Patients with longstanding, extensive ulcerative colitis are at increased risk of developing colorectal cancer. The risk is lower than previously reported, but colonoscopic surveillance is recommended still to detect intraepithelial neoplasia early and to reduce colitis-associated mortality. Surveillance relies on the detection of premalignant dysplastic tissue. Here, adenomatous changes should be differentiated from colitis-associated dysplasia, because the management is fundamentally different. Adenomas can be removed safely endoscopically, whereas multiple low-grade or at least 1 high-grade, colitis-associated dysplastic tissue requires proctocolectomy.
Detection of Adenomas and Colitis-Associated Dysplasia in Inflammatory Bowel Disease
Adenomas occur usually as clearly demarcated lesions using white light colonoscopy. Adenomas can be either polypoid, flat, or depressed. The development follows the adenoma–carcinoma sequence and adenomas are increasingly prevalent with age.
Colitis-associated neoplasia can occur in addition to adenomas in patients with longstanding ulcerative colitis. These lesions are triggered by inflammation and the macroscopic appearances are often flat and multifocal. The borders of the lesions are often ill defined and biopsies of the subtle changes as well as of the surrounding mucosa are recommended.
There are no clear-cut, endoscopic, histologic, or immunohistochemical discriminators to permit absolute accurate stratification between adenomas and colitis-associated dysplasia. However, optimal diagnosis combines endoscopic and histologic features. The term “intraepithelial neoplasia” in accordance to the new Vienna classification was established, which summarizes adenomas and colitis-associated neoplasia.
Multiple, untargeted, random biopsies are recommended to diagnose intraepithelial neoplasia. Four random biopsies per site over 9 sites throughout the colon should be undertaken, with increased sampling from the rectosigmoid and with additional biopsies from raised or suspicious lesions. However, this approach is time consuming and dysplastic lesions might still be overlooked.
Chromoendoscopy can help greatly to identify premalignant and malignant lesions. A multitude of randomized, controlled trials, as well as a recently published meta-analysis, have underscored the value of chromoendoscopy. Chromoendoscopy-guided biopsies have a significantly higher diagnostic yield compared with random biopsies. Furthermore, magnifying endoscopy enables analysis of surface structure, whereas confocal laser endomicroscopy (CLE) enables in vivo histology, which further decreases the number of biopsies needed per patient.
Chromoendoscopy
Intravital staining is the oldest and simplest method used to improve the diagnosis of epithelial changes. Chromoendoscopy, vital staining, and contrast endoscopy are synonyms for the same technique: Dye solutions are applied to the mucosa of the gastrointestinal tract, enhancing the recognition of details to uncover mucosal changes not perceivable by purely optical methods before targeted biopsy and histology ( Fig. 1 ). Three classes of dyes used for chromoendoscopy are mainly differentiated.
Contrast Dyes
Contrast dyes coat the colonic mucosal surface and highlight tissue architecture because of the higher contrast of pooled dye within the small grooves between the colonic crypts and within the colonic pits. An example is indigo carmine, which is commonly used throughout the gastrointestinal tract. When indigo carmine (concentration, 0.2%–0.4%) is sprayed on the surface, the pit pattern of the colonic surface becomes evident, and disruption, indicating inflammation or changes of the normal pattern indicating hyperplasia or intraepithelial neoplasia, can be readily identified. Contrast staining lasts for few minutes and disappears owing to dilution throughout the colon.
Absorptive Dyes
Absorptive dyes are absorbed by different cells to different degrees, highlighting distinct cell types. An example is methylene blue (concentration, 0.1%), which avidly stains noninflamed mucosa, but is poorly taken up by areas of active inflammation and intraepithelial neoplasia. Methylene blue reacts initially as a contrast stain and is subsequently absorbed. The absorption requires about 60 seconds. However, stable staining patterns occur, which allows examination times of up to 20 minutes of the stained area (see Fig. 1 ).
Reactive Dyes
The binding of reactive coloring agents with certain mucosal areas is used to identify reactions. Their use is less common and their diagnostic relevance is low.
In patients with ulcerative colitis, the most commonly used dyes are indigo carmine and methylene blue. Chromoendoscopy has 2 main goals. First, it improves the detection of subtle colonic lesions, raising the sensitivity of the endoscopic examination; this is important in ulcerative colitis, because flat dysplastic lesions can be difficult or impossible to detect with white light endoscopy. Second, once a lesion is detected, chromoendoscopy can improve lesion characterization, increasing the specificity of the examination. This can be further refined with magnifying and/or high-definition colonoscopes. Surface analysis of colorectal lesions using magnifying endoscopes has led to new optical impression for endoscopists. First in 1996, Kudo and associates described that some of the regular staining patterns are often seen in hyperplastic polyps or normal mucosa, whereas unstructured surface architecture was associated with malignancy. Also, the kind of adenoma (tubular or villous) can be seen by detailed inspection. This experience has led to a categorization of the different staining patterns in the colon. The so-called pit-pattern classification differentiated 5 types and several subtypes. Types 1 and 2 are staining patterns predicting non-neoplastic lesions, whereas types 3 to 5 are predicting neoplastic lesions. With the help of this classification, the endoscopist can predict histology with good accuracy in patients with ulcerative colitis.
Several prospective, randomized trials using methylene blue or indigo carmine for panchromoendoscopy in patients with longstanding ulcerative colitis have shown the unique benefit of chromoendoscopy for the diagnosis of intraepithelial neoplasia ( Table 1 ).
| Author | Year | Country | Dye | Staining | Endoscopy | Design | No of Patients | Patients with Dysplasia | Outcome Chromo vs Standard |
|---|---|---|---|---|---|---|---|---|---|
| Kiesslich et al | 2003 | Germany | MB | Pancolonic | Magnification | Randomized 1:1 | 165 | 19 | 32 vs 10 dysplastic lesions |
| Matsumoto et al | 2003 | Japan | IC | Pancolonic | WLE | Prospective cohort | 57 | 12 | 86% vs 38% sensitivity |
| Rutter et al | 2004 | UK | IC | Pancolonic | WLE | Prospective cohort | 100 | 7 | 9 vs 2 dysplastic lesions |
| Hurlstone et al | 2005 | UK | IC | Targeted | Magnification | Prospective cohort | 700 | 81 | 69 vs 24 dysplastic lesions |
| Kiesslich et al | 2007 | Germany | MB | Pancolonic | CLE | Randomized 1:1 | 153 | 15 | 19 vs 4 dysplastic lesions |
| Marion et al | 2008 | US | MB | Pancolonic | WLE | Tandem colonoscopy | 102 | 19 | 17 vs 3 patients with dysplastic lesions |
| Günther et al | 2011 | Germany | IC | Pancolonic | CE | Randomized 1:1:1 | 150 | 6 | 0 vs 6 patients with dysplastic lesions |
| Hlavaty et al | 2011 | Slovakia | IC | Pancolonic | CE | Tandem colonoscopy | 30 | 7 | 0 vs 7 dysplastic lesions |
Chromoendoscopy
Intravital staining is the oldest and simplest method used to improve the diagnosis of epithelial changes. Chromoendoscopy, vital staining, and contrast endoscopy are synonyms for the same technique: Dye solutions are applied to the mucosa of the gastrointestinal tract, enhancing the recognition of details to uncover mucosal changes not perceivable by purely optical methods before targeted biopsy and histology ( Fig. 1 ). Three classes of dyes used for chromoendoscopy are mainly differentiated.
Contrast Dyes
Contrast dyes coat the colonic mucosal surface and highlight tissue architecture because of the higher contrast of pooled dye within the small grooves between the colonic crypts and within the colonic pits. An example is indigo carmine, which is commonly used throughout the gastrointestinal tract. When indigo carmine (concentration, 0.2%–0.4%) is sprayed on the surface, the pit pattern of the colonic surface becomes evident, and disruption, indicating inflammation or changes of the normal pattern indicating hyperplasia or intraepithelial neoplasia, can be readily identified. Contrast staining lasts for few minutes and disappears owing to dilution throughout the colon.
Absorptive Dyes
Absorptive dyes are absorbed by different cells to different degrees, highlighting distinct cell types. An example is methylene blue (concentration, 0.1%), which avidly stains noninflamed mucosa, but is poorly taken up by areas of active inflammation and intraepithelial neoplasia. Methylene blue reacts initially as a contrast stain and is subsequently absorbed. The absorption requires about 60 seconds. However, stable staining patterns occur, which allows examination times of up to 20 minutes of the stained area (see Fig. 1 ).
Reactive Dyes
The binding of reactive coloring agents with certain mucosal areas is used to identify reactions. Their use is less common and their diagnostic relevance is low.
In patients with ulcerative colitis, the most commonly used dyes are indigo carmine and methylene blue. Chromoendoscopy has 2 main goals. First, it improves the detection of subtle colonic lesions, raising the sensitivity of the endoscopic examination; this is important in ulcerative colitis, because flat dysplastic lesions can be difficult or impossible to detect with white light endoscopy. Second, once a lesion is detected, chromoendoscopy can improve lesion characterization, increasing the specificity of the examination. This can be further refined with magnifying and/or high-definition colonoscopes. Surface analysis of colorectal lesions using magnifying endoscopes has led to new optical impression for endoscopists. First in 1996, Kudo and associates described that some of the regular staining patterns are often seen in hyperplastic polyps or normal mucosa, whereas unstructured surface architecture was associated with malignancy. Also, the kind of adenoma (tubular or villous) can be seen by detailed inspection. This experience has led to a categorization of the different staining patterns in the colon. The so-called pit-pattern classification differentiated 5 types and several subtypes. Types 1 and 2 are staining patterns predicting non-neoplastic lesions, whereas types 3 to 5 are predicting neoplastic lesions. With the help of this classification, the endoscopist can predict histology with good accuracy in patients with ulcerative colitis.
Several prospective, randomized trials using methylene blue or indigo carmine for panchromoendoscopy in patients with longstanding ulcerative colitis have shown the unique benefit of chromoendoscopy for the diagnosis of intraepithelial neoplasia ( Table 1 ).
| Author | Year | Country | Dye | Staining | Endoscopy | Design | No of Patients | Patients with Dysplasia | Outcome Chromo vs Standard |
|---|---|---|---|---|---|---|---|---|---|
| Kiesslich et al | 2003 | Germany | MB | Pancolonic | Magnification | Randomized 1:1 | 165 | 19 | 32 vs 10 dysplastic lesions |
| Matsumoto et al | 2003 | Japan | IC | Pancolonic | WLE | Prospective cohort | 57 | 12 | 86% vs 38% sensitivity |
| Rutter et al | 2004 | UK | IC | Pancolonic | WLE | Prospective cohort | 100 | 7 | 9 vs 2 dysplastic lesions |
| Hurlstone et al | 2005 | UK | IC | Targeted | Magnification | Prospective cohort | 700 | 81 | 69 vs 24 dysplastic lesions |
| Kiesslich et al | 2007 | Germany | MB | Pancolonic | CLE | Randomized 1:1 | 153 | 15 | 19 vs 4 dysplastic lesions |
| Marion et al | 2008 | US | MB | Pancolonic | WLE | Tandem colonoscopy | 102 | 19 | 17 vs 3 patients with dysplastic lesions |
| Günther et al | 2011 | Germany | IC | Pancolonic | CE | Randomized 1:1:1 | 150 | 6 | 0 vs 6 patients with dysplastic lesions |
| Hlavaty et al | 2011 | Slovakia | IC | Pancolonic | CE | Tandem colonoscopy | 30 | 7 | 0 vs 7 dysplastic lesions |
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