Abstract
Thalidomide, because of its anti-inflammatory properties, as re-emerged as an option for the treatment of Crohn's disease refractory to standard therapy. We studied the effect of thalidomide on the healing of colonic anastomosis. Sixty male rats (Rattus norvegicus), were divided into 3 groups of 20 animals each, respectively receiving 0.5 or 1.0 mg/kg thalidomide by the oral route for 7 days, or saline solution (control). All animals were submitted to continuous end-to-end anastomosis with 6-0 Prolene sutures. After sacrifice the anastomoses were analyzed macroscopically and submitted to determination of hydroxyproline, to histology and to immunohistochemistry for metalloproteinase 1, metalloproteinase 1 inhibitor and vascular endothelial growth factor (VEGF). Statistical analysis of the data showed no significant difference in macroscopic aspect or hydroxyproline determination (p= 0.5403). In the immunohistochemical analysis, the following p values were obtained: p = 0.5817 for VEGF, p = 0.1854 for metalloproteinase 1, and p = 0.0023 for metalloproteinase 1 inhibitor, with this last value being considered statistically significant. We conclude that thalidomide influenced collagen maturation. There was a stronger action of metalloproteinases, possibly indicating a negative tendency for the healing process.
Highlights
The healing process in general and the healing of digestive anastomosis in particular has been the subject of exhaustive studies and has long raised heated debate in the history of Surgery
The healing of anastomosis is of fundamental importance for the favorable results that all surgeons expect for their patients and its failure, with dehiscence, is one of the main causes of complications in surgeries of the intestinal tract since dehiscence is accompanied by high morbidity and mortality due to peritonitis and sepsis.[1,2,3,4,5]
Healing is a complex process mediated by multiple factors which culminates in organized collagen synthesis
Summary
The healing of anastomosis is influenced by the general condition of the patient,[6] the blood supply and oxygenation of tissue,[7] the quality of the local vascular network,[8] oxygen tension,[9] tension along the anastomosis line,[10] blood volume,[11] peritoneal infection,[12] sepsis,[13] vitamin deficiency,[14] surgical technique,[15] surgeon experience,[6] as well as the nature of the surgical intervention and the site of the anastomosis, whether extra- or intraperitoneal.[6] Other influencing factors are blood transfusions,[16] radiotherapy,[17] blood viscosity,[18] presence of drains close to the anastomosis,[19] patient age,[20] clinical nutritional situation,[2] dehydration,[21] uremia,[22] and mechanical intestinal preparation,[23] use of antibiotic prophylaxis in colorectal surgeries,[24] diabetes mellitus,[5] obstructive jaundice,[25] and surgical adhesives,[26] among other clinical conditions. Thalidomide, banned several decades back due to its teratogenic effects, has been pointed out in recent papers as beneficial for the treatment of Crohn’s disease resistant to corticotherapy and of difficult clinical management with conventional drugs.[31,32] Thalidomide has an important immunomodulatory action, inhibiting the action of tumor necrosis factor (TNF) and having anti-angiogenic activity, among others.[33]
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