Longer operative time is associated with increased post-operative complications in patients undergoing minimally-invasive surgery for endometrial cancer.

OBJECTIVE: To examine the impact of operative time on the development of post-operative medical and surgical complications in patients undergoing minimally-invasive surgery for endometrial cancer. METHODS: Patients who underwent laparoscopic surgery for endometrial cancer from 2005 to 2014 were identified from the ACS-NSQIP database. Operative times were initially divided into hour-long intervals and complication rates were determined. Outcomes included development of any complication, medical complication, or surgical complication. Subsequent analysis were based on dividing patients into 2 groups based on operative times <240min and operative times ≥240min. Associations between categorical variables were determined using Chi-Squared and Fisher's exact tests. Differences between means of continuous variables were determined using Student's t-tests. Univariate and multivariate analysis using logistic regression were used to identify predictors of post-operative complications. RESULTS: 9145 patients were included, of which 639 (7%) experienced a complication. As operative time increased, rates of complications also increased. Operative time ≥240min was associated with increased overall complication rate (11.7% vs. 6%, p<0.001), medical complication rate (9.3% vs. 4.2%, p<0.001), and surgical complication rate (3.9% vs. 2.4%, p=0.001). When performing multi-variate logistic regression of factors associated with increased complication rates, increased operative time, COPD, hypertension, diabetes, ASA class ≥3, dependent functional status, and chronic steroid use were found to be independently associated with increased complications. Lymphadenectomy was not associated with increased operative time or increase in complications. CONCLUSION: Increased operative time is independently associated with increased risk of developing complications after laparoscopic surgery for endometrial cancer.

Lynch Syndrome and Endometrial Cancer.

In patients with Lynch syndrome, gynecologic cancer often can be the first presenting malignancy. In this review, we summarize the genetics of Lynch syndrome and review the various modalities of identifying patients at risk for this syndrome. The clinical characteristics of Lynch-associated endometrial cancer and screening and risk-reducing strategies also are described.

Preoperative predictors of delay in initiation of adjuvant chemotherapy in patients undergoing primary debulking surgery for ovarian cancer.

OBJECTIVE: The objective of this study was to identify preoperative characteristics of patients that experience a delay in initiation of adjuvant chemotherapy after primary debulking surgery for ovarian cancer. MATERIALS/METHODS: We performed a retrospective review of patients with Stage II to IV high-grade epithelial ovarian, tubal, and peritoneal carcinoma who underwent primary debulking surgery followed by adjuvant chemotherapy from 2005 to 2013. Patients were divided into 2 groups: Control (those who received their first cycle of chemotherapy within 6weeks of debulking surgery) vs. chemotherapy delay (those who received their first cycle of chemotherapy at an interval >6weeks from primary debulking surgery). Relevant clinical variables and survival outcomes were compared between the 2 groups using standard statistical methods. RESULTS: A total of 221 patients were included in the analyses - 169 (76.5%) were in the control group and 52 (23.5%) were in the chemo delay group. On multi-variate analysis, risk factors that were significantly associated with a delay in initiation in chemotherapy included: age >65, albumin <3.5, and high age-adjusted Charlson Comorbidity Index score. Delay in chemotherapy initiation was associated with a shorter progression-free (p=0.014) but not overall survival (p=0.19). CONCLUSIONS: Delay in initiation of chemotherapy affected 23.5% of patients in our study population. Easily identifiable risk factors for chemotherapy delay exist that can help us pre-operatively identify patients for which neoadjuvant chemotherapy may be a better treatment option. Further study into prospective modeling with these identified risk factors is warranted.

Patterns of First Recurrence in African American Patients with High Grade Epithelial Ovarian Carcinoma.

BACKGROUND/AIMS: The aim of this study is to compare the distribution of anatomic sites of first recurrence in African American (AA) patients with ovarian carcinoma compared to Caucasians. METHODS: Patients diagnosed with high-grade epithelial ovarian, fallopian tube or peritoneal carcinoma from 2007 to 2013 were identified. Patterns of recurrence were compared for AA and Caucasian patients. Progression-free survival (PFS) and overall survival (OS) were compared. RESULTS: A total of 238 patients were included - 210 Caucasians and 28 AAs. At a follow-up time of 28 months, AAs were more likely to have multiple anatomic sites of recurrence rather than a single site when compared to Caucasians (63.6 vs. 35.5%, p = 0.01). Time to first recurrence was shorter for AA patients (12 vs. 18 months, p < 0.01). PFS and OS did not differ. AA patients with multiple sites of first recurrence had a significantly shorter OS than Caucasian patients with multiple sites of first recurrence (24 vs. 30 months, p = 0.022). CONCLUSION: Patterns of first recurrence differ between AAs and Caucasians. AAs have shorter times to first recurrence and are more likely to have multiple anatomic sites involved. AA patients with multiple sites of recurrence have a shorter OS than Caucasian patients with multiple sites.

Impact of adjuvant chemotherapy and pelvic radiation on pattern of recurrence and outcome in stage I non-invasive uterine papillary serous carcinoma. A multi-institution study.

OBJECTIVES: To determine the impact of adjuvant chemotherapy or pelvic radiation on risk of recurrence and outcome in stage IA non-invasive uterine papillary serous carcinoma (UPSC). METHODS: This is a multi-institutional retrospective study for 115 patients with stage IA non-invasive UPSC (confined to endometrium) treated between 2000 and 2012. Kaplan-Meier and multivariable Cox proportional hazards regression modeling were used. RESULTS: Staging lymphadenectomy and omentectomy were performed in 84% and 57% respectively. Recurrence was seen in 26% (30/115). Sites of recurrences were vaginal in 7.8% (9/115), pelvic in 3.5% (4/115) and extra-pelvic in 14.7% (17/115). Adjuvant chemotherapy did not impact risk of recurrence (25.5% vs. 26.9%, p=0.85) even in subset of patients who underwent lymphadenectomy (20% vs. 23.5%, p=0.80). These findings were consistent for pattern of recurrence. Among those who underwent lymphadenectomy, adjuvant chemotherapy did not impact progression-free survival (p=0.34) and overall survival (p=0.12). However among patients who did not have lymphadenectomy, adjuvant chemotherapy or pelvic radiation was associated with longer progression-free survival (p=0.04) and overall survival (p=0.025). In multivariable analysis, only staging lymphadenectomy was associated with improved progression-free survival (HR 0.34, 95% CI 0.12-0.95, p=0.04) and overall survival (HR 0.35, 95% CI 0.12-1.0, p=0.05). Neither adjuvant chemotherapy nor pelvic radiation were predictors of progression-free or overall survivals. CONCLUSION: In stage IA non-invasive UPSC, staging lymphadenectomy was significantly associated with recurrence and outcome and therefore, should be performed in all patients. Adjuvant chemotherapy or pelvic radiation had no impact on outcome in surgically staged patients but was associated with improved outcome in unstaged patients.

Adjuvant vaginal brachytherapy decreases the risk of vaginal recurrence in patients with stage I non-invasive uterine papillary serous carcinoma. A multi-institutional study.

OBJECTIVES: To investigate the impact of adjuvant vaginal brachytherapy on vaginal recurrence in stage I non-invasive uterine papillary serous carcinoma (UPSC). METHODS: This is a retrospective multi-institutional study from 2000-2012. 103 patients who underwent surgical treatment with non-invasive stage IA UPSC were included. RESULTS: 85% and 55% underwent staging lymphadenectomy and omentectomy respectively. 28.2% (29/103) developed recurrence. Vaginal, pelvic and extra-pelvic recurrences developed in 7.8% (8/103), 3.9% (4/103) and 16.5% (17/103) respectively. Among patients who were observed or received only chemotherapy, the rate of vaginal recurrence was 10.9% (7/64) compared to 2.6% (1/39) among those who received vaginal brachytherapy +/- chemotherapy (p=0.035). The rate of vaginal recurrence was not different between those who were observed and those who received only chemotherapy (9.3% vs. 14.3%, p=0.27). The 5-year progression free survival (PFS) and overall survival (OS) for the entire cohort were 88.3% and 90.6%. Patients who underwent surgical staging had longer PFS (p=0.001) and OS (p=0.0005) compared to those who did not. In multivariable analysis controlling for age, histology, chemotherapy, brachytherapy, and staging lymphadenectomy, only lymphadenectomy was an independent predictor of PFS (HR 0.28, 95% CI 0.11-0.71, p=0.0037) and OS (HR 0.27, 95% CI 0.10-0.71, p=0.0035). Neither chemotherapy nor brachytherapy were predictors of PFS or OS. CONCLUSIONS: This is the largest study reported in stage I non-invasive UPSC. The majority of recurrences were extra-pelvic. Vaginal brachytherapy has a significant role in reducing the risk of vaginal recurrence and surgical staging was the only predictor of outcome. Therefore, both should be considered in these patients.

Wandering Spleen. A Case of Spontaneous Hemoperitoneum in an HIV-positive Patient with Recurrent Tuboovarian Abscess.

BACKGROUND: Wandering spleen is a rare and potentially devastating condition that can present in a variety of ways. Here we present a case that led to acute abdomen and hemoperitoneum in a young woman. CASE: A 27-year-old woman with a history of human immunodeficiency virus (HIV), pelvic inflammatory disease, and tuboovarian abscess was readmitted to the hospital for intravenous antibiotic treatment. When her clinical picture did not improve, she underwent placement of a pelvic drain for abscess drainage. Overnight she developed an acute abdomen and hemorrhagic shock. She was taken to the operating room for an exploratory laparotomy, which revealed a ruptured spleen with a single, elongated vascular pedicle. CONCLUSION: Wandering spleen is a rare diagnosis, more common in reproductive-aged women, with potentially fatal complications. It is a necessary component of a differential diagnosis for acute abdomen in reproductive-aged women.

Evaluation of the cost of CA-125 measurement, physical exam, and imaging in the diagnosis of recurrent ovarian cancer.

OBJECTIVE: Ovarian cancer accounts for 50% of deaths from gynecologic malignancies. We sought to determine the cost of common methods of surveillance of women with ovarian cancer in first clinical remission. The current standard for post treatment surveillance is the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: We retrospectively determined how recurrence was initially detected at our institution and a cost model was created and applied to the United States population to calculate surveillance costs using the Surveillance Epidemiology & End Results (SEER) database. RESULTS: 57% (n=60) of first recurrences were identified by increasing CA 125 level. Routine office visit identified 27% (n=29) of recurrences, and 15% (n=16) were diagnosed initially with CT scan. In 5% (5/105), CT abnormality was the only finding. 95% (100/105) of patients had either elevated CA 125 or office visit findings at time of recurrence. Of the 22,000 women diagnosed with ovarian cancer yearly, 60% (n=13,266) will have advanced disease and are likely to recur. The surveillance cost for this population for 2 years using our model is $32,500,000 using NCCN guidelines and $58,000,000 if one CT scan is obtained. CONCLUSIONS: Our data suggests that following NCCN guidelines will detect 95% of recurrences. An additional $26 million will be needed to identify the 5% of women with recurrence seen on CT only. Post treatment surveillance of ovarian cancer patients contributes significantly to health care costs. Use of CT scan to follow these patients largely increases cost with only a small increase in recurrence detection.

Small-Molecule-Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death.

High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061-induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.

Fetal intracardiac potassium chloride injection to expedite second-trimester dilation and evacuation.

OBJECTIVE: To determine whether potassium chloride (KCl)-induced feticide prior to termination by dilation and evacuation (D&E) improves surgical outcome. METHODS: We conducted a retrospective study of women who underwent second-trimester (13 0/7 to 23 6/7 weeks) D&E at an urban university-based hospital between January 2000 and July 2010. Women were divided into 3 cohorts: (1) D&E for termination of pregnancy after feticide, (2) D&E without feticide, and (3) D&E for spontaneous pregnancy loss. We compared maternal characteristics, various perioperative variables, and surgical outcomes for all 3 groups. Anesthesia time was used as a surrogate for operative time in the primary outcome. RESULTS: We analyzed 128 pregnancies (group 1: n = 23, group 2: n = 53, group 3: n = 52). Baseline maternal characteristics did not differ among the 3 groups. Anesthesia time was longest in the termination with KCl group (group 1: 116.9 min vs. group 2: 94.5 min and group 3: 90.3 min, p = 0.004), however, the effect was mitigated after controlling for fetal size (p = 0.176). There was no difference in blood loss (p = 0.968). Complications were uncommon, however, cervical lacerations were more common in the termination with KCl group (2 vs. 0 and 0, p = 0.010). CONCLUSION: Presurgical feticide with KCl was not associated with shorter anesthesia time. The decision to perform feticide should be based on other considerations, such as patient preference.

Cervical ripening with laminaria tents prior to second trimester induction of labor.

BACKGROUND: Induction abortion in the second trimester may be favored in some instances, such as in women with compounding medical conditions or when skilled providers are not available. Various methods of pre-induction cervical preparation have been used to shorten the length of induction and decrease the risk of complications. The benefits of cervical preparation with laminaria before D&E have been well studied, but the benefits of laminaria before medical induction are less clear. OBJECTIVE: To determine if overnight cervical preparation with laminaria tents shortens delivery interval in women undergoing 2nd trimester induction of labor (IOL) with misoprostol. STUDY DESIGN: This was a retrospective cohort study comparing overnight intracervical laminaria placement followed by misoprostol to misoprostol alone for 2nd trimester IOL between 1/2000 and 12/2010. Women were excluded if the reason for IOL was preterm labor or preterm premature rupture of membranes or if misoprostol was not used as the primary induction agent. The primary outcome was time from misoprostol administration to delivery. RESULTS: 126 women were analyzed including 36 (29%) who received laminaria + misoprostol and 90 (71%) who received misoprostol alone. Women in the laminaria + misoprostol group were significantly older (30 yrs [14-44] vs. 27 yrs [17-43], p = .029). Induction for fetal anomaly (92% vs. 34%, p ≤ .001) and the use of feticide (56% vs. 13%, p ≤ .001) were more common in the laminaria + misoprostol group. The mean time to delivery in the laminaria + misoprostol group was 6 h longer compared to the misoprostol only group; 19 ± 8 h compared to 13 ± 12hrs (p = .007). There was no difference in fetal to placental delivery time (p = .329), total misoprostol dose (p = .182), or length of hospitalization (p = .144) however, significantly more women completed abortion at 24 hrs in the misoprostol alone group (90% vs. 61%, p ≤ .001). CONCLUSIONS: The use of laminaria tents for overnight cervical preparation does not expedite delivery times in patients undergoing 2nd trimester IOL with misoprostol.

Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study.

PURPOSE: Clinical utility of up-front multigene panel testing (MGPT) is directly related to the frequency of pathogenic variants (PVs) in the population screened and how genetic findings can be used to guide treatment decision making and cancer prevention efforts. The benefit of MGPT for many common malignancies remains to be determined. In this study, we evaluated up-front MGPT in unselected patients with endometrial cancer (EC) to determine the frequency of PVs in cancer susceptibility genes. METHODS: Patients with EC were prospectively enrolled at nine Ohio institutions from October 1, 2017, to December 31, 2020. Nine hundred and sixty-one patients with newly diagnosed EC underwent clinical germline MGPT for 47 cancer susceptibility genes. In addition to estimating the prevalence of germline PVs, the number of individuals identified with Lynch syndrome (LS) was compared between MGPT and tumor-based screening. RESULTS: Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). LS was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs. CONCLUSION: This prospective, multicenter study revealed potentially actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes.

The Highly Recurrent PP2A Aα-Subunit Mutation P179R Alters Protein Structure and Impairs PP2A Enzyme Function to Promote Endometrial Tumorigenesis.

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma-specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined. Here, we used a series of structural, biochemical, and biological approaches to investigate the impact of the P179R missense mutation on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at the P179 residue changes the protein's stable conformation profile. A crystal structure of the tumor-derived PP2A mutant revealed marked changes in A-subunit conformation. Binding to the PP2A catalytic subunit was significantly impaired, disrupting holoenzyme formation and enzymatic activity. Cancer cells were dependent on PP2A disruption for sustained tumorigenic potential, and restoration of wild-type Aα in a patient-derived P179R-mutant cell line restored enzyme function and significantly attenuated tumorigenesis and metastasis in vivo. Furthermore, small molecule-mediated therapeutic reactivation of PP2A significantly inhibited tumorigenicity in vivo. These outcomes implicate PP2A functional inactivation as a critical component of high-grade endometrial carcinoma disease pathogenesis. Moreover, they highlight PP2A reactivation as a potential therapeutic strategy for patients who harbor P179R PPP2R1A mutations. SIGNIFICANCE: This study characterizes a highly recurrent, disease-specific PP2A PPP2R1A mutation as a driver of endometrial carcinoma and a target for novel therapeutic development.See related commentary by Haines and Huang, p. 4009.

Preoperative frailty is a risk factor for non-home discharge in patients undergoing surgery for endometrial cancer.

OBJECTIVE: Our objective was to examine the association of the modified frailty index (mFI) and non-home discharge in patients undergoing surgery for endometrial cancer (EMCA). METHODS: Patients who underwent surgery for EMCA from 2011 to 2012 were identified from the American College of Surgeons - Nastional Surigical Quality Improvement Project (ACS-NSQIP) database. Current Procedural Terminology (CPT) codes were used to identify surgical characteristics. We excluded patients who were already living in a non-home facility. To determine frailty, we used the NSQIP frailty index. For analysis purposes, patients with an mFI score ≥0.18 were defined as frail. Patients were divided into groups based on discharge destination. Logistic regression were used to identify predictors of post-operative non-home discharge. RESULTS: 1216 patients were identified. 26 (2.1%) were discharged to a non-home facility. On multivariate analysis, patients who were discharged to a non-home facility were older (OR 1.09, 95% CI 1.04-1.14, p < 0.001), had a higher Body Mass Index (BMI) (OR 1.08, 95% CI 1.04-1.12, p < 0.001), were more likely to have disseminated cancer (OR 10.02, 95% CI 2.28-44.1, p = 0.002), and were frail (OR 1.95, 95% CI 1.91-5.01, p = 0.008). Undergoing minimally-invasive surgery was independently associated with discharge to home (OR 0.165, 95% CI 0.059-0.458, p = 0.001). CONCLUSION: Frailty is associated with increased risk of non-home discharge in patients undergoing surgery for EMCA. The mFI can be easily calculated using patient characteristics that are readily available pre-operatively. This information can be used for pre-op counseling and to facilitate appropriate and timely discharge planning.

The Prognostic Value of Baseline Lymphocyte, Neutrophil, and Monocyte Counts in Locally Advanced Cervical Carcinoma Treated with Radiation.

Background. To determine the prognostic significance of pretreatment levels of circulating lymphocyte (CLC), neutrophil (CNC), and monocyte (CMC) counts in patients with locally advanced cervical carcinoma (CC) treated with definitive radiation. Methods. A retrospective, dual-institution review of patients with Stage IB2-IVA CC from 2005 to 2015. Progression-free (PFS) and Overall Survival (OS) were determined for high and low CLC, CNC, and CMC groups. Multivariate analysis was used to confirm prognostic value of baseline leukocyte counts. Results. 181 patients were included. Median follow-up time was 26 (3-89) months. CNC had no effect on PFS or OS. PFS was similar between CMC groups; however, OS was significantly improved for patients with low CMC (62.5 versus 45.3 months, p = 0.016). High CLC was associated with improved PFS (48.5 versus 27.8 months, p = 0.048) and OS (58.4 versus 34.9 months, p = 0.048). On multivariate analysis, high CNC was associated with increased relapse risk (HR 1.12, p = 0.006) and low CLC was associated with increased mortality risk (HR 0.67, p = 0.027). Conclusion. This study demonstrates that leukocyte values can provide prognostic information in CC. These hypothesis-generating findings warrant further prospective investigations.

High-dose chemotherapy and stem-cell rescue for salvage therapy for relapsed malignant mixed ovarian germ cell tumor: A case report.

BACKGROUND: Malignant ovarian germ cell tumors are rare, and often treatable with surgery and chemotherapy. Few data are available for treatment of platinum-resistant tumors. CASE: A 31 year old gravida 0 with a 20 cm pelvic mass was found to have a malignant ovarian germ cell tumor after she underwent debulking surgery. She initially responded to chemotherapy; however her AFP began to rise before all cycles were completed. She underwent additional debulking surgery that was again suboptimal. She was then referred for salvage therapy with high-dose chemotherapy with stem cell transplant, which was successful and she has had no evidence of disease for over two years. CONCLUSION: High-dose chemotherapy with stem cell transplant is a viable salvage therapy for patients with platinum-resistant germ cell tumors.

Fertility-sparing management of a stage IB1 small cell neuroendocrine cervical carcinoma with radical abdominal trachelectomy and adjuvant chemotherapy.

•Neuroendocrine (NEC) tumors of the cervix are very rare and aggressive.•We present a case of Stage IB1 disease managed with fertility-sparing surgery.•Further investigation into fertility-sparing surgery is warranted.

Critical role of Wnt/ß-catenin signaling in driving epithelial ovarian cancer platinum resistance.

Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/ß-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/ß-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/ß-catenin signaling is activated in ovarian CICs, and targeted inhibition of ß-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/ß-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/ß-catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option.

Cyberknife radiotherapy and anastrozole for the treatment of advanced progressive low-grade papillary serous ovarian carcinoma: A case report.

•Low-grade papillary serous ovarian carcinoma has unique epidemiologic and disease-specific characteristics•Cyberknife radiotherapy is a unique treatment that may successfully be used to treat unresectable disease•Anastrozole is an effective treatment for hormone receptor-positive low-grade papillary serous ovarian carcinoma.

Management of early stage, high-risk endometrial carcinoma: preoperative and surgical considerations.

Endometrial cancer is the most common gynecologic malignancy in the developed world. Most cases are diagnosed at an early stage and have low-grade histology, portending an overall excellent prognosis. There exists a subgroup of patients with early, high-risk disease, whose management remains controversial, as current data is clouded by inclusion of early stage tumors with different high-risk features for recurrence, unstandardized protocols for surgical staging, and an evolving staging system by which we are grouping these patients. Here, we present preoperative and intraoperative considerations that should be taken into account when planning surgical management for this population of patients.