Chromoendoscopy

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 uses

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.

Colorectal adenoma

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.

Colorectal cancer

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, ¹². The accumulation of evidence may have an impact on chronic ulcerative colitis surveillance guidelines ³¹. Evidence with regard to carcinoma detection in this setting is equivocal ³².

Chromoendoscopy contraindications

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.

Chromoendoscopy technique

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 ¹⁹. Table 1 below details the properties and uses of each agent ¹⁹.

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 ¹⁹.

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 ¹⁹.

Table 1. Properties of and clinical indications for common stains used in endoscopy

Stain	Property	Clinical Indication
Absorptive
Lugol solution (iodine and potassium iodide)	Glycogen-containing normal squamous epithelium is stained dark brown; inflammation, columnar mucosa, dysplasia, and cancer remain unstained	Esophageal squamous cell cancer and dysplasia Barrett esophagus
Methylene blue (methylthioninium chloride)	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	Barrett esophagus 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	Barrett esophagus Colonic neoplasms
Contrast
Indigo carmine (indigotindisulfonate sodium)	Nonabsorbed dark bluish dye highlighting mucosal topography	Colonic neoplasms Chronic ulcerative colitis
Reactive
Congo red (biphenylenenaphthadene sulfonic acid)	Color change from red to dark blue/black in presence of acid at pH 3	Ectopic gastric mucosa Gastric cancer 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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