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Inhibition of Intra-abdominal Adhesion Formation in a Rabbit Model with the Angiogenesis Inhibitor Sunitinib

Jonathon Meisel, Hau D. Le, MD, Vincent E. de Meijer, MD, MSc
Children’s Hospital Boston; Boston, MA


PURPOSE OF STUDY
To determine the effects of sunitinib, a vascular endothelial growth factor receptor (VEGFR) antagonist, on intra-abdominal adhesion formation. Adhesions are the abnormal joining of two normally separate surfaces after surgery, trauma, or infection, and are the number one cause of bowel obstruction and secondary infertility worldwide. They develop as a result of abnormal vascularity, fibrin deposition, inflammatory cell infiltration, and ultimately the formation of a fibrous matrix. More than $2 billion in excess surgical costs and hospitalizations in the United States are a direct result of adhesions.

METHODS USED:
Twenty New Zealand white rabbits underwent a standard uterine adhesion procedure. One day prior to surgery, the rabbits were randomly assigned to be treated with sunitinib (10 mg/kg) or saline control, daily for a total of ten days. On postoperative day ten, the rabbits were sacrificed and their adhesions scored. Adhesions were graded from 0-4 in two categories: tenacity of the adhesions to the uterus and the percentage of the uterus involved.

SUMMARY OF RESULTS:
Thirty-eight percent of the sunitinib treated rabbits were completely adhesion free. The sunitinib treated rabbits had a median tenacity score of 1.0 [IQR 0-1.75; range 0-2] compared to a score of 3.25 (IQR 3-3.5; range 0-4) in the control animals (p=0.004). Median percent involvement score for the sunitinib treated rabbits vs. controls was 1.0 (IQR 0-1.0; range 0-1) and 4.0 (IQR 4.0-4.0; range 0-4) respectively (p=0.003).

CONCLUSIONS:
Adhesion formation is angiogenesis-dependent and is in part mediated through the VEGFR. Sunitinib, a VEGFR antagonist, significantly reduces adhesion formation in a rabbit model.

 

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