Hyaluronic acid secretion during carbon dioxide pneumoperitoneum and its association with port-site metastasis in a murine model

Background: The mechanism of port-site metastasis after laparoscopic cancer surgery is unclear. This study aimed to determine whether carbon dioxide (CO2) pneumoperitoneum caused an increase in hyaluronic acid, which is secreted from mesothelial cells of the peritoneal cavity, and to assess the risk for port-site metastasis using a murine pneumoperitoneal model. Methods: Sandwich-binding protein assay was used to measure the concentration of hyaluronic acid in the peritoneal cavity at 6, 12, 18, 24, 48, and 72 h after CO2 pneumoperitoneum or laparotomy for 30 min. The concentrations of hyaluronic acid during pneumoperitoneum were compared among different gases (CO2, helium, air), intervals (5, 30, 60 min), and pressures (0-2, 4-6, 8-10 mmHg). To investigate the effects of exogenous hyaluronic acid, the development of port-site metastasis was examined using mouse adenocarcinoma cell-line colon 26 cells. Results: The intraperitoneal concentration of hyaluronic acid after CO2 pneumoperitoneum had increased already at 6 h, had reached the maximum level at 24 h, and had begun to decrease at 72 h. The concentration of hyaluronic acid at 24 h and 48 h in the CO2 pneumoperitoneum group was higher than that in the laparotomy group. This increase in hyaluronic acid also was found during helium and air pneumoperitoneum, and the concentration of hyaluronic acid in the peritoneal cavity was at its maximum when CO2 pneumoperitoneum lasted 30 min at 4 to 6 mmHg. The frequency of port-site metastasis was the highest when hyaluronic acid was injected during CO2 pneumoperitoneum (100%). Conclusions: In a murine model, the intraperitoneal concentration of hyaluronic acid was significantly increased after CO2 pneumoperitoneum, and the increase was more evident than that after laparotomy. Increased hyaluronic acid during pneumoperitoneum may be associated with port-site metastasis after laparoscopic cancer surgery.