The Complex Morphopathogenetic Aspects of Intraabdominal Adhesions Development and Course in Infants. Summary of the Doctoral Thesis

Abstract

Intraabdominal adhesions are fibrous connections between the abdominal organs and/or the abdominal wall. These can be acquired or inborn. Most of the acquired adhesions occur due to inflammatory processes or postoperatively. Inborn adhesions are believed to be the result of a perturbated embrional development and/or even genetically determined defects in embriongenesis. Intraabdominal adhesions can be assymptomatic, but they also can cause dangerous complications, such as bowel obstruction. The morphopathogenesis of intraabdominal adhesions is a complex process, characterized by the accumulation of extracellular matrix, tissue hypoxia and inflammation. It was the aim of this study to determine and describe the morphopathogenic factors, accompanying intraabdominal adhesion formation and their interactions. 50 specimen from 49 patients with total or partial bowel obstruction and eight control peritoneal samples, obtained during hernioplasty, were analyzed in the study. All tissue samples were obtained from patients aged one year or younger. Transforming growth factor β (TGFβ), hepatocyte growth factor (HGF), fibroblast growth factor (FGF-2), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor (VEGF), protein gene product 9.5 (PGP 9.5), chromogranin A (CgA), interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), tumour necrosis factor alpha (TNF-α), human beta defensine-2 (HBD-2), matrix metaloproteinase-2 (MMP-2) and matrix metaloproteinase-2 tissue inhibitor (TIMP-2) containing structures were analyzed, using immunohistochemical methods. Neonatal adhesions are characterized by unspecific changes, such as fibrosis and neoangiogenesis, as well as changes specific to chronic inflammation, such as mesotheliocytes and fibroblasts of modified shape, due to a phenotypic change in the cell, as well as giant cells. Intraabdominal adhesions ar characterized by an increased TGFβ, VEGF, FGFR1 and decreased FGF-2, HGF, PGP 9.5, IL-1, IL-4, IL-8, TIMP-2 findings. Key factors, contributing to the formation and persistance of adhesions, are remodelation of the extracellular matrix, neoangiogenesis and persisting iflammation, that, in times of a depleted inflammatory response, results in a peculiar circulus vitiosus. Thus, the most significant markers in the progonosis and diagnosis of adhesions in newborns are TGFβ, VEGF, HGF, IL-1 un IL-4.