Abstract
Background
The aim of this pilot study is to investigate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) in the evaluation of depth of invasion in colorectal lesions.
Methods
Patients with colorectal lesions eligible for either endoscopic treatment or surgery were enrolled in the study. Tumor’s depth of invasion was classified as mucosal or slight submucosal (M-SM1) and deep submucosal invasion or deeper (SM2 or deeper). White light endoscopy (WLE), magnifying narrow band imaging (M-NBI), and magnifying chromoendoscopy (M-CE) were used to assess colorectal lesions, and pCLE was used to identify tumor’s features related to SM2 or deeper. The diagnostic classification of depth of invasion was obtained by correlating pCLE findings with histology results (on-site diagnosis). All colorectal lesions were stratified by a second endoscopist who was blinded to any clinical and histological information with the use of WLE, M-NBI, M-CE, and pCLE (off-line review).
Results
A total of 22 colorectal lesions were analyzed: seven were adenoma, ten intramucosal cancer, and five SM2 or deeper cancer. With respect to pCLE findings, loss of crypt structure was seen in all SM2 or deeper cancers and only in one M-SM1 lesion. Sensitivity, specificity, and accuracy of WLE, M-NBI, and M-CE in off-line review were 60/94/86, 60/94/86, and 80/94/91%, respectively. Sensitivity/specificity/accuracy of pCLE in off-line review were 80/94/91%, respectively. The inter-observer agreement of pCLE between on-site diagnosis and off-line review was 0.64 (95%CI 0.27–1.0).
Conclusions
pCLE may represent a useful tool to evaluate the depth of invasion in colorectal lesions.
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References
Saito Y, Uraoka T, Yamaguchi Y, Hotta K, Sakamoto N, Ikematsu H, Fukuzawa M, Kobayashi N, Nasu J, Michida T, Yoshida S, Ikehara H, Otake Y, Nakajima T, Matsuda T, Saito D (2010) A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video). Gastrointest Endosc 72:1217–1225. https://doi.org/10.1016/j.gie.2010.08.004
Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, Repici A, Vieth M, De Ceglie A, Amato A, Berr F, Bhandari P, Bialek A, Conio M, Haringsma J, Langner C, Meisner S, Messmann H, Morino M, Neuhaus H, Piessevaux H, Rugge M, Saunders BP, Robaszkiewicz M, Seewald S, Kashin S, Dumonceau JM, Hassan C, Deprez PH (2015) Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 47:829–854. https://doi.org/10.1055/s-0034-1392882
Oka S, Tanaka S, Saito Y, Iishi H, Kudo SE, Ikematsu H, Igarashi M, Saitoh Y, Inoue Y, Kobayashi K, Hisabe T, Tsuruta O, Sano Y, Yamano H, Shimizu S, Yahagi N, Watanabe T, Nakamura H, Fujii T, Ishikawa H, Sugihara K (2015) Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan. Am J Gastroenterol 110:697–707. https://doi.org/10.1038/ajg.2015.96
Kitajima K, Fujimori T, Fujii S, Takeda J, Ohkura Y, Kawamata H, Kumamoto T, Ishiguro S, Kato Y, Shimoda T, Iwashita A, Ajioka Y, Watanabe H, Watanabe T, Muto T, Nagasako K (2004) Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol 39:534–543. https://doi.org/10.1007/s00535-004-1339-4
Tanaka S, Kashida H, Saito Y, Yahagi N, Yamano H, Saito S, Hisabe T, Yao T, Watanabe M, Yoshida M, Kudo SE, Tsuruta O, Sugihara K, Watanabe T, Saitoh Y, Igarashi M, Toyonaga T, Ajioka Y, Ichinose M, Matsui T, Sugita A, Sugano K, Fujimoto K, Tajiri H (2015) JGES guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection. Dig Endosc Off J Jpn Gastroenterol Endosc Soc 27:417–434. https://doi.org/10.1111/den.12456
Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, Hamaguchi T, Ishida H, Ishiguro M, Ishihara S, Kanemitsu Y, Kawano H, Kinugasa Y, Kokudo N, Murofushi K, Nakajima T, Oka S, Sakai Y, Tsuji A, Uehara K, Ueno H, Yamazaki K, Yoshida M, Yoshino T, Boku N, Fujimori T, Itabashi M, Koinuma N, Morita T, Nishimura G, Sakata Y, Shimada Y, Takahashi K, Tanaka S, Tsuruta O, Yamaguchi T, Yamaguchi N, Tanaka T, Kotake K, Sugihara K (2017) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23:1–34. https://doi.org/10.1007/s10147-017-1101-6
Hayashi N, Tanaka S, Hewett DG, Kaltenbach TR, Sano Y, Ponchon T, Saunders BP, Rex DK, Soetikno RM (2013) Endoscopic prediction of deep submucosal invasive carcinoma: validation of the narrow-band imaging international colorectal endoscopic (NICE) classification. Gastrointest Endosc 78:625–632. https://doi.org/10.1016/j.gie.2013.04.185
Matsuda T, Fujii T, Saito Y, Nakajima T, Uraoka T, Kobayashi N, Ikehara H, Ikematsu H, Fu KI, Emura F, Ono A, Sano Y, Shimoda T, Fujimori T (2008) Efficacy of the invasive/non-invasive pattern by magnifying chromoendoscopy to estimate the depth of invasion of early colorectal neoplasms. Am J Gastroenterol 103:2700–2706. https://doi.org/10.1111/j.1572-0241.2008.02190.x
Ikehara H, Saito Y, Matsuda T, Uraoka T, Murakami Y (2010) Diagnosis of depth of invasion for early colorectal cancer using magnifying colonoscopy. J Gastroenterol Hepatol 25:905–912. https://doi.org/10.1111/j.1440-1746.2010.06275.x
Sano Y, Tanaka S, Kudo SE, Saito S, Matsuda T, Wada Y, Fujii T, Ikematsu H, Uraoka T, Kobayashi N, Nakamura H, Hotta K, Horimatsu T, Sakamoto N, Fu KI, Tsuruta O, Kawano H, Kashida H, Takeuchi Y, Machida H, Kusaka T, Yoshida N, Hirata I, Terai T, Yamano HO, Kaneko K, Nakajima T, Sakamoto T, Yamaguchi Y, Tamai N, Nakano N, Hayashi N, Oka S, Iwatate M, Ishikawa H, Murakami Y, Yoshida S, Saito Y (2016) Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team. Digest Endosc Off J Jpn Gastroenterol Endosc Soc 28:526–533. https://doi.org/10.1111/den.12644
Buchner AM, Shahid MW, Heckman MG, Krishna M, Ghabril M, Hasan M, Crook JE, Gomez V, Raimondo M, Woodward T, Wolfsen HC, Wallace MB (2010) Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology 138:834–842. https://doi.org/10.1053/j.gastro.2009.10.053
De Palma GD, Staibano S, Siciliano S, Persico M, Masone S, Maione F, Siano M, Mascolo M, Esposito D, Salvatori F, Persico G (2010) 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 Off J Italian Soc Gastroenterol Italian Assoc Stud Liver 42:791–797. https://doi.org/10.1016/j.dld.2010.03.009
Fujimoto K, Fujishiro M, Kato M, Higuchi K, Iwakiri R, Sakamoto C, Uchiyama S, Kashiwagi A, Ogawa H, Murakami K, Mine T, Yoshino J, Kinoshita Y, Ichinose M, Matsui T (2014) Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc Off J Jpn Gastroenterol Endosc Soc 26:1–14. https://doi.org/10.1111/den.12183
Wallace M, Lauwers GY, Chen Y, Dekker E, Fockens P, Sharma P, Meining A (2011) Miami classification for probe-based confocal laser endomicroscopy. Endoscopy 43:882–891. https://doi.org/10.1055/s-0030-1256632
Rectum JSfCotCa (2009) Japanese Society for Cancer of the Colon and Rectum. Japanese classification of colorectal carcinoma. 7th edn. Revised Version. Kanehara and Co Ltd, Tokyo
Watanabe T, Itabashi M, Shimada Y, Tanaka S, Ito Y, Ajioka Y, Hamaguchi T, Hyodo I, Igarashi M, Ishida H, Ishihara S, Ishiguro M, Kanemitsu Y, Kokudo N, Muro K, Ochiai A, Oguchi M, Ohkura Y, Saito Y, Sakai Y, Ueno H, Yoshino T, Boku N, Fujimori T, Koinuma N, Morita T, Nishimura G, Sakata Y, Takahashi K, Tsuruta O, Yamaguchi T, Yoshida M, Yamaguchi N, Kotake K, Sugihara K (2015) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2014 for treatment of colorectal cancer. Int J Clin Oncol 20:207–239. https://doi.org/10.1007/s10147-015-0801-z
Hamilton SRBF, Boffetta P et al (2010) Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH et al (eds) WHO classification of tumours of the digestive system, 4th edn. IARC, Lyon, pp 134–146
Dixon MF (2002) Gastrointestinal epithelial neoplasia: Vienna revisited. Gut 51:130–131
Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244
Sano Y, Ikematsu H, Fu KI, Emura F, Katagiri A, Horimatsu T, Kaneko K, Soetikno R, Yoshida S (2009) Meshed capillary vessels by use of narrow-band imaging for differential diagnosis of small colorectal polyps. Gastrointest Endosc 69:278–283. https://doi.org/10.1016/j.gie.2008.04.066
Ikematsu H, Matsuda T, Emura F, Saito Y, Uraoka T, Fu KI, Kaneko K, Ochiai A, Fujimori T, Sano Y (2010) Efficacy of capillary pattern type IIIA/IIIB by magnifying narrow band imaging for estimating depth of invasion of early colorectal neoplasms. BMC Gastroenterol 10:33. https://doi.org/10.1186/1471-230x-10-33
Kudo S, Hirota S, Nakajima T, Hosobe S, Kusaka H, Kobayashi T, Himori M, Yagyuu A (1994) Colorectal tumours and pit pattern. J Clin Pathol 47:880–885
Sakamoto T, Saito Y, Nakajima T, Matsuda T (2011) Comparison of magnifying chromoendoscopy and narrow-band imaging in estimation of early colorectal cancer invasion depth: a pilot study. Dig Endosc Off J Jpn Gastroenterol Endosc Soc 23:118–123. https://doi.org/10.1111/j.1443-1661.2010.01049.x
Sakamoto T, Nakajima T, Matsuda T, Murakami Y, Ishikawa H, Yao K, Saito Y (2018) Comparison of the diagnostic performance between magnifying chromoendoscopy and magnifying narrow-band imaging for superficial colorectal neoplasm: an online survey. Gastrointest Endosc 87:1318–1323. https://doi.org/10.1016/j.gie.2017.12.021
Higashi R, Uraoka T, Kato J, Kuwaki K, Ishikawa S, Saito Y, Matsuda T, Ikematsu H, Sano Y, Suzuki S, Murakami Y, Yamamoto K (2010) Diagnostic accuracy of narrow-band imaging and pit pattern analysis significantly improved for less-experienced endoscopists after an expanded training program. Gastrointest Endosc 72:127–135. https://doi.org/10.1016/j.gie.2010.01.054
Neumann H, Vieth M, Atreya R, Neurath MF, Mudter J (2011) Prospective evaluation of the learning curve of confocal laser endomicroscopy in patients with IBD. Histol Histopathol 26:867–872. https://doi.org/10.14670/hh-26.867
Kiesslich R, Burg J, Vieth M, Gnaendiger J, Enders M, Delaney P, Polglase A, McLaren W, Janell D, Thomas S, Nafe B, Galle PR, Neurath MF (2004) Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 127:706–713
Kudo SE, Wakamura K, Ikehara N, Mori Y, Inoue H, Hamatani S (2011) Diagnosis of colorectal lesions with a novel endocytoscopic classification—a pilot study. Endoscopy 43:869–875. https://doi.org/10.1055/s-0030-1256663
Kim B, Kim YH, Park SJ, Cheon JH, Kim TI, Kim WH, Kim H, Hong SP (2017) Probe-based confocal laser endomicroscopy for evaluating the submucosal invasion of colorectal neoplasms. Surg Endosc 31:594–601. https://doi.org/10.1007/s00464-016-5003-x
Goetz M, Wang TD (2010) Molecular imaging in gastrointestinal endoscopy. Gastroenterology 138:828–833.e821. https://doi.org/10.1053/j.gastro.2010.01.009
Kiesslich R, Duckworth CA, Moussata D, Gloeckner A, Lim LG, Goetz M, Pritchard DM, Galle PR, Neurath MF, Watson AJ (2012) Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut 61:1146–1153. https://doi.org/10.1136/gutjnl-2011-300695
Acknowledgements
We would like to thank Dr. Hiyoyuki Takamaru and Masau Sekiguchi, Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan, and Dr. Flaminia Purchiaroni, Wolfson Unit for Endoscopy, St Mark’s Hospital, London, UK, for her kind support to this paper. Moreover, we would like to thank the Japan Agency for Medical Research and Development (AMED), which supported this study under Grant Number 15ck0106028h0002.
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The study was carried on according to the ethical principles included in the Declaration of Helsinki. As intravenous fluorescein for pCLE has not been approved yet for clinical use in Japan, prior to the start of the study, we obtained the approval from the institutional review board for off-label use of intravenous fluorescein. Written informed consent was obtained from all patients.
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There was no conflict of interest to be disclosed in relation to this study.
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Abe, S., Saito, Y., Oono, Y. et al. Pilot study on probe-based confocal laser endomicroscopy for colorectal neoplasms: an initial experience in Japan. Int J Colorectal Dis 33, 1071–1078 (2018). https://doi.org/10.1007/s00384-018-3059-x
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DOI: https://doi.org/10.1007/s00384-018-3059-x