Placental site trophoblastic tumor: Successful treatment of 13 cases.

Placental site trophoblastic tumor (PSTT) is a rare variant of gestational trophoblastic neoplasia (GTN) that is characterized by slow growth resulting in mostly uterine-confined disease, low human chorionic gonadotropin (hCG) levels, and resistance to chemotherapy. Our objective was to update our center's experience with PSTT with respect to presentation, prognostic factors, treatment, and outcomes from 2003 to 2019. Thirteen women with PSTT were identified. Mean age was 32 years. The most frequent presenting symptom was abnormal uterine bleeding (69%). A uterine mass was noted in 62%. The diagnosis was usually established by endometrial biopsy or curettage (62%). Nonmolar pregnancy was the preceding gestation in 85%. Median time from last pregnancy to diagnosis was 13 months (range 0-240 months). Serum hCG levels at diagnosis ranged from 1 to 2606 mIU/mL (median 98 mIU/mL). Three women (23%) presented with metastatic disease. All 13 women underwent surgery: 12 had a hysterectomy, 1 had a fertility-sparing hysteroscopic resection, and 2 underwent pulmonary metastatectomy. Nine women (69%) also received chemotherapy for persistently elevated hCG levels after hysterectomy (2), high-risk factors (4), or metastatic disease (3). Overall survival was 100% with a median survival of 65 months (range 30-167 months). Survival for PSTT increased from 57% to 100%, including from 33% to 100% for metastatic disease, at our center from 1982 to 2003 to 2003-2017. Surgery is the most important component in the treatment of women with PSTT. Multidrug platinum/etoposide- chemotherapy should be used in women with metastatic disease and considered in women with nonmetastatic disease with high-risk features.

Perivascular epithelioid cell tumors (PEComa) in pregnancy with uterine rupture and ongoing abdominal gestation: A case report.

Perivascular epithelioid cell tumors (PEComa) represent a rare family of tumors characterized by distinct histology and immunohistochemistry characteristics. Approximately one-quarter of reported cases are gynecologic in origin and associated pregnancies are rare. We report a case of PEComa in pregnancy with initial undiagnosed presentation at 18 weeks of gestation and subsequent presentation and diagnosis at 30 weeks of gestation. Abdominal pain led to the use of magnetic resonance imaging, which raised concerns about placentation abnormality and abdominal pregnancy. Exploratory laparotomy was notable for a 10 cm by 15 cm posterior uterine defect through which the placenta and amniotic sac containing the fetus were extruded. Placenta-like tissue was noted to be invading through the anterior wall of the uterus, which led to concern regarding placenta percreta. A total abdominal hysterectomy and bilateral salpingectomy were then performed, given the complete loss of normal uterine architecture. Pathology returned with findings of placenta accreta and PEComa. Indolent uterine rupture in the setting of PEComa led to an ongoing viable abdominal pregnancy. Uterine PEComa can masquerade as a placenta and lead to obstetrical complications.

Examining Disparities in Route of Surgery and Postoperative Complications in Black Race and Hysterectomy.

OBJECTIVE: To estimate the associations among race, route of hysterectomy, and postoperative complications among women undergoing hysterectomy for benign indications. METHODS: A cohort study was performed. All patients undergoing hysterectomy for benign indications, recorded in the National Surgical Quality Improvement Program and its targeted hysterectomy file in 2015, were identified. The primary exposure was patient race. The primary outcome was route of hysterectomy and the secondary outcome was postoperative complication. Associations were examined using both bivariable tests and logistic regression. RESULTS: Of 15,136 women who underwent hysterectomy for benign indications, 75% were white and 25% were black. Black women were more likely to undergo an open hysterectomy than white women (50.1% vs 22.9%; odds ratio [OR] 3.36, 95% CI 3.11-3.64). Black women had larger uteri (median 262 g vs 123 g; 60.7% vs 25.6% with uterus greater than 250 g), more prior pelvic surgery (58.5% vs 53.2%), and higher body mass indices (32.7 vs 30.4). After adjusting for these and other clinical factors, black women remained more likely to undergo an open hysterectomy (adjusted OR 2.02, 95% CI 1.85-2.20). Black women experienced more major complications than white women (4.1% vs 2.3%; P<.001) and more minor complications (11.4% vs 6.7%; OR 1.78, P<.001). Again these disparities persisted with adjustment (major adjusted OR 1.56, 95% CI 1.25-1.95; minor adjusted OR 1.27, 95% CI 1.11-1.47). CONCLUSIONS: Black women undergo a higher proportion of open hysterectomy and experience more major and minor postoperative complications. These differences persisted even after adjusting for confounding medical, surgical, and gynecologic factors.

Discussing sarcoma risks during informed consent for nonhysterectomy management of fibroids: an unmet need.

There is no reliable way to distinguish symptomatic uterine fibroids from sarcoma without a surgical specimen. Many women with a uterine sarcoma are initially managed without hysterectomy under a presumed fibroid diagnosis, without understanding sarcoma risks. Currently many alternatives to hysterectomy, including medical and procedural interventions, for treatment of fibroids are promoted. The sarcoma incidence among women with presumed fibroids is 0.29% (1/340) to 0.05% (1/2000). Nonmetastatic leiomyosarcoma has a 63% 5-year survival rate whereas metastatic leiomyosarcoma has a 14% 5-year survival rate. In uterine sarcoma, we often cannot identify who has sarcoma before making a potentially cure-denying decision by delaying surgery. Therefore, women electing an alternative to hysterectomy for fibroids should undergo an informed consent process that specifically includes discussion of uterine sarcoma incidence and mortality. Alternatives to hysterectomy for presumed fibroids remain preferable treatment options for many women with symptomatic fibroids, so long as underlying sarcoma risks are adequately discussed. The challenge for obstetrician- gynecologists then is how to provide better informed consent and maintain the primacy of patient autonomy over our concern to "First, do no harm." Major threats to patient's autonomy are faced in the sarcoma risk discussion. How we should present sarcoma risk information to avoid being dismissive of sarcoma or frightening women toward hysterectomy is unstudied. Research is needed to determine how to provide sarcoma risk information with less bias during informed consent.

Prognosis and treatment of positive peritoneal cytology in early endometrial cancer: matched cohort analyses from the National Cancer Database.

BACKGROUND: While positive peritoneal cytology is no longer included among the endometrial cancer staging criteria, Federation International de Gynecologie et Obstetrique recommends continued collection of pelvic washings for cytology to produce additional data that may be used to determine the significance of positive cytology for prognosis and treatment of endometrial cancer. OBJECTIVES: The objectives of the study was to validate that positive cytology is a predictor of decreased survival in early endometrial cancer and to test whether adjuvant chemotherapy for positive cytology is associated with increased survival. STUDY DESIGN: We performed an observational retrospective cohort analysis of the 2010-2013 National Cancer Database including women with cytology status and Federation International de Gynecologie et Obstetrique stage IA-II endometrial cancer. Overall cohort and matched cohort survival analyses were performed with and without imputation of missing data. We also performed survival analyses of women with positive cytology grouped by chemotherapy exposure. Multivariable Cox proportional-hazards regressions were performed to adjust for possible confounders. A variety of sensitivity analyses, including robustness of results to possible unmeasured confounding, were reported. RESULTS: A total of 16,851 women including 953 with positive cytology were included. Four-year overall survival was 79.5% (range, 76.2-83.0%) for women with stage I/II with positive cytology vs 92.2% (range, 91.5-92.9%), 83.3% (range, 81.6-84.9%), and 86.8% (range, 85.1-88.5%) for stage IA, IB, and II with negative cytology, respectively (P ≤ .001). Positive cytology was associated with decreased survival (hazard ratio [95% confidence interval], 1.85 [range, 1.54-2.21], P < .001). For women with Federation International de Gynecologie et Obstetrique grade 1/2 endometrioid adenocarcinoma, the hazard of death associated with positive cytology was similar (hazard ratio [95% confidence interval], 1.85 [1.28-2.67], P < .001). Use of adjuvant chemotherapy by women with positive cytology was associated with increased survival (hazard ratio [95% confidence interval], 0.62 [0.40-0.95], P = .03). CONCLUSION: Positive peritoneal cytology was associated with decreased overall survival of women with Federation International de Gynecologie et Obstetrique stage I/II endometrial cancer, including low-grade endometrioid endometrial cancer. Treatment of women with stage I/II endometrial cancer and positive cytology with adjuvant chemotherapy was associated with increased survival.

Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone.

Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3 Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O3 To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-ß-methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild-type and PAI-1-deficient mice. With the exception of MIP-2, which was significantly lower in PAI-1-deficient as compared to wild-type mice 24 h following cessation of exposure to O3, no other genotype-related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI-1 neither regulates pulmonary expression of IL-6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3.

Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1ß)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1ß, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-ß-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.

Multidimensional measure of display clutter and pilot performance for advanced head-up display.

INTRODUCTION: This study was conducted to: develop a multidimensional measure of display clutter for advanced head-up displays (HUDs) incorporating enhanced and synthetic vision; assess the influence of HUD configuration on perceptions of display clutter, workload, and flight performance; model clutter scores in terms of visual display properties; and model flight performance in terms of subjective and objective clutter indices. METHODS: In a flight simulator, 18 pilots with different levels of flight experience flew approaches divided into three segments. Three HUD configuration sets were presented under two levels of flight workload. Pilot ratings of overall display clutter, its underlying dimensions, and mental workload were recorded along with flight performance measures. Display image analysis software was used to measure visual properties of the HUDs. RESULTS: The multidimensional measure of clutter showed internal consistency with overall perceived clutter. Calculated clutter scores were sensitive to HUD configurations and in agreement with a priori display classifications. There was a trend for the extremes of display clutter to cause higher workload and less stable performance due to cognitive complexity and a lack of information for high and low clutter displays, respectively. Multiple linear regression models of perceived clutter were developed based on HUD visual properties with predictive utility. Models of flight performance based on the clutter score and workload ratings were also developed, but with less predictive power. DISCUSSION: Measures and models of display clutter are expected to be applicable to the evaluation of a range of display concepts.

Perceived clutter in advanced cockpit displays: measurement and modeling with experienced pilots.

INTRODUCTION: Synthetic and enhanced vision systems (SVS and EVS) are being introduced into the cockpit to promote safety under workload conditions. Integration of existing iconic imagery with SVS and EVS displays may lead to perceptions of clutter. This research evaluated head-up display (HUD) features, including SVS, EVS, traffic collision avoidance system symbology, flight pathway (TUNNEL) guidance, and different primary flight display symbol sets, on pilot perceptions of clutter. A perceptual decomposition of the construct of clutter was also conducted. METHOD: During a simulated landing, 4 expert pilots viewed images of 16 HUD configurations. Pilots rated clutter for each image and the utility of pairs of terms for describing clutter. RESULTS: Results revealed all HUD features and two-way interactions to be significant in perceived clutter. Ratings increased with additional features. The presence of EVS, TUNNEL, and an expanded symbol set contributed the most. Regression models were developed to predict the likelihood of clutter ratings based on pilot perceptions of display characteristics. Pairs of terms found to have the greatest use for describing clutter included "redundant/orthogonal," "monochromatic/colorful," "salient/not salient," "safe/unsafe," and "dense/sparse" (in that order). A factor analysis revealed underlying display qualities explaining approximately 78% of variability in perceived clutter, including global density, feature similarity, feature clarity, and the dynamic nature of displays. These qualities corresponded with the display descriptor terms plus the terms "static/dynamic." DISCUSSION: The study provided information on the relationship of display features and pilot perceptions of clutter. We identified terminology pilots use to describe clutter and latent display variables that drive perceived clutter.

Synthetic vision systems: the effects of guidance symbology, display size, and field of view.

Two experiments conducted in a high-fidelity flight simulator examined the effects of guidance symbology, display size, and geometric field of view (GFOV) within a synthetic vision system (SVS). In Experiment 1, 18 pilots flew highlighted and low-lighted tunnel-in-the-sky displays, as well as a less cluttered follow-me aircraft (FMA), through a series of curved approaches over rugged terrain. The results revealed that both tunnels supported better flight path tracking and lower workload levels than did the FMA because of the availability of more preview information. Increasing tunnel intensity had no benefit on tracking and, in fact, degraded traffic awareness because of clutter and attentional tunneling. In Experiment 2, 24 pilots flew a lowlighted tunnel configured according to different display sizes (small or large) and GFOVs (30 degrees or 60 degrees). Measures of flight path tracking and terrain awareness generally favored the 60 degrees GFOV; however, there were no effects of display size. Actual or potential applications of this research include understanding the impact of SVS properties on flight path tracking, traffic and terrain awareness, workload, and the allocation of attention.

The role of highlighting in visual search through maps.

Two experiments were conducted in which participants performed a vehicle dispatching task. The intensity of one information source (vehicles in Experiment 1, destinations in Experiment 2) was varied to examine the effects of salience and discrimination on both searching for and processing the information in a cluttered display. Response times were recorded for questions either requiring focused attention on or divided attention between the different information domains in the map. The results of the present experiments indicate that it is possible to declutter a display without erasing any information. By 'lowlighting' one information domain and keeping the other domain at a fairly high intensity level, dividing attention between the information sources is optimal, as is focusing attention on either of the information domains exclusively. These results are discussed in conjunction with a computational model of confusion and salience which serves to predict search and integration performance in a cluttered display with separate domains of information displayed at different intensities.