Danielle M. Greer

Tumor diameter as a predictor of lymphatic dissemination in endometrioid endometrial cancer

OBJECTIVES To assess the utility of tumor diameter (TD) for predicting lymphatic dissemination (LD) and determining need for lymphadenectomy following diagnosis of endometrioid endometrial cancer. METHODS Patients diagnosed with stage I-III endometrioid endometrial cancer during 2003-2013 who underwent pelvic or para-aortic lymphadenectomy during hysterectomy were studied. Intraoperative predictors of LD included TD, grade, myometrial invasion (MI), age, body mass index, and race/ethnicity. Candidate logistic regression models of LD were evaluated for model fit and predictive power. RESULTS Of 737 cancer patients, 68 (9.2%) were node-positive. Single-variable models with only continuous TD (c-statistic 0.77, 95% CI 0.71-0.83) and dichotomous TD with 50-mm cut-off (TD50; c-statistic 0.73, 95% CI 0.67-0.78) were significantly more predictive than with the standard 20-mm cut-off (c-statistic 0.56, 95% CI 0.53-0.59). Overall, the most important LD predictors were TD50 and MI3rds (three-category form). The best candidate model (c-statistic 0.84, 95% CI 0.80-0.88) suggested odds of LD were five times greater for TD >50mm than ≤50mm (OR 4.91, 95% CI 2.73-8.82) and six and ten times greater for MI >33% to ≤66% (OR, 5.70; 95% CI, 2.25-14.5) and >66% (OR 10.2, 95% CI 4.11-25.4), respectively, than ≤33%. Best-model false-negative (0%) and positive (57.2%) rates demonstrated marked improvement over traditional risk-stratification false-negative (1.5%) and positive (76.2%) rates (c-statistic 0.77, 95% CI 0.72-0.82). CONCLUSIONS Tumor diameter is an important predictor of LD. Our risk model, containing modified forms of MI and TD, yielded a lower false-negative rate and can significantly decrease the number of lymphadenectomies performed on low-risk women.

EFFECTS OF TESTOSTERONE SUPPLEMENT THERAPY ON CARDIOVASCULAR OUTCOMES IN MEN WITH LOW TESTOSTERONE

Cardiovascular (CV) effects of testosterone supplement therapy in men with low testosterone levels have been inconsistently documented across studies. Data for men with low total testosterone levels (<300 ng/dL) during 2007-13 were obtained from a large community-based healthcare system. Cox

Management of the third stage of labor in second-trimester deliveries: How long is too long?

BACKGROUND Retained placenta is the most common second-trimester delivery complication. As the optimal third stage of labor duration remains undefined, complications associated with retained placentas are difficult to study. OBJECTIVE(S) To determine the optimal third stage of labor duration in second-trimester deliveries based on estimates of time-specific probabilities of placental delivery, placental intervention, and postpartum complication. STUDY DESIGN We retrospectively studied adult women with singleton second-trimester vaginal deliveries. We identified third stage of labor duration, placental delivery method (spontaneous vs. manual/operative intervention), and indication for intervention. Postpartum complication was examined as a composite outcome. Differences among groups defined by delivery method and postpartum complication were tested using parametric and nonparametric tests. Probability curves describing the time-specific probabilities of placental delivery were derived using lifetable methods with group differences tested using the log-rank test. Probability of placental intervention and complication by time to placental delivery were examined using logistic regression with adjustment for confounders and other predictors. RESULTS We identified 215 second-trimester placental deliveries (77% spontaneous, 23% intervention). Overall, 27% experienced postpartum complication, primarily hemorrhage (91%). Complication rates differed significantly between spontaneous placental deliveries (16%) and interventions (61%, P < 0.01). Both placental intervention and postpartum complication were strongly associated with longer time to placental delivery. Spontaneous placental deliveries occurred earlier than deliveries requiring intervention (P < 0.01). At 2 h, placental delivery rates were 93% in spontaneous deliveries and 39% in those requiring intervention. The overall postpartum complication rate for spontaneous placental deliveries (16%) was used as the threshold of tolerable risk and the criterion for placental intervention. Adjusted probability curves for deliveries of average gestational age (21.6 weeks) suggested that most patients (63.9%) may not require intervention until approximately 2 h following fetal delivery. Patients with PPROM would require intervention by 34 min, and those with intrapartum fever or delivery EBL ≥500 mL would already exceed the risk threshold at fetal delivery. CONCLUSIONS Our study suggests that an optimal third stage of labor duration of approximately 2 h maximizes probability of spontaneous delivery and minimizes complication risk. Timing of intervention may be further individualized for patients based on maternal characteristics and intrapartum conditions.

Robustness of a Newly Proposed Risk Schema for Lymphatic Dissemination in Endometrioid Endometrial Cancer

High Any TD, grade 1 or 2, MI >66% Any TD, grade 3, MI >50% TD >50 mm, any grade, MI >66% TD >50 mm, grade 2 or 3, 33% < MI ≤ 66% Risk Schema & Level Model Development Cohort Model Validation Cohort No LD (N=669) LD (N=68) No LD (N=218) LD (N=29) Standard Schema: Low ** 159 (23.8%) ** 1 (1.47%) ** 56 (25.7%) ** 2 (6.90%) Low-Intermediate 271 (40.5%) 12 (17.6%) 76 (34.9%) 6 (20.7%) High-Intermediate 99 (14.8%) 14 (20.6%) 25 (11.5%) 3 (10.3%) High 140 (20.9%) 41 (60.3%) 61 (28.0%) 18 (62.1%) Proposed Schema: Low ** 286 (42.8%) ** 0 (0%) ** 99 (45.4%) ** 4 (13.8%) Low-Intermediate 215 (32.1%) 17 (25.0%) 67 (30.7%) 5 (17.2%) High-Intermediate 77 (11.5%) 14 (20.6%) 20 (9.17%) 9 (31.0%) High 91 (13.6%) 37 (54.4%) 32 (14.7%) 11 (37.9%)