Fertility sparing treatment of vaginal clear cell adenocarcinoma in a DES-Naïve young woman.

Background: Primary vaginal cancer is rare and comprises 1-2% of female genital tract cancers. Among the types of vaginal cancer, adenocarcinoma accounts for only 10% with the peak incidence in women less than 20 years old. Clear cell type vaginal adenocarcinoma is most associated with exposure to diethylstilbestrol (DES) in-utero. Case: We present a case of an 18-year-old nulliparous woman, DES-exposure naive, who was diagnosed with stage I clear cell vaginal adenocarcinoma during a routine pelvic exam for abnormal vaginal bleeding. She underwent a fertility-preserving radical vaginectomy and pelvic lymphadenectomy with neovagina creation and uterovaginal cervical reconstruction. She has been without disease for 28 months. Conclusion: Although rare, vaginal cancer can be diagnosed on routine women's health exams. Early screening and diagnosis allow for innovative fertility-preserving surgical approaches without compromising oncologic outcomes. To our knowledge, this is the first case of a fertility-preserving radical vaginectomy, neovagina creation using a vertical rectus abdominis myocutaneous (VRAM) flap, and uterocervicovaginal reconstruction to successfully treat early stage clear cell vaginal adenocarcinoma with surgery alone, sparing the patient from adjuvant chemotherapy or radiation.

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006).

PURPOSE: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer. METHODS: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light. RESULTS: From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor-positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported. CONCLUSION: This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

Rapid progression of cervical squamous cell carcinoma with delayed treatment in pregnancy.

•Delayed treatment of cervical cancer in pregnancy can result in progression.•Surveillance of cervical cancer in pregnancy with pelvic MRIs every 6 weeks.•Comprehensive multidisciplinary care is essential in setting of treatment delays.

Clinical outcomes of patients with endometrioid epithelial ovarian cancer following surgical treatment.

BACKGROUND: Endometrioid epithelial ovarian cancer (EEOC) is rare, and its management poorly defined. We examined factors associated with 5-year progression-free survival (PFS) after surgery for EEOC. METHODS: Retrospective study: treatment and outcomes of all EEOC patients undergoing initial surgery at, or presenting to, our institution within 3 months of initial surgery, 1/2002-9/2017. RESULTS: In total, 212 patients were identified. Median follow-up, 63.9 months (range, 0.7-192); median age at diagnosis, 52 years (range, 20-88); disease stage: I, n = 145 (68%); II, n = 47 (22%); III/IV, n = 20 (9%); FIGO grade: 1, 127 (60%); 2, 66 (31%); 3, 17 (8%); unknown, 2 (1%). One hundred twenty-eight (60%) had endometriosis; 75 (35%), synchronous endometrioid endometrial cancer (80%, IA); 101 (48%), complete surgical staging; 8 (5%), positive pelvic lymph nodes (LNs); 6 (4%), positive para-aortic LNs; 176 (97%), complete gross resection; 123 (60%), postoperative chemotherapy; 56(28%), no additional treatment. Five-year PFS, 83% (95% confidence interval [CI]: 76.6%-87.8%); 5-year overall survival (OS), 92.7% (95% CI: 87.7%-95.8%). Age, stage, and surgical staging were associated with improved 5-year PFS, and younger age at diagnosis with improved 5-year OS (p < 0.001). Chemotherapy did not improve 5-year PFS in IA/IB versus observation, but improved survival in IC (hazard ratio [HR]: 1.01, 95% CI: 0.22-4.59, p = 0.99; HR: 0.17, 95% CI: 0.04-0.7, p = 0.006). CONCLUSIONS: Age, stage, and full surgical staging were associated with improved 5-year PFS. Chemotherapy showed no benefit in IA/IB disease.

A 61-year-old woman with jejunal lymphatic malformation visualized on computed tomography: a case report.

BACKGROUND: Jejunal lymphatic malformations are congenital lesions that are seldom diagnosed in adults and rarely seen on imaging. CASE PRESENTATION: A 61-year-old Caucasian woman was initially diagnosed and treated for mucinous ovarian carcinoma. After an exploratory laparotomy with left salpingo-oophorectomy, a computed tomography scan of the abdomen and pelvis demonstrated suspicious fluid-containing lesions involving a segment of jejunum and adjacent mesentery. Resection of the lesion during subsequent debulking surgery revealed that the lesion seen on imaging was a jejunal lymphatic malformation and not a cancerous implant. CONCLUSIONS: Abdominal lymphatic malformations are difficult to diagnose solely on imaging but should remain on the differential in adult cancer patients with persistent cystic abdominal lesions despite chemotherapy and must be differentiated from metastatic implants.

Vaginal metastasis of gestational trophoblastic neoplasia resulting in hemorrhage: A case report.

Complete molar pregnancies complicate approximately 1 in 1500 pregnancies in the United States and result in gestational trophoblastic neoplasia in about 15-20% of these cases. Vaginal metastasis is the second most common site of metastasis and may present with vaginal bleeding and hemorrhage. This report describes a case of a 19-year-old Hispanic primigravida who presented with hemorrhage from an anterior vaginal wall metastasis two weeks after dilation and curettage for complete molar pregnancy. Hemorrhage resolved after extrusion of the lesion from the anterior vaginal wall. Pathology showed markedly atypical trophoblastic tissue from the lesion. Vaginal involvement of gestational trophoblastic neoplasia can present with life-threatening hemorrhage.

Robotic Surgery in the Frail Elderly: Analysis of Perioperative Outcomes.

PURPOSE: The frail are considered at higher risk for unfavorable surgical outcomes (major complications/mortality). We assessed the safety of and outcomes associated with robotic surgery in the frail elderly undergoing gynecologic procedures. METHODS: We identified patients aged ≥ 65 years who underwent a robotic procedure between May 2007 and December 2016. Frailty was defined as the presence of at least three of five frailty factors-more than five comorbidities, low physical activity, weight loss, exhaustion, and fatigue. Perioperative outcomes were recorded. We compared variables among frail and non-frail patients and performed a multivariate logistic regression to detect variables associated with major complications (≥ grade 3) or 90-day mortality. RESULTS: We identified 982 patients: 71 frail and 911 non-frail patients. Median age was 71 years. Median BMI was 29.8 kg/m2. Thirty-four patients (3.5%) had a 30-day readmission. Seventy-seven (7.8%) had a postoperative complication, of which 23 (2.3%) were major. Ninety-day mortality was 0.5%. There were significant differences with regard to age (P < 0.001), body mass index (BMI) (P < 0.001) and performance status (P < 0.001); the frail were more likely to have had surgery for oncologic reasons (P = 0.047). There were differences in hospital stay (P < 0.001), postoperative (P = 0.042) and major complications (P = 0.007), and 90-day mortality (P = 0.05). At multivariable logistic regression, age ≥ 85 was associated with major complications. BMI, performance status, and major complications were associated with 90-day mortality. CONCLUSIONS: The frail elderly have longer hospital stays and more complications after surgery than the general population, consistent with the reported literature. Careful selection of surgical candidates is required.

Molecular profiling and molecular classification of endometrioid ovarian carcinomas.

OBJECTIVE: Endometrioid ovarian carcinomas (EOCs) comprise 5-10% of all ovarian cancers and commonly co-occur with synchronous endometrioid endometrial cancer (EEC). We sought to examine the molecular characteristics of pure EOCs in patients without concomitant EEC. METHODS: EOCs and matched normal samples were subjected to massively parallel sequencing targeting 341-468 cancer-related genes (n = 8) or whole-genome sequencing (n = 28). Mutational frequencies of EOCs were compared to those of high-grade serous ovarian cancers (HGSOCs; n = 224) and EECs (n = 186) from The Cancer Genome Atlas, and synchronous EOCs (n = 23). RESULTS: EOCs were heterogeneous, frequently harboring KRAS, PIK3CA, PTEN, CTNNB1, ARID1A and TP53 mutations. EOCs were distinct from HGSOCs at the mutational level, less frequently harboring TP53 but more frequently displaying KRAS, PIK3CA, PIK3R1, PTEN and CTNNB1 mutations. Compared to synchronous EOCs and pure EECs, pure EOCs less frequently harbored PTEN, PIK3R1 and ARID1A mutations. Akin to EECs, EOCs could be stratified into the four molecular subtypes: 3% POLE (ultramutated), 19% MSI (hypermutated), 17% copy-number high (serous-like) and 61% copy-number low (endometrioid). In addition to microsatellite instability, a subset of EOCs harbored potentially targetable mutations, including AKT1 and ERBB2 hotspot mutations. EOCs of MSI (hypermutated) subtype uniformly displayed a good outcome. CONCLUSIONS: EOCs are heterogeneous at the genomic level and harbor targetable genetic alterations. Despite the similarities in the repertoire of somatic mutations between pure EOCs, synchronous EOCs and EECs, the frequencies of mutations affecting known driver genes differ. Further studies are required to define the impact of the molecular subtypes on the outcome and treatment of EOC patients.

Is Robotic-Assisted Surgery Safe in the Elderly Population? An Analysis of Gynecologic Procedures in Patients ≥ 65 Years Old.

BACKGROUND: The elderly population is expanding worldwide but is underrepresented in clinical trials. We sought to assess the safety of robotic gynecologic surgery in an elderly cohort and to identify factors associated with unfavorable outcomes. METHODS: All patients ≥ 65 years who underwent a robotically assisted procedure at a single institution between May 2007 to December 2016 were divided into three age groups: 65-74 (Group 1); 75-84 (Group 2); ≥ 85 (Group 3). Perioperative outcomes were recorded in patients who did not require conversion to laparotomy. We compared clinical variables among groups and performed multivariate logistic regression to detect variables associated with major complications (≥ Grade 3) or 90-day mortality. RESULTS: We retrospectively identified 982 cases: 685 in Group 1; 249 in Group 2; 48 in Group 3. Median age = 71 years. Median BMI = 28.9. Malignancy was documented in 72.8% of cases; the majority were endometrial cancer (61.8%). Thirty-four patients (3.5%) were readmitted within 30 days. Seventy-seven (7.8%) had a postoperative complication, and 23 (2.3%) had a major complication. Ninety-day mortality was 0.5%. There was significant difference between groups with respect to body mass index (P = 0.026), ECOG PS (P ≤ 0.001), > 5 comorbidities (P = 0.005), hospital stay (P < 0.001), major complications (P = 0.001), and 90-day mortality (P < 0.001). On multivariable logistic regression, age ≥ 85 years was associated with major complications. Body mass index, age ≥ 85 years, and major complications were significantly associated with 90-day mortality. CONCLUSIONS: Robotic-assisted surgery appears to be safe in an elderly cohort. The incidence of overall and major complications is consistent with those reported in the literature. Patients ≥ 85 years old appear to be at higher risk of unfavorable outcomes.

Patterns of FIRST recurrence of stage IIIC1 endometrial cancer with no PARAAORTIC nodal assessment.

OBJECTIVE: To assess the rates and distribution of first recurrence in patients with FIGO stage IIIC1 endometrial cancer (EC) who did not undergo paraaortic dissection at surgical staging. METHODS: We retrospectively selected all (n = 207) stage IIIC1 patients treated at a single institution from 5/1993-1/2017. Sites of first recurrence were identified, disease-free (DFS) and overall survival (OS) calculated, multivariate logistic regression performed to identify factors associated with recurrence. RESULTS: Three-year DFS and OS were 66.5% and 85.7%, respectively. The most common histology was endometroid (64.2%). Three-year DFS was 81% (SE±3.8%) endometrioid vs. 39.5% (SE±6.6%) non-endometrioid (P < 0.001). Three-year OS was 96.9% (SE±1.8%) endometrioid vs. 65.6% (SE±6.7%) non-endometrioid (P < 0.001). Sixty-two (30.1%) patients recurred. Patterns of recurrence were: 14 (8.3%) multiple sites, 17 (8.2%) abdominal, 14 (6.8%) extra-abdominal, 17 (8.3%) isolated nodal (8 of these (3.9%) paraaortic). Patients with isolated tumor cells (ITCs) in lymph nodes only had 12/71 (17%) recurrence rate vs. 50/135 (37%) for patients with micro-/macrometastasis. On univariate analysis, grade (HR 4.67 95%CI 1.5-14.5, P = 0.008), histology (HR 4.9 95%CI 2.6-9.3, P < 0.001), myometrial invasion (HR 1.9 95%CI 1.04-3.5, P = 0.04), pelvic washing (HR 2.2 95%CI 1.1-4.5, P = 0.03), tumor volume in pelvic LNs (ITC vs. micro-/macrometastasis; HR 0.3 95%CI 0.2-0.7, P = 0.003) were associated with recurrence. On multivariate analysis, only histology was associated with recurrence (HR 7.88 95%CI 3.43-18.13, P < 0.001). CONCLUSIONS: Isolated paraaortic recurrence in stage IIIC1 EC is uncommon. Micro-/macrometastasis were associated with twice the recurrence rate compared to ITC. These data will help clinicians counsel patients with stage IIIC1 EC regarding paraaortic assessment.

Perioperative epidural use and survival outcomes in patients undergoing primary debulking surgery for advanced ovarian cancer.

OBJECTIVE: Epidurals are associated with improved outcomes in some solid tumors, presumably due to their effect on surgical stress response. There are limited data on the prognostic significance of epidural anesthesia in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer. We sought to assess the impact of epidural anesthesia on the survival outcomes of patients undergoing PDS for advanced ovarian cancer. METHODS: In this retrospective study, consecutive patients with stage IIIB-IV epithelial ovarian, fallopian tube, or peritoneal carcinoma who underwent PDS at our institution from 01/2005-12/2013 were identified. Progression-free survival (PFS) and overall survival (OS) with regard to epidural use were analyzed. RESULTS: Of 648 patients, 435 received an epidural and 213 did not. Patients in the former group were more likely to have higher stage disease (stage IV disease, 26% vs. 16%, respectively; P = .005), carcinomatosis (87% vs. 80%, respectively; P = .027), and bulky upper abdominal disease (66% vs. 58%, respectively; P = .046). Complete gross resection was achieved in 48% and 32%, respectively (P < .001). For the epidural vs. non-epidural groups, median PFS was 20.8 months and 13.9 months, respectively (P = .021); median OS was 62.4 months and 41.9 months, respectively (P < .001). After controlling for confounding factors, including residual disease, epidural use was independently associated with a decreased risk of progression (HR = 1.327; 95% CI, 1.066-1.653) and death (HR = 1.588; 95% CI, 1.224-2.06). CONCLUSIONS: Perioperative epidural use was independently associated with improved PFS and OS in these patients. Epidural anesthesia at the time of PDS may be warranted in this setting.

Continuous improvement in primary Debulking surgery for advanced ovarian cancer: Do increased complete gross resection rates independently lead to increased progression-free and overall survival?

OBJECTIVES: To assess complete gross resection (CGR) rates and survival outcomes in patients with advanced ovarian cancer who underwent primary debulking surgery (PDS) during a 13-year period in which specific changes to surgical paradigm were implemented. METHODS: We identified all patients with stage IIIB-IV high-grade ovarian carcinoma who underwent PDS at our institution, with the intent of maximal cytoreduction, from 1/2001-12/2013. Patients were categorized by year of PDS based on the implementation of surgical changes to our approach to ovarian cancer debulking (Group 1, 2001-2005; Group 2, 2006-2009; Group 3, 2010-2013). RESULTS: Among 978 patients, 78% had stage IIIC disease and 89% had disease of serous histology. Carcinomatosis was found in 81%, and 60% had bulky upper abdominal disease (UAD). Compared to Group 1, those who underwent PDS during the latter 2 time periods had higher ASA scores (p < 0.001), higher-stage disease (p < 0.001), and more often had carcinomatosis (p = 0.015) and bulky UAD (p = 0.009). CGR rates for Groups 1-3 increased from 29% to 40% to 55%, respectively (p < 0.001). Five-year progression-free survival (PFS) rates increased over time (15%, 16%, and 20%, respectively; p = 0.199), as did 5-year overall survival (OS) rates (40%, 44%, and 56%, respectively; p < 0.001). On multivariable analysis, CGR was independently associated with PFS (p < 0.001) and OS (p < 0.001). CONCLUSIONS: Despite higher-stage disease and greater tumor burden, CGR rates, PFS and OS for patients who underwent PDS increased over a 13-year period. Surgical paradigm shifts implemented specifically to achieve more complete surgical cytoreduction are likely the reason for these improvements.

Long-Term Oncologic Outcomes of Uterine-Preserving Surgery in Young Women With Stage Ib1 Cervical Cancer.

OBJECTIVE: This study aimed to evaluate oncologic outcomes of women with stage IB1 cervical cancer treated with uterine-preserving surgery (UPS) (defined as conization or trachelectomy) versus non-UPS (defined as hysterectomy of any type). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women younger than 45 years diagnosed with stage IB1 cervical cancer from 1998 to 2012. Only those who underwent lymph node (LN) assessment were included. Outcomes of UPS versus non-UPS were analyzed. RESULTS: Among 2717 patients, 125 were treated with UPS and 2592 were treated with non-UPS. Those in the UPS group were younger (median age 33 vs 37 years, P < 0.001), less commonly had tumor size greater than 2 cm (27% vs 45%, P < 0.001), and less commonly received adjuvant radiation therapy (18% vs 29%, P = 0.006). There was no difference in distribution of tumor grade, histology, or rate of LN positivity. Median follow-up was 79 months (range, 0-179). There was no difference in 5-year disease-specific survival (DSS) between the UPS versus non-UPS groups (93% vs 94%, respectively, P = 0.755). When stratified by tumor size, DSS for UPS versus non-UPS was as follows: tumors 2 cm or less, 96.8% versus 96.3% (P = 0.683); tumors greater than 2 cm, 82.4% versus 90.4% (P = 0.112). Factors independently associated with worsened survival included adenosquamous histology (hazard ratio [HR] 2.29, 95% confidence interval [CI]1.51-3.47), G3 disease (HR 2.44, 95% CI 1.01-5.89), tumor size greater than 2 cm (HR 1.93, 95% CI 1.36-2.75) and LN positivity (HR 2.29, 95% CI 1.64-3.22). The UPS was not associated with a higher risk of death. CONCLUSIONS: The UPS does not seem to compromise oncologic outcomes in a select group of young women with stage IB1 cervical cancer, especially in the setting of tumors 2 cm or less. Further studies are needed to clarify the role of UPS in tumors greater than 2 cm.

Less versus more radical surgery in stage IB1 cervical cancer: A population-based study of long-term survival.

BACKGROUND: Standard surgical treatment for women with stage IB1 cervical cancer consists of radical hysterectomy. This study assesses survival outcomes of those treated with less radical surgery (LRS; conization, trachelectomy, simple hysterectomy) compared to more radical surgery (MRS; modified radical, radical hysterectomy). METHODS: Using the Surveillance, Epidemiology and End Results database, we identified women <45 years with FIGO stage IB1 cervical cancer diagnosed from 1/1998 to 12/2012. Only those who underwent lymph node (LN) assessment were analyzed. Disease-specific survivals (DSSs) of LRS were compared with those of MRS. RESULTS: Of 2571 patients, 807 underwent LRS and 1764 underwent MRS, all with LN assessment. For LRS vs. MRS, 28% vs. 23% were diagnosed with adenocarcinoma (p = 0.024), 31% vs. 39% had G3 disease (p < 0.001), 40% vs. 45% had tumor size >2 cm (p < 0.001), and 27% vs. 29% received adjuvant radiation therapy (p = 0.005). Median follow-up was 79 months (range, 0-179). Ten-year DSS for LRS vs. MRS was 93.5% vs. 92.3% (p = 0.511). There was no difference in 10-year DSS when stratified by tumor size ≤2 cm (LRS 95.1% vs. MRS 95.6%, p = 0.80) or > 2 cm (LRS 90.1% vs. MRS 88.2%, p = 0.48). Factors independently associated with increased risk of death included adenosquamous histology (HR 2.37), G3 disease (HR 2.86), tumors >2 cm (HR 1.82), and LN positivity (HR 2.42). Compared to MRS, LRS was not associated with a higher risk of death. CONCLUSIONS: In a select group of young women with stage IB1 cervical cancer, LRS compared to MRS does not appear to compromise DSS.

Exploring the impact of income and race on survival for women with advanced ovarian cancer undergoing primary debulking surgery at a high-volume center.

OBJECTIVE: To evaluate patients with advanced ovarian cancer (OC) undergoing primary debulking surgery (PDS) at a high-volume center (HVC), to determine whether socio-demographic disparities in PDS outcome and overall survival (OS) were present. METHODS: All patients with stages IIIB-IV high-grade OC undergoing PDS at our institution from 1/2001-12/2013 were identified. Patients self-identified race/ethnicity as non-Hispanic White (NHW), non-Hispanic Black (NHB), Asian (A), or Hispanic (H). Income level for the entire cohort was estimated using the census-reported income level for each patient's zip code as a proxy for SES. Main outcome measures were PDS outcome and median OS. Cox proportional hazards model was used to examine differences in OS by racial/ethnic and income category, controlling for selected clinical factors. RESULTS: 963 patients were identified for analysis: 855 NHW; 43 A, 34H, 28 NHB, and 3 unknown. PDS outcome was not significantly different among NHB and H as compared to NHW. Compared to NHW, Asians were more likely to have >1cm residual (AOR 2.32, 95%CI 1.1-4.9, p=0.03). Median income for the entire cohort was $85,814 (range $10,926-$231,667). After adjusting for significant prognostic factors, there were no significant differences in PDS outcome between income groups (p=0.7281). Median OS was 55.1mos (95%CI 51.8-58.5) with no significant differences in OS between the income (p=0.628) or racial/ethnic (p=0.615) groups. CONCLUSION: Statistically significant socio-demographic disparities in PDS and survival outcomes were not observed among women with advanced OC treated at this HVC. Increased efforts are needed to centralize care to and increase the diversity of pts treated at HVCs.

Feasibility, safety and clinical outcomes of cardiophrenic lymph node resection in advanced ovarian cancer.

OBJECTIVES: Surgical resection of enlarged cardiophrenic lymph nodes (CPLNs) in primary treatment of advanced ovarian cancer has not been widely studied. We report on a cohort of patients undergoing CPLN resection during primary cytoreductive surgery (CRS), examining its feasibility, safety, and potential impact on clinical outcomes. METHODS: We identified all patients undergoing primary CRS/CPLN resection for Stages IIIB-IV high-grade epithelial ovarian cancer at our institution from 1/2001-12/2013. Clinical and pathological data were collected. Statistical tests were performed. RESULTS: 54 patients underwent CPLN resection. All had enlarged CPLNs on preoperative imaging. Median diameter of an enlarged CPLN: 1.3cm (range 0.6-2.9). Median patient age: 59y (range 41-74). 48 (88.9%) underwent transdiaphragmatic resection; 6 (11.1%) underwent video-assisted thoracic surgery. A median of 3 nodes (range 1-23) were resected. A median of 2 nodes (range 0-22) were positive for metastasis. 51/54 (94.4%) had positive nodes. 51 (94.4%) had chest tube placement; median time to removal: 4d (range 2-12). 44 (81.4%) had peritoneal carcinomatosis. 19 (35%) experienced major postoperative complications; 4 of these (7%) were surgery-related. Median time to adjuvant chemotherapy: 40d (range 19-205). All patients were optimally cytoreduced, 30 (55.6%) without visible residual disease. Median progression-free survival: 17.2mos (95% CI 12.6-21.8); median overall survival: 70.1mos (95% CI 51.2-89.0). CONCLUSIONS: Enlarged CPLNs can be identified on preoperative imaging and may indicate metastases. Resection can identify extra-abdominal disease, confirm Stage IV disease, obtain optimal cytoreduction. In the proper setting it is feasible, safe, and does not delay chemotherapy. In select patients, it may improve survival.

Compliance with research standards within gynecologic oncology fellowship: A Gynecologic Oncology Fellowship Research Network (GOFRN) study.

OBJECTIVES: Participation in clinical and basic science research is emphasized in gynecologic oncology training. We sought to identify trends in adherence to expected research practices and reasons for non-adherence among gynecologic oncology fellows. METHODS: An anonymous 31-question online survey assessing academic behaviors, including IRB compliance, authorship assignment, data sharing, and potential barriers to non-adherence was distributed to all SGO gynecologic oncology fellow members in July 2016. Descriptive statistics and univariate analyses were performed. RESULTS: Of 190 members, 35.3% (n=67) responded. 73% (n=49) of respondents reported personal non-compliance and 79.1% (n=53) reported having witnessed others being non-complaint with at least one expected research practice. Areas of compliance failure included changing a research question without appropriate IRB amendment (20%; n=14), conducting research under a nonspecific IRB (13.9%; n=9), and performing research without IRB approval (6.1%; n=4). Longer institutional time for IRB approval was significantly associated with IRB non-adherence (p<0.05). First year fellows were more likely to use a nonspecific IRB (p=0.04) or expand a question without amending the IRB (p=0.04). When asked about storage of protected health information (PHI) for research, 53% reported non-secure storage with 17.1% (n=6) having done so for >1000 patients. Thirty respondents (45.5%) assigned authorship to someone who failed to meet ICMJE criteria and twelve (18.5%) accepted authorship without meeting ICMJE criteria. Most commonly cited reasons for non-adherence were: cumbersome IRB processes (80.3%), pressure from senior authors (78.8%), fear of someone else publishing first, (74.2%) and lack of support navigating appropriate research practices (71.2%). CONCLUSIONS: Fellow non-compliance with expected research practices is high, particularly with regards to secure storage of PHI and appropriate authorship assignment. Time-consuming and cumbersome IRB procedures, perceived pressure from senior authors, and lack of research support contribute to non-adherence. Further support and education of gynecologic oncology fellows is needed in order to help address these barriers.

miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas.

Uterine carcinosarcomas (UCSs) are highly aggressive malignancies associated with poor prognoses and limited treatment options. These tumors are hypothesized to develop from the endometrial adenocarcinoma (EAC) through epithelial-mesenchymal transition (EMT). We test this long-standing hypothesis by depleting miR-200, a family of microRNAs critical for EMT, in EAC cell lines. Our data suggest that UCSs do not develop from EACs via EMT. Clinically more relevant, we show that miR-200 expression in UCS cells induces a robust mesenchymal-epithelial transition (MET). Using in vitro and murine xenograft models, we demonstrate decreased growth and aggressiveness of miR-200-overexpressing UCS cell lines. Whole transcriptome analysis confirmed changes consistent with an MET and also revealed changes in angiogenic genes expression. Finally, by treatment of UCS-xenografted mice with miR-200c incorporated in DOPC nanoliposomes, we demonstrate anti-tumor activities. These findings suggest that ectopic miR-200 expression using advanced microRNA therapeutics may be a potential treatment approach for patients with UCS.

The EMSY threonine 207 phospho-site is required for EMSYdriven suppression of DNA damage repair.

BRCA1 and BRCA2 are essential for the repair of double-strand DNA breaks, and alterations in these genes are a hallmark of breast and ovarian carcinomas. Other functionally related genes may also play important roles in carcinogenesis. Amplification of EMSY, a putative BRCAness gene, has been suggested to impair DNA damage repair by suppressing BRCA2 function. We employed direct repeat GFP (DR-GFP) and RAD51 foci formation assays to show that EMSY overexpression impairs the repair of damaged DNA, suggesting that EMSY belongs to the family of BRCAness proteins. We also identified a novel phospho-site at threonine 207 (T207) and demonstrated its role in EMSY-driven suppression of DNA damage repair. In vitro kinase assays established that protein kinase A (PKA) directly phosphorylates the T207 phospho-site. Immunoprecipitation experiments suggest that EMSY-driven suppression of DNA damage repair is a BRCA2-independent process. The data also suggest that EMSY amplification is a BRCAness feature, and may help to expand the population of patients who could benefit from targeted therapies that are also effective in BRCA1/2-mutant cancers.