Value of magnifying chromoendoscopy and narrow band imaging (NBI) in classifying colorectal polyps: a prospective controlled study

• Introduction
• Patients and methods
• Patients and study design
• Chromoendoscopy with magnification
• Magnifying NBI endoscopy
• Image evaluation
• Statistics
• Results
• Mucosal patterns
• Vascular patterns
• Discussion
• Acknowledgment
• References

Background and study aims: Chromoendoscopy in combination with magnifying endoscopy is useful in distinguishing neoplastic from non-neoplastic colorectal polyps. Narrow band imaging (NBI) has been developed as a new technique to differentiate tissue patterns in vivo. The aim of the present study was to directly compare the diagnostic values of chromoendoscopy and NBI for the differentiation of neoplastic from non-neoplastic colorectal polyps.

Patients and methods: In total, 200 colorectal polyps from 99 patients were distributed in a 1 : 1 ratio in order to analyze the surface according to the pit pattern classification and vascular patterns by either magnifying chromoendoscopy or NBI magnification. Histologic analysis was performed on all lesions.

Results: Using the Kudo classification of mucosal patterns, NBI with magnification resulted in a sensitivity of 90.5 % and a specificity of 89.2 % for the differentiation of neoplastic vs. non-neoplastic lesions. This performance was comparable to magnifying chromoendoscopy with a sensitivity of 91.7 % and a specificity of 90 %, respectively. Using vascular patterns for differentiation, NBI with magnification correctly identified 93.7 % of neoplastic polyps and 89.2 % of non-neoplastic colorectal lesions, whereas magnifying chromoendoscopy had a specificity of 95 % but a sensitivity of only 66.7 %.

Conclusion: NBI in combination with magnifying endoscopy is a promising tool for the differentiation of neoplastic from non-neoplastic colorectal polyps in vivo without the necessity of using dye. The detection of capillary vessels with NBI allows the evaluation of colorectal lesions based on the vascular patterns with high diagnostic accuracy.

Introduction

Colorectal carcinoma is one of the most common cancers in Europe and the United States. Early cancers and adenomatous precursor lesions can be safely and entirely removed endoscopically, which has revolutionized the management of these lesions within the past decades. Therefore, one of the outstanding aims of screening colonoscopy is the detection and removal of adenomatous lesions and early cancers. However, conventional colonoscopy has not always been able to differentiate between hyperplastic and neoplastic polyps, leading to potentially unnecessary removal of a large proportion of lesions.

Hence, it has been important to show that magnifying endoscopy in combination with chromoendoscopy is useful in discriminating between neoplastic and non-neoplastic colonic polyps, based on the pit-pattern classification by Kudo and colleagues [1] [2] [3] [4]. However, chromoendoscopy is operator dependent and labor intensive, requiring the use of staining solutions and spraying catheters [5]. Furthermore, the mucosal morphology consists of both mucosal and vascular patterns, and the detection of superficial vascular patterns might be difficult with chromoendoscopy as the staining solution can obscure visualization of blood vessels.

Recently, the new technique narrow band imaging (NBI) has been developed, which is based on the substitution of current optical filters in sequential-lighting endoscopes to spectral narrow-band filters [6]. Use of a higher intensity of the blue light with narrow band filters enables imaging of the superficial tissue structures and supports the imaging of important features such as capillary and mucosal patterns. The usefulness of the NBI system for examination of colonic lesions has been demonstrated in a pilot study by Machida and co-workers [7], but larger controlled trials examining the clinical usefulness of NBI are still lacking.

Therefore, it was the aim of this randomized prospective study to evaluate the diagnostic value of chromoendoscopy and NBI in the differentiation of neoplastic from non-neoplastic colorectal polyps in routine endoscopy.

Patients and methods

Patients and study design

A total of 623 patients underwent colonoscopy between May 2006 and October 2006. Patients with chronic inflammatory bowel disease, adenomatosis coli, coagulopathy, insufficient bowel preparation, or previous colonoscopy within the last 3 years (except for patients who were sent for polypectomy of known polyps) were excluded from the study. All patients who did not meet the exclusion criteria were included in the study. Overall, 210 of 623 patients could be included in the study and underwent colonoscopy with an NBI endoscope, which is able to magnify the image to a maximum of 150-fold (CF-Q160ZI, Olympus Medical Systems Europe, Hamburg, Germany). In 99 of the 210 patients, 200 colorectal polyps were detected and consecutively distributed in a 1 : 1 ratio either to magnifying chromoendoscopy or to NBI magnification ([Fig. 1]). Distribution was strictly performed in an alternating way. The size, morphology, and location of the polyps were documented. Afterwards, all colorectal polyps were either removed endoscopically or biopsied for histologic examination when carcinoma was macroscopically suspected. The study protocol was approved by the local ethics committee of Aachen University, and written informed consent for participation in the study was obtained from patients.

Chromoendoscopy with magnification

Polyps were stained with 0.3 % indigo carmine solution in a standardized fashion. Mucus was removed from the mucosa with tap water, and indigo carmine solution was delivered with a dye spray catheter (PW-1L-1, Olympus). The amount of indigo carmine solution used depended on the size of the lesion. Prior to and after staining, the magnified surface of the polyps was photographed.

Magnifying NBI endoscopy

The sequential lighting method in current videoendoscopes has a rotation disc with RGB (red, green, blue) optical filters in front of a xenon light source. NBI is a novel technique that uses spectral narrow-band optical filters instead of the full spectrum of white light. As the penetration depth of light is dependent on its wavelength, visible blue light penetrates only superficial parts of the tissue under examination. In contrast, the use of blue light with special narrow band filters also enables imaging of the superficial tissue structures.

The polyps were initially visualized with standard white light followed by the NBI light source. If mucus decreased visualization of surface details, the mucosa was rinsed with water. The magnified surface of the lesions - using standard white light as well as the NBI light source - was documented by photography and stored electronically.

Image evaluation

For every polyp, two undyed images and two images with either NBI or dying were stored. All images of the three different methods (magnifying endoscopy using white light, chromoendoscopy with magnification, magnifying NBI endoscopy) were independently evaluated by two investigators (J. T. and R. W.), who were blinded to histologic data. All NBI images, white light images with dying, and white light images without dying were reviewed at three different sessions in a random order of polyps. Thereby, both images (using the same technique) of each polyp were analyzed together. In case of discrepancy, images of these polyps were re-evaluated by the two investigators together and a consensus classification was achieved. The pit-pattern classification by Kudo and co-workers was used to differentiate neoplastic from non-neoplastic colorectal polyps [1]. Pit pattern types I - II were classified as non-neoplastic whereas types III - V were classified as neoplastic leasions. Additionally, the vascular pattern was classified according to intensity and shape of small blood vessels (non-neoplastic: fine capillary pattern, normal size and distribution; neoplastic: increased number, tortuous, corkscrew-type). This classification is based on two recently published studies examining the diagnostic value of NBI in Barrett’s esophagus and colorectal polyps [8] [9]. Before starting this prospective study, 10 ”learning” polyps photographed with all three techniques (magnifying endoscopy using white light, chromoendoscopy with magnification, magnifying NBI endoscopy) were evaluated for mucosal and especially vascular patterns according to histology. Five of the 10 polyps were non-neoplastic whereas the other colorectal lesions were neoplastic. The diagnostic accuracy of the three endoscopic methods was analyzed by comparison with the pathologic diagnosis. In case of combination of vascular and mucosal pattern evaluation by NBI system, we classified polyps as neoplastic when mucosal and/or vascular pattern classified the leasion as neoplastic.

Statistics

The two-sided chi-squared test was used to compare clinical characteristics between both groups. Sensitivity, specificity, positive and negative predictive value, and accuracy were compared by applying the chi-squared test in the case of independent samples and the generalized linear model for correlated data using the generalized estimating equations (GEE) method for dependent samples. A P value of < 0.05 was considered to be statistically significant. The 95 % confidence intervals were computed for the differences of proportions using the R-program prop.test for independent samples and the GEE method for dependent samples. The GEE analysis was performed using the GENMOD procedure of SAS 9.1.

Results

In this study 200 polyps in 99 patients were identified during colonoscopy. The mean age of patients with polyps was 68.7 years (range 40 - 87 years), 51 (52 %) patients were men. Among the 200 polyps, 102 (51 %) were located in the right colon, 69 (34.5 %) in the left colon, and 29 (14.5 %) in the rectum. The mean size of the polyps was 9.9 mm (range 2 - 50 mm), and 166 (83.0 %) of the colorectal lesions were polypoid, whereas 34 (17.0 %) flat lesions were detected. Overall, 77 (38.5 %) colorectal lesions were non-neoplastic upon histologic evaluation, whereas 123 (61.5 %) polyps were neoplastic (78 tubular adenomas, 35 tubulovillous adenomas, seven colorectal carcinomas, three villous adenomas). After distribution of the 200 polyps into two groups, magnified endoscopic images were obtained for all colorectal lesions, followed by either chromoendoscopy or NBI endoscopy at a ratio of 1 : 1 ([Fig. 1]). Subsequently all polyps were removed endoscopically or biopsied. The clinicopathologic parameters of both groups are shown in [Table 1].

Mucosal patterns

Photographic images of the 200 polyps were classified according to the pit-pattern classification of Kudo and colleagues. Pit pattern types I - II and III - V were used for distinguishing between non-neoplastic and neoplastic lesions, respectively. Among the 200 polyps, magnifying endoscopy without additional staining or NBI system resulted in a sensitivity of 63.4 % and a specificity of 51.9 %. The diagnostic accuracy was not statistically different between two groups, which were subsequently evaluated with chromoendoscopy or NBI endoscopy, respectively. Successive chromoendoscopy with indigo carmine increased the sensitivity to 91.7 % and the specificity to 90.0 % for the differentiation of 60 neoplastic and 40 non-neoplastic lesions, respectively ([Fig. 2]). In the group distributed to NBI endoscopy, 37 non-neoplastic and 63 neoplastic lesions were identified ([Fig. 3] and [4]). NBI with magnification resulted in a sensitivity of 90.5 % and a specificity of 89.2 %, respectively. The diagnostic accuracy of the NBI system was statistically not different compared with chromoendoscopy. However, both NBI und chromoendoscopy with magnification had a significant higher sensitivity and specificity for distinguishing between non-neoplastic and neoplastic lesions than magnifying endoscopy alone (P < 0.0001). The seven colorectal carcinomas with pit-pattern classification type V were correctly classified by all methods. The predictive values for each technique are summarized in [Table 2].

In evaluation of pit-pattern classification there was a discrepancy between the two investigators in 20 polyps (15 with white light endoscopy without staining, two with chromoendoscopy, three with NBI). Images of these 20 polyps were re-evaluated by the two investigators together and a consensus classification was achieved. The five polyps that were discrepantly classified using NBI and chromoendoscopy were all found within neoplastic group (pit-pattern type III - V). Therefore, these differences had no impact on the results.

Vascular patterns

Photographic images of the 200 polyps were also classified according to vascular patterns. No case of discrepancy in vascular pattern analysis between the two investigators was found. Normal vascularity was defined as the presence of thin-caliber vessels with a uniform branching pattern ([Fig. 3] ). Abnormal vascularity was defined as dilated, corkscrew vessels with increased vascularity and abnormal, non-uniform branching patterns ([Fig. 4]). Using this vascular classification, magnifying endoscopy without staining or NBI system resulted in a sensitivity of 47.2 % and a specificity of 97.4 % for differentiation of non-neoplastic and neoplastic lesions. One hundred colorectal lesions were additionally stained with indigo carmine, resulting in an increased sensitivity (66.7 %) and specificity (95.0 %) upon magnifying chromoendoscopy. In the second group, 100 polyps were evaluated for vascular classification by NBI with magnification. The color features of images obtained by NBI differ from those of the conventional video endoscope system by visualizing the blood vessels as a dark complex. NBI with magnification identified 93.7 % of neoplastic polyps and 89.2 % of non-neoplastic colorectal lesions, respectively ([Fig. 3] and [4]). The predictive values of all three methods are summarized in [Table 3]. The predictive value of the vascular pattern classification with NBI was statistically not different compared with the pit pattern classification obtained by NBI or by chromoendoscopy. However, a combination of vascular and mucosal pattern evaluation by the NBI system results in an increased sensitivity of 96.8 %, whereas specificity is still 81.1 %. Notably, we did not find significant differences in the vascular patterns between the different types of adenomas.

Discussion

Chromoendoscopy with non-vital stains is currently considered as the method of choice for detecting mucosal patterns within the gastrointestinal tract. Kudo and colleagues classified colonic polyps according to their appearance, structure, and staining pattern. Types I and II describe benign changes (e. g. normal, hyperplastic or inflammatory lesions), whereas pit-pattern classes III to V are designated to an increasing extent of dysplastic and malignant changes [1]. However, chomoendoscopy is highly operator dependent and labor intensive, which reduces its usefulness in routine clinical practice. Therefore, other techniques for the differentiation of neoplastic and non-neoplastic lesions based on the Kudo classification are warranted. The recently developed NBI technique is a new method of high-resolution endoscopic imaging with application of optical characteristics of light for the superior detection of mucosal and vascular details. The wavelength range of the NBI filters covers the 410 nm absorption wavelengths for hemoglobin. This optical absorption of light by hemoglobin distinctly emphasizes the vascularity of the mucosa to distinguish between normal and abnormal vessels structures [6] [10]. In a recent pilot study, Machida and co-workers could demonstrate the usefulness of NBI for the evaluation of colorectal lesions [7]. However, the usefulness of NBI endoscopy compared with chromoendoscopy in a routine clinical setting has not yet been sufficiently demonstrated.

The aim of our study was therefore to evaluate the diagnostic value of magnifying chromoendoscopy and NBI for the differentiation of neoplastic from non-neoplastic colorectal polyps in a head-to-head comparison. Using the Kudo classification of mucosal patterns, NBI with magnification resulted in a sensitivity of 90.5 % and specificity of 89.2 %, respectively, and was comparable to the sensitivity of 91.7 % and specificity of 90.0 % achieved by magnifying chromoendoscopy for distinguishing between non-neoplastic and neoplastic lesions. Of note, however, we could demonstrate that illustration of capillary vessels differ significantly between NBI technique and chromoendoscopy. Using the vascular patterns, NBI with magnification correctly identified 93.7 % of neoplastic polyps and 89.2 % of non-neoplastic colorectal lesions, whereas magnifying chromoendoscopy had a specificity of 95.0 % but a sensitivity of only 66.7 % for differentiation between neoplastic and non-neoplastic lesions. These results indicate that evaluation of vascular patterns by NBI is a valuable method for classification of colorectal polyps.

The usefulness of vascular patterns is also supported by a recent NBI study that reported a higher capillary intensity in 99 % of tubular adenoma and in only 6 % of colorectal hyperplasia [11]. In two other studies, NBI is reported to detect high-grade intraepithelial neoplasia in Barrett’s esophagus with high sensitivity and specificity [9] [12]. Interestingly, Barrett’s esophagus with dysplasia had similar changes of vascular patterns compared with neoplastic polyps. This might be explained by general mechanisms of neoangiogenesis, which occurs in pathologic settings such as tumor growth [13] [14]. Increased intensity and changed structure of capillary vessels might therefore allow diagnosis of neoplasia without classification of the mucosal pattern.

In our study, we could demonstrate that predictive values of vascular pattern classification with NBI were comparable with the pit pattern classification obtained by NBI or by chromoendoscopy. Notably, a combination of vascular and mucosal pattern classification by NBI system resulted in an increased sensitivity of 96.8 % in differentiation between neoplastic and non-neoplastic colorectal polyps, whereas specificity was still 81.1 %. This indicates that adjunction of vascular to pit pattern classification might be clinically useful for the evaluation of colorectal lesions. However, classification of vascular patterns of colorectal lesions is still not objectively standardized. Therefore, a computer-assisted evaluation and classification of vascularity would be very helpful in order to minimize investigator-dependent results.

Additionally to the good visibility of capillary vessels, NBI has several advantages compared with chromoendoscopy. Firstly, no staining solutions are required. Secondly, it is user friendly as it solely depends on the use of optical filters that are easily enabled by a manual switch on the handle of the endoscope. Problems associated with chromoendoscopy, such as difficulty in achieving complete and even coating of the mucosal surface with the dye are eliminated. However, the NBI system requires a new processor, and a detailed cost analysis is required.

In conclusion, NBI in combination with magnifying endoscopy is a promising tool for the differentiation of non-neoplastic from neoplastic colorectal polyps in vivo without using dye. The positive predictive value for neoplastic lesions of NBI and chromoendoscopy based on the mucosal pattern is comparable. The good visibility of capillary vessels by NBI technique makes an evaluation of colorectal lesions with a high diagnostic accuracy possible based on the vascular patterns.

Acknowledgment

The NBI system was provided by Olympus Medical Systems Europe.

Competing interests: None

References

• 1 Kudo S, Tamura S, Nakajima T. et al . Diagnosis of colorectal tumorous lesions by magnifying endoscopy.  Gastrointest Endosc. 1996;  44 8-14
  CrossrefPubMedSearch in Google Scholar
• 2 Kato S, Fujii T, Koba I. et al . Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished?.  Endoscopy. 2001;  33 306-310
  Thieme ConnectPubMedSearch in Google Scholar
• 3 Eisen G M, Kim C Y, Fleischer D E. et al . High-resolution chromoendoscopy for classifying colonic polyps: a multicenter study.  Gastrointest Endosc. 2002;  55 687-694
  CrossrefPubMedSearch in Google Scholar
• 4 Konishi K, Kaneko K, Kurahashi T. et al . A comparision of magnifying and nonmagnifying colonoscopy for diagnosis of colorectal polyps: a prospective study.  Gastrointest Endosc. 2003;  57 48-53
  PubMedSearch in Google Scholar
• 5 Connor M J, Sharma P. Chromoendoscopy and magnification endoscopy for diagnosing esophageal cancer and dysplasia.  Thorac Surg Clin. 2004;  14 87-94
  PubMedSearch in Google Scholar
• 6 Gono K, Obi T, Yamaguchi M. et al . Appearance of enhanced tissue features in narrow-band endoscopic imaging.  J Biomed Opt. 2004;  9 568-577
  CrossrefPubMedSearch in Google Scholar
• 7 Machida H, Sano Y, Hamamoto Y. et al . Narrow-band imaging in the diagnosis of colorectal mucosal lesions: a pilot study.  Endoscopy. 2004;  36 1094-1098
  Search in Google Scholar
• 8 East J E, Suzuki N, Swain D. et al . Vascular pattern intensity: a new classification system to differentiate neoplastic and non-neoplastic lesions in the colon using narrow band imaging (NBI) with magnification.  Gastrointest Endosc. 2006;  63 AB 230
  PubMedSearch in Google Scholar
• 9 Sharma P, Bansal A, Mathur S. et al . The utility of a novel narrow band imaging endoscopy system in patients with Barrett’s esophagus.  Gastrointest Endosc. 2006;  64 167-175
  CrossrefPubMedSearch in Google Scholar
• 10 Shibuya K, Hoshino H, Chiyo M. et al . High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer.  Thorax. 2003;  58 989-995
  CrossrefPubMedSearch in Google Scholar
• 11 Tanaka S, Oka S, Hirata M. et al . Quantitative diagnosis for colorectal neoplasia using narrow band imaging (NBI) magnification.  Gastrointest Endosc. 2006;  63 AB 230
  PubMedSearch in Google Scholar
• 12 Kara M A, Ennahachi M, Fockens P. et al . Detection and classification of the mucosal and vascular patterns (mucosal morphology) in Barrett’s esophagus by using narrow band imaging.  Gastrointest Endosc. 2006;  64 155-166
  CrossrefPubMedSearch in Google Scholar
• 13 Risau W. Mechanisms of angiogenesis.  Nature. 1997;  386 671-674
  CrossrefPubMedSearch in Google Scholar
• 14 Hanahan D. Signaling vascular morphogenesis and maintenance.  Science. 1997;  277 48-50
  CrossrefPubMedSearch in Google Scholar

C. Trautwein, MD

Medical Department III (Gastroenterology, Hepatology and Metabolic Diseases)

University Hospital Aachen

Pauwelsstr. 30

D-52074 Aachen

Germany

Fax: +49-241-80-82455

Email: ctrautwein@ukaachen.de

References

• 1 Kudo S, Tamura S, Nakajima T. et al . Diagnosis of colorectal tumorous lesions by magnifying endoscopy.  Gastrointest Endosc. 1996;  44 8-14
  CrossrefPubMedSearch in Google Scholar
• 2 Kato S, Fujii T, Koba I. et al . Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished?.  Endoscopy. 2001;  33 306-310
  Thieme ConnectPubMedSearch in Google Scholar
• 3 Eisen G M, Kim C Y, Fleischer D E. et al . High-resolution chromoendoscopy for classifying colonic polyps: a multicenter study.  Gastrointest Endosc. 2002;  55 687-694
  CrossrefPubMedSearch in Google Scholar
• 4 Konishi K, Kaneko K, Kurahashi T. et al . A comparision of magnifying and nonmagnifying colonoscopy for diagnosis of colorectal polyps: a prospective study.  Gastrointest Endosc. 2003;  57 48-53
  PubMedSearch in Google Scholar
• 5 Connor M J, Sharma P. Chromoendoscopy and magnification endoscopy for diagnosing esophageal cancer and dysplasia.  Thorac Surg Clin. 2004;  14 87-94
  PubMedSearch in Google Scholar
• 6 Gono K, Obi T, Yamaguchi M. et al . Appearance of enhanced tissue features in narrow-band endoscopic imaging.  J Biomed Opt. 2004;  9 568-577
  CrossrefPubMedSearch in Google Scholar
• 7 Machida H, Sano Y, Hamamoto Y. et al . Narrow-band imaging in the diagnosis of colorectal mucosal lesions: a pilot study.  Endoscopy. 2004;  36 1094-1098
  Search in Google Scholar
• 8 East J E, Suzuki N, Swain D. et al . Vascular pattern intensity: a new classification system to differentiate neoplastic and non-neoplastic lesions in the colon using narrow band imaging (NBI) with magnification.  Gastrointest Endosc. 2006;  63 AB 230
  PubMedSearch in Google Scholar
• 9 Sharma P, Bansal A, Mathur S. et al . The utility of a novel narrow band imaging endoscopy system in patients with Barrett’s esophagus.  Gastrointest Endosc. 2006;  64 167-175
  CrossrefPubMedSearch in Google Scholar
• 10 Shibuya K, Hoshino H, Chiyo M. et al . High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer.  Thorax. 2003;  58 989-995
  CrossrefPubMedSearch in Google Scholar
• 11 Tanaka S, Oka S, Hirata M. et al . Quantitative diagnosis for colorectal neoplasia using narrow band imaging (NBI) magnification.  Gastrointest Endosc. 2006;  63 AB 230
  PubMedSearch in Google Scholar
• 12 Kara M A, Ennahachi M, Fockens P. et al . Detection and classification of the mucosal and vascular patterns (mucosal morphology) in Barrett’s esophagus by using narrow band imaging.  Gastrointest Endosc. 2006;  64 155-166
  CrossrefPubMedSearch in Google Scholar
• 13 Risau W. Mechanisms of angiogenesis.  Nature. 1997;  386 671-674
  CrossrefPubMedSearch in Google Scholar
• 14 Hanahan D. Signaling vascular morphogenesis and maintenance.  Science. 1997;  277 48-50
  CrossrefPubMedSearch in Google Scholar

C. Trautwein, MD

Medical Department III (Gastroenterology, Hepatology and Metabolic Diseases)

University Hospital Aachen

Pauwelsstr. 30

D-52074 Aachen

Germany

Fax: +49-241-80-82455

Email: ctrautwein@ukaachen.de