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Recent advances to improve the endoscopic detection and differentiation of early colorectal neoplasia

2014; Wiley; Volume: 17; Issue: s1 Linguagem: Inglês

10.1111/codi.12818

1463-1318

Giuseppe Galloro, Simona Ruggiero, Teresa Russo, Brian P. Saunders,

Esophageal Cancer Research and Treatment

One of the primary aims of colonoscopy is to detect and resect pre-cancerous lesions, thereby preventing cancer development and early colorectal cancers, avoiding the growth of advanced and deep-infiltrating malignant tumours. Failure to find and remove polyps and early cancers results in a delayed cancer diagnosis and treatment, with the potential for poor patient outcomes and the risk of litigation 1. In recent years, industry has made many efforts to improve the technology to enhance the performance of endoscopic examination: many of these innovations are included under the term 'augmented endoscopy'. Augmented endoscopy includes topical dyes 2, 3, optical filtering 4, 5, zoom-magnification 6, 7 and allows for various analyses of gastro-intestinal lesions, such as minute structure of crypts on the mucosal surface and superficial micro-vessels. This kind of enhanced endoscopy provides new tools for identifying the abnormalities in the size, density, and shape of crypts and vessels in either the normal colon or a tumour lesion. Today, colonoscopy is a universally accepted method for colorectal cancer screening and diagnosis 8. Endoscopists may, however, miss up to 6% of advanced adenomas (≥10 mm in size) or cancer and as many as 26–30% of all adenomas when using standard white-light colonoscopy 9, probably because of the location of the lesion, the skill of the endoscopist 10 and the image contrast of the endoscopic picture. Augmented endoscopy, enhancing the endoscopic appearances of colon lesions, has the potential to improve detection and differentiation of colon neoplasms from other lesions 11. Clinical trials testing the usefulness of augmented endoscopy for the diagnosis of colon neoplasia show conflicting results 12. This may be related to the limitations of each technology and variation in the diagnostic skill of the participants. Therefore, as reported by Fujiya and Kohgo, '… two factors related to the usefulness of these novel technologies need to be evaluated: at which step(s) is that technology applicable for the diagnosis of colon neoplasms (detection, differentiation, or staging) and by what level(s) of endoscopists (experts or less experienced endoscopists) can the technology be used …' 13. Technology alone, however, is not enough to ensure optimal results and to achieve the best outcome. All variables affecting rates of detection by the endoscopist and the endoscopic method used are important. These include the operator's experience, bowel preparation, examination technique and the use of instruments or devices able to increase visual identification. Recent studies clearly show that patients examined by colonoscopists with a low adenoma detection rate (ADR) have an increased risk of unexpected cancer in the 3 year period after colonoscopy compared with those examined by colonoscopists with a high adenoma detection rate 14. The ADR has therefore been adopted as a key colonoscopist performance indicator and may be used in the future for credentialing and recognition of practice rights/payment guarantee. For average-risk (>50 years) screening colonoscopy patients, American guidelines recommend colonoscopists achieve an ADR of >25% for men and 15% for women 15, 16. In the British Bowel Cancer Screening programme an ADR of >35% is expected for faecal occult blood test screenees over the age of 60 years. It may not be possible with current techniques and technology to reduce the miss rate to zero but to optimise performance a number of factors must be addressed. There is a clear correlation between the quality of bowel preparation and the polyp detection rate. Good bowel preparation also allows more frequently a complete examination and improved levels of satisfaction for endoscopist and patient 17. Certain general principles apply when optimising bowel preparation. Patients should have clear instructions and support with a telephone help line. Recent innovations include text reminders and specifically designed computer applications to guide the process. Regardless of the bowel preparation used, a split dose regimen is crucial with clear fluids encouraged up until the procedure. Most regimens encourage 1–3 days of dietary (low fibre intake) prior to the bowel preparation. Patients with a previously poor bowel preparation, who often have delayed transit times demand special attention and need a more prolonged purge that may require hospital supervision. Patient preference for bowel preparation should also be taken into account as a previous poor experience with one preparation may not occur with another. The preparation instructions should always include advice for the patient to attend one hour before the scheduled appointment if it is felt that the preparation has not worked satisfactorily, so that a phosphate enema can be given if needed. Despite all best endeavours there will still be a small percentage (<5%) of patients who present with a suboptimal preparation. Solid stool usually requires a repeated bowel preparation and rescheduling of the procedure, however liquid or small amounts of semi-solid stool can usually be managed with the help of a washing pump. New systems incorporate a washing jet and may be helpful as rescue therapy to avoid abandoning procedures 18. Many endoscopists aim to pass to the caecum quickly and do not perform polypectomy during insertion. This strategy assumes, however, that small polyps will be easily visible during withdrawal, which is not always the case. It is safer to remove all small polyps when they are first seen leaving only the larger lesions that are unlikely to be missed during the withdrawal phase. Caecal intubation should always be confirmed with photo documentation of the caecal pole (appendix orifice and ileo-caecal valve). At this point withdrawal with examination can the commence. Each segment of the colon should be carefully inspected using backward and forward manipulations of the tip of the 'scope to hold down haustral folds and ensure visualisation around the back of folds 19. The examination technique, when independently judged on video replay clearly correlates with the individual's adenoma detection rate 20. Additional washing of debris and suction is often necessary. Changes in the position of the patient will allow areas of the colon to become easier to visualise, through gravity. The right colon is often most easily seen with the patient in the left lateral position, the transverse colon with the patient supine, the splenic flexure and descending colon with the patient tipped towards the right lateral position and the sigmoid and rectum with the patient in the left lateral position 21. Retroflexion is generally possible in capacious parts of the latge bowel such as the rectum and the caecum but when used routinely it only leads to modest increases in adenoma yield compared with careful examination in the forward view 22. The use of intravenous hyoscine (Buscopan) is an effective anti-spasmodic that reduces haustral tone and improves visualisation in the forward view. Some data support the routine use of Buscopan to enhance adenoma yields and increase the efficiency of the withdrawal examination and this approach is preferred by the authors although available data are conflicting 23, 24. Most colonoscopy withdrawals should take more than 6 min and there is some evidence that even longer withdrawal times further increase the ADR 10, 25. Fatigue may be a major factor for the colonoscopist performing many same day procedures. Some data show a reduction in adenoma detection as the colonoscopy list proceeds, particularly before the lunch break and towards the end of the afternoon 26. All colonoscopists should be aware of the variable appearances of flat and serrated lesions 27. Subtle changes in colour, vasculature or mucosal contour should be closely examined with the use of 'blue light' imaging modes and indigocarmine dye application used to improve the mucosal view. There has been considerable recent interest in instruments that widen the field of view making withdrawal examination technically easier and more effective. The Third Eye Retroscope (Avantis, Sunnyvale, CA, USA) is an auxillary imaging device that is passed through the biopsy channel of the colonoscope and is recurved in front of the tip of the 'scope to provide a separate backward pointing video image, which complements the standard forward view and allows near 360 degree visualisation. In preliminary trials significantly more lesions and adenomas (11–25%) were seen on the proximal side of haustral folds than with a conventional forward view 28, 29. The efficiency of the withdrawal may, however, be slightly reduced by the need to withdraw the device to allow washing, suction and passage of the snare. An alternative is to increase the angle of view of the conventional colonoscope lens which currently provides a 140 degree field of view. New generation scopes have increased this angle to 170 degrees and prototype instruments have up to 210 degrees of forward view. Few data exist comparing wide angle to conventional 'scopes but to date there is little evidence that there is a significant increase in adenoma detection although the withdrawal examination may become more efficient. A radically new 'scope design has now been introduced, Fuse Scope (Full Spectrum Endoscopy, Endochoice, Alpharetta, GA, USA), which has three optical viewing lenses, front, right lateral and left lateral and which provides 330 degrees of view from the tip of the 'scope. The endoscopist views simultaneous video images on three screens alongside each other. A preliminary tandem, multicentre study demonstrated a significant reduction in adenoma miss rate with the Fuse scope when compared to a conventional forward viewing scope 30. Cap-assisted colonoscopy involves the placement of a clear plastic cap at the tip of the colonoscope which may help to manipulate mucosal folds and improve visualisation particularly on the proximal side of folds thereby increasing adenoma detection. Only a few evaluations of this technology are available so far 31. An alternative attachment device at the tip of the colonoscope is the Endocuff (ARC Medical, Leeds, England) which has backward pointing soft plastic projections that help open up folds and improve visualisation during colonoscopic withdrawal 32. Several large studies are currently under way evaluating the potential of the Endocuff to improve adenoma detection rates. In the authors' experience the Endocuff dramatically changes the ease of examination during withdrawal allowing the scope tip to stay in the centre of the colonic lumen and also stabilising access and visualisation for polypectomy. Chromoendoscopy refers to the topical application of stains at the time of endoscopy in an effort to enhance diagnosis of neoplastic lesions (particularly non polypoid flat and depressed lesions), tissue characterization and differentiation 2, 5, 13. The stains used for chromoendoscopy are classified as contrast, absorptive (or vital), and reactive. Contrast stains, such as indigo carmine, seep through irregularities and pool in crevices in the surface of the polyp to highlight the mucosal features. Absorptive stains, such as crystal violet, identify specific epithelial cell types by preferential absportion or diffusion across the cell membrane. Absorbtive chromoendoscopic techniques require pretreatment and removal of excess mucus from the mucosal surface using N-acetylcysteine solution (4% up to 10%). Chromoendoscopy with non-absorbed indigo carmine is a classic technique and still one of the best for enhancing the margin and surface pattern of colonic lesions. Pan-chromo colonoscopy improves the detection of adenomatous polyps in several studies 2, 3, 33-35. Targeted chromoendoscopy also facilitates the detection of colorectal neoplasms, particularly the flat and depressed type 36, 37. Chromoendoscopy with magnification is capable of differentiating adenomas from non-neoplastic polyps by analyzing the surface structure of mucosal crypt openings 6, 38. Kudo classified the pattern of the crypt openings (pit patterns) into five categories (types I–V) and showed the association between each category and histological features 6, 38. Chiu showed the accuracy, sensitivity, and specificity of chromoendoscopy in differentiating colon adenomas from hyperplasias to be 91.1%, 91.3%, and 90.5% versus 68.3%, 62.1%, and 85.4%, respectively, for SD-WLE in one study participant and 92.2%, 97.2%, and 74.4% versus 67.2%, 65.2% and 74.4%, respectively, for SD-WLE in another participant 39. Indigo carmine staining combined with magnification endoscopy appears to be a useful technique for the detection of aberrant crypt foci in the rectum, a potential biomarker for proximal flat colonic neoplasia 37, 40. A double-staining technique using indigo carmine and crystal violet with magnification endoscopy predicted incomplete endoscopic mucosal resection (EMR) of flat, sessile colonic neoplasms with high accuracy, although the use of indigo carmine staining alone to assess depth of invasion was found to be inaccurate. Evaluation of the chromoendoscopic findings is based on the morphological features of the lesion, and therefore objectivity and reproducibility are both very important for assessing the significance of the method. Huang 41 showed a good up to excellent inter and intra-observer agreement (k = 0.716 and 0.810, respectively) for assessing pit patterns by using the Kudo classification. In contrast, East 42 found a fair interobserver agreement for the Kudo pit pattern (k = 0.25). The wide discrepancies in the results of these studies are probably related to selection bias and to the different diagnostic skills of the endoscopist. In conclusion, chromoendoscopy is a labour-intensive and time-consuming procedure, requiring significant skill to perform and interpretation of the endoscopic pictures. Nevertheless, it seems to be one of the most reliable endoscopic methods for the differentiation between non-neoplastic and neoplastic colorectal lesions. Standard-resolution and high-resolution endoscopes magnify the endoscopic image 30 to 35 times. Zoom-magnification endoscopes are defined by their capacity to perform optical zoom by using a movable lens in the tip of the endoscope. A translucent cap may be used to stabilize the focal length between the lens and the target tissue to improve image quality 43. Optical zoom obtains a closer image of the target while maintaining image display resolution. This is distinguished from electronic magnification, which simply moves the image closer on the display and results in a decreased number of pixels that compose the area of the display, with no improvement in resolution. Zoom endoscopes can magnify images up to 150 times, depending on the size of the monitor. High-resolution and zoom-magnification endoscopy enhances the detection of colonic tumours, including flat or depressed types, and improves the differentiation between neoplastic and non-neoplastic lesions. In the accuracy of this technique was 92% in distinguishing neoplastic from non-neoplastic lesions greater than 10 mm compared with 68% for non-magnifying colonoscopy 44. Magnification chromoendoscopy was accurate in distinguishing between non-neoplastic and neoplastic polyps 38 and in another study comparing conventional colonoscopy, chromoendoscopy with indigo carmine and SD magnification chromoendoscopy the respective accuracy was 84%, 89.4% and 95.6%, being significantly greater with the last of these techniques 45. In relation to the depth of invasion of colorectal neoplastic lesions, Kudo's classification of colonic crypts suggests that type I and II pit patterns are found on non-neoplastic lesions, type III S, III L, and IV pit patterns are found on adenomatous polyps, while type V N is strongly suggestive of sub-mucosal (sm) deep infiltrating cancers 6, 7. This classification system yielded a high level of interobserver and intra-observer agreement 46 even if in practice, there were limitations using only the morphological classification of the pit pattern to discriminate between mucosal-sm 1 and sm2 or beyond. Zoom-magnified chromoendoscopy with detailed analysis of the pit pattern has been proposed as the best in vivo method to evaluate the depth of invasion, however, validation in very large-scale studies is lacking 34, 38, 39. Computed virtual chromoendoscopy technologies (CVC) are real-time, on-demand endoscopic imaging techniques designed to enhance visualization of the vascular network and surface texture of the mucosa in an effort to improve tissue characterization, differentiation, and diagnosis. They are considered as potential alternatives to chromoendoscopy because they provide contrast enhancement of tissue surface structures, although they have not been as extensively studied as chromoendoscopy. Enhancement of particular mucosal features is achieved by observation of light transmission at selected wavelengths because the interaction of particular tissue structures with light is wavelength-dependent. The main computed virtual chromoendoscopy systems are NBI (Narrow Band Imaging, Olympus, Tokyo, Japan), FICE (Fujinon Intelligent Color Enhancement, Fujinon, Tokyo, Japan) and more recently iScan system (Pentax, Tokyo, Japan). FICE, NBI, and iScan constitute technologic siblings and are based on the same physical principle but have distinct modes of action. All three techniques narrow the bandwidth of white light and maximize the relative intensity of blue light. Because blue light is highly absorbed by haemoglobin, images from CVC systems result in higher vascular contrast compared with standard white-light endoscopic images. These modifications are available at the push of a button and have dramatic effects on image quality, with increased vascular contrast and some improvement of mucosal topography. NBI alters the spectrum of wavelengths by optical filters situated in the light source and illuminates tissues with modified light. In contrast, FICE is based on a computed spectral estimation technology that arithmetically processes the reflected photons of an ordinary illuminated tissue to reconstitute virtual images. FICE has the potential advantage of allowing the endoscopist to choose up to ten different filters, each providing a virtual image with a dedicated wavelength pattern for optimal observation of the targeted tissue. Despite these differences, applications of FICE and NBI produce similar imaging, with increased vascular contrast, and so far, studies have shown broadly similar results. Colorectal adenoma and cancer frequently induce alterations of vessels structure around the lesions, with images of mucosal redness or paleness. Therefore, evaluating any abnormalities of the capillary architecture and microvessels by CVC is considered to be a reasonable diagnostic modality for characterizing early colonic neoplasms, but FICE-enhanced and NBI-enhanced mucosal and vascular patterns are not yet sufficiently standardized or validated to establish guidelines for routine practice. Indeed, most published studies propose several classifications for surface patterns that are based on different enhanced lesion characteristics 47. Hence, the interobserver agreement is sometimes reported as fair up to moderate, although the FICE system to investigate the in vivo prediction of lesion histology, has been reported to show very encouraging results 47. The histology of 309 colorectal lesions (size 1–50 mm) was predicted by adopting a microvascular classification system solely based on five different capillary patterns (different number, morphology, and distribution of the fine blood vessels). Interestingly, mucosal pit patterns were not considered. The overall accuracy of the capillary vessel classification system in determining the neoplastic or non-neoplastic nature of the lesions was very high (98.3%). The positive predictive value of capillary patterns III, IV, and V for neoplastic tissue was 99.2%, with a specificity of 94.9%. The two endoscopists involved in the study had a high interobserver agreement with disagreement in only 8.6% of all lesions. The results of this and other studies indicate that assessment of magnified CVC-enhanced capillary patterns could replace conventional chromoendoscopy for the prediction of histology, although at the moment the technique can be time-consuming and there is a recognised learning curve. Some authors think that the pivotal question is whether a commonly accepted and user-friendly classification for CVC-enhanced surface imaging can be developed 48. A combination of CVC with the zoom-magnification mode might further increase the accuracy of non-polypoid early colorectal lesions, but is no prerequisite for successful application. CVC imaging systems are an important development that complement the diagnostic armamentarium, but in their present form, they also have limitations. In conclusion a significant minority of polypoid and non polypoid lesions are missed at colonoscopy which reduces the effectiveness of cancer prevention. When assessing the quality of colonoscopy, the adenoma detection rate has emerged as a key performance indicator and all colonoscopists should monitor and be aware of their adenoma detection rate. They should be prepared to undergo additional training if the ADR is unacceptably low. Good bowel preparation, optimal examination technique and an understanding of subtle lesion appearances are fundamental to reducing lesion miss rates. New instruments, devices, and technologies that enhance or widen the field of view can often be employed in combination and offer realistic possibilities for easier and more accurate examinations in the future. Prof. Saunders has been a paid consultant and received loan equipment from Olympus Medical Ltd.