Univariable analysis for prognostic factors for the development of postoperative venous thromboembolism between patients who had development of a postoperative venous thromboembolism compared with those who did not is shown in Table 3. The factors associated with a postoperative venous thromboembolism were: BMI (P=.005); estimated blood loss (P=.03); operative room time (P=.003); and operative time (P=.01). Additionally, median length of postoperative stay also was associated with venous thromboembolism development (P=.005). Venous thromboembolism was diagnosed in five patients after initial discharge (patients were postoperatively discharged on day 1 in one case, day 2 in three cases, and day 4 in one case). Venous thromboembolism was diagnosed in the other two cases on days 1 and 2 and resulted in a length of stay of 15 days and 7 days, respectively. The cause-and-effect relation of length of stay and postoperative venous thromboembolism could not be assessed further in such a small number of events, but the increased length of stay could possibly be attributable to the management of the venous thromboembolism event. The use of postoperative anticoagulation, stage, tumor grade, and tumor histology were not associated with venous thromboembolism development. Only one patient who had development of a symptomatic venous thromboembolism had a history of venous thromboembolism and none had a documented history of smoking (Table 2). Therefore, the effect of these patient characteristics on the development of postoperative venous thromboembolism was not analyzable beyond mere description. Of note, there were no venous thromboembolisms noted in the 76 cases that were planned for an minimally invasive surgery approach and then converted to laparotomy.
Obesity and operative time were the two most important prognostic factors identified in our univariable analysis (Table 4). Morbidly obese patients with a BMI of 40 or more had an incidence of venous thromboembolism of 5.8% (4 of 69) compared with 0.6% (3 of 504) in patients with BMI less than 40 (P=.005). The relative risk of venous thromboembolism in these morbidly obese patients is 9.7 (95% confidence interval 2.2–42.6; P=.003). The lowest operative time in patients with venous thromboembolism was 180 minutes. A high-risk group was determined to be patients with a BMI of 40 or more and an operative time of 180 minutes or more. In this group, the incidence of venous thromboembolism was 9.5% (4 of 42) compared with 0.6% (3 of 531) in all others (P=.001). The relative risk of venous thromboembolism in this high-risk group is 17.2 (95% confidence interval 3.97–74.2; P<.005). Postoperative LMW heparin was used in 19 of 42 (45%) of the high-risk cases compared with 106 of 530 (20%) in the other cases (Table 3). One (5.3%) of the 19 patients who received postoperative LMW heparin experienced a venous thromboembolism compared with 3 (13%) of the 23 patients who did not receive postoperative LMW heparin (P=.613).
Overall, 4% to 20% of patients with cancer have venous thromboembolism diagnosed, and this is believed to be an underestimation.15,16 Several studies have reported a higher risk of venous thromboembolism in patients with gynecologic cancer, with the rate of deep venous thromboembolism ranging from 11% to 18%17,18 and the rate of PE ranging between 1% and 2%.19 Patients with cancer undergoing surgery have a twofold higher risk of postoperative deep venous thromboembolism and a threefold greater risk of a fatal PE compared with patients without cancer undergoing similar surgery.20
Recommendations regarding the use of thromboprophylaxis after laparoscopic procedures are limited and controversial. Longer operative times, unique patient positioning, and increased intra-abdominal pressures may alter vascular hemodynamics, resulting in venous stasis in the lower extremities. Conversely, factors such as less surgical trauma, infrequent use of retractors, Trendelenburg positioning, and shorter hospital stays may reduce the risk of venous thromboembolism.24–26 In a retrospective review of 849 patients who underwent laparoscopic gynecologic surgery, Nick et al25 reported a symptomatic venous thromboembolism rate of 0.7% (6 of 849 patients). In the subgroup of patients with a history of gynecologic malignancy, 1.2% (5 of 430) had development of postoperative thromboembolic events.25 Malignancy was not found to be a significant factor in the increase of venous thromboembolism; however, surgical complexity was associated with increased risk of venous thromboembolism. The authors concluded that postoperative anticoagulation may be beneficial in patients undergoing high-complexity, minimally invasive procedures.25 Similar to the 0.87% incidence of PE in our cohort of patients, the percentage of patients with PE in the LAP2 study was 1% in both the laparotomy and laparoscopy groups.5 Ritch et al retrospectively reviewed 60,013 cases, both benign and oncologic, that underwent laparoscopic hysterectomy. The rate of symptomatic venous thromboembolism was 1.0%. Although the risk of venous thromboembolism was higher in the cancer cases (2.3%) compared with benign cases (0.9%), this was not reported to be statistically significant on multivariable analysis.27
Similar to previous retrospective reviews, we found the incidence of venous thromboembolism was 1.2% in our cohort of patients. All patients had sequential compression devices placed intraoperatively, and the majority (78%) did not receive postoperative thromboprophylaxis. Body mass index, estimated blood loss, operative time, and length of postoperative stay were found to be significant factors in the development of venous thromboembolism. Specifically, risk group stratification revealed that morbidly obese patients with operative times more than 3 hours were at an increased risk of development of venous thromboembolism. Blood product transfusions were associated with an increased risk of venous thromboembolism in women who underwent surgery for ovarian, tubal, or peritoneal surgery.28 Although packed red blood cell transfusion was found to be statistically significant in our study, only three patients received a packed red blood cell transfusion, thereby making it difficult to formulate any definitive conclusions. Other factors such as the use of postoperative anticoagulation, stage, tumor grade, and tumor histology were not associated with venous thromboembolism development. Previous studies have reported surgical complexity as a risk factor in the development of venous thromboembolism; however, when we compared procedures including pelvic and periaortic lymph node dissection compared with those without, no statistical significance was noted in the rate of venous thromboembolism.
Our study is limited by the inherent biases of retrospective data analyses. The patients in our cohort are from a single institution and therefore possibly limit the ability to generalize our findings. A common criticism of retrospective studies is the heterogeneity of the study population. This is a valid criticism that we acknowledge. However, our cohort all had endometrial cancer diagnosed, and the majority of cases were of low grade, low stage, and endometrioid histology. A potential criticism of our study is that we report the incidence of symptomatic postoperative venous thromboembolism during 90 days of surgery. This follow-up period is significantly longer than that reported by previous studies, including the @RISTOS project, which limited the assessment of venous thromboembolism to 31 days after surgery.22 It is our clinical impression that patients do not have development of venous thromboembolism at later time points unless they receive further cancer therapies or have development of recurrent disease, which is exceedingly uncommon in this cohort of patients.
In this study, we evaluated the incidence of postoperative venous thromboembolism among patients undergoing minimally invasive surgery for newly diagnosed endometrial cancer. Although our study was not designed to determine the most efficacious method of thromboprophylaxis, based on the low incidence of venous thromboembolism (1.2%) there seems to be no clear justification for the routine use of unfractionated heparin or LMW heparin for perioperative thromboprophylaxis in the majority of these patients. Mechanical thromboprophylaxis with sequential compression devices appears to be sufficient based on this retrospective review in the prevention of the majority of venous thromboembolism. One of the key findings of our analysis is the identification of a high-risk group of patients who are morbidly obese and undergo prolonged procedures lasting 3 hours or more. Thromboprophylaxis with unfractionated or LMW heparin, possibly preoperatively and postoperatively, may be a consideration in this select group but would require further prospective analysis. We did note a nearly 2.5-fold increased rate of venous thromboembolism in this group without the use of LMW heparin postoperatively, although not statistically significant, further highlighting the need for further investigation. Data are limited to recommend extended prophylaxis at this point without further study. Further trials are recommended to evaluate the timing of the dose, the duration, and the efficacy in patients undergoing minimally invasive surgery for endometrial cancer.
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