Increased risk of recurrence in early-stage endometrial carcinoma after delays in adjuvant radiation treatment.

OBJECTIVE: The benefits of adjuvant radiation treatment after hysterectomy have been confirmed in select patients with early-stage endometrial carcinoma. The goal of this study was to evaluate the prognostic impact of the time interval between hysterectomy and starting adjuvant radiation treatment in patients with early-stage endometrial carcinoma. METHODS: Our database was searched for women with early-stage endometrioid endometrial cancer who received adjuvant radiation therapy after hysterectomy. The patients were classified into two groups based on the time interval to adjuvant radiation therapy (≤8 weeks or >8 weeks) after hysterectomy. Recurrence-free survival, disease-specific survival, and overall survival were compared between the two groups. RESULTS: Four hundred and sixty patients were identified. Median follow-up was 70.5 months (range 1-360). One hundred and seventy-six patients (38%) were 2009 International Federation of Gynecology and Obstetrics stage IA, 207 (45%) stage IB, and 77 (17%) stage II. Three hundred and fifty-four women (77%) received adjuvant radiation therapy within 8 weeks after hysterectomy. There was no statistically significant difference between the two groups in baseline demographics, disease and treatment characteristics, except for the modality of adjuvant radiation therapy. Patients who received adjuvant radiation therapy within 8 weeks experienced significantly less disease recurrence (9% vs 18%; p=0.01) and particularly less isolated vaginal recurrence (0% vs 6%, p=0.04). Five-year recurrence-free survival was 89% versus 80% (p=0.04), 5-year disease-specific survival was 93% for both groups, and 5-year overall survival was 86% versus 85% for patients who received adjuvant radiation therapy ≤8 and >8 weeks, respectively (p=0.88). CONCLUSION: Our study suggests that delaying adjuvant radiation therapy beyond 8 weeks after hysterectomy is associated with significantly more cancer recurrences for women with early-stage endometrial carcinoma.

Clinicopathological Evaluation of the Potential Anatomic Pathways of Systemic Metastasis from Primary Breast Cancer Suggests an Orderly Spread Through the Regional Lymph Nodes.

BACKGROUND: Two conflicting hypotheses as to how breast cancer (BC) accesses the systemic circulation dominated the 20th century and affected surgical treatment. We hypothesized that tumor lymphovascular invasion (LVI) at the primary tumor site favors lymphatic and not blood vessel, capillaries, and systemic metastases (Smets) are dependent upon regional lymph node (RLN) mets. METHODS: Data from BC patients undergoing RLN biopsy was professionally abstracted and maintained in a prospective, precisely managed, single-institution database. Associations of RLN, LVI, and Smets were estimated by univariate and multivariate backward logistic regression models and patient-affiliated demographic, clinicopathologic, treatment type, and molecular marker data. RESULTS: Of 3329 patients, followed 1-22 years (mean 7.8), 463 of 3329 (13.9%) showed LVI, 742 of 3329 (22.3%) had RLN mets, and 262 of 3329 (7.9%) had Smets. Smets occurred in 52 of 252 (21% with LVI+/RLN+); 116 of 2301 (5% with LVI-/RLN-); 65 of 465 (14% with LVI-/RLN+); and 17 of 207 (8% with LVI+/RLN-), p = 0.021 for association between LVI and Smets for RLN+ patients but not for RLN- patients (p = 0.051). Positive RLN, larger tumor size, and higher grade (all p < 0.001) were predictive of Smets by the multivariable model, whereas positive LVI was not. CONCLUSIONS: LVI predicts RLN mets in BC. RLN is critical to Smets from BC, whereas LVI on its own is not. Smets occur significantly more commonly when both LVI and RLN mets occur together. LVI is, thus, likely to be primarily lymphatic invasion, and rarely, blood vessel invasion, supporting the Halsted paradigm. LVI and RLN together predict clinical outcome better than either alone.

Prenatal airshed pollutants and preterm birth in an observational birth cohort study in Detroit, Michigan, USA.

Detroit, Michigan, currently has the highest preterm birth (PTB) rate of large cities in the United States. Disproportionate exposure to ambient air pollutants, including particulate matter ≤2.5 µm (PM2.5), PM ≤ 10 µm (PM10), nitrogen dioxide (NO2) and benzene, toluene, ethylbenzene, and xylenes (BTEX) may contribute to PTB. Our objective was to examine the association of airshed pollutants with PTB in Detroit, MI. The Geospatial Determinants of Health Outcomes Consortium (GeoDHOC) study collected air pollution measurements at 68 sites in Detroit in September 2008 and June 2009. GeoDHOC data were coupled with 2008-2010 Michigan Air Sampling Network measurements in Detroit to develop monthly ambient air pollution estimates at a spatial density of 300 m2. Using delivery records from two urban hospitals, we established a retrospective birth cohort of births by Detroit women occurring from June 2008 to May 2010. Estimates of air pollutant exposure throughout pregnancy were assigned to maternal address at delivery. Our analytic sample size included 7961 births; 891 (11.2%) were PTB. After covariate adjustment, PM10 (P = 0.003) and BTEX (P < 0.001), but not PM2.5 (P = 0.376) or NO2 (P = 0.582), were statistically significantly associated with PTB. In adjusted models, for every 5-unit increase in PM10 there was a 1.21 times higher odds of PTB (95% CI 1.07, 1.38) and for every 5-unit increase in BTEX there was a 1.54 times higher odds of PTB (95% CI 1.25, 1.89). Consistent with previous studies, higher PM10 was associated with PTB. We also found novel evidence that higher airshed BTEX is associated with PTB. Future studies confirming these associations and examining direct measures of exposure are needed.

Recognizing odontogenic sinusitis: A national survey of otolaryngology chief residents.

PURPOSE: Odontogenic sinusitis is underrepresented in sinusitis literature as well as in the otolaryngology teaching curriculum sponsored by the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngologists and residents in training may therefore have a decreased awareness of the condition. The objective of this study was to survey otolaryngology chief residents toward the ends of their training to determine how often they considered odontogenic sinusitis as a cause of unilateral sinus disease. MATERIALS AND METHODS: An online REDCap survey was conducted from December 2018 to January 2019. Online surveys were emailed to 119 Otolaryngology residency program directors in the United States of America, which were then forwarded to their chief residents. Surveys included 3 demographic and 4 clinical questions. Clinical questions included 3 computed tomography-based questions requiring either differential diagnoses or most likely diagnosis, and 1 question on residents' perceived prevalence of odontogenic sinusitis as a cause of unilateral sinus opacification. Answer choices were tabulated and compared based on geographic region and post-residency career plans. RESULTS: Of 293 chief residents emailed, 94 completed the survey (32.1%). While answer choices on imaging-based questions varied, odontogenic sinusitis was generally underrecognized. Approximately 70% of residents felt odontogenic sinusitis represented 0%-40% of unilateral sinus opacification. There were no statistically significant differences in answers based on geographic distribution or post-residency career plans. CONCLUSIONS: Otolaryngology chief residents recognized odontogenic sinusitis with variable accuracy on imaging, and generally underestimated its prevalence as a cause of unilateral sinus opacification. Efforts should be made to teach otolaryngology residents about odontogenic sinusitis.

A Matched Analysis on the Prognostic Impact of Race on Survival Endpoints of Women with Early-Stage Endometrial Cancer.

OBJECTIVE: To compare survival endpoints between African American (AA) and non-AA (NAA) women with endometrial carcinoma (EC) stage I-II using a robust matching analysis. METHODS AND MATERIALS: Patients were matched by stage, grade, adjuvant management (surveillance, vaginal brachytherapy or pelvic radiation treatment), age, and year of hysterectomy. Recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were calculated. RESULTS: A total of 758 patients were included. Body mass index and Age-Adjusted Charlson comorbidity index was significantly higher in AA compared to NAA women. There were no significant differences between the AA and NAA groups in regard to 5-year RFS (94 vs. 93%), DSS (96 vs. 98%) or 5-year OS (90 vs. 92%). On multivariate analysis of survival endpoints for the entire study cohort, it was found that race (AA vs. NAA) was not a significant predictor of RFS, DSS, or OS. Grade 3 tumors and the presence of lymphovascular space invasion (LVSI) were the only 2 independent predictors of RFS and DSS, while age-adjusted Charlson comorbidity score, grade 3, stage II and the presence of LVSI were independent predictors of shorter OS. CONCLUSIONS: When matched based on the tumor stage, grade, adjuvant treatment, age, and year of surgery, our study suggests that there is no statistically significant difference in any survival endpoints between AA and NAA women with early-stage EC. Based on these data, disparities in outcome likely do not stem from uterine cancer-related causes. The increased comorbidity burden in AA women is likely a factor contributing to the racial disparity in endometrial cancer.

What Is the Optimal Adjuvant Treatment Sequence for Node-Positive Endometrial Cancer? Results of a National Cancer Database Analysis.

OBJECTIVE: The optimal sequence of administering chemotherapy (CT) and radiation treatment (RT) in women with node-positive endometrial carcinoma (EC) remains controversial. We used the National Cancer Database to evaluate overall survival (OS) in women with advanced EC receiving different sequences of adjuvant therapy. METHODS: The National Cancer Database was queried for female adults with International Federation of Gynecology and Obstetrics 2009 stage IIIC1 to IIIC2 EC diagnosed from 2004 to 2012 treated with hysterectomy and adjuvant CT and RT. Overall survival was compared between sequential treatment (CT followed by RT) and concurrent treatment (CT and RT within 4 weeks). χ tests assessed differences by sequence and various clinical variables. Log-rank test and Cox proportional hazards models evaluated OS. Risk factors related to OS were identified by univariate and multivariate analyses. RESULTS: Of 1826 patients, 67% (1218) received sequential treatment and 33% (608) received concurrent treatment. The median follow-up was 49.2 months. The sequential treatment group had a better 5-year OS (67% [95% confidence interval = 64%-70%]) than the concurrent treatment group (62% [95% confidence interval = 57%-66%]) (P = 0.004). On multivariate analysis, the strongest predictors of worse OS were increasing age (hazard ratio [HR] = 1.04 [1.02-1.06], P = 0.0003), type 2 versus type 1 EC (HR = 1.60 [1.06-2.43], P = 0.03), grade 3 versus 1 (HR = 2.64 [1.23-5.67], P = 0.01), residual disease or positive margin versus negative margin (HR = 2.25 [1.43-3.56], P = 0.0005), and concurrent versus sequential treatment (HR = 1.67 [1.15-2.40], P = 0.006). CONCLUSIONS: This study suggests that upfront CT followed by RT may be a better treatment sequence for adjuvant therapy in women with advanced EC.

INCIDENTAL THYROID NODULES: RACE/ETHNICITY DISPARITIES AND OUTCOMES.

OBJECTIVE: Black patients have a significantly lower incidence of well-differentiated thyroid cancer (WDTC) compared to all other race/ethnic groups, while white patients appear to be at greater risk. This study examines incidental thyroid nodules (ITNs) to assess whether racial disparities in WDTC arise from a differential discovery of ITNs-perhaps due to socioeconomic disparities-or reflect true differences in thyroid cancer rates. METHODS: A retrospective review was performed of all patients who underwent fine-needle aspiration (FNA) of thyroid nodules by our academic medical center's endocrinology division between January 2006 and December 2010. Medical records were reviewed to identify whether the biopsied thyroid nodule was discovered incidentally through nonthyroid-related imaging or identified by palpation. RESULTS: FNAs were performed on 1,369 total thyroid nodules in 1,141 study patients; 547 (48%) were classified as white, and 593 (52%) were classified as nonwhite. Among this cohort, 36.6% of patients underwent biopsy for an ITN. White patients were 1.6 times more likely to have undergone a biopsy for a nodule that was incidentally identified compared to nonwhites ( P<.0001). Indicators of socioeconomic status (SES) did not have a significant association with ITNs. Within the ITN cohort, 4.9% of nonwhite patients were found to have a thyroid malignancy compared to 12.9% of white patients ( P<.01). CONCLUSION: The higher incidence of thyroid cancer in white patients appears to be not only due to diagnostic bias, but also to a true difference in cancer prevalence. ABBREVIATIONS: FNA = fine-needle aspiration; ITN = incidental thyroid nodule; SEER = Surveillance Epidemiology and End Results; SES = socioeconomic status; WDTC = well-differentiated thyroid cancer.

Does Age-Adjusted Charlson Comorbidity Score Impact Survival Endpoints in Women with Federation of Gynecology and Obstetrics-Stage III Endometrial Cancer?

OBJECTIVES: We sought to evaluate the impact of age-adjusted Charlson comorbidity index (AACCI) score on survival endpoints for women with advanced stage endometrial carcinoma (EC). METHODS AND MATERIALS: We identified 238 women with stage III EC. AACCI score was calculated and 3 groups were created accordingly; group 1 with a score of 0-2, group 2 with score 3-4, and group 3 with score ≥5. Significant predictors of recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were analyzed. RESULTS: Median follow-up was 54 months and median age was 65 years. Stage IIIC was the most common stage (69%). The 3 groups were well-balanced except for less utilization of adjuvant chemotherapy in group 3 (p = 0.01). Five-year OS was significantly lower in group 3 compared to groups 1 and 2 (23 vs. 65 and 51%, respectively). Similarly, 5-year RFS was 54, 41, and 33% and DSS was 65, 54, and 35% for groups 1, 2, and 3 respectively. On multivariate analyses, AACCI group 3, cervical stromal involvement, positive peritoneal cytology, and higher tumor grade were predictors for shorter OS. Cervical stromal involvement and higher grade were independent predictors for worse RFS and DSS. Additionally, positive cytology, lymphovascular space invasion, and stage IIIC2 were significantly detrimental for RFS. CONCLUSIONS: Our study suggests that comorbidity burden is a strong predictor of worse OS in women with stage III EC. Women with higher AACCI are less likely to receive adjuvant chemotherapy. Comorbidity score can significantly impact survival endpoints for women with advanced EC.

Is Older Age a Real Adverse Prognostic Factor in Women With Early-Stage Endometrial Carcinoma? A Matched Analysis.

OBJECTIVES: The aim of this study was to evaluate if older age alone negatively impacts survival endpoints in women with early-stage uterine endometrioid carcinoma (EC), or its reported prognostic impact is due to an interaction with other well-known adverse factors using matched-analysis methodology. METHODS: We identified 1254 patients with International Federation of Gynecology and Obstetrics stage I-II EC who underwent hysterectomy at our institution. We created 2 matched groups based on International Federation of Gynecology and Obstetrics stage, tumor grade, lymph node dissection status, and the type of adjuvant management. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were calculated. RESULTS: A total 297 women 70 years or older were matched with 297 women younger than 70 years. The 2 groups were well balanced except for age and higher body mass index in younger patients. There were no significant difference between older and younger patients in regard to 5-year RFS (85% vs 87%; P = 0.52) or DSS (93% for both groups with P = 0.77). Five-year OS was shorter in older patients (76% vs 88% with P < 0.001). On multivariate analysis for RFS and DSS, high tumor grade and the presence of lymphovascular space invasion (LVSI) were the only 2 predictors of shorter RFS and DSS (P = 0.01 and P = 0.02, and P = 0.01 and P = 0.01, respectively). Tumor grade and LVSI also were predictors of shorter OS. CONCLUSIONS: Our study suggests that when older patients with EC are matched with younger patients based on tumor stage, grade, and adjuvant management the prognostic impact of old age disappears. High tumor grade and LVSI remained as independent predictors of survival endpoints.

Volume of Plasma Expansion and Functional Outcomes in Stroke.

BACKGROUND: Plasma expansion in acute ischemic stroke has potential to improve cerebral perfusion, but the long-term effects on functional outcome are mixed in prior trials. The goal of this study was to evaluate how the magnitude of plasma expansion affects neurological recovery in acute stroke. METHODS: This was a secondary analysis of data from the Albumin in Acute Stroke Part 2 trial investigating the relationship between the magnitude of overall intravenous volume infusion (crystalloid and colloid) to clinical outcome. The data were inclusive of 841 patients with a mean age of 64 years and a median National Institutes of Health Stroke Scale (NIHSS) of 11. In a multivariable-adjusted logistic regression model, this analysis tested the volume of plasma expansion over the first 48 h of hospitalization as a predictor of favorable outcome, defined as either a modified Rankin Scale score of 0 or 1 or a NIHSS score of 0 or 1 at 90 days. This model included all study patients, irrespective of albumin or isotonic saline treatment. RESULTS: Patients that received higher volumes of plasma expansion more frequently had large vessel ischemic stroke and higher NIHSS scores. The multivariable-adjusted model revealed that there was decreased odds of a favorable outcome for every 250 ml additional volume plasma expansion over the first 48 h (OR 0.91, 95 % CI, 0.88-0.94). CONCLUSIONS: The present study demonstrates an association between greater volume of plasma expansion and worse neurological recovery.

Predictors of Survival After Recurrence in Women With Early-Stage Endometrial Carcinoma.

OBJECTIVE: Factors predictive of survival after recurrent early-stage endometrial carcinoma have not been thoroughly investigated. The purpose of this study was to explore factors that impact disease-specific survival (DSS) and overall survival (OS) after recurrence in women with early-stage endometrial carcinoma. MATERIALS AND METHODS: After institutional review board approval, we identified 104 women with 2009 International Federation of Gynecology and Obstetrics stage I to II uterine endometrioid carcinoma who developed disease recurrence between January 1990 and December 2014. The Kaplan-Meier approach and Cox regression analysis were used to assess DSS and OS after recurrence and to determine factors influencing these survival end points. RESULTS: Median age of the study cohort was 65 years with a median follow-up time of 42.8 months after hysterectomy. Median time to recurrence was 15.8 months. Recurrences were diagnosed in 60 patients (57.7%) who were originally managed with observation after hysterectomy and in 44 patients (42.3%) who were initially managed with adjuvant radiation treatment. Fifty-six patients (54%) had pelvic recurrence (vaginal and/or pelvic), whereas 48 (46%) had extrapelvic recurrence. Five-year DSS and OS for the entire study population was 44% and 37%, respectively. Five-year DSS and OS were longer for patients with pelvic recurrence compared with patients with extrapelvic recurrence (66% vs 18% and 55% vs 17%, P < 0.0001). Five-year DSS was also longer for radiation-naive patients than for radiation-treated patients (51% vs 34%, P = 0.023). On multivariate analysis of DSS and OS, pelvic recurrence (P < 0.001) was the only significant predictor of longer DSS and OS. CONCLUSIONS: In women with recurrent early-stage endometrioid carcinoma, our study suggests that site of recurrence (pelvic vs extra pelvic) is the only predictor of survival. In addition, we found that radiation naivete and pelvic recurrence correlated with longer DSS and OS.

Salvage Versus Adjuvant Radiation Treatment for Women With Early-Stage Endometrial Carcinoma: A Matched Analysis.

OBJECTIVES: Adjuvant radiation treatment (ART) has been shown to reduce local recurrences in early-stage endometrial carcinoma (EC); however, this has not translated into improved overall survival (OS) benefit. As a result, some physicians forgo ART, citing successful salvage rates in cases of recurrence. Survival end points were compared between women treated with salvage RT (SRT) for locoregional recurrence and similarly matched women treated upfront with ART. MATERIALS AND METHODS: We identified 40 patients with stage I to II type 1 EC who underwent hysterectomy and received no adjuvant RT but later developed locoregional recurrence and subsequently received SRT. An additional 374 patients who underwent hysterectomy followed by ART during the same period were identified. Patients in the SRT group were matched to those in the ART group based on FIGO (International Federation of Gynecology and Obstetrics) stage and tumor grade in a 1:3 ratio. Disease-specific survival (DSS) and OS were calculated. RESULTS: A total of 156 women were matched (39:117). Median follow-up was 56 months. The 2 groups were generally well balanced. With regard to the site of tumor recurrence, it was commonly vaginal in the SRT group (74.3% vs 28.6%, P = 0.01). More SRT patients received a combination of pelvic external-beam RT with vaginal brachytherapy (94.8% vs 35%, P < 0.001). The ART group had significantly better 5-year DSS (95% vs 77%, P < 0.001) and 5-year OS (79% vs 72%, P = 0.005) compared with those of the SRT group. CONCLUSIONS: Our study suggests that women who receive SRT for their locoregional recurrence have worse DSS and OS compared with those matched patients who received ART. Further studies are warranted to develop a high-quality cost-effectiveness analysis as well as accurate predictive models of tumor recurrence. Until then, ART should at least be considered in the management of early-stage EC patients with adverse prognostic factors.

Predictive Capacity of 3 Comorbidity Indices in Estimating Survival Endpoints in Women With Early-Stage Endometrial Carcinoma.

OBJECTIVE: The negative impact of comorbidity on survival in women with endometrial carcinoma (EC) is well-known. Few validated comorbidity indices are available for clinical use, such as the Charlson Comorbidity Index (CCI), the Age-Adjusted CCI (AACCI), and the Adult Comorbidity Evaluation-27 (ACE-27). The aim of the study is to determine which index best correlates with survival endpoints in women with EC. MATERIALS AND METHODS: We identified 1132 women with early-stage EC treated at an academic center. Three scores were calculated for each patient using CCI, AACCI, and ACE-27 at the time of hysterectomy. Univariate and multivariable modeling was used to determine predictors of survival. RESULTS: For each of the studied comorbidity indices, the highest scores were significantly correlated with poorer overall survival. The hazard ratio of death from any cause was 3.92 for AACCI, 2.25 for CCI, and 1.57 for ACE-27. All 3 indices were independent predictors of overall survival with a P value of less than 0.001 on multivariate analysis. In addition, lymphovascular space invasion, lower uterine segment involvement, and tumor grade were predictors of overall survival. Lymphovascular space invasion, grade (P < 0.001), and high AACCI score were the only significant predictors of recurrence-free survival (RFS). Lymphovascular space invasion and tumor grade were the only 2 predictors of disease-specific survival. CONCLUSIONS: Although all 3 studied comorbidity indices were significant predictors of overall survival in women with early-stage EC, AACCI showed a stronger association. It should be considered for evaluating comorbidity in women with early-stage EC.

Time Spent on the Internet and Adolescent Blood Pressure.

Internet use is nearly ubiquitous among adolescents. Growing evidence suggests heavy Internet use negatively impacts health, yet the relationship between time spent on the Internet and adolescent blood pressure (BP) is unknown. We examined the association between Internet use and elevated BP in a racially diverse cross-sectional sample of 331 healthy adolescents (ages 14-17 years). Heavy Internet use was defined as ≥ 2 hr/day, moderate use as <2 hr/day and ≥ 5 days/week, and light use as < 2 hr/day and ≤ 4 days/week. Elevated BP was defined as systolic or diastolic BP ≥ 90 th percentile. Heavy Internet users had statistically significantly higher odds of elevated BP compared to light Internet users. School nurses can play an important role in preventing high BP through assessment of BP and other health behaviors including Internet use, and health teaching to individuals, student groups, faculty, and parents to increase awareness of the relationship between Internet use and health.

The Impact of Environmental Benzene, Toluene, Ethylbenzene, and Xylene Exposure on Blood-Based DNA Methylation Profiles in Pregnant African American Women from Detroit.

African American women in the United States have a high risk of adverse pregnancy outcomes. DNA methylation is a potential mechanism by which exposure to BTEX (benzene, toluene, ethylbenzene, and xylenes) may cause adverse pregnancy outcomes. Data are from the Maternal Stress Study, which recruited African American women in the second trimester of pregnancy from February 2009 to June 2010. DNA methylation was measured in archived DNA from venous blood collected in the second trimester. Trimester-specific exposure to airshed BTEX was estimated using maternal self-reported addresses and geospatial models of ambient air pollution developed as part of the Geospatial Determinants of Health Outcomes Consortium. Among the 64 women with exposure and outcome data available, 46 differentially methylated regions (DMRs) were associated with BTEX exposure (FDR adjusted p-value < 0.05) using a DMR-based epigenome-wide association study approach. Overall, 89% of DMRs consistently exhibited hypomethylation with increasing BTEX exposure. Biological pathway analysis identified 11 enriched pathways, with the top 3 involving gamma-aminobutyric acid receptor signaling, oxytocin in brain signaling, and the gustation pathway. These findings highlight the potential impact of BTEX on DNA methylation in pregnant women.

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women With FIGO Stage II Uterine Endometrioid Carcinoma.

OBJECTIVE: The objective of this study was to investigate the prognostic significance of the depth of cervical stromal invasion (CSI) in women with FIGO stage II uterine endometrioid adenocarcinoma (EC). METHODS: Our database of women with EC was quired for patients with stage II EC. Pathologic slides were retrieved and reviewed by gynecologic pathologists to determine cervical stromal thickness and depth of CSI as a percentage of stromal thickness (%CSI). Kaplan-Meier, univariate, and multivariate analyses were used to compare recurrence-free, disease-specific (DSS), and overall survival (OS) between women who had<50% versus ≥50% CSI. Univariate and multivariate analyses were used to assess other prognostic variables associated with survival endpoints. RESULTS: A total of 117 patients were included in our study who had hysterectomy between 1/1990 and 8/2021. Seventy-nine patients (68%) with <50% and 38 (32w%) with ≥50% CSI. After a median follow-up of 131 months, 5-year DSS was significantly worse for women with ≥50% CSI (78% vs. 91%; P =0.04). However, %CSI was not an independent predictor for any of the studied survival endpoints. Independent predictors of worse 5-year recurrence-free survival and DSS included FIGO grade 3 tumors ( P =0.02) and the presence of lymphovascular space invasion ( P =0.03). Grade 3 tumors were the only independent predictor of worse 5-year OS ( P =0.02). CONCLUSIONS: Our results suggest that deep CSI is not an independent prognostic factor for survival endpoints in women with stage II uterine endometroid adenocarcinoma. The lack of independent prognostic significance of the depth CSI needs to be validated in a multi-institutional analysis.

The Impact of Adjuvant Management Strategies on Outcomes in Women With Early Stage Uterine Serous Carcinoma.

Objective To determine the impact of different adjuvant strategies on outcomes in women with early-stage uterine serous carcinoma (USC). Methods Our retrospective database for women with endometrial carcinoma was queried for women with 2009 International Federation of Gynecology and Obstetrics (FIGO) stages I-II USC who underwent surgical staging between January 1991 and April 2019 followed by adjuvant management (observation, radiation therapy (RT), chemotherapy (CT), or combined modality treatment (CRT)). Chi-square tests were performed to compare differences in outcome by type of adjuvant management. Recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were assessed by Kaplan-Meier and log-rank tests. Univariate and multivariate analyses (MVA) were performed to identify statistically significant predictors of survival endpoints. Results We identified 171 women who met our inclusion criteria. The median follow-up time was 70.5 months. Seventy-five percent of the study cohort was FIGO stage IA, 13% were stage IB, and 12% were stage II. All women underwent pelvic lymph node dissection with a median number of dissected lymph nodes of 14. Omentectomy was performed in 64% of patients. Adjuvant RT was utilized in 56% of women (65 patients received vaginal brachytherapy alone, 10 patients received pelvic RT, and 21 patients received a combination of both). The most commonly used chemotherapy regimen was carboplatin and paclitaxel with a median number of cycles of six. A total of 44% of the cohort received CRT, 12% received RT alone, 19% received chemo alone, and 25% were observed. Five-year RFS was 73% for those who received CRT, 84% for those who received RT alone, 68% for those who received CT alone, and 55% for those who were observed (p=0.13). Five-year DSS was 81%, 94%, 71%, and 60%, respectively (p=0.02). Five-year OS was 76%, 70%, 60%, and 56%, respectively (p=0.11). On MVA of OS and DSS, a higher percentage of myometrial invasion, the presence of lower uterine segment involvement, positive peritoneal cytology, and receipt of chemotherapy alone/observation were independent predictors of worse outcomes. The sole independent predictor of worse RFS on MVA was the presence of positive peritoneal cytology. Conclusion In this cohort of women with early-stage USC who underwent surgical staging, adjuvant radiation treatment with or without chemotherapy was associated with improved survival endpoints and trended toward improved recurrence rates.

Matched-pair Analysis for Survival Endpoints Between Women With Early-stage Uterine Carcinosarcoma and Uterine Serous Carcinoma.

OBJECTIVE: The objective of this study was to compare survival endpoints between women with uterine carcinosarcoma and those with uterine serous carcinoma utilizing matching analysis. METHODS: Patients with stages I to II who underwent hysterectomy at our institution were included in this analysis. Patients with carcinosarcoma were then matched to patients with serous carcinoma based on stage, and adjuvant management received (observation, radiation treatment alone, chemotherapy alone, or combined modality with radiotherapy and chemotherapy. Recurrence-free survival, disease-specific survival, and overall survival were calculated for the 2 groups. RESULTS: A total of 134 women were included (67 women with carcinosarcoma and 67 with serous carcinoma, matched 1:1). There was no statistically significant difference between the 2 groups regarding 5-year recurrence-free survival (59% vs. 62%), disease-specific survival (66% vs. 67%), or overall survival (53% vs. 57%), respectively. The only independent predictor of shorter recurrence-free survival for the entire cohort was the lack of adjuvant combined modality therapy, while lower uterine segment involvement was the only independent predictor for shorter disease-specific survival. Lack of lymph node dissection and lack of adjuvant combined modality therapy were independent predictors of shorter overall survival. DISCUSSION: When matched based on stage and adjuvant treatment, our study suggests that there is no statistically significant difference in survival endpoints between women with early-stage carcinosarcoma and serous carcinoma. Adjuvant combined modality treatment is an independent predictor of longer recurrence-free survival and overall survival.

Quantification of recurrence risk based on number of adverse prognostic factors in women with stage I uterine endometrioid carcinoma

Objective: The goal was to develop an updated model to predict the risk of recurrence, based on the number of adverse pathologic features in women with International Federation of Gynecology and Obstetrics stage I uterine endometrioid carcinoma, who did not undergo any adjuvant treatment. Material and Methods: Women at a single center who underwent surgical staging without adjuvant therapy between January 1990 and December 2019 were included. Cox proportional hazards model was used to identify independent predictors of relapse free survival (RFS). Prognostic groups were then created based on the number of independent predictors of recurrence that were identified (0, 1, or 2-3 risk factors). Overall survival (OS) and disease specific survival (DSS) were also calculated for each group. Results: In total 1133 women were eligible for inclusion. Median follow-up was 84 months. Independent prognostic factors of recurrence included: age ≥60; grade 2 or 3 differentiation; and presence of lymphovascular space invasion (LVSI). Due to the small number of patients with either 2 or 3 risk factors, these groups were combined into one (group 2/3). Isolated vaginal cuff recurrence was the most common site of recurrence in all study groups (2%, 7%, and 17% for groups 0, 1, and 2/3, respectively). Five-year RFS rates were 96%, 85%, and 57% for groups 0, 1, and 2/3 (p<0.01), respectively. Five-year DSS rates were 99%, 96%, and 85% and 5-year OS rates were 94%, 85%, and 62% (p<0.01), respectively. Conclusion: We identified older age, high grade, and presence of LVSI as independent predictors of recurrence for women with stage I uterine endometrioid carcinoma. Using these prognostic factors, recurrence risk can be quantified for individual patients, and these factors can be used in deciding the appropriate adjuvant management course.

Ambient BTEX exposure and mid-pregnancy inflammatory biomarkers in pregnant African American women.

Air pollution is associated with preterm birth (PTB), potentially via inflammation. We recently showed the mixture benzene, toluene, ethylbenzene, and xylene (BTEX) is associated with PTB. We examined if ambient BTEX exposure is associated with mid-pregnancy inflammation in a sample of 140 African-American women residing in Detroit, Michigan. The Geospatial Determinants of Health Outcomes Consortium study collected outdoor air pollution measurements in Detroit; these data were coupled with Michigan Air Sampling Network measurements to develop monthly BTEX concentration estimates at a spatial density of 300 m2. First trimester and mid-pregnancy BTEX exposure estimates were assigned to maternal address. Mid-pregnancy (mean 21.3 ± 3.7 weeks gestation) inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin [IL]-6, IL-10, IL-1ß, and tumor necrosis factor-α) were measured with enzyme immunoassays. After covariate adjustment, for every 1-unit increase in first trimester BTEX, there was an expected mean increase in log-transformed IL-1ß of 0.05 ± 0.02 units (P = 0.014) and an expected mean increase in log-transformed tumor necrosis factor-α of 0.07 ± 0.02 units (P = 0.006). Similarly, for every 1-unit increase in mid-pregnancy BTEX, there was a mean increase in log IL-1ß of 0.06 ± 0.03 units (P = 0.027). There was no association of either first trimester or mid-pregnancy BTEX with high-sensitivity C-reactive protein, IL-10, or IL-6 (all P > 0.05). Ambient BTEX exposure is associated with inflammation in mid-pregnancy in African-American women. Future studies examining if inflammation mediates associations between BTEX exposure and PTB are needed.