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Chromoendoscopy: Role in Modern Endoscopic Imaging Review Article Chromoendoscopy: role in modern endoscopic imaging Rajvinder Singh1,2, Keng Hoong Chiam1, Florencia Leiria1, Leonardo Zorron Cheng Tao Pu2,3, Kun Cheong Choi1, Mariana Militz1 1Gastroenterology Department, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia; 2Faculty of Health Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia; 3Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan Contributions: (I) Conception and design: R Singh, KH Chiam; (II) Administrative support: None; (III) Provision of study materials or patients: R Singh; (IV) Collection and assembly of data: None; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Professor Rajvinder Singh, MBBS, MRCP, Mphil, FRACP, AM FRCP. Professor of Medicine, University of Adelaide; Director of the Gastroenterology Department & Head of Endoscopy, Endoscopy Unit, Lyell McEwin Hospital, Elizabeth Vale, Australia. Email: [email protected]. Abstract: Detection of early gastrointestinal tract malignancy can be challenging on white light endoscopy especially as lesions can be subtle and inconspicuous. With the advent of electronic chromoendoscopy technologies, lesions which have already been detected can be quickly and “conveniently” characterised. This review will discuss some of the indications and modern applications of chromoendoscopy in various conditions including Barrett’s oesophagus, oesophageal squamous cell carcinoma, early gastric cancer, inflammatory bowel disease and neoplastic colonic lesions. In carefully selected situations, chromoendoscopy could still be a useful adjunct to white light endoscopy in day-to-day clinical practice. Keywords: Chromoendoscopy; endoscopy dyes; narrow band imaging (NBI); digestive system diagnostic techniques; endoscopy procedures Received: 24 September 2019; Accepted: 04 December 2019; Published: 05 July 2020. doi: 10.21037/tgh.2019.12.06 View this article at: http://dx.doi.org/10.21037/tgh.2019.12.06 Introduction protruding spraying catheter) is directed in spiral movements onto the mucosa and simultaneously, the dye Chromoendoscopy aids the endoscopist in highlighting is sprayed continuously. In a stepwise manner, segments of and characterising lesions in the gastrointestinal tract approximately 20 cm should be stained each time and then (GIT). This is generally achieved by using a variety of carefully inspected. Special caution should be exercised dyes to distinguish normal from abnormal mucosa (1). whilst staining the upper oesophagus, due to the risk of The technique encourages endoscopists to study a aspiration. In addition, a foot pump can be useful in some particular area of interest with greater clarity and sharpness. cases, such as for pancolonic dye spraying in patients with Chromoendoscopy can complement imaging through inflammatory bowel disease (IBD). enhancing features of mucosal surface topography and may In colonoscopy, good bowel preparation is critical; the assist in providing in-depth details that enables subsequent use of spasmolytic agents such as scopolamine or glucagon therapeutic decisions to be made with greater precision (2). can be used to avoid bowel peristalsis and an uneven Spraying catheters allow the most controlled and precise distribution of the dye in some cases. application of the dye as a fine mist onto the GIT surface. The use of chromoendoscopy has demonstrated good The amount of staining solution required depends on diagnostic yield in the evaluation of dysplastic lesions in the surface area to be stained. The endoscope should be Barrett’s oesophagus (BO) and oesophageal adenocarcinoma slowly withdrawn, while the endoscope tip (with a 1–2 cm by facilitating targeted biopsies of suspicious areas (3-5). It also © Translational Gastroenterology and Hepatology. All rights reserved. Transl Gastroenterol Hepatol 2020;5:39 | http://dx.doi.org/10.21037/tgh.2019.12.06 Page 2 of 10 Translational Gastroenterology and Hepatology, 2020 A B Figure 1 Acetic acid reaction in Barrett’s oesophagus. (A) Barret’s oesophagus on white light endoscopy; (B) acetic acid on Barrett’s oesophagus: “aceto-whitening reaction” in intestinal metaplasia due to lack of normal stratified squamous epithelium. plays a key role in gastric metaplasia and adenocarcinoma, as (II) The non-absorptive or contrast stains include indigo well as in the colon particularly in patients with chronic colitis carmine where on application they seep between (6-8). Over the years, the introduction and adoption of ´virtual´ grooves and crevices providing an overall detail of the or electronic chromoendoscopy has rendered dye-based contour of the mucosal surface. Indigo carmine is used chromoendoscopy less relevant in day-to-day clinical practise. throughout the GIT for various dysplastic lesions. Virtual chromoendoscopy is technically less cumbersome, (III) Reactive stains include Congo red and phenol red. The easier to apply and saves time (9,10). Nevertheless, dye undergoes chemical reactions with specific cellular chromoendoscopy still plays a major role in several conditions. components and gives rise to a colour change. They are not commonly encountered in endoscopy (13). Classification of stains AA chromoendoscopy in Barrett’s neoplasia Dyes used in chromoendoscopy have a transient effect. With the exclusion of known prior allergic reactions, This novel use of AA chromoendoscopy in BO was these dyes are generally safe (11) Traditionally, they can be introduced in 2001 by Guelrud and colleagues (14). The classified into three distinct types based on their staining principle is not dissimilar to AA employment in the field of properties. gynaecology to screen for dysplastic uterine cervical lesions Although chromoendoscopy may be replaced by virtual which was well established in the early 1990s (15). When chromoendoscopy with similar results (12), for some sprayed onto the Barrett’s mucosa, a reversible acetylation specific cases the literature still shows advantages on using of cellular proteins occurs leading to a so-called “aceto- dyes. For each dye, scenarios where chromoendoscopy still whitening reaction” (Figure 1) (16). With neoplastic lesions has a role will be discussed in the following section: which lack cellular proteins, the aceto-whitening reaction (I) The absorptive or vital stains are absorbed by is not visible or is lost quickly compared to normal non- specific cells and give rise to sharp detail of the dysplastic BO epithelium. The duration of the aceto- cellular surface. Some examples of these stains whitening effect was further studied by Longcroft- include Lugol’s iodine (LI); which can be used Wheaton and colleagues who objectively measured and in delineating squamous dysplasia and squamous compared the effect of AA on dysplastic and non-dysplastic cell cancer in the oesophagus. Methylene blue lesions. Not surprisingly, high-grade dysplastic lesions and and crystal violet have been used in Barrett’s intramucosal cancer took between 23–53 seconds to lose oesophagus, gastric intestinal metaplasia and the aceto-whitening effect compared to non-dysplastic lesions colorectal dysplasia. Acetic acid (AA) used in which continued to hold on to this effect for up to a median detecting dysplastic Barrett’s lesions, are also duration of 311 seconds (P<0.05). In addition, using AA had categorized under these types of stains (13). a sensitivity and specificity of 98% and 84% respectively (17). © Translational Gastroenterology and Hepatology. All rights reserved. Transl Gastroenterol Hepatol 2020;5:39 | http://dx.doi.org/10.21037/tgh.2019.12.06 Translational Gastroenterology and Hepatology, 2020 Page 3 of 10 This increases the yield of detecting dysplastic lesions and colleagues introduced the “pink colour sign”, which has facilitates targeted biopsies. Coletta and colleagues also shown high sensitivity and specificity (91.9% and 94.0%) highlighted the role of AA in a recent meta-analysis where for diagnosing high-grade dysplasia and OSCC (Figure 2). the pooled sensitivity and specificity was 92% and 96% This observation assists in the distinction between high for the diagnosis of high-grade dysplasia and oesophageal and low-grade dysplasia/inflammation as the former gives a adenocarcinoma (18). Both these large studies were able to more distinct and pinkish hue, while the latter appears pale. achieve the desired American Society for Gastrointestinal An additional 2 to 3 minutes to observe this discoloration is Endoscopy Preservation and Incorporation of Valuable necessary with the authors reporting that false positive LI Endoscopic Innovations (ASGE-PIVI) criteria (19). In terms stained areas (initially with yellow decolouration) could be of cost-efficacy, Bhandari and colleagues went on to compare ignored if they are not pink after this period of observation (29). protocol-guided random biopsies and AA guided biopsies Similar to AA, LI has significant diagnostic potential in high-risk groups. They found that despite a 4% miss rate in early cancer detection where targeted biopsies can be in the latter, substantial cost savings could be achieved (20). facilitated. In addition, a clear demarcation between normal The gain in neoplasia detection was also tested by Tholoor and abnormal margins can be easily delineated enabling and colleagues in a retrospective cohort study where a planning for endoscopic resection at
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