Confocal laser endomicroscopy (CLE) is a new endoscopic imaging
technology that allows real-time, high-resolution observation of tomographic
images of mucosal cells and subcellular
levels in vivo, detecting microscopic
structural changes in mucosal morphology, and its in vivo immediate pathological diagnostic
capability can avoid delays in mucosal pathological diagnosis and reduce the pain caused by repeated biopsies. CLE is known as “optical biopsy” and
compared with other endoscopic techniques,it has
obvious advantages.CLE
systems include probe-based confocal laser endomicroscopy (pCLE) and
endoscope-based confocal laser endomicroscopy (eCLE).Since 2006, CLE has been widely used for the
evaluation of various lesions in the digestive system, includingesophageal, gastric, and colonic neoplasia,
pancreatic cysts and solid lesions, and inflammatory bowel disease. The advent
of CLE has made in vivo microscopic
imagingpossible, which has changedthe endoscopic screening and diagnosis of multiple
gastrointestinal (GI) lesions.However,
the value of its use in GI diseases is still controversial. In this review, we
focus on the application of CLE in the field of esophageal diseases.
References
[1]
Fitzgerald, R.C., di Pietro, M., Ragunath, K., et al. (2014) British Society of Gastroenterology Guidelines on the Diagnosis and Management of Barrett’s Oesophagus. Gut, 63, 7-42. https://doi.org/10.1136/gutjnl-2013-305372
[2]
Sampliner, R.E. (2002) Updated Guidelines for the Diagnosis, Surveillance, and Therapy of Barrett’s Esophagus. The American Journal of Gastroenterology, 97, 1888-1895.
[3]
Kim, T., Grobmyer, S.R., Smith, R., et al. (2011) Esophageal Cancer—The Five Year Survivors. Journal of Surgical Oncology, 103, 179-183.
https://doi.org/10.1002/jso.21784
[4]
van Munster, S., Nieuwenhuis, E., Weusten, B., et al. (2022) Long-Term Outcomes after Endoscopic Treatment for Barrett’s Neoplasia with Radiofrequency Ablation ± Endoscopic Resection: Results from the National Dutch Database in a 10-Year Period. Gut, 71, 265-276. https://doi.org/10.1136/gutjnl-2020-322615
[5]
Thrift, A.P. (2018) Barrett’s Esophagus and Esophageal Adenocarcinoma: How Common Are They Really? Digestive Diseases and Sciences, 63, 1988-1996.
https://doi.org/10.1007/s10620-018-5068-6
[6]
Wilson, K.T., Fu, S., Ramanujam, K.S. and Meltzer, S.J. (1998) Increased Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Barrett’s Esophagus and Associated Adenocarcinomas. Cancer Research, 58, 2929-2934.
[7]
Shaheen, N.J., Sharma, P., Overholt, B.F., et al. (2009) Radiofrequency Ablation in Barrett’s Esophagus with Dysplasia. The New England Journal of Medicine, 360, 2277-2288. https://doi.org/10.1056/NEJMoa0808145
[8]
Phoa, K.N., van Vilsteren, F.G., Weusten, B.L., et al. (2014) Radiofrequency Ablation vs Endoscopic Surveillance for Patients with Barrett Esophagus and Low-Grade Dysplasia: A Randomized Clinical Trial. JAMA, 311, 1209-1217.
https://doi.org/10.1001/jama.2014.2511
[9]
Shaheen, N.J., Falk, G.W., Iyer, P.G. and Gerson, L.B. (2016) ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. The American Journal of Gastroenterology, 111, 30-50. https://doi.org/10.1038/ajg.2015.322
[10]
Wani, S., Puli, S.R., Shaheen, N.J., Westhoff, B., Slehria, S., Bansal, A., Rastogi, A., Sayana, H. and Sharma, P. (2009) Esophageal Adenocarcinoma in Barrett’s Esophagus after Endoscopic Ablative Therapy: A Meta-Analysis and Systematic Review. American Journal of Gastroenterology, 104, 502-513.
https://doi.org/10.1038/ajg.2008.31
[11]
Wani, S., Falk, G.W., Post, J., et al. (2011) Risk Factors for Progression of Low-Grade Dysplasia in Patients with Barrett’s Esophagus. Gastroenterology, 141, 1179-1186. https://doi.org/10.1053/j.gastro.2011.06.055
[12]
Abrams, J.A., Kapel, R.C., Lindberg, G.M., Saboorian, M.H., Genta, R.M., Neugut, A.I. and Lightdale, C.J. (2009) Adherence to Biopsy Guidelines for Barrett’s Esophagus Surveillance in the Community Setting in the United States. Clinical Gastroenterology and Hepatology, 7, 736-742. https://doi.org/10.1016/j.cgh.2008.12.027
[13]
Peters, F.P., Curvers, W.L., Rosmolen, W.D., De Vries, C.E., Ten Kate, F.J.W., Krishnadath, K.K., Fockens, P. and Bergman, J.J.G.H.M. (2008) Surveillance History of Endoscopically Treated Patients with Early Barrett’s Neoplasia: Nonadherence to the Seattle Biopsy Protocol Leads to Sampling Error. Diseases of the Esophagus, 21, 475-479. https://doi.org/10.1111/j.1442-2050.2008.00813.x
[14]
Vithayathil, M., Modolell, I., Ortiz-Fernandez-Sordo, J., et al. (2022) Image-Enhanced Endoscopy and Molecular Biomarkers Vs Seattle Protocol to Diagnose Dysplasia in Barrett’s Esophagus. Clinical Gastroenterology and Hepatology, 20, 2514-2523. https://doi.org/10.1016/j.cgh.2022.01.060
[15]
Gerson, L.B. and Triadafilopoulos, G. (2002) Screening for Esophageal Adenocarcinoma: An Evidence-Based Approach. The American Journal of Medicine, 113, 499-505. https://doi.org/10.1016/S0002-9343(02)01234-2
[16]
Curvers, W., Baak, L., Kiesslich, R., et al. (2008) Chromoendoscopy and Narrow-Band Imaging Compared with High-Resolution Magnification Endoscopy in Barrett’s Esophagus. Gastroenterology, 134, 670-679.
https://doi.org/10.1053/j.gastro.2008.01.003
[17]
Curvers, W.L., van Vilsteren, F.G., Baak, L.C., et al. (2011) Endoscopic Trimodal Imaging versus Standard Video Endoscopy for Detection of Early Barrett’s Neoplasia: A Multicenter, Randomized, Crossover Study in General Practice. Gastrointestinal Endoscopy, 73, 195-203. https://doi.org/10.1016/j.gie.2010.10.014
[18]
Evans, J.A., Poneros, J.M., Bouma, B.E., et al. (2006) Optical Coherence Tomography to Identify Intramucosal Carcinoma and High-Grade Dysplasia in Barrett’s Esophagus. Clinical Gastroenterology and Hepatology, 4, 38-43.
https://doi.org/10.1016/S1542-3565(05)00746-9
[19]
Kiesslich, R., Gossner, L., Goetz, M., et al. (2006) In Vivo Histology of Barrett’s Esophagus and Associated Neoplasia by Confocal Laser Endomicroscopy. Clinical Gastroenterology and Hepatology, 4, 979-987.
https://doi.org/10.1016/j.cgh.2006.05.010
[20]
Dunbar, K.B., Okolo, P., Montgomery, E. and Canto, M.I. (2009) Confocal Laser Endomicroscopy in Barrett’s Esophagus and Endoscopically Inapparent Barrett’s Neoplasia: A Prospective, Randomized, Double-Blind, Controlled, Crossover Trial. Gastrointestinal Endoscopy, 70, 645-654. https://doi.org/10.1016/j.gie.2009.02.009
[21]
Wallace, M.B., Sharma, P., Lightdale, C., et al. (2010) Preliminary Accuracy and Interobserver Agreement for the Detection of Intraepithelial Neoplasia in Barrett’s Esophagus with Probe-Based Confocal Laser Endomicroscopy. Gastrointestinal Endoscopy, 72, 19-24. https://doi.org/10.1016/j.gie.2010.01.053
[22]
di Pietro, M., Bird-Lieberman, E.L., Liu, X., et al. (2015) Autofluorescence-Directed Confocal Endomicroscopy in Combination with a Three-Biomarker Panel Can Inform Management Decisions in Barrett’s Esophagus. Gastrointestinal Endoscopy, 110, 1549-1558.
[23]
Gao, L.J. (2010) Diagnostic Value of Confocal Laser Endomicroscopy in Early Esophageal Squamous Cell Carcinoma and Precancerous Lesions. Master’s Thesis, Shandong University, Jinan.
[24]
Sharma, P., Meining, A.R., Coron, E., et al. (2011) Real-Time Increased Detection of Neoplastic Tissue in Barrett’s Esophagus with Probe-Based Confocal Laser Endomicroscopy: Final Results of an International Multicenter, Prospective, Randomized, Controlled Trial. Gastrointestinal Endoscopy, 74, 465-472.
https://doi.org/10.1016/j.gie.2011.04.004
[25]
Long, P.Q. (2012) A Study on the Diagnosis Value of I-Scan Endoscopy and Confocal Laser Endomicroscopy in Barrett’s Esophagus and Argon Plasma Coagulation Treatment for Barrett’s Esophagus. Master’s Thesis, South Medical University, Guangzhou.
[26]
Xiong, Y.Q., Ma, S.J., Hu, H.Y., Ge, J., Zhou, L.-Z., Huo, S.T., Qiu, M. and Chen, Q. (2018) Comparison of Narrow-Band Imaging and Confocal Laser Endomicroscopy for the Detection of Neoplasia in Barrett’s Esophagus: A Meta-Analysis. Clinics and Research in Hepatology and Gastroenterology, 42, 31-39.
https://doi.org/10.1016/j.clinre.2017.05.005
[27]
Leggett, C.L., Gorospe, E.C., Chan, D.K., et al. (2016) Comparative Diagnostic Performance of Volumetric Laser Endomicroscopy and Confocal Laser Endomicroscopy in the Detection of Dysplasia Associated with Barrett’s Esophagus. Gastrointestinal Endoscopy, 83, 880-888. https://doi.org/10.1016/j.gie.2015.08.050
[28]
Caillol, F., Godat, S., Poizat, F., et al. (2017) Probe Confocal Laser Endomicroscopy in the Therapeutic Endoscopic Management of Barrett’s Dysplasia. Annals of Gastroenterology, 30, 295-301. https://doi.org/10.20524/aog.2017.0138
[29]
Richardson, C., Colavita, P., Dunst, C., et al. (2019) Real-Time Diagnosis of Barrett’s Esophagus: A Prospective, Multicenter Study Comparing Confocal Laser Endomicroscopy with Conventional Histology for the Identification of Intestinal Metaplasia in New Users. Surgical Endoscopy, 33, 1585-1591.
https://doi.org/10.1007/s00464-018-6420-9
[30]
Tofteland, N., Singh, M., Gaddam, S., et al. (2014) Evaluation of the Updated Confocal Laser Endomicroscopy Criteria for Barrett’s Esophagus among Gastrointestinal Pathologists. Diseases of the Esophagus, 27, 623-629.
https://doi.org/10.1111/dote.12121
[31]
Canto, M.I., Anandasabapathy, S., Brugge, W., et al. (2014) In Vivo Endomicroscopy Improves Detection of Barrett’s Esophagus-Related Neoplasia: A Multicenter International Randomized Controlled Trial (with Video). Gastrointestinal Endoscopy, 79, 211-221. https://doi.org/10.1016/j.gie.2013.09.020
[32]
O’Neil, R.G., Wu, L. and Mullani, N. (2005) Uptake of a Fluorescent Deoxyglucose Analog (2-NBDG) in Tumor Cells. Molecular Imaging and Biology, 7, 388-392.
https://doi.org/10.1007/s11307-005-0011-6
[33]
Thekkek, N., Maru, D.M., Polydorides, A.D., Bhutani, M.S., Anandasabapathy, S. and Richards-Kortum, R. (2011) Pre-Clinical Evaluation of Fluorescent Deoxyglucose as a Topical Contrast Agent for the Detection of Barrett’s-Associated Neoplasia during Confocal Imaging. Technology in Cancer Research & Treatment, 10, 431-441.
https://doi.org/10.7785/tcrt.2012.500220
[34]
Langsner, R.J., Middleton, L.P., Sun, J., et al. (2011) Wide-Field Imaging of Fluorescent Deoxy-Glucose in ex Vivo Malignant and Normal Breast Tissue. Biomedical Optics Express, 2, 1514-1523. https://doi.org/10.1364/BOE.2.001514
[35]
Gorospe, E.C., Leggett, C.L., Sun, G., et al. (2012) Diagnostic Performance of Two Confocal Endomicroscopy Systems in Detecting Barrett’s Dysplasia: A Pilot Study Using a Novel Bioprobe in ex Vivo Tissue. Gastrointestinal Endoscopy, 76, 933-938.
https://doi.org/10.1016/j.gie.2012.07.005
[36]
Boerwinkel, D.F., Shariff, M.K., di Pietro, M., et al. (2014) Fluorescence Imaging for the Detection of Early Neoplasia in Barrett’s Esophagus: Old Looks or New Vision? European Journal of Gastroenterology & Hepatology, 26, 691-698.
[37]
Gaddam, S., Mathur, S.C., Singh, M., et al. (2011) Novel Probe-Based Confocal Laser Endomicroscopy Criteria and Interobserver Agreement for the Detection of Dysplasia in Barrett’s Esophagus. The American Journal of Gastroenterology, 106, 1961-1969.
[38]
di Pietro, M., Bertani, H., O'Donovan, M., et al. (2019) Development and Validation of Confocal Endomicroscopy Diagnostic Criteria for Low-Grade Dysplasia in Barrett's Esophagus. Clinical and Translational Gastroenterology, 10, e00014.
[39]
Pohl, H., Rösch, T., Vieth, M., Koch, M., Becker, V., Anders, M., Khalifa, A.C. and Meining, A. (2008) Miniprobe Confocal Laser Microscopy for the Detection of Invisible Neoplasia in Patients with Barrett’s Oesophagus. Gut, 57, 1648-1653.
https://doi.org/10.1136/gut.2008.157461
[40]
Bajbouj, M., Vieth, M., Rösch, T., Miehlke, S., Becker, V., Anders, M., Pohl, H., Madisch, A., Schuster, T., Schmid, R.M. and Meining, A. (2010) Probe-Based Confocal Laser Endomicroscopy Compared with Standard Four-Quadrant Biopsy for Evaluation of Neoplasia in Barrett’s Esophagus. Endoscopy, 42, 435-440.
https://doi.org/10.1055/s-0029-1244194
[41]
Shah, T., Lippman, R., Kohli, D., Mutha, P., Solomon, S. and Zfass, A. (2018) Accuracy of Probe-Based Confocal Laser Endomicroscopy (pCLE) Compared to Random Biopsies during Endoscopic Surveillance of Barrett’s Esophagus. Endoscopy International Open, 6, E414-E420. https://doi.org/10.1055/s-0043-124868
[42]
Jayasekera, C., Taylor, A.C., Desmond, P.V., Macrae, F. and Williams, R. (2012) Added Value of Narrow Band Imaging and Confocal Laser Endomicroscopy in Detecting Barrett’s Esophagus Neoplasia. Endoscopy, 44, 1089-1095.
https://doi.org/10.1055/s-0032-1325734
[43]
Wallace, M.B., Crook, J.E., Saunders, M., et al. (2012) Multicenter, Randomized, Controlled Trial of Confocal Laser Endomicroscopy Assessment of Residual Metaplasia after Mucosal Ablation or Resection of GI Neoplasia in Barrett’s Esophagus. Gastrointestinal Endoscopy, 76, 539-547. https://doi.org/10.1016/j.gie.2012.05.004
[44]
Bertani, H., Frazzoni, M., Dabizzi, E., Pigò, F., Losi, L., Manno, M., Manta, R., Bassotti, G. and Conigliaro, R. (2013) Improved Detection of Incident Dysplasia by Probe-Based Confocal Laser Endomicroscopy in a Barrett’s Esophagus Surveillance Program. Digestive Diseases and Sciences, 58, 188-193.
https://doi.org/10.1007/s10620-012-2332-z
[45]
Vranić, L., Nadarević, T. and Štimac, D. (2022) Probe-Based Confocal Laser Endomicroscopy and Barrett’s Esophagus: Just a Scientific Toy or Significant Improvement in Diagnosis? Digestive Diseases, 40, 97-105.
https://doi.org/10.1159/000516257
[46]
Leung, K.K., Maru, D., Abraham, S., Hofstetter, W.L., Mehran, R. and Anandasabapathy, S. (2009) Optical EMR: Confocal Endomicroscopy-Targeted EMR of Focal High-Grade Dysplasia in Barrett’s Esophagus. Gastrointestinal Endoscopy, 69, 170-172. https://doi.org/10.1016/j.gie.2008.03.1068
[47]
Konda, V.J., Chennat, J.S., Hart, J. and Waxman, I. (2010) Confocal Laser Endomicroscopy: Potential in the Management of Barrett’s Esophagus. Diseases of the Esophagus, 23, E21-E31. https://doi.org/10.1111/j.1442-2050.2010.01088.x
[48]
Johnson, E.A., De Lee, R., Agni, R., Pfau, P., Reichelderfer, M. and Gopal, D.V. (2012) Probe-Based Confocal Laser Endomicroscopy to Guide Real-Time Endoscopic Therapy in Barrett’s Esophagus with Dysplasia. Case Reports in Gastroenterology, 6, 285-292. https://doi.org/10.1159/000338835
[49]
Dolak, W., Mesteri, I., Asari, R., et al. (2015) A Pilot Study of the Endomicroscopic Assessment of Tumor Extension in Barrett’s Esophagus-Associated Neoplasia before Endoscopic Resection. Endoscopy International Open, 3, E19-E28.
https://doi.org/10.1055/s-0034-1377935
[50]
Krajciova, J., Kollar, M., Maluskova, J., et al. (2020) Confocal Laser Endomicroscopy vs Biopsies in the Assessment of Persistent or Recurrent Intestinal Metaplasia/Neoplasia after Endoscopic Treatment of Barrett’s Esophagus related Neoplasia. r Journal of Gastrointestinal and Liver Diseases, 29, 305-312.
https://doi.org/10.15403/jgld-2467
[51]
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA, 68, 394-424.
https://doi.org/10.3322/caac.21492
[52]
Weidenbaum, C. and Gibson, M.K. (2022) Approach to Localized Squamous Cell Cancer of the Esophagus. Current Treatment Options in Oncology, 23, 1370-1387.
https://doi.org/10.1007/s11864-022-01003-w
[53]
Pech, O., Rabenstein, T., Manner, H., Petrone M.C., Pohl, J., Vieth, M., Stolte, M. and Ell, C. (2008) Confocal Laser Endomicroscopy for in Vivo Diagnosis of Early Squamous Cell Carcinoma in the Esophagus. Clinical Gastroenterology and Hepatology, 6, 89-94. https://doi.org/10.1016/j.cgh.2007.10.013
Guo, J., Li, C.Q., Li, M., et al. (2015) Diagnostic Value of Probe-Based Confocal Laser Endomicroscopy and High-Definition Virtual Chromoendoscopy in Early Esophageal Squamous Neoplasia. Gastrointestinal Endoscopy, 81, 1346-1354.
https://doi.org/10.1016/j.gie.2014.10.041
[56]
Hongo, M., Kinoshita, Y., Miwa, H. and Ashida, K. (2008) The Demographic Characteristics and Health-Related Quality of life in a Large Cohort of Reflux Esophagitis Patients in Japan with Reference to the Effect of Lansoprazole: The REQUEST Study. Journal of Gastroenterology, 43, 920-927.
https://doi.org/10.1007/s00535-008-2257-7
[57]
Klauser, A.G., Schindlbeck, N.E. and Müller-Lissner, S.A. (1990) Symptoms in Gastro-Oesophageal Reflux Disease. The Lancet, 335, 205-208.
https://doi.org/10.1016/0140-6736(90)90287-F
[58]
Cu, C.L. (2012) The Clinical Feature in and the Diagnostic Value of In-Vivo Confocal Laser Endomicroscopy on Patients with Non Erosive Reflux Disease. Ph.D. Thesis, Shandong University, Jinan.
[59]
Mutha, P.R., Fasullo, M., Chu, S., et al. (2022) Correlation of Probe-Based Confocal Laser Endomicroscopy (pCLE) and Mucosal Integrity Testing (MIT) with Epithelial Barrier Function and Presence of Gastroesophageal Reflux Disease (GERD). Digestive Diseases and Sciences, 67, 1773-1782.
https://doi.org/10.1007/s10620-021-06980-w
[60]
Pittayanon, R., Aumkaew, S., Rerknimitr, R., Wisedopas, N. and Kullavanijaya, P. (2016) Flexible Spectral Imaging Color Enhancement and Probe-Based Confocal Laser Endomicroscopy in Minimal Change Esophageal Reflux Disease. The Korean Journal of Gastroenterology, 68, 29-35. https://doi.org/10.4166/kjg.2016.68.1.29
[61]
Jeong, E., Yoo, I.K., Yeniova, A., Yon, D.K. and Cho, J.Y. (2021) Confocal Laser Endomicroscopic Findings of Refractory Erosive Reflux Disease versus Non-Erosive Reflux Disease with Anti-Reflux Mucosectomy: An in Vivo and ex Vivo Study. Clinical Endoscopy, 54, 55-63. https://doi.org/10.5946/ce.2020.040
[62]
Yun, S.H., Tearney, G.J., Vakoc, B.J., et al. (2006) Comprehensive Volumetric Optical Microscopy in Vivo. Nature Medicine, 12, 1429-1433.
https://doi.org/10.1038/nm1450
[63]
Verna, C., Feyles, E., Lorenzi, L., et al. (2014) I-SCAN Targeted versus Random Biopsies in Barrett’s Oesophagus. Digestive and Liver Disease, 46, 131-134.
https://doi.org/10.1016/j.dld.2013.10.005
[64]
Rogart, J.N., Nagata, J., Loeser, C.S., et al. (2008) Multiphoton Imaging Can Be Used for Microscopic Examination of Intact Human Gastrointestinal Mucosa ex Vivo. Clinical Gastroenterology and Hepatology, 6, 95-101.
https://doi.org/10.1016/j.cgh.2007.10.008
[65]
Kang, D., Suter, M.J., Boudoux, C., et al. (2010) Comprehensive Imaging of Gastroesophageal Biopsy Samples by Spectrally Encoded Confocal Microscopy. Gastrointestinal Endoscopy, 71, 35-43. https://doi.org/10.1016/j.gie.2009.08.026
