Luo H-X, Yu P-W, Hao Y-X, Zhao Y-L, Shi Y, Tang B
Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Eur Surg Res. 2012;48(1):40-7. doi: 10.1159/000334282. Epub 2011 Dec 22.
Whether laparoscopy with CO(2) pneumoperitoneum affects the peritoneal metastasis of gastric cancer is a pressing question. In light of the important impact change in peritoneal macrophage function has on the peritoneal metastasis of gastric cancer, this study investigated the change in peritoneal macrophage function in gastric cancer in the CO(2) pneumoperitoneum environment, as well as its effect on the peritoneal metastasis of gastric cancer.
An orthotopic transplantation model of murine forestomach carcinoma was established using the 615 mouse line. The mice bearing tumors were randomly divided into four groups (30 mice each group): anesthesia alone, laparotomy, mini-laparotomy, and CO(2) insufflation. After the operation, peritoneal macrophages were collected from 6 mice in each group and cultured. The phagocytosis of neutral red by macrophages and the levels of NO, TNF-α, IL-10, and VEGF produced by macrophages were measured after 12, 24, 48, and 72 h of culture. The remaining mice were observed after 2 weeks for the rate of peritoneal metastasis of forestomach carcinoma cells and the total weight of implanted nodules.
In the laparotomy group, 4 mice died intraoperatively and 2 died in the CO(2) insufflation group. The uptake of neutral red by peritoneal macrophages and the levels of NO, TNF-α, IL-10, and VEGF secreted by peritoneal macrophages in the laparotomy group and mini-laparotomy group after 12 h of culture were all significantly higher than those in the anesthesia-alone group (p < 0.05). The corresponding levels in the CO(2) insufflation group after 12 h were all significantly lower than those in the anesthesia-alone group (p < 0.05). There were no significant differences among the four groups at 24, 48, and 72 h after culture. Comparing with those in the laparotomy group, the uptake of neutral red by peritoneal macrophages and the levels of NO, TNF-α, IL-10, and VEGF secreted by peritoneal macrophages in the CO(2) insufflation group were all significantly lower after 12 h of culture (p < 0.05), but did not differ significantly at 24, 48, and 72 h of culture (p > 0.05), and did not differ significantly in the mini-laparotomy group at all the time (p > 0.05). The rate of peritoneal metastasis of mouse forestomach carcinoma was 50% in the laparotomy group, 45.83% in the mini-laparotomy group, and 45.45% in the CO(2) insufflation group; this difference was not statistically significant (p > 0.05). The total weight of implanted nodules of mouse forestomach carcinoma was 1.02 ± 0.38 g in the laparotomy group, 0.97 ± 0.41 g in the mini-laparotomy group, and 0.93 ± 0.45 g in the CO(2) insufflation group, which was not a statistically significant difference (p > 0.05).
CO(2) pneumoperitoneum neither significantly changes the phagocytosis and cytokine secretion functions of peritoneal macrophages in gastric cancer-bearing mice nor significantly promotes peritoneal metastasis of gastric cancer.
二氧化碳气腹腹腔镜手术是否会影响胃癌的腹膜转移是一个亟待解决的问题。鉴于腹膜巨噬细胞功能的改变对胃癌腹膜转移具有重要影响，本研究探讨了在二氧化碳气腹环境下胃癌小鼠腹膜巨噬细胞功能的变化及其对胃癌腹膜转移的影响。
采用615小鼠品系建立小鼠前胃癌原位移植模型。将荷瘤小鼠随机分为四组（每组30只）：单纯麻醉组、开腹组、小切口开腹组和二氧化碳气腹组。术后，每组取6只小鼠收集腹膜巨噬细胞并进行培养。培养12、24、48和72小时后，检测巨噬细胞对中性红的吞噬作用以及巨噬细胞产生的一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）和血管内皮生长因子（VEGF）水平。其余小鼠在2周后观察前胃癌细胞的腹膜转移率和种植结节的总重量。
开腹组有4只小鼠术中死亡，二氧化碳气腹组有2只小鼠死亡。培养12小时后，开腹组和小切口开腹组腹膜巨噬细胞对中性红的摄取以及腹膜巨噬细胞分泌的NO、TNF-α、IL-10和VEGF水平均显著高于单纯麻醉组（p < 0.05）。二氧化碳气腹组培养12小时后的相应水平均显著低于单纯麻醉组（p < 0.05）。培养24、48和72小时后，四组之间无显著差异。与开腹组相比，二氧化碳气腹组培养12小时后腹膜巨噬细胞对中性红的摄取以及腹膜巨噬细胞分泌的NO、TNF-α、IL-10和VEGF水平均显著降低（p < 0.05），但在培养24、48和72小时时无显著差异（p > 0.05），小切口开腹组在所有时间均无显著差异（p > 0.05）。小鼠前胃癌的腹膜转移率在开腹组为50%，小切口开腹组为45.83%，二氧化碳气腹组为45.45%；差异无统计学意义（p > 0.05）。小鼠前胃癌种植结节的总重量在开腹组为1.02±0.38 g，小切口开腹组为0.97±0.41 g，二氧化碳气腹组为0.93±0.45 g，差异无统计学意义（p > 0.05）。
二氧化碳气腹既不会显著改变荷胃癌小鼠腹膜巨噬细胞的吞噬和细胞因子分泌功能，也不会显著促进胃癌的腹膜转移。
