Endoscopic submucosal dissection for nonpolypoid colorectal dysplasia in patients with inflammatory bowel disease: in medias res  Roy Soetikno, MD, MS, MSM  Gastrointestinal Endoscopy  Volume 87, Issue 4, Pages 1085-1094 (April 2018) DOI: 10.1016/j.gie.2018.01.013 Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 1 Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC) endoscopic classification of superficial colorectal dysplasia in patients with inflammatory bowel disease (IBD). The classification is a modification of the Paris endoscopic classification of superficial neoplastic lesions. The modifications included the addition of terms (presence or absence) to describe ulceration and border of the lesion. The SCENIC classification replaces the terms dysplasia-associated lesion or mass and adenoma-like and non–adenoma-like. Note that in patients with IBD, the nonpolypoid colorectal dysplasia in IBD is often completely flat (or the same level) compared with the surrounding mucosa. This is different from patients without IBD, who rarely have completely flat dysplasia. Thus, in patients without IBD “flat lesion” is colloquially used to describe lesions that are slightly (superficially) elevated in comparison with the surrounding mucosa. Descriptions of the terms are listed below.Modified from Soetikno et al, Dig Endosc 2016;28:266-73, and Laine et al, Gastrointest Endosc 2015;81:489-501e26.TermDescriptionVisible dysplasiaDysplasia identified on targeted biopsy specimens from a lesion visualized at colonoscopyPolypoidLesion protruding from the mucosa into the lumen ≥2.5 mmPedunculatedLesion attached to the mucosa by a stalkSessileLesion not attached to the mucosa by a stalk; entire base is contiguous with the mucosaNonpolypoidLesion with little (<2.5 mm) or no protrusion above the mucosaSuperficial elevatedLesion with protrusion but <2.5 mm above the lumen (less than the height of the closest cup of a biopsy forceps)FlatLesion without protrusion above the mucosaDepressedLesion with at least a portion depressed below the level of the mucosaGeneral descriptorsUlceratedUlceration (fibrinous-appearing base with depth) within the lesionBorderDistinct borderLesion’s border is discrete and can be distinguished from surrounding mucosaIndistinct borderLesion’s border is not discrete and cannot be distinguished from surrounding mucosaInvisible dysplasiaDysplasia identified on random (nontargeted) biopsy specimens of colon mucosa without a visible lesion Gastrointestinal Endoscopy 2018 87, 1085-1094DOI: (10.1016/j.gie.2018.01.013) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 2 Preparation and application of chromoendoscopy for detection and detailed inspection of nonpolypoid colorectal dysplasia in patients with inflammatory bowel disease. ∗Chromoendoscopy for detection with indigo carmine: 1. American Regent, Shirley, NY, 5 mL (0.8%) - Mix two 5-mL ampules (0.8%) with 250 mL water. The manufacturer’s suggested retail price (MSRP) is approximately $330 ($165 per 5 mL 0.8% solution). 2. Microtech, Ann Arbor, Michigan, 5 mL (0.4%) - Mix four 5-mL ampules (0.4%) with 250 mL water. The MSRP is approximately $156.80 ($39.2 per 5 mL 0.4% solution). Methylene blue: 1. American Regent, Shirley, NY, 10 mL (0.5%) - Mix one 10-mL ampule (0.5%) with 300 mL water. The MSRP is approximately $202.69 ($202.69 per 10 mL 0.5% solution). †Chromoendoscopy for detailed viewing with indigo carmine: 1. American Regent, Shirley, NY, 5 mL (0.8%) - Mix one 5-mL ampule (0.8%) with 20 mL water in a 60-mL syringe to approximate a 0.16% dilution. The MSRP is approximately $165 ($165 per 5 mL 0.8% solution). 2. Microtech, Ann Arbor, MI, 5 mL (0.4%) - Mix two 5-mL ampules (0.4%) with 15 mL water in a 60-mL syringe to approximate a 0.16% dilution. The MSRP is approximately $78.60 ($39.2 per 5 mL 0.4% solution). Methylene blue: 1. American Regent, Shirley, NY, 10 mL (0.5%) - Mix one 10-mL ampule (0.5%) with 20 mL water in a 60-mL syringe to approximate a 0.16% dilution. The MSRP is approximately $202.69 ($202.69 per 10 mL 0.5% solution). Gastrointestinal Endoscopy 2018 87, 1085-1094DOI: (10.1016/j.gie.2018.01.013) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 3 The red-in-blue sign: the lesion, which appears red, is in a blue surrounding. One way the dye improves our visualization of a flat lesion is by making some lesions appear redder than its surroundings. These observations are derived from the detection of early gastric cancer. A, There was spontaneous bleeding on white light. B, After dye spraying, a large superficial elevated lesion could be visualized. C, Closer view of the lesion. D, Similarly to the study by Kinoshita et al,9 the dye helped determine the margin of the lesion for endoscopic submucosal dissection (ESD). E, Pathologic appearance of the lesion showing dysplasia-associated colitic and horizontal or vertical margin free of dysplasia. F, Artist’s rendition of the phenomena seen: dysplasia often has shallower and narrower glands, and there was a slight elevation of the lesion. These reasons were likely to have contributed to the lesion having less dye on its surface. The sensitivity and specificity of this sign is not known at present. Gastrointestinal Endoscopy 2018 87, 1085-1094DOI: (10.1016/j.gie.2018.01.013) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 4 The pit patterns of nonpolypoid colorectal dysplasia (NP-CRD). Detailed evaluation of the pit pattern can be complex and tedious and requires magnification. Also, many patterns require a significant learning curve. In patients with inflammatory bowel disease (IBD), in general, we need to focus on only a few general patterns: type 1 (normal mucosa), type 2 (hyperplastic tissue), NP-CRD, and type VN (invasive cancer). Note that patterns for sessile serrated adenoma are not included. Gastrointestinal Endoscopy 2018 87, 1085-1094DOI: (10.1016/j.gie.2018.01.013) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 5 A to G, Examples of lesions showing signs of nonpolypoid colorectal dysplasia (NP-CRD) during chromoendoscopy examination. H, A sessile serrated adenoma/polyp. Gastrointestinal Endoscopy 2018 87, 1085-1094DOI: (10.1016/j.gie.2018.01.013) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 6 Simplified endoscopic submucosal dissection (ESD) / hybrid ESD. A patient with long-standing colonic inflammatory bowel disease (IBD) was referred after chromoendoscopy with targeted biopsy specimen from a 2-cm flat lesion in the rectosigmoid colon showed low-grade dysplasia. A, Chromoendoscopic view of lesion, a 1.7-cm NP-CRD, superficial elevated (flat). B, The border of the lesion was marked with brief bursts of cautery; the Dual knife (Olympus Corp, Tokyo, Japan) was used. C, After injection with saline mixed with indigo carmine, a circumferential incision was made around the lesion. The lesion was completely isolated from its lateral surroundings. D, Underwater viewing of the submucosa below the lesion showing severe fibrosis. The lesion was on the top part of the image, and the muscle layer, which was white, was at the lower part. E, The lesion was captured using a stiff snare. The stiff snare was closed completely to the hub prior to applying cautery in order to prevent entrapment of the muscularis mucosa. F, Exposed submucosa and muscularis propria after en-bloc resection. The result of pathologic analysis was low-grade dysplasia. Gastrointestinal Endoscopy 2018 87, 1085-1094DOI: (10.1016/j.gie.2018.01.013) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 7 Example of full endoscopic submucosal dissection (ESD) to remove a large area of nonpolypoid colorectal dysplasia (NP-CRD). A, A large area of dysplasia was seen between the 6 o’clock and 12 o’clock positions. The periphery of the lesion had been marked. After circumferential marking for the margin of an NP-CRD, B, the submucosa was carefully dissected with a flash knife coupled with a Sumitomo Bakelite knife (Shinagawa-ku, Tokyo, Japan). Severe fibrosis could be visualized. C, Minor bleeding was encountered frequently during the dissection. D, The lesion was completely removed by en bloc resection. Gastrointestinal Endoscopy 2018 87, 1085-1094DOI: (10.1016/j.gie.2018.01.013) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions