Conditioning of the abdominal cavity reduces tumor implantation in a laparoscopic mouse model

Abstract

PurposeThe addition of 4 % O2 and 10 % N2O to the CO2 pneumoperitoneum (PP), together with slight cooling and humidification (conditioning), contributes to reducing adhesions by preventing mesothelial damage. We investigated the effect of peritoneal damage during laparoscopy on tumor implantation.MethodsIn Experiment 1, different tumor cell concentrations were injected into control mice without PP and into mice with 60-min dry CO2PP (mesothelial damage). In Experiment 2, tumor cells were injected into control mice (group I) and in mice with mesothelial damage (group II). In groups III to VI, mesothelial damage was decreased by adding humidification, humidification + 10 % N2O, humidification + 10 % N2O + 4 % O2, and conditioning, respectively.ResultsIn Experiment 1, the tumors increased with the number of cells injected and with mesothelial damage in the abdominal cavity (p = 0.018) and abdominal wall (p < 0.0001). Experiment 2 confirmed that 60 min of dry CO2PP increased the number of tumors in the abdominal cavity and wall (p = 0.026 and p = 0.003, respectively). The number of tumors was decreased in the abdominal cavity by conditioning (p = 0.030) and in the abdominal wall using humidified CO2 (p = 0.032) or conditioning (p = 0.026).ConclusionsTumor implantation was enhanced by peritoneal damage (60 min of dry CO2PP and desiccation), but this was prevented by conditioning. If confirmed in humans, conditioning would become important for oncologic surgery.

Laparoscopic management and prevention of pelvic adhesions and postoperative pain

“…The single most effective factor, however, is the addition of > 5% of N 2 O to the pneumoperitoneum. In animal models, N 2 O has a half maximal effect at a concentration of 2.5% and a full effect from 5% onward as demonstrated for 100% N 2 O , Koninckx et al 2014. This points to an unknown drug-like effect of N 2 O, although the mechanism of action is unknown.…”

“…Prevention of acute inflammation strongly reduces pain during surgery, reduces CO 2 adsorption and metabolic acidosis, and reduces adhesions by about 85%. It is expected that this also will reduce postoperative fatigue , tumor cell implantation (Binda et al 2014), ovarian damage, and leaks after bowel surgery. It is unclear to what extent the faster recovery of bowel movements and metabolism plays a role.…”

Changes in the coelomic microclimate during carbon dioxide laparoscopy: morphological and functional implications

“…Reducing peritoneal desiccation, peritoneal inflammation [5,69] and cytokine generation can also potentially inhibit cancer cell interaction with peritoneal mesothelial cells and the ECM [18,90,91]. This, however, does not completely prevent tumour cell adherence and proliferation [18].…”

“…Prevention of initial tumour implantation by warmed humidified CO 2 vs. cold-dry CO 2 -pneumoperitoneum may be related to preservation of the peritoneal mesothelial glycocalyx, microvilli and high molecular weight HA [13,18,29,91]. Reducing peritoneal desiccation, peritoneal inflammation [5,69] and cytokine generation can also potentially inhibit cancer cell interaction with peritoneal mesothelial cells and the ECM [18,90,91].…”

“…The contribution of high vs. low pressure pneumoperitoneum in modifying perioperative complications, adhesion formation, postoperative pain, anastomotic healing, tumour metastasis, and venous thromboembolism in human subjects remains to be established [40-43, 67, 94]. To enhance the protective effects of humidified pneumoperitoneum in the prevention of transcoelomic metastasis, additional interventions must be capable of protecting peritoneal mesothelial cells and the peritoneal glycocalyx, decreasing free radical, cytokine and growth factor production, inhibiting adhesion, attachment and activation of cancer cells, preventing peritoneal mesothelial cell senescence/MMT and macrophage immunotolerance [5,18,72,80,85,88,90,91].…”