Risk of thrombosis and bleeding in gynecologic cancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice. STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L. METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty. RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures. CONCLUSION: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.

Risk of thrombosis and bleeding in gynecologic noncancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk for symptomatic venous thromboembolism and major bleeding in noncancer gynecologic surgeries. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials that addressed the effects of thromboprophylaxis. STUDY ELIGIBILITY CRITERIA: Eligible studies were observational studies that enrolled ≥50 adult patients who underwent noncancer gynecologic surgery procedures and that reported the absolute incidence of at least 1 of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding that required reintervention (including re-exploration and angioembolization), bleeding that led to transfusion, or postoperative hemoglobin level <70 g/L. METHODS: A teams of 2 reviewers independently assessed eligibility, performed data extraction, and evaluated the risk of bias of the eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine the cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors and used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the evidence certainty. RESULTS: We included 131 studies (1,741,519 patients) that reported venous thromboembolism risk estimates for 50 gynecologic noncancer procedures and bleeding requiring reintervention estimates for 35 procedures. The evidence certainty was generally moderate or low for venous thromboembolism and low or very low for bleeding requiring reintervention. The risk for symptomatic venous thromboembolism varied from a median of <0.1% for several procedures (eg, transvaginal oocyte retrieval) to 1.5% for others (eg, minimally invasive sacrocolpopexy with hysterectomy, 1.2%-4.6% across patient venous thromboembolism risk groups). Venous thromboembolism risk was <0.5% for 30 (60%) of the procedures; 0.5% to 1.0% for 10 (20%) procedures; and >1.0% for 10 (20%) procedures. The risk for bleeding the require reintervention varied from <0.1% (transvaginal oocyte retrieval) to 4.0% (open myomectomy). The bleeding requiring reintervention risk was <0.5% in 17 (49%) procedures, 0.5% to 1.0% for 12 (34%) procedures, and >1.0% in 6 (17%) procedures. CONCLUSION: The risk for venous thromboembolism in gynecologic noncancer surgery varied between procedures and patients. Venous thromboembolism risks exceeded the bleeding risks only among selected patients and procedures. Although most of the evidence is of low certainty, the results nevertheless provide a compelling rationale for restricting pharmacologic thromboprophylaxis to a minority of patients who undergo gynecologic noncancer procedures.

Risk-stratification of endometrial carcinomas revisited: a combined preoperative and intraoperative scoring system for a reliable prediction of an advanced disease.

OBJECTIVE: The aim of this study is to develop a risk-scoring system for predicting lymph node and distant metastasis in endometrial carcinoma. METHODS: A total of 1166 patients, treated at a single institution between 1-2007 and 12-2013, were included in the study. The association of stage IIIC-IV disease with demographic factors (age, body mass index), biochemical factors (complete blood count, serum CA125), preoperative histology and tumor size was examined in unadjusted analyses. Logistic regression analysis was used for the identification of variables that independently predict an advanced disease. RESULTS: Thrombocytosis, serum CA125>35 U/mL, preoperative high-risk histology (nonendometrioid or grade 3 endometrioid carcinoma) and tumor size≥3 cm were independently associated with an advanced disease. These predictors were internally validated by a bootstrapping method with statistical significance. A risk-scoring system with an area under the receiver operating characteristic curve of 0.852 (95% confidence interval, 0.821-0.883) was developed. Total risk score points ranged from 0 to 8 for individual patients. With a cut-off of 1 point, stratifying 66.3% of patients to surgical staging, the model predicted stage IIIC-IV carcinomas with a sensitivity of 100%, specificity of 38.0%, positive predictive value of 17.1%, and negative predictive value of 100%. With the same cut-off, the corresponding values were 100%, 34.7%, 16.5% and 100% in predicting stage IIIC carcinomas in a subgroup that underwent lymphadenectomy and had a stage I-IIIC disease. CONCLUSIONS: This risk-scoring system is highly sensitive in predicting an advanced stage endometrial carcinoma at a cut-off of risk score points that is associated with an acceptable lymphadenectomy rate.

Magnetic resonance imaging in the assessment of high-risk features of endometrial carcinoma: a meta-analysis.

OBJECTIVE: The aim of this study was to review the available literature on the reliability of contemporary magnetic resonance imaging (MRI) techniques in the assessment of high-risk features of endometrial carcinoma, that is, deep myometrial invasion, cervical stromal involvement, and lymph node metastasis. METHODS: The PubMed and Scopus databases were searched for studies published before March 2014. Studies on plain MRI were excluded. RESULTS: Fifty-two eligible studies were identified. For the assessment of deep (≥ 50%) myometrial invasion (50 studies, 3720 patients), the pooled sensitivity, specificity, positive predictive value, and negative predictive value were 80.7%, 88.5%, 77.6%, and 89.5%, respectively, by random-effects analysis. For predicting cervical stromal involvement (12 studies, 1153 patients), the pooled values were 57.0%, 94.8%, 68.7%, and 90.5%, respectively. For lymph node metastasis on a per-patient basis (10 studies, 862 patients), they were 43.5%, 95.9%, 66.3%, and 92.2%, respectively. In a meta-regression analysis, dynamic imaging was associated with a higher sensitivity in detecting deep myometrial invasion, as compared with contrast-enhanced imaging (P = 0.021). The improvement by diffusion-weighted imaging was of a borderline significance (P = 0.057). Significant small-study effects were found for the sensitivity of MRI in detecting deep myometrial invasion (P < 0.0001) and cervical stromal involvement (P = 0.049). CONCLUSIONS: Considering the poor-to-moderate sensitivity of MRI in detecting high-risk features of endometrial carcinoma, patients with negative findings on MRI may not safely forgo surgical staging unless the findings are confirmed by a backup method. The high specificities allow the targeting of staging procedures by MRI alone in patients with positive findings. Compared with contrast-enhanced imaging, dynamic and diffusion-weighted imaging may be more reliable in the radiological staging of endometrial carcinoma.

Combined use of endometrial sample and magnetic resonance imaging in the preoperative risk-stratification of endometrial carcinomas.

OBJECTIVE: To compare two treatment strategies in women undergoing surgery for endometrial carcinoma. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. POPULATION: 1166 patients. Uterine biopsy/curettage was obtained in 1140 women, of whom 229 also had pelvic magnetic resonance imaging (MRI). METHODS: We compared two strategies: (i) routine pelvic lymphadenectomy and (ii) selective pelvic lymphadenectomy for women with high-risk carcinomas as determined from preoperative histology and MRI. High-risk carcinomas included grade 1-2 endometrioid carcinomas with ≥50% myometrial invasion, grade 3 endometrioid carcinomas, and nonendometrioid carcinomas. Others were considered low-risk carcinomas. MAIN OUTCOME MEASURES: Diagnostic indices, treatment algorithms. RESULTS: Of the women who underwent lymphadenectomy, positive pelvic nodes were found in 2.3% of low-risk carcinomas and 18.3% of high-risk carcinomas. The combination of preoperative histology and MRI detected high-risk carcinomas with a sensitivity of 85.7%, a specificity of 75.0%, a positive predictive value of 74.4%, and a negative predictive value of 86.1%. Area under curve was 0.804. In the routine lymphadenectomy algorithm, 54.1% of lymphadenectomies were performed for low-risk carcinomas. In the selective lymphadenectomy algorithm, 14.3% of women with high-risk carcinomas did not receive lymphadenectomy. Missed positive pelvic nodes were estimated to occur in 2.1% of patients in the selective strategy. Similarly, the estimated risk for isolated para-aortic metastasis was 2.1%, regardless of treatment strategy. CONCLUSIONS: The combination of preoperative histology and MRI is moderately sensitive and specific in detecting high-risk endometrial carcinomas. The clinical utility of the method is hampered by the relatively high proportion of high-risk cases that remain unrecognized preoperatively.

Prediction of para-aortic spread by gross pelvic lymph node findings in patients with endometrial carcinoma.

OBJECTIVE: Isolated para-aortic lymph node metastases are rare in patients with endometrial carcinoma. We wanted to determine the reliability of macroscopic pelvic lymph node findings at surgery in predicting para-aortic space involvement in these patients. METHODS: We identified all women with surgically treated endometrial carcinoma at our institution between January 2008 and February 2013 (n = 854). One hundred seventeen patients received pelvic-aortic lymphadenectomy. Lymph nodes were considered grossly positive based on size and morphology. RESULTS: In patients who underwent comprehensive lymphadenectomy, grossly positive pelvic nodes predicted para-aortic metastasis with a sensitivity of 52.4% and specificity of 93.8%. The positive and negative likelihood ratios were 8.4 and 0.51, respectively. The predictive power of grossly positive pelvic nodes remained significant (odds ratio, 18; 95% confidence interval, 4.1-78; P < 0.0001) after correcting for deep myometrial invasion, poor tumor differentiation, and nonendometrioid histology as confounders. The whole sample of 854 patients was used for Bayesian calculations. The cutoff for a clinically useful test was set at the negative predictive value of 98.0%. The negative predictive value of the test (ie, grossly positive pelvic nodes at surgery in predicting the likelihood of para-aortic metastasis) was 99.7% for patients with superficial grade 1 to 2 endometrioid carcinomas and 98.0% for patients with deeply invasive grade 1 to 2 endometrioid carcinomas. For patients with grade 3 endometrioid and nonendometrioid carcinomas, the negative predictive values were 97.3% and 92.2%, respectively. For the whole study population, the value was 98.4%. CONCLUSIONS: When uterine factors are used for risk stratification of endometrial carcinomas, selective para-aortic lymphadenectomy, based on gross findings of pelvic nodes, is feasible for patients with grade 1 to 2 endometrioid carcinomas, regardless of the depth of myometrial invasion. Similarly, gross findings of pelvic nodes can be used to evaluate the need for para-aortic lymphadenectomy in the strategy of routine pelvic lymphadenectomy.

[Treatment of endometrial carcinoma]. / Kohdunrunkosyövän hoito.

The mainstay of the initial treatment for endometrial carcinoma is surgery with total hysterectomy and bilateral salpingo-oophorectomy. Pelvic-aortic lymphadenectomy may be appropriate for patients having tumors with a high risk for extrauterine spread. Most importantly, these include carcinomas with deep (≥ 50%) myometrial invasion, poor differentiation, or nonendometrioid histology, in which lymphadenectomy aids in prognostication and tailoring of adjuvant treatments. Vaginal cuff brachytherapy ensures vaginal control in stage I endometrioid carcinomas with high-risk features. For advanced carcinomas, chemotherapy is the adjuvant treatment of choice, combined with whole pelvic external beam radiotherapy in selected cases.

Prediction of lymph node and distant metastasis in patients with endometrial carcinoma: a new model based on demographics, biochemical factors, and tumor histology.

OBJECTIVE: To develop a model that might predict the probability of lymph node and distant metastasis (stages IIIC-IV) in endometrial carcinoma. METHODS: We studied 774 patients with endometrial carcinoma treated in a single institution. Demographic factors, biochemical factors and preoperative tumor characteristics, identified as potential risk factors for advanced carcinoma in unadjusted analyses, were used to create a logistic regression model with lymph node and distant metastasis as the dependent variable. Statistically significant odds ratios in the regression model were rounded to the nearest whole number. These rounded values were the estimated weights for each factor that were summed to generate a score that might predict the probability of stage IIIC-IV carcinoma. RESULTS: Biochemical factors and preoperative tumor characteristics predicted lymph node and distant metastasis in the regression model, whereas demographic factors were without effect. The score combining weighted risk factors was: (2 × leukocytosis)+(3 × thrombocytosis)+(7 × elevated CA125)+(4 × high-risk histology). The area under curve (AUC) for this total score was 0.823, with 71.6% sensitivity, 75.2% specificity, 25.9% positive predictive value, and 95.7% negative predictive value, using 6 as cut-point. After excluding stage IV carcinomas from the dataset, the AUC was 0.813 for the total score in predicting nodal involvement (P=0.82 vs. total score in predicting stage IIIC-IV carcinomas in the complete dataset). CONCLUSIONS: Based on the high negative predictive value, this prediction model could be applied for identifying patients who may not benefit from lymphadenectomy for endometrial carcinoma staging.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Climate change and reindeer management in Finland: Co-analysis of practitioner knowledge and meteorological data for better adaptation.

We studied interannual variability and changes over time in selected climate indices in the reindeer management area (RMA) in northern Finland. We present together the knowledge possessed by reindeer herders with information from meteorological measurements over three decades. The practitioner knowledge was gathered via a survey questionnaire addressing herder observations of long-term changes (approximately during the past 30 years) in climatic conditions and their impacts on herding during the four seasons. A set of temperature-, precipitation- and snow-related indices relevant for herding within the RMA was derived from spatially interpolated daily meteorological data (1981-2010). Climatic changes detected based on the measurement data were mainly consistent with earlier studies, and practitioner knowledge was generally in line with the meteorological data. The herders had experienced the largest number of changes during the winter, and the smallest number of changes during the summer. The herders reported various impacts of changing seasonal weather on reindeer condition and behavior, and on herding practices. Adaptation to the changing conditions requires adoption of various coping strategies by the herders in their everyday work, continuous development of professional techniques and practices, as well as support received from the governance of reindeer management. We conclude that holistic understanding of the impacts of climate change and adaptation to changes in the future requires simultaneous analyses of data from different sources, more research co-defined with local practitioners, and co-planned governance solutions. The approach presented in this work can ease the dialogue between the local practitioners, researchers and policy makers.