A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes.

Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Using data from large endometriosis and EOC genome-wide association meta-analyses, we estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and EOC histotypes, and identify shared susceptibility loci. We estimate a significant genetic correlation (rg) between endometriosis and clear cell (rg = 0.71), endometrioid (rg = 0.48), and high-grade serous (rg = 0.19) ovarian cancer, associations supported by Mendelian randomization analyses. Bivariate meta-analysis identified 28 loci associated with both endometriosis and EOC, including 19 with evidence for a shared underlying association signal. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlights several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases.

Effect of obesity on survival in epithelial ovarian cancer.

BACKGROUND: Epidemiologic studies suggest that obese women are more likely to die of ovarian cancer than those of ideal body weight, but it is not known whether increased incidence, comorbidities common to obese women, or altered tumor biology is responsible for this difference. The current study attempted to determine the influence of excess body weight on ovarian cancer survival, disease progression, and clinicopathologic factors. METHODS: The records of patients undergoing surgery for epithelial ovarian cancer at Cedars Sinai Medical Center between January 1, 1996 and June 30, 2003 were reviewed for height, weight, age, comorbidities, and treatment-specific details. Statistical analyses included the Fisher exact test, Kaplan-Meier survival, and Cox regression analyses. RESULTS: In all, 216 patients were identified. Eight percent were underweight (body mass index [BMI] < 18.5), 50% were ideal body weight (18.5 /= 30). Age, comorbidities including coronary artery disease and venous thromboembolism, and rates of optimal surgical cytoreduction were similar among BMI strata. Diabetes and hypertension were more common in obese women. Ten (29%) of the obese patients had International Federation of Gynecology and Obstetrics (FIGO) Stage I disease, compared with 19 (10%) of the patients with BMI < 30 (P = .01). In a subcohort of 149 patients with Stage III or IV disease, a significant trend was identified favoring increased BMI as an independent negative factor for disease-free (P = .02) and overall (P = .02) survival. CONCLUSIONS: Obese patients were more likely to have disease limited to the ovaries. For patients with advanced stage disease, obesity was independently associated with both shorter time to recurrence and shorter overall survival. These findings suggest an effect of excess body weight on tumor biology, and studies are under way to elucidate the molecular and hormonal mechanisms underlying these clinical observations.

Lower urinary tract reconstruction with ileum in the treatment of gynecologic malignancies.

INTRODUCTION: Advanced or recurrent gynecologic malignancies can invade or obstruct the lower urinary tract. If extirpation is necessary for cytoreduction or repair of radiation sequelae, treatment has typically involved creation of either an ileal conduit or a cutaneous continent urinary diversion. As an alternative, a more limited resection with urinary tract reconstruction using ileum for interposition or augmentation may allow for the preservation of urethral voiding. CASES: We describe the use of ileal segments for lower urinary tract reconstruction in the treatment of ten patients with advanced or recurrent gynecologic malignancies. The clinical history, surgical technique, and patient outcomes are reviewed. DISCUSSION: These cases demonstrate that limited bladder or ureteral resection with reconstruction using ileal segments may offer select patients preservation of urethral voiding.

The prognostic significance of thrombocytosis in epithelial ovarian carcinoma.

OBJECTIVE: The objective of this study was to determine the incidence of thrombocytosis in epithelial ovarian carcinoma and examine associations with clinico-pathologic features. Thrombocytosis (platelet counts >400 x 10(9)/l) has been identified as a poor prognostic factor in many cancers. Platelet-secreted factors may contribute to metastasis, invasion, and primary tumor growth. METHODS: One hundred eighty-three patients with invasive epithelial ovarian or primary peritoneal carcinomas were identified between January 1996 and December 2000. Records were retrospectively reviewed and data analyzed using chi(2), Student's t test, and Cox proportional hazards model; survival was analyzed by the method of Kaplan and Meier. RESULTS: Forty-one of 183 (22.4%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis were found to have greater elevations of CA-125 (P = 0.026), more advanced stage disease (P = 0.016), higher grade tumors (P = 0.010), more frequent lymph node metastases (P = 0.018), and greater volume of ascites (P < 0.0001). One hundred sixty of 183 (87.4%) patients achieved optimal cytoreduction; patients with thrombocytosis demonstrated a greater likelihood of suboptimal resection (residual disease >1 cm; 19/41 vs. 4/142 in patients without thrombocytosis, P < 0.0001). Patients with thrombocytosis had a shorter disease-free interval (12 vs. 34 months, P < 0.0001) and overall survival (28 vs. 79 months, P < 0.0001). On multivariate analysis, thrombocytosis retained significance as a poor prognostic indicator in patients with stage III and IVA disease (P = 0.04). CONCLUSIONS: Thrombocytosis is a frequent preoperative finding in ovarian and peritoneal carcinomas and may be a marker of aggressive tumor biology.