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Published in: Techniques in Coloproctology 7/2017

01-07-2017 | Original Article

Confocal laser endomicroscopy in ulcerative colitis: beyond endoscopic assessment of disease activity

Authors: F. Maione, M. C. Giglio, G. Luglio, A. Rispo, M. D’Armiento, B. Manzo, G. Cassese, P. Schettino, N. Gennarelli, S. Siciliano, F. P. D’Armiento, G. D. De Palma

Published in: Techniques in Coloproctology | Issue 7/2017

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Abstract

Background

The aim of this study was to investigate the role of confocal laser endomicroscopy (CLE) in the assessment of disease activity in ulcerative colitis (UC).

Methods

Consecutive patients with UC referred to our inflammatory bowel disease unit for colonoscopy were enrolled. Patients without UC were used as controls. UC activity was evaluated by white light endoscopy and classified according to the Mayo Ulcerative Colitis Endoscopic Score of Severity. Endoscopic biopsies were also taken for histological assessment of disease activity and then assessed with CLE. Three parameters were evaluated; crypt architecture (crypt diameter, inter-crypt distance, presence of fused crypts, crypts regularity), microvascular pattern (regular, dilated, irregular and deformed), fluorescein leakage.

Results

Fifty patients with UC and 10 controls were enrolled. At colonoscopy, 11 patients (22%), 19 patients (38%), 12 patients (24%) and 8 patients (16%) presented a Mayo score of 0, 1, 2 and 3, respectively. At CLE, fused crypts were present in all the patients with UC and absent in controls. Crypt diameter and inter-crypt distance showed a parallel increase with the Mayo score. Fluorescein leakage and irregular vessels were more frequently found in case of a high level of endoscopic severity, but were also identified in about 20% of UC patients with normal mucosa. Biopsies also demonstrated the presence of histological activity in 4 patients with endoscopically inactive colitis.

Conclusions

CLE might be a useful tool to determine inflammatory activity in UC. Fused crypts appeared to be a CLE marker of UC, while other abnormalities, like microvascular alteration and fluorescein leakage, have also been identified in patients with mucosal healing at endoscopy. Larger series are required to validate these results and the advantages of a CLE-based assessment of UC activity.
Literature
1.
go back to reference Dignass A, Eliakim R, Magro F, Maaser C, Chowers Y, Geboes K, Mantzaris G, Reinisch W, Colombel J-F, Vermeire S, Travis S, Lindsay JO, Van Assche G (2012) Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohns Colitis 6:965–990. doi:10.1016/j.crohns.2012.09.003 CrossRefPubMed Dignass A, Eliakim R, Magro F, Maaser C, Chowers Y, Geboes K, Mantzaris G, Reinisch W, Colombel J-F, Vermeire S, Travis S, Lindsay JO, Van Assche G (2012) Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohns Colitis 6:965–990. doi:10.​1016/​j.​crohns.​2012.​09.​003 CrossRefPubMed
2.
go back to reference Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I (2000) Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 119:15–22CrossRefPubMed Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I (2000) Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 119:15–22CrossRefPubMed
3.
go back to reference Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, Williams C, Price A, Talbot I, Forbes A (2004) Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 126:451–459CrossRefPubMed Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, Williams C, Price A, Talbot I, Forbes A (2004) Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 126:451–459CrossRefPubMed
4.
go back to reference Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W et al (2015) Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol 110(9):1324–1338CrossRefPubMed Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W et al (2015) Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol 110(9):1324–1338CrossRefPubMed
6.
go back to reference 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 127:706–713CrossRefPubMed 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 127:706–713CrossRefPubMed
7.
go back to reference Mascolo M, Staibano S, Ilardi G, Siano M, Vecchione ML, Esposito D, De Rosa G, De Palma GD (2012) Probe-based confocal laser endomicroscopy evaluation of colon preneoplastic lesions, with particular attention to the aberrant crypt foci, and comparative assessment with histological features obtained by conventional endoscopy. Gastroenterol Res Pract 2012:645173. doi:10.1155/2012/645173 CrossRefPubMedPubMedCentral Mascolo M, Staibano S, Ilardi G, Siano M, Vecchione ML, Esposito D, De Rosa G, De Palma GD (2012) Probe-based confocal laser endomicroscopy evaluation of colon preneoplastic lesions, with particular attention to the aberrant crypt foci, and comparative assessment with histological features obtained by conventional endoscopy. Gastroenterol Res Pract 2012:645173. doi:10.​1155/​2012/​645173 CrossRefPubMedPubMedCentral
8.
go back to reference 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 42:791–797. doi:10.1016/j.dld.2010.03.009 CrossRefPubMed 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 42:791–797. doi:10.​1016/​j.​dld.​2010.​03.​009 CrossRefPubMed
9.
go back to reference De Palma GD, Maione F, Esposito D, Luglio G, Giglio MC, Siciliano S, Gennarelli N, Cassese G, Campione S, D’Armiento FP, Bucci L (2016) In vivo assessment of tumour angiogenesis in colorectal cancer: the role of confocal laser endomicroscopy. Colorectal Dis 18:O66–O73. doi:10.1111/codi.13222 CrossRefPubMed De Palma GD, Maione F, Esposito D, Luglio G, Giglio MC, Siciliano S, Gennarelli N, Cassese G, Campione S, D’Armiento FP, Bucci L (2016) In vivo assessment of tumour angiogenesis in colorectal cancer: the role of confocal laser endomicroscopy. Colorectal Dis 18:O66–O73. doi:10.​1111/​codi.​13222 CrossRefPubMed
10.
go back to reference Tontini GE, Mudter J, Vieth M, Atreya R, Günther C, Zopf Y, Wildner D, Kiesslich R, Vecchi M, Neurath MF, Neumann H (2015) Confocal laser endomicroscopy for the differential diagnosis of ulcerative colitis and Crohn’s disease: a pilot study. Endoscopy 47:437–443. doi:10.1055/s-0034-1391226 CrossRefPubMed Tontini GE, Mudter J, Vieth M, Atreya R, Günther C, Zopf Y, Wildner D, Kiesslich R, Vecchi M, Neurath MF, Neumann H (2015) Confocal laser endomicroscopy for the differential diagnosis of ulcerative colitis and Crohn’s disease: a pilot study. Endoscopy 47:437–443. doi:10.​1055/​s-0034-1391226 CrossRefPubMed
11.
go back to reference Rispo A, Castiglione F, Staibano S, Esposito D, Maione F, Siano M, Salvatori F, Masone S, Persico M, De Palma GD (2012) Diagnostic accuracy of confocal laser endomicroscopy in diagnosing dysplasia in patients affected by long-standing ulcerative colitis. World J Gastrointest Endosc 4:414–420. doi:10.4253/wjge.v4.i9.414 CrossRefPubMedPubMedCentral Rispo A, Castiglione F, Staibano S, Esposito D, Maione F, Siano M, Salvatori F, Masone S, Persico M, De Palma GD (2012) Diagnostic accuracy of confocal laser endomicroscopy in diagnosing dysplasia in patients affected by long-standing ulcerative colitis. World J Gastrointest Endosc 4:414–420. doi:10.​4253/​wjge.​v4.​i9.​414 CrossRefPubMedPubMedCentral
12.
go back to reference van den Broek FJC, van Es JA, van Eeden S, Stokkers PCF, Ponsioen CY, Reitsma JB, Fockens P, Dekker E (2011) Pilot study of probe-based confocal laser endomicroscopy during colonoscopic surveillance of patients with longstanding ulcerative colitis. Endoscopy 43:116–122. doi:10.1055/s-0030-1255954 CrossRefPubMed van den Broek FJC, van Es JA, van Eeden S, Stokkers PCF, Ponsioen CY, Reitsma JB, Fockens P, Dekker E (2011) Pilot study of probe-based confocal laser endomicroscopy during colonoscopic surveillance of patients with longstanding ulcerative colitis. Endoscopy 43:116–122. doi:10.​1055/​s-0030-1255954 CrossRefPubMed
14.
go back to reference Hurlstone DP, Thomson M, Brown S, Tiffin N, Cross SS, Hunter MD (2007) Confocal endomicroscopy in ulcerative colitis: differentiating dysplasia-associated lesional mass and adenoma-like mass. Clin Gastroenterol Hepatol 5:1235–1241. doi:10.1016/j.cgh.2007.06.003 CrossRefPubMed Hurlstone DP, Thomson M, Brown S, Tiffin N, Cross SS, Hunter MD (2007) Confocal endomicroscopy in ulcerative colitis: differentiating dysplasia-associated lesional mass and adenoma-like mass. Clin Gastroenterol Hepatol 5:1235–1241. doi:10.​1016/​j.​cgh.​2007.​06.​003 CrossRefPubMed
16.
go back to reference De Palma GD (2009) Confocal laser endomicroscopy in the ‘in vivo’ histological diagnosis of the gastrointestinal tract. World J Gastroenterol 15:5770–5775CrossRefPubMedPubMedCentral De Palma GD (2009) Confocal laser endomicroscopy in the ‘in vivo’ histological diagnosis of the gastrointestinal tract. World J Gastroenterol 15:5770–5775CrossRefPubMedPubMedCentral
17.
go back to reference Travis SPL, Schnell D, Krzeski P, Abreu MT, Altman DG, Colombel J-F, Feagan BG, Hanauer SB, Lichtenstein GR, Marteau PR, Reinisch W, Sands BE, Yacyshyn BR, Schnell P, Bernhardt CA, Mary J-Y, Sandborn WJ (2013) Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology 145:987–995. doi:10.1053/j.gastro.2013.07.024 CrossRefPubMed Travis SPL, Schnell D, Krzeski P, Abreu MT, Altman DG, Colombel J-F, Feagan BG, Hanauer SB, Lichtenstein GR, Marteau PR, Reinisch W, Sands BE, Yacyshyn BR, Schnell P, Bernhardt CA, Mary J-Y, Sandborn WJ (2013) Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology 145:987–995. doi:10.​1053/​j.​gastro.​2013.​07.​024 CrossRefPubMed
18.
go back to reference Samuel S, Bruining DH, Loftus EV, Thia KT, Schroeder KW, Tremaine WJ, Faubion WA, Kane SV, Pardi DS, de Groen PC, Harmsen WS, Zinsmeister AR, Sandborn WJ (2013) Validation of the ulcerative colitis colonoscopic index of severity and its correlation with disease activity measures. Clin Gastroenterol Hepatol 11(49–54):e1. doi:10.1016/j.cgh.2012.08.003 Samuel S, Bruining DH, Loftus EV, Thia KT, Schroeder KW, Tremaine WJ, Faubion WA, Kane SV, Pardi DS, de Groen PC, Harmsen WS, Zinsmeister AR, Sandborn WJ (2013) Validation of the ulcerative colitis colonoscopic index of severity and its correlation with disease activity measures. Clin Gastroenterol Hepatol 11(49–54):e1. doi:10.​1016/​j.​cgh.​2012.​08.​003
19.
go back to reference Daperno M, Comberlato M, Bossa F, Biancone L (2012) Concordance in IBD endoscopic scoring requires expertise and training: preliminary results of an ongoing IG-IBD study. J Crohns Colitis 6(Suppl 1):S125. doi:10.1016/S1873-9946(12)60309-2 Daperno M, Comberlato M, Bossa F, Biancone L (2012) Concordance in IBD endoscopic scoring requires expertise and training: preliminary results of an ongoing IG-IBD study. J Crohns Colitis 6(Suppl 1):S125. doi:10.​1016/​S1873-9946(12)60309-2
23.
go back to reference Li C-Q, Xie X-J, Yu T, Gu X-M, Zuo X-L, Zhou C-J, Huang W-Q, Chen H, Li Y-Q (2010) Classification of inflammation activity in ulcerative colitis by confocal laser endomicroscopy. Am J Gastroenterol 105:1391–1396. doi:10.1038/ajg.2009.664 CrossRefPubMed Li C-Q, Xie X-J, Yu T, Gu X-M, Zuo X-L, Zhou C-J, Huang W-Q, Chen H, Li Y-Q (2010) Classification of inflammation activity in ulcerative colitis by confocal laser endomicroscopy. Am J Gastroenterol 105:1391–1396. doi:10.​1038/​ajg.​2009.​664 CrossRefPubMed
24.
go back to reference Hassan C, Bretthauer M, Kaminski MF, Polkowski M, Rembacken B, Saunders B, Benamouzig R, Holme O, Green S, Kuiper T, Marmo R, Omar M, Petruzziello L, Spada C, Zullo A, Dumonceau JM (2013) Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 45:142–150. doi:10.1055/s-0032-1326186 CrossRefPubMed Hassan C, Bretthauer M, Kaminski MF, Polkowski M, Rembacken B, Saunders B, Benamouzig R, Holme O, Green S, Kuiper T, Marmo R, Omar M, Petruzziello L, Spada C, Zullo A, Dumonceau JM (2013) Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 45:142–150. doi:10.​1055/​s-0032-1326186 CrossRefPubMed
25.
go back to reference Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJS, Present D, Sands BE, Colombel JF (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353:2462–2476. doi:10.1056/NEJMoa050516 CrossRefPubMed Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJS, Present D, Sands BE, Colombel JF (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353:2462–2476. doi:10.​1056/​NEJMoa050516 CrossRefPubMed
26.
go back to reference Wallace MB, Meining A, Canto MI, Fockens P, Miehlke S, Roesch T, Lightdale CJ, Pohl H, Carr-Locke D, Löhr M, Coron E, Filoche B, Giovannini M, Moreau J, Schmidt C, Kiesslich R (2010) The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment Pharmacol Ther 31:548–552. doi:10.1111/j.1365-2036.2009.04207.x CrossRefPubMed Wallace MB, Meining A, Canto MI, Fockens P, Miehlke S, Roesch T, Lightdale CJ, Pohl H, Carr-Locke D, Löhr M, Coron E, Filoche B, Giovannini M, Moreau J, Schmidt C, Kiesslich R (2010) The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment Pharmacol Ther 31:548–552. doi:10.​1111/​j.​1365-2036.​2009.​04207.​x CrossRefPubMed
28.
go back to reference Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Löfberg R (2000) A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut 47(3):404–409CrossRefPubMedPubMedCentral Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Löfberg R (2000) A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut 47(3):404–409CrossRefPubMedPubMedCentral
34.
go back to reference Lemmens B, Arijs I, Van Assche G, Sagaert X, Geboes K, Ferrante M, Rutgeerts P, Vermeire S, De Hertogh G (2013) Correlation between the endoscopic and histologic score in assessing the activity of ulcerative colitis. Inflamm Bowel Dis 19:1194–1201. doi:10.1097/MIB.0b013e318280e75f CrossRefPubMed Lemmens B, Arijs I, Van Assche G, Sagaert X, Geboes K, Ferrante M, Rutgeerts P, Vermeire S, De Hertogh G (2013) Correlation between the endoscopic and histologic score in assessing the activity of ulcerative colitis. Inflamm Bowel Dis 19:1194–1201. doi:10.​1097/​MIB.​0b013e318280e75f​ CrossRefPubMed
36.
go back to reference Bessissow T, Lemmens B, Ferrante M, Bisschops R, Van Steen K, Geboes K, Van Assche G, Vermeire S, Rutgeerts P, De Hertogh G (2012) Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing. Am J Gastroenterol 107:1684–1692. doi:10.1038/ajg.2012.301 CrossRefPubMed Bessissow T, Lemmens B, Ferrante M, Bisschops R, Van Steen K, Geboes K, Van Assche G, Vermeire S, Rutgeerts P, De Hertogh G (2012) Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing. Am J Gastroenterol 107:1684–1692. doi:10.​1038/​ajg.​2012.​301 CrossRefPubMed
38.
go back to reference Rubio CA, Johansson C, Kock Y (1982) A quantitative method of estimating inflammation in the rectal mucosa. III. Chronic ulcerative colitis. Scand J Gastroenterol 17:1083–1087PubMed Rubio CA, Johansson C, Kock Y (1982) A quantitative method of estimating inflammation in the rectal mucosa. III. Chronic ulcerative colitis. Scand J Gastroenterol 17:1083–1087PubMed
39.
go back to reference Rubio CA, Johansson C, Uribe A, Kock Y (1984) A quantitative method of estimating inflammation in the rectal mucosa. IV. Ulcerative colitis in remission. Scand J Gastroenterol 19:525–530PubMed Rubio CA, Johansson C, Uribe A, Kock Y (1984) A quantitative method of estimating inflammation in the rectal mucosa. IV. Ulcerative colitis in remission. Scand J Gastroenterol 19:525–530PubMed
Metadata
Title
Confocal laser endomicroscopy in ulcerative colitis: beyond endoscopic assessment of disease activity
Authors
F. Maione
M. C. Giglio
G. Luglio
A. Rispo
M. D’Armiento
B. Manzo
G. Cassese
P. Schettino
N. Gennarelli
S. Siciliano
F. P. D’Armiento
G. D. De Palma
Publication date
01-07-2017
Publisher
Springer International Publishing
Published in
Techniques in Coloproctology / Issue 7/2017
Print ISSN: 1123-6337
Electronic ISSN: 1128-045X
DOI
https://doi.org/10.1007/s10151-017-1654-4

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