The demarcation line between the cancerous lesion and the surrounding area could be easily recognized with flexible spectral imaging color enhancement (FICE) system compared with conventional white light images. The characteristic finding of depressed-type early gastric cancer (EGC) in most cases was revealed as reddish lesions distinct from the surrounding yellowish non-cancerous area without magnification. Conventional endoscopic images provide little information regarding depressed lesions located in the tangential line, but FICE produces higher color contrast of such cancers. Histological findings in depressed area with reddish color changes show a high density of glandular structure and an apparently irregular microvessel in intervening parts between crypts, resulting in the higher color contrast of FICE image between cancer and surrounding area. Some depressed cancers are shown as whitish lesion by conventional endoscopy. FICE also can produce higher color contrast between whitish cancerous lesions and surrounding atrophic mucosa. For nearly flat cancer, FICE can produce an irregular structural pattern of cancer distinct from that of the surrounding mucosa, leading to a clear demarcation. Most elevated-type EGCs are detected easily as yellowish lesions with clearly contrasting demarcation. In some cases, a partially reddish change is accompanied on the tumor surface similar to depressed type cancer. In addition, the FICE system is quite useful for the detection of minute gastric cancer, even without magnification. These new contrasting images with the FICE system may have the potential to increase the rate of detection of gastric cancers and screen for them more effectively as well as to determine the extent of EGC.

Modest changes in morphology and color of the mucosa are important factors for the diagnosis of early gastric cancer (EGC). The morphological characteristics of EGC include mild elevation and shallow depression of the mucosa, as well as discontinuity with surrounding mucosa and areas of uneven surface. For changes in color, pale redness or fading is important. However, these endoscopic features have not been sufficient to achieve an accurate diagnosis for EGC. The flexible spectral imaging color enhancement (FICE) system was developed as a selection system of the narrow band image and introduced in 2005 as a novel image-processing tool for video endoscopy[1-4]. FICE enhances the contrast of mucosal surface without the use of dyes. Additionally, FICE provides optimal band image with the same light intensity as conventional endoscope, implying that the FICE system can display clear images even without magnification. Indeed, FICE can facilitate detection of changes in EGC without magnification and confirm accurately the diagnosis of cancer with low or half magnification[5-7].

Endoscopic submucosal dissection (ESD) was developed in the past 10 years as a more reliable method of endoscopic resection than endoscopic mucosal resection (EMR)[8-10]. In Japan, ESD has now been officially approved as an endoscopic treatment for EGC, and the mainstream of therapy for EGC has shifted from EMR to ESD. However, the accurate diagnosis of extent of gastric cancer is needed to achieve complete resection by ESD. FICE is very useful for the diagnosis of extent without or with magnification.

In this report, advance in endoscopic diagnosis for the extent of EGCs will be reviewed particularly focusing on FICE images.

Chromoendoscopy is often carried out by spraying dyes such as indigo carmine after thoroughly washing out the mucus and is useful to determine the extent of the tumor by clearer detection of the morphological feature of depressed or protruded cancerous margin. By contrast, FICE is often carried out not only by such detection of morphological feature but also higher color contrast between cancer and surrounding atrophic mucosa. Therefore, tumor margin may be easily identified in FICE images even without magnification.

The characteristic finding of depressed-type EGC in most cases was revealed as reddish lesions distinct from the surrounding yellowish non-cancerous area without magnification. Compared with conventional white light images, the demarcation line between the cancerous lesion and the surrounding area could be easily recognized with FICE system (Figure 1). Conventional endoscopic images provide little information regarding depressed lesions located in the tangential line, but FICE produces higher color contrast of such cancers, even with the small caliber-size scope for transnasal route[11] (EG 530NW) (Figure 1A and B). Histological findings in depressed area with reddish color changes show a high density of glandular structure and an apparently irregular microvessel in intervening parts between crypts. Such histological features differ from those of surrounding mucosa and may cause higher color contrast of FICE images between them.

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Figure 1 Image findings and specimen, A: Conventional image with small caliber endoscope (EG530-NW) reveals a slightly reddish mucosal change in the lesser curvature of the upper body; B: Flexible spectral imaging color enhancement (FICE) image with small caliber endoscope enhances a reddish cancerous lesion and can determine with precision a clear line of demarcation between cancer and the yellowish surrounding mucosa; C: FICE image with low magnification (EG590-ZW) also detects much clearer demarcation line; D: Specimen after endoscopic submucosal dissection shows a high density of glandular structure and an apparently irregular microvessel in intervening parts between crypts, which may cause a reddish mucosal change in depressed area.

Some depressed cancers are shown as whitish lesion by conventional endoscopy (Figure 2). FICE also can produce higher color contrast between whitish cancerous lesions and surrounding atrophic mucosa. For nearly flat cancer, FICE can produce an irregular structural pattern of cancer distinct from that of the surrounding mucosa, leading to a clear demarcation (Figure 3). On the other hand, most elevated-type EGCs are detected easily as yellowish lesions with clearly contrasting demarcation (Figure 4). In some cases, a partially reddish change is accompanied on the tumor surface similar to depressed type cancer (Figure 5)[5]. In addition, the FICE system is quite useful for the detection of minute gastric cancer, even without magnification. These new contrasting images with the FICE system may have the potential to increase the rate of detection of gastric cancers and screen for them more effectively as well as to determine the extent of EGC.

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Figure 2 Some depressed cancers are shown as whitish lesion by conventional endoscopy. A: Conventional image (EG590-ZW) reveals a slightly whitish mucosal change in the anterior wall of antrum; B: Flexible spectral imaging color enhancement (FICE) image enhances a whitish cancerous lesion and can determine a line of demarcation between cancer and surrounding mucosa; C: FICE image in a close-up view (EG590-WR) detects with precision a clearer demarcation line; D: FICE image with half magnification (EG590-ZW) reveals a finer microstructural pattern on mucosal surface of cancer and higher contrasting mucosa between cancer and the surrounding area, leading a clearer demarcation line.

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Figure 3 Conventional image and Flexible spectral imaging color enhancement image findings. A: Conventional image (EG590-ZW) reveals a slightly enriched vascular structure of gastric mucosa in the lesser curvature of the lower body; B: Flexible spectral imaging color enhancement (FICE) image enhances such a structure and shows reddish lesions in its anal side near angle; C: Conventional image near angle in a close-up view shows slightly reddish changes on the flat mucosa; D: FICE image near angle in a close-up view shows an irregular structural pattern distinct from the surrounding area, leading to a clearer demarcation line; E: Conventional image (EG590-WR) reveals a slightly enriched vascular structure in nearly flat mucosa in the antrum in a close-up view; F: FICE image enhances such a structure accompanied by a clear margin of cancer distinct from the surrounding mucosa. It is noted that these images can be obtained without magnification.

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Figure 4 Most elevated-type early gastric cancers are detected easily as yellowish lesions with clearly contrasting demarcation. A: Conventional image (EG590-ZW) in a distant view reveals a slightly elevated lesion similar to the mucosal color of surrounding area in the anterior wall of lower body; B: Flexible spectral imaging color enhancement (FICE) image shows an uneven surface on the elevated tumor; C: A close-up FICE image without magnification exhibits an irregular microstructural pattern on uneven tumor surface distinct from the surrounding mucosa; D: FICE image with low magnification distinguishes an apparently irregular microstructural pattern of cancer from a normal microstructural pattern of the surrounding mucosa.

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Figure 5 In some cases, a partially reddish change is accompanied on the tumor surface similar to depressed type cancer. A: Conventional image (EG590-ZW) in a distant view reveals an elevated lesion with slightly reddish portion in the posterior wall of antrum; B: Flexible spectral imaging color enhancement image enhances a reddish portion on tumor surface with more contrasting demarcation line. In addition, tumor margin of flat area in the right side of this figure can be more clearly visualized than conventional image.

Magnified FICE images are quite useful for an accurate diagnosis for EGC and determination of extent of EGC[5-7]. The irregular microstructural or nonstructural pattern is clearly identified on the tumor surface with magnification, despite the morphological types of EGC (Figures 1-4 and 6). Such patterns were found in none of the surrounding mucosa, resulting in the accurate demarcation line[5-7]. In addition, the irregular microvascular pattern of lesions is clearly visualized with half magnification (Figure 6). These findings were also helpful to confirm a definitely endoscopic diagnosis for EGC and are quite useful for marking in the noncancerous mucosa around the tumor after the determination of tumor margin, even in lesions with a blurred tumor margin by conventional images. Thus, en-bloc specimens with free lateral margins can be obtained by ESD. Low or half magnification in the FICE system allows endoscopists to more easily maintain the proper distance between the tip of endoscope and the gastric mucosa and to observe broad areas that include both cancerous and surrounding noncancerous portions simultaneously on the same endoscopic images.

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Figure 6 The irregular microvascular pattern of lesions is clearly visualized with half magnification. A: Conventional image (EG590-ZW) in a close-up view reveals a nearly flat lesion with a slightly reddish portion in the anterior wall of middle body; B: Flexible spectral imaging color enhancement (FICE) image enhances a reddish lesion leading to a clear demarcation line; C: Conventional image with half magnification shows an enriched microvascular structure on the tumor surface; D: FICE image with half magnification allows a clear visualization of irregular microvascular and microstructural pattern suggesting gastric cancer with the possible histological type of well-differentiated adenocarcinoma.

Histological types of gastric cancer do not influence the diagnosis of its extent and therefore an extremely high accuracy of demarcation line is maintained in most cases. However, an unclear demarcation line is evident in a few cases of EGC. The extent of gastric cancer with more than 20 mm in diameter may be misdiagnosed in a few cases even by an experienced endoscopists using FICE. Also, it is difficult to diagnose the extent of cancers with similar structural pattern to the surrounding area or accompanied by flat invasion, even though such lesions are observed with magnification.

In summary, even though targeted areas of the mucosa can be removed precisely by ESD, a complete resection cannot be expected without determining the extent of EGCs. The diagnostic accuracy of extent of gastric cancer using FICE is superior to that using conventional white light image. It is noted that endoscopic diagnosis of EGC with FICE system can be performed even with non-magnified images and half magnified images. FICE can yield higher color contrast between cancerous lesion and the surrounding area and reveal an irregular structural pattern in cancerous lesions without magnification. In addition, FICE can also produce a microvascular patterns with magnification. These findings contribute to the precise determination of extent of EGC.