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Objective: Aberrant DNA methylation is an early event in carcinogenesis which could be leveraged to detect ovarian cancer (OC) in plasma., Methods: DNA from frozen OC tissues, benign fallopian tube epithelium (FTE), and buffy coats from cancer-free women underwent reduced representation bisulfite sequencing (RRBS) to identify OC MDMs. Candidate MDM selection was based on receiver operating characteristic (ROC) discrimination, methylation fold change, and low background methylation among controls. Blinded biological validation was performed using methylated specific PCR on DNA extracted from independent OC and FTE FFPE tissues. MDMs were tested using Target Enrichment Long-probe Quantitative Amplified Signal (TELQAS) assays in pre-treatment plasma from women newly diagnosed with OC and population-sampled healthy women. A random forest modeling analysis was performed to generate predictive probability of disease; results were 500-fold in silico cross-validated., Results: Thirty-three MDMs showed marked methylation fold changes (10 to >1000) across all OC subtypes vs FTE. Eleven MDMs (GPRIN1, CDO1, SRC, SIM2, AGRN, FAIM2, CELF2, RIPPLY3, GYPC, CAPN2, BCAT1) were tested on plasma from 91 women with OC (73 (80%) high-grade serous (HGS)) and 91 without OC; the cross-validated 11-MDM panel highly discriminated OC from controls (96% (95% CI, 89-99%) specificity; 79% (69-87%) sensitivity, and AUC 0.91 (0.86-0.96)). Among the 5 stage I/II HGS OCs included, all were correctly identified., Conclusions: Whole methylome sequencing, stringent filtering criteria, and biological validation yielded candidate MDMs for OC that performed with high sensitivity and specificity in plasma. Larger plasma-based OC MDM studies, including testing of pre-diagnostic specimens, are warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Surgical site infection (SSI) following epithelial ovarian cancer (EOC) primary surgery (PS) occurs in 10-15% of women. Perioperative factors associated with SSI and impact of SSI on survival were determined., Methods: EOC cases that underwent PS from 1/2/2003 to 12/30/2011 were retrospectively reviewed. SSIs were defined according to ACS NSQIP. Logistic regression models were fit to identify factors associated with SSI. Cox proportional hazards models were utilized to evaluate the association of patient and perioperative characteristics with overall survival (OS) and disease-free survival (DFS)., Results: Among 888 cases, 96 (10.8%) developed SSI: 32 superficial, 2 deep, and 62 organ/space. Factors independently associated with superficial SSI were increasing BMI (odds ratio 1.41 [95% confidence interval, 1.12, 1.76] per 5kg/m(2)), increasing operative time (1.24 [1.02, 1.50] per hour), and advanced stage (III/IV) (10.22 [1.37, 76.20]). Factors independently associated with organ/space SSI were history of gastroesophageal reflux disease (2.13 [1.23, 3.71]), surgical complexity (intermediate 3.11 [1.02, 9.49]; high 8.07 [2.60, 25.09]; referent: low), and residual disease (RD) (measureable ≤1cm 1.77 [0.96, 3.27]; suboptimal >1cm (3.36 [1.48, 7.61]; referent: microscopic). Occurrence of superficial (hazard ratio 1.69 [1.12, 2.57]) or organ/space (1.46 [1.07, 2.00]) SSI was independently associated with worse OS. SSI occurrence was not independently associated with DFS., Conclusions: SSI after PS is associated with decreased OS. Most risk factors for SSI are not modifiable. Alternative measures to lower rates of SSIs are needed as this may improve OS. Preoperative identification of SSI risk factors may assist in risk-assessment and operative planning., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to determine the incidence and the risk factors of venous thromboembolism (VTE) within 30 days after primary surgery for epithelial ovarian cancer (EOC)., Methods: In a historical cohort study, we estimated the postoperative 30-day cumulative incidence of VTE among consecutive Mayo Clinic patients undergoing primary cytoreduction for EOC between January 2, 2003, and December 29, 2008. We tested perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program, >130 variables) as potential predictors of postoperative VTE using the Cox proportional hazards modeling., Results: Among 569 cases of primary EOC cytoreduction and/or staging and no recent VTE, 35 developed symptomatic VTE within 30 days after surgery (cumulative incidence = 6.5%; 95% confidence interval, 4.4%-8.6%). Within the cohort, 95 (16.7%) received graduated compression stockings (GCSs), 367 (64.5%) had sequential compression devices + GCSs, and 69 (12.1%) had sequential compression devices + GCSs + postoperative heparin, with VTE rates of 1.1%, 7.4%, and 5.8%, respectively (P = 0.07, χ(2) test). The remaining 38 (6.7%) received various other chemical and mechanical prophylaxis regimens. In the multivariate analysis, current or past tobacco smoking, longer hospital stay, and a remote history of VTE significantly increased the risk for postoperative VTE., Conclusions: Venous thromboembolism is a substantial postoperative complication among women with EOC, and the high cumulative rate of VTE within 30 days after primary surgery suggests that a more aggressive strategy is needed for VTE prevention. In addition, because longer hospital stay is independently associated with a higher risk for VTE, methods to decrease length of stay and minimize factors that contribute to prolonged hospitalization are warranted.

Objective: Perioperative packed red blood cell transfusion (PRBCT) has been implicated as a negative prognostic marker in surgical oncology. There is a paucity of evidence on the impact of PRBCT on outcomes in epithelial ovarian cancer (EOC). We assessed whether PRBCT is an independent risk factor of recurrence and death from EOC., Methods: Perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program) were retrospectively abstracted from 587 women who underwent primary EOC staging between January 2, 2003, and December 29, 2008. Associations with receipt of PRBCT were evaluated using univariate logistic regression models. The associations between receipt of PRBCT and disease-free survival and overall survival were evaluated using multivariable Cox proportional hazards models and using propensity score matching and stratification, respectively., Results: The rate of PRBCT was 77.0%. The mean ± SD units transfused was 4.1 ± 3.1 U. In the univariate analysis, receipt of PRBCT was significantly associated with older age, advanced stage (≥ IIIA), undergoing splenectomy, higher surgical complexity, serous histologic diagnosis, greater estimated blood loss, longer operating time, the presence of residual disease, and lower preoperative albumin and hemoglobin. Perioperative packed red blood cell transfusion was not associated with an increased risk for recurrence or death, in an analysis adjusting for other risk factors in a multivariable model or in an analysis using propensity score matching or stratification to control for differences between the patients with and without PRBCT., Conclusions: Perioperative packed red blood cell transfusion does not seem to be directly associated with recurrence and death in EOC. However, lower preoperative hemoglobin was associated with a higher risk for recurrence. The need for PRBCT seems to be a stronger prognostic indicator than the receipt of PRBCT.

Objective: Thorough primary cytoreduction for epithelial ovarian carcinoma (EOC) improves survival. The incidence of postoperative ileus (POI) in these patients may be underreported because of varying POI definitions and the evolving, increasingly complex contemporary surgical approach to EOC. We sought to determine the current incidence of POI and its risk factors in women undergoing debulking and staging for EOC., Methods: We retrospectively identified the records of women who underwent primary staging and cytoreduction for EOC between 2003 and 2008. POI was defined as a surgeon's diagnosis of POI, return to nothing-by-mouth status, or reinsertion of a nasogastric tube. Perioperative patient characteristics and process-of-care variables were analyzed. Univariate analyses were used to identify POI risk factors; variables with P ≤.20 were included in multivariate analysis., Results: Among 587 women identified, the overall incidence of POI was 30.3% (25.9% without bowel resection, 38.5% with bowel resection; P=.002). Preoperative thrombocytosis, involvement of bowel mesentery with carcinoma, and perioperative red blood cell transfusion were independently associated with increased POI. Postoperative ibuprofen use was associated with decreased POI risk. Women with POI had a longer length of stay (median, 11 vs 6 days) and increased time to recovery of the upper (7.5 vs 4 days) and lower (4 vs 3 days) gastrointestinal tract (P<.001 for each)., Conclusions: The rate of POI is substantial among women undergoing staging and cytoreduction for EOC and is associated with increased length of stay. Modifiable risk factors may include transfusion and postoperative ibuprofen use. Alternative interventions to decrease POI are needed., (Copyright © 2012 Elsevier Inc. All rights reserved.)