Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV-negative cervical cancer.

Cervical carcinogenesis, the second leading cause of cancer death in women worldwide, is caused by multiple types of human papillomaviruses (HPVs). To investigate a possible role for HPV in a cervical carcinoma that was HPV-negative by PCR testing, we performed HPV DNA hybridization capture plus massively parallel sequencing. This detected a subgenomic, URR-E6-E7-E1 segment of HPV70 DNA, a type not generally associated with cervical cancer, inserted in an intron of the B-cell lymphoma/leukemia 11B (BCL11B) gene in the human genome. Long range DNA sequencing confirmed the virus and flanking BCL11B DNA structures including both insertion junctions. Global transcriptomic analysis detected multiple, alternatively spliced, HPV70-BCL11B, fusion transcripts with fused open reading frames. The insertion and fusion transcripts were present in an intraepithelial precursor phase of tumorigenesis. These results suggest oncogenicity of HPV70, identify novel BCL11B variants with potential oncogenic implications, and underscore the advantages of thorough genomic analyses to elucidate insights into HPV-associated tumorigenesis.

Risk factors associated with delayed discharge following robotic assisted surgery for gynecologic malignancy.

BACKGROUND: The risk factors for extended length of stay (LOS) have not been examined in a cohort of patients with complex social and medical barriers who undergo robotic assisted (RA) surgery for gynecologic malignancies. We sought to identify those patients with a LOS > 24 h after robotic surgery and the risk factors associated with delayed discharge. Then we aimed to develop a predictive model for clinical care and identify modifiable pre-operative risk factors. METHODS: After IRB approval, data was abstracted from medical records of all patients with a gynecologic malignancy who underwent a RA laparoscopic surgery from 2010 to 2015. Univariable and multivariable logistic regression was performed to identify independent risk factors associated with delayed discharge defined as LOS > 24 h. A multi-variable logistic regression model was performed using a stepwise backward selection for the final prediction model. All testing was two-sided and a p-value < 0.05 was considered statistically significant. RESULTS: Of the 406 eligible and evaluable patients, 194 (48%) had a LOS > 24 h. Age ≥ 60 years, a higher usage of narcotic medication, a longer surgical time, and a larger estimated blood loss were all associated with LOS > 24 h (p < 0.05). Many of these women had a social work consultation and went home with home care services despite no surgical or post-operative complications. Our prediction model has the potential to correctly classified 75% of the patients discharged within 24 h. CONCLUSIONS: The development of a pre-hospitalization risk stratification and anticipating the possible need for home care services pre-operatively shows promise as a strategy to decrease LOS in patients classified as high-risk. These findings warrant prospective validation through the use of this prediction model in our institution.

Association of obesity with survival in patients with endometrial cancer.

BACKGROUND: Obesity confers an overall increased risk for development of endometrial cancer. However there are conflicting reports regarding the effect of obesity on patients' overall and disease specific survival. The purpose of this study was to evaluate the effect of obesity on survival in women with endometrial cancer. METHODS: After IRB approval, records of women with diagnosis and treatment of endometrial cancer from 1999 to 2016 were abstracted for histopathological, treatment and demographic data. Death was confirmed by query of the Social Security Death Index. Kaplan Meier survival curves and Cox regression modeling was performed with Stata version 14.0. RESULTS: Of 1732 evaluable patients, there were significant differences in age at diagnosis, histology (endometrioid versus non-endometrioid), stage, race, grade, hypertension, hyperlipidemia, diabetes, and treatment between normal weight, overweight, obese, and morbidly obese patients (p < 0.01). There was a linear association of younger age at diagnosis with increasing obesity (p < 0.01) R2 = 0.04. Younger age, endometrioid histology, lower stage, and statin use were independently associated with decreased hazard of death (p < 0.01). However, in stratified analysis of non-endometrioid histologies, patients with Stage 3 and 4 disease over the age of 65 showed a survival benefit for women associated with obesity (p = 0.02). CONCLUSIONS: Obesity is associated with younger age at diagnosis and earlier stage disease. Obesity is associated with improved disease specific survival for stage 3 and 4 non-endometrioid endometrial cancers.

Neutrophilia and mortality in women with uterine carcinosarcoma.

OBJECTIVE: The objective of this study was to investigate the relationship between pre-treatment absolute neutrophil count and clinical outcomes in patients with uterine carcinosarcoma. METHODS: In an Institutional Review Board approved, retrospective cohort study of 103 patients with uterine carcinosarcoma, the pre-treatment absolute neutrophil count data were obtained from the medical records, along with clinical, pathologic, treatment, and outcome data. Kaplan-Meier survival estimates were calculated and compared by the log rank test. Univariable and multivariable Cox proportional hazard regression models were used to examine the relationship of pre-treatment absolute neutrophil count with progression-free survival and overall survival. RESULTS: Uterine carcinosarcoma patients in the highest quartile of pre-treatment absolute neutrophil count had significantly reduced progression-free survival (p<0.001, log rank test), and overall survival (p<0.001, log rank test), compared with patients in the lower absolute neutrophil count quartiles. On multivariable analysis, high absolute neutrophil count was an independent poor prognostic factor for disease recurrence, HR 2.97 (95% CI 1.35 to 6.53, p=0.007) for highest versus lowest quartile absolute neutrophil count, and for mortality, HR 4.43 (95% CI 1.64 to 12.00, p= 0.003). CONCLUSIONS: High pre-treatment absolute neutrophil count is an independent poor prognostic factor in patients with uterine carcinosarcoma and may be useful as a potential biomarker in clinical trials. The mechanistic relationship of neutrophilia and uterine carcinosarcoma progression merits further investigation.

Acceptability and feasibility of a Fitbit physical activity monitor for endometrial cancer survivors.

OBJECTIVE: Endometrial cancer survivors are the least physically active of all cancer survivor groups and exhibit up to 70% obesity. While studies suggest lifestyle interventions result in improved health outcomes, recruitment and availability of these programs are limited. The purpose was to evaluate the acceptability and validity of the Fitbit Alta™ physical activity monitor (Fitbit) for socioculturally diverse endometrial cancer survivors. METHODS: Thirty endometrial cancer survivors were given wrist-worn Fitbits to wear for 30 days. Participants then returned the Fitbits, completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ), Technology Acceptance Questionnaire, and answered qualitative prompts. Correlations between daily Fitbit step counts, demographic factors, body mass index (BMI), and GLTEQ Index, were analyzed using Stata 13.0. Concordance Correlation Coefficient using U statistics was used to examine convergent validity. RESULTS: Twenty-five participants completed the study. Mean age was 62 ±â€¯9 years. Mean BMI was 32 ±â€¯9 kg·m-2. Self-identified race/ethnicity was 36% Hispanic, 36% non-Hispanic white, 16% non-Hispanic black and 12% Asian. Participants wore the Fitbits a median of 93% of possible days. Median daily Fitbit step count was 5325 (IQR: 3761-8753). Mean Technology Acceptance score was 2.8 ±â€¯0.5 out of 4.0. Younger (<65 years) and employed participants were more likely to achieve at least 6000 daily steps (p < 0.05). There was no correlation (CCC = 0.00, p = 0.99) between step count and GLTEQ Index. Most free responses reflected positive experiences. CONCLUSIONS: The Fitbits were well accepted in this sample. Self-reported physical activity was not associated with steps recorded. The physical activity data indicate an insufficiently active population.

Expression of ßV-Tubulin in Secretory Cells of the Fallopian Tube Epithelium Marks Cellular Atypia.

OBJECTIVES: Class V Beta tubulin isotype (ßV-tubulin) was recently found to have tissue-specific expression patterns in epithelial tissues with secretory function and aberrant expression in tumors. The aims of this pilot study were (a) to examine expression of ßV-tubulin in the fallopian tube epithelium (FTE) of patients who underwent salpingectomy, (b) to characterize FTE atypia in high-risk patients with BRCA mutations, and (c) to determine expression of ßV-tubulin in serous ovarian neoplasms. METHODS: Immunohistochemistry, with a highly specific antibody developed in our laboratory against human ßV-tubulin, was used to evaluate expression in paraffin-embedded sections of the fallopian tube (n = 82) and tumors (n = 13), from prospectively selected cases, categorized by reason for salpingectomy. RESULTS: ßV-tubulin, when present, was expressed in secretory cells and essentially never in ciliated cells of the FTE. Histologically "normal" FTE had very rare, scattered ßV-tubulin-positive cells; percentage positivity increased in cases of serous ovarian neoplasms. The highest expression was observed in FTE from patients with BRCA mutant breast cancer. Four distinct types of FTE atypia were delineated in patients with known BRCA mutations. In a few additional test cases of ovarian neoplasms, ßV-tubulin was highly expressed, with the extent and intensity of staining elevated in high-grade serous carcinomas compared with serous borderline tumors. CONCLUSIONS: In summary, ßV-tubulin was localized to secretory cells of the distal FTE and its expression varied according to the clinical diagnosis. The frequency of these cells and thus expression of ßV-tubulin were dramatically enriched in tissue obtained from BRCA mutant cases, which also exhibited pronounced histologic atypia indicative of early predysplastic aberrations. Furthermore, elevated expression of ßV-tubulin correlated with poor differentiation status in serous ovarian neoplasms.

Prevalence and factors associated with cognitive deficit in women with gynecologic malignancies.

OBJECTIVE: Cognitive impairment has implications in counseling, treatment, and survivorship for women with gynecologic malignancies. The purpose of our study was to evaluate the prevalence and risk factors associated with cognition in women with gynecologic malignancies. METHODS: After Institutional Review Board approval, 165 women at an urban ambulatory gynecologic oncology facility were queried using a Montreal Cognitive Assessment (MoCA), Wong-Baker pain scale, neuropathy scale, Patient Health Questionnaire 9 (PHQ-9) Depression Scale, and Generalized Anxiety Disorder Scale (GAD 7). Univariate and multivariate analyses were utilized to evaluate the association of cognitive deficit with age, education, race/ethnicity, disease site, stage, treatment, pain, neuropathy, anxiety, and depression. RESULTS: The mean MoCA score for the entire cohort was 24.1 (range 13-30.) 24% of patients had MoCA scores less than 22. Low scores (<22) were associated with older age, non-white race/ethnicity, lower education level, uterine and vulvar cancers, and pain ≥5 (p<0.05). There was a trend toward lower cognition scores for women treated with both chemotherapy and radiation (p=0.10). While clinically significant pain was associated with low cognition, there was no association with use of opioid pain medication and low cognition scores. CONCLUSIONS: There was a high prevalence of cognitive deficit in women with gynecologic malignancies. The association of low cognition with report of clinically significant pain, but not with use of opioid pain medications, should be further explored. Research is needed to evaluate the impact of cognitive deficits on treatment adherence and outcomes for women with gynecologic malignancies.

Metformin use and endometrial cancer survival.

OBJECTIVE: Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancers using metformin has been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). METHODS: We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. RESULTS: Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio=0.54, 95% CI: 0.30-0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and the presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. CONCLUSION: Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.

The role and timing of palliative medicine consultation for women with gynecologic malignancies: association with end of life interventions and direct hospital costs.

OBJECTIVE: Aggressive care interventions at the end of life (ACE) are reported metrics of sub-optimal quality of end of life care that are modifiable by palliative medicine consultation. Our objective was to evaluate the association of inpatient palliative medicine consultation with ACE scores and direct inpatient hospital costs of patients with gynecologic malignancies. METHODS: A retrospective review of medical records of the past 100 consecutive patients who died from their primary gynecologic malignancies at a single institution was performed. Timely palliative medicine consultation was defined as exposure to inpatient consultation ≥ 30 days before death. Metrics utilized to tabulate ACE scores were ICU admission, hospital admission, emergency room visit, death in an acute care setting, chemotherapy at the end of life, and hospice admission <3 days. Inpatient direct hospital costs were calculated for the last 30 days of life from accounting records. Data were analyzed using Fisher's Exact, Mann-Whitney U, Kaplan-Meier, and Student's T testing. RESULTS: 49% of patients had a palliative medicine consultation and 18% had timely consultation. Median ACE score for patients with timely palliative medicine consultation was 0 (range 0-3) versus 2 (range 0-6) p=0.025 for patients with untimely/no consultation. Median inpatient direct costs for the last 30 days of life were lower for patients with timely consultation, $0 (range 0-28,019) versus untimely, $7729 (0-52,720), p=0.01. CONCLUSIONS: Timely palliative medicine consultation was associated with lower ACE scores and direct hospital costs. Prospective evaluation is needed to validate the impact of palliative medicine consultation on quality of life and healthcare costs.

Structure and transcription of integrated HPV DNA in vulvar carcinomas.

HPV infections are associated with a fraction of vulvar cancers. Through hybridization capture and DNA sequencing, HPV DNA was detected in five of thirteen vulvar cancers. HPV16 DNA was integrated into human DNA in three of the five. The insertions were in introns of human NCKAP1, C5orf67, and LRP1B. Integrations in NCKAP1 and C5orf67 were flanked by short direct repeats in the human DNA, consistent with HPV DNA insertions at sites of abortive, staggered, endonucleolytic incisions. The insertion in C5orf67 was present as a 36 kbp, human-HPV-hetero-catemeric DNA as either an extrachromosomal circle or a tandem repeat within the human genome. The human circularization/repeat junction was defined at single nucleotide resolution. The integrated viral DNA segments all retained an intact upstream regulatory region and the adjacent viral E6 and E7 oncogenes. RNA sequencing revealed that the only HPV genes consistently transcribed from the integrated viral DNAs were E7 and E6*I. The other two HPV DNA+ tumors had coinfections, but no evidence for integration. HPV-positive and HPV-negative vulvar cancers exhibited contrasting human, global gene expression patterns partially overlapping with previously observed differences between HPV-positive and HPV-negative cervical and oropharyngeal cancers. A substantial fraction of the differentially expressed genes involved immune system function. Thus, transcription and HPV DNA integration in vulvar cancers resemble those in other HPV-positive cancers. This study emphasizes the power of hybridization capture coupled with DNA and RNA sequencing to identify a broad spectrum of HPV types, determine human genome integration status of viral DNAs, and elucidate their structures.

Targeted in silico characterization of fusion transcripts in tumor and normal tissues via FusionInspector.

Here, we present FusionInspector for in silico characterization and interpretation of candidate fusion transcripts from RNA sequencing (RNA-seq) and exploration of their sequence and expression characteristics. We applied FusionInspector to thousands of tumor and normal transcriptomes and identified statistical and experimental features enriched among biologically impactful fusions. Through clustering and machine learning, we identified large collections of fusions potentially relevant to tumor and normal biological processes. We show that biologically relevant fusions are enriched for relatively high expression of the fusion transcript, imbalanced fusion allelic ratios, and canonical splicing patterns, and are deficient in sequence microhomologies between partner genes. We demonstrate that FusionInspector accurately validates fusion transcripts in silico and helps characterize numerous understudied fusions in tumor and normal tissue samples. FusionInspector is freely available as open source for screening, characterization, and visualization of candidate fusions via RNA-seq, and facilitates transparent explanation and interpretation of machine-learning predictions and their experimental sources.

Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women.

OBJECTIVE: To determine predictors of treatment failure and recurrence after surgical excisional procedures for CIN in HIV-infected women. METHODS: A retrospective cohort study was conducted in which 136 eligible HIV-infected women treated for CIN between 1999 and 2005 were included. Data were abstracted from charts and computer databases. Treatment failures were defined as the presence of CIN 1+ at initial follow-up. Recurrences were defined as the presence of CIN 1+ subsequent to initial normal follow-up. RESULTS: Treatment failure at initial follow-up was common, occurring in 51% of CIN 1 and 55% of CIN 2+. Most lesions detected at treatment failure were high grade (>70%), regardless of the grade of initial lesion. Significant risk factors for treatment failure were loop electrosurgical excision procedure (LEEP) compared to cold knife conization (RR=1.76; 95% CI: 1.15-2.64), and low CD4+ count (p=0.04). Among those with an initial normal clinical evaluation, 55% eventually recurred. As with treatment failure, most lesions detected at recurrence were high grade. Risk factors for recurrence included use of LEEP (hazard ratio [HR]=3.38; 95% CI: 1.55-7.39), higher HIV RNA level, and the presence of positive margins at treatment (HR=6.12; 95% CI: 1.90-19.73). CONCLUSIONS: Most CIN treatment of HIV-infected women studied either failed or resulted in recurrence. Of particular concern, many of these subsequent lesions were high grade. Conization, however, was associated with significantly less failure/recurrence than LEEP. Clinicians treating CIN in HIV-infected women should avoid raising expectations of cure and instead focus on the achievable goal of cancer prevention until there are better therapies for this patient population.

Endometrial thickness, Caucasian ethnicity, and age predict clinical pregnancy following fresh blastocyst embryo transfer: a retrospective cohort.

BACKGROUND: In-vitro fertilization (IVF) with blastocyst as opposed to cleavage stage embryos has been advocated to improve success rates. Limited information exists on which to predict which patients undergoing blastocyst embryo transfer (BET) will achieve pregnancy. This study's objective was to evaluate the predictive value of patient and cycle characteristics for clinical pregnancy following fresh BET. METHODS: This was a retrospective cohort study from 2003-2007 at an academic assisted reproductive program. 114 women with infertility underwent fresh IVF with embryo transfer. We studied patients undergoing transfer of embryos at the blastocyst stage of development. Our main outcome of interest was clinical pregnancy. Clinical pregnancy and its associations with patient characteristics (age, body mass index, FSH, ethnicity) and cycle parameters (thickness of endometrial stripe, number eggs, available cleaving embryos, number blastocysts available, transferred, and cryopreserved, and embryo quality) were examined using Student's T test and Mann-Whitney-U tests as appropriate. Multivariable logistic regression models were created to determine independent predictors of CP following BET. Receiver Operating Characteristic analyses were used to determine the optimal thickness of endometrial stripe for predicting clinical pregnancy. RESULTS: Patients achieving clinical pregnancy demonstrated a thicker endometrial stripe and were younger preceding embryo transfer. On multivariable logistic regression analyses, Caucasian ethnicity (OR 2.641, 95% CI 1.054-6.617), thickness of endometrial stripe, (OR 1.185, 95% CI 1.006-1.396) and age (OR 0.879, 95% CI 0.789-0.980) predicted clinical pregnancy. By receiver operating characteristic analysis, endometrial stripe >or= 9.4 mm demonstrated a sensitivity of 83% for predicting clinical pregnancy following BET. CONCLUSION: In a cohort of patients undergoing fresh BET, thicker endometrial stripe, Caucasian ethnicity, and younger age are positive predictors of clinical pregnancy after fresh BET. These findings may be useful in clinical management of infertile patients undergoing fresh BET cycles.

Insulin-like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma.

The objective of this study was to investigate the relationship of insulin-like growth factor 2 (IGF2) expression and survival in women with uterine carcinosarcoma (UCS). Insulin-like growth factor 2 protein expression was determined by immunohistochemical staining of tumor tissues from 103 patients with UCS. The H-score (product of staining intensity and percentage positive cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear (EN), and malignant stromal compartments. Multivariable Cox proportional hazard regression models were used to examine the relationship of IGF2 levels with progression-free survival (PFS) and overall survival (OS). Adjusting for stage, race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H-score ≥ median) in the EC and EN compartments. Black race was independently associated with reduced PFS and OS in patients with early-stage disease, and IGF2 levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon test). In a race-stratified multivariable analysis, high IGF2 in the epithelial compartments more than doubled the risk of death in black women; HR = 2.43 (95% CI: 1.18-5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25-4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2 expression is an independent risk factor for reduced PFS and OS in UCS. Black women have elevated tumor IGF2 compared with white women, and decreased survival associated with high IGF2. These findings identify IGF2 as a candidate biomarker for survival linked to racial disparity in women with UCS.

The gynecologic oncology fellowship interview process: Challenges and potential areas for improvement.

The application and interview process for gynecologic oncology fellowship is highly competitive, time-consuming and expensive for applicants. We conducted a survey of successfully matched gynecologic oncology fellowship applicants to assess problems associated with the interview process and identify areas for improvement. All Society of Gynecologic Oncology (SGO) list-serve members who have participated in the match program for gynecologic oncology fellowship were asked to complete an online survey regarding the interview process. Linear regression modeling was used to examine association between year of match, number of programs applied to, cost incurred, and overall satisfaction. Two hundred and sixty-nine eligible participants reported applying to a mean of 20 programs [range 1-45] and were offered a mean of 14 interviews [range 1-43]. They spent an average of $6000 [$0-25,000], using personal savings (54%), credit cards (50%), family support (12%) or personal loans (3%). Seventy percent of respondents identified the match as fair, and 93% were satisfied. Interviewees spent a mean of 15 [0-45] days away from work and 37% reported difficulty arranging coverage. Linear regression showed an increase in number of programs applied to and cost per applicant over time (p < 0.001) between 1993 and 2016. Applicants who applied to all available programs spent more (p < 0.001) than those who applied to programs based on their location or quality. The current fellowship match was identified as fair and satisfying by most respondents despite being time consuming and expensive. Suggested alternative options included clustering interviews geographically or conducting preliminary interviews at the SGO Annual Meeting.

Comparison of Subcuticular Suture Type for Skin Closure After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To compare the rate of wound complications among women who underwent cesarean delivery through a Pfannenstiel skin incision followed by subcuticular closure with either poliglecaprone 25 suture or polyglactin 910 suture. METHODS: Patients undergoing nonemergent cesarean delivery at or beyond 37 weeks of gestation were randomized to undergo subcuticular skin closure with either poliglecaprone 25 or polyglactin 910. The primary outcome was a wound composite outcome of one or more of the following: surgical site infection, wound separation, hematoma, or seroma within the first 30 days postpartum. To detect a reduction in the primary outcome rate from 12% to 4%, with a power of 0.90 and a two-tailed α of 0.05, 237 women per study group were required. Analysis was performed according to the intent-to-treat principle. RESULTS: From May 28, 2015, to August 5, 2016, 275 women were randomized to poliglecaprone 25 and 275 to polyglactin 910, of whom 520 (95%) were included in the final analysis: 263 in the poliglecaprone 25 group [of whom 231 (88%) actually underwent poliglecaprone 25 closure) and 257 in the polyglactin 910 group [of whom 209 (81%) actually underwent polyglactin 910 closure]. The groups were similar in demographic characteristics, medical comorbidities, and perioperative characteristics. Poliglecaprone 25 was associated with a significantly decreased rate of overall wound complications when compared with polyglactin 910, 8.8% compared with 14.4% (relative risk 0.61, 95% CI 0.37-0.99; P=.04). CONCLUSION: Closure of the skin after cesarean delivery with poliglecaprone 25 suture decreases the rate of wound complications compared with polyglactin 910 suture. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02459093.

Skin Preparation for Prevention of Surgical Site Infection After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To compare chlorhexidine with alcohol, povidone-iodine with alcohol, and both applied sequentially to estimate their relative effectiveness in prevention of surgical site infections after cesarean delivery. METHODS: Women undergoing nonemergent cesarean birth at greater than 37 0/7 weeks of gestation were randomly allocated to one of three antiseptic skin preparations: povidone-iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions. The primary outcome was surgical site infection reported within the first 30 days postpartum. Based on a surgical site infection rate of 12%, an anticipated 50% reduction for the combination group relative to either single skin preparation group, with a power of 0.90 and an α of 0.05, 430 women per group were needed to detect a difference. RESULTS: From January 2013 to July 2014, 1,404 women were randomly assigned to one of three groups: povidone-iodine with alcohol (n=463), chlorhexidine with alcohol (n=474), or both (n=467). The groups were similar with respect to demographics, medical disorders, indication for cesarean delivery, operative time, and blood loss. The overall rate of surgical site infection-4.3%-was lower than anticipated. The skin preparation groups had similar surgical site infection rates: povidone-iodine 4.6%, chlorhexidine with alcohol 4.5%, and sequential 3.9% (P=.85). CONCLUSION: The skin preparation techniques resulted in similar rates of surgical site infections. Our study provides no support for any particular method of skin preparation before cesarean delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01870583. LEVEL OF EVIDENCE: I.

Association Between Statin Use and Endometrial Cancer Survival.

OBJECTIVE: To evaluate the association of 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) use and concordant polypharmacy with disease-specific survival from endometrial cancer. METHODS: A retrospective cohort study was conducted of 985 endometrial cancer cases treated from January 1999 through December 2009 at a single institution. Disease-specific survival was estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to study factors associated with survival. All statistical tests were two-sided and performed using Stata. RESULTS: At the time of analysis, 230 patients (22% of evaluable patients) died of disease and median follow-up was 3.28 years. Disease-specific survival was greater (179/220 [81%]) for women with endometrial cancer taking statin therapy at the time of diagnosis and staging compared with women not using statins (423/570 [74%]) (log rank test, P=.03). This association persisted for the subgroup of patients with nonendometrioid endometrial tumors who were statin users (59/87 [68%]) compared with nonusers (93/193 [43%]) (log rank test, P=.02). The relationship remained significant (hazard ratio 0.63, 95% confidence interval [CI] 0.40-0.99) after adjusting for age, clinical stage, radiation, and other factors. Further evaluation of polypharmacy showed an association between concurrent statin and aspirin use with an especially low disease-specific mortality (hazard ratio 0.25, 95% CI 0.09-0.70) relative to those who used neither. CONCLUSION: Statin and aspirin use was associated with improved survival from nonendometrioid endometrial cancer.

Obesity and age at diagnosis of endometrial cancer.

OBJECTIVE: Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. METHODS: A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. RESULTS: A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, P<.001). This association persisted after multivariable adjustment (R=0.181, P<.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. CONCLUSIONS: Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. LEVEL OF EVIDENCE: II.