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Background & Aims: The diagnosis and management of Barrett's esophagus (BE) are controversial. We conducted a critical review of the literature in BE to provide guidance on clinically relevant issues. Methods: A multidisciplinary group of 18 participants evaluated the strength and the grade of evidence for 42 statements pertaining to the diagnosis, screening, surveillance, and treatment of BE. Each member anonymously voted to accept or reject statements based on the strength of evidence and his own expert opinion. Results: There was strong consensus on most statements for acceptance or rejection. Members rejected statements that screening for BE has been shown to improve mortality from adenocarcinoma or to be cost-effective. Contrary to published clinical guidelines, they did not feel that screening should be recommended for adults over age 50, regardless of age or duration of heartburn. Members were divided on whether surveillance prolongs survival, although the majority agreed that it detects curable neoplasia and can be cost-effective in selected patients. The majority did not feel that acid-reduction therapy reduces the risk of esophageal adenocarcinoma but did agree that nonsteroidal antiinflammatory drugs are associated with a cancer risk reduction and are of promising (but unproven) value. Participants rejected the notion that mucosal ablation with acid suppression prevents adenocarcinoma in BE but agreed that this may be an appropriate strategy in a subgroup of patients with high-grade dysplasia. Conclusions: Based on this review of BE, the opinions of workshop members on issues pertaining to screening and surveillance are at variance with published clinical guidelines.

BACKGROUND: The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria. AIM: To conduct a systematic comparative examination of gastric histology and function. SUBJECTS: Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status. METHODS: All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection. RESULTS: The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics. CONCLUSIONS: Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.

BACKGROUND: Recent data have suggested that cardia biopsy specimens may be more reflective of gastro-oesophageal reflux disease (GORD) than squamous biopsy specimens. AIMS: To assess the distribution, severity, and types of mucosal injury in GORD. PATIENTS: Thirty patients with symptomatic GORD with no or minimal erosions. METHODS: Biopsies were performed at the squamocolumnar junction (Z-line) and 1-2 cm below the Z-line. Injury to the columnar mucosa was scored for inflammatory cells, epithelial cell abnormalities, and for the presence of intestinal metaplasia and Helicobacter pylori. A carditis score above 2 was considered positive (maximum score = 9). RESULTS: Mean carditis scores and percentages of patients with a positive carditis score were higher in Z-line biopsy specimens containing both squamous and columnar mucosa than in those with just columnar mucosa or in specimens taken 1-2 cm below the Z-line. Carditis at the Z-line was focal in 49% of the specimens and was always present adjacent to the squamous epithelium. Goblet cells were present more frequently in the specimens immediately at the Z-line than in those 1-2 cm below the Z-line. H pylori was present in only four patients. The mean carditis scores of specimens 1-2 cm below the Z-line in these patients was significantly higher than in those patients without H pylori. CONCLUSIONS: Mucosal injury at the gastric cardia is highly localised to the region adjacent to the squamocolumnar junction in patients with GORD. Morphological studies of the cardia in GORD should focus on tissue samples that contain both squamous and columnar epithelium in order to obtain an accurate picture of the spectrum of injury.

A simple method was developed whereby immunoperoxidase and immunofluorescence techniques were applied in consecutive steps to demonstrate the presence of two antigens in the same tissue section. This method was applied in three model, two antigens were shown: a) each (gastrin and pepsinogen II) inside one of two different cell types (gastrin (G) and antral peptic cells), b) each (kappa or gamma light chains) inside different cells of the same type (plasma cells); also, both (kamma and gamma light chains) inside the same cell (Reed-Sternberg cell), and c) both (pepsinogen I and II) inside the same cell (chief cell of oxyntic glands). The results could be viewed and photographed either simultaneously, when the antigens were in different cells, or sequentially, when the antigens were in the same cells.

Background: To understand the pathophysiology of duodenal ulcer disease, it is important to identify and quantitate gastric metaplasia of the duodenum. Methylene blue dye is absorbed well by intestinal mucosa, but not by gastric mucosa. Our aim was to validate a methylene blue staining technique for measurement of gastric metaplasia in the duodenum. Methods: Eight subjects with chronic duodenal ulcer disease and seven subjects with other upper intestinal disorders underwent duodenal methylene blue staining after application of a mucolytic agent. Biopsy specimens were obtained from blue-stained and pale unstained areas and assessed for gastric metaplasia histologically. Results: Pink or pale unstained duodenal areas had more gastric surface cell metaplasia than blue-stained areas. Unstained duodenum was also more likely to have extensive (more than 25% of the biopsy specimens) gastric metaplasia (60%) than blue-stained areas (9%). Subjects with duodenal ulcer disease had more unstained mucosa than controls. Conclusion: Methylene blue staining of the duodenum is useful to identify and quantitate gastric metaplasia. (Gastrointest Endosc 1998;48:32-8.)

Abstract: Usingd-glucose as the probe molecule, we analysed conditions which must be fulfilled in mucosal biopsy studies before the kinetic nature of the transport process can be established. Mucosal biopsies were obtained from the region of the ligament of Treitz from four healthy volunteers and from 47 patients: 29 of the 47 had histologically normal mucosa; seven had mild abnormalities; and 11 had moderate or severe (ldquoflatrdquo) abnormalities in villus architecture. The rate of uptake of 40 mM glucose was constant only between 4 and 10 min, extrapolating through zero uptake at zero time with a constant adherent mucosal fluid volume. Incubation for shorter or longer periods was associated with over- or underestimation of the rate of uptake. Failure to use a nonabsorbable marker was also associated with overestimation of the rate of uptake. When biopsies were incubated for 6 min, a curvilinear relationship was observed between uptake rate and concentration. In biopsies with moderate and severe abnormalities, there was a marked reduction in the magnitude of the maximal transport rate and the apparent passive permeability coefficient, with little change in the magnitude of the apparent affinity constant. When human mucosal biopsies are used to study nutrient absorption, certain criteria must be fulfilled to establish valid rate constants and to make comparisons between normal and abnormal mucosa.

The image of an incoherently illuminated edge is shown to have a simple structure with no diffraction fringes for any state of correction of the imaging system. The light distribution in the defocused image is calculated and numerical results are given. A comparison is made with the predictions of geometrical optics.

General expressions for the transmissivity and reflectivity of multi-layer coatings of any number of components, for light polarized in any way and incident at any angle, are derived.

When an optical system is illuminated by a pinhole of unresolvable size, light flux is lost by diffraction at the pinhole if the usual conditions for full-cone illumination are satisfied. Formulas are given for this loss and it is shown that for a pinhole small enough to appear as a true point source an illuminating cone of three or more times the angle of the cone accepted by the optical system must be used to avoid substantial light loss. Experimental confirmation is given.

Experiments have been carried out to determine the systematic errors in the measurement of the diameters of opaque cylinders by scanning microscopy. It was found that for cylinders of diameter near the optical resolution limit, the scanning microscope gives too large a size estimate. The variation of the error with aberrations and numerical aperture of the scanning objective, and with the wavelength and state of polarization of the light were determined. Optimum conditions for size determination are suggested.