned images of esophageal mucosa without the administration of exogenous contrast. OBJECTIVE In this study, we investigated the capability of a high-speed form of RCM, termed spectrally encoded confocal microscopy (SECM), to count intraepithelial esophageal eosinophils and characterize other microscopic findings of EoE. DESIGN A total of 43 biopsy samples from 35 pediatric patients and 8 biopsy samples from 8 adult patients undergoing EGD for EoE were imaged by SECM immediately after their removal and then processed for routine histopathology. Two SECM readers, trained on adult cases, prospectively counted intraepithelial eosinophils and detected the presence of abscess, degranulation, and basal cell hyperplasia on SECM images from the pediatric patients. A pathologist blinded to the SECM data analyzed the same from corresponding slides. SETTING The Gastrointestinal Unit, Massachusetts General Hospital. RESULTS Eosinophils by SECM demonstrated a higher reflectance than the surrounding cells and other inflammatory cells. There was good correlation between SECM and histology maximum eosinophil counts/high-power field (R = 0.76, P < .0001). Intra- and interobserver correlations for SECM counts were very good (R = 0.93 and R = 0.92, respectively; P < .0001). For the commonly used eosinophil count cutoff of 15 per high-power field, the sensitivity and specificity of SECM for EoE were 100%. The sensitivity and specificity for abscess, degranulation, and basal cell hyperplasia were 100% and 82%, 91% and 60%, and 94% and 80%, respectively. Intra- and interobserver agreements for these microscopic features of EoE were very good (κ = 0.9/0.9, 0.84/1.0, 0.91/0.81, respectively). LIMITATION Ex vivo study. CONCLUSIONS This study demonstrates that RCM can be used to accurately count intraepithelial eosinophils and identify other microscopic abnormalities associated with EoE on freshly excised biopsy samples. These findings suggest that RCM may be developed into a tool for assessing eosinophilic infiltration in the esophagus in vivo.
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Affiliation(s)
- Hongki Yoo
- Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA,Department of Dermatology Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - DongKyun Kang
- Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA,Department of Dermatology Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aubrey J. Katz
- Department of Gastrointestinal Unit, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA,Food Allergy Center, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Gregory Y. Lauwers
- Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Norman S. Nishioka
- Department of Gastrointestinal Unit, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Yukako Yagi
- Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Pornthep Tanpowpong
- Department of Gastrointestinal Unit, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA,Food Allergy Center, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Jacqueline Namati
- Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA,Department of Dermatology Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Brett E. Bouma
- Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA,Harvard-MIT Health Sciences and Technology, Cambridge, Massachusetts, USA
| | - Guillermo J. Tearney
- Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA,Department of Dermatology Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA,Harvard-MIT Health Sciences and Technology, Cambridge, Massachusetts, USA
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Kiesslich R, Goetz M, Hoffman A, Galle PR. New imaging techniques and opportunities in endoscopy. Nat Rev Gastroenterol Hepatol 2011; 8:547-53. [PMID: 21894196 DOI: 10.1038/nrgastro.2011.152] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Gastrointestinal endoscopy is undergoing major improvements, which are driven by new available technologies and substantial refinements of optical features. In this Review, we summarize available and evolving imaging technologies that could influence the clinical algorithm of endoscopic diagnosis. Detection, characterization and confirmation are essential steps required for proper endoscopic diagnosis. Optical and nonoptical methods can help to improve each step; these improvements are likely to increase the detection rate of neoplasias and reduce unnecessary endoscopic treatments. Furthermore, functional and molecular imaging are emerging as new diagnostic tools that could provide an opportunity for personalized medicine, in which endoscopy will define disease outcome or predict the response to targeted therapy.
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Affiliation(s)
- Ralf Kiesslich
- Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
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Gheonea DI, Cârţână T, Ciurea T, Popescu C, Bădărău A, Săftoiu A. Confocal laser endomicroscopy and immunoendoscopy for real-time assessment of vascularization in gastrointestinal malignancies. World J Gastroenterol 2011; 17:21-7. [PMID: 21218080 PMCID: PMC3016676 DOI: 10.3748/wjg.v17.i1.21] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2010] [Revised: 10/19/2010] [Accepted: 10/26/2010] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal cancers represent a major cause of morbidity and mortality, with incomplete response to chemotherapy in the advanced stages and poor prognosis. Angiogenesis plays a crucial part in tumor growth and metastasis, with most gastrointestinal cancers depending strictly on the development of a new and devoted capillary network. Confocal laser endomicroscopy is a new technology which allows in vivo microscopic analysis of the gastrointestinal mucosa and its microvascularization during ongoing endoscopy by using topically or systemically administered contrast agents. Targeting markers of angiogenesis in association with confocal laser endomicroscopic examination (immunoendoscopy), as a future challenge, will add functional analysis to the morphological aspect of the neoplastic process. This review describes previous experience in endomicroscopic examination of the upper and lower digestive tract with emphasis on vascularization, resulting in a broad spectrum of potential clinical applications, and also preclinical research that could be translated to human studies.
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21
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De Palma GD, Staibano S, Siciliano S, Persico M, Masone S, Maione F, Siano M, Mascolo M, Esposito D, Salvatori F, Persico G. In vivo characterisation of superficial colorectal neoplastic lesions with high-resolution probe-based confocal laser endomicroscopy in combination with video-mosaicing: a feasibility study to enhance routine endoscopy. Dig Liver Dis 2010; 42:791-7. [PMID: 20409761 DOI: 10.1016/j.dld.2010.03.009] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2009] [Revised: 02/16/2010] [Accepted: 03/02/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND Recent technological advances in miniaturisation have allowed for a confocal scanning microscope to be integrated into trans-endoscopic probes enabling endoscopists to collect in vivo virtual biopsies of the gastrointestinal mucosa during endoscopy. AIMS The aim of the present study was to assess prospectively the clinical applicability and predictive power of a probe-based confocal laser endomicroscopy for the in vivo diagnosis of colorectal neoplasia. METHODS Patients with evidence of colorectal superficial neoplasia at routine endoscopy, were included prospectively in this study. Lesions were identified using white-light endoscopy followed by pCLE imaging recorded by a Coloflex UHD-type probe. The images were interpreted as either neoplastic or not according to vascular and cellular changes. pCLE readings were then compared with histopathological results from endoscopically resected lesions and/or targeted biopsy specimens. RESULTS A total of 32 lesions were identified in 20 consecutive patients. Histopathology diagnosis was of adenomas in 19 cases, hyperplastic polyps in 11 cases and adenocarcinoma in 2 cases. For the detection of neoplastic tissue pCLE had a sensitivity of 100%, a specificity of 84.6%, an accuracy of 92.3, a PPV of 90.5% and a NPV of 100%. CONCLUSIONS pCLE permits high-quality imaging, enabling prediction of intraepithelial neoplasia with a high level of accuracy.
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Affiliation(s)
- Giovanni D De Palma
- Department of Surgery and Advanced Technologies, Center of Excellence for Technical Innovation in Surgery (ITC), University of Naples Federico II, School of Medicine, Via Pansini, 5, 80131, Naples, Italy.
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Advances in endoscopic imaging of colorectal neoplasia. Gastroenterology 2010; 138:2140-50. [PMID: 20420951 DOI: 10.1053/j.gastro.2009.12.067] [Citation(s) in RCA: 94] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2009] [Revised: 11/19/2009] [Accepted: 12/08/2009] [Indexed: 12/12/2022]
Abstract
Colon cancer screening is arguably the most important activity performed by gastroenterologists. Recent decreases in rates of death from colorectal cancer indicate that screening methods such as colonoscopy have a positive impact. There is still room for improvement, however, particularly in prevention of right-sided colon cancer. Practice issues, such as making colonoscopy more comfortable, safer, and less costly, are keys to continued success in cancer prevention. Colonoscopy techniques, technologies, and quality control measures have advanced to improve detection, classification, and removal of early neoplasias. In particular, slow, careful inspection of the colon by gastroenterologists who have been trained in lesion recognition has improved rates of detection of polypoid and flat neoplasias. Image enhancement methods such as chromoendoscopy have greatly improved neoplasia detection in patients with chronic colitis, but are not widely used because they are perceived as inconvenient. More convenient methods, such as "digital" chromoendoscopy, show promise but have had mixed results. Ultra-high magnification systems, including optical magnification and confocal endomicroscopy, can be used during the colonoscopy examination to evaluate small polyps, allowing physicians to make immediate diagnoses and decisions about whether to remove polyps. In patients with inflammatory bowel disease, improved imaging techniques could eliminate the needs for analysis of randomly selected biopsy samples and resection of all (neoplastic and non-neoplastic) polyps. It is important to maintain high standards of quality for colonoscopy examination, detection, and removal of high-risk lesions, as well as to make colon cancer screening more widely accepted and affordable for the entire at-risk population.
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Quelles perspectives pour l’imagerie photonique in vivo en pratique clinique ? ONCOLOGIE 2010. [DOI: 10.1007/s10269-010-1862-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Kang D, Suter MJ, Boudoux C, Yoo H, Yachimski PS, Puricelli WP, Nishioka NS, Mino-Kenudson M, Lauwers GY, Bouma BE, Tearney GJ. Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy. Gastrointest Endosc 2010; 71:35-43. [PMID: 19922916 PMCID: PMC3135336 DOI: 10.1016/j.gie.2009.08.026] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2009] [Accepted: 08/23/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique that has the potential to be used for acquiring comprehensive images of the entire distal esophagus endoscopically with subcellular resolution. OBJECTIVE The goal of this study was to demonstrate large-area SECM in upper GI tissues and to determine whether the images contain microstructural information that is useful for pathologic diagnosis. DESIGN A feasibility study. SETTING Gastrointestinal Unit, Massachusetts General Hospital. PATIENTS Fifty biopsy samples from 36 patients undergoing routine EGD were imaged by SECM, in their entirety, immediately after their removal. RESULTS The microstructure seen in the SECM images was similar to that seen by histopathology. Gastric cardia mucosa was clearly differentiated from squamous mucosa. Gastric fundic/body type mucosa showed more tightly packed glands than gastric cardia mucosa. Fundic gland polyps showed cystically dilated glands lined with cuboidal epithelium. The presence of intraepithelial eosinophils was detected with the cells demonstrating a characteristic bilobed nucleus. Specialized intestinal metaplasia was identified by columnar epithelium and the presence of goblet cells. Barrett's esophagus (BE) with dysplasia was differentiated from specialized intestinal metaplasia by the loss of nuclear polarity and disorganized glandular architecture. LIMITATIONS Ex vivo, descriptive study. CONCLUSIONS Large-area SECM images of gastroesophageal biopsy samples enabled the visualization of both subcellular and architectural features of various upper GI mucosal types and were similar to the corresponding histopathologic slides. These results suggest that the development of an endoscopic SECM probe is merited.
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25
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Palma GDD. Confocal laser endomicroscopy in the “ in vivo” histological diagnosis of the gastrointestinal tract. World J Gastroenterol 2009; 15:5770-5. [PMID: 19998496 PMCID: PMC2791268 DOI: 10.3748/wjg.15.5770] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.5] [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
Recent technological advances in miniaturization have allowed for a confocal scanning microscope to be integrated into a conventional flexible endoscope, or into trans-endoscopic probes, a technique now known as confocal endomicroscopy or confocal laser endomicroscopy. This newly-developed technology has enabled endoscopists to collect real-time in vivo histological images or “virtual biopsies” of the gastrointestinal mucosa during endoscopy, and has stimulated significant interest in the application of this technique in clinical gastroenterology. This review aims to evaluate the current data on the technical aspects and the utility of this new technology in clinical gastroenterology and its potential impact in the future, particularly in the screening or surveillance of gastrointestinal neoplasia.
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Stasche N. [Endoscopy in otorhinolaryngology]. HNO 2009; 57:1218-20. [PMID: 19924361 DOI: 10.1007/s00106-009-2021-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- N Stasche
- Westpfalz-Klinikum, Hellmut-Hartert-Strasse 1, 67655, Kaiserslautern, Deutschland.
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Abstract
The articles published this last year in the field of Helicobacter pylori diagnosis reported the development of in vivo histology, small improvements in some invasive methods (urease test, culture, and histology) and new kits for the stool antigen tests. They also contributed to increasing our knowledge, by further exploration into specific conditions for the urea breath test and into the significance of cagA antibodies. The role of serum markers of atrophy was also confirmed. Molecular methods are still being developed for direct genotyping, detection of H. pylori and its clarithromycin resistance, either by polymerase chain reaction or fluorescent in-situ hybridization. For the first time, there was a report on a possible interest of magnetic resonance spectroscopy.
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Affiliation(s)
- Lurdes Monteiro
- Departamento de Doenças Infecciosas, Instituto Nacional Saúde Dr Ricardo Jorge, Lisbon, Portugal
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