***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: PURPOSE Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism . There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment . Furthermore , the incidence of such events in these patients is dependent on the achieved International Normalized Ratio ( INR ) . The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR . PATIENTS AND METHODS In a retrospective analysis , the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy . Eligible patients participated in two multicenter , r and omized clinical trials on the initial treatment of venous thromboembolism . Patients were initially treated with heparin ( st and ard or low-molecular weight ) . Treatment with vitamin K antagonists was started within 1 day and continued for 3 months , with a target INR of 2.0 to 3.0 . RESULTS In 1,303 eligible patients ( 264 with malignancy ) , 35  recurrences  and 12  bleeds occurred . Patients with malignancy , compared with nonmalignant patients , had a clinical ly and statistically significantly increased overall incidence of recurrence ( 27.1 v 9.0 , respectively , per 100 patient-years ) as well as bleeding ( 13.3 v 2.1 , respectively , per 100 patient-years ) . In both groups of patients , the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0 . CONCLUSION Although adequately dosed vitamin K antagonists are effective in patients with malignant disease , the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy Cancer patients are at high risk for  venous thromboembolism ( VTE ) . Laboratory parameters with a predictive value for VTE could help stratify patients into high- or low-risk groups . The cell adhesion molecule P-selectin was recently identified as risk factor for VTE . To investigate  soluble P-selectin ( sP-selectin )  in cancer patients as risk predictor for VTE , we performed a prospect i ve cohort study of 687 cancer patients and followed them for a median ( IQR ) of 415 ( 221 - 722 ) days . Main tumor entities were malignancies of the breast ( n = 125 ) , lung ( n = 86 ) , gastrointestinal tract ( n = 130 ) , pancreas ( n = 42 ) , kidney ( n = 19 ) , prostate ( n = 72 ) , and brain ( n = 80 ) ; 91 had hematologic malignancies ; 42 had other tumors .  VTE occurred in 44 ( 6.4 % ) patients . In multivariable analysis , elevated sP-selectin ( cutoff level , 53.1 ng/mL , 75th percentile of study population ) was a statistically significant risk factor for VTE after adjustment for age , sex , surgery , chemotherapy , and radiotherapy ( hazard ratio = 2.6 , 95 % confidence interval , 1.4 - 4.9 , P = .003 ) . The cumulative probability of VTE after 6 months was 11.9 % in patients with sP-selectin above and 3.7 % in those below the 75th percentile ( P = .002 ) . High sP-selectin plasma levels independently predict VTE  in cancer patients . Measurement of sP-selectin at diagnosis of cancer could help identify patients at increased risk for VTE Summary Background Data : The epidemiology of venous thromboembolism ( VTE ) after cancer surgery is based on clinical trials on VTE prophylaxis that used venography to screen deep vein thrombosis ( DVT ) . However , the clinical relevance of asymptomatic venography-detected DVT is unclear , and the population of these clinical trials is not necessarily representative of the overall cancer surgery population . Objective : The aim of this study was to evaluate the incidence of clinical ly overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and to identify risk factors for VTE . Methods : @RISTOS was a prospect i ve observational study in patients undergoing general , urologic , or gynecologic surgery . Patients were assessed for clinical ly overt VTE occurring up to 30 ± 5 days after surgery or more if the hospital stay was longer than 35 days . All outcome events were evaluated by an independent Adjudication Committee . Results : A total of 2373 patients were included in the study : 1238 ( 52 % ) undergoing general , 685 ( 29 % ) urologic , and 450 ( 19 % ) gynecologic surgery . In-hospital prophylaxis was given in 81.6 % and postdischarge prophylaxis in 30.7 % of the patients . Fifty patients ( 2.1 % ) were adjudicated as affected by clinical ly overt VTE ( DVT , 0.42 % ; nonfatal pulmonary embolism , 0.88 % ; death 0.80 % ) . The incidence of VTE was 2.83 % in general surgery , 2.0 % in gynecologic surgery , and 0.87 % in urologic surgery . Forty percent of the events occurred later than 21 days from surgery . The overall death rate was 1.72 % ; in 46.3 % of the cases , death was caused by VTE . In a multivariable analysis , 5 risk factors were identified : age above 60 years ( 2.63 , 95 % confidence interval , 1.21–5.71 ) , previous VTE ( 5.98 , 2.13–16.80 ) , advanced cancer ( 2.68 , 1.37–5.24 ) , anesthesia lasting more than 2 hours ( 4.50 , 1.06–19.04 ) , and bed rest longer than 3 days ( 4.37 , 2.45–7.78 ) . Conclusions : VTE remains a common complication of cancer surgery , with a remarkable proportion of events occurring late after surgery . In patients undergoing cancer surgery , VTE is the most common cause of death at 30 days after surgery Deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) are well recognized complications of cancer . However , our current knowledge of this association is derived from studies conducted more than a decade ago . In light of the changes in medical practice and the improvement in cancer care in recent years , a re-evaluation of the relationship between malignancy and venous thrombosis is in order . Of a total of 1041 patients with solid tumors admitted to 3 major medical centers , there were 81 ( 7.8 % ) diagnosed with DVT/PE .  Patients were more likely to develop DVT/PE during chemotherapy ( p = .0001 ) . Advanced malignancies ( p = .001 ) , renal carcinoma ( p = .005 ) , pancreatic ( p = .001 ) , gastric ( p = .014 ) and brain tumors ( p = .001 ) were independent variables strongly associated with the occurrence of venous thrombosis . The occurrence of thrombotic events in the population tested in this study did not adversely affect survival ( p = .082 ) . The study identifies subset of patients with cancer at high risk for venous thrombosis . Early prophylaxis with anticoagulants in these patients may be warranted . Most importantly , further clinical trials are desperately awaited to detect possible new trends in the frequency and types of thrombotic events and to better define prevention strategies in cancer patients at risk for thrombosis . The association between venous thromboembolic disease ( VTD ) and malignant neoplastic disorders is well known and has been the subject of several reports for more than a century . There is a general agreement among investigators that thrombotic complications in patients with cancer occur at a rather high frequency , and that other circumstantial factors such as surgery or chemotherapy potentiates this risk . However , several important considerations pertaining to cancer and thrombosis continue to be shrouded in controversy . For example , there are inexplicable differences in the proportion of patients with cancer diagnosed with deep venous thrombosis ( DVT ) or pulmonary embolism ( PE ) reported in the literature . In the absence of large well-controlled studies , one may only postulate on the reasons that contributed to these differences . The inclusion of different types of VTD such as superficial , venous , arterial or vascular access device-induced thrombosis may have led to overestimation of the incidence of these events in patients with underlying malignancy . Another possible explanation for this discrepancy relates to the use of a variety of diagnostic and method ological criteria ranging from observation and clinical suspicion to more invasive procedures result ing in considerable differences in the rate of reported clotting events . Along the same line of discussion , one may argue whether VTD is a r and om event or constitutes a complication that occurs more commonly in patients with distinct characteristics and certain tumor types . To further investigate the association between malignancy and thrombosis , we evaluated 1041 patients with solid tumors for the risk of DVT/PE .  The main objectives of the study were to determine the frequency of DVT/PE based on vali date d diagnostic criteria and to identify patients with cancer at high risk for developing these thrombotic episodes . Also , we evaluated the impact of VTD  on the survival of these patients BACKGROUND The B-20 study of the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative , estrogen receptor-positive breast cancer . METHODS Eligible patients ( n = 2306 ) were r and omly assigned to one of three treatment groups following surgery . A total of 771 patients with follow-up data received tamoxifen alone ; 767 received methotrexate , fluorouracil , and tamoxifen ( MFT ) ; and 768 received cyclophosphamide , methotrexate , fluorouracil , and tamoxifen ( CMFT ) . The Kaplan-Meier method was used to estimate disease-free survival , distant disease-free survival , and survival . Reported P values are two-sided . RESULTS Through 5 years of follow-up , chemotherapy plus tamoxifen result ed in significantly better disease-free survival than tamoxifen alone ( 90 % for MFT versus 85 % for tamoxifen [ P = .01 ] ; 89 % for CMFT versus 85 % for tamoxifen [ P = .001 ] ) . A similar benefit was observed in both distant disease-free survival ( 92 % for MFT versus 87 % for tamoxifen [ P = .008 ] ; 91 % for CMFT versus 87 % for tamoxifen [ P = .006 ] ) and survival ( 97 % for MFT versus 94 % for tamoxifen [ P = .05 ] ; 96 % for CMFT versus 94 % for tamoxifen [ P = .03 ] ) . Compared with tamoxifen alone , MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local , regional , and distant sites . Risk of treatment failure was reduced after both types of chemotherapy , regardless of tumor size , tumor estrogen or progesterone receptor level , or patient age ; however , the reduction was greatest in patients aged 49 years or less . No subgroup of patients evaluated in this study failed to benefit from chemotherapy . CONCLUSIONS Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria , regardless of age , lymph node status , tumor size , or estrogen receptor status , are c and i date s for chemotherapy PURPOSE A substantial clinical need exists for an alternative to vitamin K antagonists for treating deep-vein thrombosis in cancer patients who are at high risk of both recurrent venous thromboembolism and bleeding .  Low-molecular-weight heparin , body-weight adjusted , avoids anticoagulant monitoring and has been shown to be more effective than vitamin-K-antagonist therapy . SUBJECTS AND METHODS Subjects were patients with cancer and acute symptomatic proximal-vein thrombosis . We performed a multi-centre r and omized , open-label clinical trial using objective outcome measures comparing long-term therapeutic tinzaparin subcutaneously once daily with usual-care long-term vitamin-K-antagonist therapy for 3 months . Outcomes were assessed at 3 and 12 months . RESULTS Of 200 patients , 100 received tinzaparin and 100 received usual care . At 12 months , the usual-care group had an excess of recurrent venous thromboembolism ; 16 of 100 ( 16 % ) versus 7 of 100 ( 7 % ) receiving low-molecular-weight heparin ( P=.044 ; risk ratio=.44 ; absolute difference -9.0 ; 95 % confidence interval [ CI ] , -21.7 to -0.7 ) . Bleeding , largely minor , occurred in 27 patients ( 27 % ) receiving tinzaparin and 24 patients ( 24 % ) receiving usual care ( absolute difference -3.0 ; 95 % CI , -9.1 to 15.1 ) . In patients without additional risk factors for bleeding at 
    Output:
    
There is convincing evidence to recommend the use of heparins or fondaparinux for prevention of VTE in selected cancer patients , and , especially in some particular types of malignancies and cancer treatments .
Management of VTE in patients with cancer is more challenging and bleeding complications associated with the use of anticoagulants are significantly higher in cancer patients than in those without malignancy .