- 1 Background
- 2 Evidence
- 2.1 Systematic review evidence
- 2.1.1 Neoplasia detection rate
- 2.1.2 Neoplasia detection diagnostic accuracy
- 2.1.3 Dysplasia detection rate
- 2.1.4 Intraepithelial neoplasia detection rate
- 2.2 Diagnostic accuracy studies
- 2.1 Systematic review evidence
- 3 Evidence summary and recommendations
- 4 References
- 5 Appendices
Prevention of colorectal cancer (CRC) relies on early and adequate detection of dysplasia. Detection of dysplasia, in turn, depends on the efficacy of endoscopic visualisation of dysplasia and the adequacy of mucosal sampling. These two differing notions reflect a recent paradigm shift in the techniques used in endoscopic surveillance for CRC in inflammatory bowel disease (IBD). There is widespread acceptance of this approach in Australia.
Colonic dysplasia was previously thought to be difficult to visualise endoscopically. Therefore,the practice of taking random biopsies of the colonic mucosa was considered to be the only method of conducting a widespread survey of the colonic mucosa. Random mucosal sampling is now thought to sample only 1% of colonic mucosa, at best.
In order to improve visualisation of the mucosa for subtle dysplasia, the colon should be well prepared and to minimise histological confusion between inflammation and dysplasia, colitis should be in remission at the time of surveillance colonoscopy, wherever possible.
To improve the identification of dysplasia, especially flat-dysplastic lesions associated with colitis, dye-spray chromoendoscopy is recommended. Dye-spray chromoendoscopy is the most intensively studied technique for enhancing visualisation of colonic dysplasia in patients with IBD. Chromoendoscopy improves visualisation of discrete colonic lesions, and is also used to improve evaluation of pit pattern allowing differentiation between benign and dysplastic lesions.
Two dyes commonly used are methylene blue and indigo carmine. Methylene blue is a vital stain that is absorbed by normal colonic mucosa but less so by inflamed or dysplastic tissue. Indigo carmine is a surface-enhancing dye that pools in pits and folds, enhancing visibility of the mucosal architecture.
These dyes have similar yields and can be sprayed topically onto the mucosal surface or via the water pump delivered through the colonoscope working channel. Careful endoscopic examination is then needed to detect alteration in the colonic mucosal architecture.
The diagnostic accuracy of chromoendoscopy for dysplasia in ulcerative colitis (UC) is high. Prospective controlled studies indicate a consistently increased sensitivity of chromoendoscopy versus standard (as opposed to high definition) white-light endoscopy (WLE). A meta-analysis of six studies involving 1277 patients reported the difference in dysplasia detection between chromoendoscopy and WLE to be 7% (95% confidence intervalA measure that quantifies the uncertainty in measurement. When reported as 95% CI, it is the range of values within which we can be 95% sure that the true value for the whole population lies. [CI] 3.2–11.3). The number needed to treat to detect one extra patient with dysplasia or cancer was 14.3 for chromoendoscopy versus WLE. The absolute difference in lesions detected by targeted biopsies was 44% (95% CI 28.6–59.1) and flat lesions was 27% (95% CI 11.2–41.9), both in favour of chromoendoscopy.
An Australian tandem colonoscopy study compared the yield of dysplasia for a first-pass procedure performed using high-definition WLE and the second-pass procedure with methylene blue dye spray. The yield of dysplasia on first-pass WLE with targeted biopsies was 18.0% (95% CI 10.0–26.0, n=16/89 biopsies in 9 subjects), and the yield on second-pass chromoendoscopy and targeted biopsies was 13.5% (95% CI 5.7–21.3, n=10/74 biopsies in 10 subjects). Chromoendoscopy identified 8 subjects from a cohort of 52 with histological dysplasia, six of whom did not have dysplasia identified during the first-pass colonoscopy.Back to top
Narrow-band imaging (NBI), using a light filter, may also increase dysplasia detection. The current SCENIC international consensus statement on surveillance and management of dysplasia in IBD does not advocate NBI in place of either standard- or high-definition WLE. Two controlled studies found NBI not to be superior to WLE and numerically it identified fewer dysplastic lesions. In a randomised parallel-group trial in 112 patients, the proportion of patients with dysplasia detected using NBI was 5 of 56 (9%) versus 5 of 56 (9%) with WLE. A randomised crossover trial in 48 patients found the proportion of patients with dysplasia identified using NBI was 9 of 48 (19%), versus 13 of 48 (27%) with WLE.
The SCENIC consensus statement also recommended that NBI should not replace chromoendoscopy. In four controlled studies the proportion of patients with dysplasia detected was numerically higher with chromoendoscopy than with NBI (0.1–22% difference) but these differences were not statistically significant.
An analysis of pit pattern amongst experts in IBD surveillance found that the inter-observer agreement for pit pattern was significantly higher for chromoendoscopy than for NBI (0.322 versus 0.224, p<0.001). However, in differentiating between non-neoplastic patterns and neoplastic patterns, NBI outperformed chromoendoscopy (kappa 0.65 versus 0.50, p<0.001).Back to top
The relevance of other advanced imaging technologies is under active investigation. Full Spectrum Endoscopy (FUSE) significantly reduced missed dysplasia, compared with forward-viewing colonoscopy, by achieving 330° panoramic views using three contiguous cameras. In an Australian study in patients with IBD, mean dysplasia identified with conventional forward-viewing colonoscope was 0.13, compared with 0.37 with FUSE (p=0.044), with or without chromoendoscopy.
Other advanced imaging techniques such as confocal laser endomicroscopyAn endoscopy procedure that uses a specialised endoscope capable of visualising the mucosal layer of the colon at very high magnification., although more accurate in providing in vivo diagnosis of dysplasia, have limited applicability for ulcerative colitis surveillance. Even without the use of these limited technologies, high-definition WLE with or without NBI or dye-spray chromoendoscopy may identify visible dysplasia without relying on random biopsies.
The European Crohn's and Colitis Organisation recommends that surveillance colonoscopy should take into account local expertise. Chromoendoscopy with targeted biopsies has been shown to increase dysplasia detection rate. Alternatively, random biopsies (quadrantic biopsies every 10 cm) and targeted biopsies of any visible lesion should be performed if WLE is used. High-definition endoscopy should be used if available.Back to top
Targeted versus random biopsies
Targeted biopsies have been shown to be non-inferior to random biopsies. In a tandem colonoscopy study using FUSE, the dysplasia yield of random colonic biopsies was only 0.3% (95% CI 0.0–0.7, n=2/687 biopsies) with no additional unique subjects identified, versus 16.0% (95% CI 10.3–21.6, n=26/163) for targeted biopsies (p<0.0001). Chromoendoscopy therefore increases the yield of dysplasia compared with WLE. However, chromoendoscopy increases the duration of colonoscopy by a mean of 11 minutes.
Random biopsies may identify invisible dysplasia missed by high-definition colonoscopy and chromoendoscopy. Random biopsies are still recommended in patients at high risk of invisible dysplasia, i.e. those with previous colorectal dysplasia, primary sclerosing cholangitis (PSC) or a tubular colon.Back to top
What are the recommended surveillance strategies for surveillance in IBD patients? (SUR3)
Systematic review evidence
A total of 24 studies reported IBD cohorts with varying clinical manifestations (including UC, Crohn’s disease and undefined colitis with and without PSC) in relation to surveillance endoscopy technologies for the detection of colonic neoplasia (including dysplasia, or intraepithelial neoplasia). Seventeen studies were level II evidence and six studies were level III-2 evidence. Two studies were at high-risk of bias, one study was at moderate risk of bias, six studies were at low risk of bias, seven studies were at risk of bias, and eight studies had unclear risk of bias.Back to top
Neoplasia detection rate
Chromoendoscopy versus narrow-band imaging
Three randomised controlled trials (RCTs) reported neoplasia detection rates comparing those in whom chromoendoscopy surveillance was used with those in whom NBI was used. In a study by Bisschops et al (2012) with 68 patients, no significant difference was reported for neoplasia detection in chromoendoscopy versus NBI per patient (0.919) or per lesion (p=0.225) analysis. Pellisé et al (2011) reported no significant difference in the detection of suspicious lesions, on a per-patient (p=0.43) or per-lesion (p=0.644) basis. Watanabe et al (2016) reported identical detection rates (2.3%) for high-grade dysplasia (HGD) or cancer in a trial in 263 patients.
High-definition endoscopy versus standard-definition endoscopyA single study comparing high-definition endoscopy with standard-definition endoscopy reported no significant difference (p=0.50) for the detection of HGD or cancer in a cohort of 369 patients
Chromoendoscopy versus white-light endoscopyNeoplasia detection was reported in a cohort of 236 comparing chromoendoscopy with WLE. This study reported no significant difference between chromoendoscopy and WLE on per-patient (p=1.0) or per-procedure analysis (p=0.80).
Narrow-band imaging versus high-definition endoscopy
Only one cohort study (of 48 patients) reported neoplasia detection comparing NBI to high-definition WLE. On per-lesion analysis, NBI detected a significantly greater proportion of lesions than high-definition endoscopy (p<0.001). The same significant difference was not seen (p=1.0) for per-patient analysis.Back to top
Neoplasia detection diagnostic accuracy
Iacucci et al (2016) reported on the diagnostic accuracy of various modalities for neoplasia detection in a cohort of 75 patients. With a reported detection rate of 28%, high-definition endoscopy had a sensitivity of 93.6% and a specificity of 85%. With a reported detection rate of 22.6%, high-definition dye-chromoendoscopy had a sensitivity of 86.6% and a specificity of 89.6%. With a reported detection rate of 17.3%, high-definition virtual chromoendoscopy had a sensitivity of 92% and a specificity of 73.3%.
Dysplasia detection rateSeveral studies compared two imaging technologies, and found no significant difference in dysplasia detection rates. These included chromoendoscopy versus NBI, high-definition endoscopy versus standard-definition endoscopy, NBI versus WLE, and WLE versus NBI.
Chromoendoscopy versus white-light endoscopy
Three studies reported dysplasia detection using chromoendoscopy compared with WLE. Marion et al (2016) compared chromoendoscopy-targeted biopsies with either WLE-targeted, or random biopsies in a cohort of 68 patients. Chromoendoscopy-targeted biopsy detected significant greater dysplasia than random biopsies (p<0.001) or WLE-targeted biopsies (p=0.001) while WLE-targeted biopsies were no better than random biopsies (p = 0.054). Picco et al (2013) did not report statistical analysis of the differences in HGD and low-grade dysplasia detection rates with chromoendoscopy and WLE in a cohort of 75 patients. Rates of dysplasia detection were similar for targeted WLE biopsies and targeted chromoendoscopy biopsies. In a large cohort of 1000 IBD patients undergoing more than 35,000 biopsies. Moussata et al (2017) reported that the dysplasia detection rate was almost 14 times greater with chromoendoscopy-targeted biopsy than with random biopsy.
High-definition chromoendoscopy versus high-definition white-light endoscopy
Two RCTs reported dysplasia detection comparing high-definition chromoendoscopy with high-definition WLE. Mohammed et al (2015) (n=103) reported that the rate of dysplasia detection per patient was significantly (p=0.04) greater with chromoendoscopy than WLE. Park et al (2015) reported no difference in rates of colitis-associated dysplastic lesions or sporadic adenoma in a trial of 210 participants using the same endoscopy methods.
High-definition forward-viewing colonoscopy versus FUSELeong et al (2017) reported the dysplasia detection miss rate in a crossover RCT in 52 patients with IBD undergoing surveillance for neoplasia. Conventional high-definition forward-viewing colonoscopy missed 71.4% of dysplastic lesions on per lesion analysis, whereas FUSE missed 25.0% per lesion (p<0.0001). Forward-viewing colonoscopy missed 75.0% of dysplastic lesions per subject and FUSE missed 25.0% per subject (p=0.046).
Intraepithelial neoplasia detection rate
Hlavaty et al (2011) reported intraepithelial neoplasia detection in a diagnostic accuracy study of 45 participants. Combining WLE and chromoendoscopy significantly improved the detection of intraepithelial neoplasia in per-patients analysis (p=0.002), compared to random biopsies only. White light endoscopy alone was superior to random biopsies (p=0.04). All other analyses show no significant difference. Günther et al (2011) reported a significant difference (p<0.05) in the rate of detection of flat polypoid lesions (with high-grade intraepithelial neoplasia) in 4819 biopsies taken in 150 participants by confocal endomicroscopy-guided targeted biopsies, compared with either chromoendoscopy or high-definition WLE-guided random biopsies.
Freire et al (2014) reported no significant differences in the rate of intraepithelial neoplasia detection between chromoendoscopy and WLE in an RCT with 162 participants.
Diagnostic accuracy studies
Wanders et al (2017) reported the diagnostic accuracy of chromoendoscopy for dysplasia detection in a cohort of 61 patients. With a reported detection rate of 9.8%, this technique had a sensitivity of 28.6% and a specificity of 86.4%.
Confocal laser endomicroscopyAn endoscopy procedure that uses a specialised endoscope capable of visualising the mucosal layer of the colon at very high magnification.
Rispo et al (2012) reported the diagnostic accuracy of confocal laser endomicroscopyAn endoscopy procedure that uses a specialised endoscope capable of visualising the mucosal layer of the colon at very high magnification. for dysplasia detection in a cohort of 51 patients. With a reported detection rate of 27%, confocal laser endomicroscopyAn endoscopy procedure that uses a specialised endoscope capable of visualising the mucosal layer of the colon at very high magnification. had a sensitivity of 100% and a specificity of 90%.
Wanders et al (2017) also reported the diagnostic accuracy of integrated confocal laser endomicroscopyAn endoscopy procedure that uses a specialised endoscope capable of visualising the mucosal layer of the colon at very high magnification. combined with chromoendoscopy for dysplasia detection in a cohort of 61 patients. With a reported detection rate of 9.8%, these combined techniques had a sensitivity of 42.9% and a specificity of 92.5%.Dlugosz et al (2016) reported the diagnostic accuracy of probe-based confocal laser endoscopy for dysplasia detection in a cohort of 644 patients. With a reported detection rate of 3.0%, probe-based confocal laser endoscopy had a sensitivity of 89% and a specificity of 96%.
High-definition endoscopyThe Dlugosz et al study also reported the diagnostic accuracy of high definition endoscopy for dysplasia detection in a cohort of 644 patients. With a reported detection rate of 3.0%, high-definition endoscopy had a sensitivity of 68%, but a specificity of 97%.
White-light endoscopyMatsumoto et al (2010) reported the diagnostic accuracy of WLE for dysplasia detection in a cohort of 48 patients. With a reported detection rate of 8.3%, WLE had a sensitivity of 78.6% and a specificity of 78.6%.
The Matsumoto study also reported the diagnostic accuracy for autofluorescence imaging for dysplasia detection in a cohort of 48 patients. With a reported detection rate of 8.3%, autofluorescence imaging had a sensitivity of 100%, but a specificity of only 18.2%.Back to top
Evidence summary and recommendations
|Current evidence continues to demonstrate the superiority of chromoendoscopy in the detection of dysplasia in patients with IBD.||II, III-2||, , |
| Targeted biopsies are non-inferior to random biopsies in dysplasia detection.
Invisible dysplasia is defined by histological dysplasia identified by random biopsies and not seen either by white light endoscopy or chromoendoscopy. Patients with both IBD and PSC, prior dysplasia, or intestinal damage (stricture, colonic foreshortening) have an increased risk of invisible dysplasia found on random biopsies.
|II, III-2||, |
|Chromoendoscopy should be incorporated into surveillance procedures, especially in high-risk patients.||A|
|Taking targeted, rather than random, biopsies is the recommended method of identifying dysplasia in patients with inflammatory bowel disease.||B|
|Random biopsies are recommended in IBD patients with PSC, prior dysplasia, and intestinal damage (colonic stricture or foreshortening).||C|
|Standard-definition colonoscopy is not recommended for surveillance procedures, especially in the absence of chromoendoscopy||B|
Proceduralists performing surveillance colonoscopy in patients with IBD should be familiar with and adhere to surveillance guidelines.
IBD surveillance requires high-quality colonoscopy:
Dye spray chromoendoscopy can be applied with a spray catheter or by incorporating dye in the reservoir of the water pump.
Either methylene blue or indigo carmine is an appropriate dye for chromoendoscopy.
Upon identification of invisible dysplasia on random biopsies, confirmation of diagnosis and grade is required by at least two GI pathologists. Chromoendoscopy is then recommended to determine if there is multifocal dysplasia.
Considerations in making these recommendations
Emerging evidence, suggests that digital non-dye-based chromoendoscopy in combination with high definition imaging may replace dye-based chromoendoscopy in expert IBD surveillance centres and be able to reduce overall colonoscopy duration.
The optimal withdrawal time for dye-spray and non-dye digital chromoendoscopy has not been identified.
Whether non-NBI non-dye digital chromoendoscopy provided by other endoscope companies provides similar benefits as NBI remains unknown.
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|PICO question SUR3||Evidence statement form SUR3||Systematic review report SUR3|