Although magnifying chromoendoscopy had been a reliable diagnostic tool, narrow-band imaging (NBI) has been developed in Japan since 1999 and has now replaced the major role of chromoendoscopy because of its convenience and simplicity. In this paper, we principally describe the efficacy of magnifying chromoendoscopy and magnifying colonoscopy with NBI for detection, histological prediction, estimation of the depth of early colorectal cancer, and future prospects. Although some meta-analyses have concluded that NBI is not superior to white light imaging for detection of adenomatous polyps in screening colonoscopy, NBI with magnification colonoscopy is useful for histological prediction, or for estimating the depth of invasion. To standardize these diagnostic strategies, we will focus on the NBI International Colorectal Endoscopic (NICE) classification proposed for use by endoscopists with or without a magnifying endoscope. However, more prospective research is needed to prove that this classification can be applied with satisfactory availability, feasibility, and reliability. In the future, NBI might contribute to the evaluation of real-time histological prediction during colonoscopy, which has substantial benefits for both reducing the risk of polypectomy and saving the cost of histological evaluation by resecting and discarding diminutive adenomatous polyps (resect and discard strategy).
Narrow-band imaging (NBI) is a technique by which spectral features are modified by narrowing the band width of spectral transmittance using filters adjusted to the characteristics of hemoglobin absorption [
This paper highlights the efficacy of magnifying chromoendoscopy and NBI colonoscopy with/without optical zoom magnification for diagnosis of colorectal lesions and discusses future perspectives.
Colorectal lesions are initially diagnosed by conventional-view colonoscopy, and then, if possible, by magnifying view and/or chromoendoscopy using indigo carmine. We routinely use a magnifying colonoscope because the insertion technique and manipulation are similar to those for an ordinary colonoscope [
When a colonoscopist intends to perform chromoendoscopy, 3–5 mL of an aqueous solution of dye is sprayed onto the mucosa via the biopsy channel, along with 15 mL of air, using a 20-cc syringe. Common dyes used for characterization of the colorectum are indigo carmine as a contrast stain (0.1–0.4%), and crystal violet (0.05%) and methylene blue (0.1%) as absorptive stains. Although indigo carmine and methylene blue are often used to screen for sporadic adenoma, crystal violet, as an absorptive stain, offers advantages for patients with early invasive cancer or for detailed observation using a nontraumatic catheter after washing the lesion with lukewarm water containing pronase (Pronase MS) (Figures
Preparations for magnifying observation. (a, b) Pronase MS. Washing of the target lesion surface can be done with 500 cc of lukewarm water containing a packet of Pronase MS (20000 U). (c) Indigo carmine (Daiichi Pharmaceutical Corp., Tokyo, Japan). (d) The dye is a blue stain that accentuates the contours of a lesion, providing a detailed view of its border and shape. The dye is used as a 0.1–0.4% aqueous solution. (e) This solution is flushed through the biopsy channel of the scope using a 20-cc syringe. Generally, 3–5 cc is delivered in 5 s along with 15 cc of air. (f) Crystal violet (Honzo Pharmaceutical Corp., Nagoya, Japan). The dye is a vital stain and is preferentially taken up by the Lieberkuhn gland openings (crypts), which appear as dots or pits. (g) A few small drops of crystal violet in 0.05% solution are applied using a nontraumatic catheter (Olympus 6233064; Olympus Optical Co., Ltd., Tokyo, Japan).
Nontraumatic, globular-tip catheter. This catheter is used to remove mucus and to drop crystal violet solution onto the lesion. Better positioning for magnifying observation can be obtained by pushing and holding the surrounding mucosa.
Is it advisable to spray dye over the whole of the colon and rectum to identify significant lesions? When should magnification be employed? Certainly, pan-mucosal chromoendoscopy significantly increases the rate of detection of small neoplastic and flat lesions, but this technique requires an excessive volume of dye and a significantly prolonged procedure [
Usefulness of indigo carmine. (a) Disruption of the mucosal fold and a slightly reddish area are observed, but the whole lesion is unclear. (b) After spraying with indigo carmine dye, a 7 mm depressed lesion (0–II c) is identified clearly. (c) A slightly elevated lesion with an obscure superficial vascular component is evident, but the whole lesion is not recognized. (d) A slightly elevated lesion measuring 18 mm is obviously detected using indigo carmine.
Kudo has proposed a gross classification of pit patterns into 7 types. It has been suggested that type I and II pit patterns are characteristic of nonneoplastic lesions such as normal mucosa or hyperplastic polyps. However, most lesions showing pattern types IIIS, IIIL, IV, and a subset of VI are intramucosal neoplastic lesions such as adenoma or intramucosal carcinoma. Lesions with a type VN pattern and a subset of type VI suggest deep invasive carcinoma (Figure
Pit pattern classification and invasive pattern.
Cases of invasive pattern. (a) Endoscopic examination demonstrates a small (7 mm) flat elevated lesion in the sigmoid colon. (b) Chromoscopy with indigo carmine demonstrates a definite central depression. (c) Magnification with crystal violet staining demonstrates an invasive pattern in a demarcated area. Based on these findings, the tumor was diagnosed as an early colon cancer with deep submucosal invasion, and surgical resection was recommended. Histopathological examination of the resected specimen demonstrated well differentiated adenocarcinoma, invasive to the submucosa (sm deep; 4000
We have conducted a prospective study to examine whether magnification and/or indigo carmine dye-spraying is more reliable than the conventional view for distinguishing nonneoplastic from neoplastic lesions of the colon and rectum [
Also, our recent large prospective series has demonstrated that the clinical classification of pit patterns (as invasive or noninvasive) is effective for differentiating intramucosal or sm superficial invasion (<1000
Therefore, based on these results, we are able to conclude that at present, a combination of magnifying colonoscopy and chromoendoscopy is the one of the most reliable methods for distinguishing nonneoplastic from neoplastic lesions, as well as for estimating the depth of early colorectal cancer.
The colon and rectum are sites where neoplastic lesions occur most frequently. The National Polyp Study Group in the USA has reported that resection of all neoplastic polyps led to a 76–90% reduction in the incidence of colorectal cancer and a subsequent 53% reduction in mortality [
Neoplastic lesions are recognizable as a brownish area using NBI without magnification, which emphasizes neoplastic angiogenesis. Is NBI without magnification more useful for detecting neoplastic lesion than white light imaging (WLI)? Uraoka et al. have reported that NBI is superior to WLI (
In accordance with our previous investigations, the microvascular architecture (capillary pattern: CP) was classified into three types (CP types I, II, and III), and CP type III lesions were further classified into two groups: types IIIA and IIIB (Figure
Capillary pattern (CP) classification and diagnostic ability (published data).
In Japan, there is growing evidence to support the theory that lesions with submucosal invasion limited to <1000
Ikematsu and colleagues conducted a prospective study to determine whether CP type IIIA/IIIB identified by magnifying NBI was effective for estimating the depth of invasion in 130 early colorectal neoplasms [
Submucosal saline injection is another useful method for estimating the depth of tumor invasion, not only when used for endoscopic mucosal resection (EMR) but also as a simple diagnostic tool for deeply invasive cancers. In Japan, Uno and Munakata were the first to propose the “nonlifting sign” in 1994, and considered it to be positive in cases where the surrounding mucosa, but not the lesion, was elevated [
Comparison of endoscopic diagnosis of the depth of submucosal deeply invasive colon cancer.
Diagnostic method | Number of adenoma, m-ca#sm-slight-ca## | Number of sm deep-ca### | Overall accuracy (%) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) |
---|---|---|---|---|---|---|---|
Magnifying chromoendoscopy (Invasive pattern) | 4035 | 180 | 98.8 | 85.6 | 99.4 | 86.5 | 99.4 |
NBI with magnifying colonoscopy (capillary pattern classification) | 97 | 33 | 87.7 | 84.8 | 88.7 | 71.8 | 94.5 |
Nonlifting sign | 245 | 26 | 94.8 | 61.5 | 98.4 | 80.0 | 96.0 |
#Intramucosal cancer.
##sm slight invasive (<1000
###sm deep invasive (
Considering the available evidence, we have suggested a three-step strategy for management of colorectal lesions using conventional colonoscopy, NBI colonoscopy, and chromoendoscopy (Figure
Modified 3-step strategy of NBI colonoscopy.
In 2011, we proposed an international classification system for conventional endoscopic observation assisted by NBI, and for applying this system to NBI magnifying observation (Table
NICE classification.
Type 1 | Type 2 | Type 3 | |
---|---|---|---|
Color | Same or lighter than background | Browner relative to background (verify color arises from vessels) | Brown to dark brown relative to background; sometimes patchy whiter areas |
| |||
Vessels | None, or isolated lacy vessels may be present coursing across the lesion | Brown vessels surrounding white structures** | Has area(s) of disrupted or missing vessels |
| |||
Surface pattern | Dark or white spots of uniform size, or homogeneous absence of pattern | Oval, tubular or branched white structures** surrounded by brown vessels | Amorphous or absent surface pattern |
| |||
Most likely pathology | Hyperplastic | Adenoma*** | Deep submucosalinvasive cancer |
| |||
Treatment | Followup | Polypectomy/EMR/ESD | Surgery |
*Can be applied using colonoscopes with/without optical (zoom) magnification.
**These structures (regular or irregular) may represent the pits and the epithelium of the crypt opening.
***Type 2 consists of Vienna classification types 3, 4 and superficial 5 (all adenomas with either low or high grade dysplasia, or with superficial submucosal carcinoma). The presence of high grade dysplasia or superficial submucosal carcinoma may be suggested by an irregular vessel or surface pattern, and is often associated with atypical morphology (e.g., depressed area).
Figures to illustrate the NBI International Colorectal Endoscopic (NICE) classification.
Table
NICE classification and Each NBI magnifying classification in Japan.
NICE clasification | Type1 | Type2 | Type3 |
---|---|---|---|
Sano classification | Type I | Type II~IIIA | Type IIIB |
Hiroshima classification | Type A | Type B~C2 | Type C3 |
Showa classification | Faint pattern | Dens/Network pattern |
Sparse pattern |
Resection of all adenomatous polyps during colonoscopy has been the world standard treatment since the National Polyp Study demonstrated that colonoscopic resection of all adenomatous polyps reduced both the incidence of and mortality due to colorectal cancer [
Two typical cases of small invasive colorectal cancer (≤5 mm). (A): (a) Conventional view: There is a small polyp (lesion size: 4 mm) located in the sigmoid colon. It is rather difficult to visualize any depressed area in this lesion. (b) NBI view: Magnification with NBI clearly demarcates the margin of the depressed area. The vascular pattern is capillary pattern Type IIIB of the Sano classification, indicative of deep invasion into the submucosa. The center of the depressed area has a dome-like appearance, and the macroscopic type is “0-I s + II c”, which requires attention in view of its frequent deep invasion into the submucosa. (c) Crystal violet view: magnification with crystal violet staining also demonstrates an invasive pattern and VN pits, strongly indicative of deep submucosal invasion. We decided to treat this lesion surgically without endoscopic resection. (d) Pathological findings: well to moderately differentiated adenocarcinoma, pSM (3000–4000
Currently, many endoscopic modalities are available, including NBI, autofluence imaging, Fuji Intelligent Chromo Endoscopy, i-scan, and so on. What kind of modality can best determine colorectal polyp pathology endoscopically? The American Society for Gastrointestinal Endoscopy (ASGE) has suggested that the necessary thresholds of endoscopic technology for accurate assessment of histology are >90% agreement in determining postpolypectomy surveillance intervals and a negative predictive value of ≥90% (when used with high confidence) for recto-sigmoid polyps with adenomatous histology [
Performance of NBI without magnification for real-time assessment with high diagnostic confidence.
HC rate | Accuracy | Sensitivity | Specificity | PPV | NPV |
---|---|---|---|---|---|
78% | 92% | 93% | 88% | 93% | 82% |
80% | 95% | 91% | 93% | 91% | 95% |
NBI with magnification colonoscopy is useful for histological prediction, and for estimating the depth of invasion of colorectal cancer. To standardize the diagnostic strategies currently available, the NICE classification would be helpful for endoscopists irrespective of whether they have access to magnifying endoscopy. However, more prospective research is needed to prove that this international classification can be applied with satisfactory availability, feasibility, and reliability. In the near future, NBI might make a valuable contribution to real-time histological prediction during colonoscopy, which would have substantial benefits for reducing both the risk of polypectomy and the costs of histological evaluation by allowing adenomatous polyps to be resected and discarded.
The authors declare that they have no conflict of interests.
All authors have contributed significantly and are in agreement with the content of this paper.