What can be expected from magnification endoscopy?
C.J. Lightdale (New York)
Adenocarcinoma of the distal esophagus and gastric cardia is increasing in the United States and Western Europe . Barrett's esophagus (BE) is the only known risk factor for these tumors . Dysplasia and adenocarcinomas have been seen not only in long segment BE, but also in short segments of intestinal metaplasia at the squamo-columnar junction . In a recent study, random biopsies directed at the esophagogastric junction detected intestinal metaplasia in 18% . We decided to explore the esophagogastric junction in detail using magnification endoscopy in an effort to define macroscopic abnormalities.
We carried out our examination of the esophagogastric junction using the Olympus GIF-200Z (Olympus Optical Co., Tokyo, Japan) zoom lens magnifying endoscope. This instrument is similar in appearance to standard endoscopes, but provides adjustable image magnification in a continuous range from 10x to 35x. Zoom magnification is easily carried out by turning a dial on the handle, which controls the varifocal lens system in the instrument tip.
The endoscope has a 0° forward viewing direction. With progressive zoom magnification, however, the field of view narrows from 120° in the standard wide position to 60° at the maximum tele setting. More importantly, the depth of field becomes smaller with magnification. The focal area in the standard setting ranges from 7 mm to 100 mm, but falls to a range of 4-11 mm at highest magnification.
At maximum magnification, because of the small focal range, movements of the esophagogastric junction including pulsation, respiration, and peristalsis may continually bring an area for inspection in and out of focus. Thus, the examination is most easily documented on videotape. Focused frozen images are more difficult to obtain, although this is certainly almost always possible with patience, anticipation, and reasonably fast hand-eye coordination.
The instrument is relatively easy to pass into the esophagus, with its 11.9 mm distal end and 10.5 mm insertion shaft making it more comparable in handling characteristics to a therapeutic endoscope. It has a standard 2.8 mm instrument channel, and at normal magnification a biopsy forceps can be seen when it protrudes 3 mm from the endoscope tip.
Retroflexion of the endoscope tip is an important maneuver in examination of the esophagogastric junction. The Olympus GIF-200Z has a 180° tip angulation with the control knob turned to the full "up" position and 100° angulation to the left and right. This allows relatively easy retroflexion and withdrawal of the endoscope in the gastric body for close examination of the cardia and squamo-columnar junction from below.
We have previously reported our initial observations in patients with Barrett's metaplasia and in patients with gastroesophageal reflux disease without known Barrett's [5, 6]. In addition to observation with the GIF-200Z endoscope, we also utilized dye spraying in the area of the esophagogastric junction with 0.4% solution of indigo carmine. This blue dye does not stain the mucosa, but rather enhances observation of topographic morphology by pooling in lower areas. This serves to emphasize the definition of raised or depressed lesions.
We found that at 35x magnification Barrett's epithelium had a villiform appearance, which was more like the appearance of the normal duodenum than the flatter mucosa of the normal gastric cardia . In 32 patients with chronic gastroesophageal reflux symptoms, we found focal villiform areas at the squamo-columnar junction . We biopsied these areas and also systematically biopsied all patients at the squamo-columnar junction, gastric cardia, fundus, body, and antrum.
In the 23 patients with villiform areas at the esophagogastric junction, biopsies of these areas showed glandular mucosa with hyperplasia of the surface and foveolar mucous cells, distention of the gastric pits, and varying amounts of infiltration by lymphocytes and plasma cells. In addition, in 10 patients the villiform lesions contained intestinalized areas with Alcian-blue positive staining for goblet cells. None of these patients had intestinal metaplasia on biopsies from elsewhere in the stomach, and none showed histologic evidence of Helicobacter pylori.
In three patients with long segment Barrett's esophagus, we found raised areas of villiform mucosa, with a broader leaf-like villous pattern compared to surrounding metaplastic areas. Biopsies of these areas showed low grade dysplasia in two patients and high grade dysplasia in the third.
The development of the magnifying endoscope represents an important advance in diagnostic endoscopy. Magnification of surface abnormalities offers the potential of instantaneous tissue characterization with an accuracy approaching that of histologic analysis of biopsy samples .
Initial research with endoscopic magnification has been carried out largely with colonoscopes, where it is possible to use larger instruments that can provide greater magnification.
For example, the Olympus CF-200Z colonoscope can provide zoom lens magnification of the mucosal surface up to 100x. This degree of real-time magnification is comparable to that of a dissecting microscope.
The use of magnifying colonoscopes shows considerable promise for evaluating the pit pattern of colorectal tumorous lesions to provide an instantaneous analysis [8, 9]. Inflammatory or hyperplastic lesions can be differentiated from neoplastic polyps, and early malignant changes can be identified with high accuracy. Magnifying colonoscopes have been used to screen patients with ulcerative colitis, and have identified flat adenomatous areas unrecognized with standard examination .
With a tip diameter of 15.4 mm, the CF-200Z colonoscope is too large for upper gastrointestinal endoscopy, and the very short focal range of 2-3 mm at maximum magnification would also likely present more difficulties in the esophagus and esophago-gastric junction area than in the colon. However, we have been able to use the Olympus GIF-200Z magnifying endoscope with relative ease to examine the esophagus and cardia in patients with gastroesophageal reflux disease and Barrett's esophagus.
With zoom magnification up to 35x, we have shown that Barrett's epithelium has a villiform surface appearance similar to that of intestine. We have identified a broader leaf-like villous pattern in slightly raised dysplastic areas .
In patients with gastroesophageal reflux symptoms without long-segment Barrett's, we have identified focal villiform mucosal changes at the squamo-columnar junction . Histologic evaluation of these areas showed them to consist of hyperplastic surface and foveolar mucous cells and distended gastric pits, and in some patients intestinalized metaplasia with goblet cells.
In our preliminary studies with magnification endoscopy, all the patients with intestinalized mucosa at the esophago-gastric junction had macroscopic villiform changes. Thus, the sensitivity of villiform surface areas on magnification endoscopy for detection of intestinalized metaplasia was 100%, but since intestinalized mucosa was not seen in most patients with villiform areas, the specificity for intestinalized mucosa was low at 44%. Similarly, with magnification endoscopy of the esophagogastric junction, the positive predictive value of observing villiform changes for the presence of intestinalized mucosa was only 44%, but the negative predictive value was 100% .
In conclusion, magnification endoscopy seems to enhance observations in patients with gastroesophageal reflux disease and Barrett's esophagus. Barrett's epithelium has a villiform surface appearance, and raised dysplastic areas demonstrate a broader leaf-like villous pattern. Macroscopic focal villiform areas at the squamo-columnar junction have a high sensitivity for intestinalized mucosa. These observations can identify sites for precision biopsy. Further studies are needed in patients and in normal controls.
In the near future, high resolution standard videoscopes or special lens magnifying endoscopes may allow specific characterization of abnormal areas in the esophagus, esophagogastric junction, and gastric cardia. These observations may become sufficiently accurate in some cases to defer biopsy and bypass the pathologist. This could potentially decrease costs and increase efficiency, allowing immediate endoscopic therapy when indicated.
5. Stevens PD, Lightdale CJ, Green PHR, Siegel LM, Garcia-Carrasquillo RJ, Rotterdam H. Combined magnification endoscopy with chromoendoscopy for the evaluation of Barrett's esophagus. Gastrointest Endosc 1994;40:747-749.
6. Finegold J, Green PHR, Rotterdam H, Garcia-Carrasquillo RJ, Stevens PD, Lightdale CJ. Use of magnification endoscopy and chromoendoscopy in the characterization of the GE junction in patients with GERD. Gastroenterology 1996;110:A511.
9. Axelrad AM, Fleischer DE, Geller AJ, et al. High resolution chromoendoscopy for the diagnosis of diminutive colon polyps: implications for colon cancer screening. Gastroenterology 1996;110:1253-1258.
10. Jaramillo E, Watanabe M, Befrits R, Ponce de Leon E, Rubio C, Slezak P. Small, flat colorectal neoplasias in long-standing ulcerative colitis detected by high-resolution electronic video endoscopy. Gastrointest Endosc 1996;44:15-22.