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Pessarelli T, Tontini GE, Neumann H. Advanced Endoscopic Imaging for Assessing Mucosal Healing and Histologic Remission in Inflammatory Bowel Diseases. Gastrointest Endosc Clin N Am 2025; 35:159-177. [PMID: 39510685 DOI: 10.1016/j.giec.2024.04.008] [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: 11/15/2024]
Abstract
Recent advances in the field of endoscopy have found fertile ground for application in inflammatory bowel diseases (IBD). Mucosal healing is a primary goal of IBD therapy, and current evidence shows that histologic remission (HR) is an additional desirable outcome. However, with the use of standard endoscopy, a considerable number of patients with histologically active disease go unrecognized. This narrative article examines the role, current or potential, of each endoscopic technique, from standard white-light endoscopy to molecular imaging, in the assessment of mucosal healing and HR in IBD.
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Affiliation(s)
- Tommaso Pessarelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, Milano 20122, Italy
| | - Gian Eugenio Tontini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, Milano 20122, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
| | - Helmut Neumann
- Department of Interdisciplinary Endoscopy, I. Medizinische Klinik und Poliklinik, University Hospital, Mainz, Germany; GastroZentrum LippeLange Street 55, Bad Salzuflen, Germany
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2
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Misawa M, Kudo SE, Takashina Y, Akimoto Y, Maeda Y, Mori Y, Kudo T, Wakamura K, Miyachi H, Ishida F, Inoue H. Clinical Efficacy of Endocytoscopy for Gastrointestinal Endoscopy. Clin Endosc 2021; 54:455-463. [PMID: 34233111 PMCID: PMC8357585 DOI: 10.5946/ce.2021.165] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 06/10/2021] [Indexed: 12/15/2022] Open
Abstract
Endocytoscopy (EC) is a contact-type optical endoscope that allows in vivo cellular observation during gastrointestinal endoscopy and is now commercially available not only in Japan but also in Asian, European Union, and Middle Eastern countries. EC helps conduct a highly accurate pathological prediction without biopsy. Initially, EC was reported to be effective for esophageal diseases. Subsequently, its efficacy for stomach and colorectal diseases has been reported. In this narrative review, we searched for clinical studies that investigated the efficacy of EC. EC seems to accurately diagnose gastrointestinal diseases without biopsy. Most of the studies aimed to clarify the relationship between endocytoscopic findings of gastrointestinal neoplasia and pathological diagnosis. Some studies have investigated non-epithelial lesions or diseases, such as inflammatory bowel disease or infectious diseases. However, there are few high-level pieces of evidence, such as randomized trials; thus, further studies are needed.
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Affiliation(s)
- Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Shin-Ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Yuki Takashina
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Yoshika Akimoto
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Yasuharu Maeda
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan.,Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Toyoki Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Kunihiko Wakamura
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Hideyuki Miyachi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Fumio Ishida
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Haruhiro Inoue
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
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Clapper ML, Chang WCL, Cooper HS. Dysplastic Aberrant Crypt Foci: Biomarkers of Early Colorectal Neoplasia and Response to Preventive Intervention. Cancer Prev Res (Phila) 2021; 13:229-240. [PMID: 32132117 DOI: 10.1158/1940-6207.capr-19-0316] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 10/04/2019] [Accepted: 10/25/2019] [Indexed: 12/15/2022]
Abstract
The discovery of aberrant crypt foci (ACF) more than three decades ago not only enhanced our understanding of how colorectal tumors form, but provided new opportunities to detect lesions prior to adenoma development and intervene in the colorectal carcinogenesis process even earlier. Because not all ACF progress to neoplasia, it is important to stratify these lesions based on the presence of dysplasia and establish early detection methods and interventions that specifically target dysplastic ACF (microadenomas). Significant progress has been made in characterizing the morphology and genetics of dysplastic ACF in both preclinical models and humans. Image-based methods have been established and new techniques that utilize bioactivatable probes and capture histologic abnormalities in vivo are emerging for lesion detection. Successful identification of agents that target dysplastic ACF holds great promise for intervening even earlier in the carcinogenesis process to maximize tumor inhibition. Future preclinical and clinical prevention studies should give significant attention to assessing the utility of dysplastic ACF as the earliest identifiable biomarker of colorectal neoplasia and response to therapy.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.
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Affiliation(s)
- Margie L Clapper
- Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
| | - Wen-Chi L Chang
- Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Harry S Cooper
- Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.,Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
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AL-Kandari A, Neumann H. Endocytoscopy for Luminal Gastrointestinal Diseases: A Systematic Review. TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY 2021; 23:77-86. [DOI: 10.1016/j.tige.2020.09.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Sinicrope FA, Velamala PR, Song LMWK, Viggiano TR, Bruining DH, Rajan E, Gostout CJ, Kraichely RE, Buttar NS, Schroeder KW, Kisiel JB, Larson MV, Sweetser SR, Sedlack RR, Sinicrope SN, Richmond E, Umar A, Della'Zanna G, Noaeill JS, Meyers JP, Foster NR. Efficacy of Difluoromethylornithine and Aspirin for Treatment of Adenomas and Aberrant Crypt Foci in Patients with Prior Advanced Colorectal Neoplasms. Cancer Prev Res (Phila) 2019; 12:821-830. [PMID: 31484660 DOI: 10.1158/1940-6207.capr-19-0167] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 06/27/2019] [Accepted: 08/27/2019] [Indexed: 11/16/2022]
Abstract
Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, was shown to act synergistically with a NSAID for chemoprevention of colorectal neoplasia. We determined the efficacy and safety of DFMO plus aspirin for prevention of colorectal adenomas and regression of rectal aberrant crypt foci (ACF) in patients with prior advanced adenomas or cancer. A double-blinded, placebo-controlled trial was performed in 104 subjects (age 46-83) randomized (1:1) to receive daily DFMO (500 mg orally) plus aspirin (325 mg) or matched placebos for one year. All polyps were removed at baseline. Adenoma number (primary endpoint) and rectal ACF (index cluster and total) were evaluated at a one year colonoscopy. ACF were identified by chromoendoscopy. Toxicity was monitored, including audiometry. Eighty-seven subjects were evaluable for adenomas or ACF modulation (n = 62). At one year of treatment, adenomas were detected in 16 (38.1%) subjects in the DFMO plus aspirin arm (n = 42) versus 18 (40.9%) in the placebo arm (n = 44; P = 0.790); advanced adenomas were similar (n = 3/arm). DFMO plus aspirin was associated with a statistically significant reduction in the median number of rectal ACF compared with placebo (P = 0.036). Total rectal ACF burden was also reduced in the treatment versus the placebo arm relative to baseline (74% vs. 45%, P = 0.020). No increase in adverse events, including ototoxicity, was observed in the treatment versus placebo arms. While adenoma recurrence was not significantly reduced by one year of DFMO plus aspirin, the drug combination significantly reduced rectal ACF number consistent with a chemopreventive effect.
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Affiliation(s)
- Frank A Sinicrope
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota.
| | - Pruthvi R Velamala
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Thomas R Viggiano
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David H Bruining
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Elizabeth Rajan
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Robert E Kraichely
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Navtej S Buttar
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Kenneth W Schroeder
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John B Kisiel
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Mark V Larson
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Seth R Sweetser
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Robert R Sedlack
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Stephen N Sinicrope
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Ellen Richmond
- Biomedical Statistics & Informatics, Mayo Clinic, Rochester, Minnesota
| | - Asad Umar
- Biomedical Statistics & Informatics, Mayo Clinic, Rochester, Minnesota
| | - Gary Della'Zanna
- Biomedical Statistics & Informatics, Mayo Clinic, Rochester, Minnesota
| | - Joni S Noaeill
- Divisions of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Jeffrey P Meyers
- Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland
| | - Nathan R Foster
- Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland
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Utsumi T, Sano Y, Iwatate M, Sunakawa H, Teramoto A, Hirata D, Hattori S, Sano W, Hasuike N, Ichikawa K, Fujimori T. Prospective real-time evaluation of diagnostic performance using endocytoscopy in differentiating neoplasia from non-neoplasia for colorectal diminutive polyps (≤ 5 mm). World J Gastrointest Oncol 2018; 10:96-102. [PMID: 29666668 PMCID: PMC5900455 DOI: 10.4251/wjgo.v10.i4.96] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Revised: 01/10/2018] [Accepted: 03/06/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To clarify the diagnostic performance of endocytoscopy for differentiation between neoplastic and non-neoplastic colorectal diminutive polyps. METHODS Patients who underwent endocytoscopy between October and December 2016 at Sano Hospital were prospectively recruited. When diminutive polyps (≤ 5 mm) were detected, the lesions were evaluated by endocytoscopy after being stained with 0.05% crystal violet and 1% methylene blue. The diminutive polyps were classified into five categories (EC 1a, 1b, 2, 3a, and 3b). Endoscopists were asked to take a biopsy from any lesion diagnosed as EC1b (indicator of hyperplastic polyp) or EC2 (indicator of adenoma). We have assessed the diagnostic performance of endocytoscopy for EC2 and EC1b lesions by comparison with the histopathology of the biopsy specimen. RESULTS A total of 39 patients with 63 diminutive polyps were analyzed. All polyps were evaluated by endocytoscopy. The mean polyp size was 3.3 ± 0.9 mm. Among the 63 diminutive polyps, 60 were flat and 3 were pedunculated. The mean time required for EC observation, including the time for staining with crystal violet and methylene blue, was 3.0 ± 1.9 min. Histopathologic evaluation showed that 13 polyps were hyperplastic and 50 were adenomas. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of EC2 for adenoma compared with EC1b for hyperplastic polyp were 98.0%, 92.3%, 96.8%, 98.0% and 92.3%, respectively. There were only two cases of disagreement between the endoscopic diagnosis made by endocytoscopy and the corresponding histopathological diagnosis. CONCLUSION Endocytoscopy showed a high diagnostic performance for differentiating between neoplastic and non-neoplastic colorectal diminutive polyps, and therefore has the potential to be used for "real-time histopathology".
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Affiliation(s)
- Takahiro Utsumi
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
| | - Yasushi Sano
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
| | - Mineo Iwatate
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
| | - Hironori Sunakawa
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
| | - Akira Teramoto
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
| | - Daizen Hirata
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
| | - Santa Hattori
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
| | - Wataru Sano
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
| | - Noriaki Hasuike
- Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Hyogo 655-0031, Japan
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Beintaris I, Rutter M. Advanced imaging in colonoscopy: contemporary approach to dysplasia surveillance in inflammatory bowel disease. Frontline Gastroenterol 2016; 7:308-315. [PMID: 28839872 PMCID: PMC5369495 DOI: 10.1136/flgastro-2016-100735] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 07/19/2016] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) (ulcerative colitis (UC) and Crohn's disease (CD)) is a chronic relapsing/remitting condition characterised by intestinal inflammation. One of the main concerns in patients with longstanding ulcerative and Crohn's colitis is development of colonic dysplasia and colorectal cancer (CRC), a risk higher than that of the general population. Colonoscopy surveillance programmes have been developed by major societies worldwide to improve early dysplasia detection and treatment, thus preventing progression to colorectal cancer. Colonoscopy is an imperfect tool as lesions can be missed, an issue even more relevant to colitic patients, where mucosal inspection and lesion recognition may prove challenging. Extensive research has been undertaken on performance improvement in this area while technical advances in optical imaging, such as high-definition, have made their way into modern endoscopy units. Techniques and technologies available to enhance optical diagnosis of dysplasia in inflammatory bowel disease are reviewed in this paper, focusing on those that are realistic, widely available and feasible for everyday practice.
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Affiliation(s)
| | - Matt Rutter
- University Hospital of North Tees, Cleveland, UK
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Takeda K, Kudo SE, Misawa M, Mori Y, Kudo T, Kodama K, Wakamura K, Miyachi H, Hidaka E, Ishida F, Inoue H. Comparison of the endocytoscopic and clinicopathologic features of colorectal neoplasms. Endosc Int Open 2016; 4:E397-402. [PMID: 27547815 PMCID: PMC4990025 DOI: 10.1055/s-0042-101753] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Accepted: 01/18/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIM Permeation of a vein or lymphatic vessel by a tumor is a key risk factor for lymph node metastasis. We examined the features of colorectal tumor vessel permeation using endocytoscopy, an ultra-high magnifying endoscopic system combined with a narrow-band imaging capability (EC-NBI). PATIENTS AND METHODS We examined 188 colorectal lesions using EC-NBI before treatment was started. We measured the diameters of tumor vessels on EC-NBI images. We used the tumor vessel diameter (the mean diameter of four tumor-associated vessels) and the variation in tumor vessel caliber (the difference between the maximum and minimum diameters of the vessels expressed as a proportion) to judge changes in vessel formation. We examined the relationship between these variables and the extent of venous or lymphatic vessel permeation (vessel invasion) established by immunohistochemical examination of the resected specimen using monoclonal antibodies against the CD34 and D2 - 40 antigens. We also analyzed the relationships between tumor vessel diameter, tumor vessel caliber variation, and depth of tumor invasion. RESULTS There were significant differences in tumor vessel diameter and caliber variation between tumors in situ and T1 - T3 carcinomas. In T1 carcinomas, larger tumor vessel diameter and greater tumor vessel caliber variation were significantly associated with venous permeation. In T2 and T3 carcinomas, greater tumor vessel caliber variation was significantly associated with venous permeation. CONCLUSIONS The vessel diameter and caliber variation of colorectal tumor microvasculature are associated with depth of invasion and venous permeation, especially in T1 carcinomas.
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Affiliation(s)
- Kenichi Takeda
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Shin-ei Kudo
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan,Corresponding author Shin-ei Kudo, MD PhD Digestive Disease CenterShowa UniversityNorthern Yokohama Hospital35-1 Chigasaki-ChuoTsuzukiYokohama 224-8503Japan+81-45-9497535
| | - Masashi Misawa
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Yuichi Mori
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Toyoki Kudo
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Kenta Kodama
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Kunihiko Wakamura
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Hideyuki Miyachi
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Eiji Hidaka
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Fumio Ishida
- Digestive Disease Center, Showa University, Yokohama Northern Hospital, Kanagawa, Japan
| | - Haruhiro Inoue
- Digestive Disease Center, Showa University, Koto Toyosu Hospital, Tokyo, Japan
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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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10
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Kudo T, Kudo SE, Wakamura K, Mori Y, Misawa M, Hayashi T, Kutsukawa M, Ichimasa K, Miyachi H, Ishida F, Inoue H. Diagnostic performance of endocytoscopy for evaluating the invasion depth of different morphological types of colorectal tumors. Dig Endosc 2015; 27:754-761. [PMID: 25777505 DOI: 10.1111/den.12469] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 03/06/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM Endocytoscopy (EC) is a next-generation endoscopic technique that enables diagnostic imaging at 450× magnification. In the present study, we retrospectively evaluated the diagnostic performance of EC and magnifying chromoendoscopy (MCE) for diagnosing the invasion depth of colorectal tumors. METHODS We investigated 330 lesions with a ≥10-mm tumor diameter that could be diagnosed by both MCE and EC. The lesions were classified according to morphological type as follows: laterally spreading type-granular (LST-G), laterally spreading type-non-granular (LST-NG), protruding, or depressed. After all lesions had been classified by both pit pattern and EC, qualitative and quantitative (invasion depth) diagnoses were made. The diagnostic accuracy was then compared between pit pattern classification and EC classification. RESULTS Diagnostic accuracy of EC classification was significantly higher for LST-NG lesions (90.5%) than for protruding lesions (80.6%) (P < 0.05). Diagnostic accuracy for LST-NG lesions was significantly higher with EC classification (90.5%) than with pit pattern classification (79.3%) (P < 0.001). Comparison of the diagnostic performance of EC3a findings using EC classification between LST-NG and protruding lesions revealed a sensitivity of 92.9% versus 11.3% (P < 0.001), positive predictive value of 78.0% versus 27.3% (P < 0.001), negative predictive value of 95.5% versus 56.1% (P < 0.001), and diagnostic accuracy of 87.9% versus 51.2% (P < 0.001), respectively. CONCLUSION EC is a very useful method for evaluating the invasion depth of LST-NG lesions.
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Affiliation(s)
- Toyoki Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Shin-ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Kunihiko Wakamura
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Takemasa Hayashi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Makoto Kutsukawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Katsuro Ichimasa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Hideyuki Miyachi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Fumio Ishida
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama
| | - Haruhiro Inoue
- Digestive Disease Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan
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11
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Rath T, Tontini GE, Neurath MF, Neumann H. From the surface to the single cell: Novel endoscopic approaches in inflammatory bowel disease. World J Gastroenterol 2015; 21:11260-11272. [PMID: 26523101 PMCID: PMC4616203 DOI: 10.3748/wjg.v21.i40.11260] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 07/31/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) comprise the two major entities Crohn's disease and ulcerative colitis and endoscopic imaging of the gastrointestinal tract has always been an integral and central part in the management of IBD patients. Within the recent years, mucosal healing emerged as a key treatment goal in IBD that substantially decides about the clinical outcome of IBD patients, thereby demanding for a precise, timely and detailed endoscopic assessment of the mucosal inflammation associated with IBD. Further, 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 therapy response. Within this review we describe novel endoscopic approaches and advanced endoscopic imaging methods for the diagnosis, treatment and surveillance of IBD patients. We begin by providing an overview over novel and advanced imaging techniques such as magnification endoscopy and dye-based and dye-less chromoendoscopy, endomicroscopy and endocytoscopy. We then describe how these techniques can be utilized for the precise and ultrastructural assessment of mucosal inflammation and dysplasia development associated with IBD and outline how they have enabled the endoscopist to gain insight onto the cellular level in real-time. Finally, we provide an outlook on how molecular imaging has rapidly evolved in the recent past and can be used to make individual predictions about the therapeutic response towards biological treatment.
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12
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Cheon JH. Advances in the Endoscopic Assessment of Inflammatory Bowel Diseases: Cooperation between Endoscopic and Pathologic Evaluations. J Pathol Transl Med 2015; 49:209-217. [PMID: 26018512 PMCID: PMC4440932 DOI: 10.4132/jptm.2015.04.09] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 04/09/2015] [Indexed: 12/17/2022] Open
Abstract
Endoscopic assessment has a crucial role in the management of inflammatory bowel disease (IBD). It is particularly useful for the assessment of IBD disease extension, severity, and neoplasia surveillance. Recent advances in endoscopic imaging techniques have been revolutionized over the past decades, progressing from conventional white light endoscopy to novel endoscopic techniques using molecular probes or electronic filter technologies. These new technologies allow for visualization of the mucosa in detail and monitor for inflammation/dysplasia at the cellular or sub-cellular level. These techniques may enable us to alter the IBD surveillance paradigm from four quadrant random biopsy to targeted biopsy and diagnosis. High definition endoscopy and dye-based chromoendoscopy can improve the detection rate of dysplasia and evaluate inflammatory changes with better visualization. Dye-less chromoendoscopy, including narrow band imaging, iScan, and autofluorescence imaging can also enhance surveillance in comparison to white light endoscopy with optical or electronic filter technologies. Moreover, confocal laser endomicroscopy or endocytoscopy have can achieve real-time histology evaluation in vivo and have greater accuracy in comparison with histology. These new technologies could be combined with standard endoscopy or further histologic confirmation in patients with IBD. This review offers an evidence-based overview of new endoscopic techniques in patients with IBD.
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Affiliation(s)
- Jae Hee Cheon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Tontini GE, Vecchi M, Pastorelli L, Neurath MF, Neumann H. Differential diagnosis in inflammatory bowel disease colitis: State of the art and future perspectives. World J Gastroenterol 2015; 21:21-46. [PMID: 25574078 PMCID: PMC4284336 DOI: 10.3748/wjg.v21.i1.21] [Citation(s) in RCA: 138] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 07/31/2014] [Accepted: 09/16/2014] [Indexed: 02/06/2023] Open
Abstract
Distinction between Crohn’s disease of the colon-rectum and ulcerative colitis or inflammatory bowel disease (IBD) type unclassified can be of pivotal importance for a tailored clinical management, as each entity often involves specific therapeutic strategies and prognosis. Nonetheless, no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations. Hence, we have performed a literature search to address the problem of differential diagnosis in IBD colitis, revised current and emerging diagnostic tools and refined disease classification strategies. Nowadays, the differential diagnosis is an untangled issue, and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis. This topic is receiving emerging attention, as medical therapies, surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients. The optimization of standard diagnostic approaches based on clinical features, biomarkers, radiology, endoscopy and histopathology appears to provide only marginal benefits. Conversely, emerging diagnostic techniques in the field of gastrointestinal endoscopy, molecular pathology, genetics, epigenetics, metabolomics and proteomics have already shown promising results. Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD, better reflecting diverse disease behaviors based on specific pathogenic pathways.
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14
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Neumann H, Kudo SE, Kiesslich R, Neurath MF. Advanced colonoscopic imaging using endocytoscopy. Dig Endosc 2015; 27:232-8. [PMID: 25311804 DOI: 10.1111/den.12395] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Accepted: 10/06/2014] [Indexed: 12/14/2022]
Abstract
Optical biopsy techniques were recently introduced to luminal gastrointestinal endoscopy. These include confocal laser endomicroscopy, spectroscopic imaging techniques and endocytoscopy. Optical biopsy techniques allow on demand in vivo histology during ongoing endoscopy, thereby potentially accelerating clinical diagnosis and specific therapy. In the present review, we focus on endocytoscopy as one of the rapidly emerging optical biopsy techniques. We provide technical details of currently available endocytoscopy systems and give tips on their use in clinical practice. We also summarize applications of endocytoscopy for colorectal pathologies.
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Affiliation(s)
- Helmut Neumann
- Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany; Ludwig Demling Endoscopy Center of Excellence, University Hospital Erlangen, Erlangen, Germany
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Abstract
The assessment of extent and severity of IBD is crucial for directing treatment decisions. Clinical symptoms alone are neither sensitive nor specific for the assessment of lesion severity in IBD. Cross-sectional imaging techniques, as well as small-bowel capsule endoscopy (SBCE) and device-assisted enteroscopy, have a high accuracy for assessing the extent of mucosal lesions, and are reliable alternatives to ileocolonoscopy. New endoscopic techniques and devices are emerging for improved follow-up and surveillance. In this Review, we discuss different imaging techniques that are used to assess IBD activity and to survey patients with IBD, and highlight the latest developments in each area. Moreover, technical improvements and new tools that aim to measure intestinal fibrosis, postoperative recurrence, activity indices and endoscopic features are analysed. All of these imaging techniques are aimed at changing the paradigm from symptom-driven to lesion-driven treatment of IBD.
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Coda S, Thillainayagam AV. State of the art in advanced endoscopic imaging for the detection and evaluation of dysplasia and early cancer of the gastrointestinal tract. Clin Exp Gastroenterol 2014; 7:133-50. [PMID: 24868168 PMCID: PMC4028486 DOI: 10.2147/ceg.s58157] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Ideally, endoscopists should be able to detect, characterize, and confirm the nature of a lesion at the bedside, minimizing uncertainties and targeting biopsies and resections only where necessary. However, under conventional white-light inspection – at present, the sole established technique available to most of humanity – premalignant conditions and early cancers can frequently escape detection. In recent years, a range of innovative techniques have entered the endoscopic arena due to their ability to enhance the contrast of diseased tissue regions beyond what is inherently possible with standard white-light endoscopy equipment. The aim of this review is to provide an overview of the state-of-the-art advanced endoscopic imaging techniques available for clinical use that are impacting the way precancerous and neoplastic lesions of the gastrointestinal tract are currently detected and characterized at endoscopy. The basic instrumentation and the physics behind each method, followed by the most influential clinical experience, are described. High-definition endoscopy, with or without optical magnification, has contributed to higher detection rates compared with white-light endoscopy alone and has now replaced ordinary equipment in daily practice. Contrast-enhancement techniques, whether dye-based or computed, have been combined with white-light endoscopy to further improve its accuracy, but histology is still required to clarify the diagnosis. Optical microscopy techniques such as confocal laser endomicroscopy and endocytoscopy enable in vivo histology during endoscopy; however, although of invaluable assistance for tissue characterization, they have not yet made transition between research and clinical use. It is still unknown which approach or combination of techniques offers the best potential. The optimal method will entail the ability to survey wide areas of tissue in concert with the ability to obtain the degree of detailed information provided by microscopic techniques. In this respect, the challenging combination of autofluorescence imaging and confocal endomicroscopy seems promising, and further research is awaited.
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Affiliation(s)
- Sergio Coda
- Section of Gastroenterology and Hepatology, Department of Medicine and Photonics Group, Department of Physics, Imperial College London, London, UK ; Endoscopy Unit, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Andrew V Thillainayagam
- Section of Gastroenterology and Hepatology, Department of Medicine and Photonics Group, Department of Physics, Imperial College London, London, UK ; Endoscopy Unit, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
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17
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Ichimasa K, Kudo SE, Mori Y, Wakamura K, Ikehara N, Kutsukawa M, Takeda K, Misawa M, Kudo T, Miyachi H, Yamamura F, Ohkoshi S, Hamatani S, Inoue H. Double staining with crystal violet and methylene blue is appropriate for colonic endocytoscopy: an in vivo prospective pilot study. Dig Endosc 2014; 26:403-408. [PMID: 24016362 PMCID: PMC4232925 DOI: 10.1111/den.12164] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 08/02/2013] [Indexed: 01/20/2023]
Abstract
BACKGROUND AND AIM Endocytoscopy (EC) at ultra-high magnification enables in vivo visualization of cellular atypia of gastrointestinal mucosae. Clear images are essential for precise diagnosis by EC. The aim of the present study was to evaluate the optimal staining method for EC in the colon. METHODS Thirty prospectively enrolled patients were allocated 1:1:1 to three distinct staining methods: 0.05% crystal violet (CV) alone, 1% methylene blue (MB) alone, or CV+MB (CM double). Normal rectal mucosae were stained with each dye and videos of EC images were recorded. Visibility of nuclei and gland formation after staining were evaluated as 'recognizable' or 'not recognizable'. Time for each parameter to become 'recognizable' was measured, and the average times for the three staining regimens were compared. RESULTS MB alone and CM double staining resulted in 'recognizable' (102 ± 27 vs 89 ± 22 s, P=0.263) nuclei within comparable periods of time, whereas CV alone was unable to identify nuclei. Gland formation became 'recognizable' sooner after CM double staining than after MB alone (61 ± 16 vs 108 ± 24 s, P<0.001). CONCLUSIONS Double staining with CV and MB, which rapidly provided recognizable images of both nuclei and gland formation, is an appropriate staining regimen for colonic EC.
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Affiliation(s)
- Katsuro Ichimasa
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Shin-ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Kunihiko Wakamura
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Nobunao Ikehara
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Makoto Kutsukawa
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Kenichi Takeda
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Toyoki Kudo
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Hideyuki Miyachi
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Fuyuhiko Yamamura
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Shogo Ohkoshi
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Shigeharu Hamatani
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
| | - Haruhiro Inoue
- Digestive Disease Center, Showa University Northern Yokohama HospitalYokohama, Japan
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18
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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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19
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Hosoe N, Ogata H, Hibi T. Endoscopic imaging of parasites in the human digestive tract. Parasitol Int 2014; 63:216-220. [PMID: 23993997 DOI: 10.1016/j.parint.2013.08.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Accepted: 08/09/2013] [Indexed: 02/08/2023]
Abstract
There are various diagnostic approaches for parasitic infections, including microscopic identification of parasites in the stool or biopsy samples from the intestinal mucosa, antigen testing of feces or serum, polymerase chain reaction (PCR) testing, and serology. Endoscopy is sometimes used for direct confirmation of parasite infection and as a therapeutic option for removal. In recent years, innovations in endoscopy have advanced remarkably with regards to endoscopic devices as well as diagnostic and therapeutic endoscopical methods. Several new endoscopic devices are now used for diagnostic and therapeutic approaches to parasitic infections. In the present article, we have focused on in vivo imaging of parasitic infections. In vivo images of parasites were obtained using various endoscopic methods such as high-definition endoscopy, super-magnifying endoscopy, and video capsule endoscopy.
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Affiliation(s)
- Naoki Hosoe
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
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20
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Urquhart P, DaCosta R, Marcon N. Endoscopic mucosal imaging of gastrointestinal neoplasia in 2013. Curr Gastroenterol Rep 2013; 15:330. [PMID: 23771504 DOI: 10.1007/s11894-013-0330-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The holy grail of gastrointestinal endoscopy consists of the detection, in vivo characterization, and endoscopic removal of early or premalignant mucosal lesions. While our ability to achieve this goal has improved substantially since the development of the modern video-endoscope, inadequate visual inspection, errors of interpretation, and lesion subtlety all contribute to the continued suboptimal detection and assessment of early neoplasia. A myriad of new technologies has thus emerged that may help resolve these shortcomings; high magnification endoscopes, as well as the techniques of dye-based and virtual chromoendoscopy, are now widely available, while confocal laser endomicroscopy and endocystoscopy, optical coherence tomography, and autofluorescence imaging are generally applicable only in a research setting. Such technologies can be broadly categorized according to whether they potentially afford endoscopists improved detection, or real-time characterization, of mucosal lesions. Enhanced detection of otherwise "invisible" lesions, such as a flat area of intramucosal adenocarcinoma within Barrett's esophagus, carries the potential of an endoscopic cure prior to the development into a more advanced or metastatic disease. The ability to characterize a lesion to achieve an in vivo diagnosis, such as a colonic polyp, potentially affords endoscopists the ability to decide which lesions require removal and which can be safely left behind or discarded without histological assessment. Furthermore targeted biopsies, such as in the surveillance of chronic colitis, may prove to be more accurate and efficacious than the current protocol of random biopsies. An important caveat in the discussion of developing technologies in early cancer detection is the fundamental importance of a health-care system that promotes screening programs to recruit at-risk individuals. The ideal tool to optimize the use of endoscopy in population screening would be a panel of reliable biomarkers (blood, stool, or urine) that could effectively select a high-risk group, thus reducing the indiscriminate use of an expensive technology. The following review summarizes the current endoscopic imaging techniques available, and in development, for the early identification of gastrointestinal neoplasia.
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Affiliation(s)
- P Urquhart
- St Michael's Hospital, Toronto, ON, Canada
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21
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Abstract
Gastrointestinal endoscopy had major technological improvements and novel technologies in recent years. High-definition endoscopy has permitted an increasingly detailed view of the mucosa during colonoscopy. Filter techniques that enhance analysis of vessel and surface structures. Autofluorescence imaging relies on functional imaging of tissue alterations. Endocytoscopy is an ultrahigh-contact microscopy procedure for cellular analysis of the epithelium. Endomicroscopy is an adaption of laser scanning microscopy for real-time intravital surface and subsurface microscopy during endoscopy. With these technologies, endoscopy has moved from prediction of histology based on morphologic patterns toward visualization of cellular and subcellular details, providing real-time histology.
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Affiliation(s)
- Martin Goetz
- Innere Medizin I, Universitätsklinikum Tübingen, Otfried-Müller-Street 10, Tübingen 72076, Germany.
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22
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Abstract
Endoscopy is an indispensible diagnostic and therapeutic instrument for gastrointestinal diseases. Endocytoscopy and confocal endomicroscopy are two types of ultra high magnification endoscopy techniques. Standard endoscopy allows for 50 × magnification, whereas endocytoscopy can magnify up to 1400 × and confocal endomicroscopy can magnify up to 1000 ×. These methods open the realm of real time microscopic evaluation of the GI tract, including cellular and subcellular structures. Confocal endomicroscopy has the additional advantage of being able to visualize subsurface structures. The use of high magnification endoscopy in conjunction with standard endoscopy allows for a real-time microscopic assessment of areas with macroscopic abnormalities, providing “virtual biopsies” with valuable information about cellular and subcellular changes. This can minimize the number of biopsies taken at the time of endoscopy. The use of this technology may assist in detecting pre-malignant or malignant changes at an earlier state, allowing for earlier intervention and treatment. High magnification endoscopy has shown promising results in clinical trials for Barrett’s esophagus, esophageal adenocarcinoma, esophageal squamous cell cancer, gastric cancer, celiac disease, colorectal cancer, and inflammatory bowel disease. As the use of high magnification endoscopy techniques increases, the clinical applications will increase as well. Of the two systems, only confocal endomicroscopy is currently commercially available. Like all new technologies there will be an initial learning curve before operators become proficient in obtaining high quality images and discerning abnormal from normal pathology. Validated criteria for the diagnosis of the various gastrointestinal diseases will need to be developed for each method. In this review, the basic principles of both modalities are discussed, along with their clinical applicability and limitations.
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Affiliation(s)
- Aman V Arya
- Aman V Arya, Brian M Yan, Division of Gastroenterology, Department of Medicine, Western University, London, ON N6G 5W9 Ontario, Canada
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23
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Abstract
AIM Aberrant crypt foci (ACFs) are clusters of colonic crypts that can be identified after staining and that have a different behaviour than the surrounding crypts. They have been hypothesized to be the potential precursors of colonic neoplastic lesions. Since they are detectable in vivo with endoscopic stains, they have been proposed as early biomarkers for colonic carcinogenesis. Our aim was to examine the literature regarding the role of ACFs in the pathogenesis of colorectal cancer (CRC). METHOD An intensive PubMed search was performed with the following terms: aberrant crypt foci, colorectal cancer, biomarker, carcinogenesis. RESULTS Aberrant crypt foci have a variable prevalence and little is known about their natural history. They can be classified as hyperplastic or dysplastic. There is evidence that supports their role as preneoplastic lesions and features detectable by chromoendoscopy have been related to CRC risk. Moreover, ACFs have been shown to harbour genetic and epigenetic alterations common in adenomas and CRC. However, contradictory results have been obtained and difficulties in endoscopic detection and characterization have been described in large-scale studies. CONCLUSION Despite the inconsistencies in ACF detection and characterization, several genetic and epigenetic changes common in both ACFs and CRC have been verified throughout the studies. This evidence is increasingly strong and it grows along with progress in the knowledge of carcinogenesis molecular pathways. Clinical application of ACFs as an intermediate endpoint for colorectal carcinogenesis is under development and a deeper knowledge of cancer mechanisms is needed before it can be applied or discarded.
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Affiliation(s)
- M Lopez-Ceron
- Department of Gastroenterology, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Barcelona, Spain
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24
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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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Neumann H, Fuchs FS, Vieth M, Atreya R, Siebler J, Kiesslich R, Neurath MF. Review article: in vivo imaging by endocytoscopy. Aliment Pharmacol Ther 2011; 33:1183-93. [PMID: 21457290 DOI: 10.1111/j.1365-2036.2011.04647.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Endocytoscopy (EC) enables in vivo microscopic imaging at 1400-fold magnification, thereby allowing the analysis of mucosal structures at the cellular level. In contrast to fluorescence imaging with confocal laser endomicroscopy which allows analysis of mucosal structures up to 250 μm in depth, EC is based on the principle of contact light microscopy and only allows visualisation of the very superficial mucosal layer. AIM To systematically review the feasibility and diagnostic yield of EC for in vivo diagnosis of diseases. METHODS A systematic search of the literature on diagnostic interventions in the gastrointestinal tract using EC was performed by searches in MEDLINE, Current Contents, PubMed, cross-references and references from relevant articles using the search terms 'endocytoscopy', 'endocytoscope', 'magnification endoscopy', 'endocytoscopic imaging', 'virtual histology' and 'optical biopsy'. Only full manuscripts and case reports published in English were included. RESULTS Overall twenty-nine relevant reports were identified. EC was feasible to detect oesophageal squamous cell cancer with sensitivity, specificity and accuracy of 95%, 84% and 82%, respectively. Moreover, EC reached excellent sensitivity and specificity for in vivo diagnosis of colon polyps (91% and 100%, respectively). Other diagnostic applications of EC included diagnosis of Barrett's oesophagus, Helicobacter pylori, coeliac disease and small cell lung cancer. No serious complications of EC have yet been reported. CONCLUSIONS Endocytoscopy is a safe and effective new endoscopic imaging technique to obtain in vivo histology and guided biopsies with high diagnostic accuracy. Therefore, endocytoscopy has the potential to facilitate both diagnosis and patient management.
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Affiliation(s)
- H Neumann
- Department of Medicine I, University of Erlangen-Nuremberg, Ulmenweg 18, Erlangen, Germany.
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26
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Shibuya K, Fujiwara T, Yasufuku K, Alaa RM M, Chiyo M, Nakajima T, Hoshino H, Hiroshima K, Nakatani Y, Yoshino I. In vivo microscopic imaging of the bronchial mucosa using an endo-cytoscopy system. Lung Cancer 2011; 72:184-90. [DOI: 10.1016/j.lungcan.2010.08.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2010] [Revised: 08/01/2010] [Accepted: 08/08/2010] [Indexed: 01/13/2023]
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27
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Takayama T, Nagashima H, Maeda M, Nojiri S, Hirayama M, Nakano Y, Takahashi Y, Sato Y, Sekikawa H, Mori M, Sonoda T, Kimura T, Kato J, Niitsu Y. Randomized double-blind trial of sulindac and etodolac to eradicate aberrant crypt foci and to prevent sporadic colorectal polyps. Clin Cancer Res 2011; 17:3803-11. [PMID: 21385928 DOI: 10.1158/1078-0432.ccr-10-2395] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE On the basis of the results of our preliminary trial suggesting that aberrant crypt foci (ACF) could be eradicated by short-term administration of sulindac, in the present study, we explored the feasibility of using ACF as surrogate markers for chemoprevention of colorectal cancer. EXPERIMENTAL DESIGN Randomly assigned to sulindac (300 mg daily), etodolac (400 mg daily), and placebo groups were 189 subjects without polyps or who had undergone polypectomy. Drugs were administered for 2 months. ACF in the rectal region were counted by magnifying endoscopy. Occurrence of polyps was evaluated at 12 months. A planned interim analysis was conducted. RESULTS ACF number at 2 months was significantly suppressed in the sulindac group (P = 0.0075), but not in the etodolac group (P = 0.73). In the sulindac group, the numbers of adenomas plus hyperplastic polyps (total polyps) and adenomas at 12 months were significantly (P = 0.02) and marginally (P = 0.064) lower, respectively, in comparison with the placebo group; no such difference was observed in the etodolac group. In analysis of only polypectomized subjects, the numbers of total polyps and adenomas in the sulindac group were even more markedly lower, with P values of 0.014 and 0.034, respectively. A similar tendency was confirmed by analyses of the incidence of polyps at 12 months. Suppression rates of total polyps and adenomas in ACF responders to sulindac were significantly greater than in nonresponders. In all groups, compliance was more than 90% and no intolerable adverse effects were observed. CONCLUSIONS ACF may be useful as surrogate lesions for chemoprevention of colorectal cancer.
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Affiliation(s)
- Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan
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Neumann H, Vieth M, Neurath MF, Fuchs FS. In Vivo Diagnosis of Small-Cell Lung Cancer by Endocytoscopy. J Clin Oncol 2011; 29:e131-2. [DOI: 10.1200/jco.2010.31.8097] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
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29
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Newton RC, Kemp SV, Shah PL, Elson D, Darzi A, Shibuya K, Mulgrew S, Yang GZ. Progress Toward Optical Biopsy: Bringing the Microscope to the Patient. Lung 2011; 189:111-9. [DOI: 10.1007/s00408-011-9282-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2010] [Accepted: 01/28/2011] [Indexed: 11/29/2022]
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30
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Neumann H, Neurath MF, Mudter J. New endoscopic approaches in IBD. World J Gastroenterol 2011; 17:63-8. [PMID: 21218085 PMCID: PMC3016681 DOI: 10.3748/wjg.v17.i1.63] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2010] [Revised: 12/01/2010] [Accepted: 12/08/2010] [Indexed: 02/06/2023] Open
Abstract
Recent advances in endoscopic imaging techniques have revolutionized the diagnostic approach of patients with inflammatory bowel disease (IBD). New, emerging endoscopic imaging techniques visualized a plethora of new mucosal details even at the cellular and subcellular level. This review offers an overview about new endoscopic techniques, including chromoendoscopy, magnification endoscopy, spectroscopy, confocal laser endomicroscopy and endocytoscopy in the face of IBD.
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31
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Singh R, Mei SLCY, Tam W, Raju D, Ruszkiewicz A. Real-time histology with the endocytoscope. World J Gastroenterol 2010; 16:5016-5019. [PMID: 20976836 PMCID: PMC2965276 DOI: 10.3748/wjg.v16.i40.5016] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2010] [Revised: 04/27/2010] [Accepted: 05/04/2010] [Indexed: 02/06/2023] Open
Abstract
Endoscopic Imaging has progressed tremendously over the last few decades. Novel imaging technologies such as high-resolution and high-magnification white light endoscopy, narrow band imaging, optimal band imaging, autoflourescence imaging and optical coherence tomography not only aid the endoscopist in detecting malignant or pre-malignant lesions but also assist in predicting histology. Recently, the introduction of Endocytoscopy (EC) and Confocal Endomicroscopy has taken us into a new realm of diagnostic endoscopy. With the ability to magnify up to 1000 ×, cellular structures can be visualized in real-time. This advance in technology could potentially lead to a paradigm shift negating the need to obtain biopsies. EC is, however, still in the early stages of development and further research needs to be carried out before it can be accepted as standard practice. This review will focus on the diagnostic utility of the Endocytoscope.
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Endocytoscopic classification of preneoplastic lesions in the colorectum. Int J Colorectal Dis 2010; 25:1111-6. [PMID: 20532533 DOI: 10.1007/s00384-010-0969-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/21/2010] [Indexed: 02/06/2023]
Abstract
PURPOSE The aim of this study is to assess the capability of endocytoscopy (ECS) in differentiating neoplastic from nonneoplastic lesions in the colorectum and to validate an ECS classification. METHODS Patients with colorectal polypoid and nonpolypoid lesions < or =10 mm were prospectively included. ECS classification subgrouped nonneoplastic (EC 0) and neoplastic (EC 1-3) lesions. Lesions were observed at super-magnified view (450x) before endoscopic resection. Blinded pathological assessment was obtained. RESULTS Fifty-two lesions were examined in 49 patients (17 polypoid and 35 nonpolypoid). Final pathological diagnosis was normal mucosa or hyperplastic polyp in ten cases, low-grade adenoma in 29, high-grade adenoma in 11, and submucosal invasive cancer in two cases. Positive predictive values of each EC group were 100%, 93.1%, 90.1%, and 100%, respectively. ECS diagnosis correlated completely with pathology in the differentiation between neoplastic and nonneoplastic lesions. CONCLUSIONS ECS enabled observation of colorectal lesion at a subcellular level in vivo. The classification of ECS images had a good correlation with the final pathological diagnosis. ECS was useful to differentiate between neoplastic and nonneoplastic lesions.
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Hosoe N, Kobayashi T, Kanai T, Bessho R, Takayama T, Inoue N, Imaeda H, Iwao Y, Kobayashi S, Mukai M, Ogata H, Hibi T. In vivo visualization of trophozoites in patients with amoebic colitis by using a newly developed endocytoscope. Gastrointest Endosc 2010; 72:643-646. [PMID: 20579647 DOI: 10.1016/j.gie.2010.04.031] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2010] [Accepted: 04/19/2010] [Indexed: 12/15/2022]
Abstract
BACKGROUND The endocytoscopy system (ECS) is a new method to provide real-time super-magnifying microscopic imaging in vivo. Routine diagnosis of amebic colitis requires multiple tests that are both time consuming and costly. OBJECTIVE To determine the feasibility of ECS to directly detect the amebic parasites in vivo. DESIGN Prospective, single-center, pilot study. SETTING Tertiary-care university hospital. PATIENTS This study involved 5 patients who were suspected to have amebic colitis by conventional colonoscopy in our institute. INTERVENTIONS A super-magnifying ECS with 450 x magnification. MAIN OUTCOME MEASUREMENTS We compared ECS findings with those of conventional methods-serum antibody tests and histology of colon biopsy specimens. RESULTS We successfully visualized the amebic trophozoites in all 5 cases. In contrast, 3 specimens had positive results on serology, and 3 had positive histology results on hematoxylin and eosin staining. LIMITATIONS Pilot study with a limited number of patients. Findings were compared only with serology and histology findings. CONCLUSIONS ECS would be a useful tool for the prompt diagnosis of amebic colitis via the real-time in vivo visualization of amebic trophozoites.
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Affiliation(s)
- Naoki Hosoe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Shinjuku, Tokyo, Japan
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Kwon RS, Wong Kee Song LM, Adler DG, Conway JD, Diehl DL, Farraye FA, Kantsevoy SV, Kaul V, Kethu SR, Mamula P, Pedrosa MC, Rodriguez SA, Tierney WM. Endocytoscopy. Gastrointest Endosc 2009; 70:610-3. [PMID: 19788978 DOI: 10.1016/j.gie.2009.06.030] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2009] [Accepted: 06/25/2009] [Indexed: 02/08/2023]
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