Endoscopy in premalignant conditions of the esophagus

0016-5107/84/3005-0308$02.00/0 GASTROINTESTINAL ENDOSCOPY Copyright © 1984 by the American Society for Gastrointestinal Endoscopy

Symposium Refinements in gastrointestinal endoscopy Selected articles from the New York Society for Gastrointestinal Endoscopy course, November 17 and 18, 1983 Guest Editor: Robert P. Yatto, MD Nyack, New York

Endoscopy in premalignant conditions of the esophagus Charles J. Lightdale, MD

Five-year survival rates after surgery for esophageal cancer remain in the 0 to 10% range in spite of the best medical treatments. l In an effort to detect the disease at a more localized, curable stage, endoscopic examination of asymptomatic individuals at increased risk for esophageal cancer has been proposed. 2 In China, a country with high risk areas for esophageal carcinoma, surveillance using cytology and endoscopy has recently detected 115 cases of early esophageal cancer.3 If the Chinese experience can be applied to high risk groups with premalignant conditions in low risk areas, periodic endoscopic screening with acceptably long intervals in the range of 1 to 2 years will still allow detection of esophageal cancer in most cases at an early, potentially curable stage. Patients affected with tylosis are at high risk for epidermoid carcinoma and require a yearly endoscopy with biopsy at multiple levels of the esophagus, concentrating on the distal two thirds. Particular attention should be paid to any area that appears abnormal, but even if the esophagus appears normal, systematic brushings and cytology should be performed. The Chinese mass screening results indicate that up to 20% of patients with early cancers will not have a specific lesion seen at the first endoscopy.4 A positive cytology or biopsy is an indication for esophagectomy in this setting. Waiting for a lesion to present has been associated with the development of metastatic disease. 5 In a patient with the now uncommon PlummerVinson syndrome, a similar recommendation for From the Gastroenterology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, and the Department of Medicine, Cornell University Medical College, New York.

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yearly endoscopy would seem reasonable, directing attention to the upper third of the esophagus. Longstanding strictures due to ingestion of caustic substances should be examined yearly. Dilation should be accomplished at the time of surveillance so that the entire affected area can be examined endoscopically. Patients with head and neck cancer should be screened endoscopically for esophageal cancer at some point during their treatment. In patients with achalasia, periodic endoscopy also seems indicated. Particular attention should be paid to the midesophagus. In patients with celiac disease, a role for periodic esophagoscopy has not been established, although the literature suggests an increased risk. In any of these high risk patients in whom esophageal biopsy reveals dysplasia, particularly if graded severe, more frequent endoscopic surveillance is indicated. Careful inspection and systematic tissue sampling at 6-month intervals would seem most prudent with this finding. Very similar recommendations apply to the surveillance of patients with Barrett's esophagus for adenocarcinoma. Whereas the precise risk awaits better definition, there are enough data at this time to justify a yearly endoscopy. Direct visualization of the full length of the columnar mucosa is desirable. Inflammatory stenoses and strictures should be dilated to allow passage of the endoscope. Since dysplasia and carcinoma in situ may be present in the absence of obvious surface changes, multiple brushings and biopsies should be obtained along the length of the columnar mucosa. The finding of dysplasia in biopsy material is again an indication for shortening the surveillance interval to 6 months. 6 Antireflux measures, including surgery, may relieve symptoms in Barrett's esophagus. Whether reversion of mucosal changes and decreased risk of adenocarcinoma occurs after such measures, however, has not been established. In a GASTROINTESTINAL ENDOSCOPY

recent article,? reversion occurred in four of 10 patients after surgery, but biopsies were not endoscopically controlled. Instances of the development of adenocarcinoma have been reported in patients with Barrett's esophagus, who have had apparently successful antireflux surgery.8 Patients with Barrett's esophagus should remain under surveillance after treatment. The esophagoscopic diagnosis of dysplasia and small, early cancer is a great challenge for the endoscopist. Very careful observations are mandatory. Because the dysplastic process causes compression of the submucosal microvasculature, dysplastic areas may appear as punctate red spots. Patchy thickening and atrophy may give an irregular roughened appearance to the usually smooth mucosa. White plaques and areas of leukoplakia are often innocent glycogenic acanthosis without malignant potential, but areas of dysplasia and carcinoma in situ may appear in this manner and must be brushed and biopsied for diagnosis. 9 ,10 Early carcinoma was differentiated into four types by Chinese endoscopists who proposed a classification somewhat different than that previously suggested by endoscopists from Switzerland. 3. 11 In type 1, called "congestive," the mucosa is flat with red spots, and probably represents an early progression from dysplasia with compression of capillaries. In type 2, called "erosive," the malignant area appears slightly depressed with gray erosive spots on a reddened background, producing a map-like appearance. In type 3, named "plaque-like," the cancerous area appears slightly elevated with a coarse granular surface, sometimes presenting an orange-peel appearance. Type 4, named "polypoid type," has a protrusion with a wide base, is less than 3 em, and is sometimes ulcerated. The "erosive" type 2 was seen most commonly, occurring in 45% of the 115 cases studied. The earliest lesions were the type 1 "congestive" variety.3 Staining the esophageal mucosa with iodine (Lugol's) solution or methylene or toluidine blue has been used to help define early esophageal cancer and to define multifocal areas of carcinoma in situ. The areas of mucosa not involved with malignant change stain a dark gray-brown or black with iodine, while areas of carcinoma in situ do not stain. l l The method is not reliable in detecting dysplasia, which stains like normal mucosa with iodine about half the time. 12 Toluidine blue (2%) has been used after an acetic acid (1 %) rinse to stain early esophageal cancers an intense violet color. Areas that take the stain are aggressively biopsied and brushed. Both dysplastic and malignant areas will stain positively. The method is not specific, however, and peptic erosions, fissures, and ulcers will also be positively colored. However, vital staining may be particularly applicable to enhance selective screening in high-risk groups.13 VOLUME 30, NO, 5, 1984

Iodine staining may be helpful in Barrett's esophagus to help localize the squamocolumnar junction, which may be very irregular. Barrett's epithelium is usually a deeper red and more granular or opaque than normal gastric epithelium, and contrasts with the grayer esophageal squamous mucosa. In some cases, however, there is a great deal of inflammation present, making the diagnosis more difficult. Lugol's solution stains the glycogen in the squamous epithelium black, but it does not stain the Barrett's mucosa. Islands of one type of epithelium within t!le other may become evident. Toluidine blue may be helpful in Barrett's esophagus to localize areas of dysplasia or carcinoma in situ. Again, the usefulness of this method is limited by the esophagitis usually present in the columnarlined esophagus. There is usually some friability and erythema and some erosions and exudate at the squamocolumnar junction. Deep benign ulcers and strictures are characteristic, usually just distal to the junction.14 Adenocarcinomas superimposed on Barrett's esophagus arise in columnar epithelium and may be infiltrative, producing a stricture, ulcerative or polypoid. 15 Abnormal areas should be investigated with multiple biopsies and cytologies. Irregular ulcers and strictures well below the squamocolumnar junction are particularly suspect for malignancy. Multifocal malignant changes of carcinoma in situ are common in Barrett's esophagus. The mucosa in these areas may be indistinguishable from benign Barrett's epithelium, and systematic sampling of the entire length of columnar lined esophagus is advised. A positive cytology or biopsy is an indication for esophagectomy even if a definite lesion cannot be identified. 1O This approach has been shown capable of diagnosing adenocarcinoma complicating Barrett's esophagus at an early, surgically curable stageP

REFERENCES 1. Cancer facts and figures. New York: American Cancer Society, 1982. 2. Winawer SJ. Screening for gastrointestinal cancer. Front Gastrointest Res 1979; 5:35-43. 3. Guanrei Y, He H, Sungliang Q, Yuming C. Endoscopic diagnosis of 115 cases of early esophageal carcinoma. Endoscopy 1982;14:157-61. 4. Shu YJ. Cytopathology of the esophagus. An overview of esophageal cytopathology in China. Acta CytoI1983;27:7-16. 5. Maimon HN, Dreskin RB, Cocco AE. Positive esophageal cytology without detectable neoplasm. Gastrointest Endosc 1974;20:156-8. 6. Haggitt RC, Tryzelaar J, Ellis FH, Colcher H. Adenocarcinoma complicating columnar epithelium-lined Barrett's esophagus. Am J Clin PathoI1978;70:1-5. 7. Brand DL, Ylvisaker JT, Gelfand M, Pope CE II. Regression of columnar esophageal (Barrett's) epithelium after anti-reflux surgery. N Engl J Med 1980;302:844-8. 8. Hamilton SR, Hutcheon DF, Ravich WJ, Campron JL, Paulson M. Adenocarcinoma in Barrett's esophagus after elimination of gastroesophageal reflux. Gastroenterology 1984;86:356-00. 9. Endo M, Kobayashi S, Suzuki H, Takemote T, Nakayama K. Diagnosis of early esophageal cancer. Endoscopy 1971;3:60-6. 10. Winawer SJ, Sherlock P, Belladonna JA, Melamed M, Beattie

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EJ Jr. Endoscopic brush cytology in esophageal cancer. JAMA 1975;232:1358. 11. Mandard AM, Tourneaux J, Gignois M, et al. In-situ carcinoma of the oesophagus. Macroscopic study with particular reference to the Lugol test. Endoscopy 1980;12:51-7. 12. Jass JR, Morson BC. Epithelial dysplasia in the gastrointestinal tract. In: Sherlock P, Jerzy-Glass G, eds. Progress in gastroenterology, vol. 4. New York: Grune & Stratton, 1983:345-71. 13. Jessen K, Paolucci P, Classen M. Endoscopic vital staining of

the oesophagus in high risk patients: detection of dysplasia and early. carcinoma. In: Sherlock P, Morson BC, Barbara L, Veronesi V, eds. Precancerous lesions of the gastrointestinal tract. New York: Raven Press, 1983:65-70. 14. Sjogren RW Jr, Johnson LF. Barrett's esophagus. a review. Am J Med 1983;74:313-21. 15. Witt TR, Bains MS, Zaman MB, Martini N. Adenocarcinoma in Barrett's esophagus. J Thorac Cardiovasc Surg 1983;85:33745.

An approach to malignant polyps

If malignant cells are present in the head of an adenoma, whether pedunculated or sessile, but do not invade the stroma, colonoscopic excision is sufficient. This entity is called carcinoma in situ, or severe dysplasia by pathologists. The term is based on the strict criterion of absence of malignant cells crossing the muscularis mucosae within the polyp. After resection, further follow-up should be performed as if the original lesions were benign. 5 Any degree of invasion into the stroma of the adenoma (i.e., carcinoma cells crossing the muscularis mucosae) places the patient at risk for metastases since lymphatics are present within the stroma. Evidence is accumulating that any degree of invasion, whether in a pedunculated or sessile adenoma, is associated with a risk of spread to lymph nodes regardless of whether carcinoma does or does not reach the line of resection. 6 Simple polypectomy and observation of the site for subsequent healing are no longer considered adequate since the polypectomy site may heal and endoscopy is inadequate to ascertain whether extraluminal metastases are present. Therefore, all patients with any degree of invasive carcinoma in a resected adenoma should undergo laparotomy and surgical resection. Decision for bowel surgery may be altered in patients who are elderly or infirm or in those patients in whom the carcinoma-within-an-adenoma is located near the rectum, and abdominoperineal resection would be required. Pedunculated adenomas (tubular or villous) removed in toto by severing the stalk endoscopically are cured and do not recur. Total excision of sessile adenomatous polyps provides the same results, but determination of total removal may be difficult at the time of polypectomy. In sessile lesions, the site ofresection should be reinspected in 6 to 12 months, and further surveillance should be the same as that of any high risk patient. If several adenomas are removed at the time of original endoscopic examination, there is a high chance of discovering more polyps on follow-up examination, some having newly grown and others having been missed at colonoscopy. The follow-up interval for a patient with a single benign adenoma, totally removed, in whom the entire colon was endos-

Jerome D. Wave, MD

Current medical opmIOn holds that most coldnic and rectal carcinomas develop via malignant changes that occur in previously benign colon adenomas. The incidence of cancer rises with the increasing size of the polyp and is dependent on its histology.! The risk of carcinoma is 0.1% in polyps less than 6 mm in diameter, increases to 1% when an adenoma is 1 cm in diameter, and may reach 20 to 40% in tumors over 3 cm in size. 2 The larger polyps (over 1 cm) and adenocarcinoma both appear to be most prominent in the rectum and sigmoid portions of the colon. Recent studies, however, show that the location of colonic carcinoma is changing, so that there is an increasing . incidence of malignancy in the right colon and the transverse colon, whereas the actual number of such tumors in the distal bowel is diminishing in frequency.3 Because of the risk of carcinoma in polyps, all those over 1 cm in diameter should be removed by polypectomy and submitted for histologic review. The advent of colonoscopy has rendered the removal of polyps relatively easy and risk free. 4 As there is a low risk of carcinoma in polyps less than 6 mm in diameter, their finding on a double contrast barium enema examination should not be the impetus for colonoscopic resection; however, if they are encountered during colonoscopy, they should be removed by biopsy and fulguration. Small polyps are rarely the cause of colonic bleeding, but if bleeding (visible or occult) is persistent, colonoscopy should be performed to determine the cause of bleeding. Although most lesions present within the colon will be diagnosed by x-ray, a normal barium enema (or one that is interpreted as showing diverticulosis as the only abnormality) in the patient with persistent bleeding does not mean that the colon is free of significant lesions. In this particular group of patients, colonoscopy has demonstrated polyps over 5 mm in diameter in 15% and infiltrating carcinoma in 10%.5 From the Division of Gastroenterology, Department of Medicine, Mt. Sinai School of Medicine, New York, New York. 310

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