*Section of Colon and Rectal Surgery, Department of Surgery, Hospital del Mar, Barcelona, Spain †Colorectal Cancer Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain ‡Biomed Division, Leitat Technological Center, Barcelona, Spain §Consulting Service on Methodology for Biomedical Research, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Ann Surg. 2014 Nov;260(5):939-43; discussion 943-4. doi: 10.1097/SLA.0000000000000958.
The aim of this study was to investigate the effect of postoperative peritoneal infection on proliferation, migration, and invasion capacities of cancer cells lines in vitro after surgery for colorectal cancer.
Anastomotic leakage is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may enhance tumor progression features of residual cancer cells.
Prospective matched cohort study. Patients undergoing surgery for colorectal cancer with curative intent (January 2008-March 2012) were included. Patients who had an anastomotic leak or intra-abdominal abscess were included in the infection group (n=47). For each case patient, another patient with an uncomplicated postoperative course was selected for the control group (n=47).In vitro treatments on cancer cell lines (MDA-MB-231 and SW620) were performed using baseline and postoperative serum and peritoneal fluid samples to determine cell proliferation and cell migration/invasion activities.
Postoperative peritoneal fluid from infected patients enhanced both cell migration (infection: 140±85 vs control: 94±30; P=0.016) and cell invasion (infection: 117±31 vs control: 103±16; P=0.024) capacities of cancer cell lines. With serum samples, these effects were only observed in cell migration assays (infection: 98±28 vs control: 87±17; P=0.005). Some minor activation of cell proliferation was observed by treatment with serum from infection group. Two-year cumulative disease-free survival was significantly lower in patients with postoperative peritoneal infection (infection: 77.6% vs control: 90.6%; P=0.032).
Our results suggest that postoperative peritoneal infection enhances the invasive capacity of residual tumor cells after surgery, thus facilitating their growth to recurrent tumors.
本研究旨在探讨结直肠癌术后腹膜感染对癌细胞系体外增殖、迁移和侵袭能力的影响。
吻合口漏与结直肠癌手术后复发率较高有关。然而，其机制尚不清楚。我们假设感染引起的炎症反应可能增强残留癌细胞的肿瘤进展特征。
前瞻性匹配队列研究。纳入 2008 年 1 月至 2012 年 3 月接受结直肠癌根治术的患者。吻合口漏或腹腔脓肿患者纳入感染组（n=47）。对于每个病例患者，选择另一名术后无并发症的患者作为对照组（n=47）。使用基线和术后血清和腹腔液样本对癌细胞系（MDA-MB-231 和 SW620）进行体外处理，以确定细胞增殖和细胞迁移/侵袭活性。
感染患者的术后腹腔液增强了癌细胞系的迁移能力（感染：140±85 比对照：94±30；P=0.016）和侵袭能力（感染：117±31 比对照：103±16；P=0.024）。使用血清样本，仅在细胞迁移测定中观察到这些效应（感染：98±28 比对照：87±17；P=0.005）。用感染组血清处理后观察到细胞增殖有轻微激活。术后腹膜感染患者的 2 年无复发生存率明显较低（感染：77.6%比对照：90.6%；P=0.032）。
我们的结果表明，术后腹膜感染增强了手术后残留肿瘤细胞的侵袭能力，从而促进了它们向复发性肿瘤的生长。
