Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery

Abstract

BACKGROUND: The association between cancer, major surgery and venous thromboembolism (VTE) is well established. Multimodal therapy is increasingly being used as standard treatment for localised gastrointestinal cancer. The aim of this study was to examine the markers of pro-coagulation response and VTE risk in an exemplar multimodal model of pre-operative combination chemotherapy and radiation therapy, followed by complex cancer surgery. METHODS: Consecutive patients (n ¼ 36) with localised oesophageal cancer were studied at baseline after the first and second cycles of chemoradiation, and on post-operative days 1 -28, and at 3, 6 and 9 months. Factors regulating the pro-and anti-coagulant response, as well as pro-inflammatory markers including NFkB activation in peripheral blood mononuclear cells, were examined. All patients received enoxaparin 40 mg s.c. postoperatively up to discharge, and underwent pulmonary CT-pulmonary angiography and venography on day 10 postoperatively. RESULTS: Four (11%) non-fatal thromboembolic events were documented, all after hospital discharge. Neoadjuvant therapy before surgery activated factor VIII (FVIII) and pro-inflammatory NFkB, and increased D-dimers, pro-thrombin fragment 1 þ 2 (F1 þ 2) and the thrombin-anti-thrombin complex (TAT). Surgery significantly (Po0.05) increased pro-thrombin time (PT), activated partial thromboplastin time, fibrinogen, D-dimers, TAT, F1 þ 2 and FVIII up to 6 months. CONCLUSION: These data highlight the linked pro-coagulant and immunoinflammatory pathways in the multimodal management of oesophageal cancer, and suggest that the duration of current standard thromboprophylaxis regimens warrants further study.

Identifying Esophagectomy Patients at Risk for Predischarge Versus Postdischarge Venous Thromboembolism

“…The issue, therefore, is to determine which patients truly benefit from extended-duration Multimodality therapy, which is the standard of care, may also increase the VTE risk for esophageal cancer patients being properly treated within a multidisciplinary treatment plan [21]. One recent study demonstrated that modern trimodality (chemoradiation plus surgery) esophageal therapy is associated with a measurable prothrombotic state, persistent for as long as 6 months after surgery [22]. In that study, neoadjuvant therapy was associated with activation of factor VIII, proinflammatory nuclear factor-kb, prothrombin, and the thrombinantithrombin complex.…”

Independent predictors of complication following surgery for spinal metastasis

“…Deep vein thrombosis and pulmonary embolus were also one of the most common complications experienced in our cohort and a cause of death in one patient. It is well known that patients with cancer are intrinsically hypercoagulable, and even more so following surgery [17]. As deep vein thrombosis and pulmonary embolus are highly morbid and can lead to mortality, in addition to low molecular weight heparin prophylaxis, it is highly recommended that patients be mobilized as soon as it is deemed safe [4].…”

Persistence of Hypercoagulable State after Resection of Intra-Abdominal Malignancies

“…[14][15][16][17] However, there is a paucity of literature describing longitudinal coagulation changes in cancer patients. 14,18 The purpose of this study was to use ROTEM to prospectively evaluate the coagulation status of patients undergoing operative resection of intra-abdominal malignancies for curative intent. We hypothesized that the majority of patients would be hypercoagulable preoperatively and the hypercoagulable state would reverse after tumor resection.…”