In Vivo Diagnosis and Classification of Colorectal Neoplasia by Chromoendoscopy- Guided Confocal Laser Endomicroscopy Silvia Sanduleanu, Ann Driessen,

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In Vivo Diagnosis and Classification of Colorectal Neoplasia by Chromoendoscopy- Guided Confocal Laser Endomicroscopy Silvia Sanduleanu, Ann Driessen, Encarna Gomez–Garcia, Wim Hameeteman, Adriaan de Bruïne, Ad Masclee Clinical Gastroenterology and Hepatology Volume 8, Issue 4, Pages 371-378 (April 2010) DOI: 10.1016/j.cgh.2009.08.006 Copyright © 2010 AGA Institute Terms and Conditions

Figure 1 Study methodology. Clinical Gastroenterology and Hepatology 2010 8, 371-378DOI: (10.1016/j.cgh.2009.08.006) Copyright © 2010 AGA Institute Terms and Conditions

Figure 2 Algorithm of confocal imaging acquisition during the study. Clinical Gastroenterology and Hepatology 2010 8, 371-378DOI: (10.1016/j.cgh.2009.08.006) Copyright © 2010 AGA Institute Terms and Conditions

Figure 3 (A) Normal colonic mucosa. (A-1) Endomicroscopy (acriflavine) shows regular crypt architecture. Crypt detail showing normal nuclei (white dots) within the epithelial cells (arrow). (A-2) The corresponding histologic specimens of normal colonic mucosa (hematoxylin-eosin staining, ×30 original magnification; crypt detail, ×50 original magnification). (B) Hyperplastic polyp. The luminal openings of crypts show stellar appearance (arrows) by CLE (acriflavine) (B-1) and by conventional histology (B-2, hematoxylin-eosin, ×20 original magnification). (C) Serrated adenoma. (C-1) CLE (acriflavine) shows epithelial surface maturation (arrow), regular crypts, and pseudostratification of nuclei (arrowhead). (C-2) Corresponding histologic specimens (×20 original magnification). (D) Adenomatous polyp. Slight irregularity of the crypts in a tubular adenoma by endomicroscopy (fluorescein) (D-1) and by conventional histology (D-2, ×15 original magnification). (E) Invasive carcinoma. (E-1) Endomicroscopy of a poorly differentiated adenocarcinoma shows cryptal destruction, distorted vessels, leakage of fluorescein into the surrounding tissue (neoangiogenesis, arrow), and islands of malignant (dark) cells (arrowhead). (E-2) Corresponding histologic specimens (×20 original magnification). Clinical Gastroenterology and Hepatology 2010 8, 371-378DOI: (10.1016/j.cgh.2009.08.006) Copyright © 2010 AGA Institute Terms and Conditions

Figure 4 ADS was calculated by adding up scores corresponding to the following parameters: epithelial surface maturation, crypt morphology, vascular pattern, and cytonuclear atypia. Median ADS was significantly higher in adenomas with HGD vs those with LGD (P < .0001). Clinical Gastroenterology and Hepatology 2010 8, 371-378DOI: (10.1016/j.cgh.2009.08.006) Copyright © 2010 AGA Institute Terms and Conditions

Figure 5 Grading of dysplasia in adenomatous polyps. (A) Adenoma with LGD. Endoscopic appearance of flat adenoma (Paris IIa) in a patient with familial CRC (A-1). CLE (acriflavine) shows enlarged, slightly irregular crypts and pseudostratification of nuclei within the crypt (A-2, arrow), and the surface epithelium (A-3, arrowhead). Conventional histology of targeted biopsies shows similar findings (A-4, ×15 original magnification). (B) Adenoma with HGD. Endoscopic appearance of adenoma (Paris IIa+IIc) in a patient with familial CRC (B-1). Endomicroscopy (acriflavine) shows complex crowding of crypts (B-2, arrow), reaching the surface epithelium, that clearly lacks normal differentiation (B-3, arrowhead). Similar findings by conventional histology (B-4, ×12 original magnification). Clinical Gastroenterology and Hepatology 2010 8, 371-378DOI: (10.1016/j.cgh.2009.08.006) Copyright © 2010 AGA Institute Terms and Conditions