Do differences in medical comorbidities and treatment impact racial disparities in epithelial ovarian cancer?

BACKGROUND: Population-based studies of women with epithelial ovarian cancer suggest that black women have worse survival compared to white women. The primary objective of this study was to determine if, at a National Cancer Institute (NCI)-Designated Comprehensive Cancer Center (CCC) serving a diverse racial and socioeconomic population, race is independently associated with differences in survival. METHODS: A retrospective review of women with EOC diagnosed between 2004-2009 undergoing treatment with follow-up at our institution was performed. Records were reviewed for demographics, comorbidities (as defined by the Charlson Comorbidity Index (CCI)), tumor characteristics, treatment, progression-free (PFS), and overall survival (OS). Survival was calculated using the Kaplan-Meier method and compared with the log-rank test. Multivariate survival analysis was performed with Cox (proportional hazards) model. RESULTS: 367 patients met inclusion criteria. 54 (15%) were black and 308 (84%) were white. Compared to white women, black women had higher BMI, lower rates of optimal surgical cytoreduction, lower rates of intraperitoneal chemotherapy, and higher CCI scores. The median PFS for black and white women were 9.7 and 14.6months, respectively (p=0.033). The median overall survival was 21.7months for black women and 42.6months for white women (p<0.001). On multivariate analysis, black race independently correlated with a worse overall survival (HR 1.61, 95% CI 1.06-2.43). CONCLUSION: In this cohort, racial disparities may be due to higher medical comorbidities and lower rates of optimal surgical cytoreduction. After accounting for these differences, race remained an independent predictor of worse overall survival.

Does a standardized preoperative algorithm of clinical data improve outcomes in patients with ovarian cancer? A quality improvement project.

OBJECTIVE: To evaluate the potential impact of a standardized preoperative algorithm on outcomes of patients with suspected ovarian cancer. METHODS: From January 1 to December 31, 2013, patients with suspected ovarian cancer were triaged to primary debulking surgery or neoadjuvant chemotherapy/interval debulking surgery (NACT/IDS) based on a comprehensive review of preoperative clinical data as part of a quality improvement project. Demographics, surgical, and postoperative data were collected. RESULTS: A total of 110 patients with newly diagnosed ovarian cancer were identified: 68 (62%) underwent PDS with an 85% optimal debulking rate. The 30-day readmission rate was 14.7% with a 2.9% 60-day mortality rate. Forty-two patients (38%) underwent NACT. Two patients (4.8%) died before receiving NACT. Thirty-five patients have undergone IDS with an 89% optimal debulking rate. The 30-day readmission rate was 8.5% with a 5.7% 60-day mortality rate after IDS. CONCLUSIONS: Although it is difficult to predict which patients will undergo optimal debulking at the time of PDS, surgical morbidity and mortality can be decreased by using NACT in select patients. The initiation of a quality improvement project has contributed to an improvement in patient outcomes at our institution.

Ovarian cancer stem cells: are they real and why are they important?

The cancer stem cell hypothesis has been put forward as a paradigm to describe varying levels of aggressiveness in heterogeneous tumors. Specifically, many subpopulations have been clearly demonstrated to possess increased tumorigenicity in mice, broad differentiating capacity, and resistance to therapy. However, the extent to which these experimental findings are potentially clinically significant is still not clear. This review will describe the principles of this emerging hypothesis, ways in which it may be appropriate in ovarian cancer based on the clinical course of the disease, and how we might exploit it to improve outcomes in ovarian cancer patients.

Reasons for failure to deliver National Comprehensive Cancer Network (NCCN)-adherent care in the treatment of epithelial ovarian cancer at an NCCN cancer center.

OBJECTIVE: The National Comprehensive Cancer Network (NCCN) has established guidelines for treating epithelial ovarian cancer (EOC) which includes cytoreductive surgery and platinum and taxane-based chemotherapy (CT). The objective of this study was to determine the reasons for failure to deliver NCCN-adherent care at an NCCN cancer center serving a diverse racial and socioeconomic population. METHODS: Medical records of women with EOC diagnosed between 2004 and 2009 were reviewed for demographic, clinical, tumor, treatment, and survival data. Independent reviewers determined if their treatment met criteria for being NCCN-adherent. Progression-free survival (PFS) and overall survival (OS) were calculated with Kaplan-Meier estimates and compared with the log-rank test. RESULTS: 367 patients were identified. 79 (21.5%) did not receive NCCN-adherent care. Non-adherent CT in 75 patients was the most common reason for failure to receive NCCN-adherent care. 39 patients did not complete CT due to treatment toxicities or disease progression. 12 patients received single agent CT only and 4 received no CT due to comorbidities. 2 patients declined CT. 18 patients died in the postoperative period without receiving CT. 8 patients did not undergo cytoreduction due to disease progression or comorbidities. PFS and OS were improved in the NCCN-adherent cohort (PFS: 5.7 vs. 18.3 months, p<.005) (OS: 11.4 vs. 49.5 months, p<.005). CONCLUSIONS: The vast majority of patients at an NCCN cancer center received NCCN-adherent treatment. Reasons for failure to receive NCCN-adherent care were variable, but most did not receive chemotherapy in accordance with guidelines due to comorbidities or disease progression.

An ex vivo assay of XRT-induced Rad51 foci formation predicts response to PARP-inhibition in ovarian cancer.

OBJECTIVE: BRCA-positive ovarian cancer patients derive benefit PARP inhibitors. Approximately 50% of ovarian cancer tumors have homologous recombination (HR) deficiencies and are therefore "BRCA-like," possibly rendering them sensitive to PARP inhibition. However, no predictive assay exists to identify these patients. We sought to determine if irradiation-induced Rad51 foci formation, a known marker of HR, correlated to PARP inhibitor response in an ovarian cancer model. METHODS: Ovarian cancer cell lines were exposed to PARP-inhibitor ABT-888 to determine effect on growth. Rad51 protein expression prior to irradiation was determined via Western blot. Cultured cells and patient-derived xenograft tumors (PDX) were irradiated and probed for Rad51 foci. In vivo PDX tumors were treated with ABT-888 and carboplatin; these results were correlated with the ex vivo ionizing radiation assay. RESULTS: Three of seven cell lines were sensitive to ABT-888. Sensitive lines had the lowest Rad51 foci formation rate after irradiation, indicating functional HR deficiency. Approximately 50% of the PDX samples had decreased Rad51 foci formation. Total Rad51 protein levels were consistently low, suggesting that DNA damage induction is required to characterize HR status. The ex vivo IR assay accurately predicted which PDX models were sensitive to PARP inhibition in vitro and in vivo. ABT-888 alone reduced orthotopic tumor growth by 51% in A2780ip2 cell line, predicted to respond by the ex vivo assay. Three PDX models' response also correlated with the assay. CONCLUSIONS: The ex vivo IR assay correlates with response to PARP inhibition. Analysis of total Rad51 protein is not a reliable substitute.

Diabetes mellitus and ovarian cancer: more complex than just increasing risk.

OBJECTIVE: Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC. METHODS: A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan-Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients. RESULTS: 62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p=0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7kg/m(2), p<0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3months, p=0.024) and OS (26.1 vs. 42.2months, p=0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS. CONCLUSIONS: EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.

Quality of venous thromboembolism prophylaxis in patients undergoing oncologic surgery.

OBJECTIVE: We analyzed use of venous thromboembolism (VTE) prophylaxis in patients undergoing oncologic surgery and examined the influence of surgeon and hospital characteristics on prophylaxis. BACKGROUND: Cancer patients undergoing surgery are at high-risk for VTE. Despite the risk of VTE, the use of prophylaxis is variable. Little is known about the patient, surgeon, and hospital characteristics that influence the use of prophylaxis. METHODS: Patients undergoing oncologic surgery from 2003 to 2007 and recorded in the Perspective database were analyzed. Surgeons and hospitals were stratified into volume-based tertiles for analysis. The effects of surgeon and hospital volume on use of any prophylaxis and pharmacologic prophylaxis were examined using generalized estimating equations adjusted for confounding variables. RESULTS: In the cohort of 252,950 patients, some form of prophylaxis was given to 79% of patients whereas 46% received pharmacologic prophylaxis. The rate of VTE prophylaxis was 82.7% at high-volume hospitals compared with 75.6% at low-volume facilities (P < 0.0001). After adjustment for case mix and surgeon volume, the odds ratio for receipt of prophylaxis at high- versus low-volume hospitals was 1.40 (95% CI, 1.20-163). The odds ratio for prophylaxis for patients treated by high-volume surgeons was 1.35 (95% CI, 1.14-160) after adjusting for case mix and hospital volume. The rate of pharmacologic VTE prophylaxis was 53.1% in high-volume hospitals versus 38.8% in low-volume hospitals (P < 0.0001). Treatment at a high-volume hospital was associated with an odds ratio of 1.42 (95% CI, 1.22-1.66) for pharmacologic prophylaxis whereas the odds ratio for pharmacologic prophylaxis for patients treated by high-volume surgeons was 1.28 (95% CI, 1.08-1.51). CONCLUSION: VTE prophylaxis is underutilized in patients undergoing oncologic surgery. Patients treated by high-volume surgeons and at high-volume hospitals are more likely to receive appropriate prophylaxis.

Predictors of massive blood loss in women with placenta accreta.

OBJECTIVE: We examined predictors of massive blood loss for women with placenta accreta who had undergone hysterectomy. STUDY DESIGN: A retrospective review of women who underwent peripartum hysterectomy for pathologically confirmed placenta accreta was performed. Characteristics that are associated with massive blood loss (≥ 5000 mL) and large-volume transfusion (≥ 10 units packed red cells) were examined. RESULTS: A total of 77 patients were identified. The median blood loss was 3000 mL, with a median of 5 units of red cells transfused. There was no association among maternal age, gravidity, number of previous deliveries, number of previous cesarean deliveries, degree of placental invasion, or antenatal bleeding and massive blood loss or large-volume transfusion (P > .05). Among women with a known diagnosis of placenta accreta, 41.7% had an estimated blood loss of ≥ 5000 mL, compared with 12.0% of those who did not receive the diagnosis antenatally with ultrasound scanning (P = .01). CONCLUSION: There are few reliable predictors of massive blood loss in women with placenta accreta.

Management of endometrial cancer in young women.

Endometrial cancer is the most common gynecologic cancer and its incidence is rising among premenopausal women. Hysterectomy and bilateral salpingo-oophorectomy, traditional treatment for endometrial cancer, causes loss of fertility and ovarian function, both of which can significantly negatively impact a young woman's physical and mental well-being. Recently, conservative management with progestational agents has been reported with success from both oncologic and reproductive perspectives. However, there are no randomized trials comparing conservative versus surgical therapy. Patients who are candidates for conservative therapy must be extensively counseled regarding the risks and must comply with close surveillance.

The role of radiation in improving survival for early-stage carcinosarcoma and leiomyosarcoma.

OBJECTIVE: We examined the effect of radiation on survival for early-stage uterine carcinosarcomas and leiomyosarcomas. STUDY DESIGN: The surveillance, epidemiology, and end results database was used to identify patients with stage I/II carcinosarcomas and leiomyosarcomas. Logistic regression and Cox models were developed to determine radiation use and survival. RESULTS: Among 1819 women with carcinosarcomas and 1088 women with leiomyosarcomas, radiation was administered to 667 of the patients (37%) with carcinosarcomas and to 235 of the patients (22%) with leiomyosarcomas. In a multivariate model, adjuvant radiation reduced the risk of death by 21% in women with carcinosarcomas (hazard ratio, 0.79; 95% CI, 0.7-0.9). Radiation reduced mortality rates in patients with carcinosarcomas who had not undergone node dissection but had only a marginal effect on survival in node-negative women. Adjuvant radiation had no effect on survival for early-stage leiomyosarcomas (hazard ratio, 1.1; 95% CI, 0.9-1.4). CONCLUSION: Adjuvant radiotherapy improves survival for select patients with early-stage carcinosarcomas but is of limited value for leiomyosarcomas.

Fertility and reproductive disorders in female solid organ transplant recipients.

Solid organ transplantation can prolong the life of individuals with end-stage diseases that affect the kidney, liver, lung, heart, and pancreas. The improved survival of transplant recipients has led to increased attention on quality of life issues, including controlling fertility and having children. Perturbations of the hypothalamic-pituitary-ovarian axis in women with chronic renal failure or severe hepatic dysfunction result in anovulation and reduced fertility. Most often, fertility is restored with successful organ transplantation and good overall health. Although there are case reports of children born subsequent to assisted reproductive technologies (ART) in female transplant recipients, the approach to infertility in this population has not been described. Recognizing the unique medical, ethical, and psycho-social concerns involved in treating infertile female transplant recipients, reproductive endocrinologists must work with a multi-disciplinary team to ensure a successful pregnancy outcome without compromising graft function or maternal health. The primary goal of ART is a singleton pregnancy without complications, such as ovarian hyperstimulation syndrome, that pose greater risks in transplant recipients.

Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer.

A cornerstone of preclinical cancer research has been the use of clonal cell lines. However, this resource has underperformed in its ability to effectively identify novel therapeutics and evaluate the heterogeneity in a patient's tumor. The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy, but also basic tenets of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor's heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of six pair of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer.

Vulvar histoplasmosis as a rare cause of genital ulceration.

BACKGROUND: Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum and primarily presents with pulmonary symptoms. Immunocompromised individuals are at high risk for contracting disseminated histoplasmosis, which can be fatal if left untreated. CASE: We present a case involving a 50-year-old woman with acquired immunodeficiency syndrome with an ulcerated vulvar lesion concerning for carcinoma. Extensive workup revealed disseminated histoplasmosis without pulmonary manifestations. She was treated with an extended course of an antifungal agent. Her vulvar lesion resolved. CONCLUSION: Vulvar histoplasmosis is a rare etiology of vulvar pathology but one that should be considered in immunocompromised patients.

NOTCH2 expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype.

BACKGROUND: Notch family members function as both oncogenes and tumor suppressors. NOTCH2 is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival. NOTCH2 has also been shown to have pro-apoptotic and growth suppressive effects in thyroid carcinoma, and carcinoid tumors. The expression pattern of NOTCH2 in ovarian cancer is unknown. METHODS: An immunohistochemical analysis using a polyclonal antibody to the NOTCH2 intracellular domain was performed on a total of 119 ovarian carcinomas, and 7 serous borderline tumors, arranged onto tissue arrays. Normal ovarian and fallopian tube epithelium were used as controls. Specimens were scored as low or high NOTCH2 expression. The score distributions for the subtypes were analyzed with the chi square test. RESULTS: Fifty two of 61 (85.2%) papillary serous, eight of 13 (61.5%) clear cell, and 23 of 30 (76.7%) endometrioid, demonstrated negative or lower NOTCH2 expression than normal fallopian tubal epithelium or ovarian surface epithelium. In contrast, 10 of 15 (66.7%) mucinous carcinomas had a high level of NOTCH2 expression and consistently demonstrated intense polarized staining (P<.001). The apical expression of NOTCH2 protein present in the normal fallopian tube epithelium and many borderline tumors was absent in the high grade carcinomas, most notably in papillary serous. CONCLUSION: Decreased NOTCH2 expression is associated with the poorly differentiated serous epithelial ovarian carcinoma histology. Further studies are needed to assess the functional role of NOTCH2 in ovarian cancer and its effect on prognosis.

The role of Notch and gamma-secretase inhibition in an ovarian cancer model.

BACKGROUND: The Notch pathway is dysregulated in ovarian cancer. We sought to examine the role of Notch and gamma-secretase (GS) inhibition in ovarian cancer. MATERIALS AND METHODS: Established ovarian cancer cell lines were used. Quantitative polymerase chain reaction (qPCR) was used to determine the relative expression of Notch receptor and ligands. Effects of GS inhibition on proliferation, colony formation, and downstream effectors were examined via methylthiazole tetrazolium (MTT) and Matrigel assays, and qPCR, respectively. In vivo experiments with a GS inhibitor and cisplatin were conducted on nude mice. Tumors were examined for differences in microvessel density, proliferation, and apoptosis. RESULTS: Notch3 was the most up-regulated receptor. The ligands JAGGED1 and DELTA-LIKE4 were both up-regulated. GS inhibition did not affect cellular proliferation or anchorage-independent cell growth over placebo. The GS inhibitor Compound-E reduced microvessel density in vivo. CONCLUSION: GS inhibition does not directly affect cellular proliferation in ovarian carcinoma, but Notch pathway blockade may result in angiogenic alterations that may be therapeutically important.

Endoglin (CD105) contributes to platinum resistance and is a target for tumor-specific therapy in epithelial ovarian cancer.

PURPOSE: Endoglin (CD105) is a membranous protein overexpressed in tumor-associated endothelial cells, chemoresistant populations of ovarian cancer cells, and potentially stem cells. Our objective was to evaluate the effects and mechanisms of targeting endoglin in ovarian cancer. EXPERIMENTAL DESIGN: Global and membranous endoglin expression was evaluated in multiple ovarian cancer lines. In vitro, the effects of siRNA-mediated endoglin knockdown with and without chemotherapy were evaluated by MTT assay, cell-cycle analysis, alkaline comet assay, γ-H2AX foci formation, and quantitative PCR. In an orthotopic mouse model, endoglin was targeted with chitosan-encapsulated siRNA with and without carboplatin. RESULTS: Endoglin expression was surprisingly predominantly cytoplasmic, with a small population of surface-positive cells. Endoglin inhibition decreased cell viability, increased apoptosis, induced double-stranded DNA damage, and increased cisplatin sensitivity. Targeting endoglin downregulates expression of numerous DNA repair genes, including BARD1, H2AFX, NBN, NTHL1, and SIRT1. BARD1 was also associated with platinum resistance, and was induced by platinum exposure. In vivo, antiendoglin treatment decreased tumor weight in both ES2 and HeyA8MDR models when compared with control (35%-41% reduction, P < 0.05). Endoglin inhibition with carboplatin was associated with even greater inhibitory effect when compared with control (58%-62% reduction, P < 0.001). CONCLUSIONS: Endoglin downregulation promotes apoptosis, induces significant DNA damage through modulation of numerous DNA repair genes, and improves platinum sensitivity both in vivo and in vitro. Antiendoglin therapy would allow dual treatment of both tumor angiogenesis and a subset of aggressive tumor cells expressing endoglin and is being actively pursued as therapy in ovarian cancer.

Smoothened antagonists reverse taxane resistance in ovarian cancer.

The hedgehog pathway has been implicated in the formation and maintenance of a variety of malignancies, including ovarian cancer; however, it is unknown whether hedgehog signaling is involved in ovarian cancer chemoresistance. The goal of this study was to determine the effects of antagonizing the hedgehog receptor, Smoothened (Smo), on chemotherapy response in ovarian cancer. Expression of hedgehog pathway members was assessed in three pairs of parental and chemotherapy-resistant ovarian cancer cell lines (A2780ip2/A2780cp20, SKOV3ip1/SKOV3TRip2, HeyA8/HeyA8MDR) using quantitative PCR and Western blot analysis. Cell lines were exposed to increasing concentrations of two different Smo antagonists (cyclopamine, LDE225) alone and in combination with carboplatin or paclitaxel. Selective knockdown of Smo, Gli1, or Gli2 was achieved using siRNA constructs. Cell viability was assessed by MTT assay. A2780cp20 and SKOV3TRip2 orthotopic xenografts were treated with vehicle, LDE225, paclitaxel, or combination therapy. Chemoresistant cell lines showed higher expression (>2-fold, P < 0.05) of hedgehog signaling components compared with their respective parental lines. Smo antagonists sensitized chemotherapy-resistant cell lines to paclitaxel, but not to carboplatin. LDE225 treatment also increased sensitivity of ALDH-positive cells to paclitaxel. A2780cp20 and SKOV3TRip2 xenografts treated with combined LDE225 and paclitaxel had significantly less tumor burden than those treated with vehicle or either agent alone. Increased taxane sensitivity seems to be mediated by a decrease in P-glycoprotein (MDR1) expression. Selective knockdown of Smo, Gli1, or Gli2 all increased taxane sensitivity. Smo antagonists reverse taxane resistance in chemoresistant ovarian cancer models, suggesting combined anti-hedgehog and chemotherapies could provide a useful therapeutic strategy for ovarian cancer.

Therapeutic role of lymphadenectomy for cervical cancer.

BACKGROUND: Despite the diagnostic value of lymphadenectomy for early-stage cervical cancer, its therapeutic role is unknown. We examined the therapeutic potential of extensive lymphadenectomy in women with early-stage cervical cancer. METHODS: Women with stage IA2-IIA cervical cancer who underwent radical hysterectomy with lymphadenectomy in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients were stratified according to the number of nodes removed. The effect of the extent of lymphadenectomy on overall and cancer-specific survival was examined using multivariable Cox proportional hazards models. Separate analyses were performed for node positive and node negative patients. RESULTS: Among 5522 women, 893 (16%) had <10 nodes, 2030 (37%) had 11-20, 1487 (27%) had 21-30 nodes, and 1112 (20%) had >30 nodes removed. Black women, those >65 years of age and those diagnosed later in the study, were less likely to have 10 or more nodes removed (P < .05 for all). Among women with positive lymph nodes, a more extensive lymphadenectomy had no effect on survival (HR = 0.75; 95% CI, 0.47-1.22). For women with negative lymph nodes, a more extensive lymphadenectomy was associated with improved survival. Compared with node negative patients with less than 10 nodes removed, patients with 21-30 nodes removed were 24% (HR = 0.76; 95% CI, 0.53-1.09) less likely to die, whereas those with >30 nodes removed were 37% (HR = 0.64; 95% CI, 0.43-0.96) less likely to die from their tumors. CONCLUSIONS: Node negative, early-stage cervical cancer patients who undergo a more extensive lymphadenectomy have an improved survival.

Quality of perioperative venous thromboembolism prophylaxis in gynecologic surgery.

OBJECTIVE: To estimate the use of venous thromboembolism prophylaxis in women undergoing gynecologic surgery and to estimate the patient, physician, and hospital characteristics associated with guideline-based prophylaxis. METHODS: A commercial database was used to examine women who underwent major gynecologic surgery from 2000 to 2010. Venous thromboembolism prophylaxis was classified as none, mechanical, pharmacologic, or a combination. Multivariable logistic regression models of factors associated with any prophylaxis and pharmacologic and combination prophylaxis were developed. RESULTS: We identified a total of 738,150 women who underwent gynecologic surgery. No prophylaxis was given to 292,034 (39.6%) women, whereas 344,068 (46.6%) received mechanical prophylaxis, 40,268 (5.5%) pharmacologic prophylaxis, and 61,780 (8.4%) combination prophylaxis. Use of prophylaxis increased from 53.5% in 2000 to 67.5% in 2010. Prophylaxis was more commonly used in older women, those with Medicare, women with more comorbidities, white women, patients treated at rural hospitals, teaching facilities, and in patients treated by high-volume surgeons and at high-volume centers (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.23-1.27, P<.05 for all). Factors associated with use of pharmacologic prophylaxis included advanced age, white race, noncommercial insurance, later year of diagnosis, greater comorbidity, treatment at large hospitals and urban facilities, and treatment by a high-volume surgeon (OR 1.47, 95% CI 1.44-1.49). CONCLUSION: Despite clear recommendations from evidence-based guidelines, venous thromboembolism prophylaxis is underused in women undergoing gynecologic surgery.

Adherence to evidence-based guidelines for preoperative testing in women undergoing gynecologic surgery.

OBJECTIVE: To examine adherence to evidence-based recommendations for preoperative testing and health care costs associated with excessive testing. METHODS: An institutional review of women who underwent gynecologic surgery between 2005 and 2007 was performed. Data on the type of surgery, age, comorbidities, and perioperative testing was extracted. We noted the preoperative performance of chest X-ray, electrocardiogram, metabolic panel, complete blood count, coagulation studies, liver function tests, and urinalysis. Each test was classified as being guideline-based (appropriate) or non-guideline-based (inappropriate) as described by the National Institute of Clinical Excellence perioperative guidelines. RESULTS: A total of 1,402 patients were identified. Ninety-five percent of patients underwent all of the guideline-recommended preoperative testing. Ninety percent of women underwent at least one nonindicated preoperative test. None of the 749 urinalyses, 407 liver function tests, or 1,046 coagulation studies performed was appropriate. Ninety-nine percent of the 427 chest X-rays ordered were inappropriate. Only 17% of metabolic panels, 36% of electrocardiograms, and 29% of complete blood counts were in accordance with evidence-based guidelines. Inappropriate perioperative tests led to a direct cost of more than $418,000. Of the inappropriate tests ordered, abnormalities were noted frequently but rarely changed management. CONCLUSION: Adherence to evidence-based recommendations for preoperative testing is poor. Inappropriate preoperative tests represent a major health care expenditure. LEVEL OF EVIDENCE: III.