Chromoendoscopy as an Adjunct to Colonoscopy - CAM 20184

Description:
Chromoendoscopy refers to the use of dyes or stains during endoscopy to enhance tissue differentiation or characterization. When used with colonoscopy, the intent is to increase the sensitivity of the procedure by facilitating the identification of mucosal abnormalities. There are 2 types of chromoendoscopy: one involves actual spraying of dyes or stains through the working channel of an endoscope; the other, known as virtual chromoendoscopy, uses a computer algorithm to simulate different colors of light that result from dye or stain spraying.

Chromoendoscopy
For individuals who have an average risk of colorectal cancer (CRC) who receive chromoendoscopy, the evidence includes a randomized controlled trial (RCT) evaluating this population. Relevant outcomes are overall survival, disease-specific survival, test validity, and change in disease status. The single RCT did not find that high-definition chromoendoscopy identified more clinically meaningful lesions than high-definition white-light colonoscopy. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have an increased risk of CRC who receive chromoendoscopy, the evidence includes multiple RCTs, back-to-back colonoscopy studies, and systematic reviews. Relevant outcomes are overall survival, disease-specific survival, test validity, and change in disease status. A Cochrane systematic review of trials comparing chromoendoscopy with standard colonoscopy in high-risk patients (but excluding those with inflammatory bowel disease) found significantly higher rates of adenoma detection and rates of 3 or more adenomas with chromoendoscopy than with standard colonoscopy. The evidence for detecting larger polyps, defined as greater than 5 mm or greater than 10 mm, is less robust. While 1 study reported a significantly higher detection rate for polyps greater than 5 mm, no studies reported increased detection of polyps greater than 10 mm. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have inflammatory bowel disease who receive chromoendoscopy, the evidence includes observational studies and meta-analyses of observational data. Relevant outcomes are overall survival, disease-specific survival, test validity, and change in disease status. One meta-analysis found a statistically significant higher yield of chromoendoscopy over white-light colonoscopy for detecting dysplasia. This evidence established that chromoendoscopy improves polyp detection rates; however, it is unclear whether the additional polyps detected are clinically important and, therefore, whether improved polyp detection rates will translate into improved health outcomes. Moreover, there are concerns about comparison groups used in some of these trials. It is uncertain whether the control groups received optimal colonoscopy; therefore, the improved detection rates by chromoendoscopy might have been a function of suboptimal standard colonoscopy. The evidence is insufficient to determine the effects of the technology on health outcomes.

Virtual Chromoendoscopy
For individuals who have an average risk of CRC who receive virtual chromoendoscopy, the evidence includes several RCTs and a meta-analysis. Relevant outcomes are overall survival, disease-specific survival, test validity, and change in disease status. The available RCTs have not found that virtual chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies assessing the impact of virtual chromoendoscopy on CRC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have an increased risk of CRC who receive virtual chromoendoscopy, the evidence includes several RCTs and a meta-analysis. Relevant outcomes are overall survival, disease-specific survival, test validity, and change in disease status. The available RCTs have not found that virtual chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies assessing the impact of virtual chromoendoscopy on CRC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have inflammatory bowel disease who receive virtual chromoendoscopy, the evidence includes an RCT and nonrandomized comparative study. Relevant outcomes are overall survival, disease-specific survival, test validity, and change in disease status. The RCT found a significantly greater likelihood that virtual chromoendoscopy would correctly identify the extent of disease inflammation than standard colonoscopy but no significant difference in the likelihood of identifying disease activity. A retrospective cohort study found that targeted biopsy resulted in a higher rate of neoplasia detection regardless of the endoscopy method used. There is a lack of studies assessing the impact of virtual chromoendoscopy CRC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background
Colonoscopy
Colonoscopy, a procedure during which colonic and rectal polyps can be identified and removed, is considered the criterion standard test for colorectal cancer (CRC) screening and diagnosis of colorectal disease. However, colonoscopy is an imperfect procedure. A systematic review by van Rijn et al. (2006) pooled findings from tandem (i.e., back-to-back) colonoscopy studies and found that 22% of polyps were missed on the first colonoscopy.¹ Most polyps missed were small and thus had a lower risk of becoming cancerous. The pooled miss rate by polyp size was 2% for polyps 10 mm and larger, 13% for polyps 5 to 10 mm, and 26% for polyps 1 to 5 mm.

Adjunctive Procedures
Several adjunct endoscopic techniques, including chromoendoscopy, could enhance the sensitivity of colonoscopy. Chromoendoscopy, also known as chromoscopy and chromocolonoscopy, refers to the application of topical stains or dyes during endoscopy to enhance tissue differentiation or characterization and facilitate identification of mucosal abnormalities. Chromoendoscopy may be particularly useful for detecting flat or depressed lesions. Standard colonoscopy uses white-light to view the colon. In chromoendoscopy, stains are applied, resulting in color highlighting of areas of surface morphology of epithelial tissue. The dyes or stains are applied via a spray catheter that is inserted down the working channel of the endoscope. Chromoendoscopy can be used in the whole colon (pancolonic chromoendoscopy) on an untargeted basis or can be directed to a specific lesion or lesions (targeted chromoendoscopy). Chromoendoscopy differs from endoscopic tattooing in that the former uses transient stains, whereas tattooing involves the use of a long-lasting pigment for future localization of lesions.

Stains and dyes used in chromoendoscopy can be placed in the following categories:

Absorptive stains are preferentially absorbed by certain types of epithelial cells.
Contrast stains seep through mucosal crevices and highlight surface topography.
Reactive stains undergo chemical reactions when in contact with specific cellular constituents, which results in a color change.

Indigo carmine, a contrast stain, is the most commonly used stain with colonoscopy to enhance the detection of colorectal neoplasms. Several absorptive stains are also used with colonoscopy. Methylene blue, which stains the normal absorptive epithelium of the small intestine and colon, has been used to detect colonic neoplasia and to aid in the detection of intraepithelial neoplasia in patients with chronic ulcerative colitis. In addition, crystal violet (also known as gentian violet) stains cell nuclei and has been applied in the colon to enhance visualization of pit patterns (i.e., superficial mucosal detail). Reactive stains are primarily used to identify gastric abnormalities and are not used with colonoscopy.

Potential applications of chromoendoscopy as an adjunct to standard colonoscopy include:

Diagnosis of colorectal neoplasia in symptomatic patients at increased risk of CRC due to family history of CRC, personal history of adenomas, etc.
Identification of mucosal abnormalities for targeted biopsy as an alternative to multiple random biopsies in patients with inflammatory bowel disease.
Screening the general population for CRC.

The equipment used in regular chromoendoscopy is widely available. Several review articles and technology assessments have indicated that, although the techniques are simple, the procedure (e.g., the concentration of dye and amount of dye sprayed) is variable, and thus classification of mucosal staining patterns for identifying specific conditions is not standardized.

Virtual chromoendoscopy (also called electronic chromoendoscopy) involves imaging enhancements with endoscopy systems that could be an alternative to dye spraying. One system is the Fujinon Intelligent Color Enhancement feature (Fujinon Inc.). This technology uses postprocessing computer algorithms to modify the light reflected from the mucosa from conventional white-light to various other wavelengths.

Regulatory Status
In 2014, the Fujifilm EPX-4440HD Digital Video Processor with Fujinon Intelligent Color Enhancement (FICE^®) and Light Source was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA documents stated that FICE^® could be used to supplement white-light endoscopy but is not intended to replace histopathologic sampling as a means of diagnosis.

In 2013, the i-SCAN™ (Pentax), used for virtual chromoendoscopy, was cleared for marketing by FDA through the 510(k) process.² This digital image enhancement technology is part of the Pentax EPK-i5010 Video Processor. The i-SCAN™ has several modes that digitally enhance images in real time during endoscopy. The FDA documents stated that i-SCAN™ is intended as an adjunct following white-light endoscopy but not intended to replace histopathologic analysis.

FDA product codes: GCT, PEA, FET (endoscopes and accessories).

No dye or stain product has been specifically approved by FDA for use in chromoendoscopy.

Related Policies
20187 Confocal Laser Endomicroscopy
60132 Virtual Colonoscopy/CT Colonography

Policy:
Chromoendoscopy is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY as an adjunct to diagnostic or surveillance colonoscopy.

Virtual chromoendoscopy isinvestigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY as an adjunct to diagnostic or surveillance colonoscopy.

Policy Guidelines
Coding
See the Codes table for details

Benefit Application:
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational, and, thus, these devices may be assessed only on the basis of their medical necessity.

Rationale
Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.

The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.

Chromoendoscopy for Patients at Average Risk of Colorectal Cancer Undergoing Colonoscopy
Clinical Context and Test Purpose
The purpose of chromoendoscopy in patients at average risk of colorectal cancer (CC) is to inform a decision whether to proceed to the standard of care or to invasive treatment.

The question addressed in this evidence review is: Does the use of chromoendoscopy improve the net health outcome in individuals at average risk of CC?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals at average risk of CC.

Interventions
The test being considered is chromoendoscopy. Chromoendoscopy involves the application of dyes to facilitate tissue visualization.

Comparators
The following test is currently being used to diagnose or monitor CC: standard white-light colonoscopy.

Outcomes
The general outcomes of interest are tumor detection and tumor recurrence for CC.

Study Selection Criteria
For the evaluation of the clinical validity of the tests included in this review, studies that meet the following eligibility criteria were considered:

Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
Included a suitable reference standard (describe the reference standard)
Patient/sample clinical characteristics were described
Patient/sample selection criteria were described.

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
There are few trials evaluating chromoendoscopy for CC screening of average-risk individuals. Some trials have included mixed populations of patients undergoing screening and diagnostic colonoscopy but have not reported results separately for each group. For example, in a study by Pohl et al. (2011), although approximately half of the study participants were undergoing screening colonoscopy, the group results were not reported separately.³

Randomized Controlled Trials
One large randomized trial by Kahi et al. (2010) evaluated 660 patients at 4 centers in the U.S.⁴ Those eligible for inclusion had an average risk of CC, were ages 50 years and older, and were undergoing screening colonoscopy for the first time. Participants were randomized to chromoendoscopy with indigo carmine dye (n = 321) or to standard colonoscopy (n = 339). The primary outcomes were the proportion of patients with at least 1 adenoma and the mean number of adenomas per patient, which were then compared between groups. No significant between-group differences were noted for either outcome. A total of 178 (55.5%) subjects in the chromoendoscopy group and 164 (48.4%) subjects in the standard colonoscopy group had 1 or more adenomas (p = .07). The mean number of adenomas per subject that were less than 5 mm in diameter differed significantly between groups (0.8 for chromoendoscopy versus 0.7 for standard endoscopy; p = .03). The difference between groups in the mean number of adenomas 10 mm or larger was not statistically significant (0.11 for chromoendoscopy versus 0.12 for standard colonoscopy; p = .70). Thirty-nine (12%) subjects in the chromoendoscopy group and 49 (15%) subjects in the standard colonoscopy group had 3 or more adenomas; the difference between groups was not statistically significant (p = .40). The trialists stated that the high rate of adenoma detection in both groups might have been due to the use of high-definition colonoscopy.

Pohl et al. (2011) in Germany published a large randomized controlled trial (RCT) comparing pancolonic chromoendoscopy using indigo carmine dye with standard colonoscopy.³ The trial included patients presenting for primary CC screening (51%) and patients undergoing diagnostic colonoscopy (49%). Patients with known inflammatory bowel disease (IBD), overt bleeding, polyposis syndromes, or a history of surgical resection were excluded. A total of 1024 patients were randomized; 16 dropped out, leaving 496 patients in the chromoendoscopy group and 512 patients in the standard colonoscopy (i.e., control) group. The primary study outcome (the proportion of patients with adenomas) differed significantly between groups (p = .002). A total of 223 (46.2%) patients in the chromoendoscopy group and 186 (36.3%) in the standard colonoscopy group had at least 1 adenoma identified. The trial also reported differences in lesion detection rates by lesion size. For lesions 5 mm or larger, 151 (30.4%) patients in the chromoendoscopy group and 119 (23.2%) patients in the standard colonoscopy group had at least 1 adenoma; the difference between groups was statistically significant (p = .012). For lesions 10 mm or larger, 64 (12.9%) patients in the chromoendoscopy group and 48 (9.4%) patients in the standard colonoscopy group had at least 1 adenoma. The between-group difference in the detection rates of adenomas 10 mm or larger did not differ significantly (p = .092), but the trial might have been underpowered for this analysis.

Clinically Useful
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, more effective therapy, or avoid unnecessary therapy or testing.

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. The single RCT performed in the U.S. did not find that use of chromoendoscopy improved identification of clinically meaningful lesions.

Section Summary: Chromoendoscopy for Patients at Average Risk of Colorectal Cancer Undergoing Colonoscopy
For individuals who have an average risk of CC who receive chromoendoscopy, the evidence includes RCTs. The single RCT performed in the U.S. did not find that high-definition chromoendoscopy identified more clinically meaningful lesions than high-definition white-light colonoscopy.

Chromoendoscopy for Patients at Increased Risk of Colorectal Cancer Undergoing Colonoscopy
Clinical Context and Test Purpose
The purpose of chromoendoscopy in patients at increased risk of CC is to inform a decision whether to proceed to the standard of care or to invasive treatment.

The question addressed in this evidence review is: Does the use of chromoendoscopy improve the net health outcome in individuals at increased risk of CC?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals at increased risk of CC.

Interventions
The test being considered is chromoendoscopy. Chromoendoscopy involves the application of dyes to facilitate tissue visualization.

Comparators
The following test is currently being used to diagnose or monitor CC: standard white-light colonoscopy.

Outcomes
The general outcomes of interest are tumor detection and tumor recurrence for CC.

Study Selection Criteria
For the evaluation of the clinical validity of the tests included in this review, studies that meet the following eligibility criteria were considered:

Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
Included a suitable reference standard (describe the reference standard)
Patient/sample clinical characteristics were described
Patient/sample selection criteria were described.

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
Individuals may be at higher risk for CC due to family or personal history or symptoms suggestive of colorectal disease (excluding patients with known IBD). Heightened surveillance is the most common approach to high-risk patients. Prophylactic colectomy is sometimes considered for those at extremely high-risk. The evidence on polyp detection with chromoendoscopy compared with standard colonoscopy, particularly higher risk polyps, such as those that are at least 5 mm to 10 mm in size, is described in this section.

Systematic Reviews
Har-Noy et al. (2019) conducted a meta-analysis of 4 studies that compared neoplasia detection rates with white-light colonoscopy and chromoendoscopy in patients with Lynch syndrome, who are at an increased risk of CC.⁵ Overall, chromoendoscopy was associated with improved overall lesion detection (pooled rate ratio, 1.97; 95% confidence interval [CI], 1.63 to 2.38), adenoma detection (pooled rate ratio, 1.53; 95% CI, 1.07 to 2.17), flat lesion detection (pooled rate ratio, 3.4; 95% CI, 2.47 to 4.67), and proximally-located lesion detection (pooled rate ratio, 2.93; 95% CI, 1.91 to 4.5). Additionally, chromoendoscopy was associated with higher odds of having any lesion detected as compared to white-light colonoscopy (odds ratio, 2.42, 95% CI, 1.56 to 3.75); however, the odds of having any adenoma detected were not significantly different between the modalities (odds ratio, 1.81; 95% CI, 0.65 to 5.01). The authors noted that none of the included studies were of a randomized, controlled design and that sample sizes were small; however, the heterogeneity between studies was minimal for most evaluated outcomes.

A Cochrane review by Brown and Baraza (2010) identified RCTs that compared chromoendoscopy with conventional colonoscopy for the detection of colorectal lesions in individuals at increased risk of colorectal neoplasia due to family history, previous polyp detection, or previous CC resection.⁶ Reviewers excluded studies of individuals with IBD or a known polyposis syndrome. Five RCTs (N = 1059 participants) met inclusion criteria; only 1 of the 5 studies had sites in the U.S. Three studies used some type of “back-to-back” design in which each participant underwent the equivalent of 2 colonoscopies. (An update of this Cochrane review by Brown et al. [2016] included studies of patients at increased risk of CC and those at average risk; meta-analyses did not stratify by patient population.⁷ The individual studies, none of which was published more recently than 2011, are discussed in the appropriate sections of this evidence review.)

A meta-analysis pooling results of the 5 studies in the 2010 Cochrane review found that a significantly higher number of polyps (all types) were detected with chromoendoscopy rather than with nonchromoendoscopy interventions (pooled mean difference, 0.80; 95% CI, 0.60 to 1.00; p < .001). Further, a meta-analysis found that the mean number of neoplastic lesions detected was significantly higher with chromoendoscopy than with nonchromoendoscopy interventions (pooled mean difference, 0.39; 95% CI, 0.27 to 0.50; p<.001). Tests for heterogeneity were statistically significant in both analyses. According to reviewers, potential reasons for clinical heterogeneity might have been differences in study design and differing levels of experience among endoscopists performing the procedure.

In a pooled analysis of per-patient data from the 5 studies, 234 (45%) of 524 patients in the chromoendoscopy group and 176 (33%) of 535 patients in the nonchromoendoscopy group had at least 1 neoplastic lesion detected. The difference between groups was statistically significant (odds ratio, 1.67; 95% CI, 1.29 to 2.15; p < .001). A pooled analysis of 4 studies found that 47 (9%) of 497 in the chromoendoscopy group and 20 (4%) of 512 in the nonchromoendoscopy group had 3 or more neoplastic lesions (odds ratio, 2.55; 95% CI, 1.49 to 4.36; p = .006). Reviewers concluded: “There appears to be strong evidence that chromoscopy enhances the detection of neoplasia in the colon and rectum. Patients with neoplastic polyps, particularly those with multiple polyps, are at increased risk of developing CC. Such lesions, which presumably would be missed with conventional colonoscopy, could contribute to the interval cancer numbers on any surveillance programme.” Reviewers did not report differences between groups in the number of large lesions.

Randomized Controlled Trials
Haanstra et al. (2019) conducted a prospective, multicenter, randomized study in the Netherlands that evaluated the effect of chromoendoscopy (n = 123) versus conventional white-light colonoscopy (n = 123) in the proximal colon on detection of neoplastic lesions in patients with Lynch syndrome.^8, The primary outcome was the proportion of patients with at least 1 neoplastic lesion at baseline and at the follow-up colonoscopy after 2 years. Results revealed a baseline neoplasia detection rate of 27% for white-light colonoscopy versus 30% for chromoendoscopy (odds ratio, 1.23; 95% CI, 0.69 to 2.2; p = .56). Similar nonsignificant findings were observed in the proximal colon, with detection rates of 16% for white-light colonoscopy versus 24% for chromoendoscopy (odds ratio, 1.6; 95% CI, 0.9 to 3.1; p = .13). At 2 years follow-up, neoplasia detection rates remained similar (26% for white-light colonoscopy versus 28% for chromoendoscopy; p = .81).

Stoffel et al. (2008) published findings of a study drawing on 5 sites across the U.S., Canada, and Israel.⁹ Eligibility criteria included a personal history of CC or at least 3 colorectal adenomas. The study involved back-to-back colonoscopies, the first of which was a standard colonoscopy with removal of all visualized polyps. Patients were then randomized to a second standard colonoscopy with intensive inspection (n = 23) or chromoendoscopy (n = 27). During the first colonoscopy, 17 (34%) of 50 patients had adenomas identified: 11 (48%) of 23 in the intensive inspection group and 6 (27%) in the chromoendoscopy group (p not reported). During the second colonoscopy, additional adenomas were found in 4 (17%) of 23 in the intensive inspection group and 12 (44%) of 27 in the chromoendoscopy group (p not reported). The mean size of adenomas found on the second examination was 3.2 mm in the intensive inspection group and 2.7 mm in the chromoendoscopy group. This compared with a mean size of 3.6 mm in the intensive inspection group and 4.7 mm in the chromoendoscopy group during the first examination. In a multivariate analysis, the use of chromoendoscopy was significantly associated with an increased likelihood of finding at least 1 additional adenoma on the second examination (p = .04).

Le Rhun et al. (2006) published findings of a French study involving 203 patients with a history of familial or personal colonic neoplasia or alarm symptoms (eg, change in bowel habit, abdominal pain) after age 60 years.¹⁰ Patients were randomized to standard colonoscopy (n = 100) or high-resolution colonoscopy with chromoendoscopy (n = 103). In the chromoendoscopy group, each segment of the colon was examined before and after spraying indigo carmine dye. The primary endpoint of the total number of adenomas per patient did not differ significantly between groups. The mean standard deviation number of adenomas was 0.5 (0.9) in the standard colonoscopy group and 0.6 (1.0) in the chromoendoscopy group. The number of flat adenomas (at least 5 mm) per patient also did not differ significantly between groups, with a mean standard deviation of 0.04 (0.20) in the standard colonoscopy group and 0.10 (0.39) in the chromoendoscopy group (p = .17).

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. No controlled studies have evaluated the effect on health outcomes, such as a lower incidence of CC.

Section Summary: Chromoendoscopy for Patients at Increased Risk of Colorectal Cancer Undergoing Colonoscopy
For individuals who have an increased risk of CC who receive chromoendoscopy, the evidence includes multiple RCTs and systematic reviews. A Cochrane systematic review of trials comparing chromoendoscopy with standard colonoscopy in high-risk patients (but excluding those with IBD) found significantly higher rates of adenoma detection and rates of 3 or more adenomas with chromoendoscopy than with standard colonoscopy. The evidence for detecting larger polyps, defined as greater than 5 mm or greater than 10 mm, is less robust. While 1 study reported a significantly higher detection rate for polyps greater than 5 mm, no studies reported increased detection of polyps greater than 10 mm. A recent RCT and systematic review involving patients with Lynch syndrome also found equivocal results. Results from the RCT showed similar neoplasia detection rates with chromoendoscopy and conventional white-light colonoscopy while the systematic review concluded that chromoendoscopy is associated with significantly improved detection of certain lesions; however, the odds of having an adenoma detected were not significantly different between the modalities.

Chromoendoscopy for Patients With Inflammatory Bowel Disease Undergoing Colonoscopy
Clinical Context and Test Purpose
The purpose of chromoendoscopy in patients with IBD is to inform a decision whether to proceed to the standard of care or to invasive treatment.

The question addressed in this evidence review is: Does the use of chromoendoscopy improve the net health outcome in individuals with IBD?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with IBD.

Interventions
The test being considered is chromoendoscopy. Chromoendoscopy involves the application of dyes to facilitate tissue visualization.

Comparators
The following test is currently being used to diagnose or monitor IBD: standard white-light colonoscopy.

Outcomes
The general outcomes of interest are tumor, dysplasia, and other mucosal abnormalities detection in IBD.

Based on pathology results, the follow-up would be similar to standards for colonoscopy.

Study Selection Criteria
For the evaluation of the clinical validity of the tests included in this review, studies that meet the following eligibility criteria were considered:

Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
Included a suitable reference standard (describe the reference standard)
Patient/sample clinical characteristics were described
Patient/sample selection criteria were described.

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
Systematic Reviews
Feuerstein et al. (2019) completed a systematic review and meta-analysis that evaluated the comparative efficacy of standard white-light colonoscopy or high-definition white-light colonoscopy versus dye-based chromoendoscopy in patients with IBD at an increased risk of CC.¹¹ The review included 10 studies, 6 of which were RCTs. Results from an analysis of the RCTs revealed a small benefit favoring chromoendoscopy for dysplasia detection as compared to white-light endoscopy (17% versus 11%; relative risk, 1.50; 95% CI, 1.08 to 2.10). However, when evaluating standard-definition and high-definition white-light colonoscopy individually, chromoendoscopy was only shown to be beneficial when compared to the standard-definition approach (relative risk, 2.2; 95% CI, 1.15 to 3.91); no benefit was seen when chromoendoscopy was compared to the high-definition modality (relative risk, 1.36; 95% CI, 0.84 to 2.18). The overall quality of the evidence in the RCTs was moderate.

A meta-analysis by Wu et al. (2012) on the diagnostic accuracy of chromoendoscopy for identifying dysplasia in patients with IBD and using the histopathologic diagnosis as the reference standard included 6 studies.¹² The primary endpoints were the sensitivity and specificity of chromoendoscopy compared with the histologic diagnosis. Pooled sensitivity of chromoendoscopy was 83.3% (95% CI, 35.9% to 99.6%) and the pooled specificity was 91.3% (95% CI, 43.8% to 100%). Reviewers concluded that chromoendoscopy had high diagnostic accuracy compared with white-light colonoscopy for patients with colonic IBD.

Subramanian et al. (2011) published a meta-analysis of studies evaluating the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with IBD.¹³ To be included in the meta-analysis, studies had to be prospective, evaluate surveillance colonoscopy in patients with IBD, and compare chromoendoscopy with white-light colonoscopy. Six published studies (N = 1277 patients) met the inclusion criteria. Only 1 study was conducted in the U.S.; 3 used indigo carmine dye and 3 used methylene blue dye.

In a pooled analysis of all 6 studies, the incremental yield of chromoendoscopy over white-light endoscopy for the detection of any grade of dysplasia on a per-patient basis was 7% (95% CI, 3% to 11%). The number needed to treat with chromoendoscopy to detect 1 extra patient with dysplasia was 14. Reviewers did not report separately the difference in detection of high-grade dysplasia. A pooled analysis of 4 studies (n = 1118 patients) found a 27% (95% CI, 11% to 42%) increase in the detection of flat dysplastic lesions with chromoendoscopy than with white-light colonoscopy.

In another pooled analysis of data from the 6 studies, there was a 44% (95% CI, 29% to 59%) increase in the detection of dysplasia using targeted biopsies obtained by chromoendoscopy versus targeted biopsies obtained by white-light colonoscopy. Reviewers also calculated the miss rates (lesions found only on random biopsies) with chromoendoscopy and white-light endoscopy. Significantly fewer dysplastic lesions were detected by random biopsy when chromoendoscopy was used versus white-light endoscopy. The pooled reduction in dysplastic lesions detected by random biopsy alone with chromoendoscopy versus white-light colonoscopy was -40% (95% CI, -53% to -27%). The meta-analysis did not address the miss rate of larger lesions.

Prospective and Retrospective Studies
Alexandersson et al. (2020) conducted a single-center, prospective study on 305 patients with longstanding (at least 8 years) ulcerative colitis or Crohn colitis.¹⁴ The study compared high-definition chromoendoscopy with high-definition white-light endoscopy. Patients were randomized into each group: chromoendoscopy (n = 152) and white-light endoscopy (n = 153). The primary outcome was the number of patients with dysplastic lesions. Dysplastic lesions were detected in 17 patients in the chromoendoscopy group (11%) and in 7 patients in the white-light endoscopy group (5%), which was statistically significant (p = .032). The total number of macroscopic lesions detected in the chromoendoscopy group versus the white-light endoscopy group (n = 89 vs. 41, respectively) was statistically significant (p < .001), and the total number of macroscopic lesions containing dysplasia was higher in the chromoendoscopy group (n = 24; p = .029). The study found that chromoendoscopy was superior to white-light endoscopy in the detection of dysplastic lesions during colonoscopy; however, the study was limited to a single-center institution in Sweden and the expertise of the endoscopists was not detailed.

Wan et al. (2021) conducted a prospective, multicenter randomized controlled study on patients with longstanding (at least 6 years) ulcerative colitis.¹⁵ The study compared chromoendoscopy with targeted biopsies to white-light endoscopy with targeted biopsies and random biopsies. In the full-analysis data set, a total of 122 patients with 447 colonoscopies were analyzed, and the randomized groups were as follows: chromoendoscopy (n = 39), white-light endoscopy-targeted (n = 43), and white-light endoscopy-random (n = 40). The primary outcome of the study was the number of colonoscopies that diagnosed dysplasia in each group. The median follow-up period during the study was 55 months; white-light endoscopy-random and chromoendoscopy treated patients had more colonoscopies that diagnosed dysplasia than white-light endoscopy-targeted treated patients (8.0% vs. 1.9%, p = .013; 9.3% vs. 1.9%, p = .004, respectively). There was no significant difference found between the white-light endoscopy-random and chromoendoscopy groups. In a sub-group analysis in the second half of the follow-up period (37 to 69 months), chromoendoscopy had more colonoscopies that diagnosed dysplasia than white-light endoscopy-targeted (13.3% vs. 1.6%, p = .015) and had results that indicated a trend for increasing dysplasia detection rates compared to white-light endoscopy-random (13.3% vs. 4.9%, p = .107).

Gasia et al. (2016) retrospectively analyzed data from a cohort of 454 patients who had IBD for at least 8 years and were undergoing surveillance at a single tertiary care center.¹⁶ The endoscopic approach used was at physician discretion; however, only 1 of the 8 endoscopists had training in chromoendoscopy. A total of 126 patients had a standard colonoscopy, 182 had a high-definition colonoscopy (124 with random biopsies, 58 with targeted biopsies), 28 had chromoendoscopy (4 with random biopsies, 24 with targeted biopsies), and 118 had virtual chromoendoscopy (64 with random biopsy, 54 with targeted biopsies). Rates of neoplasia detection were significantly higher in the targeted biopsy groups (19.1%; 95% CI, 13.4% to 26.5%) than in the random biopsy groups (8.2%; 95% CI, 5.6% to 11.7%). Rates of neoplasia detection did not differ significantly across the high-definition colonoscopy, chromoendoscopy, and virtual chromoendoscopy groups that received a targeted biopsy.

Mooiweer et al. (2015) retrospectively analyzed data on 937 patients with ulcerative colitis or Crohn disease who were undergoing surveillance with colonoscopy.¹⁷ The study compared neoplasia detection with chromoendoscopy (440 procedures in 401 patients) and white-light colonoscopy (1802 procedures in 772 patients). Neoplasia was detected in 48 (11%) of 440 colonoscopies performed with chromoendoscopy (95% CI, 8% to 14%) and in 189 (10%) of 1802 procedures performed with white-light colonoscopy (95% CI, 9% to 12%). The between-group difference in the detection rate was not statistically significant (p = .80). Chromoendoscopy was not associated with an increased rate of neoplasia detection; however, patients were not randomized to the treatment groups and might not have been comparable.

Freire et al. (2014) reported on 162 patients with a confirmed diagnosis of longstanding (at least 8 years) left-sided or extending ulcerative colitis that was clinically inactive.¹⁸ Patients were randomized to conventional colonoscopy or to colonoscopy with chromoendoscopy (using methylene blue). Seventeen patients were excluded from the analysis (poor bowel preparation). A total of 104 lesions were identified in the chromoendoscopy group, and 63 were identified in the conventional colonoscopy group. The primary study outcome (number of intraepithelial neoplasias detected) did not differ significantly between groups (7 in the chromoendoscopy group versus 6 in the conventional colonoscopy group). All neoplasias were low grade. Compared with standard histologic evaluation, the sensitivity and specificity of chromoendoscopy for detecting intraepithelial neoplasia were 85.7% and 97.9%, respectively.

Marion et al. (2008) reported on a prospective cohort of patients with ulcerative colitis or Crohn colitis.¹⁹ Data were available on 102 patients. The study involved a single examination with 2 passes of the colonoscope. During the first pass, 4 random biopsies were taken every 10 cm for a total of at least 32 biopsies. At that time, any visible lesions were either biopsied or removed using a targeted biopsy protocol. During the second pass, methylene blue dye was segmentally applied throughout the colon, accompanied by a targeted biopsy of any abnormality or lesion identified through spraying. The study included a blinded evaluation of specimens. In the first pass of the colonoscope using random biopsy, 3 (3%) of 102 patients were found to have dysplasia. In 1 of the 3 patients, an additional dysplastic lesion was found using chromoendoscopy during the second pass. No carcinomas were identified by either method. A total of 3264 random biopsies were taken using standard colonoscopic analysis; 3 (0.09%) samples showed low-grade dysplasia, and 16 (0.4%) were indeterminate. Moreover, before dye spraying, 50 biopsies or resections of visible lesions were performed; 12 (24%) showed low-grade dysplasia, 1 (2%) showed high-grade dysplasia, and 2 (4%) were indeterminate. After dye spraying, 82 biopsies were taken. Of these, 21 (26%) showed low-grade dysplasia, 1 (1%) showed high-grade dysplasia, and 13 (16%) were indeterminate.

Follow-up data were reported by Marion et al. (2016) on 68 (67%) of the 102 patients in the cohort.²⁰ The median length of follow-up was 28 months. Surveillance intervals varied from 6 to 12 months, depending on findings from the initial examination. During follow-up, patients underwent a mean of 3.15 endoscopy procedures (range, 1 to 5) with random biopsies. Follow-up endoscopies appeared to use a protocol similar to the index examination. Using random biopsies, 6 dysplastic lesions were identified in 5 patients. White-light targeted biopsy identified 11 dysplastic lesions in 11 patients, and methylene blue dye with targeted biopsy identified 27 dysplastic lesions from 27 patients. Targeted biopsy with chromoendoscopy and targeted biopsy with white-light colonoscopy were each significantly more likely to detect dysplasia than random biopsy. Four patients were referred for colectomy after the index examination, and 6 additional patients were referred during follow-up. A positive chromoendoscopy examination was significantly associated with having colectomy sooner (hazard ratio, 12.1; 95% CI, 3.2 to 46.2; p < .001). The study was not powered to estimate survival rates with white-light versus chromoendoscopy targeted biopsies. No carcinomas were found in any patient during the study, and no adverse events were reported.

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. It is uncertain whether chromoendoscopy is more accurate for detecting dysplasia.

Section Summary: Chromoendoscopy for Patients With Inflammatory Bowel Disease Undergoing Colonoscopy
For individuals who have IBD who receive chromoendoscopy, the evidence includes prospective and retrospective studies and meta-analyses. One meta-analysis found a statistically significant higher yield of chromoendoscopy over white-light colonoscopy for detecting dysplasia. This evidence established that chromoendoscopy improves polyp detection rates; however, it is unclear whether the additional polyps detected are clinically important and, therefore, whether improved polyp detection rates will translate into improved health outcomes. Moreover, there are concerns about comparison groups used in some of these trials. It is uncertain whether the control groups received optimal colonoscopy; therefore, the improved detection rates by chromoendoscopy might have been a function of suboptimal standard colonoscopy.

Virtual Chromoendoscopy for Patients at Average Risk of Colorectal Cancer Undergoing Colonoscopy
Clinical Context and Test Purpose
The purpose of virtual chromoendoscopy in patients at average risk of CC is to inform a decision whether to proceed to the standard of care or to invasive treatment.

The question addressed in this evidence review is: Does the use of virtual chromoendoscopy improve the net health outcome in individuals at average risk of CC?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals at average risk of CC.

Interventions
The test being considered for each indication is virtual chromoendoscopy. Virtual chromoendoscopy involves the application of dyes to highlight tissue to facilitate imaging.

Comparators
The following test is currently being used to diagnose or monitor CC: standard white-light colonoscopy.

Outcomes
The general outcome of interest is tumor detection and tumor recurrence in patients at risk of colorectal cancer.

Based on pathology results, the follow-up would be similar to standards for colonoscopy.

Study Selection Criteria
For the evaluation of the clinical validity of the tests included in this review, studies that meet the following eligibility criteria were considered:

Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
Included a suitable reference standard (describe the reference standard)
Patient/sample clinical characteristics were described
Patient/sample selection criteria were described.

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
Systematic Reviews
In 2019, Desai et al. published a systematic review and meta-analysis that assessed the adenoma miss rate of white-light colonoscopy compared with virtual chromoendoscopy (eg, narrow-band imaging (NBI) Fujinon intelligent chromoendoscopy, blue-light imaging, linked-color imaging, and i-SCAN) in a total of 3507 patients (CC risk status not stated) from 7 eligible RCTs.²¹ Of these patients, 1423 underwent a white-light colonoscopy as the first of tandem examinations; the remaining patients underwent virtual chromoendoscopy first. Results revealed a pooled adenoma miss rate for virtual chromoendoscopy compared to white-light colonoscopy of 17.9% versus 21% (odds ratio, 0.72; 95% CI: 0.67 to 1.11; p = .13). Additionally, the pooled adenoma detection rate was not significantly different with virtual chromoendoscopy as compared to white-light colonoscopy (odds ratio, 1.02; 95% CI, 0.88 to 1.19; p = .78).

A systematic review by Omata et al. (2014) compared rates of polyp detection by virtual chromoendoscopy (ie, Fujinon Intelligent Color Enhancement [FICE] or i-SCAN) with white-light colonoscopy.²² Reviewers included patients of all risk levels and selected only RCTs. Five trials on FICE and i-SCAN met eligibility criteria. Analyses did not find significantly higher detection rates with virtual chromoendoscopy. The pooled relative risk for the adenoma and neoplasia detected by virtual chromoendoscopy versus conventional chromoendoscopy was 1.09 (95% CI, 0.97 to 1.23; p > .05).

Randomized Controlled Trials
Two studies using modified back-to-back designs in patients undergoing screening colonoscopy were conducted by Chung et al. (2014) in South Korea. The larger study included 1,650 adults at average risk of CC, who were randomized across 3 groups.²³ During the colonoscopy, the endoscope was fully inserted, and each of 3 colonic segments (ascending, transverse, descending) was inspected twice during withdrawal. Participants received first withdrawal with NBI , virtual chromoendoscopy using FICE, or white-light colonoscopy (n = 550 each group). White-light was used in all groups for the second inspection. Ninety-one (5.5%) patients were excluded from the analysis due to inadequate bowel preparation. For the primary outcome of adenoma detection rate, no statistically significant differences were found among the 3 groups. The percentage of patients with at least 1 adenoma was 24.5% in the NBI group, 23.6% in the FICE group, and 25.3% in the white-light group (p = .75). Moreover, the mean number of adenomas per patient was 0.35 in the NBI group, 0.36 in the FICE group, and 0.37 in the white-light group (p = .59). The adenoma miss rate, defined as an adenoma identified only during the second inspection, was 22.9% in the NBI group, 26.0% in the FICE group, and 20.8% in the white-light only group; the difference was not statistically significant (p = .30). The mean size of the missed adenomas was 3.6 mm, which was smaller than the mean size of adenomas found during the first withdrawal (4.4 mm).

The other study by Chung et al. (2010) included 359 asymptomatic patients receiving screening colonoscopies.²⁴ All received back-to-back examinations with white-light colonoscopy or FICE in random order (n = 181 received white-light first, n = 178 received FICE first). During the initial colonoscopy, 60 (33.7%) of patients in the FICE group and 55 (30.4%) in the white-light group were found to have at least 1 adenoma; the difference between groups was not statistically significant (p = .74). The adenoma miss rate was 6.6% in the FICE group and 8.3% in the white-light group; again, the difference was not statistically significant (p = .59). All missed adenomas were low-grade and nonpedunculated. All but 1 (which was 6 mm) was 5 mm or less in size. In both the Chung et al. (2010, 2014) studies, virtual chromoendoscopy did not improve rates of adenoma detection compared with white-light endoscopy and did not identify more large adenomas.

An industry-supported multicenter RCT by Pohl et al. (2009) in Germany compared FICE with targeted standard chromoendoscopy using indigo carmine stain.²⁵ The trial enrolled 871 patients presenting for screening (57%) or diagnostic (43%) colonoscopy. All patients were examined using high-resolution zoom endoscopes. Patients in the group receiving standard chromoendoscopy underwent withdrawal using white-light colonoscopy. Indigo carmine was applied. In the FICE group, withdrawal was performed using FICE at the preset for examining colorectal mucosa. Data were available for 764 patients (368 in the FICE group, 396 in the standard chromoendoscopy group); 107 patients were excluded for poor bowel preparation, incomplete colonoscopy, or incomplete documentation. A total of 131 (35.6%) patients in the FICE group and 140 (35.4%) patients in the standard chromoendoscopy group had at least 1 adenoma (p = 1.0). The number of small adenomas (defined as ≤ 10 mm) did not differ significantly between groups (p = .41). The proportion of large adenomas greater than 10 mm identified in both groups was not reported. The proportion of patients with carcinoma was small in both groups and did not differ significantly (12 [3.3%] in the FICE group versus 12 [3.0%] in the standard chromoendoscopy group; p = .85).

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. No RCTs found improvement in the detection of clinically important polyps.

Section Summary: Virtual Chromoendoscopy for Patients at Average Risk of Colorectal Cancer Undergoing Colonoscopy
For individuals who have an average risk of CC who receive virtual chromoendoscopy, the evidence includes several RCTs and systematic reviews. The available RCTs have not found that virtual chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies assessing the impact of virtual chromoendoscopy on CC incidence and mortality rates compared with standard colonoscopy.

Virtual Chromoendoscopy for Patients at Increased Risk of Colorectal Cancer Undergoing Colonoscopy
Clinical Context and Test Purpose
The purpose of virtual chromoendoscopy in patients at increased risk of CC is to inform a decision whether to proceed to the standard of care or to invasive treatment.

The question addressed in this evidence review is: Does the use of virtual chromoendoscopy improve the net health outcome in individuals at increased risk of CC?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals at increased risk of CC.

Interventions
The test being considered for each indication is virtual chromoendoscopy. Virtual chromoendoscopy involves the application of dyes to highlight tissue to facilitate imaging.

Comparators
The following test is currently being used to diagnose or monitor CC: standard white-light colonoscopy.

Outcomes
The general outcome of interest is tumor detection and tumor recurrence in patients at risk of colorectal cancer.

Based on pathology results, the follow-up would be similar to standards for colonoscopy.

Study Selection Criteria
For the evaluation of the clinical validity of the tests included in this review, studies that meet the following eligibility criteria were considered:

Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
Included a suitable reference standard (describe the reference standard)
Patient/sample clinical characteristics were described
Patient/sample selection criteria were described.

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
Randomized Trials
A study using a modified back-to-back colonoscopy design was published by Kiriyama et al. (2012) in Japan.²⁶ It included 102 consecutive patients who received virtual chromoendoscopy using FICE or white-light colonoscopy in random order. Patients were eligible for study inclusion if they had been referred for a colonoscopy following sigmoidoscopy or for postoperative surveillance after anterior resection. Those with known IBD, bleeding, and polyposis syndrome were excluded; the right-sided colon was examined in the remaining patients. All lesions identified during either examination were removed, and specimens were evaluated. Two patients were excluded from the analysis because insertion was not possible, leaving 100 patients in the analysis. A total of 110 lesions were detected. Of these, 65 lesions were detected using FICE and 45 with white-light; the difference in the number of detected lesions did not differ significantly between groups. Most lesions detected were neoplastic; of these, 59 (91%) were found using FICE and 38 (84%) using white-light colonoscopy. The miss rate was defined as the proportion of total lesions in that grouping detected on the second examination. The miss rate for all polyps with FICE (12/39 [31%] lesions) was significantly lower than with white-light (28/61 [46%] lesions; p = .03). Twenty-six (44%) of 59 neoplastic lesions detected by FICE and 14 (37%) of 38 neoplastic lesions detected by white-light colonoscopy were at least 5 mm in size. For neoplastic lesions larger than 5 mm, there was no statistically significant difference between the FICE and white-light examinations in terms of the number of lesions detected.

Cha et al. (2010) evaluated South Korean patients at increased risk of CC due to a personal history of polyps or gastrointestinal symptoms.²⁷ A total of 135 patients underwent colonoscopy. Seven were excluded due to poor bowel preparation or diagnosis of colon cancer or intestinal disease. Thus, 128 patients were randomized to white-light colonoscopy (n = 65) or virtual chromoendoscopy with FICE (n = 63). The overall percentage of adenomas and the overall number of polyps did not differ significantly between groups. Thirty-one (49.2%) patients in the FICE group and 23 (35.4%) in the white-light group had 1 or more adenomas (p = .12). The mean number of adenomas identified per patient was also similar between groups: 1.39 in the FICE group and 1.96 in the white-light group (p = .46). The number of adenomas less than 5 mm in size (the primary study outcome) differed significantly between groups. Twenty-eight (44.4%) patients in the FICE group and 14 (21.5%) in the white-light group (p = .006) were found to have adenomas between 0 mm and 5 mm. All adenomas identified were low grade and no complications were reported in either group.

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. No RCTs found improvement in the detection of clinically important polyps.

Section Summary: Virtual Chromoendoscopy for Patients at Increased Risk of Colorectal Cancer Undergoing Colonoscopy
For individuals who have an increased risk of CC who receive virtual chromoendoscopy, the evidence includes RCTs. The available RCTs have not found that virtual chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies assessing the impact of virtual chromoendoscopy on CC incidence and mortality rates compared with standard colonoscopy.

Virtual Chromoendoscopy for Patients With Inflammatory Bowel Disease Undergoing Colonoscopy
Clinical Context and Test Purpose
The purpose of virtual chromoendoscopy in patients with IBD is to inform a decision whether to proceed to the standard of care or to invasive treatment.

The question addressed in this evidence review is: Does the use of virtual chromoendoscopy improve the net health outcome in individuals with IBD?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with IBD.

Interventions
The test being considered is virtual chromoendoscopy. Virtual chromoendoscopy involves the application of dyes to highlight tissue to facilitate imaging.

Comparators
The following test is currently being used to diagnose or monitor IBD: standard white-light colonoscopy.

Outcomes
The general outcome of interest is tumor detection, dysplasia, and other mucosal abnormalities in IBD.

Based on pathology results, the follow-up would be similar to standards for colonoscopy.

Study Selection Criteria
For the evaluation of the clinical validity of the tests included in this review, studies that meet the following eligibility criteria were considered:

Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
Included a suitable reference standard (describe the reference standard)
Patient/sample clinical characteristics were described
Patient/sample selection criteria were described.

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
Randomized Controlled Trials
One RCT has evaluated virtual chromoendoscopy in patients with IBD. This trial by Neumann et al. (2013) in Germany randomized 83 patients with mild or inactive IBD to high-definition white-light endoscopy or virtual chromoendoscopy.²⁸ Seventy-eight (94%) patients completed the trial; 5 were excluded due to insufficient bowel preparation. During endoscopy, biopsies were taken from the most distal part of mucosal inflammation; random biopsies were taken to determine the extent and severity of inflammation. Histopathologic analysis was done by a pathologist blinded to endoscopic findings. Endoscopic examination findings on the extent of disease concurred with histopathologic findings in 19 (48.7%) of 39 patients in the white-light group and in 36 (92.3%) of 39 patients in the virtual chromoendoscopy group. The difference between groups was statistically significant, favoring virtual chromoendoscopy (p = .001). In terms of disease activity, the agreement between the endoscopic prediction of disease activity and histopathologic findings was 21 (53.9%) of 39 white-light patients and 35 (89.7%) of 39 virtual chromoendoscopy patients (p = .066). Although the agreement was higher in the virtual chromoendoscopy group, the between-group difference was not statistically significant at p less than 0.05.

Kandiah et al. (2021), in the United Kingdom, published a multicenter RCT comparing the performance of high-definition white light versus high-definition virtual chromoendoscopy in patients with longstanding (at least 8 years) ulcerative or Crohn colitis.²⁹ Patients were randomized, prior to starting surveillance colonoscopy, to either white light (n = 92) or virtual chromoendoscopy (n = 92) for a total of 184 patients included in the final analysis. The primary outcome was the difference in neoplasia detection rate between the 2 arms. Twenty-five neoplastic lesions were found in 14 patients in the virtual chromoendoscopy arm; 27 lesions were found in 22 patients in the white light arm. Compared to the virtual chromoendoscopy arm, neoplasia detection rate was higher in the white light arm (23.4% vs. 14.9%), but this was not statistically significant (p = .14). The mean number of biopsies taken per patient was 35.9 in each arm of the study, and the difference in the mean number of neoplasia per patient was not statistically significant between the 2 arms (p = .75).

Retrospective Studies
The retrospective cohort study by Gasia et al. (2016), discussed in the section on chromoendoscopy, included a group assigned to virtual chromoendoscopy.¹⁶ In brief, this study included 454 patients with IBD undergoing surveillance. Rates of neoplasia detection did not differ significantly for a high-definition colonoscopy, chromoendoscopy, or virtual chromoendoscopy when used with targeted biopsy. However, rates of neoplasia detection were significantly higher in patients who had targeted biopsy with high-definition colonoscopy, chromoendoscopy, and virtual chromoendoscopy (19.1%; 95% CI, 13.4% to 26.5%) than those undergoing random biopsy (8.2%; 95% CI, 5.6% to 11.7%).

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs. One RCT found no improvement in identifying disease activity.

Section Summary: Virtual Chromoendoscopy for Patients With Inflammatory Bowel Disease Undergoing Colonoscopy
For individuals who have IBD who receive virtual chromoendoscopy, the evidence includes 2 RCTs and a nonrandomized comparative study. One RCT found a significantly greater likelihood that virtual chromoendoscopy would correctly identify the extent of disease inflammation than standard colonoscopy but no significant difference in the likelihood of identifying disease activity. The other RCT found that there was no significant difference in the detection of neoplasia between high definition white light versus high-definition virtual chromoendoscopy in patients with long-standing IBD. A retrospective cohort study found that targeted biopsy resulted in a higher rate of neoplasia detection regardless of the endoscopy method used. There is a lack of studies assessing the impact of virtual chromoendoscopy on CC incidence and mortality rates compared with standard colonoscopy.

Summary of Evidence
Chromoendoscopy
For individuals who have an average risk of CC who receive chromoendoscopy, the evidence includes RCTs evaluating this population. Relevant outcomes are OS, DSS, test validity, and change in disease status. The single RCT performed in the U.S. did not find that high-definition chromoendoscopy identified more clinically meaningful lesions than high-definition white-light colonoscopy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have an increased risk of CC who receive chromoendoscopy, the evidence includes multiple RCTs and systematic reviews. Relevant outcomes are OS, DSS, test validity, and change in disease status. A Cochrane systematic review of trials comparing chromoendoscopy with standard colonoscopy in high-risk patients (but excluding those with inflammatory bowel disease) found significantly higher rates of adenoma detection and rates of 3 or more adenomas with chromoendoscopy than with standard colonoscopy. The evidence for detecting larger polyps, defined as greater than 5 mm or greater than 10 mm, is less robust. While 1 study reported a significantly higher detection rate for polyps greater than 5 mm, no studies reported increased detection of polyps greater than 10 mm. A recent RCT and systematic review involving patients with Lynch syndrome also found equivocal results. Results from the RCT showed similar neoplasia detection rates with chromoendoscopy and conventional white-light colonoscopy while the systematic review concluded that chromoendoscopy is associated with significantly improved detection of certain lesions; however, the odds of having any adenoma detected were not significantly different between the modalities. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have IBD who receive chromoendoscopy, the evidence includes prospective and retrospective studies and meta-analyses. Relevant outcomes are OS, DSS, test validity, and change in disease status. One meta-analysis found a statistically significant higher yield of chromoendoscopy over white-light colonoscopy for detecting dysplasia. This evidence established that chromoendoscopy improves polyp detection rates; however, it is unclear whether the additional polyps detected are clinically important and, therefore, whether improved polyp detection rates will translate into improved health outcomes. Moreover, there are concerns about comparison groups used in some of these trials. It is uncertain whether the control groups received optimal colonoscopy; therefore, the improved detection rates by chromoendoscopy might have been a function of suboptimal standard colonoscopy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Virtual Chromoendoscopy
For individuals who have an average risk of CC who receive virtual chromoendoscopy, the evidence includes several RCTs and systematic reviews. Relevant outcomes are OS, DSS, test validity, and change in disease status. The available RCTs have not found that virtual chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies assessing the impact of virtual chromoendoscopy on CC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome

For individuals who have an increased risk of CC who receive virtual chromoendoscopy, the evidence includes RCTs. Relevant outcomes are OS, DSS, test validity, and change in disease status. The available RCTs have not found that virtual chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies assessing the impact of virtual chromoendoscopy on CC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have IBD who receive virtual chromoendoscopy, the evidence includes 2 RCTs and nonrandomized comparative study. Relevant outcomes are OS, DSS, test validity, and change in disease status. The RCT found a significantly greater likelihood that virtual chromoendoscopy would correctly identify the extent of disease inflammation than standard colonoscopy but no significant difference in the likelihood of identifying disease activity. The other RCT found that there was no significant difference in the detection of neoplasia between high definition white light versus high-definition virtual chromoendoscopy in patients with long-standing IBD. A retrospective cohort study found that targeted biopsy resulted in a higher rate of neoplasia detection regardless of the endoscopy method used. There is a lack of studies assessing the impact of virtual chromoendoscopy on CC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Clinical Input From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

2012 Input
In response to requests, input was received through 1 physician specialty society and 5 academic medical centers while this policy was under review in 2012. There was general agreement that chromoendoscopy and virtual chromoendoscopy are considered investigational as adjuncts to diagnostic or surveillance colonoscopy. However, for chromoendoscopy, 2 reviewers and, for virtual chromoendoscopy, 1 reviewer argued that the technology may have a role in screening select higher-risk patients. Most respondents, including 4 of the 5 academic medical centers, did not think that chromoendoscopy could easily be adopted into routine clinical use as an adjunct to colonoscopy. Reviewers were split on whether the detection of adenomatous polyps of any size is clinically important. Of the 3 reviewers who thought that only detection of larger adenomatous polyps is clinically important, 2 considered the size threshold to be 5 mm; the other considered it to be 10 mm.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in ‘Supplemental Information’ if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Society for Gastrointestinal Endoscopy and American Gastroenterological Association
In 2021, the American Gastroenterological Association (AGA) published a clinical practice update on the surveillance and management of colorectal dysplasia in patients with inflammatory bowel disease (IBD).30, This was an expert review that underwent internal peer review by the AGA Clinical Practice Updates Committee and external peer review through standard procedures undertaken by the publishing journal (Gastroenterology). Table 1 summarizes relevant best practice statements.

Table 1. Best Practice Advice on Surveillance and Management of Dysplasia in Patients With Inflammatory Bowel Disease

Best Practice Statement

"Dye spray chromoendoscopy, performed by appropriately trained endoscopists, should be considered in all persons with colonic inflammatory bowel disease undergoing surveillance colonoscopy, particularly if a standard definition endoscope is used or if there is a history of dysplasia"

"Virtual chromoendoscopy is a suitable alternative to dye spray chromoendoscopy for dysplasia detection in persons with colonic inflammatory bowel disease when using high-definition endoscopy."

"Extensive nontargeted biopsies (roughly 4 adequately spaced biopsies every 10 cm) should be taken from flat colorectal mucosa in areas previously affected by colitis when white light endoscopy is used without dye spray chromoendoscopy or virtual chromoendoscopy. Additional biopsies should be taken from areas of prior dysplasia or poor mucosal visibility. Nontargeted biopsies are not routinely required if dye spray chromoendoscopy or virtual chromoendoscopy is performed using a high-definition endoscope, but should be considered if there is a history of dysplasia or primary sclerosing cholangitis."

"A finding of invisible dysplasia should prompt repeat examination by an experienced endoscopist using high-definition dye spray chromoendoscopy under optimized viewing conditions, with extensive nontargeted biopsies in the area of prior dysplasia if no lesion is seen. A finding of unresectable visible dysplasia or of invisible multifocal or high-grade dysplasia on histology should prompt colectomy. For visible lesions that can be resected or if histologic dysplasia is not confirmed on a high-quality dye spray chromoendoscopy examination, continued endoscopic surveillance at frequent intervals is appropriate.

"Targeted biopsies of representative or concerning pseudopolyps is appropriate during colonoscopy. Removal and sampling of all lesions is neither required nor practical. Surgery should be a last resort to manage colorectal cancer risk in the setting of severe pseudopolyposis. Dye spray chromoendoscopy should not be used to detect flat or subtle lesions within a field of pseudopolyps."

In 2015, the American Society for Gastrointestinal Endoscopy (ASGE) and the American Gastroenterological Association (AGA) published a SCENIC consensus statement on the surveillance and management of dysplasia in patients with inflammatory bowel disease (IBD).³¹ This statement, developed by an international multidisciplinary group representing a variety of stakeholders, incorporated systematic reviews of the literature. Table 2 summarizes relevant recommendations.

Table 2. Recommendations on Surveillance and Management of Dysplasia in Patients With Inflammatory Bowel Disease

Recommendation	LOA	SOR	QOE
"When performing surveillance with white-light colonoscopy, high definition is recommended rather than standard definition."	80%	Strong	Low
"When performing surveillance with standard-definition colonoscopy, chromoendoscopy is recommended rather than white-light colonoscopy."	85%	Strong	Moderate
"When performing surveillance with high-definition colonoscopy, chromoendoscopy is suggested rather than white-light colonoscopy."	84%	Conditional	Low

LOA: level of agreement; QOE: quality of evidence; SOR: strength of recommendation.

Panelists did not reach consensus on the use of chromoendoscopy in random biopsies of patients with IBD undergoing surveillance.

Commentaries in 2 gastroenterology journals questioned whether the SCENIC guidelines would be accepted as the standard of care in IBD surveillance.32,33, Both commentaries noted that the guidelines considered the outcome of the detection of dysplasia and not disease progression or survival. Moreover, the commentators noted the lack of longitudinal data on clinical outcomes in patients with dysplastic lesions detected using chromoendoscopy

Then ASGE (2015) issued guidelines on endoscopy in the diagnosis and treatment of IBD, which made the following recommendations about chromoendoscopy: "Chromoendoscopy with pancolonic dye spraying and targeted biopsies is sufficient for surveillance in inflammatory bowel disease; consider 2 biopsies from each colon segment for histologic staging."³⁴

The ASGE (2015) also published a systematic review and meta-analysis assessing narrow-band imaging, i-SCAN, and Fujinon Intelligent Color Enhancement for predicting adenomatous polyp histology of small or diminutive colorectal polyps to determine whether they have met previously established criteria or thresholds to incorporate into clinical practice.³⁵ The ASGE assessment confirmed that:

"... The thresholds have been met for narrow-band imaging with endoscopists who are experts in using these advanced imaging technologies and when assessments are made with high confidence. The ASGE Technology Committee endorsed the use of NBI [narrow band imaging] for both the ‘diagnose-and-leave’ strategy for diminutive (≤5 mm) rectosigmoid hyperplastic polyps and the ‘resect-and-discard’ strategy for diminutive (≤5 mm) adenomatous polyps."

The report addressed the “trepidation” of patients, endoscopists, and pathologists with the “diagnose-and-leave” strategy, indicating there are challenges for implementation for the use of these strategies in clinical practice.

U.S. Multi-Society Task Force on Colorectal Cancer
In 2020, the U.S. Multi-Society Task Force issued guidelines on the endoscopic removal of colorectal lesions. Regarding lesion assessment and description, the Task Force suggested "proficiency in the use of electronic- (eg, NBI, i-SCAN, and Fuji Intelligent Chromoendoscopy, or blue light imaging) or dye (chromoendoscopy)-based image-enhanced endoscopy techniques to apply optical diagnosis classifications for colorectal lesion histology [conditional recommendation, moderate-quality evidence)."³⁶ The Task Force also suggested "careful examination of the post-mucosectomy scar site using enhanced imaging, such as dye-based (chromoendoscopy) or electronic-based methods, as well as obtaining targeted biopsies of the site. Post-resection scar sites that show both normal macroscopic and microscopic (biopsy) findings have the highest predictive value for long-term eradication [conditional recommendation, moderate-quality evidence]."

In 2012, the U.S. Multi-Society Task Force guidelines on colonoscopy surveillance after screening and polypectomy (consensus update) stated that chromoendoscopy and narrow-band imaging might enable endoscopists to accurately determine if lesions are neoplastic and if there is a need to remove them and send specimens to pathology.³⁷ The guidelines noted that these technologies currently do not have an impact on surveillance intervals. In 2020, the U.S. Multi-Society Task Force published updated recommendations for follow-up after colonoscopy and polypectomy (consensus update), however, there was no mention of chromoendoscopy.³⁸

U.S. Preventive Services Task Force Recommendations
The U.S. Preventive Services Task Force (2021 ) recommendations on screening for colorectal cancer do not mention chromoendoscopy.^39,

Ongoing and Unpublished Clinical Trials
Some currently ongoing and unpublished trials that might influence this review are listed in Table 3.

Table 3. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT04192929	Chromoendoscopy or Narrow Band Imaging (NBI) for Improving Adenoma Detection in Colonoscopy	1065	May 2022
NCT04403997	Virtual Chromoendoscopy with Second Generation NBI (HQ190) vs Chromoendoscopy in Inflammatory Bowel Disease	175	Feb 2022
NCT04257084	Surveillance in Ulcerative Colitis: Narrow Band Image Versus Chromoendoscopy for High-risk Groups (SUNRISE-High)	188	Jan 2023
Unpublished
NCT01505842^†	Randomized Controlled Trial (RCT) to Compare Dysplasia Detection Rate in Colonoscopy Without Chromoendoscopy Versus Colonoscopy With Chromoendoscopy in Detecting Dysplasia in Ulcerative Colitis and Crohn's Colitis Patients	304	Apr 2019 (unknown)

NCT: national clinical trial.
^† Study has passed its completion date and status has not been verified in more than two years.

References:

Zhao S, Wang S, Pan P, et al. Magnitude, Risk Factors, and Factors Associated With Adenoma Miss Rate of Tandem Colonoscopy: A Systematic Review and Meta-analysis. Gastroenterology. May 2019; 156(6): 1661-1674.e11. PMID 30738046
Food and Drug Administration (FDA). 510(k) Summary: Pentax EPK-i5010 Video Processor. 2013; http://www.accessdata.fda.gov/cdrh_docs/pdf12/K122470.pdf. Accessed September 29, 2021.
Pohl J, Schneider A, Vogell H, et al. Pancolonic chromoendoscopy with indigo carmine versus standard colonoscopy for detection of neoplastic lesions: a randomised two-centre trial. Gut. Apr 2011; 60(4): 485-90. PMID 21159889
Kahi CJ, Anderson JC, Waxman I, et al. High-definition chromocolonoscopy vs. high-definition white light colonoscopy for average-risk colorectal cancer screening. Am J Gastroenterol. Jun 2010; 105(6): 1301-7. PMID 20179689
Har-Noy O, Yung DE, Koulaouzidis A, et al. Chromoendoscopy or white light endoscopy for neoplasia detection in Lynch syndrome, a meta-analysis. Dig Liver Dis. Nov 2019; 51(11): 1515-1521. PMID 31526715
Brown SR, Baraza W. Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum. Cochrane Database Syst Rev. Oct 06 2010; (10): CD006439. PMID 20927746
Brown SR, Baraza W, Din S, et al. Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum. Cochrane Database Syst Rev. Apr 07 2016; 4: CD006439. PMID 27056645
Haanstra JF, Dekker E, Cats A, et al. Effect of chromoendoscopy in the proximal colon on colorectal neoplasia detection in Lynch syndrome: a multicenter randomized controlled trial. Gastrointest Endosc. Oct 2019; 90(4): 624-632. PMID 31028782
Stoffel EM, Turgeon DK, Stockwell DH, et al. Chromoendoscopy detects more adenomas than colonoscopy using intensive inspection without dye spraying. Cancer Prev Res (Phila). Dec 2008; 1(7): 507-13. PMID 19139000
Le Rhun M, Coron E, Parlier D, et al. High resolution colonoscopy with chromoscopy versus standard colonoscopy for the detection of colonic neoplasia: a randomized study. Clin Gastroenterol Hepatol. Mar 2006; 4(3): 349-54. PMID 16527699
Feuerstein JD, Rakowsky S, Sattler L, et al. Meta-analysis of dye-based chromoendoscopy compared with standard- and high-definition white-light endoscopy in patients with inflammatory bowel disease at increased risk of colon cancer. Gastrointest Endosc. Aug 2019; 90(2): 186-195.e1. PMID 31009609
Wu L, Li P, Wu J, et al. The diagnostic accuracy of chromoendoscopy for dysplasia in ulcerative colitis: meta-analysis of six randomized controlled trials. Colorectal Dis. Apr 2012; 14(4): 416-20. PMID 21073646
Subramanian V, Mannath J, Ragunath K, et al. Meta-analysis: the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Aliment Pharmacol Ther. Feb 2011; 33(3): 304-12. PMID 21128987
Alexandersson B, Hamad Y, Andreasson A, et al. High-Definition Chromoendoscopy Superior to High-Definition White-Light Endoscopy in Surveillance of Inflammatory Bowel Diseases in a Randomized Trial. Clin Gastroenterol Hepatol. Aug 2020; 18(9): 2101-2107. PMID 32353535
Wan J, Zhang Q, Liang SH, et al. Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients: a multicenter randomized-controlled trial. Gastroenterol Rep (Oxf). Jan 2021; 9(1): 14-21. PMID 33747522
Gasia MF, Ghosh S, Panaccione R, et al. Targeted Biopsies Identify Larger Proportions of Patients With Colonic Neoplasia Undergoing High-Definition Colonoscopy, Dye Chromoendoscopy, or Electronic Virtual Chromoendoscopy. Clin Gastroenterol Hepatol. May 2016; 14(5): 704-12.e4. PMID 26804384
Mooiweer E, van der Meulen-de Jong AE, Ponsioen CY, et al. Chromoendoscopy for Surveillance in Inflammatory Bowel Disease Does Not Increase Neoplasia Detection Compared With Conventional Colonoscopy With Random Biopsies: Results From a Large Retrospective Study. Am J Gastroenterol. Jul 2015; 110(7): 1014-21. PMID 25823770
Freire P, Figueiredo P, Cardoso R, et al. Surveillance in ulcerative colitis: is chromoendoscopy-guided endomicroscopy always better than conventional colonoscopy? A randomized trial. Inflamm Bowel Dis. Nov 2014; 20(11): 2038-45. PMID 25185683
Marion JF, Waye JD, Present DH, et al. Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial. Am J Gastroenterol. Sep 2008; 103(9): 2342-9. PMID 18844620
Marion JF, Waye JD, Israel Y, et al. Chromoendoscopy Is More Effective Than Standard Colonoscopy in Detecting Dysplasia During Long-term Surveillance of Patients With Colitis. Clin Gastroenterol Hepatol. May 2016; 14(5): 713-9. PMID 26656297
Desai M, Viswanathan L, Gupta N, et al. Impact of Electronic Chromoendoscopy on Adenoma Miss Rates During Colonoscopy: A Systematic Review and Meta-analysis. Dis Colon Rectum. Sep 2019; 62(9): 1124-1134. PMID 31162375
Omata F, Ohde S, Deshpande GA, et al. Image-enhanced, chromo, and cap-assisted colonoscopy for improving adenoma/neoplasia detection rate: a systematic review and meta-analysis. Scand J Gastroenterol. Feb 2014; 49(2): 222-37. PMID 24328858
Chung SJ, Kim D, Song JH, et al. Comparison of detection and miss rates of narrow band imaging, flexible spectral imaging chromoendoscopy and white light at screening colonoscopy: a randomised controlled back-to-back study. Gut. May 2014; 63(5): 785-91. PMID 23853211
Chung SJ, Kim D, Song JH, et al. Efficacy of computed virtual chromoendoscopy on colorectal cancer screening: a prospective, randomized, back-to-back trial of Fuji Intelligent Color Enhancement versus conventional colonoscopy to compare adenoma miss rates. Gastrointest Endosc. Jul 2010; 72(1): 136-42. PMID 20493487
Pohl J, Lotterer E, Balzer C, et al. Computed virtual chromoendoscopy versus standard colonoscopy with targeted indigocarmine chromoscopy: a randomised multicentre trial. Gut. Jan 2009; 58(1): 73-8. PMID 18838485
Kiriyama S, Matsuda T, Nakajima T, et al. Detectability of colon polyp using computed virtual chromoendoscopy with flexible spectral imaging color enhancement. Diagn Ther Endosc. 2012; 2012: 596303. PMID 22474404
Cha JM, Lee JI, Joo KR, et al. A prospective randomized study on computed virtual chromoendoscopy versus conventional colonoscopy for the detection of small colorectal adenomas. Dig Dis Sci. Aug 2010; 55(8): 2357-64. PMID 19834809
Neumann H, Vieth M, Gunther C, et al. Virtual chromoendoscopy for prediction of severity and disease extent in patients with inflammatory bowel disease: a randomized controlled study. Inflamm Bowel Dis. Aug 2013; 19(9): 1935-42. PMID 23839228
Kandiah K, Subramaniam S, Thayalasekaran S, et al. Multicentre randomised controlled trial on virtual chromoendoscopy in the detection of neoplasia during colitis surveillance high-definition colonoscopy (the VIRTUOSO trial). Gut. Sep 2021; 70(9): 1684-1690. PMID 33214162
Murthy SK, Feuerstein JD, Nguyen GC, et al. AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review. Gastroenterology. Sep 2021; 161(3): 1043-1051.e4. PMID 34416977
Laine L, Kaltenbach T, Barkun A, et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology. Mar 2015; 148(3): 639-651.e28. PMID 25702852
Higgins PD. Miles to Go on the SCENIC Route: Should Chromoendoscopy Become the Standard of Care in IBD Surveillance?. Am J Gastroenterol. Jul 2015; 110(7): 1035-7. PMID 26148262
Marion JF, Sands BE. The SCENIC consensus statement on surveillance and management of dysplasia in inflammatory bowel disease: praise and words of caution. Gastroenterology. Mar 2015; 148(3): 462-7. PMID 25702851
Shergill AK, Lightdale JR, Bruining DH, et al. The role of endoscopy in inflammatory bowel disease. Gastrointest Endosc. May 2015; 81(5): 1101-21.e1-13. PMID 25800660
Abu Dayyeh BK, Thosani N, Konda V, et al. ASGE Technology Committee systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. Mar 2015; 81(3): 502.e1-502.e16. PMID 25597420
Kaltenbach T, Anderson JC, Burke CA, et al. Endoscopic Removal of Colorectal Lesions-Recommendations by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. Mar 2020; 158(4): 1095-1129. PMID 32122632
Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. Sep 2012; 143(3): 844-857. PMID 22763141
Gupta S, Lieberman D, Anderson JC, et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. Mar 2020; 115(3): 415-434. PMID 32039982
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Coding Section

Codes	Number	Description
CPT		No specific code
	44799	Unlisted procedure, intestine
ICD-10-CM		Investigational for all relevant diagnoses
ICD-10-PCS		ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this procedure.
Type of Service	Medicine
Place of Service	Inpatient/Outpatient

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

History From 2014 Forward

06/22/2022	Annual review, no change to policy intent. Updating rationale and references.
06/14/2021	Annual review, no change to policy intent. UPdating guidelines, coding, rationale and references.
06/16/2020	Annual review, no change to policy intent. Updating rationale and references.
06/03/2019	Annual review, no change to policy intent. Updating description, background, regulatory status, rationale and references.
06/12/2018	Annual review, no change to policy intent. Updating rationale and references.
06/13/2017	Annual review, no change to policy intent. Updating background, description, regulatory status, rationale and references.
05/12/2017	Corrected review date. No other change made.
06/01/2016	Annual review, no change to policy intent. Updating background, description, regulatory status, rationale and references.
06/16/2015	Annual review, no change to policy intent. Updated background, description, rationale and references. Added coding and guidelines.
06/05/2014	Annual review. Added related policies, updated regulatory status, rationale and references. No change to policy intent.

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Chromoendoscopy as an Adjunct to Colonoscopy - CAM 20184