Diagnostic inconsistencies in Barrett's esophagus. Department of Veterans Affairs Gastroesophageal Reflux Study Group.

BACKGROUND/AIMS: Few studies have compared the precision of various diagnostic tests used to determine the presence of Barrett's esophagus. The aim of this study was to compare the results of histological, endoscopic, and manometric tests for patients with Barrett's esophagus in two closely spaced examinations. METHODS: In a Veterans Administration Cooperative Study, 192 patients with complicated gastroesophageal reflux disease had esophageal manometry and endoscopy performed at baseline and after 6 weeks. At each examination, the endoscopist localized the most proximal level of Barrett's epithelium and the lower esophageal sphincter and obtained esophageal biopsy specimens. RESULTS: One hundred sixteen patients met the criteria for Barrett's esophagus on at least one of the two endoscopic examinations. Among patients with specialized columnar epithelium, 20% had specialized columnar epithelium found on only one of the two examinations. Although the mean lower esophageal sphincter level did not change, approximately 10% of patients had a change > or = 4 cm on endoscopy and manometry between examinations. This led to an apparent change in the diagnosis in 18% of patients with Barrett's esophagus. CONCLUSIONS: From one endoscopic examination to another, inconsistencies in the ability to detect specialized columnar epithelium are common. This may lead to substantial problems in establishing an accurate diagnosis of Barrett's esophagus.

Identification of orbital lymphatics: enzyme histochemical light microscopic and electron microscopic studies.

The presence of orbital lymphatics in the primate model is demonstrated using light and electron microscopic enzyme histochemistry. In addition, strictly morphological definitions of lymphatics, such as discontinuous basal lamina, thin and irregular walls, anchoring filaments, and attenuated endothelial cell cytoplasm, were applied. This study confirmed the presence of conjunctival lymphatics reported by others. It also clearly demonstrated the presence of orbital arachnoid and lacrimal gland lymphatics that have not been previously described. A few areas of the extraocular muscles and connective tissue at the orbital apex also showed evidence of the presence of lymphatic vessels. Additional work is needed to define the nature and extent of orbital lymphatics as well as their connection to the extraorbital lymphatic system.

Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett's epithelium.

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.

Bacteriologic status of necrotic tissue in necrotizing pancreatitis.

To confirm the accuracy of guided percutaneous aspiration (GPA) in distinguishing sterile from infected pancreatic necrosis, we have performed Brown-Brenn tissue Gram stains on pancreatic and peripancreatic necrotic tissue removed operatively in 15 patients. In eight patients judged to have sterile necrosis on the basis of negative cultures of pancreatic exudate obtained first preoperatively (by GPA) and then intraoperatively, necrotic tissue debrided at surgery was also free of bacteria. In seven patients judged to have infected necrosis on the basis of positive cultures of pancreatic exudate obtained first preoperatively (by GPA) and then intraoperatively, necrotic tissue debrided at surgery harbored a considerable number of bacteria. We conclude that GPA targeted to areas of necrosis accurately distinguishes infected necrosis from sterile necrosis, and in infected necrosis, the solid necrotic tissue as well as the fluid component contains bacteria. We therefore believe that infected necrosis is not likely to be eradicated by catheter drainage and should be treated by surgical debridement.

The increasing frequency of adenocarcinoma of the esophagus.

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.

Esophageal intramural pseudodiverticulosis: a report of two cases with analysis of similar, less extensive changes in "normal" autopsy esophagi.

Esophageal intramural pseudodiverticulosis (EIPD) is an uncommon cause of dysphagia. In this report, we describe two cases we encountered at autopsy. In both cases, the pseudodiverticula represented dilated excretory ducts of submucosal mucous glands. In addition, we retrospectively examined histologic sections of esophagus taken randomly from 100 autopsies, and prospectively studied 20 esophagi in a standardized fashion. Our findings suggest that the early pathologic changes of EIPD are more common than is appreciated in the literature. We found submucosal chronic inflammation surrounding mucous glands in more than 60% of esophagi at autopsy. Excretory duct dilatation and small pseudodiverticula were also commonly found, their prevalence related to the number of sections of esophagus studied. The finding of chronic inflammation associated with the earliest degrees of duct dilatation and pseudodiverticula formation suggests that inflammation may play a role in the etiology of this disorder.

Gallbladder adenocarcinoma: the prognostic significance of histologic grade.

Gallbladder adenocarcinoma (GBA) postresection 5-year survival rates are less than 5%, but when histologically confined to the mucosa or submucosa, survival rates of 64% (5 years) and 44% (10 years) have been reported. Whether any other histologic features of GBA have prognostic significance is unknown. This investigation was conducted to determine if GBA histologic grade correlates with survival. Thirty patients with advanced stage GBA participating in Eastern Cooperative Oncology Group (ECOG) treatment protocol EST-2273 served as the study material. Using glandular tumor grade criteria recommended by others, a panel of 7 ECOG pathologists categorized the GBA as either predominantly low or high histologic grade. Each patient's GBA histologic section measured no less than 1.0 X 1.0 cm. Predominant grade was defined as being that grade present in greater than 75% of the histologic section. Patient survival times by grade were calculated from date of initiation of chemotherapy until date of death. The 13-week low grade GBA patient survival was significantly longer than the 7-week high grade GBA patient survival (p less than 0.01). Stratification of patients by either high or low predominant histologic grade is recommended in future GBA treatment studies.

Gallbladder adenocarcinoma: prognostic significance of tumor acid mucopolysaccharide content.

The gall bladder mucosa is composed of neutral mucopolysaccharide and protein radical containing secretory cells, protein radical containing migratory cells, and neutral and acid mucopolysaccharides plus sialic acid containing goblet cells. The prognostic significance of histologic or histochemical parameters in gall bladder adenocarcinoma (GBA) are unknown. To determine if histochemical acid mucopolysaccharide content in GBA has prognostic value, GBA histologic sections from 26 advanced stage disease patients participating in Eastern Cooperative Oncology Group (ECOG) treatment study EST-2273 were stained with alcian blue at pH. 1.0, assessed by a pathology panel for either high (greater than 50%) or low (less than 50%) acid mucopolysaccharide content, and correlated with patient survival. Initial panel unanimous concurrence rate on acid mucopolysaccharide content was 88.9%. Median survival times from the start of chemotherapy to date of death for high acid mucopolysaccharide content GBA was 14 weeks versus five weeks for the low content GBA (P less than 0.0001). The results indicate that high acid mucopolysaccharide content in GBA significantly improves prognosis. ECOG recommends stratification by acid mucopolysaccharide content in future GBA treatment investigations.

13-cis-retinoic acid in the treatment of oral leukoplakia.

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.

Carcinoids: the prognostic effect of primary site histologic type variations.

Carcinoids are histologically classified as insular (A), trabecular (B) glandular (C), undifferentiated (D) or mixed. These have prognostic significance, i.e. Group 1 (most favorable, A + C); 2 (favorable, A, B, A + B); 3 (relatively unfavorable, all non A + C or A + B mixed types); and 4 (unfavorable, C, D). Midgut primaries have a better prognosis than either foregut or hindgut/cloacal primaries. Carcinoids from 114 Eastern Cooperative Oncology Group patients were studied to determine if primary site prognostic differences result from histologic prognostic group occurrence rate differences across primary sites. By primary site the following rates were observed: Foregut: 1 (0%), 2 (79.2%), 3 (12.5%), 4 (8.3%); midgut: 1 (26.7%), 2 (58.7%), 3 (6.6%), 4 (8.0%); hindgut/cloaca: 1 (0%), 2 (42.9%), 3 (42.9%), 4 (14.2%); nongut: 1 (0%), 2 (75.0%), 3 (12.5%), 4 (12.5%), p less than 0.01. The results demonstrate that primary site prognostic differences are highly dependent upon histologic prognostic group occurrence rate variations across primary sites. In addition multivariate analysis of survivorship by both histologic type (p less than 0.05) and primary site (p less than 0.05) demonstrated that each variable has independent prognostic significance.

Scanning electron microscopy of Barrett's epithelium and its correlation with light microscopy and mucin stains.

The surface epithelial cells of Barrett's esophagus were characterized using quantitative scanning electron microscopy and light microscopy with mucin histochemical stains. Fifty-one biopsy specimens of Barrett's esophagus from 15 patients and 31 control specimens of the stomach and intestines from 9 patients were examined. Three distinct surface cell types, in addition to the goblet cell, were recognized in Barrett's epithelium: the gastric-like cell in 31% of specimens, which was similar to the normal gastric surface cell by quantitative scanning electron microscopy; the intestinal-like cell in 41%, which was most similar to the normal small intestinal surface cell; and the variant cell in 80%, which had a range of surface features. By light microscopy, all specimens with variant and intestinal-like cells were classified as specialized columnar epithelium. The surface mucous cells in Barrett's epithelium displayed a variety of mucin staining patterns with acid nonsulfated (small intestinal-like) mucin present in 90% of specimens and acid sulfated (colonic-like) mucin in 43% of specimens. Quantitative scanning electron microscopy and mucin histochemical stains reveal a striking cellular heterogeneity not apparent by routine light microscopy.

Silicone-induced endocarditis. A complication of transvenous cardiac pacing catheterization.

We report a case of silicone-induced endocarditis as a newly recognized complication of transvenous cardiac pacing catheterization. Silicone was found embedded in thrombotic vegetations on the tricuspid valve of a patient who had a long-standing pacing catheter in the right side of his heart. Scanning electron microscopy and energy-dispersive x-ray analysis confirmed the presence of silicone in the vegetations and in the catheter tip.

Transformation of lymphoma to amyloidoma following radiation therapy.

A 62-year-old man presented with a localized upper-extremity small cell lymphoma with plasmacytoid features and an associated IgM lambda serum immunoglobulin level of 1,730 g/dl. The tumor was treated with 5,960 rad over 47 days. On completion of radiation therapy, the tumor had regressed only minimally, and the monoclonal immunoglobulin level had decreased by 63 per cent; repeat biopsy revealed that the lymphoma had been replaced by a virtually acellular mass of amyloid. It is postulated that radiation therapy accelerated the tissue conversion of lambda light chain into the beta-pleated sheet structure characteristic of amyloid fibrils.

Chemoprevention of head and neck cancer. Potential use of retinoids.

Research on retinoid treatment of neoplastic lesions will ultimately determine the long-term effect of these substances on cancer development. However, until specific indications are firmly established through clinical trials, retinoid compounds cannot be routinely recommended.

The reticular pattern as a radiographic sign of the Barrett esophagus: an assessment.

A two-part retrospective study was conducted to assess the value of a reticular pattern as a sign of columnar-lined esophagus. Radiographic, endoscopic, and histologic findings were reviewed in 124 patients with known Barrett esophagus; then all barium esophagrams done at our institution during a 3 1/2 month period were reviewed and presence of a reticular pattern was correlated with available endoscopic and histologic data. In patients with known Barrett esophagus, the reticular pattern was found in 26% of double-contrast examinations. Twelve of these patients underwent careful esophageal mapping biopsies: the pattern was in squamous mucosa with ulceration in two, in columnar epithelium with ulceration in six, and in columnar epithelium without ulceration in four. In the group of 314 unselected patients who had double-contrast examinations, the reticular pattern was found in 26 (8%). Thirteen of the 26 had had endoscopy and biopsy: the site of the pattern was located in a squamous carcinoma in one, in squamous epithelium adjacent to squamous carcinoma in three, in squamous epithelium with esophagitis in five (two of whom had columnar mucosa distally), in normal squamous mucosa in one, and in columnar epithelium with esophagitis in three. The reticular pattern is a strong indicator of important esophageal disease, but is not specific for Barrett esophagus.

Adenocarcinoma and Barrett's esophagus. An overrated risk?

The risk of developing esophageal cancer in Barrett's esophagus has been estimated at about 10%. This estimate is based primarily on data concerning the prevalence of that association in series of hospitalized patients and autopsies--a practice that tends to exaggerate the risk. We have reviewed retrospectively our experience with 115 patients whom we treated for Barrett's esophagus between September 1962 and March 1983, and have distinguished our data on the prevalence of esophageal cancer from that on incidence. For 8 patients, we found both Barrett's esophagus and esophageal adenocarcinoma during the initial evaluations for a prevalence ratio of 7%. We followed 105 patients not found to have esophageal cancer initially for a total of 350 person-years. Only 2 patients developed adenocarcinoma during that follow-up period for an incidence of 1 case per 175 person-years. This incidence, although some 40-fold greater than that of the general population, is substantially lower than previously estimated. Routine endoscopic and histologic surveillance has been recommended for patients with Barrett's esophagus because of the alleged high incidence of esophageal cancer. Inasmuch as that incidence now appears to be low, we question the value of such surveillance for these patients.