Toxicity Study in a Pig Model of Intraperitoneal Collagenase as an "Enzymatic Scalpel" Directed to Breaks Stroma in Order to Generate a New Perspective for Peritoneal Carcinomatosis Approach. An Experimental Research.

Abstract

Background: The purpose of this study was to evaluate the toxicity using collagenase in peritoneal cavity as a preliminary step to generate a treatment that breaks the stroma surrounds the tumors.Methods: 8 pigs were treated at 2 different collagenase concentrations, previously tested in rats by our groups, with time and temperature control using peritoneal lavage system (PRS System, Combat Medical Ltd) identical to use in human surgeries to treatments through HIPEC, plus 2 pigs were treated with peritoneal lavage only. Blood and peritoneal fluid samples were collected pre-treatment, post-treatment and at 24h after treatment. Histological studies and blood collagenase levels were measured.Results: No complications were observed during the surgeries. Images during treatments showed the release of peritoneal tissue during collagenase washes. After surgery the animals showed no signs of pain. Diet and mobility were normal at 4h. There were no significant differences in hematological and biochemical parameters. MMP1 and MMP2 were quantified in all samples and no differences were found in blood collagenase levels between pre-treatment, post-treatment and 24 h post-treatment.None of collagenase treated animals showed peritoneal adhesions at the second surgery. Histologically, peritoneal organs and serous structures, did not show any microscopic alteration associated with collagenase treatment in any groupsConclusion: Lavage of the peritoneal cavity with doses of up to (100,000 Collagen Digestion Unit/animal for 30 minutes is safe and removes connective tissue from the peritoneal cavity.