According to the World Health Organization (WHO), colorectal cancer (CRC) was the third-most common type of cancer with regard to morbidity and had the fourth highest rate of mortality among all cancers in 2012.¹ In Japan, there were 149,500 cases and 53,000 deaths among a population of 126 million in 2017, making CRC the most common type of cancer with regard to morbidity and the second-most common cause of cancer-related death—and the incidence is still increasing.² Due to the aging of the population, the incidence of CRC and the number of colonoscopy procedures are expected to increase in the future. The effective tumor detection, accurate diagnosis, and treatment of tumors are important for reducing the rate of CRC death.

For these reasons, a light amplification by stimulated emission of radiation (LASER) endoscopic system (LASEREO; Fujifilm Co., Tokyo, Japan) was developed in 2012.³ The system allows for blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) to be performed as modes of narrow-band light observation; these modes have been reported to be useful for tumor detection and characterization.^4–18 Furthermore, an innovative endoscopy system using four-light emitting diode (LED) multilight technology (Fujifilm Co.) was released in 2016 to 2017 for some areas in which LASER endoscopes have not been approved for use, including the United States and Europe.¹⁹ This system enables blue light imaging (this is also called as BLI) and LCI with an LED light source instead of a LASER light source.

In this paper, we review the efficacy of BLI and LCI with LASER and LED endoscopes in colorectal tumor detection and characterization.

The new endoscope system “LASEREO,” which was developed by Fujifilm, uses a semiconductor LASER as a light source. It has a narrow-band light observation function without a customized optical filter. The LASEREO system consists of a light source (LL-7000), a processor (VP-7000), and a series of special scopes. The LL-7000 light source has two types of lasers with wavelengths of 410 and 450 nm (Fig. 1)^4,5 and peak wavelength ranges of 410±10 and 450±10 nm, respectively. In addition, both bandwidths are less than approximately 2 nm. In contrast, the wavelengths of narrow band imaging (NBI; Olympus, Tokyo, Japan) with a xenon lamp are 415 nm and 540 nm and the bandwidth of it is 30 nm.⁴ The irradiation of phosphor by the 450-nm wavelength LASER achieves fluorescent light. The combination of strong LASER light with a 450-nm wavelength LASER and fluorescent light provides an enough degree of illumination for white-light imaging (WLI). The 410-nm wavelength LASER is used for BLI and functions as narrow-band light.

BLI light is made from the combination of the strong LASER light with a wavelength of 410 nm, weak LASER light with a wavelength of 450 nm, and fluorescent light. BLI light is useful for acquiring information about the mucosal surface, such as the patterns of surface blood vessels and structures. The use of LASERs with a specific wavelength and precisely regulated light power allows the blood vessels to be observed in detail and makes the surface patterns clear. The “BLI-bright” mode is generated by the appropriate combination of white light and BLI light, which is controlled by adjusting the power of the two LASERs. This mode is brighter than the BLI mode and is expected to be useful for tumor detection. LCI can also be performed using the light balance of similar power to BLI-bright and is useful for tumor detection. LCI makes lesions more reddish and the surrounding mucosa more whitish, creating good contrast for detecting tumors.

On the other hand, high-intensity illumination based on 4-LED Multi Light technology (BL-7000) provides high-quality images with white light and new observation modes of BLI and LCI. The system has four types of light: blue-violet, blue, green, and red (Fig. 1).¹⁹

NBI and pit pattern observation are the gold standard for tumor characterization.^20,21 BLI magnification is also regularly used to this end as well. This enables us to clearly observe the surface structures and vessel patterns.^4,5 Some reports have shown the efficacy of BLI magnification (Table 1).^4–6 Our previous study compared BLI and NBI. Endoscopic images of surface structures and vessel patterns obtained using BLI magnification were slightly different from those obtained with NBI magnification (Fig. 2).⁴ In detail, 104 colorectal neoplasms were examined with both BLI and NBI magnification. The Hiroshima classification was an NBI classification and was used to assess the surface structures and vessel patterns observed with NBI magnification in that study.²² The diagnostic accuracy of BLI magnification in the NBI classification was 74.0% (77/104), which was similar to that of NBI magnification (77.8%). The rate of consistency between BLI and NBI magnification in the NBI classification was 74.0%. Another study from our group showed that the diagnostic accuracy of BLI magnification was 84.3% among 314 polyps (hyperplastic polyps and sessile serrated polyps [SSP], n=41; low-grade adenoma, n=168; high-grade adenoma, n=80; T1 cancer, n=25) using the Hiroshima classification.⁵ The accuracy of differentiation between non-neoplastic and neoplastic lesions was 99.3% (312/314), while that between adenomatous and cancerous lesions was 85.0% (232/273). The diagnostic accuracy for polyps <20 mm in diameter was better than that for polyps ≥20 mm in diameter (92.1% vs 72.5%, p<0.001). The diagnostic accuracy with regard to the morphology was significantly lower for superficial polyps of ≥20 mm in diameter than for superficial polyps of <20 mm in diameter (70.0% vs 82.9%, p=0.03). In addition, the diagnostic accuracy of BLI without magnification for differentiating between neoplastic and non-neoplastic polyps <10 mm in diameter was 95.2%, which was greater than that of white light (83.2%).

The removal of adenomas by colonoscopy has been proven to reduce the incidence of CRC and CRC-related death.^24–26 However, it was reported that 20% to 27% of polyps were missed by WLI.^27,28 Various factors have been reported to be associated with an increased risk of missing polyps, including a flat morphology, small size, presence in the ascending colon, male sex, multiple polyps at the time of first colonoscopy, and a history of polyps.^29,30

BLI-bright is brighter than BLI and is expected to show improved rates of tumor detection. For colorectal tumors, BLI-bright makes a neoplastic lesion appear brownish in color, facilitating their detection. Our previous study on polyp visibility was performed with short movies of polyps recorded with BLI-bright and WLI and an original polyp visibility scoring system (score 4, excellent visibility; score 3, good; score 2, fair; score 1, poor).⁸ In the movies of 100 whole neoplastic and non-neoplastic polyps, BLI-bright achieved higher scores than WLI (experts: 3.10±0.95 vs 2.90±1.09, p=0.00013; non-experts: 3.04±0.94 vs 2.78±1.03, p<0.0001) (Fig. 7). In addition, a subgroup analysis of experts only showed that the mean visibility score of BLI-bright mode was significantly higher than that of WLI for flat polyps, neoplastic polyps, and polyps located in the left-sided colon and rectum.

There have been some randomized controlled trials (RCTs) for detection using BLI (Table 2). Our previous multicenter RCT showed that BLI-bright (n=489) resulted in a greater mean number of adenomatous polyps detected per patient than WLI (n=474) (1.27±1.73 vs 1.01±1.36, p=0.008) and also improved the mean total number of polyps per patient compared with WLI (1.84±2.09 vs 1.43±1.64, p=0.001).⁹ However, BLI-bright required a longer observation times than WLI (9.5±3.8 minutes vs 8.4±2.9 minutes, p<0.001). Another RCT in which patients were randomized to one of two tandem colonoscopy groups (BLI followed by WLI or WLI followed by BLI) showed that the polyp miss rate in the BLI-WLI group was 1.6%, which was significantly lower than that in the WLI-BLI group (10.0%, p=0.001).¹⁰

BLI-bright observation is not widely accepted; however, there have been some positive reports, as described above. There are two major limitations regarding the use of BLI-bright. First, the residual liquid becomes reddish, which disturbs the endoscopic view. Second, the endoscopic view of BLI-bright is darker than with WLI, and NBI has the same problems. LCI has the potential to resolve these problems because it is brighter than BLI and BLI-bright and because the residual liquid becomes yellowish with LCI (Fig. 8). We previously reported that LCI improved the polyp visibility score using endoscopic movies.¹² Among the LCI, BLI-bright, and WLI movies of 101 colorectal polyps, the mean polyp visibility scores of LCI (2.86±1.08) were higher than those of WLI (2.54±1.15, p<0.001) and BLI-bright (2.73±1.47, p<0.001). In addition, LCI resulted in a reduced number of polyps that showed poor polyp visibility scores (scores of 1 or 2) compared with WLI (experts: 35.6% vs 49.6%, p<0.015; non-experts: 33.6% vs 50.5%, p=0.046). Furthermore, this study showed the efficacy of LCI for observing non-polypoid tumors and SSPs.¹² Another study that we performed using endoscopic images showed the efficacy of LCI in the observation of diminutive polyps (<5 mm="" in="" size="" span="" class="xref">13 In that study, the color difference values between the tumor and the surrounding mucosa were calculated among endoscopic images of 54 colorectal polyps obtained by WLI and LCI in order to evaluate polyp visibility. The color difference value is thought to be an objective indicator of the polyp visibility. That study showed that LCI improved the color difference values more than WLI (33.6±13.9 vs 20.7±13.6, p<0.001) (Fig. 9). A similar study using polyp visibility scores showed that LCI improved the endoscopic visualization of non-granular colorectal lesions and also demonstrated the efficacy of LCI in the observation of SSPs.¹⁴

Several studies have shown the usefulness of LCI in polyp detection (Table 2). A Chinese RCT proved that LCI increased the adenoma detection rate (ADR) (LCI vs WLI, 37% vs 28%; 95% confidence interval, 2.3% to 19.4%) (Table 2).¹⁵ That same study also revealed that LCI resulted in significantly improved rates of adenoma and SSP detection compared with WLI (91% vs 73%, p<0.001). A Japanese RCT of LCI showed that the polyp detection rate of 6 non-expert endoscopists (92.3%±2.9%) was significantly higher than with WLI (72.7%±11.5%, p<0.01) for observations from the cecum to splenic flexure.¹⁶ Furthermore, in a tandem endoscopy setting, the SSP detection rate of the LCI group (21.6%, 8/37) was significantly higher than that of the LCI-WLI group (3.2%, 1/31; p=0.02). A European RCT of LCI with LED showed a significant difference in the adenoma miss rate in the right sided colon (cecum and ascending colon) between WLI and LCI (30.6% vs 11.8%, p<0.001).¹⁷ Furthermore, in our previous study, an additional 30-second observation with LCI after WLI observation was found to significantly improve the overall adenoma and SSP numbers compared with a second observation with WLI after initial WLI.¹⁸ In that study the cecum and ascending colon were observed with WLI first in all cases, after which the colonoscope was inserted again, and the cecum and ascending colon were observed for an additional 30 seconds using either LCI or WLI. In this additional 30-second observation, the cecum and ascending colon were sufficiently insufflated and observed from a distant view. The overall adenoma and SSP numbers in the first and second observations of the LCI and WLI groups were 48 and 36, respectively (p=0.02). In addition, in the LCI group, the number of adenomas and SSPs in the first and second observations were significantly higher than in the first observation (48 vs 35, p=0.017). However, one limitation associated with LCI involved issues with halation in the endoscopic view due to the high brightness, which might lead to missed polyps.

BLI with or without magnification and LCI without magnification with a LASER endoscope are more effective for polyp characterization than other approaches. BLI with a LASER endoscope and LCI with a LASER or LED endoscope are particularly useful for polyp detection. The BLI and LCI images obtained with a LASER endoscopy were considered to be almost similar to those obtained with an LED endoscope.

No potential conflict of interest relevant to this article was reported.