Key points

Introduction

Patients with inflammatory bowel disease (IBD) have a high risk of colitis-associated dysplasia and cancer. These types of dysplasia and cancer, as compared with sporadic adenoma/carcinoma, seem to have a distinct growth pattern, which can be flat, multifocal, or anaplastic. Therefore, it is important that careful surveillance with colonoscopy is performed for all patients with IBD and, more frequently, for those considered to be at high risk. Traditionally, flat dysplasia in ulcerative colitis (UC) has been considered to be detectable only by using random biopsy specimens of mucosa that appeared unremarkable during endoscopy. However, recent studies have shown that most of them are visible; thus, their detection as nonpolypoid colorectal neoplasms (NP-CRNs) is an integral component in the prevention of colitic cancer.

Unlike dysplasia-associated lesions or masses, which are readily visible using conventional endoscopy, the detection of NP-CRN can be more difficult. NP-CRN in colitic IBD (cIBD) is often present simply as redness or a granular patch of mucosa that may not be readily distinguishable from the surrounding inflamed mucosa. Because it is often difficult to identify NP-CRN in cIBD using white light endoscopy, random blind biopsies are still commonly practiced, especially in Western countries, to potentially help detect these lesions. An alternative to random biopsy is to enhance the appearance of NP-CRN by using image-enhanced endoscopy and, in turn, to target the biopsy on areas that appear abnormal.

Several recent trials have evaluated dye-based image enhanced endoscopy (chromoendoscopy), magnifying endoscopy, and equipment-based image-enhanced endoscopy (IEE) to detect NP-CRN in cIBD. Of these techniques, the indigo carmine dye spray IEE has been shown to effectively increase the detection of areas suspected to contain NP-CRN and to delineate the border and surface of suspected and obvious lesions. Equipment-based IEE is a promising, but unproven, method that is designed to visualize small vessels and minute mucosal patterns. Of the currently available equipment-based IEE: narrow band imaging [NBI; Olympus, Tokyo, Japan], flexible spectral imaging color enhancement [Fujifilm, Tokyo, Japan], blue laser image [Fujifilm, Tokyo, Japan], autofluorescence imaging [AFI; Olympus, Tokyo, Japan], and i-scan [Pentax, Tokyo, Japan], clinical trials on the diagnosis of NP-CRN in cIBD have been published only for NBI and AFI.

In this article, the authors describe the present status of the use of IEE to diagnose NP-CRN using magnifying colonoscope and illustrate their practice at the Hiroshima University Hospital. The authors have collated a few cases to provide examples of their practice. The authors do not reiterate data reporting on the utility of chromoendoscopy as Subramanian and Bisschops have summarized them.

Introduction

Patients with inflammatory bowel disease (IBD) have a high risk of colitis-associated dysplasia and cancer. These types of dysplasia and cancer, as compared with sporadic adenoma/carcinoma, seem to have a distinct growth pattern, which can be flat, multifocal, or anaplastic. Therefore, it is important that careful surveillance with colonoscopy is performed for all patients with IBD and, more frequently, for those considered to be at high risk. Traditionally, flat dysplasia in ulcerative colitis (UC) has been considered to be detectable only by using random biopsy specimens of mucosa that appeared unremarkable during endoscopy. However, recent studies have shown that most of them are visible; thus, their detection as nonpolypoid colorectal neoplasms (NP-CRNs) is an integral component in the prevention of colitic cancer.

Unlike dysplasia-associated lesions or masses, which are readily visible using conventional endoscopy, the detection of NP-CRN can be more difficult. NP-CRN in colitic IBD (cIBD) is often present simply as redness or a granular patch of mucosa that may not be readily distinguishable from the surrounding inflamed mucosa. Because it is often difficult to identify NP-CRN in cIBD using white light endoscopy, random blind biopsies are still commonly practiced, especially in Western countries, to potentially help detect these lesions. An alternative to random biopsy is to enhance the appearance of NP-CRN by using image-enhanced endoscopy and, in turn, to target the biopsy on areas that appear abnormal.

Several recent trials have evaluated dye-based image enhanced endoscopy (chromoendoscopy), magnifying endoscopy, and equipment-based image-enhanced endoscopy (IEE) to detect NP-CRN in cIBD. Of these techniques, the indigo carmine dye spray IEE has been shown to effectively increase the detection of areas suspected to contain NP-CRN and to delineate the border and surface of suspected and obvious lesions. Equipment-based IEE is a promising, but unproven, method that is designed to visualize small vessels and minute mucosal patterns. Of the currently available equipment-based IEE: narrow band imaging [NBI; Olympus, Tokyo, Japan], flexible spectral imaging color enhancement [Fujifilm, Tokyo, Japan], blue laser image [Fujifilm, Tokyo, Japan], autofluorescence imaging [AFI; Olympus, Tokyo, Japan], and i-scan [Pentax, Tokyo, Japan], clinical trials on the diagnosis of NP-CRN in cIBD have been published only for NBI and AFI.

In this article, the authors describe the present status of the use of IEE to diagnose NP-CRN using magnifying colonoscope and illustrate their practice at the Hiroshima University Hospital. The authors have collated a few cases to provide examples of their practice. The authors do not reiterate data reporting on the utility of chromoendoscopy as Subramanian and Bisschops have summarized them.

The prevalence of NP-CRN in patients with IBD

Data show that nonpolypoid colorectal lesions are common in patients with IBD. The true prevalence of NP-CRN in UC is difficult to estimate with the present endoscopic modality. Several studies provide a general estimate. Sada and colleagues reported that with surveillance colonoscopy in 1115 patients with UC, 39 colitic dysplasias or cancers in 31 patients were detected; 30% of dysplasias (6 of 20) were flat, and 16% of cancers (3 of 19) were depressed lesions. Toruner and colleagues reported that among 635 patients with IBD, 36 dysplasias were detected; 24 (67%) were nonpolypoid and 12 (33%) were polypoid. Rutter and colleagues reported that 77% of 110 colitic dysplasias or cancers in 525 patients with UC were detected endoscopically, with 23% being flat. In an investigation by the Japanese Ministry of Health, Labor, and Welfare, 42 lesions (79%) were polypoid and 11 lesions (21%) were nonpolypoid. Other reports have shown that more NP-CRN were detected and diagnosed using magnifying endoscopy as compared with chromoendoscopy.

Detection of NP-CRN with chromoendoscopy

The recent use of high-definition endoscopy with chromoendoscopy has enabled endoscopists to directly visualize, localize, and diagnose NP-CRN in patients with UC (see Table 1 ). Indigo carmine solution enhances the visualization of the border and surface topography of the lesion to improve contrast compared with the surrounding mucosa in patients with UC. A meta-analysis has demonstrated that chromoendoscopy has medium to high sensitivity (83.3%, 95% confidence interval [CI]: 35.9–99.6), specificity (91.3%, 95% CI: 43.8–100), and high diagnostic accuracy (odds ratio 17.544, 95% CI: 1.245–247.14) for dysplastic lesions and is superior to white light colonoscopy for the proportion of lesions detected by biopsies (44%, 95% CI: 28.6–59.1) as well as for flat dysplasia (27%, 95% CI: 11.2–41.9) in patients with UC.

Kiesslich and colleagues reported 165 patients with long-standing UC who were randomized to conventional colonoscopy or colonoscopy with chromoendoscopy using 0.1% methylene blue. More targeted biopsies were possible, and significant intraepithelial neoplasia was detected in the chromoendoscopy group (32 vs 10; P = .003). Rutter and colleagues reported the importance of indigo carmine dye spraying for the detection of dysplasia in UC. They emphasized that no dysplasia was detected in 2904 nontargeted biopsies. In comparison, chromoendoscopy with targeted biopsy led to fewer biopsies and detected 9 dysplastic lesions, 7 of which were only visible after indigo carmine application. They concluded that the indigo carmine dye spraying of the whole colon is feasible, and dysplasia detection may be more effective than taking large numbers of random biopsies. Hurlstone and colleagues also emphasized that indigo carmine–assisted high-magnification chromoendoscopy and improved the detection of intraepithelial neoplasia in the endoscopic screening of patients with UC.

However, pancolonic chromoendoscopy has potential limitations: dye on the mucosa is not always equally spread; dye pooling can lead to difficult observation; more time is needed; and some biopsies may be false negative.

In the authors’ institution, they routinely perform high-magnification colonoscopy with indigo carmine chromoendoscopy after they suspect the presence of NP-CRN in patients with cIBD. Morphologically, NP-CRN in IBD appear to be slightly elevated, completely flat, or slightly depressed as compared with the surrounding mucosa. In order to detect them, the authors look for the presence of a slightly elevated lesion, focal friability, obscure vascular pattern, discoloration (uneven redness or a patch or redness), villous mucosa (velvety appearance), and irregular nodularity. The finding of any of these signs typically alerts the authors to become suspicious of the possible presence of NP-CRN and leads them to wash out the mucus or debris from the surface on the target lesion and apply the dye for magnifying colonoscopy.

Magnifying colonoscopy using dye spraying for NP-CRN

After dye spraying but before the authors perform a biopsy or resection, they will typically evaluate the border of the lesion. The authors look for the presence of dye pooling within the lesion, which would suggest the diagnosis of a depressed lesions. The authors study the pit pattern of the mucosal surface. The authors’ experience and others’, however, suggest that the current pit pattern classification may not be completely applicable in UC, because the pit pattern of the regenerative hyperplastic villous mucosa in UC (with the pits becoming elongated and irregular, depending on the degree of inflammation) is difficult to distinguish from neoplastic pit patterns. Instead of using the current pit pattern classification, the authors have previously reported that high residual density of pits and irregular pit margins with magnification after indigo carmine dye spraying were useful to differentiate between colitis-associated neoplastic and non-neoplastic lesions. Therefore, in the authors’ practice, they focus on the high residual density of pits and irregular pit margins observed under magnifying chromocolonoscopy.

The main pit patterns of neoplasia in cIBD have been reported as type IV and type III _S with a III _L pit pattern. Sada and colleagues described that magnifying colonoscopy of 15 neoplasias and showed that the patterns being type III _S – to III _L or type IV pit. Hata and colleagues reported that they found no neoplastic lesions in regions characterized by type II or I pit patterns. However, they also noted that some non-neoplastic flat lesions also have type III and IV pit patterns, which are neoplastic patterns. After completion of the characterization of the lesion, the authors perform the biopsy or remove the lesion.

Detection of NP-CRN using equipment-based IEE

NBI

NBI is commonly used for the management of colorectal lesions in Japan. A large body of the literature has reported on the utility of NBI for the detection of colorectal polyps and for differentiating the diagnosis between neoplastic and non-neoplastic lesions. Conversely, some studies have suggested that NBI magnification is not effective for the detection of colorectal neoplasia. An advantage of NBI magnification is that it can be achieved without spraying dye, thus potentially reducing the cost. Because NBI involves a simple one-touch operation, NBI magnification may shorten the procedure time required for diagnosing NP-CRN in IBD and make the surveillance colonoscopy efficient. The major limitation of NBI, however, is that the visual field becomes too dark during its application. A newer generation of NBI has, therefore, been developed with improved brightness, although prospective trials have not been performed.

In the previous clinical research on the significance of NBI endoscopy in detecting NP-CRN in patients with UC, surveillance colonoscopy using NBI was associated with negative results ; no significant difference in the ability to detect NP-CRN was found between NBI and white light endoscopy ( Table 2 ). Dekker and colleagues reported that 52 visible lesions were identified in 17 patients during NBI endoscopy compared with 28 visible lesions identified in patients using white light endoscopy. A pathologic evaluation of target biopsies showed 11 patients with neoplasia, which was detected by both techniques in 4 patients, whereas only 4 cases were detected using NBI endoscopy alone and 3 cases using white light endoscopy. Van den Broek and colleagues also reported that 11 of 16 (69%) neoplastic lesions were detected by white light, whereas NBI endoscopy detected 13 of 16 (81%) cases (nonsignificant differences). Efthymiou and colleagues reported that when using chromoendoscopy, 131 lesions (92%) were detected as compared with 102 lesions (70%) with NBI ( P <.001); the median number of lesions detected per patient was 3 with chromoendoscopy and 1.5 with NBI ( P = .002).

Table 2

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