Chromoendoscopy is an endoscopic technique that uses stains during endoscopy to highlight differences in mucosa, as well as dysplastic and malignant changes that are not apparent in white light. Chromoendoscopy is used to increase the detection rates for various pathologic processes during endoscopy. Chromoendoscopy is often used in surveillance of the esophagus for Barrett's esophagus, evaluation of polyps in the colon, and surveillance of dysplasia in inflammatory bowel disease. 
Chromoendoscopy has been used in the evaluation of Barrett esophagus, [2, 3, 4] esophageal adenocarcinoma,  gastric metaplasia and adenocarcinoma, [6, 7, 8, 9] colon polyps,  colon cancer, [11, 12, 13, 14, 15] and surveillance in inflammatory bowel disease. 
The contraindications to chromoendoscopy would be any of the usual contraindications to endoscopy or a history of an allergic reaction to the dye or stain used in the specific clinical situation.
Chromoendoscopy is not routinely performed during general endoscopy. It is performed in centers that specialize in this field or on a case-by-case basis as indicated by the clinical situation and dictated by the endoscopist's and center's experience.
The usual preparation prior to upper endoscopy or colonoscopy and sedation administration is undertaken in the standard manner. Thereafter, specialized preparation of mucosa is done depending on the endoscopic procedure, dye or stain used, suspected lesion, and planned therapy of that lesion.
Barrett Esophagus and Esophageal Adenocarcinoma
The increasing prevalence of Barrett esophagus and its recognition as a premalignant lesion has engendered a great deal of interest in recognizing metaplastic and dysplastic changes.  The increasing use of endoscopic therapy for dysplasia and adenocarcinoma has given further impetus to this concept. Chromoendoscopy is considered by some as a tool in recognizing high risk lesions within Barrett esophagus and in facilitating definitive therapy.  The most commonly used dye is methylene blue.
Magnification chromoendoscopy is an important adjunctive technique that enhances the sensitivity and specificity.  Evaluating lesions in the absence of biopsies based on staining has also been shown to be useful.  Unfortunately, the sensitivity and specificity are wide ranging. Randomized controlled trials have shown conflicting results and also equivalency to routine endoscopy. 
Esophageal Squamous Cancer
Lugol iodine is most commonly used to survey patients at risk for squamous cell carcinoma, including patients with tobacco abuse, alcohol abuse, or past head and neck cancer.  The sensitivity is between more than 90% but the specificity is variable.  The dye may also be used to guide resection of early lesions.
Gastric Metaplasia and Cancer
Chromoendoscopy has been used to detect and demarcate dysplasia, intestinal metaplasia, or malignancy. [6, 22, 23] Methylene blue and congo red are used in a combination to differentiate abnormal gastric mucosa (which does not stain) from normal mucosa (which stains red or blue).  This may be of utility in high-risk groups targeted for intensive surveillance. 
There is some evidence that Helicobacter pylori detection in the stomach is better with phenol red chromoendoscopy, although this concept has not been evaluated in clinical trials. [26, 27] Phenol red staining is being studied in assessing the functional recovery of gastric mucosa after H. pylori eradication therapy. 
There have been many randomized trials for enhanced adenoma detection with chromoendoscopy using indigo carmine staining. [10, 29, 30] Pohl et al conducted a large randomized controlled trial comparing standard endoscopy to pancolonic chromoendoscopy and showed that chromoendoscopy significantly increased the detection rate for adenomas, flat lesions, and serrated lesions. There was an increase in the mean withdrawal time.  Other trials have shown mixed results. 
There may be a advantage to chromoendoscopy in detecting flat lesions.  An increased cancer detection rate or survival rate has not been demonstrated. Chromoendoscopy is currently not of significant utility in screening or surveillance colonoscopy.
Chromoendoscopy also has a limited and experimental role in endoscopically assessing the depth of known colorectal cancer. 
Inflammatory Bowel Disease
The difficulty in identifying dysplasia and carcinoma in chronic ulcerative colitis has led to the evaluation of chromoendoscopy in this particular high-risk situation. Many trials have shown that dysplasia detection is improved significantly and reproducibly. [16, 33, 34] The accumulation of evidence may have an impact on chronic ulcerative colitis surveillance guidelines.  Evidence with regard to carcinoma detection in this setting is equivocal. 
Preliminary evaluations of computerized virtual chromoendoscopy for screening colonoscopy have shown similar efficacy to chromoendoscopy without the logistical difficulties or preparing and applying vital dyes. [37, 38] Magnification endoscopy, spectroscopy, confocal laser endomicroscopy and endocytoscopy have a important role in the evaluation of inflammatory bowel disease and surveillance of chronic ulcerative colitis. [39, 40, 41] Use of these techniques in Barrett esophagus has also led better detection of dysplasia, particularly in the absence of discrete lesions. 
Lugol iodine can rarely cause esophagitis or gastritis. Hyperthyroidism or hypersensitivity to iodine should preclude the use of this agent. Methylene blue can cause discoloration of urine and feces. No serious adverse effects of other vital dyes have been described. General precautions should include aspiration and contact precautions. 
The agents used in chromoendoscopy are commercially available and inexpensive. They are not specifically made for endoscopy. They are prepared and diluted based on the practices of the chromoendoscopists. Common staining agents used are Lugol solution, methylene blue, toluidine blue, crystal violet, indigo carmine, congo red, and phenol red. Special spray catheters are used to spray a fine mist on to the mucosa. 
The agents are classified as absorptive, contrast, or reactive agents. Absorptive stain are absorbed by or diffuse into specific cells. Contrast agents seep between cells and enhance the surface. Reactive agents undergo chemical reactions with specific cell components and undergo color change. 
Application of some staining agents requires the application of mucolytic agents such as N-acetyl cysteine to remove mucus from epithelium to allow optimal results with staining.
The agent may be applied to a specific area or to the whole mucosal surface of interest. The abnormal mucosa may stain positively (ie, taking up the dye) or negatively (ie, remaining unstained or understained). In general, the minimum amount of dye required is used. Excess dye is suctioned or washed. The time required for optimal staining is variable and depends on the targeted tissue and the stain used.
The table below details the properties and uses of each agent. 
Lugol solution (iodine and potassium
Glycogen-containing normal squamous
epithelium is stained dark brown;
inflammation, columnar mucosa, dysplasia,
and cancer remain unstained
Esophageal squamous cell cancer and
Methylene blue (methylthioninium
Absorptive epithelial cells of the small
bowel, colon, and intestinal metaplasia at
any site are stained blue; dysplasia and
cancer is variably stained or unstained
Gastric intestinal metaplasia and cancer
Chronic ulcerative colitis
|Toluidine blue (tolonium chloride)||Nuclei of malignant cells are stained blue||Oral and esophageal squamous cell cancer|
|Crystal violet (methylrosaniline chloride||
Absorbed into intestinal and neoplastic
cells; nuclear stain
Indigo carmine (indigotindisulfonate
Nonabsorbed dark bluish dye highlighting
Chronic ulcerative colitis
Congo red (biphenylenenaphthadene
Color change from red to dark blue/black
in presence of acid at pH 3
Ectopic gastric mucosa
Adequacy of vagotomy
|Phenol red (phenolsulfonephthalein)||
Color change from yellow to red in
presence of alkali (eg, from hydrolysis of
urea to ammonia and carbon dioxide by
urease-producing H. pylori)
|H. pylori infection|
Chromoendoscopy is not an advanced endoscopic technique and is not technically difficult to learn. However, interpretation of the staining patterns requires training and may not always be easy. There is evidence that there is significant intraobserver and interobserver variation. [42, 43]