After VTE occurred in malignant disease was reported, the likelihood between VTE and a variety of cancer including endometrial cancer was extensively investigated. The recent study reported that endometrial cancer patients with high incidence of VTE were corrected with an increased risk of death [19]. In addition, researchers investigated that VTE in endometrial cancer was related with tumor invasion and cause undesirable influence on the quality of economy and life due to its complications [20].Therefore, it is essential to identify the relevant risk factors contributing to VTE, which can help to form strategies to prevent VTE and improve the survival prognosis of women with endometrial cancer.
The present study was conducted on the basis of 8 observational studies, indicating that VTE was a relatively common complication in endometrial cancer patients after surgery. The results revealed that the pooled accidence of VTE in endometrial cancer was about 7% in endometrial cancer patients with substantial heterogeneity. In view of the huge heterogeneity may weaken the quality of the pooled estimate, we subgroup the study based on the human race. The heterogeneity didn’t reduce due to the other confounding factor such as sample size, publication time and NOS score.
The associated risk factors for developing VTE in cancer patients can be grouped into patient-related factors, tumor-related factors, treatment-related factors, and biomarkers [21]. The present study identified relevant risk factors associated with postoperative VTE in endometrial cancer patients including age>60, tumor size in uterine cavity(༞60mm), tumor extension (CT/MRI), massive ascites, clear cell cancer, advanced stage and CA125(༞35U/ml), which can help clinical physicians to make decision to help manage the specific population of relevant specific risk. For the prevention of postoperative VTE, physician guided patients wear elastic stockings after surgery or applied anticoagulant treatment by low molecular weight heparin [22].
We identified advanced age as patient-related factors associated with VTE after operation in endometrial cancer. A number of researchers have found that the age was an effective predictor for VTE in endometrial cancer patients. Krantz [23] and colleagues reported that increasing age were independent predictors of receiving unfractionated heparin. Bhayadia showed that age was a risk factor causing vascular damage, as aging and senescence induced by telomere shortening lead to endothelial dysfunction and increased the accidence of VTE [24].With increased age, women inevitable experienced menopause, which was the last menstrual period and indicated the end of women reproductive potential ability [25]. The research conducted by Huang [16] indicated the OR of menopause for VTE was 2.90 (95%CI: 1.028-8.19).However, the present meta-analysis showed that menopause was not associated with VTE in endometrial cancer patients, which need more researches included to explore exact the relationship between menopause and VTE. Another patient-related factor, the obesity not only impacts the body weight but also influences insulin resistance as well as blood coagulation [26]. Although a number of studies [8–10] have reported that the elevated body mass index (BMI) is a danger signal of venous thromboembolism in population, the present data in our study reveal that the BMI was not a certain factor of VTE for patients with endometrial cancer after operation. Considering the heterogeneity in current systematic review, the potential role of BMI should further be investigated.
Tumor-related factors including extensive tumor lesion,massive ascites, clear cell cancer and advanced stage were identified associated with VTE. The volume of ascites indicated the inflammatory conditions in tumors, which contribute to the development of venous thromboembolic events [27]. Moreover, the patients with malignant disease usually suffered with hypercoagulable state, which may be the reason of massive ascites and contribute to VTE after operation [28]. Besides༌Nakamura [29] reported that plasma D-dimer level was significantly higher in advanced endometrial cancer patients (FIGO classification III and IV) than in early stage patients (FIGO classification I and II). The clinical value of D-dimer has been widely recognized as exclusion of VTE. We hypothesized that the D-dimer associated with advanced endometrial cancer, contributing to VTE formation in endometrial cancer. Histologically, clear cell carcinoma significantly increased the odds of VTE in endometrial cancer patients. Tissue factor (TF) is a trans-membrane glycoprotein which can trigger thrombosis and extensive expressed by clear cell carcinoma [30]. Cuff reported that transcription factor hepatocyte nuclear factor 1-beta (HNF1B) was a biomarker of clear cell carcinoma and contributed to cytoplasmic prothrombin expression, which ultimately increased thromboembolic events [31].The above finding illustrate the reasons of clear cell carcinoma increased the odds of VTE on cellular-level mechanism.
CA125 was identified as a biomarker leading to VTE in the present study. Not only it is a tumor marker but also an inflammatory marker, which could also reflect the inflammatory response [32]. As such, patients with higher levels CA125 are associated with more advanced cancers, which could explain the reason why advanced cancer correlated with postoperative VTE.
The treatment of post-menopausal women affected by endometrial cancer was hysterectomy, which can be conducted by laparoscopy or laparotomy. Compared with conventional laparotomy, laparoscopy can shorten operation time and increase postoperative recovery ability. If patients maintained for a long time with the intraoperative lithotomy position or stayed in bed for a long time, it can weaken the muscle pump of both lower limbs and the cause venous reflux disorder. However, the results revealed that the type of surgery didn’t relate with VTE, which need more credible results to verify the authentic correlation between operation type and postoperative VTE.
There were a few disadvantages in the present research. First of all, although we did not apply any restrictions in the research area when we conduct literature search, the study only included researches in Asia, North Africa and UK. As a consequence, the results may not suitable for the non-involved areas, such as South Africa and Australia. Secondly, in spited of the well-rounded literature search, the underlying publication bias can’t be neglected in this study. What’s more, due to the inconsistent description of risk factors such as BMI>30, tumor size in uterine cavity(༞60mm) and CA125(༞35U/ml) in the included studies, so the relevant risk factors showed significant heterogeneity. Finally, the other influence factors such as peritoneal dissemination, operative time histology grade may be associated with VTE, which can’t be identified.