Approach Considerations

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.^[1]

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.^[1]

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.^[1]

Virtual chromoendoscopy is increasingly used; it appears to be as effective as standard chromoendoscopy, without the logistical difficulties or preparing and applying vital dyes. The implementation of artificial intelligence systems in this procedure may further improve the reliability of virtual chromoendoscopy.^[52]

Use of Staining Agents in Endoscopy

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.

Table 1 below details the properties and uses of each agent.^[1]

Table 1. Properties of and Clinical Indications for Common Stains Used in Endoscopy^[1] (Open Table in a new window)

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

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. Evidence suggests that there is significant intraobserver and interobserver variation.^{[53, 54]}

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Table 1. Properties of and Clinical Indications for Common Stains Used in Endoscopy^[1]

Table 1. Properties of and Clinical Indications for Common Stains Used in Endoscopy ^[1]

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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