Caela Miller

The impact of disease distribution on survival in patients with stage III epithelial ovarian cancer cytoreduced to microscopic residual: A gynecologic oncology group study

OBJECTIVE To assess the survival impact of initial disease distribution on patients with stage III epithelial ovarian cancer (EOC) cytoreduced to microscopic residual. METHODS We reviewed data from 417 stage III EOC patients cytoreduced to microscopic disease and given adjuvant intravenous platinum/paclitaxel on one of three randomized Gynecologic Oncology Group (GOG) trials. We subdivided patients into three groups based on preoperative disease burden: (1) minimal disease (MD) defined by pelvic tumor and retroperitoneal metastasis (2) abdominal peritoneal disease (APD) with disease limited to the pelvis, retroperitoneum, lower abdomen and omentum; and (3) upper abdominal disease (UAD) with disease affecting the diaphragm, spleen, liver or pancreas. We assessed the survival impact of potential prognostic factors, focusing on initial disease distribution using a proportional hazards model and estimated Kaplan-Meier survival curves. RESULTS The study groups had similar clinicopathologic characteristics. Median overall survival (OS) was not reached in MD patients compared to 80 and 56 months in the APD and UAD groups (P<0.05). The five-year survival percentages for MD, APD, and UAD were 67%, 63%, and 45%. In multivariate analysis, the UAD group had a significantly worse prognosis than MD and APD both individually and combined (Progression Free Survival (PFS) Hazards Ratio (HR) 1.44; P=0.008 and OS HR 1.77; P=0.0004 compared to MD+APD). CONCLUSION Stage III EOC patients with initial disease in the upper abdomen have a worse prognosis despite cytoreductive surgery to microscopic residual implying that factors beyond cytoreductive effort are important in predicting survival.

Proteomic analysis of stage i endometrial cancer tissue: Identification of proteins associated with oxidative processes and inflammation

OBJECTIVE The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection. METHODS A differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types. An independent set of endometrial cancer specimens from 394 patients were used to externally validate the differential expression of select proteins. RESULTS 209 differentially expressed proteins were identified in a comparison of stage I endometrial cancers and normal post-menopausal endometrium controls (Q<0.005). A number of differentially abundant proteins in stage I endometrial cancer were identified and independently validated by western blot and tissue microarray analyses. Multiple proteins identified with elevated abundance in stage I endometrial cancer are functionally associated with inflammation (annexins) and oxidative processes (peroxiredoxins). PRDX1 and ANXA2 were both confirmed as being overexpressed in stage I cancer compared to normal endometrium by independent TMA (Q=0.008 and Q=0.00002 respectively). CONCLUSIONS These data provide the basis for further investigation of previously unrecognized novel pathways involved in early stage endometrial carcinogenesis and provide possible targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.

Gene Expression Analysis of Early Stage Endometrial Cancers Reveals Unique Transcripts Associated with Grade and Histology but Not Depth of Invasion

Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis.

Conservative management of extra-adrenal pheochromocytoma during pregnancy.

BACKGROUND: Extra-adrenal pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin cells of the paraganglion sympathetic system. All of the previously reported cases have described surgical resection during the antepartum period. CASE: At 14 weeks of gestation, a multiparous patient was diagnosed with an extra-adrenal dopaminergic pheochromocytoma. A decision was made to delay surgical intervention until the postpartum period. Phenoxybenzamine, 10 mg per day, was subsequently started. At 35 + 2 weeks of gestation, the patient delivered a 2,600 g infant via an uncomplicated cesarean. Three weeks later, the extra-adrenal pheochromocytoma was removed, and she also underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and rectosigmoid resection with end-to-end colostomy. CONCLUSION: Conservative management of dopaminergic-secreting extra-adrenal pheochromocytomas can result in favorable maternal and fetal outcomes.

Takotsubo cardiomyopathy following laparoscopic port placement in a patient with ovarian cancer

► Gynecologic oncology patients can be exposed to both chronic and acute physical and emotional stress. ► Gynecologic oncology patients appear to represent an at-risk population for the development of Takotsubos cardiomyopathy.

Is FDA Approved Bevacizumab Cost-Effective in the Setting of Platinum-Resistant Recurrent Ovarian Cancer? [18].

INTRODUCTION: The recent FDA approval of inclusion of bevacizumab (BEV) in the treatment of platinum-resistant recurrent ovarian cancer will likely lead to more widespread adoption of this intervention. We assessed the cost effectiveness of this expensive treatment for this specific indication. METHODS: A cost effectiveness decision model was constructed using results from AURELIA, a phase III randomized trial comparing BEV plus cytotoxic chemotherapy versus chemotherapy alone in patients with platinum-resistant recurrent ovarian cancer. The BEV arm of AURELIA had improved progression free survival and quality of life (QOL). Costs, paracentesis rates, and adverse events were incorporated. RESULTS: Inclusion of BEV in the treatment of platinum-resistant recurrent ovarian cancer costs on average

The Efficacy of Cryoablation Versus LEEP for the Treatment of CIN II: A US Military Medical Centerʼs Experience [4J]

26,790 more than cytotoxic chemotherapy alone when 15 mg/kg dosing is used and

The ability of endometrial biopsies with atypical complex hyperplasia to guide surgical management

40,813 more when biweekly 10 mg/kg is used. The incremental cost-effectiveness ratio (ICER) per progression-free life year saved (PF-LYS) is

Postpartum urinary retention.

146K with 10 mg/kg dosing and

Impact of After Hour Availability of Gynecological Surgical and Clinical Supplies on Resident Satisfaction [29I]

96K with 15 mg/kg dosing. In sensitivity analysis, the ICER drops below a willingness-to-pay (WTP) threshold of