Purpose: Vascular endothelial growth factor (VEGF) is critical for angiogenesis and tumor progression; however, its role in endometrial cancer is not fully known. Therefore, we examined the clinical and therapeutic significance of VEGF in endometrial carcinoma using patient samples and an endometrioid orthotopic mouse model. Experimental Design: Following Institutional Review Board approval, VEGF expression and microvessel density (MVD) counts were evaluated using immunohistochemistry in 111 invasive endometrioid endometrial cancers by two independent investigators. Results were correlated with clinicopathologic characteristics. For the animal model, Ishikawa or Hec-1A cancer cell lines were injected directly into the uterine horn. Therapy experiments with bevacizumab alone or in combination with docetaxel were done and samples were analyzed for markers of angiogenesis and proliferation. Results: Of 111endometrial cancers, high expression of VEGF was seen in 56% of tumors. There was a strong correlation betweenVEGF expression and MVD (P < 0.001). On multivariate analysis, stage (P = 0.04), grade (P = 0.003),VEGF levels (P = 0.03), and MVD (P = 0.037) were independent predictors of shorter disease-specific survival. In the murine model, whereas docetaxel and bevacizumab alone resulted in 61% to 77% tumor growth inhibition over controls, combination therapy had the greatest efficacy (85-97% inhibition over controls; P < 0.01) in both models.In treated tumors, combination therapy significantly reduced MVD counts (50-70% reduction over controls; P < 0.01) and percent proliferation (39% reduction over controls; P < 0.001).Conclusions: Increased levels of VEGF and angiogenic markers are associated with poor outcome in endometrioid endometrial cancer patients. Using a novel orthotopic model of endometrioid endometrial cancer, we showed that combination of antivascular therapy with docetaxel is highly efficacious and should be considered for future clinical trials.
Despite strong national recommendations to vaccinate adolescents against the human papillomavirus (HPV), only 14% of teenage girls completed all 3 doses in 2010. Parental hesitancy may be one of the strongest reasons behind this low uptake rate. This review investigates sources of parental hesitancy including parental concerns associated with vaccinations in general, parental knowledge as a basis of HPV vaccine hesitancy, social qualms parents may have with regards to the HPV vaccine, and parental attitudes toward allowing their sons to be vaccinated against HPV. By better understanding these sources of hesitancy, we can focus research efforts towards addressing them in an attempt to improve HPV vaccine uptake.
Study Objective The purpose of this analysis was to compare the trends in undergoing laparoscopic hysterectomy (versus abdominal or vaginal hysterectomy) based on patient age, race, median income and insurance type, from 2003 to 2010. Methods In this retrospective cohort study, we analyzed the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample databases from 2003–2010. All women who underwent a hysterectomy for either menorrhagia or leiomyoma were included, based on ICD-9 coding. The predicted probability of undergoing laparoscopic hysterectomy was determined for each year according to patient age, race, median income, and insurance type. The slopes of these values (i.e. the trend) was compared for each subgroup (i.e. black, white, Asian, etc.) in these categories. Main Results A total of 530, 154 cases were included in this study. Total number of hysterectomies decreased by 39% from 60,364 to 36,835 from 2003 to 2010. The percent of hysterectomies that were laparoscopic increased from 11% in 2003 to 29% in 2010. All groups analyzed experienced an increase in predicted probability of undergoing a laparoscopic hysterectomy. Of all women undergoing hysterectomy, the probability of undergoing a laparoscopic hysterectomy remained highest for women who were less than 35 years old, white, with the highest median income, and with private insurance from 2003–2010. The slope was significantly greater for (1) white females versus all other races analyzed (p<0.01), (2) females in the highest income quartile versus females in the lowest income quartile (p<0.01) and (3) females with private insurance versus females with Medicaid (p<0.01) or Medicare (p<0.01). Conclusions There remains a gap in distribution of laparoscopic hysterectomies with regards to age, race, median income and insurance type that does not seem to be closing, despite the increased availability of laparoscopic hysterectomies.
Study Objective The objective of our study was to determine patient and hospital characteristics that were associated with undergoing laparoscopic hysterectomy compared with abdominal hysterectomy. Methods In this retrospective cohort study, we analyzed the 2010 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database. All women who underwent laparoscopic or abdominal hysterectomy for either menorrhagia or leiomyoma were included, based on ICD9 coding. Linear model with binomial distribution and logit link function was used to determine patient and hospital characteristics associated with hysterectomy approach. Main Results A total of 32,436 patients were included in this study. Of these, 32% patients underwent laparoscopic hysterectomies and 67% underwent abdominal hysterectomies. With regards to patient characteristics, women younger than 35 years old were more likely to undergo laparoscopic hysterectomy when compared to each of the other age categories (p<0.001). White women were more likely to undergo laparoscopic hysterectomy than black women, Hispanic women or women classified as “other” races (p<0.001 for all comparisons). With regards to median income, patients from the lowest national quartile were less likely to undergo laparoscopic hysterectomy when compared to each of the other three national quartiles for income (p=0.01, p<0.001, p=0.001, respectively). Payment by private insurance was associated with laparoscopic hysterectomy when compared to payment by Medicare or payment by insurance category “other” (p<0.001 for both). With regards to hospital characteristics, hospitals in the Northeast were more likely to have laparoscopic hysterectomies than hospitals in the Midwest or South (p<0.001 for both comparisons); urban hospitals were more likely than rural hospitals (p<0.001); teaching hospitals were more likely than non-teaching hospitals (p<0.001); and government-owned hospitals were less likely than private, non-profit or private, investor owned (p<0.001 for both comparisons). Conclusions Despite the increased popularity of and training in laparoscopic hysterectomies, there remains an obvious disparity in its delivery with regards to patient and hospital characteristics. Further investigation is needed on the etiology of this disparity and interventions that may alleviate it.
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