Commentary (Lightdale): Endoscopic Diagnosis and Management of Gastrointestinal Malignancy

Kadish and Kochman provide a superb review of the current role of endoscopy in the diagnosis, staging, palliation, and cure of gastrointestinal cancer. There is no doubt that recent technological advances have changed the focus of endoscopy; there is a much greater emphasis now on finding and treating early cancer and precancerous lesions.

The focus on early cancer diagnosis is understandable. Early diagnosis implies detection at a time when treatment is likely to be curative. Most cancers originate in the cells of the mucosa lining the lumen of the gastrointestinal tract, and invade deeper layers of the gut wall as they progress. The deeper the invasion, the more likely the spread to regional lymphatic or distant sites. Cancer confined to the mucosa at diagnosis has the best prognosis, and it is the mucosa that is directly accessible to endoscopic inspection and biopsy.

There are few who would debate that upper gastrointestinal endoscopy is the procedure of choice for the diagnosis of esophagogastric neoplasia. Increasingly, endoscopy is utilized as the initial diagnostic test rather than as a follow-up to x-ray examination.

The Road to "Endoscopy First"

Several developments have contributed to this "endoscopy first" approach to the diagnosis of esophagogastric tumors. Endoscopes have become so thin and maneuverable that there are no longer any blind areas. Until about a decade ago, the gastric fundus and cardia were difficult to see in entirety, as was the lesser curvature of the antrum behind the angularis. These areas are now routinely examined with retroflexion techniques. Thin, forward-viewing endoscopes are passed under direct vision through the upper esophageal sphincter, making this a safer more comfortable step than in the past. A barium roentgenographic "road map" is rarely necessary.

Endoscopy is perhaps more invasive than upper gastrointestinal series, but more accurate. Endoscopy is more expensive, but no longer by much, and avoids duplication. Biopsy for tissue diagnosis can be accomplished at endoscopy when an abnormality is detected. Exposure to radiation, an issue of increasing concern, is avoided with endoscopy. Complications of diagnostic upper gastrointestinal endoscopy are rare. Finally, modern video and electronic endoscope systems have solved the problem of readily providing images for documentation, analysis, and permanent record.

The Promise of Fluorescence Spectroscopy

The increased magnification and clarity provided by video-endoscopy has allowed a much more detailed visual examination of the gastrointestinal mucosa than ever before. As reviewed by Kadish and Kochman, the addition of dye spraying can further enhance visual detail. Beyond this, however, is the promising technology of fluorescence spectroscopy, which may reveal to the endoscopist dysplastic tissues in the earliest stages of neoplasia that are visually normal. Real-time fluorescence spectroscopy is under evaluation, which would allow the endoscopist to target dysplastic areas for biopsy as they are identified.

The value of endoscopic biopsies will undoubtedly be further enhanced by the application of molecular biology methods to clinical specimens. Flow cytometry is poised to emerge from the laboratory into the clinical arena in analyzing endoscopic biopsy specimens. However, beyond simple aneuploidy, the identification of oncogene or tumor- suppressor gene abnormalities in biopsy material may identify patients who have early neoplastic change for therapy or surveillance.

Esophageal Cancer: On the Rise

A focal point of endoscopy in the upper gastrointestinal tract is in the diagnosis and surveillance of Barrett's esophagus, which has a major association with the striking increase in the incidence of adenocarcinoma of the distal esophagus and gastric cardia during the past 20 years. It has been estimated that the incidence of these highly lethal cancers is accelerating at a faster rate than any other malignancy in the United States. In most US centers, more than half of the new cases of esophageal cancer are adenocarcinomas.

Barrett's esophagus is now thought to be associated with chronic gastro-esophageal acid reflux, and is characterized by metaplastic specialized columnar epithelium. Short segments of such tissue at the esophagogastric junction probably underlie most cases of cardia cancer as well. The development of cancer is thought to progress through a series of molecular events in the unstable metaplastic epithelium, leading to mutant clones of cells that progress morphologically to low-grade and then to high-grade dysplasia, to early invasive carcinoma, and finally to advanced carcinoma. With the incidence of squamous cell carcinoma of the esophagus and distal gastric cancer decreasing in the United States, the emphasis during upper GI endoscopy is onthe diagnosis of Barrett's metaplasia, and the detection of dysplasia and early adenocarcinoma in the distal esophagus and gastric cardia. Endoscopic ultrasonography has provided new power for more accurate staging of gastrointestinal cancer than ever before. High-frequency ultrasound probes allow determination of the depth of cancer invasion (T in the TNM system) with accuracy in the 80% to 90% range. Regional lymph node metastases (N) can be imaged with less specificity, but new methods allowing endoscopic ultrasound- guided needle aspiration cytology of lymph nodes in proximity to the gastrointestinal tract seem very promising in helping to distinguish malignant from benign lymph nodes.

Endoscopic treatments for palliation of advanced gastrointestinal cancer and cure of superficial cancer are detailed by Kadish and Kochman. Most notable is the application of expandable metal stents and photodynamic laser therapy for advanced malignant stenoses, and the use of photodynamic therapy for cure of early cancer and high grade dysplasia in Barrett's esophagus.

The new advances in gastrointestinal endoscopy surely represent a great challenge for oncologists. The stage of gastrointestinal cancers will be shifted earlier at the time of diagnosis, and cancers will be staged correctly before surgery. This should offer tremendous opportunities for oncologic treatment in a multimodality approach. New endoscopic treatments and minimally invasive surgical methods combined with oncologic therapy open the possibility of management options that will have fewer complications, be more tissue sparing and less mutilating, and yet be more successful and curative than current treatments for GI cancer.