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Ovarian cancer ascites fluid contains matrix proteins that can impact tumor growth via integrin receptor binding. In human ovarian tumor tissue arrays, we find that activation of the cytoplasmic focal adhesion (FAK) tyrosine kinase parallels increased tumor stage, β5 integrin, and osteopontin matrix staining. Elevated osteopontin, β5 integrin, and FAK mRNA levels are associated with decreased serous ovarian cancer patient survival. FAK remains active within ovarian cancer cells grown as spheroids, and anchorage-independent growth analyses of seven ovarian carcinoma cell lines identified sensitive (HEY, OVCAR8) and resistant (SKOV3-IP, OVCAR10) cells to 0.1 μmol/L FAK inhibitor (VS-4718, formerly PND-1186) treatment. VS-4718 promoted HEY and OVCAR8 G0–G1 cell-cycle arrest followed by cell death, whereas growth of SKOV3-IP and OVCAR10 cells was resistant to 1.0 μmol/L VS-4718. In HEY cells, genetic or pharmacological FAK inhibition prevented tumor growth in mice with corresponding reductions in β5 integrin and osteopontin expression. β5 knockdown reduced HEY cell growth in soft agar, tumor growth in mice, and both FAK Y397 phosphorylation and osteopontin expression in spheroids. FAK inhibitor–resistant (SKOV3-IP, OVCAR10) cells exhibited anchorage-independent Akt S473 phosphorylation, and expression of membrane-targeted and active Akt in sensitive cells (HEY, OVCAR8) increased growth but did not create a FAK inhibitor–resistant phenotype. These results link osteopontin, β5 integrin, and FAK in promoting ovarian tumor progression. β5 integrin expression may serve as a biomarker for serous ovarian carcinoma cells that possess active FAK signaling. Mol Cancer Ther; 13(8); 2050–61. ©2014 AACR.

PDF file - 44K, Antibodies, DNA plasmids, and probe sets used in this study.

PDF file - 138K, Integrin surface expression in HEY beta5 integrin knockdown cells.

PDF file - 66K, qPCR verification of beta5 transcripts.

PDF file - 315K, Cell survival and cell cycle progression analyses of VS-4718 FAK inhibitor sensitive (HEY and OVCAR8) and resistant (OVCAR10 and SKOV3-IP) cells.

PDF file - 112K, Pharmacological FAK inhibition decreases beta5 integrin and osteopontin (OPN) levels in ID8-IP cells in vivo.

PDF file - 894K, FAK and pY397 FAK immunostaining of human tissue array.

PDF file - 70K, Background information on the breast and ovarian carcinoma cell lines used in this study.

PDF file - 59K

Objective: Human papillomavirus (HPV) vaccination rates among Hispanic adolescents in the USA are far below recommended levels. Using a social marketing theory framework, we assessed the four Ps (product, price, place and promotion) as they relate to efforts to promote HPV vaccine initiation. Design: Qualitative study involving in-depth interviews. Setting: A large Southern city in the USA. Method: Eighty-five in-depth qualitative interviews were conducted with Spanish-speaking Hispanic mothers divided into initiated and uninitiated market segments based on whether or not their adolescent child had received the first dose of the HPV vaccine. Data were analysed using directed qualitative content analysis. Results: Results suggest that the desire to prevent illnesses and protect their child drives the decision to vaccinate (product). Most initiated mothers did not experience barriers to vaccination, and market segments described different potential barriers (price). Both marker segments reported that they needed vaccine information before vaccinating (price). Finally, interventions should target clinics, schools and community centres to raise awareness about the importance of vaccinating against HPV (place and promotion). Conclusion: Findings from this formative study can inform the development of an intervention to increase HPV vaccine initiation among Hispanic adolescents.

Rates of HPV vaccination among adolescent Hispanic males lag far behind the Healthy People 2020 80% goal. This study identified Hispanic mothers' salient beliefs regarding having their sons initiate the HPV vaccine series. Twenty-seven Hispanic mothers completed in-depth interviews. They responded to questions that elicited the salient behavioral, normative and control beliefs associated with initiating the HPV vaccine series. We content analyzed their responses. We found that, regarding having their sons initiate the HPV vaccine, mothers: (1) express mostly positive feelings; (2) believe that the vaccine has positive effects, with side effects as the main negative effect; (3) believe that their sons' father and doctor support vaccination while some friends do not; and (4) believe that vaccine affordability, transportation and the support of their sons' father facilitate vaccine initiation. Overall, mothers held positive salient beliefs about the HPV vaccine including that it protects their son's health, has minimal side effects and is recommended by physicians. We are more likely to increase vaccination rates among adolescent Hispanic males if we address mothers' salient beliefs, including reinforcing their positive beliefs.

To determine incidence of ovarian clear cell cancer (OCCC) by race ethnicity and how that relationship is affected by birthplace among Asian Pacific Islanders (API).The 18 registries of the U.S. Surveillance, Epidemiology, and End Results (SEER) dataset were queried to identify all women registered with epithelial ovarian cancer from 1973 to 2013. Relative risks of OCCC to non-OCCC based on ethnicity and birthplace were compared.We identified 72, 501 women with epithelial ovarian cancer in the dataset; of these, 5078 (7.0%) had OCCC and 4859 (6.7%) were API. The age-adjusted incidence rate/100,000 women of OCCC was significantly higher in API women (0.6, 0.5-0.6 95% CI) compared to any other ethnicity. A significantly higher proportion of API women had OCCC (14.5%) compared to their White (6.6%, RR 2.2, p 0.0001) and Black counterparts (4.3%, RR 3.4, p 0.0001). The majority of API women were foreign-born (70.8%). The relative risk of clear cell compared to non-clear cell epithelial ovarian cancer was not demonstrably different among foreign born API women with ovarian cancer (RR 1.1, 95% CI 0.9 to 1.3, p = 0.6).We have demonstrated that, in the US, there is an elevated risk of OCCC associated with API ethnicity. Place of birth does not appear to significantly modify the association, suggesting that the increased risk of OCCC in API women may not be affected by acculturation or environmental exposure. Future research exploring the complex relationships between ethnicity and risk of malignancy will be important as we make progress in understanding disease process and treatment.

Human papillomavirus (HPV) vaccine series completion among adolescent Hispanic males (35%) is lower than the Healthy People 2020 80% goal. This directed qualitative content analysis identified mothers' beliefs about their sons completing the series. We found that mothers (N = 19) (1) express positive feelings; (2) believe the vaccine has positive effects; (3) identify the father and doctors as supporters and friends as nonsupporters; (4) list health insurance, transportation, and clinic reminders as facilitators; and (5) mention affordability as a barrier to vaccine completion. Results provide guidance for interventions. Increasing HPV vaccination among boys will decrease the overall incidence of HPV in this population.

Guided by the Integrative Model of Behavioral Prediction, we identify mothers’ salient beliefs regarding their daughters’ initiation of the human papillomavirus vaccine series. In all, 34 Hispanic mothers responded to elicitation questions. Salient beliefs included the following: (1) feeling secure, happy, relieved, concerned, and fear about vaccinating; (2) believing that vaccinating prevents and protects from human papillomavirus but may result in side effects and sexual disinhibition; (3) identifying the daughter, father, mother, aunt, friends, and grandmothers as supporters/non-supporters; and (4) affordability, transportation, clinic distance, and making appointments as facilitators/barriers. This study begins the process of building a model of human papillomavirus vaccine initiation for this population.

Obesity is implicated as an important factor in the rising incidence of liver cancer in the United States. Bariatric surgery is increasingly used for treating morbid obesity and comorbidities. Using administrative data from UHC, a consortium of academic medical centers in the US, we compared the prevalence of liver cancer among admissions with and without a history of bariatric surgery within a 3-year period. Admissions with a history of bariatric surgery had a 61% lower prevalence of liver cancer compared to those without a history of bariatric surgery (prevalence ratio 0.39, 95% confidence interval 0.35 – 0.44), and these inverse associations persisted within strata of sex, race, and ethnicity. This hospital administrative records-based analysis suggests that bariatric surgery could play a role in liver cancer prevention.

Objectives To compare comorbidities of women with uterine cancer (UC) to controls so as to aid in development of survivorship care plans and programs. Methods Retrospective cohort study using the University HealthSystem Consortium (UHC) database that compared women who had a hysterectomy for UC to women without UC undergoing hysterectomy. Frequencies and odds ratios (ORs) of 26 comorbidities were calculated. Mantel–Haenszel stratified ORs were determined to correct for different age distributions between the UC and control groups using UHC predetermined age groups. Results 23,227 patients in the dataset were included in the UC cohort, and 142,601 patients served as controls. Uncorrected ORs≥2 were found for hypertension, diabetes, obesity, congestive heart failure, pulmonary circulatory diseases, peripheral vascular disease, and renal failure. Higher ORs for UC remained significant after stratification by age for hypertension (OR=1.7), diabetes (OR=2.1), obesity (OR=3.3), congestive heart failure (OR=1.5), pulmonary circulatory disorders (OR=1.7), and renal failure (OR=1.2). Conclusions Multiple comorbid conditions, specifically those related to the metabolic syndrome, were more prevalent in UC survivors than in the general population, and this difference persisted after adjustment for age. UC survivorship programs should plan to allocate resources to account for these differences in healthcare needs.

Objective To evaluate intramuscular ketorolac compared with placebo saline injection for pain control with intrauterine device (IUD) placement. Methods We conducted a randomized, double-blind, placebo-controlled trial between July 2012 and March 2014. Patients received 30 mg ketorolac or placebo saline intramuscular injection 30 minutes before IUD placement. The primary outcome was pain with IUD placement on a 10-cm visual analog scale. Sample size was calculated to provide 80% power to show a 2.0-cm difference (α=0.05) in the primary outcome. Secondary outcomes included pain with study drug injection, speculum insertion, tenaculum placement, uterine sounding, and at 5 and 15 minutes after IUD placement. Results A total of 67 women participated in the study, 33 in the ketorolac arm and 34 in the placebo arm. There were no differences in baseline demographics including age, body mass index, and race. There were no differences in median pain scores for IUD placement in the placebo compared with ketorolac groups (5.2 compared with 3.6 cm, P=.99). There was a decrease in median pain scores at 5 minutes (2.2 compared with 0.3 cm, P≤.001) and 15 minutes (1.6 compared with 0.1 cm, P≤.001) after IUD placement but no difference for all other time points. Nulliparous participants (n=16, eight per arm) had a decrease in pain scores with IUD placement (8.1 compared with 5.4 cm, P=.02). In this study, 22% of participants in the placebo group and 18% in the ketorolac group reported injection pain was as painful as IUD placement. Conclusion Ketorolac does not reduce pain with IUD placement but does reduce pain at 5 and 15 minutes after placement. Clinical trial registration ClinicalTrials.gov; www.clinicaltrials.gov, NCT01664559. Level of evidence I.

Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics. Results. Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%). Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13). A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%). Six patients sought insurance approval for a targeted therapy and two were declined (33%). One patient (4%) received a targeted therapy and this was discontinued due to tumor progression. Conclusions. There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials.

To reduce the high incidence of cervical cancer among Latinas in the United States it is important to understand factors that predict screening behavior. The aim of this study was to test the utility of theory of planned behavior in predicting cervical cancer screening among a group of Latinas. A sample of Latinas ( N = 614) completed a baseline survey about Pap test attitudes subjective norms, perceived behavioral control, and intention to be screened for cervical cancer. At 6 months postbaseline, cervical cancer screening behavior was assessed. Structural equation modeling was used to test the theory. Model fit statistics indicated good model fit: χ2(48) = 54.32, p = .246; comparative fit index = .992; root mean square error of approximation = .015; weighted root mean square residual = .687. Subjective norms ( p = .005) and perceived behavioral control ( p < .0001) were positively associated with intention to be screened for cervical cancer, and the intention to be screened predicted actual cervical cancer screening ( p < .0001). The proportion of variance ( R2) in intention accounted for by the predictors was .276 and the R2 in cervical cancer screening accounted for was .130. This study provides support for the use of the theory of planned behavior in predicting cervical cancer screening among Latinas. This knowledge can be used to inform the development of a theory of planned behavior–based intervention to increase cervical cancer screening among Latinas and reduce the high incidence of cervical cancer in this group of women.

Background Treatment for early-invasive adenocarcinoma of the cervix remains controversial. Although data have shown similar survival rates to those seen with squamous cell carcinoma, conservative options for patients with microinvasive adenocarcinoma have not been as widely accepted. Despite comparable survival outcomes, patients with early-invasive adenocarcinoma are still routinely subjected to more radical surgical techniques than their equivalently staged squamous cell counterparts. Objective The objective of the study was to evaluate how less radical surgery has an impact on 5 year survival in patients with microinvasive adenocarcinoma of the cervix. Study Design The Surveillance, Epidemiology, and End Results database was queried from 1988 through 2010 to perform a retrospective analysis of women with International Federation of Gynecology and Obstetrics stage IA1 or IA2 cervical carcinoma. Five year survival by procedure type (local excision, simple hysterectomy, or radical hysterectomy) was determined for each cell type (squamous or adenocarcinoma), as was lymph node status. Results Among 1567 patients with cervical adenocarcinoma, 5 year survival was 97.3% (confidence interval, 95.8–98.2%) for stage IA1 disease and 98.3% (confidence interval, 96.5%, 99.2%) for stage IA2. For comparison, the 5-year survival rates for 5,749 patients with stage IAI or lA2 squamous cell carcinoma were 96.7% (confidence interval, 96.0–97.3%) and 95.6% (confidence interval, 94.4–96.5%), respectively. For stage IA1 ACA, survival was 96.6%, 98.4% and 96.5% following excision, hysterectomy and radical hysterectomy, respectively. For stage IA2 ACA, survival rates were 100%, 96.9% and 99.4%, respectively. There was no statistical difference in survival between patients having either cell type undergoing local excision ( P = .26), simple hysterectomy ( P = .08), or radical hysterectomy ( P = .87). We also found no statistically significant difference in survival among patients with adenocarcinoma compared by treatment type (local excision compared with simple hysterectomy [ P = .64]; local excision compared with radical hysterectomy [ P = .82]; or simple hysterectomy compared with radical hysterectomy [ P = .70]). Among patients with adenocarcinoma, 0.97% had positive pelvic lymph nodes, none had positive aortic lymph nodes, and 91.85% had confirmed negative lymph nodes. For squamous cell carcinoma, 0.72% of patients had positive pelvic lymph nodes and 0.10% had positive aortic lymph nodes. Conclusion There was no significant difference in survival when patients were compared by cell type or procedure, suggesting that survival of patients with microinvasive adenocarcinoma is not improved by utilizing more invasive surgical methods. Regardless of histology, the frequency of nodal involvement was very low among both groups, supporting an overall excellent prognosis for all patients with microinvasive disease. We submit these data as evidence that preoperative planning of more conservative techniques is appropriate, not just for those with squamous histology or who desire future fertility, but for all patients with microinvasive cervical disease.

HPV vaccine series completion rates among adolescent Hispanic females and males (~39 and 21 %, respectively) are far below the Healthy People 80 % coverage goal. Completion of the 3-dose vaccine series is critical to reducing the incidence of HPV-associated cancers. This formative study applies social marketing theory to assess the needs and preferences of Hispanic mothers in order to guide the development of interventions to increase HPV vaccine completion. We conducted 51 in-depth interviews with Hispanic mothers of adolescents to identify the key concepts of social marketing theory (i.e., the four P's: product, price, place and promotion). Results suggest that a desire complete the vaccine series, vaccine reminders and preventing illnesses and protecting their children against illnesses and HPV all influence vaccination (product). The majority of Completed mothers did not experience barriers that prevented vaccine series completion and Initiated mothers perceived a lack of health insurance and the cost of the vaccine as potential barriers. Informational barriers were prevalent across both market segments (price). Clinics are important locations for deciding to complete the vaccine series (place). They are the preferred sources to obtain information about the HPV vaccine thus making them ideal locations to deliver intervention messages, followed by television, the child's school and brochures (promotion). Increasing HPV vaccine coverage among Hispanic adolescents will reduce the rates of HPV-associated cancers and the cervical cancer health disparity among Hispanic women. This research can inform the development of an intervention to increase HPV vaccine series completion in this population.

Objective To describe the risk of uterine malignancy among women who have had weight loss surgery. Methods We performed a retrospective cohort study among inpatient admissions of women 18years, or older, registered in the University HealthSystem Consortium (UHC) dataset. The rate of uterine malignancy per hospital admission was calculated. Rates were compared according to whether diagnoses at the time of discharge included history of bariatric surgery, and further, according to whether there was a diagnosis of obesity. Results In admissions of patients who did not have a history of prior bariatric surgery, the rate of uterine malignancy was 599/100,000 (95% CI 590 to 610). Among obese women who had not previously undergone bariatric operations, the rate was 1409/100,000 (95% CI 1380 to 1440). Of women admitted who had a history of bariatric surgery, the rate of uterine malignancy was 408/100,000 (95% CI 370 to 450). The relative risk of uterine malignancy in all admissions for women who had prior bariatric surgery, compared to obese women who had not had bariatric surgery, was 0.29 (95% CI 0.26–0.32). Among women who had bariatric surgery and were not currently obese, the relative risk of uterine malignancy was 0.19 (95% CI 0.17–0.22) compared to obese women who had not undergone bariatric surgery. Conclusion A history of bariatric surgery is associated with a 71% reduced risk for uterine malignancy overall, and an 81% reduced risk if normal weight is maintained after surgery. This finding suggests that obesity may be a modifiable risk factor related to development of endometrial cancer.

To evaluate publically available, individually identified data regarding industry payments made to obstetrician-gynecologists (ob-gyns) during 2014 posted on the Centers for MedicareMedicaid Services' Open Payments website for the purposes of encouraging ob-gyns to partake in disclosure of their fiscal relationships to patients and to take an active role in maintaining accuracy of their payment data.In this retrospective study, we reviewed the Centers for MedicareMedicaid Services' Open Payments website for all 2014 nonresearch payments to ob-gyns. We compared payments to ob-gyns with payments to those in other specialties as well as subspecialties within the field of obstetrics and gynecology. Univariate statistical analyses were performed.Payments to ob-gyns totaled $60,004,472 (3.3% of the total value transferred in 2014) and went to 29,783 physician recipients. Fifty percent of these payments were for royalties and licensing. Obstetrics and gynecology ranked seventh in total number of payments made to a single specialty (n=311,485), and 20th of 35 specialties for highest median payment ($140, interquartile range $50-347). Medtronic USA, Inc. was the leading payer to ob-gyns.Ob-gyns are listed as having received substantial payments from industry in 2014. Because this information is publically available, we suggest physicians become familiar with payment data and the correction process, keep independent records, and register for updates to most effectively manage perceived, or real, conflicts of interest.

To evaluate risk of suicide of women with invasive gynecologic malignancies, the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (1973-2007) was queried. Suicide per 100,000 women with gynecologic malignancies was compared with that of women with other malignancies; suicide was 30% more likely in those with gynecologic malignancies. Most suicides occurred within 4 years of diagnosis. Better understanding of the descriptive epidemiology of suicide among women with gynecologic malignancies could lead to improved risk assessment, screening, and prevention of this potentially avoidable cause of death.

Objective To describe changes in the cervical cancer population. Methods The SEER database 9 registries from 1973 to 2008 were queried to perform a retrospective cohort study of women with invasive cervical cancer. Estimated annual percent change (EAPC) in incidence rates and 95% confidence intervals (CI) over the entire study period were compared according to age, stage, race, and cell type (squamous [SCC] and adenocarcinoma [ACA]). Proportions and odds ratios (OR) were calculated for patients diagnosed during the second half (1990–2008) compared to first half (1973–89) of the study period. Results 40,363 women with cervical cancer were entered into SEER. The EAPC are falling fastest among those with localized disease (−2.5%; 95% CI −2.8 to −2.1), age≥50 (−3.0%; 95% CI=−3.2 to −2.8), and black women (−3.8%; 95% CI=−4.1 to −3.6). The odds of a newly diagnosed cervical cancer patient having advanced disease are 10% higher, being less than age 50 are 37% higher, and being Asian or Pacific Islander are 68% higher in the second time period as compared to the first. Conclusions In the US, the population with cervical cancer is changing. Patients are presently significantly more likely to be pre-menopausal, Asian or Pacific Islander, and more frequently have non-squamous histology than previously. These progressive and cumulative changes could be due to the disparate impact of current population based screening and prevention strategies. Understanding the implications of these evolving population characteristics may facilitate planning targeted studies and interventions for cervical cancer prevention, screening and treatment in the future.

Culture may play an important role in contraceptive preference among young Hispanic women. We examined whether acculturation predicted the use of different contraceptives, grouped by level of efficacy in preventing pregnancy.1017 sexually active Hispanic women between the ages of 16 and 24 (mean age 20.69 ± 2.42 years) responded to a self-administered questionnaire. Data were analyzed using multinomial logistic regression.Women low in acculturation (OR 1.79, CI 1.06-3.02) and bicultural (OR 2.66, CI 1.52-4.64) were more likely than women high in acculturation to have used no method of contraception than long-acting reversible contraception (LARC). Bicultural women were more likely to have used condoms than LARC (OR 2.51, CI 1.40-4.49) compared to women high in acculturation. Finally, women in low in acculturation (OR 1.98, CI 1.11-3.50) and bicultural (OR 1.88, CI 1.01-3.51) were more likely to have used cyclic hormonal contraception than LARC compared to women high in acculturation.Educational efforts should focus on young Hispanic women who are bicultural and low in acculturation in order to increase their use of more effective contraceptive methods and reduce the number of unplanned pregnancies among this population.

Gentamicin, an aminoglycoside with broad antimicrobial activity, is commonly used in both obstetrics and gynecology. Traditional dosing regimens for gentamicin have called for 3 times daily dosing, but recent insights into the pharmacodynamics of the drug have led to multiple studies of once-daily dosing regimens. Many studies have demonstrated efficacy, safety, and economy of the 24-hour dosing interval, resulting in recommendations that this become the standard for aminoglycoside administration. However, because of the unique considerations for drug administration in pregnant and postpartum women, the once-daily dosing regimens have not been widely adopted. Additional studies in pregnant and postpartum women have demonstrated therapeutic noninferiority, no increase in adverse events, and significant cost savings with once-daily dosing versus 3 times daily dosing of gentamicin. We review the literature and present rationale based on multiple-controlled studies supporting single-daily dosing of gentamicin, 5λmg/kg/d actual body weight, for many common obstetrics-gynecology infections.

Objective We hypothesized that patients with type 1 diabetes mellitus (T1DM) who were managed during their pregnancy with a continuous subcutaneous insulin infusion (CSII) would have a lower incidence of neonatal hypoglycemia (NH) than patients managed with multiple daily injections (MDI) of insulin. Study Design This was a retrospective cohort of 95 women with T1DM who delivered singleton, term neonates between 2007 and 2014. The primary outcome was incidence of NH (capillary plasma glucose ≤ 45 mg/dL) in the first 24 hours after birth. Results The incidence of NH was 66.0% (62/95). The NH rate was significantly higher in women managed with CSII versus MDI (62 vs. 38%, p = 0.024). Neonates with NH had a higher birth weight (3,867 ± 658 vs. 3,414 ± 619 g, p = 0.002). When analyzing intrapartum glucose management, mothers of neonates with NH had significantly less time managed on an insulin infusion (median interquartile range 7 [3.5–30.5] vs. 17.5 [2.0–17.5] hours, p = 0.014). In multivariable analysis, only maternal body mass index (BMI) (p = 0.035) and time on an insulin infusion (p = 0.043) were significantly associated with NH. Conclusion In our population of patients with T1DM, CSII was more prevalent in the NH group; however, when controlling for other factors, intrapartum glucose management and early maternal BMI were the only variables associated with NH.

Objective To assess the potential exposure to complex urologic procedures, specifically urinary diversion, during a gynecologic oncology fellowship. Methods We queried the University HealthSystem Consortium (UHC) database to determine the total number of urinary diversions performed from October 2008 to August 2012. This data was used to estimate the mean number of urinary diversions performed each year. Gender, primary diagnosis, type of diversion, gynecologic oncologist involvement, and medical center were explored. Results Of the nearly 21,000 urinary diversions performed in UHC participating hospitals during the study period, 6180 (29.5%) were performed in women. On average, 1648 urinary diversions are performed in women each year, with gynecologic malignancies accounting for 6.8% of cases. We estimate that a gynecologic oncologist was involved with 87 cases per year at nonprofit academic medical centers in the US. With approximately 112 clinically active fellows per year during the study period, this equates to less than one diversion per clinical fellow per year if cases are equally distributed among centers. However, the majority of urinary diversions with gynecologic oncologist involvement were performed at just a fraction of centers. Thus, only a small contingent of fellows may be getting the greatest exposure to urinary diversions. Conclusions The majority of urinary diversions in women in the US are performed for bladder carcinoma by urologists. The estimated number of cases per clinical gynecologic oncology fellow per year is less than one. Strategies to improve fellow exposure to urinary diversion and consideration of alternative surgical training modalities should be explored.

Rates of human papillomavirus (HPV) vaccine series completion among adolescent Hispanic females in Texas in 2014 (∼39%) lag behind the Healthy People 2020 goal (80%). This qualitative study identifies Hispanic mothers' salient behavioral, normative and control beliefs regarding having their adolescent daughters complete the vaccine series. Thirty-two mothers of girls (aged 11-17) that had received at least one dose of the HPV vaccine, completed in-depth interviews. Six girls had received one dose of the HPV vaccine, 10 girls had received two doses, and 16 girls had received all three doses. The questions elicited salient: (i) experiential and instrumental attitudes (behavioral beliefs); (ii) supporters and non-supporters (normative beliefs) and (iii) facilitators and barriers (control beliefs). Directed content analysis was employed to select the most salient beliefs. Mothers: (i) expressed salient positive feelings (e.g. good, secure, happy and satisfied); (ii) believed that completing the series resulted in positive effects (e.g. protection, prevention); (iii) believed that the main supporters were themselves, their daughter's father and doctor with some of their friends not supporting series completion and (iv) believed that vaccine affordability, information, transportation, ease of scheduling and keeping vaccination appointments and taking their daughter's immunization card to appointments were facilitators. This study represents the first step in building theory-based framework of vaccine series completion for this population. The beliefs identified provide guidance for health care providers and intervention developers.

Worldwide, cancers of the uterine corpus are the sixth most common cancer in women, with over 218,100 new cases diagnosed each year. Uterine cancer is ten times more common in developed countries and is the most common malignancy of the female genital tract in North America and Europe. In the USA and Europe, it is the fourth overall most common cancer diagnosed in women and the eighth most likely cause of cancer death (Jemal et al., CA Cancer J Clin 61(2):69–90, 2011). It is estimated that 49,560 US women will be diagnosed with uterine cancer in 2013 (age-adjusted incidence rate 24.5/100,000) and 8,190 will die (SEER, Stat Fact Sheets 1–10, 2013).

Ovarian cancer ascites fluid contains matrix proteins that can impact tumor growth via integrin receptor binding. In human ovarian tumor tissue arrays, we find that activation of the cytoplasmic focal adhesion (FAK) tyrosine kinase parallels increased tumor stage, β5 integrin, and osteopontin matrix staining. Elevated osteopontin, β5 integrin, and FAK mRNA levels are associated with decreased serous ovarian cancer patient survival. FAK remains active within ovarian cancer cells grown as spheroids, and anchorage-independent growth analyses of seven ovarian carcinoma cell lines identified sensitive (HEY, OVCAR8) and resistant (SKOV3-IP, OVCAR10) cells to 0.1 μmol/L FAK inhibitor (VS-4718, formerly PND-1186) treatment. VS-4718 promoted HEY and OVCAR8 G0–G1 cell-cycle arrest followed by cell death, whereas growth of SKOV3-IP and OVCAR10 cells was resistant to 1.0 μmol/L VS-4718. In HEY cells, genetic or pharmacological FAK inhibition prevented tumor growth in mice with corresponding reductions in β5 integrin and osteopontin expression. β5 knockdown reduced HEY cell growth in soft agar, tumor growth in mice, and both FAK Y397 phosphorylation and osteopontin expression in spheroids. FAK inhibitor–resistant (SKOV3-IP, OVCAR10) cells exhibited anchorage-independent Akt S473 phosphorylation, and expression of membrane-targeted and active Akt in sensitive cells (HEY, OVCAR8) increased growth but did not create a FAK inhibitor–resistant phenotype. These results link osteopontin, β5 integrin, and FAK in promoting ovarian tumor progression. β5 integrin expression may serve as a biomarker for serous ovarian carcinoma cells that possess active FAK signaling. Mol Cancer Ther; 13(8); 2050–61. ©2014 AACR.

To evaluate the relationship between county-level characteristics and the incidence of invasive squamous cell carcinoma of the cervix among Hispanic women.The Surveillance, Epidemiology and End Results (SEER) Program's 18 registries from 2000-2009 were queried. Average annual age-adjusted incidence rates for invasive squamous cell carcinoma of the cervix among Hispanic women were calculated. Patients were then stratified by residence in a county with high vs low percent language isolation (LI), income, and education levels.Among Hispanic women living in high LI, the highest incidence of cervical cancer was found among women residing in counties with low incomes and low education levels (11.3; CI: 10.8-11.8).County-level characteristics are associated with cervical cancer incidence in Hispanic women. A more precise understanding of contributing socioeconomic factors such as language may facilitate the design of targeted research studies and interventions, and community-level public policy interventions might be effective in reducing the unequal burden of cervical cancer in Hispanic women in the United States.

Endothelial cell focal adhesion kinase is a key intermediate between c-Src and the regulation of endothelial cell barrier function in the control of tumor metastasis., Pharmacological focal adhesion kinase (FAK) inhibition prevents tumor growth and metastasis, via actions on both tumor and stromal cells. In this paper, we show that vascular endothelial cadherin (VEC) tyrosine (Y) 658 is a target of FAK in tumor-associated endothelial cells (ECs). Conditional kinase-dead FAK knockin within ECs inhibited recombinant vascular endothelial growth factor (VEGF-A) and tumor-induced VEC-Y658 phosphorylation in vivo. Adherence of VEGF-expressing tumor cells to ECs triggered FAK-dependent VEC-Y658 phosphorylation. Both FAK inhibition and VEC-Y658F mutation within ECs prevented VEGF-initiated paracellular permeability and tumor cell transmigration across EC barriers. In mice, EC FAK inhibition prevented VEGF-dependent tumor cell extravasation and melanoma dermal to lung metastasis without affecting primary tumor growth. As pharmacological c-Src or FAK inhibition prevents VEGF-stimulated c-Src and FAK translocation to EC adherens junctions, but FAK inhibition does not alter c-Src activation, our experiments identify EC FAK as a key intermediate between c-Src and the regulation of EC barrier function controlling tumor metastasis.

Objective Focal adhesion kinase (FAK) is overexpressed in serous ovarian cancer. Loss of merlin, a product of the neurofibromatosis 2 tumor suppressor gene, is being evaluated as a biomarker for FAK inhibitor sensitivity in mesothelioma. Connections between merlin and FAK in ovarian cancer remain undefined. Methods Nine human and two murine ovarian cancer cell lines were analyzed for growth in the presence of a small molecule FAK inhibitor (PF-271, also termed VS-6062) from 0.1 to 1 μM for 72 h. Merlin was evaluated by immunoblotting and immunostaining of a human ovarian tumor tissue array. Growth of cells was analyzed in an orthotopic tumor model and evaluated in vitro after stable shRNA-mediated merlin knockdown. Results Greater than 50% inhibition of OVCAR8, HEY, and ID8-IP ovarian carcinoma cell growth occurred with 0.1 μM PF-271 in anchorage-independent (p < 0.001) but not in adherent culture conditions. PF-271-mediated reduction in FAK Y397 phosphorylation occurred independently of growth inhibition. Suspended growth of OVCAR3, OVCAR10, IGROV1, IGROV1-IP, SKOV3, SKOV3-IP, A2780, and 5009-MOVCAR was not affected by 0.1 μM PF-271. Merlin expression did not correlate with serous ovarian tumor grade or stage. PF-271 (30 mg/kg, BID) did not inhibit 5009-MOVCAR tumor growth and merlin knockdown in SKOV3-IP and OVCAR10 cells did not alter suspended cell growth upon PF-271 addition. Conclusions Differential responsiveness to FAK inhibitor treatment was observed. Intrinsic low merlin protein level correlated with PF-271-mediated anchorage-independent growth inhibition, but reduction in merlin expression did not induce sensitivity to FAK inhibition. Merlin levels may be useful for patient stratification in FAK inhibitor trials. © 2014 Elsevier Inc. All rights reserved.

We examined the utility of an expanded theory of planned behavior (TPB) model in predicting cervical cancer screening intentions among Latinas. The model included acculturation and past cervical cancer screening behavior along with attitude, subjective norms, and perceived behavioral control. This cross-sectional study included a sample of 206 Latinas who responded to a self-administered survey. Structural equation modeling was employed to test the expanded TPB model. Acculturation (p = .025) and past screening behavior (p = .001) along with attitude (p = .019), subjective norms (p = .028), and perceived behavioral control (p = .014) predicted the intention to be screened for cervical cancer. Our findings suggest that the TPB is a useful model for understanding cervical cancer screening intentions among Latinas when both past behavior and culture are included. This research highlights the importance of culture on behavior and indicates a need to develop culturally sensitive, theory-based interventions to encourage screening and reduce cervical cancer-related health disparities in Latinas.

To develop effective interventions to increase cervical cancer screening among Latinas, we should understand the role of cultural factors, such as time perspective, in the decision to be screened. We examined the relation between present time orientation, future time orientation, and self-reported cervical cancer screening among Latinas. A group of 206 Latinas completed a survey measuring factors associated with screening. Logistic regression analyses revealed that future time orientation was significantly associated with self-reported screening. Understanding the influence of time orientation on cervical cancer screening will assist us in developing interventions that effectively target time perspective and screening.

The purpose of this study was to determine whether the introduction of psychosocial services to gynecologic oncology outpatients by a social worker increases service use. During the initial six weeks (phase I), patients were referred for psychosocial services by clinic staff. During the second six weeks (phase II), a nurse introduced available services to each patient with a brochure. During the final 12 weeks (phase III), a social worker introduced services to each patient. The authors then compared psychosocial service referral rates. The sample included 196 patients. During phase III, the probability of a patient-initiated referral increased 3.4-fold (95 percent confidence interval [CI] [1.1, 10.4], p = .04) compared with baseline; the probability of any referral rose 2.7-fold (95 percent CI [1.1, 6.3], p = .03). The mean time to referral decreased from 79.4 days at baseline to 3.9 days during phase III (p < .001). The phase III intervention was accomplished only in 34 patients (39 percent) because of scheduling conflicts. Of these, eight requested referral, resulting in a 24 percent patient-initiated referral rate after meeting with a social worker. The introduction of psychosocial services by a social worker to gynecologic oncology outpatients increases referral rates and expedites evaluation.

Objective We sought to quantify the relationship of uterine malignancy with body mass index (BMI). Study Design The University HealthSystem Consortium database was queried to identify all women undergoing total hysterectomy with a recorded BMI in the overweight and obese categories. Least squares regression was applied to evaluate the association between increasing BMI and the proportion of women with a diagnosis of uterine malignancy. Multivariate binary logistic regression was performed to adjust for other known risk factors including age, race, and other comorbidities. Results There were 6905 women who met inclusion criteria; 1891 (27.4%) of these had uterine malignancy. There is a linear relationship (y = 0.015x - 0.23, R 2 = 0.92) of the probability of uterine malignancy vs BMI. After adjusting for other risk factors, we found that each 1-U increase in BMI was significantly, independently associated with an 11% increase in the proportion of patients diagnosed with uterine malignancy (odds ratio, 1.11; 95% confidence interval, 1.09–1.13; P Conclusion In a population of women undergoing hysterectomy, we observed a linear increase in the frequency of uterine cancer associated with increasing BMI. This finding suggests that even relatively modest weight gain may significantly raise cancer risk. In the United States, the mean BMI for women is 26.5 kg/m 2 and it is estimated that more than half of US women have a BMI within the study's range. Our results could, therefore, be relevant to a majority of the population. The findings could increase popular acceptance of weight management as a key component of general health maintenance and, possibly, as an additional approach to cancer risk reduction.

Recurrence and spread of ovarian cancer is the 5th leading cause of death for women in the United States. Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase located on chromosome 8q24.3 (gene is Ptk2), a site commonly amplified in serous ovarian cancer. Elevated FAK mRNA levels in serous ovarian carcinoma are associated with decreased (logrank P = 0.0007, hazard ratio 1.43) patient overall survival, but how FAK functions in tumor progression remains undefined. We have isolated aggressive ovarian carcinoma cells termed ID8-IP after intraperitoneal (IP) growth of murine ID8 cells in C57Bl6 mice. Upon orthotopic implantation within the peri-ovarian bursa space, ID8-IP cells exhibit greater tumor growth, local and distant metastasis, and elevated numbers of ascites-associated cells compared to parental ID8 cells. ID8-IP cells exhibit enhanced growth under non-adherent conditions with elevated FAK and c-Src tyrosine kinase activation compared to parental ID8 cells. In vitro, the small molecule FAK inhibitor (Pfizer, PF562,271, PF-271) at 0.1 uM selectively prevented anchorage-independent ID8-IP cell growth with the inhibition of FAK tyrosine (Y)397 but not c-Src Y416 phosphorylation. Oral PF-271 administration (30 mg/kg, twice daily) blocked FAK but not c-Src tyrosine phosphorylation in ID8-IP tumors. This was associated with decreased tumor size, prevention of peritoneal metastasis, reduced tumor-associated endothelial cell number, and increased tumor cell-associated apoptosis. FAK knockdown and re-expression assays showed that FAK activity selectively promoted anchorage-independent ID8-IP cell survival. These results support the continued evaluation of FAK inhibitors as a promising clinical treatment for ovarian cancer.

Objective To evaluate the causes of death among women with endometrial cancer. Methods SEER registries from 1973–1988 were queried to perform a retrospective cohort study of women with invasive epithelial endometrial cancer. Causes of death were compared according to grade and stage. Results 33,232 women with incident cases of endometrial cancer had died at the time of last follow up. Overall, women were most likely to die from cardiovascular disease (35.9%, 95% CI 35.3–36.3%), followed by other causes, other malignancies, and endometrial cancer. Women with low grade localized cancer were most likely to die of cardiovascular disease, while women with high grade advanced cancer were least likely to die of cardiovascular disease and most likely to die of endometrial cancer. For the entire population, risk of death from cardiovascular causes surpasses the risk of death from endometrial cancer 5years after diagnosis. Conclusions Higher risk of cardiac death among endometrial cancer patients likely reflects the high probability of curative cancer treatment and the prevalence of cardiac disease and risk factors. As the probability of dying of endometrial cancer decreases with time, the probability of dying of cardiovascular disease increases. Interventions and investigations aimed at addressing risk factors for cardiovascular disease may have the greatest potential to improve survival for women diagnosed with endometrial cancer and should feature prominently in treatment and survivorship plans.

In order to understand how culture influences Hispanic women's views about their health care provider (HCP), we examined the relationship between acculturation and fatalism in the HCP control expectations of Hispanic women. (A HCP control expectation is the extent to which an individual believes that her HCP has control over her health.) We predicted that acculturation would be negatively associated with HCP control expectations and fatalism would be positively associated with HCP control expectations. A group of 1,027 young Hispanic women (mean age 21.24 years; SD = 2.46) who were University of Texas Medical Branch clinic patients completed a comprehensive survey. Structural equation modeling was employed and as predicted, acculturation was negatively associated with HCP control expectations (p < .001) and fatalism was positively associated (p < .001). Understanding fatalism, acculturation, and their influence on HCP control expectations will help us understand this population's perceptions of their HCPs. This knowledge will assist HCPs in providing culturally competent care which will increase adherence to medical treatment and screening guidelines.

Objective We sought to evaluate the association between passive cigarette smoke exposure and cervical cytological abnormalities in a predominantly Hispanic sample. Study Design Data were collected as part of a larger, ongoing randomized clinical trial. Inclusion criteria were met by 4403 Hispanic (73%) and non-Hispanic (27%) women between 18-55 years of age (mean = 30.14 ± 8.7). Analysis of variance and multivariate logistic regression determined the association between passive smoke exposure and Pap abnormality. Results Passive smoke exposure was positively associated with having an abnormal Pap smear (odds ratio, 1.70; 95% confidence interval, 1.14–2.52) as was current active smoking (odds ratio 1.45; 95% confidence interval, 1.03–2.04). Neither effect was modified by ethnicity. Increasing hours per week of passive smoke exposure was associated with low-grade squamous intraepithelial lesion ( P Conclusion Passive smoke exposure is an important independent risk factor for cytological abnormalities in Hispanic and non-Hispanic women. This study adds to the growing body of evidence of the dangers of passive smoke exposure.

The study was conducted to examine the relationship between cultural adaptation (acculturation), contraceptive use, personal history of induced abortion, and emergency contraceptive (EC) awareness and acquisition among a sample of young sexually active Hispanic women.A total of 959 Hispanic women between 16 and 24 years of age (mean±SD 20.71±2.42 years) completed a survey containing questions on EC acquisition and awareness, acculturation, contraceptive used at last intercourse and history of induced abortion. Data were analyzed using logistic regression analyses.Acculturation (p=.017), income (p=.024) and education (p.001) were positively associated with awareness of EC. Additionally, acculturation (p=.003) and a history of an induced abortion (p=.026) were positively associated with acquisition of EC.Educational programs should make an effort to include Hispanic women with lower acculturation levels as increasing their knowledge about EC use and its mechanism of action may greatly reduce the number of unplanned pregnancies in this population.