The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets. IntroductionCancer remains a devastating cause of mortality worldwide, with the majority of patients dying as a result of metastasis (1-3). Currently, locoregional control in the form of complete oncologic resection remains an essential curative modality for nearly all solid tumors and provides improved overall and disease-free survival (2, 4,5). Control of distant recurrence is predominantly achieved through systemic chemotherapy, with variable results (6-8). However, standard oncologic interventions can have negative consequences. First, manipulation of the primary tumor during surgery is associated with increased numbers of circulating tumor cells (CTCs) (9). Second, infectious complications occur as a result of cancer progression itself, such as bowel obstruction or pneumonia (10, 11), and due to complications of standard cancer treatments, such as chemotherapy and surgery (12)(13)(14).Postsurgical infections occur with alarming frequency, with an incidence approaching 40% in some series (15)(16)(17). Given that the majority of the nearly 2 million patients diagnosed with cancer in 2012 in the United States alone underwent at least one surgical procedure, the tremendous potential burden of infection becomes apparent (18). One disturbing feature of severe infectious complications in patients with cancer is their association with adverse oncologic outcomes independent of the morbidity associated with the infectious insult (14,(19)(20)(21). This phenomenon has been observed across a broad range of malignancies, including lung, esophageal, breast, ovarian, and colorectal cancer, whereby severe postoperative infectious complications, such as pneumonia, peritonitis, and sepsis, are significantly associated wit...

Although circulating neutrophils are associated with distant metastasis and poor outcome in a number of epithelial malignancies, it remains unclear whether neutrophils play an active causal role in the metastatic cascade. Using in vivo models of metastasis, we found that neutrophils promote cancer cell adhesion within liver sinusoids and, thereby, influence metastasis. Neutrophil depletion before cancer cell inoculation resulted in a decreased number of gross metastases in an intrasplenic model of liver metastasis. This effect was reversed when inflamed neutrophils were co-inoculated with cancer cells. In addition, early adhesion within liver sinusoids was inhibited in the absence of neutrophils and partially restored with a short perfusion of isolated activated neutrophils. Intravital microscopy showed that cancer cells adhered directly on top of arrested neutrophils, indicating that neutrophils may act as a bridge to facilitate interactions between cancer cells and the liver parenchyma. The adhesion of lipopolysaccharide-activated neutrophils to cancer cells was mediated by neutrophil Mac-1/ICAM-1. Our findings, therefore, show a novel role for neutrophils in the early adhesive steps of liver metastasis. Cancer Res; 72(16);

The LCP is an effective bridging device used for treating comminuted fractures, but for treating simple fractures its superiority over conventional plating is yet to be proven.