Efficacy and Safety of Low-Molecular-Weight Heparin on Prevention of Venous Thromboembolism after Laparoscopic Operation for Gastrointestinal Malignancy in Japanese Patients: A Multicenter, Open-Label, Prospective, Randomized Controlled Trial

Background: The risk of venous thromboembolism (VTE) after surgery for malignancy in Japanese patients is unclear; therefore, standard prevention protocols have not been established, especially for minimally invasive procedures. We aimed to investigate the additional effect of low molecular weight heparin (LMWH) on prevention of VTE after laparoscopic surgery for gastrointestinal malignancy. Study Design: From February 2013 to January 2017, 400 patients scheduled for laparoscopic surgery were included. Cases were randomly allocated to the physical therapy group (Control group; 201 patients) or to the combination-therapy group (LMWH group; 199 patients), in which enoxaparin sodium (20 mg [= 2000 IU] twice a day) was administered for 1 week postoperatively in addition to the physical therapy. A diagnosis of VTE was made by contrast-enhanced CT or ultrasonography when symptomatic or D-dimer was ≥10 μg/mL. Results: VTE was observed in 1.2% and 4.0% of patients in the LMWH and Control groups, respectively (odds ratio [OR] 0.3, 95% confidence interval [CI] 0.03–1.53). Pulmonary embolism was confirmed only in the Control group (1.7%). No major bleeding occurred in either group. Logistic multiple regression analysis revealed that surgical time extension (OR 1.02, 95% CI 1.00–1.04) was a risk factor of VTE, while administration of LMWH (OR 0.21, 95% CI 0.03–0.99), male sex (OR 0.12, 95% CI 0.01–0.60), and early cancer (OR 0.17, 95% CI 0.02–0.82) reduced the risk of VTE. Conclusions: Postoperative LMWH administration is safe. The additional effect of LMWH administration on the physical therapy was not statistically proven in this study. However, it could be useful for the patients with risk factors such as female sex, long operation time, and higher cancer stage.