Dra. Ana Echarri Piudo
Complejo Hospitalario Universitario de Ferrol
Dra. María Pellisé Urquiza
Hospital Universitari Clínic. Barcelona
Dr. Francisco Javier Gallego Rojo
Hospital de Poniente. El Ejido (Almería)
The chromoendoscopy technique facilitates, via topical dye application, the visualisation, identification and characterisation of premalignant and malignant lesions, by increasing the diagnostic effectiveness of the biopsies when conducting directed biopsies1. When following up on dysplasia in inflammatory bowel disease, it is recommended that a panchromoendoscopy be performed with non-directed staining of the colon mucosa, versus directed staining over a specific lesion, which is generally used for delineating and marking susceptible endoscopic treatment areas2-5.
Dyes used in chromoendoscopy applied in inflammatory bowel disease
When following up on inflammatory bowel disease, basically two types of dyes are used, which we will explain1,2,6.
Absorption dyes: methylene blue
The technique is based on the different absorption capabilities of different cell types. Methylene blue is absorbed rapidly by the normal intestinal mucosa, while its absorption capability in areas with active inflammation or neoplastic changes is poor. In the colon, the lack of methylene blue staining suggest dyplastic, neoplastic or inflammatory changes.
• Concentration used for the staining solution: 0.05–0.1%
• Assessment time: methylene blue initially acts a a contrast dye and is then absorbed, a process that requires approximately 60 seconds. Post-absorption staining patterns are stable for more than 20 minutes.
• Solution preparation (Table I) contrast from the marketed 10-ml 1% ampoules.
– Panchromoendoscopy with spray catheter: 90 ml of water + 10 ml of methylene blue 1%: 100 ml of 0.1% solution. Fill 5 syringes with 20 ml of solution.
– Panchromoendoscopy by wash pump. Prepare 180 ml of water + 20 ml of methylene blue 1%. We will have 200 ml of 0.1% solution to use in the wash pump bottle.
• It is important to clean after staining and to suction the remaining dye for proper interpretation of the staining pattern. Positive staining is described as the presence of blue-coloured mucosa that persists despite irrigation wash.
• Staining with methylene blue is considered safe, since despite of its potential to induce oxidative DNA alteration in the stained tissues in contact with white light7 (usually in the colonoscopy), no increase of carcinogenesis was observed in individuals who were exposed. Patients may experience temporary blue-coloured stool and urine after use.
Contrast dyes: indigo carmine
• The technique is based on contrasting, accentuating or highlighting small changes in the mucosa. Staining patterns, especially if they are combined with magnification, may help to identify hyperplastic or neoplastic changes.
• Concentration used for the staining solution, ranging between 0.1%–0.4%).
• Assessment time: usually, it is important to wait a few seconds so that the indigo is set in the grooves and outlines the lesion. The contrast dyes remain in the colon for a few minutes and then disappear.
• Preparation of the contrast (Table II) solution of 0.1%, from the marketed 20 ml ampoules of indigo carmine 0.4%.
– Panchromoendoscopy with spray catheter: 5–6 20-ml syringes filled with an indigo carmine 0.1% solution, mixed with 15 ml of water + 5 ml of indigo 0.4%, (1 ml of water can be changed to 1 ml of dimethicone if necessary).
– Panchromoendoscopy by wash pump. Prepare 160 ml of 0.1% solution in the water pump bottle and add two 20-ml ampoules of indigo 0.4% + 120 ml of water (1 ml can be changed to dimethicone if necessary).
• Spray catheter; Olympus PW-5L.
• Dyes in staining solution.
• Mucolytic solution (N-acetylcysteine 10% solution).
• Spasmolytics (Buscopan® or glucagon).
There are a series of recommendations for the chromoendoscopy technique published by a group of experts8, that appears in the acronym SURFACE (Table III).
• Strict patient selection
Ideal patients for performing panchromoendoscopy: patients with long-standing inflammatory disease in clinical and mucosal remission.
• Unmask the mucosal surface
It is important to properly prepare in order to achieve a good cleaning. During insertion, any fecal fluid must be suctioned to ensure optimal view. The use of a mucolytic (N-acetylcysteine 10% solution) may be necessary.
Once the caecum is reached, a meticulous inspection of the mucosa must be performed during removal, since it is necessary to have adequate insufflation and, sometimes, postural changes to augment the view.
• Reduce peristaltic waves
When starting the removal process, the use of a spasmolytic such as 20 mg of buscopan i.v. (hyoscine bromide) may be necessary, or 1 mg of glucagon i.v. with additional supplements if necessary.
• Full length staining of the colon
When monitoring inflammatory bowel disease, panchromoendoscopy must be performed.
• Augment detection with dyes
The dyes used in following up on inflammatory bowel disease, as previously mentioned, are indigo carmine and methylene blue, which can be applied by using a spray catheter inserted through the working channel, or via the cleaning system, through a pump, by using the dye solution instead of water.
The spray catheter method is the most utilized: the catheter is inserted until it projects out 2–3 cm from the tip of the colonoscope. The syringe with the dye solution is handled with constant, firm pressure, causing a thin layer of dye that stains the colon mucosa, while the endoscopy is removed with a spiral movement. The stained mucosa is assessed in 20–30 cm sections. Once each section is stained, the excess dye is suctioned, and the colonoscope is reinserted up to the proximal area of the section to be analysed, bearing in mind the typical characters of each dye.
• Crypt architecture analysis
The surface of all lesions viewed in a panchromoendoscopy must be analysed and characterised according to their staining pattern (Kudo-pit Pattern Classification). The staining pattern analysis is enabled with the use of magnification and high-definition.
There are non-neoplastic staining patterns
(I and II) and others (III-IV) (Fig. 1) that suggest the presence of neoplastic intraepithelial lesions or carcinomas.
• Endoscopic targeted biopsies
It is necessary to perform a biopsy on all mucosa alterations viewed with chromoendoscopy. The specificity of the directed biopsies for detecting dysplasia is greater with a reduced total number of biopsies/endoscopy.
Limitations of the chromoendoscopy
• Patients with multiple pseudopolyps.
These are subjects who have difficulty during follow-up with chromoendoscopy, since it is very difficult to assess all existing lesions within a reasonable examination time.
• Introduction of the chromoendoscopy during the follow-up of inflammatory bowel disease is associated with its great capability of detecting dysplasia, versus the conventional endoscopy with multiple biopsies, although all tests have been performed with conventional equipment. With the development of high-definition equipment and its circulation, it will be necessary to reassess the panchromoendoscopy within this context.
The ability to augment the size of the mucosal surface of the lesion in real time, providing a detailed visualisation. It is generally used with chromoendoscopy and the combination of both techniques permits the analysis of the staining patterns1.
High-definition magnification endoscopes
Conventional endoscopes are equipped with imaging sensors or chips (charged coupled device [CCD]) of 100,000–300,000 pixels. The pixel density is directly related to the image resolution. Technological advances have been able to increase the pixel density in the CCD, by reducing its size and increasing the number of pixels, thus developing high-definition or high-resolution endoscopes up to a million pixels in their CCDs.
CDs, located at the tip of the endoscope, generate electrical signals in response to light that are transmitted through cables to the video processor, where they become an image. Standard video processors generate 480–576 lines per screen. High-definition endoscopes that require high-definition monitors and video processors generate more than 1,080 lines per screen with high increase of resolution.
Standard endoscopes digitally enables the image to be amplified 30–35 times. Magnification endoscopes amplify up to 150 time thanks to a mobile lens systems located at the tip of the endoscope (optic zoom). Via focal remote control, the mucosal surface can be examined from short distances, without losing focus while augmenting the image1,2.
• High-definition magnification endoscopes.
– Olympus®: CF-Q160ZI (magnification) or CF-H260AZL/l (magnification and high-definition).
– Fuji®: EC-590ZW (magnification and high definition).
– Pentax®: EC-3830LZ (magnification and high definition).
• CAP: Disposable Distal Attachment (Fig. 2).
The use of a transparent CAP at the tip of the endoscope stabilises the focal distance between the lens and the tissue (maintaining a constant distance of 2–3 mm between the mucosa and the endoscope), and improves the quality of the image.
The CAP used in chromoendoscopy and magnification improves visualisation of the lesions without interfering in the endoscopic process.
The magnification technique is used in combination with chromoendoscopy. Once a lesion is detected using chromoendoscopy, in order to properly asses the staining with magnification, it is important to approach the lesion closely (using the CAP enables stability of the position), activate the magnification system and assess the lesion based on its staining pattern.
Generally, regular staining patterns (I and II) are associated with normal mucosa or hyperplastic lesions, while unstructured patterns (III-V) may be associated with neoplastic lesions. With the help of this classification, the endoscopist may predict the histology of the lesion with high diagnostic precision.
Presently, there are three chromoendoscopy techniques performed without the need of dyes. These are called virtual chromoendoscopies. The objective of these techniques is similar to chromoendoscopy, namely the augmented visualisation of lesions not visible with conventional endoscopy and their characterisation1-3,6.
However, these are used less widely than chromoendoscopy since their use in the follow-up of inflammatory bowel disease has not shown any superiority, versus the conventional endoscopy, in detecting neoplastic lesions9,10.
• Narrow-band Imaging System (NBI) (Olympus).
• Fujinon Intelligent Color Enhancement (FICE).
• iScan (Pentax).
Narrow band imaging
Is an endoscopic visualisation system based on a modification of the bandwidth of the light emitted. It is based on the use of filters that narrow the wavelength of light emitted towards the spectrum of blue light (415 nm) and green light (540 nm), increasing the relative intensity of the blue light band, which has a lesser wavelength and less light penetration (Fig. 3), thus enabling visualisation of the capillary pattern of the colonic lesions and its architectural modifications (Fig. 4).
The system is included in a conventional colonoscopy, in which, by pressing a button located on the control head, the conventional optical system quickly changes to a NBI light beam.
FICE System and i-Scan system
The FICE System and i-Scan system are based on the same physical principle, but do not use optical filters in the endoscope. They use technologies that digitally intensify images thanks to the use of a software that, via image processing algorithms in the video processor, intensifies mucosal surface structures by selecting wavelengths with reconstituted virtual images.
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