Quality of gastric ulcer healing: histological and ultrastructural assessment.

It has long been assumed that the mucosa in areas of grossly 'healed' gastric or duodenal ulcers returns to normal, either spontaneously or after treatment. This assumption is based almost entirely upon visual, superficial examination by endoscopy. Few, if any, histological and ultrastructural studies examined the deeper mucosa in the areas of grossly healed ulcers. In several experimental studies, we analysed the development, evolution, and healing of acetic acid-induced gastric ulcers in rats and assessed the histological and ultrastructural features (structure and cellular composition) of the gastric mucosa in areas of grossly healed ulcers. The gastric mucosa of grossly 'healed' ulcers showed re-epithelialization of the mucosal surface at every study interval (2 weeks, 2, 3, and 4 months), but the subepithelial mucosa displayed prominent abnormalities. Two patterns of scarring were distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% thinner than normal mucosa) with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; and (b) the mucosa displayed a marked dilation of gastric glands with poor differentiation of the glandular cells and a reduction in the supportive microvascular network. It is theorized that these abnormalities could interfere with oxygenation, nutrient supply, and mucosal resistance and defence; therefore, they could be a basis for ulcer recurrence. These observations indicate that the quality of mucosal structural restoration rather than the speed of ulcer healing is the most important factor in determining risk of ulcer recurrence. The clinical relevance of these findings is supported by a preliminary study in which marked histological abnormalities were found in the subepithelial mucosa in patients with 'healed' duodenal ulcers.

Alcohol injury to the normal human gastric mucosa: endoscopic, histologic and functional assessment.

In 15 healthy volunteers, we studied the effect of intragastric administration of 100 ml 40% alcohol (in 10 experimental subjects) or isotonic saline (in 5 control subjects) on endoscopic appearance of the gastric mucosa, mucosal histology, luminal pH, and gastric mucosal potential difference. We found that a single dose of 40% alcohol produces rapid endoscopic changes (congestion and focal hemorrhagic lesions) and prominent histologic changes (exfoliation of the surface epithelium, edema of the lamina propria and hemorrhagic lesions associated with mucosal microvascular damage). The histologic changes were seen as early as 5 minutes after alcohol administration and occurred coincidentally with functional changes, which consisted of a sudden increase in luminal pH and a drop in the mucosal potential difference. The present study correlates the time sequence of the endoscopic, histological, and functional changes of the gastric mucosa following acute alcohol injury in normal human volunteers. This study confirms that many of the previous observations in animal models are also seen in normal human volunteers.

Effect of sucralfate on the normal human gastric mucosa. Endoscopic, histologic, and ultrastructural assessment.

Twelve healthy volunteers were given a single sucralfate tablet (1 gm) orally. For 60 min after ingestion they were examined endoscopically for the localization and disintegration of the tablet in the stomach, and biopsies were taken to determine the effect of sucralfate on the histology and ultrastructure of the normal gastric mucosa. After ingestion, the sucralfate tablet had disintegrated and firmly adhered to a relatively small mucosal area of the greater curvature covering 5 +/- 2 and 7 +/- 2 cm2 at 15 and 30 minutes, and 9 +/- 3 cm2 at 60 minutes after drug ingestion. Histologic and ultrastructural examination of the mucosa in direct contact with sucralfate revealed distinct changes in the surface epithelial cells: mucus release, vacuolization, and exfoliation of some of the cells. Endoscopy offers a unique opportunity for the study of gastroduodenal effects and disposition of orally administered drugs.

Does sucralfate affect the normal gastric mucosa? Histologic, ultrastructural, and functional assessment in the rat.

Although the action of sucralfate on ulcerated mucosa has been demonstrated, its effect on the histology, ultrastructure, and function of normal gastric mucosa is unknown. We investigated the effect of acute administration of sucralfate on the gastric mucosal history, ultrastructure, mucosal potential difference, and luminal release of prostaglandin E2. At 15 min, 1 h, and 3 h after intragastric instillation of sucralfate, whitish incrustations of the drug were firmly adhering to the glandular mucosa. Mucosal histology after sucralfate administration demonstrated the following: disruption and exfoliation of some of the surface epithelial cells, mucosal hyperemia, prominent release of mucus from the surface epithelial cells, and edema of lamina propria and submucosa. These changes were most prominent in the areas where sucralfate was in contact with the mucosal surface. Scanning and transmission electron microscopy confirmed the above changes. Sucralfate produced a drop in gastric mucosal potential difference and a significant increase in luminal release of prostaglandin E2. Sucralfate produces distinct morphologic and functional changes in the normal gastric mucosa, which may account for its preventive and therapeutic efficacy.

Prostaglandin protection of the human gastric mucosa against alcohol-induced injury. Endoscopic, histologic, and functional assessment.

UNLABELLED: We studied whether pretreatment with prostaglandin (16,16-dimethyl (dm) prostaglandin E2) may protect the human gastric mucosa against alcohol-induced injury. Healthy volunteers received (via an endoscope) intragastric pretreatment with either: A) placebo or B) 16,16 dm prostaglandin E2, 1 microgram/kg, and 15 min later 40 ml 60% alcohol was sprayed directly on gastric mucosa. STUDIES: endoscopic appearance of the gastric mucosa was evaluated and scored (scale 0-5) by two investigators, gastric mucosal potential difference (PD) was continuously recorded, and mucosal biopsies were obtained at 30 min after alcohol for histologic examination. Alcohol instillation in subjects pretreated with placebo (group A) produced within 30 min prominent endoscopic hemorrhagic lesions (grade 4.8 +/- 0.2). Histologic examination showed exfoliation of the surface epithelium, extensive edema of lamina propria, and deep hemorrhagic necrotic lesions in 86% +/- 10 of specimens. These morphologic changes coincided with a sudden drop in gastric PD of 42 mV. Prostaglandin pretreatment (group B) significantly reduced alcohol-induced endoscopically visible lesions (grade 3.1 +/- 0.2, P less than 0.01 vs group A). Histologically, prostaglandins reduced deep hemorrhagic erosions (4.5-fold reduction) and subepithelial hemorrhages, but did not prevent exfoliation of the surface epithelium and gastric PD drop. Thus, prostaglandin administration to human volunteers effectively reduced alcohol injury to the gastric mucosa.