Advances in Endoscopic Imaging of Colorectal Neoplasia

Colon cancer screening is arguably the most important activity performed by gastroenterologists. Recent decreases in rates of death from colorectal cancer indicate that screening methods such as colonoscopy have a positive impact. There is still room for improvement, however, particularly in prevention of right-sided colon cancer. Practice issues, such as making colonoscopy more comfortable, safer, and less costly, are keys to continued success in cancer prevention. Colonoscopy techniques, technologies, and quality control measures have advanced to improve detection, classification, and removal of early neoplasias. In particular, slow, careful inspection of the colon by gastroenterologists who have been trained in lesion recognition has improved rates of detection of polypoid and flat neoplasias. Image enhancement methods such as chromoendoscopy have greatly improved neoplasia detection in patients with chronic colitis, but are not widely used because they are perceived as inconvenient. More convenient methods, such as "digital" chromoendoscopy, show promise but have had mixed results. Ultra-high magnification systems, including optical magnification and confocal endomicroscopy, can be used during the colonoscopy examination to evaluate small polyps, allowing physicians to make immediate diagnoses and decisions about whether to remove polyps. In patients with inflammatory bowel disease, improved imaging techniques could eliminate the needs for analysis of randomly selected biopsy samples and resection of all (neoplastic and non-neoplastic) polyps. It is important to maintain high standards of quality for colonoscopy examination, detection, and removal of high-risk lesions, as well as to make colon cancer screening more widely accepted and affordable for the entire at-risk population. Colon cancer screening is arguably the most important activity performed by gastroenterologists. Recent decreases in rates of death from colorectal cancer indicate that screening methods such as colonoscopy have a positive impact. There is still room for improvement, however, particularly in prevention of right-sided colon cancer. Practice issues, such as making colonoscopy more comfortable, safer, and less costly, are keys to continued success in cancer prevention. Colonoscopy techniques, technologies, and quality control measures have advanced to improve detection, classification, and removal of early neoplasias. In particular, slow, careful inspection of the colon by gastroenterologists who have been trained in lesion recognition has improved rates of detection of polypoid and flat neoplasias. Image enhancement methods such as chromoendoscopy have greatly improved neoplasia detection in patients with chronic colitis, but are not widely used because they are perceived as inconvenient. More convenient methods, such as "digital" chromoendoscopy, show promise but have had mixed results. Ultra-high magnification systems, including optical magnification and confocal endomicroscopy, can be used during the colonoscopy examination to evaluate small polyps, allowing physicians to make immediate diagnoses and decisions about whether to remove polyps. In patients with inflammatory bowel disease, improved imaging techniques could eliminate the needs for analysis of randomly selected biopsy samples and resection of all (neoplastic and non-neoplastic) polyps. It is important to maintain high standards of quality for colonoscopy examination, detection, and removal of high-risk lesions, as well as to make colon cancer screening more widely accepted and affordable for the entire at-risk population. Ralf KiesslichView Large Image Figure ViewerDownload Hi-res image Download (PPT) Screening for colorectal cancer with colonoscopy remains the most common procedure performed by gastroenterologists in the United States. More than 14 million colonoscopies are performed annually,1Seeff L.C. Richards T.B. Shapiro J.A. et al.How many endoscopies are performed for colorectal cancer screening? Results from CDC's survey of endoscopic capacity.Gastroenterology. 2004; 127: 1670-1677Abstract Full Text Full Text PDF PubMed Scopus (375) Google Scholar so it is critical that the performance characteristics (accuracy, safety, reduction in colon cancer) be optimized. The core goal of colonoscopy is to detect premalignant polyps, primarily adenomas, and remove them completely. Although colonoscopy is widely considered a reference standard, it is well known than some polyps are not detected, and many polyps with minimal malignant potential (small hyperplastic distal polyps) are removed without benefit to the patient. Newly recognized "flat" polyps are even more challenging to detect, and require more specialized procedures, such as endoscopic mucosal resection, to remove.2Soetikno R.M. Kaltenbach T. Rouse R.V. et al.Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults.JAMA. 2008; 299: 1027-1035Crossref PubMed Scopus (526) Google Scholar The consequence of missing polyps is poorly understood, but recent studies suggest that colonoscopy may be much less protective, particularly in the right colon, than previously thought, perhaps due to missed advanced polyps.3Baxter N.N. Goldwasser M.A. Paszat L.F. et al.Association of Colonoscopy and Death From Colorectal Cancer: a population-based, case-control study.Ann Intern Med. 2009; 150: 1-8Crossref PubMed Scopus (1089) Google Scholar The consequences of removal of hyperplastic polyps, although currently necessary to establish that they are hyperplastic, include both cost and increased risk. Recent studies have shown that polypectomy, whether for adenomas or hyperplastic polyps, is the single greatest risk factor for complications of colonoscopy.4Rabeneck L. Paszat L.F. Hilsden R.J. et al.Bleeding and perforation after outpatient colonoscopy and their risk factors in usual clinical practice.Gastroenterology. 2008; 135: 1899 e1-1906 e1Abstract Full Text Full Text PDF Scopus (392) Google Scholar Although these issues are most relevant to small distal hyperplastic polyps, the clinical significance of proximal hyperplastic lesions, particularly serrated polyps, is more controversial because these may have some malignant potential.5Oka S. Tanaka S. Hiyama T. et al.Clinicopathologic and endoscopic features of colorectal serrated adenoma: differences between polypoid and superficial types.Gastrointest Endosc. 2004; 59: 213-219Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Thus, methods to both improve detection and in vivo classification of colorectal polyps are needed. In this summary, we will highlight important advances in both colonoscopy imaging techniques, and technologies that lead to higher-quality colonoscopy. In the past 40 years, we have seen remarkable advancements in optical and mechanical technologies for imaging the gastrointestinal tract. Since the first creation of flexible fiber optics and flexible endoscopy,6Hopkins H. Kapany N. A flexible fiberscope using static scanning.Nature. 1954; 173: 39-41Crossref Scopus (269) Google Scholar the field has advanced to include video imaging via electronic charge-coupled devices capable of translating light energy into electronic video signals. As electronics improved and charge-coupled device chips became more densely packaged with pixels, high-definition colonoscopy became feasible and is now integrated into standard commercial systems. Together these systems have dramatically increased the resolution with which we can image large surface areas within the gastrointestinal tract. In parallel with high-definition systems, many optical technologies were developed that increase contrast between normal and abnormal tissues. These include topical dyes, optical filtering, and color-enhancement methods. These methods highlight subtle color differences, particularly increased redness in adenomatous polyps, and thus make them easier to see and differentiate from hyperplastic or normal tissue. Finally, technologies for increased magnification of tissue have evolved with the hope of true in vivo pathology or "virtual biopsy." Standard colonoscopes typically provide up to 50× optical magnification; however, zoom systems are capable of nearly 300× magnification, thus allowing visualization of single capillaries or even single red blood cells.7Tanaka S. Kaltenbach T. Chayama K. et al.High-magnification colonoscopy (with videos).Gastrointest Endosc. 2006; 64: 604-613Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Most recently, confocal laser endomicroscopes have been miniaturized and integrated in endoscopes or probe-based catheters for in vivo imaging at 1000× magnification, capable of single-cell and subcellular imaging with resolution similar to white-light microscopy. Other mechanical technologies have made viewing the colon and looking behind folds easier, such as clear caps, miniature endoscopes that provide "retroscope" views via accessory channels of the endoscope, and even wireless capsules. Each of these methods addresses specific deficiencies in colonoscopy (eg, wide-field high-resolution imaging for polyp detection, small-field highly magnified techniques for polyp classification) and no single technology is likely to accomplish all goals. A multimodal approach to improvement is needed, and fortunately, is now at hand (Table 1).Table 1Comparison of Different Mucosal Imaging MethodsChromoendoscopyNarrow-band FICE I-scanAutofluorescenceSpectroscopyConfocalField of viewLarge fieldLarge fieldLarge fieldSmall field/detects large-field defectsSmall fieldBest suited forLesion detectionLesion detection, classificationLesion detectionClassificationClassificationMagnificationLowLowLowNAVery highResolutionLowModerateLowNAVery highCostLowModerateModerateNAHighFICE, Fujinon intelligent chromoendoscopy; NA, not available. Open table in a new tab FICE, Fujinon intelligent chromoendoscopy; NA, not available. Of all the methods currently available for colonoscopy, attention to standard, high-quality technique has the greatest potential for improvement in the effectiveness of colonoscopy. Although not definitively proven, the major reason colonoscopy fails to prevent all colon cancers is likely missed precancerous polyps, including flat, sessile, and pedunculated. Studies of missed polyps, using either back to back colonoscopy, or even surgical resection specimens, suggest that up to 26% of all adenomatous polyps and up to 2% of advanced adenomas are missed at index colonoscopy.8van Rijn J.C. Reitsma J.B. Stoker J. et al.Polyp miss rate determined by tandem colonoscopy: a systematic review.Am J Gastroenterol. 2006; 101: 343-350Crossref PubMed Scopus (1091) Google Scholar The reasons for missing adenomatous polyps appear in part to be related to standard colonoscopy technique. In a study by Rex et al using blinded review of colonoscopy among high and low adenoma detectors, techniques such as careful inspection behind folds, attention to washing the walls of residual material, proper distention of the colon, and sufficient withdrawal time were associated with high adenoma detection.9Rex D.K. Colonoscopic withdrawal technique is associated with adenoma miss rates.Gastrointest Endosc. 2000; 51: 33-36Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar More recently, time spent during withdrawal of the colonoscope was highly associated with adenoma detection rate in a large group practice.10Barclay R.L. Vicari J.J. Doughty A.S. et al.Colonoscopic withdrawal times and adenoma detection during screening colonoscopy.N Engl J Med. 2006; 355: 2533-2541Crossref PubMed Scopus (1149) Google Scholar Cognitive effects are also important, as awareness of increased prevalence and mucosal patterns of adenomas, appears to increase detection of adenomas, even with standard colonoscopy techniques. Adler et al demonstrated that use of high-definition colonoscopy increased detection of adenomas among both high-definition and standard-definition systems.11Adler A. Pohl H. Papanikolaou I.S. et al.A prospective randomised study on narrow-band imaging versus conventional colonoscopy for adenoma detection: does narrow-band imaging induce a learning effect?.Gut. 2008; 57: 59-64Crossref PubMed Scopus (246) Google Scholar Soetikno et al showed that education and exchange programs with Japanese endoscopists increased the detection of flat adenoma in Western patients.2Soetikno R.M. Kaltenbach T. Rouse R.V. et al.Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults.JAMA. 2008; 299: 1027-1035Crossref PubMed Scopus (526) Google Scholar In aggregate these studies suggest that the most important methods for improving colonoscopy quality and in turn reducing colorectal cancer risk, are careful attention to basic techniques and inspection focused on both pedunculated and flat neoplasia. In addition to these, several advanced imaging methods have also been evaluated for improving adenoma detection, with variable results. Standard colonoscopes are forward viewing, with a variable field of view, typically 140 degrees. Wide-angle colonoscopes include current standard systems with 170 degrees field of view, as well as prototype systems with field of view up to 210 degrees. The very wide field of view angle system, particularly those >170 degrees, may introduce "fish-eye" distortions. Tandem colonoscopy studies suggest that wide-angle colonoscopes >170 degrees do not significantly increase adenoma detection.12Rex D.K. Chadalawada V. Helper D.J. Wide angle colonoscopy with a prototype instrument: impact on miss rates and efficiency as determined by back-to-back colonoscopies.Am J Gastroenterol. 2003; 98: 2000-2005Crossref PubMed Scopus (115) Google Scholar Newer colonoscopes typically integrate both high-definition optics and wide angle, up to 170 degrees, so it is difficult to determine which change may be associated with improved adenoma detection. The use of a clear cap attached to the end of a colonoscopy was hypothesized to improved adenoma detection by allowing improved inspection behind folds that were "flattened" by the clear cap. The studies on cap-assisted colonoscopy (CAC) are mixed. In a recent large prospective randomized trial, Lee et al found lower overall adenoma detection with CAC compared to standard colonoscopy, although detection of advanced adenomas was similar.13Lee Y.T. Lai L.H. Hui A.J. et al.Efficacy of cap-assisted colonoscopy in comparison with regular colonoscopy: a randomized controlled trial.Am J Gastroenterol. 2009; 104: 41-46Crossref PubMed Scopus (109) Google Scholar The same author did find that CAC reduced cecal intubation time.13Lee Y.T. Lai L.H. Hui A.J. et al.Efficacy of cap-assisted colonoscopy in comparison with regular colonoscopy: a randomized controlled trial.Am J Gastroenterol. 2009; 104: 41-46Crossref PubMed Scopus (109) Google Scholar, 14Lee Y.T. Hui A.J. Wong V.W. et al.Improved colonoscopy success rate with a distally attached mucosectomy cap.Endoscopy. 2006; 38: 739-742Crossref PubMed Scopus (65) Google Scholar In contrast, in a study by Kondo et al, CAC was associated with improved cecal intubation, and higher adenoma detection, although all cases were performed without sedation and initial intubation and all withdrawals, were performed by gastroenterology trainees so results may be difficult to generalize to most US based endoscopy practices.15Kondo S. Yamaji Y. Watabe H. et al.A randomized controlled trial evaluating the usefulness of a transparent hood attached to the tip of the colonoscope.Am J Gastroenterol. 2007; 102: 75-81Crossref PubMed Scopus (138) Google Scholar It is unclear how a cap would increase cecal intubation time, although possibilities include the ability to "push" folds open during intubation. Overall, these data do not provide sufficient evidence that CAC improves colonoscopy effectiveness. The rationale for looking behind folds of the colon is that polyps are easily missed with forward-viewing optics only. Computed tomography colonography studies have suggested that most missed polyps are located on the back side of a fold.16Pickhardt P.J. Nugent P.A. Mysliwiec P.A. et al.Location of adenomas missed by optical colonoscopy.Ann Intern Med. 2004; 141: 352-359Crossref PubMed Scopus (388) Google Scholar Although clear caps and basic techniques have partially addressed this deficiency, one solution is to allow retrograde viewing using mirrors, or a 2nd imaging camera; a so-called "retroscope." One such device (Third Eye Retroscope; Avantis Medical Systems, Sunnyvale, CA) uses a small-caliber, flexible endoscope that can be passed via the accessory channel of the main colonoscope, then retroflexed to view behind folds during colonoscopy. Only animal and pilot feasibility studies in humans are available at this time, thus it is not possible to determine if these systems improve colonoscopy efficacy.17Triadafilopoulos G. Li J. Watts D. et al.First human use evaluation of the Third Eye Retroscope(TM) Auxiliary Imaging System.Gastrointest Endosc. 2007; 65: AB333Abstract Full Text Full Text PDF Google Scholar, 18Triadafilopoulos G. Li J. A pilot study to assess the safety and efficacy of the Third Eye retrograde auxiliary imaging system during colonoscopy.Endoscopy. 2008; 40: 478-482Crossref PubMed Scopus (48) Google Scholar They do require the accessory channel and thus must be exchanged for snares or biopsy forceps when a polyp is detected. The ability to visualize the large bowel with a nonendoscopic method is highly appealing to patients, although the practical obstacles, particularly the meticulous bowel preparation needed, are limiting. The wireless capsule systems that are used to examine the small bowel have been adapted to examine the colon by delaying the image acquisition start time so as to preserve limited battery reserves for image capture in the large bowel. Despite the appeal of this technique, the efficacy has been limited. In a landmark study by van Gossum et al comparing capsule colonoscopy to conventional colonoscopy, the capsule has poor sensitivity for adenomas >5 mm (sensitivity 63%), adenomas >9 mm (73%), and cancers (74%), although efficacy was higher among patient with good bowel preparation, as expected.19Van Gossum A. Munoz-Navas M. Fernandez-Urien I. et al.Capsule endoscopy versus colonoscopy for the detection of polyps and cancer.N Engl J Med. 2009; 361: 264-270Crossref PubMed Scopus (322) Google Scholar At this time, it is premature to recommend capsule methods as an alternative to standard colonoscopy for colon cancer screening. In chromoendoscopy, intravital dyes like indigo carmine or methylene blue are topically applied onto the mucosal surface to enhance superficial patterns and contrast of pathologic versus normal mucosa (Figure 1 and Supplementary Video 1, which can be found at www.gastrojournal.org). This relatively old technique can be used in an untargeted fashion ("panchromoendoscopy") to detect lesions or in a targeted mode to define the borders of a lesion and its pit pattern.20Canto M.I. Staining in gastrointestinal endoscopy: the basics.Endoscopy. 1999; 31: 479-486Crossref PubMed Scopus (79) Google Scholar In the landmark study by Kudo et al,21Kudo S. Tamura S. Nakajima T. et al.Diagnosis of colorectal tumorous lesions by magnifying endoscopy.Gastrointest Endosc. 1996; 44: 8-14Abstract Full Text Full Text PDF PubMed Scopus (919) Google Scholar a now widely adopted pit pattern classification was established differentiating 5 types of staining patterns in the colon. Types I (round pits) and II (stellar or papillary pits) predict non-neoplastic lesions, whereas types III (tubular pits), IV (gyrus-like pits), and V (nonstructural pits) predict neoplastic lesions with good accuracy. Although this classification was originally developed using magnifying endoscopes, high-resolution and/or high-definition endoscopy often provides sufficient detail to allow for a differentiation of staining patterns. Pan-chromoendoscopy in the colon has been shown to moderately improve the detection of diminutive adenomatous lesions in patients with sporadic adenoma.22Rembacken B.J. Fujii T. Cairns A. et al.Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK.Lancet. 2000; 355: 1211-1214Abstract Full Text Full Text PDF PubMed Scopus (632) Google Scholar However, targeted chromoendoscopy facilitates the detection2Soetikno R.M. Kaltenbach T. Rouse R.V. et al.Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults.JAMA. 2008; 299: 1027-1035Crossref PubMed Scopus (526) Google Scholar and characterization23Kudos K.H. Superficial types of colon cancer, focus on the differences between depressed carcinoma and so called "flat adenoma.".Dig Endosc. 1996; 8: 87-92Crossref Google Scholar of flat and depressed colorectal neoplasias, which is important because nonpolypoid neoplasias are associated with an increased cancer risk. Patients with hereditary nonpolyposis colorectal cancer syndrome might benefit, although it appears to primarily increase detection of diminutive adenomas.24Lecomte T. Cellier C. Meatchi T. et al.Chromoendoscopic colonoscopy for detecting preneoplastic lesions in hereditary nonpolyposis colorectal cancer syndrome.Clin Gastroenterol Hepatol. 2005; 3: 897-902Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 25Stoffel E.M. Turgeon D.K. Stockwell D.H. et al.Missed adenomas during colonoscopic surveillance in individuals with Lynch Syndrome (hereditary nonpolyposis colorectal cancer).Cancer Prev Res (Phila Pa). 2008; 1: 470-475Crossref PubMed Scopus (102) Google Scholar Although imaging trials have clearly shown improved dysplasia detection in colitis patients, we do not yet know how this will translate into improved clinical benefit, as recently modeling studies question.26Awais D. Siegel C.A. Higgins P.D. Modelling dysplasia detection in ulcerative colitis: clinical implications of surveillance intensity.Gut. 2009; 58: 1498-1503Crossref PubMed Scopus (33) Google Scholar There is convincing evidence from a multitude of studies that the detection of flat, circumscribed colitis-associated neoplasias is enhanced in patients with long-standing ulcerative colitis by a factor of 3 to 5.27Kiesslich R. Goetz M. Lammersdorf K. et al.Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis.Gastroenterology. 2007; 132: 874-882Abstract Full Text Full Text PDF PubMed Scopus (490) Google Scholar, 28Kiesslich R. Fritsch J. Holtmann M. et al.Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis.Gastroenterology. 2003; 124: 880-888Abstract Full Text Full Text PDF PubMed Scopus (817) Google Scholar, 29Rutter M.D. Saunders B.P. Schofield G. et al.Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis.Gut. 2004; 53: 256-260Crossref PubMed Scopus (518) Google Scholar, 30Hurlstone D.P. Sanders D.S. Lobo A.J. et al.Indigo carmine-assisted high-magnification chromoscopic colonoscopy for the detection and characterisation of intraepithelial neoplasia in ulcerative colitis: a prospective evaluation.Endoscopy. 2005; 37: 1186-1192Crossref PubMed Scopus (253) Google Scholar, 31Marion J.F. Waye J.D. Present D.H. et al.Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial.Am J Gastroenterol. 2008; 103: 2342-2349Crossref PubMed Scopus (265) Google Scholar The US guidelines endorsed the use of chromoendoscopy in the surveillance of ulcerative colitis patients.32Itzkowitz S.H. Present D.H. Consensus conference: colorectal cancer screening and surveillance in inflammatory bowel disease.Inflamm Bowel Dis. 2005; 11: 314-321Crossref PubMed Scopus (527) Google Scholar The European consensus guidelines even adopted the concept of "smart" biopsies of lesions detected and analyzed by chromoendoscopy instead of untargeted quadrant biopsies of apparently normal mucosa after chromoendoscopy.33Biancone L. Michetti P. Travis S. et al.European evidence-based consensus on the management of ulcerative colitis: special situations.J Crohns Colitis. 2008; 2: 63-92Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar The success of chromoendoscopy has triggered research activities toward "virtual chromoendoscopy" by new light filters, such as narrow band imaging (NBI) or postprocessing techniques, such as I-scan or Fujinon intelligent chromoendoscopy (Figure 2, Figure 3,Supplementary Videos 2A and B). Conventional white light endoscopy (WLE) utilizes visible light for tissue illumination. NBI uses rotating filters in front of the light source to narrow the bandwidth of the projected light to 30-nm wide spectra of blue (415 nm) and green (540 nm) to generate a pseudo-colored image. Blue light has shallow penetration to only the superficial layers and coincides.Figure 3(A) High definition white light, (B) narrow band imaging, and (C) autofluorescence imaging of a 5-mm tubular adenoma of the colon. Note the increased contrast seen in the narrow band image, and the slight purple colon on the fluorescence image characteristic of neoplastic lesions.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Initial studies have shown a good correlation between chromoendoscopy and NBI34Hirata M. Tanaka S. Oka S. et al.Magnifying endoscopy with narrow band imaging for diagnosis of colorectal tumors.Gastrointest Endosc. 2007; 65: 988-995Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar and enhanced adenoma detection rates in high-risk patients.35East J.E. Suzuki N. Stavrinidis M. et al.Narrow band imaging for colonoscopic surveillance in hereditary non-polyposis colorectal cancer.Gut. 2008; 57: 65-70Crossref PubMed Scopus (174) Google Scholar However, large follow-up studies on patients with average cancer risk could not reproduce an enhanced adenoma detection rate by NBI when compared to high-definition WLE in screening colonoscopy.11Adler A. Pohl H. Papanikolaou I.S. et al.A prospective randomised study on narrow-band imaging versus conventional colonoscopy for adenoma detection: does narrow-band imaging induce a learning effect?.Gut. 2008; 57: 59-64Crossref PubMed Scopus (246) Google Scholar, 36Rex D.K. Helbig C.C. High yields of small and flat adenomas with high-definition colonoscopes using either white light or narrow band imaging.Gastroenterology. 2007; 133: 42-47Abstract Full Text Full Text PDF PubMed Scopus (373) Google Scholar, 37Adler A. Aschenbeck J. Yenerim T. et al.Narrow-band versus white-light high definition television endoscopic imaging for screening colonoscopy: a prospective randomized trial.Gastroenterology. 2009; 136 (quiz 715): 410 e1-416 e1Abstract Full Text Full Text PDF Scopus (175) Google Scholar Probably high-definition per se contributed to high adenoma detection rates, but NBI induced a learning effect even in experienced endoscopists as to the appreciation of flat adenomas in WLE.11Adler A. Pohl H. Papanikolaou I.S. et al.A prospective randomised study on narrow-band imaging versus conventional colonoscopy for adenoma detection: does narrow-band imaging induce a learning effect?.Gut. 2008; 57: 59-64Crossref PubMed Scopus (246) Google Scholar Newer filter modalities, such as I-scan or Fujinon intelligent chromoendoscopy, use postprocessing computer algorithms to modulate the light reflected from the mucosa, highlighting surface contrast, vessel patterns, or pit pattern. I-scan and Fujinon intelligent chromoendoscopy were not able to increase the detection rate of adenomas; however, they can be used like NBI to characterize colorectal lesions as precisely as chromoendoscopy.38Hoffman A. Kagel C. Goetz M. et al.Recognition and characterization of small colonic neoplasia with high-definition colonoscopy using i-Scan is as precise as chromoendoscopy.Dig Liver Dis. 2010; 42: 45-50Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar, 39Pohl J. Nguyen-Tat M. Pech O. et al.Computed virtual chromoendoscopy for classification of small colorectal lesions: a prospective comparative study.Am J Gastroenterol. 2008; 103: 562-569Crossref PubMed Scopus (133) Google Scholar After exposure of tissues to light of a defined short wavelength, excitation of endogenous fluorophores results in the emission of light of a longer wavelength, which is termed autofluorescence. Due to changes of endogenous fluorophores in dysplastic tissue, the altered autofluorescence spectrum can be translated into a pseudo-colored image in which normal tissue appears greenish in contrast to a purple rendering of dysplastic tissue. In feasibility studies, autofluorescence imaging (AFI) was restricted to prototype scopes with poorer resolution of white light images.40Matsuda T. Saito Y. Fu K.I. et al.Does autofluorescence imaging videoendoscopy system improve the colonoscopic polyp detection rate?—a pilot study.Am J Gastroenterol. 2008; 103: 1926-1932Crossref PubMed Scopus (112) Google Scholar More recently, AFI has been combined with high-resolution endoscopy and NBI in a single endoscope with 2 charge-coupled devices, a combination termed endoscopic trimodal imaging (Figure 3). AFI images are composed of total emitted autofluorescence after blue