OBJECTIVES:The objective of this study is to assess the reliability of intraoperative uterine assessment compared with the final pathologic evaluation in patients with endometrial cancer (EC) and whether assessment improves with experience. METHODS:After Institutional Review Board approval, a prospective cohort study of women surgically managed with biopsy-proven complex atypical hyperplasia (CAH) or EC between March 2015 and December 2016 was performed. Demographics, preoperative biopsy results, procedure, intraoperative and final pathologic evaluation of lesion size, myometrial invasion, and lower uterine segment/cervical involvement were abstracted. The agreement between the intraoperative and final pathologic evaluation of tumor involvement of the uterus was determined using the kappa statistic and the intraclass correlation coefficient. RESULTS:A total of 264 patients with a preoperative diagnosis of CAH or EC were included-71 (26.9%) with CAH and 193 (73.1%) with EC. The mean age was 62.6±11.5, and mean body mass index was 37.2±10.1. The majority of women were white (67%). A total of 227 (85.9%) patients underwent a laparoscopic or robotic hysterectomy, whereas 36 (13.6%) underwent an abdominal hysterectomy. 233 (88.3%) patients had EC and 21 (7.9%) patients had CAH on final pathology. There was a fair agreement between the intraoperative estimation of myometrial invasion (κ=0.37). A moderate agreement exists between the intraoperative estimation of lower uterine segment/cervical involvement (κ=0.57). There was a strong agreement between intraoperative tumor size assessment and the final path (intraclass correlation coefficient=0.74). The intraoperative correlation of tumor size was similar for the first half of the cohort (κ=0.50) and the second half (κ=0.46) chronologically. CONCLUSIONS:Despite only a fair correlation in the myometrial invasion, intraoperative assessment of cervical involvement and especially tumor size is more readily identified and overall accurate. Therefore, intraoperative evaluation is an additional tool to use when making the decision to proceed with surgical staging.

Objective: The initial treatment for endometrial cancer (EC) involves surgical resection as well as a staging procedure. Attempts have been made to determine which patients are at an increased risk of lymph node metastasis in an effort to avoid lymphadenectomy and its associated morbidity. No study to date has evaluated a surgeon's use of the Mayo Criteria intraoperatively to determine the need for lymphadenectomy. The goal of this study is to assess the reliability of intraoperative uterine assessment compared to final pathologic evaluation in patients with EC and whether assessment improves with experience.

Objective: Intraoperative frozen section can guide operative decisions in women with known or suspected malignancies. The correlation between frozen section and final pathology varies among gynecologic malignancies. We sought to examine rates of correlation between frozen section and final pathology in women with suspected gynecologic malignancies.

Objectives The objectives of this study were to compare preoperative and postoperative tumor grade to determine if surgical staging decisions for endometrial cancer based on preoperative biopsy are feasible and whether obesity affects the agreement. Methods A retrospective cohort study of women with endometrial cancer between January 2010 and December 2011 was performed. Demographics, stage of final pathology, biopsy method, preoperative and postoperative tissue grade, and histology were abstracted and stratified by patient body mass index (obese ≥30 kg/m2 and nonobese <30 kg/m2). Patients with incomplete records or uterine sarcoma were excluded. The agreement between preoperative and postoperative tumor grade for all patients and in obese and nonobese patients was determined using weighted κ statistics. Results Four hindered forty-five patients were included: 161 nonobese patients and 284 obese patients. The proportion of preoperative sampling via office biopsy and dilation and curettage was similar in each cohort. Overall, the agreement between preoperative and postoperative pathology was only fair (weighted κ = 0.21). Stratified by body mass index, the agreement between preoperative and postoperative grade remains fair in obese and slight in nonobese patients (weighted κ = 0.21 and 0.19, respectively). Substantial increases in tumor grade from preoperative to postoperative pathologic specimens occurred in both cohorts. Conclusions Obesity does not appear to significantly alter the correlation between preoperative biopsy and final tumor grade. With only fair correlation between preoperative and postoperative pathologic evaluation, utilization of preoperative biopsy pathology results as a triage tool for surgical staging should be avoided. However, the discordance between preoperative and postoperative pathology in favor of a higher grade on final pathology in both groups may cause some surgeons to favor staging.

OBJECTIVES:Surgery is a cornerstone for patients with gynecologic malignancies. Surgical site infections (SSI) remain a source of post-operative morbidity. Consequences range from escalated costs, delay in adjuvant therapy, and increased morbidity. Our primary objective was to evaluate the effectiveness of a cyanoacrylate microbial sealant (CMS) to reduce post-operative SSI following laparotomy for suspected gynecologic malignancy.METHODS:Patients were randomized using a 1:1 allocation to receive either standard skin preparation or standard preparation with CMS and stratified by BMI. Patients were followed for 6weeks for SSI. Demographic data was collected through the EMR. Associations between SSI, use of CMS, and clinicopathologic factors were explored using descriptive statistics, chi-square and multivariate analysis.RESULTS:300 patients underwent randomization. Median age of the cohort was 58. Arms were matched and there was no difference in rate of medical comorbidities. Mean BMI was 38.8kg/m2 in patients randomized to BMI≥30 and 26.3kg/m2 randomized to BMI<30. Surgical characteristics for the entire cohort: 66% malignancy, 91% clean-contaminated, 21% bowel surgery, 25% transfusion. Seventy-six (25%) patients developed a SSI: 43 patients (28%) treated with CMS, compared to 33 (21%) patients treated without CMS (p=0.18). Multivariate model demonstrated that BMI≥30 (p<0.005), surgery for malignancy (p=0.010), transfusion in the OR (p<0.001), and closure with staples (p=0.0005) were associated with post-operative SSI.CONCLUSIONS:Patients presenting to a gynecologic oncologist for surgery frequently present with multiple risk factors for SSI and laparotomy is complicated by surgical-site complications in up to 30% of cases. The addition of CMS alone does not appear to reduce risk of overall SSI. Additional risk-reducing strategies including use of antimicrobial agents and optimization of modifiable risk factors prior to surgery should be explored as pathways for reducing this significant post-operative morbidity.

Objective. To evaluate the potential relationship between outcomes in cervical cancer patients based on distance from our Comprehensive Cancer Center (CCC).Methods. A retrospective cohort study of cervical cancer patients was performed. Abstracted data included: demographics, clinicopathologic variables, treatment, and survival. Analyses both by quartiles and distance <100 and-100 miles from our institution were performed. Data were analyzed using SAS version 9.2.Results. 390 patients living a median distance of 58.1 miles (range 1.2-571 miles) from our CCC were identified. Patients were generally white (n = 249), non-smokers (n = 226), with Stage IB disease (n = 222), squamous histology (n = 295) and underwent primary surgical therapy (n = 229). Patients were divided into both quartiles as well as two strata: <100 and 100 miles for comparison. Progression-free survival (PFS) and overall survival (OS) favored patients living closer to our center with a lower median OS for patients living ?AN miles (65.4vs. 99.4 months; p = 0.040). Cox proportional hazard modeling noted that advanced stage was predictive of inferior PFS and OS, while other clinical covariates including age, BMI, race, smoking status and histology had a variable impact on outcomes and distance >100 miles was associated with a higher risk of death (hazard ratio [HR] = 1.68, 95% confidence interval [CI] 1.11-2.54).Conclusion. Overall survival for patients living >100 miles from our CCC was worse when compared to patients in closer proximity. Outreach efforts and utilization of navigators may help decrease the impact of geographic and racial disparities on outcomes. (C) 2016 Elsevier Inc. All rights reserved.

Objectives: The purpose of this study was to evaluate the safety and efficacy of intralesional injection of the DNA plasmid vaccine, pNGVL4a-CRT-E7(detox), in combination with topical imiquimod in women with biopsy-confirmed HPV16-associated cervical intraepithelial neoplasia (CIN) 2/3. Methods: An expansion cohort was added to a phase I trial evaluating the safety, efficacy, and immunogenicity of pNGVL4a-CRT/E7(detox) administered alone, intradermally (via gene gun), intramuscularly, or directly into the cervix (intralesional), in women with HPV16+ CIN2/3. In this expansion cohort, patients received intralesional injection of pNGVL4a-CRT/E7(detox) at a dose of 3 mg, with concurrent application of 5% imiquimod cream at the injection site, at study weeks 0, 4, and 8. At week 15, patients underwent standard of care loop electrosurgical excision procedure (LEEP). Patients were monitored for clinical and laboratory adverse effects and for clinical efficacy by comparison of pre- and post-treatment histopathologic findings. Results: Twenty-one women with CIN 2/3 recruited from dysplasia clinics in participating institutions were screened for human papillomavirs (HPV) 16. Eight (42%) of 19 women were confirmed to be HPV 16+ and, of these, 7 consented to participate in this trial. pNGVL4a-CRT-E7(detox), in combination with topical imiquimod was well tolerated and no grade 3 or 4 events were seen. Five patients completed vaccination and underwent LEEP, and 2 are still in the vaccination phase. Of the 5 patients who underwent LEEP, 1 had no evidence of CIN2/3 and 4 had persistent CIN 2/3. Conclusions: Preliminary analysis demonstrates that the combination of intralesional pNGVL4a-CRT/E7(detox) and topical imiqimod is well tolerated. Accrual is ongoing and planned immunogenicity studies in the peripheral blood and in the target tissues will be performed once accrual is completed.

Objectives: Immunotherapy represents a promising approach to the treatment of ovarian cancer. We evaluated the antitumor activity of a conditionally replicative, oncolytic herpes simplex virus (oHSV) armed with murine cytokine, IL-12, and the ability of oHSV to elicit enhanced tumor-specific immune responses in ovarian cancer. Methods: We evaluated the in vitro cytotoxicity, defined as the number of plaque-forming units required to kill 50% of the cells (PFU/TD50), of oHSV toward several ovarian cancer cell lines, including syngeneic transplantable murine and paired human chemosensitive (CS) and chemoresistant (CR) lines. We also evaluated the immune response and antitumor response in Fox Chase TgMISIIR-Tag mice after intraperitoneal injection with oHSV. Specifically, immune response was assessed in various abdominal organs by quantifying CD8-specific T cells to the NIH tetramers, SV40 antigen and mesothelin. Antitumor response was assessed by measuring total tumor burden in oHSV-treated mice versus control mice. Results: The paired human CS & CR cell lines, syngeneic transplantable murine, and MISIIR cancer cells harvested and grown in tissue culture all demonstrated susceptibility to oHSV in vitro (see Table 1). Compared with controls, mice injected with oHSV demonstrated a more robust CD8-specific immune response to both SV40 antigen and mesothelin in all evaluated tissues. The mean difference in the number of SV40 antigen CD8-specific T cells was most pronounced in the omentum (471.6.cells oHSV vs 33.1 cells controls; P = .02) and the mean difference in mesothelin CD8-specific T cells was most pronounced in the peritoneal cavity (962.3 cells oHSV vs 179.5 cells control; P = .05). In the tumor burden experiment, 2 of 11 mice injected with oHSV died of disease compared with 9 of the 11 control mice. Five of 11 mice injected with oHSV showed no evidence of metastatic tumor when killed at 6 months. Conclusions: oHSV demonstrated effective antitumor activity in vitro in several ovarian cancer cell lines. A vigorous intraperitoneal CD8-specific immune response was also demonstrated in mice injected with oHSV. Lastly, oHSV was well tolerated in MISIIR mice, and led to decreased rates of intraperitoneal metastasis and ultimately less deaths. Further development of this oHSV is warranted.Table 14 and 8-hour susceptibilities to oHSV across all cell lines.

OBJECTIVE:We compared tolerability, toxicity, response, and interval debulking surgery (IDS) outcomes between patients who received weekly dose-dense paclitaxel (DDP) and every three-week platinum to standard every three-week taxane plus platinum neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC).METHODS:We conducted a retrospective study of patients receiving NACT at our center between June 1, 2012 and July 31, 2015. Patients with stage III/IV EOC who received at least one cycle of DDP (weekly paclitaxel plus every three-week carboplatin) or standard taxane (every three-week paclitaxel or docetaxel plus carboplatin) therapy were included. Abstracted data included demographics, tolerability, grade 3/4 toxicity, response, and IDS outcomes. Fisher's exact and student t-test were used for statistical significance.RESULTS:Twenty-one patients received DDP and 40 received standard taxane. Tolerability was comparable. More patients receiving DDP experienced grade 3 or 4 toxicity when considered in aggregate (86% vs. 40%; p=0.001). Pathologic complete response (pCR) was achieved in 14% of DDP patients versus 3% of standard (p=0.11). 48% of patients in the DDP group were debulked to no residual disease (NRD) versus 28% in the standard group (p=0.16).CONCLUSIONS:While associated with an increase in severe toxicity compared to standard three-week taxane, DDP appears to facilitate higher rates of pCR and NRD for patients receiving NACT in this preliminary study. These results warrant further investigation of DDP for patients with advanced EOC and assessment of impact on long-term survival outcomes.

Objectives: Initial treatment of endometrial cancer (EC) involves surgical resection including removal of pelvic and para-aortic lymph nodes. Attempts have been made to identify preoperative and intraoperative markers to determine which patients are at an increased risk of lymph node metastasis and thus need surgical staging. The goal of this study is to assess the reliability of intraoperative uterine evaluation compared with final pathologic measurements in patients with EC.Methods: After obtaining institutional review board approval, a prospective study was conducted of women who underwent surgery for biopsy-proven complex atypical hyperplasia (CAH) or EC between March 2015 and September 2015. Demographics, preoperative biopsy results, procedure, intraoperative and final pathologic evaluation of lesion size, myometrial invasion, and lower uterine segment/cervical involvement were abstracted. The level of agreement between intraoperative and final pathologic evaluation of tumor involvement of the uterus was determined using κ statistics and intraclass correlation coefficients (ICC).Results: Eighty-six patients with a preoperative diagnosis of CAH or EC were included—29 (33.7%) with CAH and 57 (66.3%) with EC. Mean age was 62 ± 10.5 years, and mean body mass index (BMI) was 38 ± 10.7. The majority of women were white (69%). Seventy (81.4%) patients underwent a laparoscopic or robotic hysterectomy, and 16 (18.6%) underwent an exploratory laparotomy. Seventy-one (82.6%) patients had EC and 15 (17.4%) patients had CAH on final pathology. There was a strong correlation between the intraoperative estimated size of the lesion and the final pathologic assessment (ICC 0.85, mean 3.8 cm, range 0–20 cm, P < .0001). However, there was fair correlation between intraoperative estimation of myometrial invasion and moderate correlation between lower uterine segment/cervical involvement compared with final pathologic evaluation (κ = 0.37 and 0.51, respectively).Conclusions: Estimated intraoperative evaluation of tumor size correlated strongly with final pathology whereas myometrial invasion and lower uterine segment/cervical involvement had moderate agreement at best. Therefore, intraoperative evaluation is inconsistent when determining the extent of disease and may not be an acceptable method for determining the need for surgical staging. Objectives: Initial treatment of endometrial cancer (EC) involves surgical resection including removal of pelvic and para-aortic lymph nodes. Attempts have been made to identify preoperative and intraoperative markers to determine which patients are at an increased risk of lymph node metastasis and thus need surgical staging. The goal of this study is to assess the reliability of intraoperative uterine evaluation compared with final pathologic measurements in patients with EC. Methods: After obtaining institutional review board approval, a prospective study was conducted of women who underwent surgery for biopsy-proven complex atypical hyperplasia (CAH) or EC between March 2015 and September 2015. Demographics, preoperative biopsy results, procedure, intraoperative and final pathologic evaluation of lesion size, myometrial invasion, and lower uterine segment/cervical involvement were abstracted. The level of agreement between intraoperative and final pathologic evaluation of tumor involvement of the uterus was determined using κ statistics and intraclass correlation coefficients (ICC). Results: Eighty-six patients with a preoperative diagnosis of CAH or EC were included—29 (33.7%) with CAH and 57 (66.3%) with EC. Mean age was 62 ± 10.5 years, and mean body mass index (BMI) was 38 ± 10.7. The majority of women were white (69%). Seventy (81.4%) patients underwent a laparoscopic or robotic hysterectomy, and 16 (18.6%) underwent an exploratory laparotomy. Seventy-one (82.6%) patients had EC and 15 (17.4%) patients had CAH on final pathology. There was a strong correlation between the intraoperative estimated size of the lesion and the final pathologic assessment (ICC 0.85, mean 3.8 cm, range 0–20 cm, P < .0001). However, there was fair correlation between intraoperative estimation of myometrial invasion and moderate correlation between lower uterine segment/cervical involvement compared with final pathologic evaluation (κ = 0.37 and 0.51, respectively). Conclusions: Estimated intraoperative evaluation of tumor size correlated strongly with final pathology whereas myometrial invasion and lower uterine segment/cervical involvement had moderate agreement at best. Therefore, intraoperative evaluation is inconsistent when determining the extent of disease and may not be an acceptable method for determining the need for surgical staging.

Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus “armed” with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin−12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin−12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8+ T cell response in the omentum and peritoneal cavity.

Objectives: Current literature suggests that disparities exist for patients with gynecologic malignancies. Race, socioeconomic status, and distance from a high-volume hospital are risk factors that have been identified as barriers to compliance with National Comprehensive Cancer Network (NCCN) treatment guidelines. We sought to evaluate the potential impact on clinical outcomes in cervical cancer patients based on distance from our NCCN cancer center.

Smith, Haller MD; Boone, Jonathan D. MD; Thomas, Eric D. MD; Brumfield, Cynthia G. MD, MSHA; Huh, Warner K. MD, FACS; Alvarez, Ronald D. MD, FACS; Leath, Charles A. III MD, MSPH, FACS; Straughn, John M. Jr. MD Author Information

Objectives: Objective measures have become an increasingly important tool used by organizations to improve health care delivery. Accurate documentation of diagnoses present on admission (POA) is another quality measure that accurately establishes acute and chronic illnesses that might affect prediction of mortality. We sought to determine whether standardized methods of documenting diagnoses POA can improve performance and accuracy of objective quality measures.

Objectives: Immunotherapy represents a promising therapeutic approach for ovarian cancer, and efforts are ongoing to optimize dendritic cell modification and various oncolytic viral vaccines for ovarian cancer immunotherapy. We evaluated the ability of camelid-derived single domain antibodies (sdAbs) to facilitate transfection of specific dendritic cell myeloid cell subsets and to enhance oncolytic specificity of conditionally replicative adenoviruses (CRAd).

Objectives: Readmissions are routinely reported by the University HealthSystem Consortium (UHC) to measure quality care at academic health centers. The objective of this study was to evaluate gynecologic oncology (GO) readmission rates and associated factors to identify potentially preventable readmissions.

Objectives: The updated American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines recommend 6-month follow-up with cytology and endocervical curettage (ECC) for women with positive margins after an excisional procedure for high-grade disease. We sought to evaluate the feasibility of recommended follow-up and clinicopathologic variables (CPV) for recurrence following loop electrosurgical excisional procedure (LEEP) with positive margins from a university-based, National Comprehensive Cancer Center (NCCN)-associated colposcopy clinic.

Objectives: Following primary chemotherapy, patients are categorized as either primary platinum-sensitive (PPS) or acquired platinum-resistant (APR). Eventually, PPS patients develop resistance to platinum therapies and can be characterized as APR. We sought to examine the natural history of APR as compared to primary platinum resistance (PPR).

Objectives: Primary platinum resistance (PPR) confers a poor prognosis for patients with epithelial ovarian carcinoma (EOC). Median overall survival (OS) is 12 months. Given the increased use of biologic agents, we sought to examine the characteristics and outcomes of patients with PPR EOC in the modern treatment era.

Objective. The aim of this study is to evaluate the effect of venous thromboembolism (VTE) chronology with respect to surgery on survival with epithelial ovarian cancer (EOC).Methods. An IRB approved, retrospective review was performed of patients treated for Stage I-IV EOC from 1996 to 2011. Cox proportional-hazards model was used to assess associations between VTE and the primary outcomes of progression free survival (PFS) and overall survival (OS). SAS 9.3 was used for statistical analyses.Results. 586 patients met study criteria. Median age was 63 years (range, 17-94); median BMI was 27.1 kg/m(2) (range, 13.7-67.0). Most tumors were high grade serous (68.3%) and advanced stage (III/IV, 75.4%). 3.7% had a preoperative VTE; 13.2% had a postoperative VTE. Upon multivariate analysis adjusting for age, stage, histology, performance status, and residual disease, preoperative VTE was predictive of OS (HR 3.1, 95% CI: 1.6-6.1, p = 0.001) but not PFS (p = 0.55). Postoperative VTE was associated with shorter PFS (HR 1.45, 95% CI: 1.04-2.02, p = 0.03) and OS (HR 1.8, 95% CI: 1.3-2.6, p = 0.001). When VTE timing was modeled, preoperative VTE (HR 3.5, 95% CI: 1.8-6.9, p < 0.001) and postoperative VTE after primary therapy (HR 2.3,95% CI: 1.4-3.6, p = 0.001) were predictive of OS.Conclusion. Preoperative and postoperative VTE appear to have a detrimental effect on OS with EOC. When modeled as a binary variable, postoperative VTE attenuated PFS; however, when VTE timing was modeled, postoperative VTE was not associated with PFS. It is unclear whether VTE is an inherent poor prognostic marker or if improved VTE prophylaxis and treatment may enable similar survival to patients without these events. (C) 2014 Elsevier Inc. All rights reserved.