The peritoneum is a serous membrane, which has a protective function for the contents of the abdominal cavity. It maintains homeostasis by allowing exchange of molecules and production of peritoneal fluid, thus providing an environment in which intra-abdominal organs can function properly. When traumatized, whether by surgery or due to inflammatory processes, a series of responses come into action to regenerate the injured part of the peritoneum. The inflammatory reaction causes influx of inflammatory cells but also activates resident mesothelial cells, ultimately leading to a fibrinous exudate. Depending on the severity of the trauma this exudate is transient due to fibrinolysis, or becomes more dense as a result of fibroblasts persisting, leading to fibrinous adhesions. A pivotal role is taken by the enzyme plasmin and its promotors and inhibitors; it is mainly the tissue-type plasminogen activator/plasminogen activator inhibitor ratio which determines the rate of fibrinolysis and therefore the rate of adhesion formation. The rate of injury determines the rate and extent of the inflammatory response to that injury; in its turn the inflammatory reaction determines the extent of adhesion formation. One should realize this when performing intra-abdominal surgery, which is in fact operating inside the peritoneal organ.
We hypothesise that reactive oxygen species (ROS) released from activated polymorphonuclear leucocytes during surgery play a crucial role in enhanced tumour recurrence seen after surgery. Therefore, the effect of ROS on adhesion of tumour cells to microvascular endothelium in a reproducible human in vitro model was studied. Preincubation of microvascular endothelial cells with the superoxide anion producing xanthine -xanthine oxidase complex significantly increased adhesion of the human colon carcinoma cells HT29 (167% vs control, Po0.01), Caco2 (164% vs control, Po0.01) and of the pancreas carcinoma cells PanC1 (180% vs control, Po0.01). Addition of the antioxidant enzymes superoxide dismutase or catalase significantly decreased tumour cell adhesion (Po0.01). Exposure of endothelial cells to superoxide anions increased the apoptotic rate to 7.9 times the normal rate. Additionally, exposure increased expression of the endothelial adhesion molecules E-Selectin, ICAM-1, and VCAM-1 of maximally 170% vs control (Po0.01). In conclusion, this study shows that superoxide anions promote the adherence of tumour cells to the microvasculature by inducing endothelial apoptosis that subsequently induces the expression of various adhesion molecules for tumour cells. This indicates that by tackling the production of ROS preventing tumour recurrence at distant sites might be feasible.
P ostoperative adhesion formation is the most frequent complication of surgery, although often not recognized as such. With an incidence of 55% to 100% in all abdominal operations, adhesions are responsible for an increased risk of small bowel obstruction, chronic abdominal pain, and infertility. 1,2 The economic burden of adhesion-related hospital readmissions and reoperations is enormous, considering the annual costs exceeding $1 billion in the United States alone. 3,4 Recently, the results of the third Surgical and Clinical Adhesions Research study were published, indicating a readmission risk of approximately 30% due to adhesions after colorectal surgery. 5 Various strategies, such as application of liquids and membranes, are used in an attempt to prevent adhesion formation. As of yet, no strategy is capable of complete prevention. Surgical trauma to the peritoneum is the main cause of postoperative adhesion formation. Peritoneal damage induces an inflammatory response that ultimately leads to up-regulation of the expression of tissue factor by macrophages and mesothelial cells. This causes activation of the extrinsic pathway of the coagulation cascade, eventually leading to the formation of a fibrinous exudate.Under normal circumstances, this fibrinogenesis is in balance with fibrinolysis. The process of fibrinolysis is driven by the enzyme plasmin, which is derived from its inactive substrate plasminogen by tissue-type plasminogen activator (tPA). On its turn, tPA is inhibited in its reaction by plasminogen activator inhibitor-1 (PAI-1), to maintain a balance. In the abdominal cavity, tPA is responsible for 95% of the plasminogen conversion. 6 Intra-abdominal surgery disturbs the balance between tPA and PAI-1 resulting in a decreased fibrinolytic activity and an increase in fibrin exudate, eventually leading to an increase in adhesion formation. 7 When the peritoneum is slightly damaged and mesothelial cells are mostly intact, there will be a dynamic balance between fibrinogenesis and fibrinolysis and adhesion-free healing may then take place; reepithelialization is complete 5 to 8 days after the initial trauma. 8 When more severe trauma is caused during an operation, loss of mesothelial integrity will occur, exposing the underlying connective tissue and extracellular matrix. Normal fibrinolytic activity will be lost for at least 48 hours post-trauma, 9 although individual differences are present in patients. The fibrinous adhesions will organize into fibrous adhesion due to ingrowth of fibroblasts and endothelial cells that is followed by capillary formation and incorporation of collagen, all stimulated by cytokines and growth factors (day 4 to day 10). 9 Statins (3-hydroxy-methylglutaryl-coenzyme A reductase inhibitors) antagonize the enzyme HMG-CoA reductase, which catalyzes the rate-limiting step in hepatic cholesterol synthesis. This leads to reduction in the synthesis and secretion of lipoproteins by the liver, as well as up-regulation of LDL receptors on hepatocytes, increasing clearance of circulati...
In Hartmann's procedure, Seprafilm placement does not provide protection against small-bowel obstruction. Incidence of chronic abdominal complaints is significantly lower after use of Seprafilm.
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