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 1). 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 esophagus, evaluation of polyps in the colon, and surveillance of dysplasia in inflammatory bowel disease (IBD) 2).
Chromoendoscopy is not routinely performed during general endoscopy. Chromoendoscopy 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 experience of the endoscopist and the center.
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 3).
Initial evaluations of computerized virtual chromoendoscopy for screening colonoscopy showed efficacy similar to that of chromoendoscopy, without the logistical difficulties or preparing and applying vital dyes 4). Magnification endoscopy, spectroscopy, confocal laser endomicroscopy and endocytoscopy have important roles in the evaluation of inflammatory bowel disease and surveillance of chronic ulcerative colitis (UC) 5). Use of these techniques in Barrett esophagus has also led better detection of dysplasia, particularly in the absence of discrete lesions 6).
Chromoendoscopy has been used in the evaluation of Barrett esophagus 7), esophageal adenocarcinoma 8), gastric metaplasia and adenocarcinoma 9), colon polyps 10), colon cancer 11) and surveillance in inflammatory bowel disease (IBD) 12).
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 13). 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 for recognizing high-risk lesions within Barrett esophagus and for facilitating definitive therapy 14). The most commonly used dye is methylene blue.
Magnification chromoendoscopy is an important adjunctive technique that enhances the sensitivity and specificity 15). Evaluating lesions in the absence of biopsies based on staining has also been shown to be useful 16). Unfortunately, the sensitivity and specificity are wide-ranging. Randomized controlled trials have shown conflicting results and also equivalency to routine endoscopy 17).
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 18). The sensitivity exceeds 90%, but the specificity is variable 19). 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 20). 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) 21). This may be of utility in high-risk groups targeted for intensive surveillance 22).
There is some evidence that Helicobacter pylori detection in the stomach is better with phenol red chromoendoscopy, though this concept has not been evaluated in clinical trials 23). Phenol red staining is being studied in assessing the functional recovery of gastric mucosa after H pylori eradication therapy 24).
There have been many randomized trials for enhanced adenoma detection with chromoendoscopy using indigo carmine staining 25). Pohl et al 26) conducted a large randomized controlled trial comparing standard endoscopy with 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 27).
There may be a advantage to chromoendoscopy in detecting flat lesions 28). 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 29).
Inflammatory bowel disease
The difficulty in identifying dysplasia and carcinoma in chronic ulcerative colitis (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 30), 31). The accumulation of evidence may have an impact on chronic ulcerative colitis surveillance guidelines 32). Evidence with regard to carcinoma detection in this setting is equivocal 33).
Contraindications for chromoendoscopy would be any of the usual contraindications for endoscopy or a history of an allergic reaction to the dye or stain used in the specific clinical situation.
The usual preparation prior to upper endoscopy or colonoscopy and sedation administration is undertaken in the standard manner. Thereafter, specialized preparation of mucosa is carried out in accordance with the endoscopic procedure to be done, the dye or stain to be used, the suspected lesion, and the planned therapy for that lesion.
The agents used in chromoendoscopy are commercially available and inexpensive. They are not specifically made for endoscopy. They are prepared and diluted in accordance with 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 34). Table 1 below details the properties and uses of each agent 35).
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 36).
Application of some staining agents requires the application of mucolytic agents such as N-acetylcysteine 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.
It should be kept in mind that Lugol iodine can cause esophagitis or gastritis in rare cases. 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 37).
Table 1. Properties of and clinical indications for common stains used in endoscopy
|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|
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