Pending Policies - Medicine


In-Vivo Analysis of Colorectal Polyps

Number:MED201.022

Effective Date:06-15-2018

Coverage:

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In-vivo analysis, including but not limited to, fiberoptic analysis, chromoendoscopy, and electronic (virtual) chromoendoscopy of colorectal polyps is considered experimental, investigational and/or unproven.

NOTE: For “Confocal Laser Endomicroscopy (CLE)” see MED201.038.

Description:

Endoscopic imaging of the gastrointestinal (GI) tract is routinely conducted by utilizing white-light endoscopy. Despite being the current gold standard, white-light endoscopy may not detect a significant amount of lesions, especially within the colorectum, potentially leading to delayed and/or suboptimal therapies. (1) In an attempt to improve detection of GI lesions, several in-vivo analysis techniques are being investigated, including but not limited to, fiberoptic analysis, chromoendoscopy, and electronic chromoendoscopy.

Fiberoptic Analysis

Benign and malignant tissues emit different patterns and wavelengths of fluorescence after exposure to a laser light. The Optical Biopsy System (SpectraScience, Minneapolis MN) was developed based on this principle. This system consists of an optical fiber emitting a laser that is directed against three different regions of the same polyp. The subsequent fluorescent signal is collected, measured, and analyzed by a proprietary system software, and classifies a polyp as “suspicious” (i.e., adenomatous) or “not suspicious” (i.e., hyperplastic). (2)

Regulatory Status

The Optical Biopsy System received premarket approval (PMA) as a Class III device from the U.S. Food and Drug Administration (FDA) in November 2000. The FDA-labeled indication for the Optical Biopsy System reads as follows: “The SpectraScience Optical Biopsy System is indicated for use as an adjunct to lower gastrointestinal endoscopy. The device is intended for the evaluation of polyps less than 1 cm in diameter that the physician has not already elected to remove. The device is only to be used in deciding whether such polyps should be removed (which includes submission for histological examination).” In 2001 the name was changed to the WavSTAT® Optical Biopsy System.

Chromoendoscopy

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.

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

Diagnosis of colorectal neoplasia in symptomatic patients at increased risk of colorectal cancer due to family history of colorectal cancer, 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 colorectal cancer.

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

Regulatory Status

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

Electronic Chromoendoscopy

Electronic chromoendoscopy (also called virtual chromoendoscopy) involves imaging enhancements with endoscopy systems that could be an alternative to dye spraying. Electronic chromoendoscopy technologies include narrow band imaging (NBI), and multi-band imaging (MBI) techniques such as flexible spectral imaging color enhancement (FICE) and i-SCAN™. (3)

Narrow Band Imaging

Narrow band imaging uses filters to illuminate the tissue at selected wavelengths. The NBI color chip system utilizes a single filter with a 2-band pass characteristic and is used to generate central wavelengths at 415 nm (blue) and 540 nm (green and red). The NBI red-green-blue sequential illumination system uses narrow spectra of red, green, and blue light and a video endoscopic system with a frame sequential lighting method. The light source unit consists of a xenon lamp and a rotation disk with 3 optical filters. The rotation disk and monochrome charge-coupled device are synchronized and sequentially generate image in 3 optical filter bands. By use of all 3 band images, a single color endoscopic image is synthesized by the video processor. NBI has limited penetration into the mucosal surface and has enhanced visualization of capillary vessels and their fine structure on the surface layer of colonic tissue.

Multi-Band Imaging

Although similar to NBI, multi-band imaging processes the white-light image digitally, reconstructing it through software rather than a filter in order to enhance the appearance of the mucosa.

Regulatory Status

NBI received FDA clearance through the 510(k) process in 2005. This clearance (K051645) added NBI with the EVIS EXERA 160A System (Olympus Medical Systems Corp) to existing endoscopic equipment. The FDA indications include endoscopic diagnosis, treatment, and video observation.

In August 2014, the Fujifilm EPX-4440HD Digital Video Processor with FICE and Light Source was cleared for marketing by the FDA through the 510(k) process. FDA documents state that FICE can be used to supplement white-light endoscopy but is not intended to replace histopathologic sampling as a means of diagnosis.

Previously, in February 2011, the FDA had sent an Urgent Medical Device Corrective Action letter advising users that the FICE feature, which had been added by the manufacturer to enhance the appearance of images for virtual chromoendoscopy, should not be used, because this feature had not been reviewed under the 510(k) process. (5)

In April 2003, the i-SCAN™ (Pentax), used for virtual chromoendoscopy, was cleared for marketing by the FDA through the 510(k) process. (6) This is a digital image enhancement technology and is part of the Pentax EPK-i5010 Video Processor. The i-SCAN™ has several modes that digitally enhance images in real-time during endoscopy. FDA documents state that i-SCAN™ is intended as an adjunct following white-light endoscopy and is not intended to replace histopathologic analysis.

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

Rationale:

This medical policy was originally created in August 2006 and has been updated regularly with literature searches, most recently through May 4, 2018.

Assessment of diagnostic technology typically focuses on 3 categories of evidence: 1) technical reliability (test-retest reliability or interrater reliability); 2) clinical validity (sensitivity, specificity, positive and negative predictive values) in relevant populations of patients; and 3) clinical utility (i.e., demonstration that the diagnostic information can be used to improve patient outcomes). This medical policy focuses on the literature reporting detection rates of clinically important adenomas and neoplastic lesions. The following is a summary of the key literature.

Fiberoptic Analysis

The U.S. Food and Drug Administration (FDA) approval for the Optical Biopsy System was based on a prospective, nonrandomized phase II study involving 101 subjects from 5 sites. The data from this trial have not been published in a peer-reviewed journal but are available as an FDA summary of safety and effectiveness. (2) Patients who participated in the study had undergone a prior lower gastrointestinal endoscopic procedure with at least 1 polyp identified, and were referred for an additional colonoscopy exam, in which fiberoptic analysis of the polyps was performed. At the time of the colonoscopy, the physicians documented whether or not the polyp was considered hyperplastic or adenomatous, and whether or not they would remove the polyp. The fiberoptic probe was then applied to 3 different portions of the polyp and a segment of normal adjacent mucosa. The physician did not know the results of the analysis and thus the test did not affect patient treatment. The effectiveness of the analysis was then calculated as its ability to correctly identify adenomatous polyps (i.e., sensitivity) and to correctly identify hyperplastic polyps (i.e., the specificity), either alone or in conjunction with physician assessment. The sensitivity and specificity of the physician assessment alone was 82.7% and 50%, respectively, compared to a combined sensitivity and specificity of 96.3% and 33%, respectively. In other words, fiberoptic analysis identified additional adenomatous polyps that the physician had classified as hyperplastic and presumably would not have removed based on visual assessment alone. This increase in sensitivity comes at the price of a decrease in specificity, as more hyperplastic polyps will undergo biopsy. However, according to the FDA, the risk of taking biopsies of additional hyperplastic polyps is minimal.

The clinical significance of these results and their effect on patient management is difficult to interpret from the data presented. It is not clear how the physician decided to select additional polyps for fiberoptic analysis (it is not entirely clear whether all polyps were analyzed and then underwent biopsy), or whether the same results could be obtained by simply randomly taking a biopsy of a subset of polyps that were considered hyperplastic on visual assessment. While adenomatous polyps are considered premalignant lesions, the evolution to cancer is a slow process requiring 7 to 8 years, and thus the immediate removal of all adenomatous polyps is not required. In addition, the finding of an adenomatous polyp serves as a marker that the patient should undergo more frequent endoscopic exams. It is well known that the current practice of visual inspection of polyps will certainly miss some adenomatous polyps, but this lack of sensitivity is considered acceptable if at least 1 adenomatous polyp is identified and the patient undergoes more frequent screening.

In 2009, Benes and Antos investigated the correlation between the results of an optical biopsy system and the histopathology report of the physical biopsy specimens of the same polyps removed at colonoscopy. Paired optical and physical biopsies were performed on 55 polyps with complete polypectomy of the same tissue. The hospital pathologist identified 53 adenomatous polyps and 2 hyperplastic polyps. Fifty-two polyps were identified as suspect (adenomatous) and 2 as non-suspect (hyperplastic) by the optical biopsy system. One villous adenoma could not be optically analyzed due to friability. The examiners concluded that the WavSTAT® Optical Biopsy System provided accurate information to the gastroenterologist to assist in distinguishing between hyperplastic and adenomatous polyps. However, a larger and thus statistically more significant data set is needed in order to further verify the results achieved. (7)

Chromoendoscopy

Individuals at Average-Risk of Colorectal Cancer

Clinical Validity

There are few trials evaluating chromoendoscopy for colorectal cancer (CRC) 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 the 2011 study by Pohl et al., although approximately half of study participants were undergoing screening colonoscopy, the group results were not reported separately. (8)

One large randomized trial (2010) involving 660 patients conducted at 4 centers in the United States was identified. (9) Those eligible for inclusion had an average risk of CRC, 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 was 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=0.07). The mean number of adenomas per subject that were less than 5 mm in diameter differed significantly between the 2 groups, which was 0.8 in the chromoendoscopy group and 0.7 in the standard endoscopy group (p=0.03). 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 group; p=0.70). 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=0.40). The authors stated that the high rate of adenoma detection in both groups might have been due to the use of high-definition colonoscopy.

In 2011, Pohl et al. in Germany published a large randomized controlled trial (RCT) comparing pancolonic chromoendoscopy with indigo carmine dye with standard colonoscopy. (8) The trial included patients presenting for primary CRC 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 mean extubation time was 11.6 minutes in the chromoendoscopy group and 10.1 minutes in the standard colonoscopy group; the difference between groups was statistically significant (p<0.001). The primary study outcome (the proportion of patients with adenomas) differed significantly between groups (p=0.002). 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 were found to have at least 1 adenoma; the difference between groups was statistically significant (p=0.012). 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 of adenomas 10 mm or larger did not differ significantly (p=0.092), but the trial might have been underpowered for this analysis.

Clinical Utility

In patients at average risk of CRC, no RCTs or nonrandomized comparative studies were identified that evaluated the impact of chromoendoscopy on subsequent development of CRC or on CRC mortality.

Section Summary: Individuals at Average-Risk of CRC

There is a lack of evidence on the use of chromoendoscopy in an average-risk screening population. The single RCT that focused on this issue did not find that high-definition chromoendoscopy identified more clinically meaningful lesions than high-definition white-light colonoscopy. Moreover, about half of the participants in a trial from Germany were average-risk individuals seeking screening colonoscopy, but the trial results were not stratified by population. No controlled studies have evaluated the impact of chromoendoscopy versus standard colonoscopy on health outcomes (e.g., CRC mortality) in this patient population.

Individuals at Increased Risk of CRC

Clinical Validity

Individuals may be at higher risk for CRC due to family or personal history, or symptoms suggestive of colorectal disease (excluding patients with known inflammatory bowel disease [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 to 10 mm in size, is described next.

A 2010 Cochrane review by Brown and Baraza identified RCTs that compared chromoendoscopy and 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 CRC resection. (10) Reviewers excluded studies of individuals with IBD or a known polyposis syndrome. Five RCTs (total N=1059 participants) met inclusion criteria; only 1 of the 5 studies had sites in the United States. Three studies used some type of “back-to-back” design in which each participant underwent the equivalent of 2 colonoscopies. (A 2016 version of the Brown et al. Cochrane review included both studies of patients at increased risk of CRC and those at average risk, meta-analyses did not stratify by patient population. [11] The individual studies, none of which was published more recently than 2011, are discussed in the appropriate sections of this medical policy.)

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 than with nonchromoendoscopy interventions (pooled mean difference, 0.80; 95% confidence interval [CI], 0.60 to 1.00; p<0.001). Further, 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<0.001). Tests for heterogeneity were statistically significant in both analyses. According to reviewers, potential reasons for clinical heterogeneity may 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 [OR], 1.67; 95% CI, 1.29 to 2.15; p<0.001). A pooled analysis of 4 of the studies found that 47 (9%) of 497 in the chromoendoscopy group and 20 (4%) of 512 in the nonchromoendoscopy group were found to have 3 or more neoplastic lesions (pooled OR=2.55; 95% CI, 1.49 to 4.36; p=0.006). The Cochrane review 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 colorectal cancer. 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.

Representative trials included in the Cochrane review and those published more recently follow.

Le Rhun et al. published findings of a French study in 2006 involving 203 patients with a history of familial or personal colonic neoplasia or alarm symptoms (e.g., change in bowel habit, abdominal pain) after age 60 years. (12) 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 end point of total number of adenomas per patient did not differ significantly between groups. Mean (SD) 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 (SD) of 0.04 (0.20) in the standard colonoscopy group and 0.10 (0.39) in the chromoendoscopy group (p=0.17).

In 2008, Stoffel et al. published findings of a study with 5 sites in the United States, Canada, and Israel. (13) Eligibility criteria included a personal history of CRC 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, use of chromoendoscopy was significantly associated with an increased likelihood of finding at least 1 additional adenoma on the second examination (p=0.04).

Clinical Utility

In patients at increased risk of CRC, no RCTs or nonrandomized comparative studies were identified that evaluated the impact of chromoendoscopy on subsequent development of CRC or CRC mortality.

Section Summary: Individuals at Increased Risk of CRC

Several RCTs and back-to-back colonoscopy studies have evaluated chromoendoscopy in patients at increased risk of CRC. A Cochrane review of trials comparing chromoendoscopy with standard colonoscopy in high-risk patients (but excluding those with IBD) found a significantly higher rate of adenoma detection and rate of 3 or more adenomas with chromoendoscopy compared with standard colonoscopy. The evidence for detecting larger polyps, either defined as those 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 for polyps greater than 10 mm. No controlled studies have evaluated the impact of chromoendoscopy versus standard colonoscopy on health outcomes (e.g., CRC mortality) in this patient population. Although increased detection of adenomas could lower the incidence rate of CRC, robust evidence of this improved detection and a strong chain of indirect evidence, such as might be provided by rigorous modeling studies, is not available.

Patients with IBD

Detection Rate of Clinically Important Adenomas/Neoplastic Lesions

In 2011, Subramanian et al. published a meta-analysis of studies evaluating the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with IBD. (14) To be included in the meta-analysis, studies had to be prospective, evaluate surveillance colonoscopy in patients with IBD, and compare chromoendoscopy to white-light colonoscopy. Six published studies (total N= 1277 patients) met the inclusion criteria. Only 1 study was conducted in the United States; 3 used indigo carmine dye, and 3 used methylene blue dye. Duration of the procedure was established by pooling data from 1120 patients across 4 studies. In this pooled analysis, procedures using chromoendoscopy took a mean of 11 minutes longer than white-light endoscopy (95% CI, 10 minutes 15 seconds to 11 minutes 43 seconds). Reviewers stated that chromoendoscopy procedures lasted significantly longer than white-light endoscopy but did not report the exact p value for this analysis.

In a pooled analysis of all 6 studies were pooled, 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 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 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.

A 2012 meta-analysis by Wu et al. on the diagnostic accuracy of chromoendoscopy for identifying dysplasia in patients with IBD and using histopathologic diagnosis as the reference standard included 6 studies. (15) The primary end points were the sensitivity and specificity of chromoendoscopy compared with 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.

A description of key studies published more recently than the meta-analyses are described next.

In 2015, Mooiweer et al. retrospectively analyzed data on 937 patients with ulcerative colitis or Crohn disease who were undergoing surveillance with colonoscopy. (16) 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 189 (10%) of 1802 procedures performed with white-light colonoscopy (95% CI, 9% to 12%). The between-group difference in the rate of detection was not statistically significant (p=0.80). 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.

In 2014, Freire et al. reported on 162 patients with a confirmed diagnosis of longstanding (at least 8 years) left-sided or extending ulcerative colitis that was clinically inactive. (17) Patients were randomized to undergo conventional colonoscopy or 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, 6 in the conventional colonoscopy group). All neoplasias were low grade. Compared with standard histological evaluation, the sensitivity and specificity of chromoendoscopy for detecting intraepithelial neoplasia were 85.7% and 97.9%, respectively.

Marion et al. reported on a prospective cohort of patients with ulcerative colitis or Crohn colitis in 2008, (18) with long-term follow-up published in 2016. (19) In the initial study, 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 targeted biopsy of any abnormality or lesion identified through spraying. The study included blinded evaluation of specimens. In the first pass of the colonoscope using random biopsy, 3 of 102 (3%) patients were found to have dysplasia. In 1 of the 3 patients, an additional dysplastic lesion was found using chromoendoscopy during the second pass of the colonoscope. No carcinomas were identified by any method. A total of 3264 random biopsies were taken using standard colonoscopic analysis; 3 (0.09%) 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.

In 2016, follow-up data were reported on 68 (67%) of the 102 patients in the cohort. (19) Median length of follow-up was 28 months. Surveillance intervals varied from 6 to 12 months, depending on findings of the initial examination. During follow-up, patients underwent a mean of 3.15 endoscopy procedures (range, 1-5) 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 [HR], 12.1; 95% CI, 3.2 to 46.2; p<0.001). 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.

In 2016, Gasia et al. retrospectively analyzed data from a cohort of 454 patients who had IBD for at least 8 years who were undergoing surveillance at a single tertiary care center. (20) The endoscopic approach used was at the discretion of the physician; however, only 1 of 8 endoscopists had training in chromoendoscopy. A total of 126 patients had standard colonoscopy, 182 had high definition (HD) 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 the random biopsy groups (8.2%; 95% CI, 5.6% to 11.7%). Rates of neoplasia detection did not differ significantly in the HD colonoscopy, chromoendoscopy and virtual chromoendoscopy groups that received targeted biopsy.

Clinical Utility

In patients with IBD, no RCTs identified evaluated the impact of chromoendoscopy on subsequent development of CRC or on mortality from CRC. The Marion study (described above) was a nonrandomized comparative study that followed patients for a mean of 28 months. (19) Authors found that chromoendoscopy was associated with earlier colectomy but the study was not powered to evaluate differences in the survival rate with chromoendoscopy and standard colonoscopy. It is difficult to generalize from this study’s finding on colectomy because only a single endoscopist was trained in chromoendoscopy techniques. More generally, concerns remain about the learning curve with chromoendoscopy and ability to use the technique in a variety of practice settings.

Section Summary: Patients With IBD

Meta-analysis of clinical trials focusing on patients with IBD has found a statistically significantly higher yield of chromoendoscopy over white light colonoscopy in detecting dysplasia. More recent studies had mixed findings. It remains uncertain whether chromoendoscopy is more accurate for detecting dysplasia, especially compared with HD colonoscopy with targeted biopsies. In addition, there are concerns about physician learning curves with chromoendoscopy, and there is a lack of evidence that increased lesions detected by chromoendoscopy results in improved health outcomes.

Electronic (Virtual) Endoscopy

A 2014 systematic review by Omata et al. compared rates of polyp detection by virtual chromoendoscopy (i.e., Fujinon Intelligent Color Enhancement [FICE] or i-SCAN) with white-light colonoscopy. (21) 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 of adenoma and neoplasia detected by virtual chromoendoscopy versus conventional chromoendoscopy was 1.09 (95% CI, 0.97 to 1.23; p>0.05).

Average-Risk Patients Undergoing Screening Colonoscopy

Clinical Validity

Two studies using modified back-to-back designs in patients undergoing screening colonoscopy were conducted by Chung et al. in South Korea. The larger study, published in 2014, included 1650 adults at average risk of CRC, who were randomly divided across 3 groups. (22) 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 narrow-band imaging (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 patients (5.5%) were excluded from analysis due to inadequate bowel preparation. For the primary outcome of adenoma detection rate, no statistically significant difference was 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=0.75). 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=0.59). 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; a difference that was not statistically significant (p=0.30). 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, which was 4.4 mm.

A 2010 study by Chung et al. included 359 asymptomatic patients receiving screening colonoscopies. (23) 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). In the initial colonoscopy, a total of 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=0.74). 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=0.59). All missed adenomas were low grade and nonpedunculated. All but 1 (which was 6 mm) were 5 mm or less in size. In both Chung studies, virtual chromoendoscopy did not improve rates of adenoma detection compared with white-light endoscopy and did not identify more large adenomas.

A 2009 industry-supported multicenter RCT by Pohl et al. in Germany compared FICE and targeted standard chromoendoscopy using indigo carmine stain. (24) 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 using a spray catheter through the working channel of the colonoscope for further assessment of any lesions that were identified. In the FICE group, withdrawal was performed using FICE at the preset for examining colorectal mucosa. Data were available for analysis on a total of 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; the difference between groups was not statistically significant (p=1.0). The number of small adenomas (defined as ≤10 mm) did not differ significantly between groups (p=0.41). The proportion of large adenomas greater than 10 mm identified in the 2 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=0.85).

Clinical Utility

In patients at average risk of CRC, no RCTs or nonrandomized comparative studies were identified that evaluated the impact of virtual chromoendoscopy on the subsequent development of CRC or on CRC mortality.

Section Summary: Average-Risk Patients Undergoing Screening Colonoscopy

Several RCTs have evaluated electronic (virtual) chromoendoscopy in average-risk patients. None found that electronic chromoendoscopy improved the detection of clinically important polyps compared with standard colonoscopy. There is a lack of studies on the impact of electronic chromoendoscopy on CRC incidence and mortality compared with standard colonoscopy.

Individuals at Increased Risk of CRC

Clinical Validity

In 2010, Cha et al. evaluated South Korean patients at increased risk of CRC due to a personal history of polyps or gastrointestinal symptoms. (25) 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 patients (49.2%) in the FICE group and 23 (35.4%) in the white-light group were found to have 1 or more adenomas (p=0.12). 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=0.46). The number of adenomas less than 5 mm in size (the primary study outcome) differed significantly between groups. Twenty-eight (44.4%) of patients in the FICE group and 14 (21.5%) in the white-light group (p=0.006) were found to have adenomas between 0 and 5 mm. All adenomas identified were low grade, and no complications were reported in either group.

A study using a modified back-to-back colonoscopy design was published in 2012 by Kiriyama et al. 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 on either examination were removed, and specimens were sent for evaluation. 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%) were found with white-light colonoscopy. The miss rate was defined as the proportion of total lesions in that grouping that were detected on the second examination. The miss rate for all polyps with FICE (12/39 lesions [31%]) was significantly less than that with white light (28/61 lesions [46%]) (p=0.03). Twenty-six (44%) of 59 neoplastic lesions detected by FICE and 14 (37%) of 38 of 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.

Clinical Utility

In patients at increased risk of CRC, no RCTs or nonrandomized comparative studies were identified that evaluated the impact of virtual chromoendoscopy on the subsequent development of CRC or on CRC mortality. There is no strong chain of evidence that would support an argument that the differences in lesion detection rates would result in improved patient outcomes.

Section Summary: Individuals at Increased Risk of CRC

A few RCTs have evaluated electronic (virtual) chromoendoscopy in patients at increased risk of CRC. None found that electronic chromoendoscopy improved the detection of clinically important polyps compared with standard colonoscopy. There is a lack of studies demonstrating the impact of electronic chromoendoscopy on CRC incidence or mortality compared with standard colonoscopy, and a strong chain of evidence cannot be constructed.

Patients With IBD

Clinical Validity

One RCT has evaluated electronic (virtual) chromoendoscopy in patients with IBD. This 2013 trial by Neumann et al. in Germany randomized 83 patients with mild or inactive IBD to high- definition white-light endoscopy or virtual chromoendoscopy. (27) Seventy-eight (94%) patients completed the study; 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 agreed with histopathologic findings in 19 (48.7%) of 39 of the white-light group and 36 (92.3%) of 39 patients in the virtual chromoendoscopy group. The difference between groups was statistically significant, favoring virtual chromoendoscopy (p=0.001). In terms of disease activity, the agreement between endoscopic prediction of disease activity and histopathologic findings was 21 (53.9%) of 39 in the white-light group and 35 (89.7%) of 39 in the virtual chromoendoscopy group (p=0.066). Although the agreement was higher in the virtual chromoendoscopy group, the between-group difference was not statistically significant at p less than 0.05.

The 2016 retrospective cohort study by Gasia et al. (discussed above in the section on chromoendoscopy) included a group assigned to virtual chromoendoscopy. (20) In brief, this study included 454 patients with IBD undergoing surveillance. Rates of neoplasia detection did not differ significantly in the HD colonoscopy, chromoendoscopy, and virtual chromoendoscopy groups used with targeted biopsy. However, rates of neoplasia detection were significantly higher in patients who had targeted biopsy with HD colonoscopy, chromoendoscopy or 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%).

Clinical Utility

In patients with IBD, no RCTs or nonrandomized comparative studies were identified that evaluated the impact of electronic (virtual) chromoendoscopy on the subsequent development of CRC or on CRC mortality.

Section Summary: Patients with IBD

One RCT compared electronic (virtual) chromoendoscopy and white-light endoscopy in patients with IBD. It found a significant likelihood that electronic chromoendoscopy would correctly identify the extent of disease inflammation 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 demonstrating the impact of electronic chromoendoscopy on CRC incidences or mortality compared with standard colonoscopy, and a strong chain of evidence supporting improved outcomes cannot be constructed.

Summary of Evidence

Fiberoptic Analysis

Due to the lack of well-designed, randomized controlled trials within the published peer-reviewed literature, there is insufficient evidence to support the use of in-vivo analysis of colorectal polyps utilizing fiberoptic analysis for the screening, diagnosis or surveillance of colorectal cancer.

Chromoendoscopy

For individuals who have an average risk of colorectal cancer (CRC) who receive chromoendoscopy, the evidence includes a randomized controlled trial (RCT) focused on this population. Relevant outcomes are overall survival, disease-specific survival, test accuracy and 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 accuracy and 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 a significantly higher rate of adenoma detection and rate of 3 or more adenomas with chromoendoscopy compared with standard colonoscopy. The evidence for detecting larger polyps, either 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 for 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 virtual chromoendoscopy, the evidence includes observational studies and meta-analyses of observational data. Relevant outcomes are overall survival, disease-specific survival, test accuracy and validity, and change in disease status. The 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 rate will translate into improved health outcomes. Moreover, there are concerns about the comparison group used in some of these trials. It is uncertain whether the control groups received optimal colonoscopy; therefore, the improved detection rate 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.

Electronic (Virtual) Chromoendoscopy

For individuals who have an average risk of CRC who receive electronic chromoendoscopy, the evidence includes several RCTs and a meta-analysis. Relevant outcomes are overall survival, disease-specific survival, test accuracy and validity, and change in disease status. The available RCTs have not found that electronic chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies on the impact of electronic chromoendoscopy on CRC incidence or mortality 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 colorectal cancer who receive electronic chromoendoscopy, the evidence includes several RCTs and a meta-analysis. Relevant outcomes are overall survival, disease-specific survival, test accuracy and validity, and change in disease status. The available RCTs have not found that electronic chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies on the impact of electronic chromoendoscopy on CRC incidence or mortality 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 electronic chromoendoscopy, the evidence includes an RCT and nonrandomized comparative study. Relevant outcomes are overall survival, disease-specific survival, test accuracy and validity, and change in disease status. The RCT found a significantly greater likelihood that electronic 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 on the impact of electronic chromoendoscopy CRC incidence or mortality compared with standard colonoscopy. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

American Society for Gastrointestinal Endoscopy and American Gastroenterological Association

In 2015, the American Society for Gastrointestinal Endoscopy (ASGE) and the American Gastroenterological Association published the SCENIC consensus statement on surveillance and management of dysplasia in patients with IBD. (28) The statement, developed by an international multidisciplinary group representing a variety of stakeholders, incorporated systematic reviews of the literature. Relevant recommendations included the following (see Table 1).

Table 1. Recommendations on Surveillance and Management of Dysplasia in Patients with IBD

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

IBD: inflammatory bowel disease; LOA: level of agreement; QOE: quality of evidence; SOR: strength of recommendation.

Panelists did not reach consensus regarding 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 standard of care in IBD surveillance. (29, 30) Both commentaries noted that the guidelines consider the outcome of detection of dysplasia and not disease progression or survival. Moreover, the authors note the lack of longitudinal data on clinical outcomes in patients with dysplastic lesions detected using chromoendoscopy.

American Society for Gastrointestinal Endoscopy

In 2015, ASGE issued guidelines on endoscopy in the diagnosis and treatment of inflammatory bowel disease, which made the following recommendations about chromoendoscopy (31): “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.”

In 2015, ASGE also published a systematic review and meta-analysis assessing narrow-band imaging (NBI), 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. (32) 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 for both the ‘diagnose-and-leave’ strategy for diminutive (≤5 mm) rectosigmoid hyperplastic polyps and the ‘resect-and-discard’ strategy for diminutive (≤5mm) 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

The 2012 Multi-Society Task Force guidelines on colonoscopy surveillance after screening and polypectomy (consensus update), stated that chromoendoscopy and narrow-band imaging may enable endoscopists to accurately determine if lesions are neoplastic, and if there is a need to remove them and send specimens to pathology. The guideline noted that these technologies currently do not have an impact on surveillance interval. (33)

U.S. Preventive Services Task Force Recommendations

The 2016 U.S. Preventive Services Task Force recommendations on screening for colorectal cancer do not mention chromoendoscopy. (34)

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 2.

Table 2. Summary of Key Trials

NCT No.

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT02822352

RCT: High Definition White Light (HDWL) vs. Virtual Chromoendoscopy in the Detection of Intraepithelial Neoplasia in Longstanding Colitis (VIRTUOSO)

204

Nov 2017

Unpublished

NCT01505842

Chromoendoscopy for Dysplasia Detection in Chronic Inflammatory Bowel Disease

300

Feb 2017 (unknown)

NCT: national clinical trial

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

There are no specific CPT codes for these services; all would most likely be reported with an unlisted CPT code.

CODING:

Disclaimer for coding information on Medical Policies

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.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

44799, 45999

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Neumann H, Fujishiro M, Wilcox CM, Monkemuller K. Present and future perspectives of virtual chromoendoscopy with i-scan and optical enhancement technology. Dig Endosc. 2014; 26 Suppl 1:43-51. PMID 24373000

2. FDA--Optical Biopsy System: Summary of Safety and Effectiveness. Food and Drug Administration – Center for Devices and Radiologic Health (2009):1-24. Available at <http://www.fda.gov> (accessed May 4, 2018).

3. ASGE Technology Committee. Electronic chromoendoscopy. Available at <http://www.asge.org> (accessed May 4, 2018).

4. ASGE Technology Committee. GI Endoscopes. Available at <http://www.asge.org> (accessed May 4, 2018).

5. Food and Drug Administration (FDA). Medical and Radiation Emitting Device Recalls. Class 2 Recall, EPX-4400 and EPX-4400HDVideo Processor. Available at <http://www.accessdata.fda.gov> (accessed May 4, 2018).

6. Food and Drug Administration (FDA). 510(k) Summary: Pentax EPK-i5010 Video Processor. 2013. Available at <http://www.accessdata.fda.gov> (accessed May 4, 2018).

7. Benes Z, Antos Z. Optical biopsy system distinguishing between hyperplastic and adenomatous polyps in the colon during colonoscopy. Anticancer Res. 2009; 29(11):4737-4739. PMID 20032428

8. 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):485-490. PMID 21159889

9. 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):1301-1307. PMID 20179689

10. 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

11. 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. 2016; 4:CD006439. PMID 27056645

12. 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):349-354. PMID 16527699

13. 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):507-513. PMID 19139000

14. 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):304-312. PMID 21128987

15. 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):416-420. PMID 21073646

16. 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):1014-1021. PMID 25823770

17. 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):2038-2045. PMID 25185683

18. 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):2342-2349. PMID 18844620

19. 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):713-719. PMID 26656297

20. 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):704-712 e704. PMID 26804384

21. 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):222-237. PMID 24328858

22. 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. Jul 12 2013. PMID 23853211

23. 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):136-142. PMID 20493487

24. 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):73-78. PMID 18838485

25. 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):2357-2364. PMID 19834809

26. 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

27. 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):1935-1942. PMID 23839228

28. 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; e628. PMID 25702852

29. 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):1035-1037. PMID 26148262

30. 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):462-467. PMID 25702851

31. Shergill AK, Lightdale JR, Bruining DH, et al. The role of endoscopy in inflammatory bowel disease. Gastrointest Endosc. May 2015; 81(5):1101-1121 e1101-1113. PMID 25800660

32. 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.e501-502.e516. PMID 25597420

33. 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

34. U.S. Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement. JAMA. Jun 21 2016; 315(23):2564-2575. PMID 27304597

35. In Vivo Analysis of Colorectal Polyps – Archived. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (November 2009) Medicine: 2.01.51.

36. Chromoendoscopy as an Adjunct to Colonoscopy. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (November 2017) Medicine: 2.01.84.

Policy History:

Date Reason
6/15/2018 Document updated with literature review. Coverage unchanged. References 31-32 added.
1/15/2018 Reviewed. No changes.
2/1/2017 Document updated with literature review. The following changes were made to Coverage: 1) Added fiberoptic analysis, chromoendoscopy, and electronic (virtual) chromoendoscopy as examples of in-vivo analysis. 2) Added “NOTE: For “Confocal Laser Endomicroscopy (CLE)” see MED201.038”.
8/15/2015 Reviewed. No changes
2/15/2014 Document updated with literature review. Coverage unchanged. CPT/HCPCS code(s) updated. Title changed from “Fiberoptic Analysis of Colorectal Polyps” to “In Vivo Analysis of Colorectal Polyps”.
5/1/2008 Policy reviewed without literature review.
11/15/2006 Revised/updated entire document
8/15/2006 New medical document

Archived Document(s):

Title:Effective Date:End Date:
In-Vivo Analysis of Colorectal Polyps01-15-201806-14-2018
In-Vivo Analysis of Colorectal Polyps02-01-201701-14-2018
In Vivo Analysis of Colorectal Polyps08-15-201501-31-2017
In Vivo Analysis of Colorectal Polyps02-15-201408-14-2015
Fiberoptic Analysis of Colorectal Polyps05-01-200802-14-2014
Fiberoptic Analysis of Colorectal Polyps11-15-200604-30-2008
Fiberoptic Analysis of Colorectal Polyps08-15-200311-14-2006
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