Magnification endoscopy

INTRODUCTION — The ability to magnify endoscopic images in real-time (magnification endoscopy) permits visualization of mucosal details that cannot be seen with standard endoscopy. The images can be further enhanced by the topical application of stains or pigments (enhanced magnification endoscopy or magnification chromoscopy).

Equipment and experience with these approaches is evolving. A growing number of reports suggest that they offer the ability to improve diagnostic accuracy for a variety of gastrointestinal disorders [1]. In addition, newer technologies, such as confocal laser endomicroscopy and endocytoscopy, are allowing for real-time visualization of the gastrointestinal tract at a microscopic level [2-4].

Magnification endoscopy will be reviewed here. Other methods for enhanced visualization of the gastrointestinal mucosa are discussed elsewhere. (See "Chromoendoscopy" and "Barrett's esophagus: Evaluation with optical chromoscopy".)

EQUIPMENT — Magnification endoscopes include an adjustable focusing mechanism that permits standard endoscopic views and the ability to enlarge the image. Most magnification endoscopes combine optical and digital zoom and permit 1.5 to 2 times digital magnification and/or an optical magnification up to 150 times [5,6]. Some magnification endoscopes provide near-focus imaging, which allows the endoscope to be moved closer (within 2 to 6 mm) to the area of interest while maintaining the images in focus and providing images with high magnification (>100 times).

Resolution is related to pixel density. Conventional endoscopes have pixel densities in the range of 100,000 to 200,000. By contrast, the available magnification endoscopes have pixel densities from 850,000 to more than 1 million, allowing them to discriminate objects that are only 10 to 71 microns in diameter [1,6].

TECHNIQUE — The technique for performing magnification endoscopy is similar to standard endoscopy. One difference is that we may administer glucagon, which can be helpful for decreasing contractility, thereby aiding in visualization and the application of stains. The magnification and staining portion of the examination adds 5 to 10 minutes to the procedure.

Several topical stains and pigments (such as methylene blue, acetic acid, crystal violet, and indigo carmine) have been used in conjunction with magnification endoscopy. The principles and techniques involved in dye application are discussed separately. (See "Chromoendoscopy".)

Other imaging techniques such as narrow band imaging have been embedded within endoscopes and have improved visualization of the mucosa during magnification endoscopy.

The following sections will focus on the technique involved in the application of acetic acid, for which there is relatively less experience in the gastrointestinal tract [7]. We have found application of acetic acid to be particularly helpful when examining Barrett's mucosa.

In translucent epithelium, the light beam reaches the subepithelial vascular network. The absorption spectrum of hemoglobin explains the red color in the surface. Instillation of acetic acid causes the epithelial surface to opacify, thereby masking the subepithelial vascular network and making the surface appear white. This change has been referred to as the "acetowhite reaction" although the exact mechanisms underlying it are unclear. One theory suggests that exposure to acetic acid causes cytokeratins, which are (filaments of proteins within the cells) to organize into large bundles, which increases the index of refraction.

Acetic acid has been used to stain abnormal tissues during examination of the cervix where it whitens immature and dysplastic cervical squamous epithelium. The technique has proven to be inexpensive, safe and clean. (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention".)

Acetic acid (1.5 to 3 percent) is sprayed through the biopsy channel of the endoscope over the surface of the mucosa beginning from the distal extent and then proceeding proximally [7]. The head of the bed should be elevated and the amount of acetic acid used minimized to reduce the risk of aspiration [8-10]. As little as 5 to 10 mL is usually sufficient to coat an area of suspected Barrett's mucosa. Excess can be removed by suction.

The esophageal and gastric epithelia initially whiten. After two to three minutes of spraying, the esophagus remains white while the gastric epithelium and columnar epithelium of Barrett's mucosa become reddish, thereby accentuating the contrast between normal and metaplastic tissue (picture 1 and picture 2).

ESOPHAGUS AND GASTRIC CARDIA — Intestinal metaplasia is frequently translucent when observed with magnification endoscopy alone. Thus, the mucosal surface is not easily examined without staining [11].

As noted above, a variety of tissue stains have been used with standard endoscopy and in conjunction with magnification to improve visualization. Considered together, these studies suggest that enhanced magnification endoscopy improves the detection of intestinal metaplasia (and possibly dysplasia) by permitting better targeting of biopsies [7,12,13]. However, not all studies have reached this conclusion [14]. The best results have been achieved in centers with experience in magnification endoscopy. Thus, training is required to achieve the benefits from this approach.

The following illustrates the range of findings:

●A randomized prospective, crossover trial that included 31 patients found that magnification endoscopy had 100 percent sensitivity and 66 percent specificity for predicting the presence of Barrett's esophagus [15]. Acetic acid guided biopsies had a significantly higher yield in detecting Barrett's esophagus compared with random biopsies (78 versus 57 percent).

●Another study included 80 patients with suspected Barrett's esophagus who underwent magnification endoscopy with indigo carmine staining, which revealed three distinct mucosal patterns (ridged/villous, circular, and irregular/distorted) [12]. The yield on targeted biopsies according to these patterns was 97 percent for the ridged/villous pattern, compared with 17 percent for the circular pattern. The irregular/distorted pattern was observed in six patients, all of whom had high-grade dysplasia.

●A similarly designed study included 247 patients undergoing elective upper endoscopy [13]. Patients were included provided that the esophagogastric junction and the squamocolumnar junction were judged to be at the same level. The final study included 195 patients after excluding 52 who had evidence of Barrett's esophagus by standard endoscopy. Enhanced magnification endoscopy was performed with 3 percent acetic acid instillation as described above. Intestinal metaplasia was detected in 44 percent of patients. Four different patterns were recognized on magnified images: round pits, reticular, villous, and ridged. The yield of detection of intestinal metaplasia of the gastric cardia according to this classification was 0, 5, 56, and 96 percent, respectively.

●A fourth study involved 67 patients who underwent upper endoscopy for upper gastrointestinal symptoms [16]. Enhanced magnification endoscopy was performed with 1.5 percent acetic acid during which the mucosal pattern was classified into three types. The overall frequency of intestinal metaplasia in the esophagus or esophagogastric junction was 39 percent. There was good correlation between the type 3 mucosal pattern and the presence of intestinal metaplasia (sensitivity 89 percent, specificity 90 percent, positive predictive value 85 percent, negative predictive value 93 percent).

●In a randomized trial, acetic acid was compared with i-Scan imaging for detecting Barrett's esophagus [17]. i-Scan imaging is a technology alternative to narrow band imaging and can provide detailed images of surface and vessel architecture. A total of 95 patients were randomized. Targeted biopsies were performed in 46 patients who underwent acetic acid staining and in 49 patients who underwent i-Scan imaging. Random biopsies were performed in 86 patients. The overall diagnostic yield for Barrett's epithelium was higher with targeted biopsies than with random biopsies (63 versus 24 percent). Acetic acid and i-Scan showed comparable results for detecting Barrett's epithelium.

●Another retrospective cohort study compared acetic acid chromoendoscopy (AAC) with the neoplasia yield from standardized random biopsy protocol (SBP)–guided biopsies in the routine surveillance of patients with Barrett's esophagus [18]. The overall neoplasia detection rates for all grades of neoplasia were higher in the SBP-guided biopsy cohort compared with the AAC cohort (13 versus 2 percent). The number of biopsies required to detect one neoplasia was 15 times lower in the AAC cohort (40 biopsies) than in the SBP cohort (604 biopsies). On per-biopsy analysis, a 14.7-fold increase in neoplasia detection was seen in the AAC cohort compared with the SBP cohort (0.025 versus 0.0017 percent of biopsies).

●However, discordant data have also been published. One controlled trial, for example, found that acetic acid enhanced magnification endoscopy was not better than standard endoscopy in detecting intestinal metaplasia in patients with symptoms of GERD [19].

Magnification endoscopy has also been combined with NBI in the esophagus:

●A study comparing magnification NBI and high-resolution magnification white-light endoscopy in the prediction of histology in Barrett's esophagus found NBI to be superior in the prediction of histology and dysplasia in Barrett's esophagus [20]. However, there was generally poor agreement between endoscopists, although agreement was significantly better with NBI. (See "Barrett's esophagus: Evaluation with optical chromoscopy".)

●A second study compared white-light endoscopy, NBI, and NBI plus magnification endoscopy in patients with head and neck cancer [21]. In the 21 patients with esophageal neoplasia, NBI with magnification had the highest combined sensitivity and specificity (100 and 80 percent, respectively) compared with NBI alone (100 and 40 percent, respectively) and white-light endoscopy (63 and 70 percent, respectively).

The clinical benefits of improved detection in the screening setting are not entirely clear. Routine application of magnification endoscopy may result in an increasing proportion of patients being diagnosed with intestinal metaplasia, particularly those with short-segment Barrett's esophagus or intestinal metaplasia of the gastric cardia, who may be at relatively less risk for progression compared with those diagnosed with long-segment Barrett's based upon standard endoscopy. As a result, an increasing proportion of patients undergoing screening for Barrett's esophagus would be subjected to the worry, bother, cost, and risk of continued surveillance, even though the majority will not develop adenocarcinoma during their lifetime.

Several classification systems for the diagnosis of Barrett’s esophagus and dysplasia using magnification endoscopy and NBI have been developed [22-25]; however, further studies are needed to validate their diagnostic accuracy [24-29]. For example, interobserver reliability of two of the classification systems was assessed in a study that focused on 51 patients with reflux-symptoms who underwent enhanced magnification endoscopy using acetic acid or methylene blue [26]. Video recording of the endoscopic sessions were shown to four experienced endoscopists in a random order. Intestinal metaplasia was detected in 61 percent of the patients overall. However, there was a higher level of interobserver variability (kappa <0.4). Overall accuracy was estimated to be only 50 percent, with no differences observed before or after instillation of acetic acid or methylene blue. The authors concluded that these techniques do not significantly improve the detection of intestinal metaplasia.

A high level of interobserver variability was also described in other reports [14,20,27]. In one study, for example, chromoendoscopy with indigo carmine and acetic acid and narrow band imaging were compared with high resolution magnification endoscopy [14]. Seven endoscopists with no expertise in Barrett's esophagus or advanced imaging techniques and five international experts evaluated 22 areas for regularity of mucosal and vascular patterns and the presence of abnormal blood vessels. The kappa coefficients range for interobserver agreement for these three features of mucosal morphology with white light images ranged from 0.51 to 0.53 for all observers, from 0.43 to 0.53 for experts, and from 0.51 to 0.64 for nonexperts (see "Glossary of common biostatistical and epidemiological terms", section on 'Terms used to describe reliability of measurements'). The yield for identifying early neoplasia with white light images was 86 percent for all observers, 90 percent for experts, and 84 percent for nonexperts. The addition of indigo carmine chromoendoscopy, acetic acid chromoendoscopy, or narrow band imaging to white light images did not improve interobserver agreement or the yield in identifying early neoplasia in Barrett's esophagus [28].

By contrast, interobserver variability was somewhat better in another series [28]. In an additional report (published in an abstract), sensitivity for detection of intestinal metaplasia and high-grade intraepithelial neoplasia or early mucosal cancer were 92 and 89 percent, respectively [29]. The kappa coefficients for inter- and intraobserver agreement (among six endoscopists) were a remarkable 0.959 and 1.0, respectively. It is likely that some of the variability across studies is due to a learning curve required to be familiar with the classification systems and other morphologic features of Barrett's esophagus.

Thus, greater standardization of the methods used to detect and classify esophageal and gastric cardia mucosa is needed before these techniques can be used routinely. At present, their greatest role may be for directing targeted biopsies in patients with established intestinal metaplasia who are undergoing surveillance. They may also be helpful for directing biopsies in patients known to have dysplasia. (See "Barrett's esophagus: Surveillance and management".)

STOMACH — A role for magnification endoscopy in the stomach has been suggested for the diagnosis of a variety of mucosal conditions. Thus far, most studies have been descriptive but have suggested an improved ability to detect premalignant and malignant lesions and to aid in assessment completeness of excision when endoscopic mucosal resection has been attempted [30-32]. (See "Overview of endoscopic resection of gastrointestinal tumors".)

The potential to discriminate between benign versus premalignant polypoid lesions has also been suggested, which may aid in assessment of patients found to have multiple gastric polyps in whom complete histologic sampling may not be feasible [31,33]. (See "Gastric polyps".)

The pit pattern may also be useful for identifying mucosal changes such as intestinal metaplasia [30,34], gastric atrophy [35], and early cancers that are potentially amenable to endoscopic mucosal resection [36,37]. When a normal tubular pattern cannot be identified, it is called "nonstructural" pattern. This finding suggests that the cancer involves the submucosal layer and precludes endoscopic mucosal resection [36].

Analysis of the microvascular architecture may also be helpful, especially if combined with narrow band imaging (NBI) [38-40]. (See "Barrett's esophagus: Evaluation with optical chromoscopy", section on 'Principles'.)

Studies that have looked at NBI for the diagnosis of gastric cancer suggest that combining magnification endoscopy with NBI and white-light endoscopy increases diagnostic sensitivity and specificity:

●A study of 56 patients with small (10 mm or smaller), depressed gastric lesions compared magnification white light endoscopy with magnification endoscopy NBI for diagnosing gastric cancer [39]. Endoscopically, gastric cancer was diagnosed if two criteria were met: (1) there was a definite demarcation line between the lesion and the normal mucosa and (2) an irregular microvascular pattern was present in the lesion. The sensitivity of magnification endoscopy was 33 percent and the specificity was 67 percent. When NBI was added, the sensitivity significantly increased to 70 percent. The specificity was also higher (89 percent), though the difference between the two modalities was not statistically significant.

●A second study examined 201 lesions in 111 patients using white-light endoscopy without magnification followed by magnification endoscopy with NBI [40]. Diagnostic criteria for gastric cancer using NBI included: disappearance of fine mucosal structure, microvascular dilation, and heterogeneity. Cancer was identified pathologically in 14 of the lesions (7 percent). The sensitivity and specificity of magnification endoscopy with NBI were 93 and 95 percent, respectively. These values were significantly higher than those seen with white light endoscopy (43 and 61 percent, respectively).

●A trial with 353 patients also compared magnification endoscopy with NBI with conventional endoscopy [41]. Patients with small gastric cancers or a history of gastric cancer treated endoscopically were assigned to either magnification endoscopy with NBI or conventional endoscopy for the detection of additional lesions. There was no significant difference in sensitivity between magnification endoscopy with NBI and conventional endoscopy for detecting gastric cancer (60 versus 40 percent), though magnification endoscopy with NBI had a higher specificity (94 versus 68 percent). When magnification endoscopy with NBI was combined with conventional endoscopy, the sensitivity increased to 95 percent and the specificity increased to 97 percent (p<0.001 compared with conventional endoscopy alone).

The authors subsequently did a post-hoc analysis and found that the combination of magnification endoscopy with NBI and conventional endoscopy had the highest diagnostic accuracy when specific criteria were used for diagnosing cancer (a demarcation line and an irregular microvascular pattern for magnification endoscopy and an irregular margin and spiny, depressed area for conventional endoscopy) [42]. The accuracy for the combination of the two techniques was 97 percent, compared with 90 percent for magnification endoscopy with NBI alone and 65 percent for conventional endoscopy alone.

SMALL INTESTINE — There is relatively little experience with magnification endoscopy in the small bowel compared with other regions of the alimentary tract. An area where it shows particular promise is in the evaluation of patients with celiac disease and other disorders associated with malabsorption where biopsies obtained during standard endoscopy may not be diagnostic since the mucosa can be affected in a patchy distribution. Magnification endoscopy has the potential to enhance diagnostic yield by improving targeting of biopsies [43-47]. In one of the largest studies, the sensitivity and specificity for determining the presence or absence of any villous abnormalities were 95 and 99 percent, respectively [44]. The study also demonstrated excellent interobserver reliability.

Magnification endoscopy has also been used as a tool for monitoring acute rejection in patients who have undergone small bowel transplantation. (See "Overview of intestinal and multivisceral transplantation".)

COLON — A role for magnification endoscopy in the colon has been suggested for the diagnosis of flat and depressed lesions [48-52], identification of dysplasia and disease severity in ulcerative colitis [53-55], discrimination among polyp types [56], and assessing completeness of endoscopic mucosal resection [51,57]. Classification systems of surface patterns in colonic lesions have been proposed, but have not yet been adopted widely [58,59]. Recognition of surface patterns may be enhanced by combining magnification endoscopy with other imaging techniques such as narrow band imaging or chromoendoscopy [60-69].

●One of largest reported series focused on 1850 patients who underwent magnification colonoscopy with indigo carmine staining by a single endoscopist [65]. A total of 1008 flat lesions were identified all of which were removed or biopsied. The sensitivity and specificity of magnification colonoscopy in distinguishing non-neoplastic from neoplastic lesions were 98 and 92 percent, respectively. However, sensitivity was poor in discriminating between neoplastic/noninvasive from neoplastic/invasive lesions. The authors concluded that magnification colonoscopy was useful but does not replace histologic assessment of flat and depressed lesions.

●Another study included 122 patients with 206 lesions that were 10 mm or smaller [61]. All lesions detected on colonoscopy were first diagnosed using the conventional view, then at chromoendoscopy using 0.2 percent indigo carmine, and finally with chromoendoscopy with magnification. Histologically, 46 lesions (22 percent) were non-neoplastic while 160 (78 percent) were neoplastic. The overall diagnostic accuracies by conventional view, chromoendoscopy, and chromoendoscopy with magnification were 84 percent (173/206), 89 percent (184/206), and 96 percent (197/206), respectively. The authors concluded that chromoendoscopy with magnification is the most reliable method for determining whether a colorectal lesion is non-neoplastic or neoplastic during colonoscopy.

●One of the only controlled trials included a total of 203 patients who were considered at increased risk for colonic neoplasia based upon either a family or personal history or the presence of alarm symptoms after age 60 [62]. Patients were randomly assigned to conventional colonoscopy or colonoscopy with indigo carmine staining combined with standard resolution and then high-resolution (1.5 fold magnification) inspection. Significantly more hyperplastic polyps and flat adenomas were detected in the high-resolution group but there was no significant difference in the total number of adenomas per patient. The authors concluded that their findings do not support routine use of high resolution colonoscopy in clinical practice.

●Narrow band imaging (NBI) was used in a series of 495 patients with a total of 617 lesions [64]. NBI uses a high-intensity blue light with narrow band filters that emphasize vascular and mucosal patterns. In this study, the sensitivity for differentiation between neoplastic (adenomas and cancers) and non-neoplastic lesions was 91 percent, with a specificity of 97 percent. However, a meta-analysis suggests that adding NBI to standard high-definition white light colonoscopy does not improve the detection rate of colorectal polyps or adenomas [70].

●In a systematic review and meta-analysis of 13 studies to distinguish sessile serrated adenomas/polyps from non-neoplastic tissue with an endoscopy-based image-enhancement modality (IEE), only NBI studies demonstrated significantly greater sensitivity [71]. The authors concluded that IEE currently cannot be recommended as a diagnostic tool for sessile serrated adenomas/polyps and validated criteria are needed for NBI modality.

●In a study of 718 colorectal polyps that were photographed using white light endoscopy (WLE), NBI magnification (NBIME), and acetic acid enhancement with NBI magnification (A-NBIME), diagnostic accuracy was determined by comparing the diagnosis based on expert review of the images with histologic results. Imaging with A-NBIME had higher diagnostic accuracy compared with WLE or NBIME (86 versus 81 and 79 percent, respectively) [72]. Interobserver agreement was fair to moderate with WLE, moderate with NBIME, and substantial with A-NBIME. When expert reviewers diagnosed colorectal polyps based on visualization, they focused on different polyp characteristics based on the imaging technique. For example, polyps viewed with WLE were assessed by size, shape, color, and mucosal surface, while for NBIME or A-NBIME, the areas of focus were the vessel and surface pattern and the pit pattern, respectively.

SUMMARY AND RECOMMENDATIONS

●The role of enhanced magnification endoscopy has been evolving. The available data have suggested that it improved the ability to identify mucosal abnormalities throughout the gastrointestinal tract and guide biopsies. However, the technique has not replaced histologic assessment. Future studies may help determine the validity and reliability of classification systems to permit better standardization of findings using magnification endoscopy.

●Chromoendoscopy involves the topical application of stains or pigments to improve tissue localization, characterization, or diagnosis during endoscopy, and this is discussed in more detail separately. (See "Chromoendoscopy".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Moises Guelrud, MD, who contributed to earlier versions of this topic review.