Inhibition of peritoneal dissemination of colon cancer by hyperthermic CO2 insufflation: A novel approach to prevent intraperitoneal tumor spread

PLoS One. 2017 Feb 16;12(2):e0172097. doi: 10.1371/journal.pone.0172097. eCollection 2017.

Abstract

Background: The increasing use of laparoscopic surgery for advanced gastrointestinal cancer raises concerns about intra-peritoneal tumor spread. Prevention of peritoneal dissemination is extremely important but a preventive modality is lacking. The aim of this study was to examine a novel approach (hyperthermic CO2 insufflation, HT-CO2) for preventing peritoneal dissemination during laparoscopic surgery.

Methods: A peritoneal dissemination model was established in Balb/c nu/nu mice by intraperitoneal injection of human colon cancer cells (SW1116, 1×106). The mice (n = 48) were subsequently randomized into two groups and subjected to hyperthermic CO2 (43°C, >95% humidity, HT-CO2 group) or standard normothermic CO2 (21°C, <1% relative humidity, NT-CO2 group) insufflation for 3 hours. The mice were sacrificed 28 days later. The peritoneal dissemination was quantitatively analyzed by counting and weighing the peritoneal nodules. The port sites and ascites volume were measured. The peritoneal damage of HT-CO2 was histologically examined with light microscopy and scanning electron microscopy. Intra-abdominal adhesions were evaluated 4 weeks later.

Results: The number of peritoneal nodules in the HT-CO2 group was significantly less than that in the NT-CO2 group (10.21±3.72 vs. 67.12±5.49, P<0.01). The mean weight of metastatic tumors in the HT-CO2 group was significantly lower than that in the NT-CO2 group (0.31±0.10g vs. 2.16±0.31g, P<0.01). Massive ascites were found in the NT-CO2 group while significantly less ascites developed in HT-CO2- treated mice (8.26±0.31ml vs. 1.27±0.28ml, P<0.01). No port-site metastases were detected in the HT-CO2 group while the incidence of the NT-CO2 group was 12.5% (3/24). HT-CO2 subjection resulted in slight peritoneal damage; the peritoneum returned to normal within five days. No adhesions formed after HT-CO2 treatment.

Conclusions: HT-CO2 can suppress peritoneal dissemination of colon cancer cells and only causes slight and transient peritoneal damage. HT-CO2 may serve as a promising adjuvant treatment for preventing peritoneal dissemination in laparoscopic resection of advanced colorectal cancer.

MeSH terms

  • Animals
  • Carbon Dioxide / administration & dosage*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery*
  • Fever*
  • Injections, Intraperitoneal
  • Insufflation / methods*
  • Laparoscopy*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Seeding
  • Peritoneal Neoplasms / prevention & control*
  • Peritoneal Neoplasms / secondary
  • Peritoneum / drug effects*
  • Peritoneum / injuries
  • Peritoneum / pathology

Substances

  • Carbon Dioxide

Grants and funding

This work was supported by the grants from National Natural Science Foundation of China (No. 81572296), the Young Backbone talents Training Foundation of the Fujian healthcare system (No.2013-ZQN-JC-9). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.