0 1991 Raven Press. Ltd.. New York
J Clin Gastroenterol 1991; 13 (Suppl. I ) : S42-S47, 1991
Quality of Gastric Ulcer Healing: A New, Emerging Concept Andrzej Tarnawski, M.D., D . s ~ . , Jerzy Stachura, M.D., William J. Krause, Ph.D., Thomas G. Douglass, P h n , and Hella Gergely
from granulation tissue. Angiogenesis-the formation of new microvessels in granulation tissue-appears to be critical for the ulcer healing process. Indomethacin delays healing of experimental gastric ulcer and impairs the overall quality of ulcer healing, by distorting restoration of mucosal architecture, blocking differentiation and maturation of glandular and surface epithelial cells, and inhibiting angiogenesis in granulation tissue. Aluminumcontaining antacid (Maalox-70) accelerates healing of experimental gastric ulcer, improves the quality of mucosal structure reconstruction, and partly reverses the deleterious effect of indomethacin on the rate and quality of ulcer healing. Key Words: Gastric ulcers-Quality of healing-Healing tissue-Angiogenesis-Growth faczone-Granulation tors-IndomethacinAntacid.
Assessment of gastric ulcer healing is usually based on a visual examination (by endoscopy in patients, or the evaluation of ulcer size in experimental studies), and not on histologic and ultrastructural assessment of subepithelial mucosal healing. This approach has led to the assumption that the mucosa of grossly “healed” gastric and/or duodenal ulcers returns to normal, either spontaneously or following treatment. However, the re-epithelialized mucosa of grossly “healed” experimental gastric ulcer has recently been found to have prominent histologic and ultrastructural abnormalities, including reduced height, marked dilation of gastric glands, poor differentiation and/or degenerative changes in glandular cells, increased connective tissue, and disorganized microvascular network. It has been postulated that these residual abnormalities might interfere with mucosal defense and may be the basis of ulcer recurrence. In the present article, the ulcer healing process and the role of luminal factors, transitional zone at the ulcer margin, and granulation tissue are discussed. The healing of an ulcer is accomplished by filling of the mucosal defect with epithelial cells and connective tissue to reconstruct mucosal architecture. Under influence of growth factors [predominantly epidermal growth factor (EGF) and transforming growth factor (TGF,)], the epithelial cells at the ulcer margin dedifferentiate and proliferate, supplying cells for re-epithelialization of the mucosal scar surface and reconstruction of glandular structures. Granulation tissue at the ulcer base supplies connective tissue cells to restore the lamina propria and endothelial cells and microvessels for mucosal microvasculature reconstruction. The final outcome of healing reflects a dynamic interaction between an “epithelial” component from the ulcer margin and a connective tissue component including microvessels originating
Gastric ulcer is a deep necrotic lesion involving the entire mucosal depth and the muscularis mucosae (1,2) (Fig. 1). It develops as a result of a marked imbalance between aggressive factors and mucosal defensive mechanisms (3-5). Numerous factors (genetic, neural, hormonal, humoral, and iatrogenic) have been postulated to have roles in ulcer development (3-5). Several experimental models of gastric ulcer have been developed in animals, including focal surgical resection of the gastric mucosa, thermal or laser injury of the mucosa, cryoinjury with cryoprobes, ligation of submucosal vessels, and application of acetic acid either as a submucosal injection or topically on the serosa (6-17). These models have been used for the study of gastric ulcer formation and for
From the Gastroenterology Section, DVA Medical Center, Long Beach (A.T.),and University of California, Irvine, California; University of Missouri, Columbia, Missouri; and California State University, Long Beach, California. Dr. Stachura was a visiting scientist from the University Medical School, Krak6w, Poland. Address correspondence and reprint requests to Dr. A. Tarnawski at Gastroenterology Section, DVA Medical Center, 5901 E. Seventh Street, Long Beach, CA 90822, U.S.A.
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J Clin Gastroenterol 1991; 13 (Suppl. I ) : S42-S47, 1991
Quality of Gastric Ulcer Healing: A New, Emerging Concept Andrzej Tarnawski, M.D., D . s ~ . , Jerzy Stachura, M.D., William J. Krause, Ph.D., Thomas G. Douglass, P h n , and Hella Gergely
from granulation tissue. Angiogenesis-the formation of new microvessels in granulation tissue-appears to be critical for the ulcer healing process. Indomethacin delays healing of experimental gastric ulcer and impairs the overall quality of ulcer healing, by distorting restoration of mucosal architecture, blocking differentiation and maturation of glandular and surface epithelial cells, and inhibiting angiogenesis in granulation tissue. Aluminumcontaining antacid (Maalox-70) accelerates healing of experimental gastric ulcer, improves the quality of mucosal structure reconstruction, and partly reverses the deleterious effect of indomethacin on the rate and quality of ulcer healing. Key Words: Gastric ulcers-Quality of healing-Healing tissue-Angiogenesis-Growth faczone-Granulation tors-IndomethacinAntacid.
Assessment of gastric ulcer healing is usually based on a visual examination (by endoscopy in patients, or the evaluation of ulcer size in experimental studies), and not on histologic and ultrastructural assessment of subepithelial mucosal healing. This approach has led to the assumption that the mucosa of grossly “healed” gastric and/or duodenal ulcers returns to normal, either spontaneously or following treatment. However, the re-epithelialized mucosa of grossly “healed” experimental gastric ulcer has recently been found to have prominent histologic and ultrastructural abnormalities, including reduced height, marked dilation of gastric glands, poor differentiation and/or degenerative changes in glandular cells, increased connective tissue, and disorganized microvascular network. It has been postulated that these residual abnormalities might interfere with mucosal defense and may be the basis of ulcer recurrence. In the present article, the ulcer healing process and the role of luminal factors, transitional zone at the ulcer margin, and granulation tissue are discussed. The healing of an ulcer is accomplished by filling of the mucosal defect with epithelial cells and connective tissue to reconstruct mucosal architecture. Under influence of growth factors [predominantly epidermal growth factor (EGF) and transforming growth factor (TGF,)], the epithelial cells at the ulcer margin dedifferentiate and proliferate, supplying cells for re-epithelialization of the mucosal scar surface and reconstruction of glandular structures. Granulation tissue at the ulcer base supplies connective tissue cells to restore the lamina propria and endothelial cells and microvessels for mucosal microvasculature reconstruction. The final outcome of healing reflects a dynamic interaction between an “epithelial” component from the ulcer margin and a connective tissue component including microvessels originating
Gastric ulcer is a deep necrotic lesion involving the entire mucosal depth and the muscularis mucosae (1,2) (Fig. 1). It develops as a result of a marked imbalance between aggressive factors and mucosal defensive mechanisms (3-5). Numerous factors (genetic, neural, hormonal, humoral, and iatrogenic) have been postulated to have roles in ulcer development (3-5). Several experimental models of gastric ulcer have been developed in animals, including focal surgical resection of the gastric mucosa, thermal or laser injury of the mucosa, cryoinjury with cryoprobes, ligation of submucosal vessels, and application of acetic acid either as a submucosal injection or topically on the serosa (6-17). These models have been used for the study of gastric ulcer formation and for
From the Gastroenterology Section, DVA Medical Center, Long Beach (A.T.),and University of California, Irvine, California; University of Missouri, Columbia, Missouri; and California State University, Long Beach, California. Dr. Stachura was a visiting scientist from the University Medical School, Krak6w, Poland. Address correspondence and reprint requests to Dr. A. Tarnawski at Gastroenterology Section, DVA Medical Center, 5901 E. Seventh Street, Long Beach, CA 90822, U.S.A.
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