Faculty Bibliography

OBJECTIVE: : To identify patient characteristics associated with bilateral oophorectomy or removal of remaining ovary at the time of benign hysterectomy, and to estimate trends in the performance of oophorectomy from 2001 to 2006. METHODS: : This was a cross-sectional analysis using the New York State Department of Health Statewide Planning and Research Cooperative System. Women aged 18 years or older undergoing hysterectomies for benign gynecologic conditions were included. We evaluated factors associated with oophorectomy on both univariable and multivariable analyses and assessed for changes in performance of oophorectomy over the course of the study. RESULTS: : Forty-seven percent of 144,877 hysterectomies included oophorectomy. Women who underwent oophorectomy were older and were more likely to have a family history of breast or ovarian cancer, a personal history of breast cancer, ovarian cysts, or endometriosis. Women who underwent vaginal or laparoscopic hysterectomy or had uterine prolapse were less likely to undergo oophorectomy. Both race and insurance status were associated with performance of oophorectomy. From 2001 to 2006, there was an 8% absolute decrease in the performance of oophorectomy at the time of benign hysterectomy for women of all ages, with a 10.4% decrease in women aged younger than 55 (P for trend <.001). CONCLUSION: : Age, route of hysterectomy, and concomitant gynecologic diagnoses influence oophorectomy rate. From 2001 to 2006, a significant decrease in the performance of oophorectomy at the time of benign hysterectomy was noted in women aged younger than 55 years. Recent studies of complications of hormone therapy and prophylactic oophorectomy may have influenced patients' and physicians' decision-making, leading to lower oophorectomy rates. LEVEL OF EVIDENCE: : II

Epithelial ovarian cancer (EOC) patients with BRCA mutations (BRCA+) benefit from platinum-based treatment more than non-carriers. Impaired ability to repair DNA by homologous recombination increases their chemosensitivity. We investigated whether BRCA+ predicts for improved outcome following pegylated liposomal doxorubicin (PLD) for recurrence. Recurrent EOC patients receiving second- or third-line PLD from 1998 to 2009 in 4 institutions (Israel, Italy, NY) were subjected to retrospective comparisons between 40(25.8%) patients who were BRCA+, and 115(74.2%) deemed non-hereditary (NH). Median age was 59 years (range 31-83); 111(72%) had a platinum-free interval >6 months (PLD alone [n=65] and PLD plus platinum[n=90]); 104 received PLD in second-line and 51 in third-line. BRCA+ versus NH comparisons: median time to treatment failure (TTF) 15.8 months (95% CI 11.4-21.6) versus 8.1 months (95% CI 6.1-10.3;p=0.009); overall survival (OS) 56.8 months (95% CI 32.5-indeterminate) versus 22.6 months (95% CI 17.0-34.1;p=0.002). In multivariate Cox models BRCA status was significantly associated with TTF (HR=1.66; 95% CI 1.08-2.55;p=0.02) and OS (adjusted HR 2.07; 95% CI 1.18-3.60;p=0.01). Adjusted HR relating platinum sensitivity to OS was 1.58 (95% CI 0.93-2.68; p=0.09); no significant association found with age at diagnosis, line of PLD or combinations, or institution. In this retrospective analysis, recurrent EOC BRCA mutation carriers treated with PLD had an improved outcome, and this result appeared to be independent of platinum sensitivity. Tumors arising in a background of defective BRCA function are more sensitive than other epithelial ovarian cancers to DNA damaging agents such as PLD, even after acquiring platinum resistance

OBJECTIVES: Lysophosphatidic acid (LPA) has potent growth-regulatory effect in many cell types and has been linked to the in vivo tumor growth and metastasis in several malignancies. The goal of this study was to assess the regulation of (EC) microenvironment by LPA through the examination of its effect on cell proliferation, migration, invasion, uPA activity, and matrix metalloproteinase (MMP) secretion/activation. METHODS: All experiments were performed in vitro using an EC cell line, HEC-1A. Cell proliferation was determined using the Promega MTS proliferation assay following 48 h of exposures to different concentrations of LPA (0.1, 1.0 and 10.0 microM). Cell invasion was assessed using a modified Boyden chamber assay with collagen I coated on the membrane. HEC-1A motility was examined by Boyden chamber migration assay as well as the scratch wound closure assay on type I collagen. MMP secretion/activation in HEC-1A conditioned medium was detected by gelatin zymography. MMP-7 mRNA expression was determined using real-time PCR. uPA activity was measured using a coupled colorimetric assay. RESULTS: LPA, at the concentrations of 0.1 and 1.0 microM, significantly induced the proliferation of HEC-1A cells (p<0.01). At 10 microM, LPA- induced HEC-1A proliferation to a less extent and showed no significant effect on HEC-1A invasion and migration (p>0.05). Gelatin zymogram showed that HEC-1A cells secreted high levels of MMP-7, while MMP-2 and MMP-9 are barely detectable. In addition, LPA significantly enhanced uPA activity in HEC-1A conditioned medium in a concentration-dependent manner. CONCLUSIONS: LPA is a potent modulator of cellular proliferation and invasion for EC cells. It also has the capacity to stimulate the secretion/activity of uPA and MMP-7. Those results suggest that LPA is a bioactive modulator of EC microenvironment and may have a distinct regulation mechanism as observed in epithelial ovarian cancer

OBJECTIVE: Imatinib mesylate (IM, Gleevec), a potent PDGF/PDGFR tyrosine kinase inhibitor, affects stroma and vascular endothelial cells. Our study sought to determine the safety and activity of paclitaxel with an intermittent schedule of IM. MATERIALS AND METHODS: rEOC patients previously treated with platinum/paclitaxel and </=2 regimens for recurrence were enrolled. Paclitaxel 80 mg/m(2) was given on days 3, 10, 17 every 28 days and oral IM 300 mg bid on days 1-4, 8-11, and 13-18. RESULTS: Between 2007-2009, 14 patients enrolled, 12 were evaluable. Nine patients were on study at 12 weeks. Objective responses (by RECIST and/or CA125) occurred in 4 patients. There were no grade 4, and only four grade 3 toxic events: diarrhea, edema and 2 cases of neutropenia. Early study closure was due to sufficient safety information with preliminary encouraging efficacy results. CONCLUSION: This weekly paclitaxel regimen with intermittent IM is tolerable with anti-tumor activity, making it suitable as part of future studies

OBJECTIVE:: To estimate whether a surgeon's case volume is related to route of hysterectomy and short-term morbidity. METHODS:: This is a cross-sectional study collecting data on inpatient hysterectomies using the New York State Department of Health database from 2001 through 2006. An acute morbidity and mortality index was created. Surgeons' license numbers were used to generate an annual average number of hysterectomies performed. A multivariable logistic regression model assessing surgical volume on acute morbidity after controlling for known confounders was created. RESULTS:: A total of 146,494 hysterectomies were performed in the state of New York. Of these, 103,181 (70.4%) were abdominal, 26,660 (18.2%) were vaginal, and 16,653 (11.4%) were laparoscopic-assisted. Twenty- six percent of hysterectomies are performed by physicians who perform, on average, fewer than 10 hysterectomies per year. The percentage of abdominal hysterectomies is 81% for surgeons performing fewer than 10 hysterectomies per year compared with 67% for surgeons performing at least 10 hysterectomies per year (P<.001). Postoperative morbidity and mortality were reported as 16.5% and 0.21%, respectively, for surgeons performing fewer than 10 hysterectomies per year as compared with 11.7% and 0.06%, respectively, for those performing at least 10 hysterectomies (P<.001). CONCLUSION:: Surgeons who perform an average of 10 hysterectomies per year are more likely to perform minimally invasive hysterectomies. These surgeons also have a decrease in morbidity and mortality rates when compared with surgeons who perform fewer than 10 hysterectomies per year. LEVEL OF EVIDENCE:: II