Perspectives of chromo and magnifying endoscopy: how, how much, when, and whom should we stain?

The goal of every routine endoscopy in the gut is the early diagnosis of malignant and premalignant changes of the mucosa. Chromo- and magnifying endoscopes are exciting new tools and offer detailed analysis of the colonic mucosal surface and pit pattern architecture. This review summarizes recent advances in endoscopic characterization of colorectal lesions using magnification endoscopy and chromoendoscopy. Surface analysis of the colon using chromoendoscopy allows a prediction between non-neoplastic and neoplastic lesions with high specificity. The precise delineation of the borders and a more detailed macroscopic analysis of the lesions are further advantages. In particular, flat adenomas and early depressed cancers are now more frequently recognized in western countries suggesting that significant lesions were overlooked by conventional endoscopy in the past. Furthermore, chromoendoscopy can be used in a targeted fashion to screen for sporadic adenomas. Finally, in surveillance colonoscopy, patients with long-standing ulcerative colitis have a valuable benefit if targeted biopsies are performed to detect intraepithelial neoplasias after pan-chromoendoscopy with methylene blue. Although there is a long learning curve, chromoendoscopy should thus belong to every endoscopists armamentarium. However, detailed knowledge about the technique, dyes, and specific staining patterns are mandatory before the yield of screening or surveillance colonoscopy can be increased. The new detailed images seen with magnifying chromoendoscopy are unequivocally the beginning of a new era where new optical developments will allow a unique look on cellular structures.     

Efficacy of magnifying chromoendoscopy for the differential diagnosis of colorectal lesions

Magnifying chromoendoscopy is an exciting new tool and offers detailed analysis of the morphological architecture of mucosal crypt orifices. In this review, we principally show the efficacy of magnifying chromoendoscopy for the differential diagnosis of colorectal lesions such as prediction between non‐neoplastic lesions and neoplastic ones, and distinction between endoscopically treatable early invasive cancers and untreatable cancers based on a review of the literature and our experience at two National Cancer Centers in Japan. Overall diagnostic accuracy by conventional view, chromoendoscopy and chromoendoscopy with magnification ranged from 68% to 83%, 82% to 92%, and 80% to 96%, respectively, and diagnostic accuracy of accessing the stage of early colorectal cancer using magnifying colonoscopy was over 85%. Although the reliability depends on the skill in magnifying observation, widespread applications of the magnification technique could influence the indications for biopsy sampling during colonoscopy and the indication for mucosectomy. Moreover, the new detailed images seen with magnifying chromoendoscopy are the beginning of a new period in which new optical developments, such as narrow band imaging system, endocytoscopy system, and laser‐scanning confocal microscopy, will allow a unique look at glandular and cellular structures.     

Endoscopic detection of early lower gastrointestinal cancer

The prognosis for patients with malignancies of the lower gastrointestinal tract is strictly dependent on early detection of premalignant and malignant lesions. What should an ideal screening and surveillance colonoscopy be able to accomplish? The technique should allow detection of large but also discrete mucosal alterations. Ideally, endoscopic discrimination between neoplastic and non-neoplastic lesions would be possible during the ongoing procedure. At present, endoscopy can be performed with powerful new endoscopes. Comparable to the rapid development in chip technology, the optical features of the newly designed endoscopes offer resolutions, which allow new surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool video colonoscopy is much easier and more impressive today than with the previously used fibre-optic endoscopes. Recently, new endoscopic technologies such as narrow band imaging, endocytoscopy, or confocal laser endoscopy have allowed the discovery of a whole new world of image details which will surely improve the diagnostic yield in the field of early malignancies. This review summarises newly available technologies and clinical data about the diagnosis of early lower gastrointestinal cancers.     

Magnifying chromoendoscopy for the detection of premalignant gastrointestinal lesions

The prognosis for patients with malignancies of the gastrointestinal tract is strictly dependent on the early detection of premalignant and malignant lesions. At present, endoscopy can be performed with new, powerful high-resolution or magnifying endoscopes. Comparable to the rapid development in chip technology, the optic features of the newly designed endoscopes offer resolutions that allow new mucosal surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool of video endoscopy is much easier to use and more impressive than previously used fibreoptic endoscopy. This review summarises the value of magnifying endoscopy in the upper and lower gastrointestinal tract and focuses on gastroesophageal reflux disease and early gastric and colorectal cancer.     

Chromo- and magnifying endoscopy for colorectal lesions

It is essential to identify patients with premalignant or early malignant changes during colonoscopy. Thus, curative resection can be offered. At present, endoscopy can be performed with new powerful high-resolution or magnifying endoscopes. Comparably to the rapid development in chip technology, the optic features of the newly designed endoscopes offer resolutions which allow new mucosal surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool video endoscopy is much easier and more impressive than with conventional fibre optics. This review summarizes the value of magnifying endoscopy in the lower gastrointestinal tract and focuses on colorectal lesions.     

New endoscopic imaging techniques in surveillance of inflammatory bowel disease

Endoscopy plays a crucial role in the management of inflammatory bowel disease(IBD). Advancesimaging techniques allow visualization of mucosal details, tissue characteristics and cellular alteration. In particular chromoendoscopy, magnification endoscopy, confocal laser endomicroscopy and endocytoscopy seem to have the possibility to radically modify the approach to surveillance and decision making. Dyebased chromoendoscopy(DBC) and magnification chromoendoscopy improve detection of dysplasia, and evaluation of inflammatory activity and extension of ulcerative colitis and are thus considered the standard of care. Dye-less chromoendoscopy could probably replace conventional DBC for surveillance. Narrow band imaging and i-scan have shown to improve activity and extent assessment in comparison to white-light endoscopy. Confocal laser endomicroscopy(CLE) can detect more dysplastic lesions in surveillance colonoscopy and predict neoplastic and inflammatory changes with high accuracy compared to histology. This technology is best used in conjunction with chromoendoscopy, narrow-band imaging, or autofluorescence because of its minute scanning area. This combination is useful for appropriate tissue classification of mucosal lesions already detected by standard or optically enhanced endoscopy. The best combination for IBD surveillance appear to be chromoendoscopy for identification of areas of suspicion, with further examination with CLE to detect intraepithelial neoplasia. However cost, availability, and experience are still an issue.     

Endoskopische Technik

Technical innovations in endoscopy enhance the detection predominantly of flat and minute lesions. High-definition endoscopes allow visualization of fine mucosal details, especially in conjunction with digital contrast enhancement. Virtual chromoendoscopy permits characterization of lesions and exact definition of their borders. Autofluorescence imaging has the potential to serve as a red flag technique to reduce the lesion miss rate. Endomicroscopy offers microscopy of lesions during ongoing endoscopy for the first time.     

Chromoendoscopy

Accurate detection of premalignant lesions and early cancers in the gastrointestinal tract is essential for curative endoscopic or surgical therapy, because prognosis of the affected patients is closely related to the size and stage of the neoplastic lesion. Recently, it has emerged new endoscopic devices that allow even cellular images in vivo during an endoscopic procedure. These technologies will change and improve endoscopic diagnosis. The combination and integration of different technologies in a multifunctional endoscope will offer new optical features in GI endoscopy. Cytoendoscopy will characterize the surface architecture, confocal laser endomicroscopy will immediately clarify the nature of the lesions by in vivo histology of the mucosal layer, and optical coherence tomography will accurately grade the invasion depth. It will need some additional time before this scenario comes true. Endoscopy will become more complex due to the new visible details. Education and training will play an important future role in GI endoscopy. However, it is not possible to use these novel technologies without before learn to identify early GI cancers lesions. Meanwhile these technologies are perfectionated and we overcome the learning curve to identify early GI lesions, chromoendoscopy will continue to be a safe, easy and inexpensive method.     

Computed virtual chromoendoscopy for classification of small colorectal lesions: a prospective comparative study

OBJECTIVES: Standard colonoscopy offers no reliable discrimination between neoplastic and nonneoplastic colorectal lesions. Computed virtual chromoendoscopy with the Fujinon intelligent color enhancement (FICE) system is a new dyeless imaging technique that enhances mucosal and vascular patterns. This prospective trial compared the feasibility of FICE, standard colonoscopy, and conventional chromoendoscopy with indigo carmine in low- and high-magnification modes for determination of colonic lesion histology. METHODS: Sixty-three patients with 150 flat or sessile lesions less than 20 mm in diameter were enrolled. At colonoscopy, each lesion was observed with six different endoscopic modalities: standard colonoscopy, FICE, and conventional chromoendoscopy with indigo carmine (0.2%) dye spraying in both low- and high-magnification modes. Histopathology of all lesions was confirmed by evaluation of endoscopic resection or biopsy specimens. Endoscopic images were stored electronically and randomly allocated to a blinded reader. RESULTS: Of the 150 polyps, 89 were adenomas and 61 were hyperplastic polyps with an average size of 7 mm. For identifying adenomas, the FICE system with low and high magnifications revealed a sensitivity of 89.9% and 96.6%, specificity of 73.8% and 80.3%, and diagnostic accuracy of 83% and 90%, respectively. Compared with standard colonoscopy, the sensitivity and diagnostic accuracy achieved by FICE were significantly better under both low (P < 0.02) and high (P < 0.03) magnification and were comparable to that of conventional chromoendoscopy. CONCLUSIONS: The FICE system identified morphological details that efficiently predict adenomatous histology. For distinguishing neoplastic from nonneoplastic lesions, FICE was superior to standard colonoscopy and equivalent to conventional chromoendoscopy.     

IMPROVEMENT OF CHOLEDOCHOSCOPY: CHROMOENDOCHOLEDOCHOSCOPY,AUTOFLUORESCENCE IMAGING,OR NARROW‐BAND IMAGING

Past and present results concerning assessment of choledochoscopy using chromoendoscopy, autofluorescence imaging (AFI), or narrow‐band imaging (NBI) are summarized herein. On chromoendocholedochoscopy using methylene blue, cancer was stained dark blue. Interestingly, normal bile duct had dimple signs that are a significant feature of non‐neoplastic mucosa. First‐generation AFI (laser‐induced fluorescence endoscopy–gastrointestine system) and system of autofluorescence endoscopy made it possible to detect neoplastic lesions as dark green–black lesions, although the image was insufficient. The sensitivity, specificity and diagnostic accuracy of white light illumination and AFI were 88.0%, 87.5%, 87.7%, and 100%, 52.5%, 70.8%, respectively. In contrast, the recently developed NBI system made it possible to emphasize the imaging of certain features such as mucosal structures and mucosal microvessels. NBI showed not only clear neoplastic findings such as irregular mucosa or tortuous tumor vessel, but also non‐neoplastic findings such as smooth surface mucosa or dimple sign. In conclusion, the diagnostic power of chromoendoscopy and AFI were low, but NBI is expected to become the new‐generation diagnostic tool for biliary tract diseases.     

Advanced precancerous lesions in the lower oesophageal mucosa: High-grade dysplasia and intramucosal carcinoma in Barrett's oesophagus

Adenocarcinoma developed in Barrett's oesophagus is a tumour with an increasing incidence and still a poor prognosis. The only marker that can be used for surveillance remains dysplasia (intraepithelial neoplasia), especially when it is high-grade, that precedes intramucosal carcinoma. New forms of dysplasia have been described in complement to the classical intestinal type (foveolar dysplasia, basal crypt dysplasia). High-grade dysplasia and intramucosal carcinoma are diagnosed on biopsies taken during endoscopy. Standard endoscopy is now challenged by various techniques that represent recent major technical improvements (chromoendoscopy, virtual chromoendoscopy, optical frequency domain imaging, confocal laser endomicroscopy). In numerous cases, high-grade dysplasia and intramucosal carcinoma can be treated by endoscopic procedures, allowing a precise histopathological diagnosis on the resected specimen (endoscopic mucosal resection, submucosal endoscopic dissection) or destroying the neoplastic tissue. Radiofrequency ablation is currently considered as the best available technique for treatment of flat high grade dysplasia and for eradication of residual Barrett's mucosa after focal endoscopic mucosal resection.     

Endomikroskopie

Endomicroscopy becomes possible due to the integration of a miniaturized confocal microscope in the distal tip of a conventional endoscope. Endomicroscopy enables subsurface analysis of the gut mucosa and in vivo histology during ongoing endoscopy in full resolution by point scanning laser fluorescence analysis. Cellular, vascular and connective structures can be seen in detail. Graduation of cellular changes with endomicroscopy allows an immediate in-vivo diagnosis of different gastrointestinal diseases. The diagnostic spectrum of confocal endomicroscopy is currently expanding from screening and surveillance for colorectal cancer towards Barrett's esophagus, Helicobacter pylori associated gastritis and early gastric cancer. The new detailed images seen with confocal laser endomicroscopy are unequivocally the beginning of a new era where this optical development will allow a unique look on cellular structures and functions at and below the surface of the gut.     

A prospective comparative study of narrow-band imaging, chromoendoscopy, and conventional colonoscopy in the diagnosis of colorectal neoplasia

BACKGROUND: Discrimination between neoplastic and non-neoplastic lesions is crucial in colorectal cancer screening. Application of narrow-band imaging (NBI) in colonoscopy visualises mucosal vascular networks in neoplastic lesions and may improve diagnostic accuracy. AIM: To compare the diagnostic efficacy of NBI in differentiating neoplastic from non-neoplastic colorectal lesions with diagnostic efficacies of standard modalities, conventional colonoscopy, and chromoendoscopy. METHODS: In this prospective study, 180 colorectal lesions from 133 patients were observed with conventional colonoscopy, and under low-magnification and high-magnification NBI and chromoendoscopy. Lesions were resected for histopathological analysis. Endoscopic images were stored electronically and randomly allocated to two readers for evaluation. Sensitivity, specificity and diagnostic accuracy of each endoscopic modality were assessed by reference to histopathology. RESULTS: NBI and chromoendoscopy scored better under high magnification than under low magnification in comparison with conventional colonoscopy. The diagnostic accuracy of NBI with low or high magnification was significantly higher than that of conventional colonoscopy (low magnification: p = 0.0434 for reader 1 and p = 0.004 for reader 2; high magnification: p<0.001 for both readers) and was comparable to that of chromoendoscopy. CONCLUSION: Both low-magnification and high-magnification NBI were capable of distinguishing neoplastic from non-neoplastic colorectal lesions; the diagnostic accuracy of NBI was better than that of conventional colonoscopy and equivalent to that of chromoendoscopy. The role of NBI in screening colonoscopy needs further evaluation.     

Novel diagnostic and therapeutic techniques for surveillance of dysplasia in patients with inflammatory bowel disease

The risk for developing dysplasia and colorectal cancer in patients with longstanding inflammatory bowel disease (IBD) involving the colon is well documented. Random biopsies during white-light, standard-definition colonoscopy (33 to 50 biopsies) with or without dye spraying chromoendoscopy has been the recommended strategy in North America to detect dysplastic lesions in IBD. However, there are several limitations to this approach including poor physician adherence, poor sensitivity, increased procedure time and considerable cost. The new generation of high-definition endoscopes with electronic filter technology provide an opportunity to visualize colonic mucosal and vascular patterns in minute detail, and to identify subtle flat, multifocal, polypoid and pseudopolypoid neoplastic and non-neoplastic lesions. The application of these new technologies in IBD is slowly being adopted in clinical practice. In addition, the advent of confocal laser endomicroscopy provides an opportunity to explore real-time histology, thus redefining the understanding and characterization of the lesions in IBD. There is emerging evidence that serrated adenomas are also associated with longstanding IBD colitis and may be recognized as another important contributing factor to colorectal cancer development. The circumscribed neoplastic lesions can be treated using endoscopic therapeutic management such as mucosal resection or, especially, endoscopic submucosal dissection. This may replace panproctocolectomy in selected patients. The authors review the potential of these techniques to transform endoscopic diagnosis and therapeutic management of dysplasia in IBD.     

Role of chromoendoscopy in colon cancer surveillance in inflammatory bowel disease

Inflammation in the intestine is a well-known risk factor for neoplastic changes in the mucosa. In fact, it has been shown that long-standing ulcerative colitis and colonic Crohn's disease have a significantly increased risk for developing colorectal cancer, although the estimates vary widely between studies. Conventional colonoscopy is effective in detecting polypoid changes in the mucosa. However, it is now generally accepted that neoplastic changes in colitis are frequently flat and depressed, which are easily missed by use of routine colonoscopy. The introduction of chromoendoscopy, especially in combination with magnifying endoscopy, has greatly advanced our means to detect and differentiate neoplastic lesions in the colorectum. Accumulating evidence-based data indicate that implementation of chromoendoscopy into colon cancer surveillance protocols for patients with inflammatory bowel disease is effective. However, the introduction of chromoendoscopy into surveillance programs requires meticulous training and further studies to compare the value of chromoendoscopy to newer endoscopic devices and techniques, such as narrow band imaging.     

Endoscopic resection of gastrointestinal lesions: Advancement in the application of endoscopic submucosal dissection

Curative endoscopic resection is now a viable option for a range of neoplastic lesions of the gastrointestinal tract (GIT) with low invasive potential. Risk of lymph node metastasis is the most important prognostic factor in selecting appropriate lesions for endoscopic therapy, and assessment of invasion depth is vital in this respect. To determine appropriate treatment, detailed endoscopic diagnosis and estimation of depth using magnifying chromoendoscopy is the gold standard in Japan. En bloc resection is the most desirable endoscopic therapy as risk of local recurrence is low and accurate histological diagnosis of invasion depth is possible. Endoscopic mucosal resection is established worldwide for the ablation of early neoplasms, but en bloc removal using this technique is limited to small lesions. Evidence suggests that a piecemeal resection technique has a higher local recurrence risk, therefore necessitating repeated surveillance endoscopy and further therapy. More advanced endoscopic techniques developed in Japan allow effective en bloc removal of early GIT neoplasms, regardless of size. This review discusses assessment of GIT lesions and options for endoscopic therapy with special reference to the introduction of endoscopic submucosal dissection into Western countries.     

Comparative study of conventional colonoscopy, chromoendoscopy, and narrow-band imaging systems in differential diagnosis of neoplastic and nonneoplastic colonic polyps

AIM: To identify the feasibility of the narrow-band imaging (NBI) method compared with that of conventional colonoscopy and chromoendoscopy for distinguishing neoplastic and nonneoplastic colonic polyps. METHOD: This study enrolled consecutive patients who underwent colonoscopy using a conventional colonoscope between January and February 2006 at Chang-Gung Memorial Hospital, Linkou Medical Center, Taiwan. These 78 patients had 110 colorectal polyps. During the procedure, conventional colonoscopy first detected lesions, and then the NBI system was used to examine the capillary networks. Thereafter indigo carmine (0.2%) was sprayed directly on the mucosa surface prior to evaluating the crypts using a conventional colonoscope. The pit patterns were characterized using the classification system proposed by Kudo. Finally, a polypectomy or biopsy was performed for histological diagnosis. RESULTS: Of the 110 colorectal polyps, 65 were adenomas, 40 were hyperplastic polyps, and five were adenocarcinomas. The NBI system and pit patterns for all lesions were analyzed. For differential diagnosis of neoplastic (adenoma and adenocarcinoma) and nonneoplastic (hyperplastic) polyps, the sensitivity of the conventional colonoscope for detecting neoplastic polyps was 82.9%, specificity was 80.0% and diagnostic accuracy was 81.8%, significantly lower than those achieved with the NBI system (sensitivity 95.7%, specificity 87.5%, accuracy 92.7%) and chromoendoscopy (sensitivity 95.7%, specificity 87.5%, accuracy 92.7%). Therefore, no significant difference existed between the NBI system and chromoendoscopy during differential diagnosis of neoplastic and nonneoplastic polyps. CONCLUSION: The NBI system identified morphological details that correlate well with polyp histology by chromoendoscopy.     

内镜窄带成像与染色技术诊断大肠肿瘤的对比研究

目的通过窄带成像技术（NBI）和染色放大方法对大肠新生性病变进行观察，比较这两种技术对大肠肿瘤及非肿瘤性病变的鉴别诊断精度差异。方法2006年6月至9月间，共302例年龄在加至80岁之间的患者进行了NBI肠镜检查，其中98例入选。内镜插入至回盲部，退镜时分别采用常规模式、NBI模式观察，发现病变后，分别用NBI模式及染色放大方法进行血管分型及腺管开口分型，然后行病理检查进行评价比较。结果在98例患者发现新生性病变147个，其中常规内镜下发现的病变有90．5％（133／147），采用NBI发现病变有98．6％（145／147），差异有统计学意义（P〈0．01），漏诊的主要为平坦型病变。NBI观察对肿瘤性或非肿瘤的判断符合率为91．8％，染色内镜为82．3％（P〈0.01）。结论NBI技术观察黏膜表面变化，判断肿瘤或非肿瘤病变的符合率比普通内镜和染色内镜高，敏感性强；操作转换简单易行，尤其有利于平坦型病变的发现及诊断。     

Präkanzerosen im Ösophagus

Modern high-resolution video endoscopes allow detailed examination of the esophageal mucosa and diagnosis of early neoplastic changes in the gastrointestinal tract. Whereas Barrett’s esophagus is a precancerous condition that can develop into adenocarcinoma, there is no defined precancerous lesion for squamous cell carcinoma. Various diseases are associated with the development of esophageal squamous cell carcinoma. Chromoendoscopy has become an established method in the diagnostic work-up for better visualization of early neoplasia. If Barrett’s esophagus is present, acetic acid spraying or virtual chromoendoscopy can be used to accentuate the display of superficial gyriform structures in the mucosa. The gold standard for detecting squamous cell carcinoma is still the use of Lugol solution. When early neoplasia is suspected, diagnostic endoscopic resection should be performed. This allows precise histological assessment of the tumor. Early diagnosis of neoplastic changes in the esophagus provides patients not only with the option of curative therapy but also with a good quality of life through preservation of the esophagus.     

Improved detection of colorectal neoplasms with selective use of chromoendoscopy in 2005 consecutive patients

Background Colorectal cancer mortality is decreased by endoscopic polypectomy, but conventional colonoscopy may be inadequate for detecting subtle colonic lesions. Methods We selectively performed chromoendoscopy in all patients undergoing colonoscopy between January 1999 and December 2005 at the International Health Union of Rome. Patients with a history of colorectal polyps, inflammatory bowel disease, colorectal surgery or coagulopathy and those with poor bowel preparation were excluded from this analysis. Whenever colonoscopy revealed suspicious mucosal areas, dye-spraying with 0.2% indigo carmine solution was also performed. Findings from conventional and dyespraying views were classified morphologically, and specimens were analyzed histologically. Non-adenomatous lesions were classified as negative findings. Results A total of 2005 patients underwent conventional colonoscopy and in 305 cases (15%) chromoendoscopy was also performed. Conventional colonoscopy identified 508 neoplasms in 381 patients (19%). Selective chromoendoscopy found an additional 244 neoplasms in 212 patients (11%). Thus, chromoendoscopy was positive in 212 (70%) of 305 patients in whom the examination was performed. Overall, 56 large, ulcerated, advanced cancers and 696 non-advanced neoplasms were found. Of the 696 nonadvanced neoplasms, 448 (65%) were polypoid and 248 (35%) were non-polypoid. All but 4 non-polypoid lesions were only detected with chromoendoscopy. Of the 248 non-polypoid lesions, 12 (5%) were depressed and 236 (95%) were flat. Advanced histology was present in 39 non-polypoid lesions (15%) and was more common in depressed lesions than in flat ones (58% vs. 13%; p<0.001). Conclusions Our study confirms the existence of flat and depressed neoplasms in an Italian population. The vast majority of non-polypoid lesions were only detected by chromoendoscopy, and many lesions with advanced histology were missed by conventional colonoscopy. We therefore recommend selectively performing chromoendoscopy when conventional colonoscopy provides clues for non-polypoid lesions. Therefore, endoscopists should be trained in the detection of these subtle mucosal clues, as well as in the use of chromoendoscopy to enhance their detection. An erratum to this article is available at .