Objective: The United States has a well-established opioid crisis. Evidence shows that abused opioids are obtained from friends or family members who initially received an opioids prescription. Gynecologic oncologists rely partially on opioids for the management of postoperative pain. This places us on the front line of this crisis. The objective of this quality improvement project is to implement a restrictive opioid prescription protocol for patients following gynecologic oncology surgery.

Objective: The aim of this study was to evaluate the exosome proteome to identify upregulated signaling pathways and potential candidates for biomarker and therapeutic targets in high-grade serous ovarian cancer (HGSOC).

Objective: The main objective of the study is to evaluate the unique signature of exosome-derived proteins as biomarkers for early detection of high-grade serous ovarian cancer (HGSOC).

Objective: TMEM205 is a novel transmembrane protein that may be associated with platinum resistance (PR) in high-grade serous ovarian cancer (HGSOC), but the specific mechanism associated with this resistance is still unknown. The goals of this study are to show that TMEM205 expression is linked with platinum-resistant HGSOC compared to platinum-sensitive and benign disease and to investigate the role of the TMEM205-CD1B (an exosome-related protein) axis in mediating this PR.

A 20 year old with recurrent low-grade serous carcinoma (LGSC) is discussed. The differential diagnosis, pathology, epidemiology, treatment options are discussed. Focus on the molecular pathways of LGSC and the implications of the diagnosis on fertility are highlighted.

Objective. Radical hysterectomy for cervical cancer is associated with increased morbidity over an extrafascial hysterectomy. The goal of this study was to determine incidence of and risk factors for parametrial involvement (PI) based on conization specimen (CS) and to potentially identify candidates for less radical surgery.Methods. Patients with FIGO IA2-IIA cervical cancer treated with radical hysterectomy and pelvic lymph node dissection (RH) from 2000 to 2010 were retrospectively identified. Data was extracted from operative and pathology reports. Statistical analyses were performed using Fisher's exact test, t-test, and asymptotic logistic regression.Results. Of 267 RH patients identified, 118 (44%) had conization prior to RH. The incidence of PI was 15.7% overall and 7.5% in patients treated with conization prior to RH. There was no association between PI and histology, stage, grade, or tumor size. Conization patients with PI were more likely to have LVSI on CS (77.8% vs. 29.4%) and positive lymph nodes (LNP) (66.7% vs. 83%). Of patients with positive endocervical curettage, a modest 12% had PI, which was not statistically significant. Tumor size, depth of invasion, and margin status on CS were not statistically associated with PI. In logistic regression analysis, LNP alone or LNP + LVSI were predictive of PI.Conclusions. The incidence of PI in early-stage cervical cancer is significant. Only LVSI on CS and LNP were predictors of PI in the current study. While there may be select patients with early stage cervical cancer who can be spared parametrectomy, additional research is warranted. (C) 2016 Elsevier Inc. All rights reserved.

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.

Background Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered. We sought to assess the functional consequences of this hotspot mutation and determine its association with cancer-relevant phenotypes. Methods MAX was sequenced in 509 endometrioid ECs, and associations between mutation status and clinicopathologic features were assessed. EC cell lines stably expressing MAXH28R were established and used for functional experiments. DNA binding was examined using electrophoretic mobility shift assays and chromatin immunoprecipitation. Transcriptional profiling was performed with microarrays. Murine flank (six to 11 mice per group) and intraperitoneal tumor models were used for in vivo studies. Vascularity of xenografts was assessed by MECA-32 immunohistochemistry. The paracrine pro-angiogenic nature of MAXH28R-expressing EC cells was tested using microfluidic HUVEC sprouting assays and VEGFA enzyme-linked immunosorbent assays. All statistical tests were two-sided. Results Twenty-two of 509 tumors harbored mutations in MAX, including 12 tumors with the p.His28Arg mutation. Patients with a MAX mutation had statistically significantly reduced recurrence-free survival (hazard ratio = 4.00, 95% confidence interval = 1.15 to 13.91, P = .03). MAXH28R increased affinity for canonical E-box sequences, and MAXH28R-expressing EC cells dramatically altered transcriptional profiles. MAXH28R-derived xenografts statistically significantly increased vascular area compared with MAXWT and empty vector tumors (P = .003 and P = .008, respectively). MAXH28R-expressing EC cells secreted nearly double the levels of VEGFA compared with MAXWT cells (P = .03, .005, and .005 at 24, 48, and 72 hours, respectively), and conditioned media from MAXH28R cells increased sprouting when applied to HUVECs. Conclusion These data highlight the importance of MAX mutations in EC and point to increased vascularity as one mechanism contributing to clinical aggressiveness of EC.

Objectives. To assess the cost-effectiveness of two commonly used strategies and an alternative triage strategy for patients with Stage IB cervical cancer in the US, Canada, and Korea. Methods. A Markov state-transition model was constructed to compare three strategies: (1) radical hysterectomy followed by tailored adjuvant therapy (primary surgery), (2) primacy chemoradiation, and (3) an MRI-based triage strategy, in which patients without risk factors in preoperative MRI undergo primary surgery and those with risk factors undergo primary chemoradiation. All relevant literature was identified to extract the probability data. Cost data were calculated from the perspective of US, Canadian, and Korean payers. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Cost-effectiveness ratios were analyzed separately using data from each country. Results. Base case analysis showed that the triage strategy was the most cost-effective of the three strategies in all countries at usual willingness-to-pay threshold (Korea: $30,000 per quality-adjusted life year (QALY), Canada and US: $100,000 per QALY). Monte Carlo simulation acceptability curves from Korea indicated that at a willingness-to-pay threshold of $30,000/QALY, triage strategy was the treatment of choice in 71% of simulations. Monte Carlo simulation acceptability curves from US and Canada indicated that at a willingness-to-pay threshold of $100,000/QALY, triage strategy was the treatment of choice in more than half of simulations. Conclusions. An MRT-based triage strategy was shown to be more cost-effective than primary surgery or primary chemoradiation in the US, Canada, and Korea.(c) 2015 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: 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.

Robotic surgery for endometrial cancer has less blood loss, shorter hospital stays, and less postoperative complications compared to laparotomies. Robotic technologic advantages over laparoscopic technique are most pronounced in obese patients. The shorter learning curve may explain the greater utilization of the robotic technique. Robotic surgery will continue as a mainstay in the treatment of uterine cancers as we become more efficient and cost conscious while maintaining the high quality outcomes that have been reported.

Sentinel lymph node assessment aims to determine lymphatic spread while preventing unnecessary interventions and morbidity for those who will not benefit from lymphadenectomy. All detection methods have demonstrated reasonable sensitivity with a low false negative rate and high negative predictive value; as long as the surgeon removes all enlarged lymph nodes and a site-specific lymphadenectomy is performed if there is no mapping. The significance of micrometastases and long term outcomes are yet to be determined.

Objective: The optimal role of bevacizumab (Bev) in the treatment of ovarian cancer has not yet been established. Furthermore, it is unclear whether there is a benefit of Bev after progression on a Bev-containing regimen in ovarian cancer. The objective of this study was to compare response rates, progression-free survival (PFS), and overall survival between patients who were treated with chemotherapy and Bev after progression on Bev (BAB) versus patients who were treated with chemotherapy without Bev (CWOB).Methods: We conducted a retrospective chart review of all patients who received treatment with Bev (with or without cytotoxic chemotherapy) for recurrent ovarian cancer at a single institution. Patients who received additional therapy after progression while on Bev were included.Results: Forty-six patients were included (16 CWOB group and 30 BAB). The median number of previous chemotherapy regimens was 2.5 for CWOB compared with 4 for BAB (P = 0.11). Fifty-two percent of patients had an objective response to the first Bev regimen before progressing on Bev. Response rates for the regimen after progression on Bev were 19% (3/16) in the CWOB group and 23% (7/30) in the BAB group (P = 1). Twenty-five percent of the patients who responded to the first Bev regimen and 18% of those who did not respond to the first Bev regimen responded to the second Bev regimen (P = 0.72). The median PFS for patients in the CWOB group was 2.6 months (95% confidence interval [CI], 1.3-5 months), compared with 5.0 months (95% CI, 3.5-7.3 months) for patients in the BAB group (P = 0.01). Overall survival was similar, 9.4 months (95% CI, 5.0-12.0 months) for CWOB versus 8.6 months (95% CI, 5.8-15.5 months) for BAB (P = 0.19). One patient in the BAB group died of a bowel perforation.Conclusions: In patients previously treated with Bev for recurrent ovarian cancer, the subsequent addition of Bev to cytotoxic chemotherapy increased the PFS compared with patients not receiving a second course of Bev, but did so without an impact on overall survival. The response to the first Bev regimen did not predict whether a patient would respond again to the next Bev regimen. Randomized, larger studies will have to be performed to confirm this observation.