Cost-effectiveness analysis of biopsy strategies for endometrial cancer diagnosis in women with postmenopausal bleeding: Pipelle sampling curette versus dilatation & curettage.

BACKGROUND: Endometrial sampling is widely used for accurate diagnosis of endometrial cancer (EC), which is the most common gynecologic cancer in US women. The objective of this study was to explore the cost-effectiveness of two endometrial sampling procedures for diagnosing EC: (1) Pipelle endometrial sampling (Pipelle), and (2) dilatation & curettage (D&C), while accounting for sampling procedure failure rates and diagnostic accuracy in women with postmenopausal bleeding (PMB). METHOD: The decision analytic model was built to compare the cost-effectiveness of Pipelle and D&C strategies in a hypothetical cohort of PMB women. The analysis was performed from the perspective of a public healthcare payer (Medicare, US). We used 2017 Medicare reimbursement data for cost estimation. The effectiveness of these two diagnostic strategies was measured by analyzing the remaining life expectancy after EC diagnosis and subsequent treatment. RESULTS: The base case analysis suggested that Pipelle was not only equally effective (32.11 vs. 32.11 years of life), but also less costly ($1897.80 vs. $2999.11) based on Medicare reimbursement when compared to D&C. In one-way sensitivity analyses and Monte Carlo probabilistic sensitivity analysis, the Pipelle remained the more cost-effective sampling strategy even after accounting for sampling failure rate associated with each sampling strategy. CONCLUSION: The Pipelle is the more cost-effective sampling strategy compared to D&C for EC diagnosis in women with PMB. From the cost-effectiveness perspective, the higher sampling failure rate of Pipelle should not be regarded as a limitation in its clinical application.

Super-Utilization of Health Care Resources Among Gynecologic Oncology Patients.

Super-utilizers account for many emergency department visits (EDV) and hospitalizations. Among Medicare/Medicaid patients, 5% to 10% account for >50% of spending. Little is known about super-utilization in gynecologic oncology. Charts of 64 gynecologic oncology patients with ≥3 EDV and/or admissions over 12 months were reviewed retrospectively. Cancer type distribution was 47% ovarian, 23% cervical, 23% endometrial, and 6% vulvar. Treatment at index visit was 61% chemotherapy, 16% no treatment, 8% recent surgery, and 6% radiation. Mean visits was 5.7 (SD 3.9, range 3-28). Most common presenting complaints were gastrointestinal and pain. Patients near end of life were more likely to be admitted. EDV frequently occurred outside standard work hours (63%). EDV/admissions resulted in total variable expenses of $1 462 581 ($982 933 direct expense, $479 648 service expense). Interventions to decrease super-utilization could target symptom management, off-hour support, patients on chemotherapy, and end of life. Approaches could include multidisciplinary resources, palliative care teams, extending office hours, and earlier initiation of hospice.

Racial and Socioeconomic Disparities in Hysterectomy Route for Benign Conditions.

BACKGROUND: The aim of this paper was to explore disparities associated with the route of hysterectomy in the University of Pittsburgh Medical Center (UPMC) health system and to evaluate whether the hysterectomy clinical pathway implementation impacted disparities in the utilization of minimally invasive hysterectomy (MIH). METHODS: We performed a retrospective medical record review of all the patients who have undergone hysterectomy for benign indications at UPMC-affiliated hospitals between fiscal years (FY) 2012 and 2014. RESULTS: A total number of 6373 hysterectomy patient cases were included in this study: 88.7% (5653) were European American (EA), 11.02% (702) were African American (AA), and the remaining 0.28% (18) were of other ethnicities. We found that non-EA, women aged 45-60, traditional Medicaid, and traditional Medicare enrollees were more likely to have a total abdominal hysterectomy (TAH). Residence in higher median income zip code (> $61,000) was associated with 60% lower odds of undergoing TAH. Both FY 2013 and 2014 were associated with significantly lower odds of TAH. Logistic regression results from the model for non-EA patients for FY 2012 and FY 2014 demonstrated that FY and zip code income group were not significant predictors of surgery type in this subgroup. Pathway implementation did not reduce racial disparity in MIH utilization. CONCLUSION: This study demonstrated that there is a significant disparity in MIH utilization, where non-EA and Medicaid/Medicare recipients had higher odds of undergoing TAH. Further research is needed to investigate how care standardization may alleviate healthcare disparities.

Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors.

BACKGROUND: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese and non-obese women. METHODS: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed. RESULTS: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10(-6)) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10(-5)). The most notable obesity-gene-hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 × 10(-6)). CONCLUSIONS: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2 Future work is needed to develop powerful statistical methods able to detect these complex interactions. IMPACT: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780-90. ©2016 AACR.

The association between socioeconomic status and tumour stage at diagnosis of ovarian cancer: A pooled analysis of 18 case-control studies.

PURPOSE: Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI) on the association was also evaluated. METHODS: From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio (pOR) using a random effects model. RESULTS: Overall, women who completed ≤high school had an increased risk of advanced tumour stage at diagnosis compared with women who completed >high school (pOR 1.15; 95% CI 1.03-1.28). The risk estimates for the different histotypes of ovarian cancer resembled that observed for ovarian cancers combined but did not reach statistical significance. Our results were unchanged when we included BMI and cigarette smoking. CONCLUSION: Lower level of education was associated with an increased risk of advanced tumour stage at diagnosis of ovarian cancer. The observed socioeconomic difference in stage at diagnosis of ovarian cancer calls for further studies on how to reduce this diagnostic delay.

Heavy cervical cancer burden in elderly women: how can we improve the situation?

OBJECTIVES: The American Cancer Society, the American College of Obstetricians and Gynecologists and the US Preventive Services Task Force recommend discontinuation of cervical cancer screening between 65 and 70 years of age in women with no abnormal test results in the preceding 10 years. This population-based study was undertaken to determine the incidence of cervical cancer in different age groups as a means to establish if current screening recommendations need reevaluation. STUDY DESIGN: Data from the SEER database were used to compute incidence rates for cervical cancer diagnosed between 2000 and 2006 by age and disease stage. RESULTS: We identified 18,003 women with cervical cancer. 12.18% were above the age of 69. The incidence in this age group was 8.7/100,000. Women younger than 30 comprised 5.7% of patients with an incidence of 5/100,000 and were most commonly diagnosed with stage IA1 disease. Women above 70 were most frequently diagnosed with stage IIIB. 79% of patients younger than 30 were diagnosed with an early disease (stage IA1-IIA) as opposed to only 41.2% of patients aged 69 or above. CONCLUSIONS: The incidence of cervical cancer does not decrease significantly in older women. Women over the age of 70 are frequently diagnosed with advanced stage disease which limits their treatment options. Failure to apply uniform screening across all at-risk age groups may account for the discrepancy.

Noninvasive assessment of cell proliferation in ovarian cancer using [18F] 3'deoxy-3-fluorothymidine positron emission tomography/computed tomography imaging.

INTRODUCTION: Positron emission tomography (PET)/computed tomography (CT) imaging of suspected new and recurrent ovarian carcinoma was performed to assess the relationship between [(18)F] 3'deoxy-3'fluorothymidine ((18)FLT) uptake and histopathological tissue markers of cellular proliferation (Ki67) and thymidine kinase-1 (TK-1) expression. METHODS: Six subjects were included in this pilot study. Subjects were injected with 5 mCi of (18)FLT prior to a planned surgery and then scanned on a GE Discovery-ST PET/CT scanner within an hour of injection. Regions of interest in tumor and control tissue were identified on the diagnostic CT scans and marked for later surgical biopsy. Surgery was performed within 2 days after the scan. At the time of surgery, the regions of interest identified on PET/CT were available to guide the surgeon to the tumor biopsy sites. Tissue from normal ovarian tissue control regions was also sampled. (18)FLT uptake in tumor and control tissue regions was calculated by measuring the maximum standardized uptake values (SUV(max)). The excised tumor and normal ovarian tissue control tissues were analyzed by immunohistochemical staining for Ki67 and CD34. TK-1 messenger RNA expression was measured by real-time polymerase chain reaction. RESULTS: (18)FLT uptake (SUV(max)) was higher in malignant (mean 4.85/range 1.7-8.8) compared to benign (1.65/range 1.4-1.9) and normal ovarian control tissue (1.12/range 0.6-1.5). Mitotic index, as determined by Ki67 staining, was higher in malignant (18.89/range 11.97-27.19) compared to benign (0.59/range 0.23-0.95) and control tissue (0.45/range 0.06-1.20). TK-1 expression was also higher in malignant (35.52/range 5.21-106.62) compared to benign (8.71/range 4.74-12.67) and control tissue (9.79/range 0.85-39.46). An increasing trend between (18)FLT uptake and Ki67 mitotic index is seen in malignant tissue CD 34 staining between malignant, benign and control tissues was not qualitatively different. CONCLUSION: An increasing trend between (18)FLT uptake and Ki67 mitotic index is seen in malignant tissue. Additional studies will determine whether (18)FLT PET/CT is specific enough to distinguish between cancerous and noncancerous cells and to assess its role in ovarian carcinoma patient management.

Assessment of buffer systems for harvesting proteins from tissue interstitial fluid for proteomic analysis.

Tissue interstitial fluid (TIF) bathes cells in tissues, and it is hypothesized that TIF proximal to a developing tumor may contain an enriched population of tumor-specific shed and secreted proteins relative to peripheral blood. Extraction of TIF proteins is typically accomplished through passive incubation of surgically resected tissues in phosphate buffered saline (PBS); however, its influence on cellular activity and viability has not been fully explored. The present investigation sought to characterize whether different buffer systems influence the recovered TIF proteome. Five TIF buffer systems were investigated including PBS, Dulbecco's modified Eagle medium (DMEM), and three organ transplantation preservative solutions: Celsior solution S (CS), histidine-tryptophan-ketoglutarate (HTK), and University of Wisconsin (UW). Kidney tumor, adjacent normal kidney, and ovarian tumor tissues were incubated in each of the buffer systems, and the harvested TIF proteins were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the present results indicate that no significant differences exist in the recovered proteins from these two neoplasms between the five solution groups, additional sample preparative steps are required prior to LC-MS/MS for TIF proteins harvested from DMEM, UW, CS, and HTK. These data support that PBS is a suitable and convenient solution for harvesting TIF proteins for MS-based proteomics.