Prognosis of ovarian cancer subsequent to venous thromboembolism: a nationwide Danish cohort study

BACKGROUND: Venous thromboembolism (VTE) is associated with ovarian cancer and may impact the prognosis of ovarian cancer. Our aims were to examine the extent of disease at the time of the diagnosis of ovarian cancer and to estimate the impact of VTE on survival of ovarian cancer. METHODS: We identified 12,835 ovarian cancer patients diagnosed from 1980 to 2003 in the Danish Cancer Registry and obtained information on previous primary VTE diagnosis from the Danish National Hospital Discharge Registry. Ovarian cancer patients with previous VTE related to other cancers, surgery, or pregnancy were excluded. The vital status was determined by linking data to the Civil Registration System. RESULTS: We identified 50 ovarian cancer patients diagnosed less than 4 months after the VTE and 78 ovarian cancer patients diagnosed more than 4 months after the VTE diagnosis. Advanced stages tended to be more common among patients with VTE. One-year survivals were 44% and 54% among the two VTE groups, compared with 63% among patients without VTE. Adjusted (for age, calendar time, comorbidity, and FIGO-stage) mortality ratios were 1.7 (95% CI = 1.2–2.5) and 1.2 (95% CI = 0.8–1.7), respectively. CONCLUSION: Ovarian cancer diagnosed less than four months before VTE is associated with an advanced stage and a poorer prognosis

High incidence of silent venous thromboembolism before treatment in ovarian cancer

Venous thromboembolism (VTE) such as deep-vein thrombosis (DVT) and pulmonary thromboembolism (PTE) often occurs after surgery and rarely occurs even before surgery in patients with ovarian cancer. It is well known that levels of plasma D-dimer (DD) before treatment in most ovarian cancer patients are increased. This study therefore examined whether increased levels of DD are associated with presence of VTE before treatment of ovarian cancer. Between November 2004 and March 2007, DD levels prior to initial treatment were measured in 72 consecutive patients with presumed epithelial ovarian cancer (final diagnosis: epithelial ovarian cancer, n=60; and epithelial ovarian borderline malignancy, n=12). Venous ultrasound imaging (VUI) of the lower extremity was conducted for all patients except for two patients in whom DVT was detected by pelvic computed tomography (CT). When DVT was found, pulmonary scintigraphy was subsequently performed to ascertain presence of PTE. D-dimer levels were above the cut-off value (0.5 μg ml−1) in 65 of 72 patients (90.2%). Venous ultrasound imaging or CT revealed DVT in 18 of 72 patients (25.0%) and pulmonary scintigraphy found PTE in 8 patients (11.1%). All patients with VTE were asymptomatic when VTE was found. D-dimer levels were associated with incidence of VTE (0–1.4 μg ml−1; 0 of 26 (0%), 1.5–7.4 μg ml−1; 9 of 30 (30%) and ⩾7.5 μg ml−1; 9 of 16 (56.3%), P for trend=0.0003). However, even if 1.5 μg ml−1 was used as a cut-off value, this had low specificity and positive predictive value (47.2, 38.3%), though it had high sensitivity and negative predictive value (100, 100%). Therefore, ovarian cancer patients with DD level ⩾1.5 μg ml−1 should be examined using VUI to detect silent DVT. Patients with VTE underwent preventive managements including anticoagulant therapy before initial treatment, chemotherapy or surgery, and after surgery. There was no clinical onset of postoperative VTE in all 72 patients. Measurement of DD levels and subsequent ultrasonography revealed that silent or subclinical VTE frequently occurs before surgery in ovarian cancer. The usefulness of preoperative assessment of VTE needs further confirmation in randomised controlled trials

Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer

Venous thromboembolism (VTE) following breast cancer chemotherapy is common. Chemotherapy-induced alterations in markers of haemostasis occur during chemotherapy. It is unclear how rapidly this occurs, whether this is upregulated in patients developing VTE and whether changes predict for VTE. Markers of haemostasis, functional clotting assays and vascular endothelial growth factor were measured before chemotherapy and at 24 h, 4 days, 8 days and 3 months following commencement of chemotherapy in early and advanced breast cancer patients and in age- and sex-matched controls. Duplex ultrasound imaging was performed after 1 month or if symptomatic. Of 123 patients, 9.8% developed VTE within 3 months. Activated partial thromboplastin time (APTT), prothrombin time (PT), D-dimer, fibrinogen, platelet count, VEGF and fibrinogen were increased in cancer. Fibrinogen, D-dimer, VEGF and tissue factor were increased, at baseline, in patients subsequently developing VTE. D-dimer of less than 500 ng ml−1 has a negative predictive value of 97%. Activated partial thromboplastin time, PT and thrombin–antithrombin showed significantly different trends, as early as within 24 h, in response to chemotherapy in patients subsequently developing VTE. Markers of coagulation and procoagulants are increased, before chemotherapy, in patients who subsequently develop VTE. A group of patients at minimal risk of VTE can be identified, allowing targeted thrombopropylaxis to the higher risk group

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

Venous thromboembolism (VTE) often occurs after surgery and can even occur before surgery in patients with gynaecological malignancies. We investigated the incidence of VTE before treatment of endometrial cancer and associated risk factors. Plasma D-dimer (DD) levels before initial treatment were examined in 171 consecutive patients with endometrial cancer. Venous ultrasound imaging (VUI) of the lower extremities was performed in patients with DD ⩾1.5 μg ml−1, as the negative predictive value of DD for VTE is extremely high. For patients with deep vein thrombosis (DVT), pulmonary scintigraphy was performed to ascertain the presence of pulmonary thromboembolism (PTE). Risk factors for VTE were analysed using univariate and multivariate analyses for 171 patients. Of these, 37 patients (21.6%) showed DD ⩾1.5 μg ml−1, 17 (9.9%) displayed DVT by VUI and 8 (4.7%) showed PTE on pulmonary scintigraphy. All patients with VTE were asymptomatic. Univariate analysis for various risk factors revealed older age, non-endometrioid histology and several variables of advanced disease as significantly associated with VTE before treatment. Obesity, smoking and diabetes mellitus were not risk factors. Multivariate analysis confirmed extrauterine spread and non-endometrioid histology as independently and significantly associated with risk of VTE. These data suggest that silent or subclinical VTE occurs before treatment in at least around 10% of patients with endometrial cancer. Risk factors for VTE before treatment might not be identical to those after starting treatment

Placental Malaria is associated with reduced early life weight development of affected children independent of low birth weight

<p>Abstract</p> <p>Background</p> <p>Infection with <it>Plasmodium falciparum </it>during pregnancy contributes substantially to the disease burden in both mothers and offspring. Placental malaria may lead to intrauterine growth restriction or preterm delivery resulting in low birth weight (LBW), which, in general, is associated with increased infant morbidity and mortality. However, little is known about the possible direct impact of the specific disease processes occurring in PM on longer term outcomes such as subsequent retarded growth development independent of LBW.</p> <p>Methods</p> <p>In an existing West-African cohort, 783 healthy infants with a birth weight of at least 2,000 g were followed up during their first year of life. The aim of the study was to investigate if <it>Plasmodium falciparum </it>infection of the placenta, assessed by placental histology, has an impact on several anthropometric parameters, measured at birth and after three, six and 12 months using generalized estimating equations models adjusting for moderate low birth weight.</p> <p>Results</p> <p>Independent of LBW, first to third born infants who were exposed to either past, chronic or acute placental malaria during pregnancy had significantly lower weight-for-age (-0.43, 95% CI: -0.80;-0.07), weight-for-length (-0.47, 95% CI: -0.84; -0.10) and BMI-for-age z-scores (-0.57, 95% CI: -0.84; -0.10) compared to infants born to mothers who were not diagnosed with placental malaria (p = 0.019, 0.013, and 0.012, respectively). Interestingly, the longitudinal data on histology-based diagnosis of PM also document a sharp decline of PM prevalence in the Sukuta cohort from 16.5% in 2002 to 5.4% in 2004.</p> <p>Conclusions</p> <p>It was demonstrated that PM has a negative impact on the infant's subsequent weight development that is independent of LBW, suggesting that the longer term effects of PM have been underestimated, even in areas where malaria transmission is declining.</p