New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040, Madrid, Spain.
Department of Surgery, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo s/n, 28034, Madrid, Spain.
World J Surg Oncol. 2022 Feb 25;20(1):53. doi: 10.1186/s12957-022-02524-2.
This study aimed to measure the toxicity resulting from collagenase administration to the peritoneal cavity in a pig model as a preliminary step to break down the stroma surrounding tumors.
Eight pigs were treated with 2 different collagenase concentrations previously tested in rats by our group. Time and temperature were controlled using a peritoneal lavage system (PRS System, Combat Medical Ltd.) identical to that used in human surgeries through hyperthermic intraperitoneal chemotherapy (HIPEC); 2 additional pigs were treated with peritoneal lavage only. Samples of blood and peritoneal fluid were collected pre-treatment, immediately after treatment, and 24 h postoperatively. In addition, histological studies and blood collagenase levels were measured.
No complications were observed during the surgeries. Intraoperative images evidenced the release of peritoneal tissue during collagenase treatment. After surgery, the animals showed no signs of pain. Diet and mobility were normal at 4 h postoperatively, and there were no significant differences in hematologic or biochemical parameters. Quantification of MMP1 and MMP2 in all samples as measured by absorbance showed no differences in blood collagenase levels between pre-treatment, post-treatment, and 24 h postoperatively. None of the animals treated with collagenase showed peritoneal adhesions during the second surgery. Histologically, peritoneal organs and serous structures did not show any microscopic alterations associated with collagenase treatment in any group.
Lavage of the peritoneal cavity with doses of up to 100,000 collagen digestion units/animal for 30 min is safe and removes connective tissue from the peritoneal cavity.
本研究旨在通过猪模型测量胶原酶腹腔给药的毒性，作为分解肿瘤周围基质的初步步骤。
8 头猪接受了我们小组之前在大鼠中测试过的 2 种不同胶原酶浓度的治疗。使用与人类腹腔热灌注化疗（HIPEC）中使用的相同的腹腔灌洗系统（PRS 系统，Combat Medical Ltd.）控制时间和温度；另外 2 头猪仅接受腹腔灌洗。在治疗前、治疗后立即和术后 24 小时采集血液和腹腔液样本。此外，还进行了组织学研究和血液胶原酶水平的测量。
手术过程中未观察到并发症。术中图像证明了胶原酶治疗过程中腹膜组织的释放。手术后，动物没有疼痛迹象。术后 4 小时饮食和活动能力正常，血液学或生化参数无显著差异。通过吸光度测量所有样本中 MMP1 和 MMP2 的定量，治疗前、治疗后和术后 24 小时的血液胶原酶水平没有差异。在第二次手术中，没有接受胶原酶治疗的动物出现腹膜粘连。组织学上，腹膜器官和浆膜结构在任何组中均未显示与胶原酶治疗相关的任何微观改变。
用高达 100,000 胶原消化单位/动物的剂量冲洗腹腔 30 分钟是安全的，可以从腹腔中清除结缔组织。
