Dra. Beatriz Sicilia
Hospital Universitario de Burgos
Dra. Ana Echarri Piudo
Complejo Hospitalario Universitario de Ferrol

INTRODUCTION

The chromoendoscopy technique, whether using dye (DCE) or without dye (virtual chromoendoscopy – VCE), facilitates, the visualisation, identification and characterisation of premalignant and malignant lesions, by increasing the diagnostic effectiveness of the biopsies when conducting directed biopsies1. Both techniques can be combined with magnification if available to increase the cost-effectiveness of optical diagnosis of lesions during the examination.

In the screening of our patients with inflammatory bowel disease for colitis-associated cancer, it is advisable to carry out a complete chromoendoscopy of the entire colonic mucosa (panchromoendoscopy), versus directed staining over a specific lesion, which is generally used for delineating and marking susceptible endoscopic treatment areas2-5.

DYE-BASED CHROMOENDOSCOPY (DCE)

1. Dyes used

When following up on colitis-associated cáncer screening of our patients with long-duration 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. This absorption dye is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency.
  • 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
Tabla_SEC1_01_01_05_T01

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 solution of 0.1%, from the marketed 20 ml ampoules of indigo carmine 0.4%. (Table II) This dye can also be easily prepared using 0.4% magistral formula, adding 1 g indigo carmine to 250 ml sterile water prepared in the hospital pharmacy as detailed in Appendix 1.
Tabla_SEC1_01_01_05_T02

2. Necessary Material

  • Spray catheter; Olympus PW-5L.
  • Dyes in staining solution.
  • Mucolytic solution (N-acetylcysteine 10% solution).
  • Spasmolytics (Buscopan® or glucagon).

3. Technique. Protocol

There are a series of recommendations for the chromoendoscopy technique published by a group of experts8, that appears in the acronym SURFACE (Table III).

Tabla_SEC1_01_01_05_T03

• Strict patient selection
Ideal patients for performing panchromoendoscopy: patients with long-standing colonic inflammation with disease of a duration of more than 8 years (left-sided (E2) or extensive (E3) ulcerative colitis or Crohn’s disease involving more than 1/3 of the colon in clinical remission and mucosal healing (UCEIS 0-1/SES-CD 0-1)). Patients with ulcerative proctitis should be excluded and those with associated primary sclerosing cholangitis should be screened a year after diagnosis. (see II.4 Endoscopy in the follow-up of dysplasia in the Intestinal Inflammatory Disease).

• 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 as long as there is mucosal healing (UCEIS 0-1/SES-CD 0-1). Staining of mucosa with endoscopically active inflammation is not recommended due to distortion of endoscopic images and the difficulty of the anatomopathological differential diagnosis of inflammation-associated dysplasia versus cancer-associated dysplasia.

• 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. When describing lesions, we must avoid terms such as dysplasia-associated lesions or masses (DALM) or “adenoma like”. (See chapter III.1 Optical diagnosis, resection and follow-up of lesions with dysplasia in the screening of colorectal cancer in patients with IBD).

• 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. In practice, with this technique and using high-definition endoscopes, what we will always try to achieve is endoscopic full-thickness resection (R0) of all lesions we see, so biopsies are relegated to lesions not eligible for endoscopic full-thickness excision or those we need to further typify before making a therapeutic decision (See chapter III.1 Optical diagnosis, resection and follow-up of lesions with dysplasia in the screening of colorectal cancer in patients with IBD).

 

VIRTUAL CHROMOENDOSCOPY (VCE)

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 with dye, namely the augmented visualisation of lesions not visible with conventional endoscopy and their characterisation1-3,6.

  • 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. 2), thus enabling visualisation of the capillary pattern of the colonic lesions and its architectural modifications (Fig. 3).

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 and i-Scan Systems

Both FICE and i-Scan systems are based on the same physical principle, but don’t use optical filter inside the endoscope. They use digital image intensification technologies thanks to the use of software that, through image processing algorithms in the video processor, intensifies mucosal surface structures by selecting wavelengths with reconstitution of virtual images.

MAGNIFICATION ENDOSCOPY

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 (HDWLE) 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.

On the other hand, we must not confuse the enlargement of lesions (already possible with standard endoscopes that can digitally magnify the image by 30-35 times) with magnification, which is only available in certain endoscopes and which increases the definition of the image 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 endoscopes are now available in most endoscopy units in our country; however, the availability of magnification in our hospitals is far from being the norm.

Equipment

  • 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. 4). 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.

Technique

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.

STANDARDISED ENDOSCOPY REPORT

Regardless of the technique used, DCE or VCE, whether or not associated with magnification, a good chromoendoscopy report should contain all the information described above11:

  • Assessment of mucosal healing (UCEIS /SES-CD).
  • Assessment of colon cleansing using objective scale (e.g.: Boston scale by sections).
  • Presence and/or absence of pseudopolyps.
  • Morphology of lesions according to the modified Paris classification. Description of borders and presence and/or absence of ulceration.
  • Crypt pattern of lesions according to Kudo classification.
  • Resectability of lesions, with description of type of excision.

BIBLIOGRAPHY

  1. Classen M, Tytgat G, Lightdale C, editors. Advanced Imaging in Endoscopy Gastroenterological Endoscopy. Stuttgart: Thieme; 2010.
  2. Iacucci M, Panaccione R, Ghosh S. Advances in novel diagnostic endoscopic imaging techniques in inflammatory bowel disease. Inflamm Bowel Dis. 2013; 0: 1-8
  3. Tontini GE, Vecchi M, Neurath MF, Neumann H. Review article: newer optical and digital chromoendoscopy techniques vs. dye-based chromoendoscopy for diagnosis and surveillance in inflammatory bowel disease. Aliment Pharmacol Ther. 2013; 38: 1198-208.
  4. Cairns S, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJW, Evans GD, et al. Developed on behalf of The British Society of Gastroenterology and the Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010; 59: 666-90.
  5. Van Assche G, Dugnass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis: Special situations. J Crohn Colitis. 2013; 7: 1-33.
  6. Kiesslich R, Neurath M. Chromoendoscopy in inflammatory bowel disease. Gastroenterol Clin N Am. 2012, 41: 291-302.
  7. Olliver JR, Wild CP, Sahay P, Dexter S, Hardie LJ. Chromoendoscopy with methylene blue and associated DNA damage in Barrett’s oesophagus. Lancet. 2003; 362(9381): 373-4.
  8. Rutter M, Bernstein C, Matsumoto T, Kiesslich R, Neurath MF. Endoscopic appearance of dysplasia in ulcerative colitis and the role of staining. Endoscopy. 2004; 36: 1109-14.
  9. Bisschops R, East JE, Hassan C, Hazewinkel Y, Kamiński MF, Neumann H, et al. Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2019. Endoscopy. 2019 Dec;51(12):1155-1179
  10. Murthy, S.K.; Feuerstein, J.D.; Nguyen, G.C.; Velayos, F.S. AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review. Gastroenterology 2021, 161, 1043–1051.e4
  11. Adamina M, Feakins R, Iacucci M, Spinelli A, Cannatelli R, D’Hoore A, et al. ECCO Topical Review Optimising Reporting in Surgery, Endoscopy, and Histopathology. J Crohns Colitis. 2021 Jul 5;15(7):1089-1105

Appendix 1: Preparation of indigo carmine 0.4%

Indigo carmine ………….. 1 g
Sterile water……………. 250 ml

MODUS OPERANDI:

  1. Weigh 1 g of indigo carmine in a beaker.
  2. Add 50 ml of sterile water from the 250 ml bottle.
  3. After complete dissolution, load the indigo carmine into a syringe and transfer to the 250 ml bottle of sterile water. (Filtration is recommended for sterilisation. Sometimes the filter gets clogged).
  4. Wrap in aluminium foil to protect from light.

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