Chromoendoscopy is based on the application of various dye solutions to the mucosa of the gastrointestinal tract, thus enhancing subtle mucosal changes not perceivable by purely optical methods. Several different dye stains are used in the upper GI tract, most of which are absorptive in function (e.g. Lugol’s solution, methylene blue, crystal violet, toluidine blue) and require additional time (2–20 min) for staining before interpretation can be carried out. Other agents used work as contrast (e.g. indigo carmine) or reactive agents (e.g. Congo red) [7].

The most widely used classification system was developed by Kudo, and it classifies colonic lesions into seven subtypes [8]. Lesions with advanced, superficially invasive neoplasia are the best candidates for ESD and are termed type V_i (irregular), with highly irregular yet intact pit patterns (Fig. 5.1) [8]. Deeply invasive lesions, which cannot be fully removed by ESD, typically have non-structural, or complete loss of pits. Unfortunately, these patterns typically require magnification and crystal violet staining, which is not widely used in the West.

The use of chromoendoscopy has remained useful in regions with high incidences of squamous cell carcinoma (SCC) of the esophagus. Lugol’s solution stains glycogen, which is found within non-keratinized squamous cells, into a dark brown color, allowing delineation of normal epithelium from glycogen-depleted cells (e.g. dysplastic epithelium, SCC, columnar epithelium, or inflammation) [7] (Fig. 5.2).

The dyes most commonly used for chromoendoscopy in Barrett’s esophagus (BE) are acetic acid and methylene blue. Acetic acid produces reversible changes on the surface proteins of columnar epithelium, causing transient whitening of the epithelium that usually lasts 2–3 min. This whitening effect is lost faster in dysplastic epithelium compared to the surrounding mucosa, therefore enhancing its identification. Methylene blue is absorbed by BE including dysplastic epithelium, but not by squamous epithelium or gastric-type metaplasia in the lower esophagus. However, the absorption is heterogenous and of a lighter intensity in high-grade dysplasia or adenocarcinoma of the esophagus, allowing differentiation from non-dysplastic BE [9].

In contrast, in areas with high incidence of BE, the use of chromoendoscopy has been declining in favor of virtual chromoendoscopy techniques (e.g. NBI or FICE), which have the advantage of providing mucosal enhancement within seconds by simply pushing a bottom within the endoscope and therefore obviating the need to spray and rinse dye. In fact, a recent meta-analysis evaluating the increased diagnostic yield for the detection of dysplasia or cancer on patients with BE found that both chromoendoscopy and virtual chromoendoscopy equally increased the diagnostic yield for dysplasia [1].

In the stomach, chromoendoscopy has long been used to detect intestinal metaplasia, dysplasia, and early gastric cancer. A combination of methylene blue with Congo red or acetic acid has been found useful for detecting early gastric cancer. In one study, the detection of synchronous lesions increased from 28 % under standard white light endoscopy up to 89 % with a combination of methylene blue and Congo red, as cancerous areas do not stain with either dye [7]. Similarly, others have also found increased early gastric cancer detection with a combination of indigo carmine and acetic acid [10, 11]. In one study, the diagnostic yield almost doubled with a combination of indigo carmine and acetic acid (94 %) versus either one alone (42 % for acetic acid and 52 % for indigo carmine; p < 0.005) [10]. In another study, this same combination was able to identify 6 of 39 lesions that were previously missed with standard white light endoscopy and using only indigo carmine [11].