David G. Hewett GASTROENTEROLOGY 2012;143:599–607

1. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging David G. Hewett GASTROENTEROLOGY 2012;143:599–607

2. Editor: • DrMohammadSadrkabir

3. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Narrow-band imaging (NBI) is an image-enhanced endoscopy modality that specifically was developed to use a narrowed wavelength light source to optimize hemoglobin light absorption. • Because the pattern and size of microvessels in the mucosa and submucosa change when tissue becomes neoplastic, NBI has the potential to allow endoscopists to characterize these lesions. • studies have shown that NBI can be used to characterize colorectal polyps with neoplastic changes.

4. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • For NBI to be useful in clinical practice, simple classification systems are needed that allow both experienced and inexperienced clinicians to apply NBI.Numerous classifications of NBI findings of polyps have been described for colonoscopes with and withoutoptical magnification. • Although the overall diagnostic performance characteristics of these classifications have been reported, the validity of their component criteria has not been established. • Evaluating the performance of the classification when used by even inexperienced endoscopists, are critical to ensure that use of the system will be effective and efficient.

5. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • In this study we sought to accomplish the following: • (1) develop a practical, simple, and internationally applicable classification for determination of colorectal polyp histology using NBI. • (2) establish the predictive validity of the components of the classification for determination of polyp histology; • (3) evaluate the predictive validity and performance characteristics of the overall classification for determination of polyp histology. • Because colonoscopy without high magnification is standard in most parts of the world, we validated our NBI International Colorectal Endoscopic (NICE) classification using NBI without magnification.

6. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Materials and Methods • The study was conducted in 4 phases: • phase 1, evaluation of interobserver agreement for NBI-experienced colonoscopists in predicting polyp histology; • phase 2, development of a classification system for endoscopic prediction of adenomatous vs hyperplastic histology by NBI-experienced colonoscopists; • phase 3, validation of the component criteria and the overall classification for real-time polyp histology by testing the criteria in endoscopy-naive subjects. • phase 4, assessment of the performance and reliability of the overall classification for predicting histology using still photographs of known histology.

7. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging

8. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • For the first 2 phases of this study, we used an existing library of 118 high-definition still endoscopic photographs of colorectal polyps, captured using narrow-band imaging by 2 of the authors (D.G.H. and D.K.R.) without optical magnification (CF-H180AL with Exera II CLV-180 light source and CV-180 processor; Olympus America, Inc, Center Valley, PA). • All polyps were less than 10 mm in diameter, and their histology was verified previously by a gastrointestinal pathologist. • It is possible that some sessile serrated polyps may have been misclassified as classic hyperplastic polyps because of interobserver variability.

9. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • We used 4 groups of participants: • (1) gastroenterologists with expert experience in NBI for polyp diagnosis (n = 5: Europe [T.P. and B.P.S.], Japan [Y.S. and S.T.], and the United States [R.S.]); • (2) gastroenterologists with variable experience in NBI for polyp diagnosis (n = 2); • (3) gastroenterology fellows with no experience in NBI for polyp diagnosis (n = 19: Indiana, 5; San Antonio, 12; and Australia, 3); and • (4) medical students with no experience in NBI or in polyp diagnosis (n = 25).

10. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Procedure • Phase 1: evaluation of reliability of histologic prediction by experienced colonoscopists • All endoscopists(experienced endoscopists) scored the polyps as an adenoma or hyperplastic polyp, and assigned a level of confidence to the prediction (high or low). Endoscopists were told to assign a prediction with high confidence when they had ≥90% certainty of the diagnosis.

11. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Phase 2: development of the classification and component criteria • We aimed to create a simple and practical classification that unified previous NBI classifications, had clear operational definitions of its components, and was readily applicable in routine practice without optical magnification by endoscopists without extensive experience in endoscopic imaging, chromoendoscopy, or pit-pattern diagnosis. • We used a modified Delphi method to achieve consensus. Three working group meetings systematically deconstructed the NBI characteristics of adenomas and hyperplastic polyps, allowing specification of the component criteria on which they made an NBI diagnosis of polyp histology (color, vessels, and surface pattern).

12. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging

13. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Phase 3: validation of the component criteria of the classification • In phase 3, we evaluated the validity of the individual criteria within the classification using 44 raters with no previous NBI experience. We presented the image library to the novice raters composed of 25 medical students and 19 gastroenterology fellows .

14. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • First, the 25 medical students scored colorectal polyps for the presence and features of each criterion individually. Students were given no training about polyps or NBI, and were not informed of the overall classification, or of the relationship between the different criteria, or of the histology of the polyps they reviewed. • Second, the 19 gastroenterology fellows scored colorectal polyps for all criteria simultaneously. They received formal standardized training in the use of NBI for real-time histology, classification, and its application to determining real-time polyp histology. Fellows also were given exemplar images showing the typical appearances of each criterion.

16. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Phase 4: prospective validation of the classification. • In phase 4, we tested the performance and reliability of the overall classification system among gastroenterology fellows. This evaluation was performed simultaneously with the component validation described earlier whereby the fellows predicted the histology of the 118 polyps according to the classification, and designated a level of confidence (high, low) for the prediction.

17. Results • Phase 1: Experienced Raters • High levels (>90%) of accuracy, sensitivity, specificity, and predictive value for predicting adenomatous from hyperplastic histology were seen (Table 2), reaching 98% or higher when ratings were made with high confidence.

18. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging

19. Overall, 80% (471 of 590) of predictions were made with high confidence, although the proportion of polyps predicted with high confidence differed significantly between experts ( P < .001).

20. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Phase 2: Development of the Classification • The classification comprised 3 simple criteria: color, vessels, and surface pattern, for which there are clear descriptors for determining adenomatous vs hyperplastic histology, althoughit is recognized that some polyps will not display all 3 criteria. Based on the component criteria, a polyp may be classified into 3 types: type 1 corresponds to the most likely pathology being hyperplastic, type 2 being adenoma, and type 3 being deep submucosal invasive cancer.

21. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Phase 3: Validation of the Component Criteria • We assessed the performance of the 3 criteria, individually and in combination, for overall prediction of polyp histology.

22. The surface pattern criterion yielded the highest sensitivity and negative predictive value for an adenoma diagnosis, achieving similar results to the vessel criterion, with some raters reaching 100% sensitivity and negative predictive value. • Color was the least sensitive and least predictive criterion, achieving significantly lower accuracy and sensitivity than both vessels and surface pattern (P < .0001). • The specificity for surface pattern (90%) was significantly lower than for color (P = .002) and vessels (P = .02). • When any 1 of the 3 adenomatous criteria was present, the sensitivity and negative predictive value was 95%, achieving significantly higher sensitivity (P < .0001) and specificity (P < .0001) than any of the 3 criteria alone. • The presence of all 3 criteria for adenomatous histology (color, vessels, and surface pattern) had a specificity of 100%, although sensitivity only reached 35%.

23. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging

24. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Surface pattern again yielded the highest accuracy, sensitivity (88%), specificity, and negative predictive value (89%). • There were no significant differences in negative or positive predictive value between the criteria. • In combination, the presence of adenomatous features for any 1 of the 3 criteria achieved an accuracy, sensitivity, and specificity of 91% and a negative predictive value of 92%. • The sensitivity of the presence of at least one adenomatous feature (91%) was significantly higher than that achieved with each criterion alone (P < .001). • Gastroenterology fellows achieved significantly higher accuracy than medical students.

25. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Phase 4: Validation of the Classification • When fellows were asked to provide a global prediction of histology using the component criteria and the overall classification, the sensitivity was 89% and the negative predictive value was 90%. • Performance improved significantly (P < .0001) when global predictions were made with high confidence, achieving sensitivity, specificity, and predictive values of greater than 95%. • The level of interobserver agreement for the overall prediction of histology was 0.75.

26. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Preliminary Clinical Evaluation • We obtained performance characteristics in our pilot evaluation of real-time application of the classification during colonoscopy. • Of the 220 prospectively enrolled patients, 108 patients had at least 1 polyp that was less than 1 cm. • The endoscopists made a diagnostic prediction with high confidence in 75% of the 236 polyps (82% in adenomas; and 64% in hyperplastic).

27. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging

28. Discussion • We showed that the classification system performed very well when applied by previously NBI-untrained fellows to the set of polyp photographs, and similar results were obtained in a pilot application during real-time colonoscopy. • The use of technology to improve the cost effectiveness of colonoscopy is needed given the high cost of colonoscopy. A significant part of the high cost is the current practice to resect and submit diminutive polyps for pathologic assessment. • Endoscopic determination of adenomatous vs hyperplastic histology of colorectal polyps has the most potential because it will reduce the need for pathologic examination.

29. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • Two clinical strategies have been proposed for the use of real-time estimation of histology. The resect-and-discard policy describes a practice of endoscopic estimation of histology of polyps ≤5 mm or <10 mm, followed by resection of such polyps and discarding them without submission to pathology. Two studies have reported that accurate endoscopic designation of histology and assignment of surveillance intervals is feasible in real time using NBI and high-definition colonoscopes without optical magnification. • The second cost-saving strategy proposed (the do-not-resect strategy) is to identify diminutive distal colon hyperplastic polyps in real time by endoscopy and then leave them in place without sampling.

30. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • The American Society for Gastrointestinal Endoscopy has provided a guideline : • 1) In order for colorectal polyps ≤5 mm in size to be resected and discarded without pathologic assessment, endoscopic technology used to determine histology of polyps ≤5 mm in size, when combined with the histopathologic assessment of polyps ≤5 mm in size, should provide a ≥90% agreement in assignment of post-polypectomy surveillance intervals when compared to decisions based on pathology assessment of all identified polyps;

31. Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging • 2) In order for a technology to be used to guide the decision to leave suspected rectosigmoid hyperplastic polyps ≤5 mm in size in place (without resection), the technology should provide ≥90% negative predictive value (when used with high confidence) for adenomatous histology. • Thus, in this study, we provided preliminary evidence of the potential of image-enhanced endoscopy technology that is supported with a well-designed and well-studied classification system to meet the criteria that has been independently and previously set forth by the endoscopy society. • Further confirmatory prospective multicenter studies would allow a paradigm shift in endoscopy.

32. Limitations • We did not use high-magnification endoscopes because high-magnification endoscopes are largely unavailable worldwide. • We focused on validating the criteria for differentiating hyperplastic vs adenomatous polyps. Previous studies have indicated that the pathologic differentiation of hyperplastic polyps (which likely included some sessile serrated adenomas/polyps) from conventional adenomas is reasonably reliable with 90% or higher agreement. • We did not evaluate the criteria for distinguishing sessile serrated adenoma/polyps from hyperplastic polyps because a pathologic gold standard for diagnosis has not been fully established, and the surveillance interval recommendations for serrated lesions are not standardized.

33. Conclusion • We present a new classification system for image-enhanced endoscopy for colorectal polyps: the NICE classification. • We established the validity of the classification for differentiating hyperplastic vs adenomatous polyps using high-definition colonoscopes. This classification holds promise to meet the standard minimum performance benchmarks for real-time endoscopic assessment of the histology of diminutive colorectal polyps. • The application of this classification may play a practical and important role in reducing the cost of colonoscopy.

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