13-cis-Retinoic acid has been reported to be effective in treating oral leukoplakia. We randomly assigned 44 patients with this disease to receive 13-cis-retinoic acid (24 patients) or placebo (20), 1 to 2 mg per kilogram of body weight per day for three months, and followed them for six months. There were major decreases in the size of the lesions in 67 percent (16 patients) of those given the drug and in 10 percent (2 patients) of those given placebo (P = 0.0002); dysplasia was reversed in 54 percent (13 patients) of the drug group and in 10 percent (2 patients) of the placebo group (P = 0.01). The clinical response to the drug correlated with the histologic response in 56 percent (9 of 16) of the patients evaluated. Relapse occurred in 9 of 16 patients two to three months after treatment ended. The toxic effects of the drug were acceptable in all but two patients. Cheilitis, facial erythema, and dryness and peeling of the skin were common; conjunctivitis and hypertriglyceridemia also occurred. All adverse reactions could be reversed by reducing the dose or temporarily discontinuing the drug. We conclude that 13-cis-retinoic acid, even in short-term use, appears to be an effective treatment for oral leukoplakia and has an acceptable level of toxicity.
Adenocarcinoma of the esophagus has been considered an uncommon tumor, accounting for fewer than 8% of all cases of esophageal cancer. To determine the current frequency of adenocarcinoma of the esophagus, we reviewed data from the tumor registries of the Commonwealth of Massachusetts, the University Hospital (UH), and the Boston VA Medical Center (BVAMC). From 1982 to 1984, 868 esophageal cancers were reported in Massachusetts, of which 231 (27%) were adenocarcinomas. In comparison with squamous cell carcinomas of the esophagus, esophageal adenocarcinomas occurred more frequently in males (P less than 0.01) and were uncommon among blacks (P less than 0.01). From 1980 to 1986, 262 cases of esophageal cancer were seen at the UH and the BVAMC, of which 81 (31%) were adenocarcinomas. An analysis of the latter group to identify true esophageal adenocarcinomas (tumors confined to the esophagus without gastric involvement) yielded 47 cases. Thus, true esophageal adenocarcinoma accounted for 18% of esophageal malignancies at our hospitals, a frequency threefold to fivefold higher than that found in four prior studies that used comparable anatomic diagnostic criteria. We conclude that adenocarcinoma of the esophagus is now being recognized at a substantially higher frequency than reported in the past.
Metaplastic columnar epithelium replaces the normal squamous epithelium in Barrett's esophagus. We characterized the surface epithelial cells of the junction between squamous and Barrett's epithelium using scanning electron microscopy and light microscopy. In four biopsy specimens from the squamous-Barrett's junction in three patients, we found a distinctive cell type having features intermediate between those of squamous and columnar epithelium. Its distinguishing characteristic is the presence on its surface of two disparate structures not normally present on the same cell in the gastrointestinal tract: microvilli (a scanning electron microscopy feature of glandular epithelium) and intercellular ridges (a scanning electron microscopy feature of squamous mucosa). The surface characteristics of this newly recognized cell were strikingly similar to those of cells found in the transformation zone of the uterine cervix, an area in which squamous epithelium physiologically replaces columnar epithelium. We also examined 28 biopsies of the gastroesophageal junction area from 14 patients with and without a history of heartburn but with no evidence of Barrett's esophagus. None of these biopsies showed the distinctive cell. We hypothesize that this distinctive cell represents an intermediate step in either the development or the healing of Barrett's epithelium, during which surface characteristics of two different cell types, columnar and squamous, coexist on the same cell.
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