Primary peritoneal clear cell carcinoma arising in the setting of abdominal wall Endometriosis: A case report and review of the literature.

•Primary peritoneal clear cell carcinoma can arise from endometriotic implants within the abdomen and pelvis.•Immunohistochemistry can be used to confirm primary disease site. Endometriotic origin can be inferred based on clinical history and intraoperative findings suggestive of endometriosis.•While no standardized treatment exists, consideration should be given to cytoreductive surgery with adjuvant chemotherapy. Adjuvant radiation can also be considered for local control.

Uterine adenosarcoma presenting as uterine inversion: A case study.

•Non-puerperal uterine inversion can be associated with uterine sarcomas.•Adenosarcoma is a tumor composed of benign epithelium and malignant stroma.•If malignancy is suspected or confirmed treatment of uterine inversion with hysterectomy is advised.

Non-islet cell tumor hypoglycemia in a patient with uterine carcinosarcoma.

•Non-islet cell tumor hypoglycemia (NICTH) is a rare cause of hypoglycemia in patients with uterine carcinosarcoma.•Complete surgical resection is the first-line treatment for NICTH.•In patients with tumors not amenable to complete resection, partial resection can provide improvement in severe hypoglycemia.

Asparagus officinalis Exhibits Anti-Tumorigenic and Anti-Metastatic Effects in Ovarian Cancer.

Ovarian cancer is one of the leading causes of female cancer death. Emerging evidence suggests that many dietary natural products have anti-tumorigenic activity, including that of asparagus officinalis. The current study aimed to assess the anti-tumorigenic and anti-metastatic effects of asparagus officinalis on serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer. Asparagus officinalis decreased cellular viability, caused cell cycle G1 phase arrest and induced apoptosis in the OVCAR5 and SKOV3 cells. Induction of apoptosis and inhibition of cell proliferation was rescued by the pan-caspase inhibitor, Z-VAD-FMK, implying that its cytotoxic effects were mainly dependent on caspase pathways. Asparagus officinalis increased levels of ROS and decreased mitochondrial membrane potential with corresponding increases in PERK, Bip, Calnexin PDI and ATF4 in both cell lines. Treatment with asparagus officinalis also reduced ability of adhesion and invasion through epithelial-mesenchymal transition and reduction of VEGF expression. The combination of Asparagus officinalis with paclitaxel had synergistic anti-proliferative activity. Furthermore, Asparagus officinalis significantly inhibited tumor growth and reduced serum VEGF in a genetically engineered mouse model of ovarian cancer under obese and lean conditions, accompanied with a decrease in the expression of Ki67, VEGF and phosphorylated S6, and in an increase in phosphorylation of AMPK in the ovarian tumor tissues. Overall, our data provide a pre-clinical rationale for asparagus officinalis in the prevention and treatment of ovarian cancer as a novel natural product.

Contemporary Incidence of Medical Inoperability in Clinical Stage I Endometrial Cancer.

BACKGROUND: Minimally invasive surgical (MIS) staging is the standard treatment approach for clinical stage I endometrial cancer. Historical rates of inoperability in endometrial cancer are approximately 10%. Given surgical and medical advancements against increasing population obesity, we aimed to describe a contemporary incidence of medical inoperability in clinical stage I endometrial cancer. PATIENTS AND METHODS: Patients diagnosed with clinical stage I endometrial cancer of any histology from April 2014 to December 2018 were included in this retrospective cohort study. The primary outcome, medical inoperability, was defined as (1) patients deemed inoperable by a gynecologic oncologist at initial consultation, (2) patients deemed inoperable during preoperative clearance, or (3) an aborted hysterectomy. Fisher's exact or χ2, and Student's t-test or Wilcoxon rank sum test were used, as appropriate, for data analysis. Multivariable logistic regression was also employed. RESULTS: Overall, 767 patients were included, of which 4.6% (35/767) were determined to be inoperable. The inoperable group had a higher body mass index (52.7 vs. 33.9, p < 0.001), and increased rates of diabetes (62.8%, 22/35 vs. 27.1%, 199/732, p < 0.001), coronary artery disease (31.4%, 11/35 vs. 7.1%, 52/732, p < 0.001), and hypertension (94.3%, 33/35 vs. 70.2%, 514/732, p < 0.001). Of those with attempted surgical staging, hysterectomy was aborted intraoperatively in 0.68% (5/737). The overall complication rate was 11.6% (86/737). CONCLUSIONS: With maximal surgical effort and MIS, hysterectomy is possible in > 95% of patients with newly diagnosed endometrial cancer treated at a high-volume center. Complication rates were comparable to other trials evaluating the safety of MIS staging for endometrial cancer.

Comparing Laparotomy with Robot-assisted Interval Debulking Surgery for Patients with Advanced Epithelial Ovarian Cancer Receiving Neoadjuvant Chemotherapy.

STUDY OBJECTIVE: Compare survival of patients with advanced epithelial ovarian cancer (EOC) undergoing interval debulking surgery (IDS) with either robot-assisted (R-IDS) or open (O-IDS) approach. Second, we assessed the impact of adjuvant and neoadjuvant chemotherapy (NACT) cycles as independent variables associated with survival in this patient population. DESIGN: Retrospective cohort study. SETTING: Single tertiary care center. PATIENTS: Total of 93 patients diagnosed with advanced EOC who underwent NACT before primary debulking surgery after consultation with a gynecologic oncologist. INTERVENTIONS: All patients underwent IDS after completion of NACT with either R-IDS or O-IDS between 2011 and 2018 at a single tertiary care center. Exclusion criteria included receiving fewer than 3 or more than 6 cycles of NACT or having concurrent diagnoses of other malignancies during the treatment period. MEASUREMENTS AND MAIN RESULTS: A total of 93 patients were identified (n = 43 R-IDS; n = 50 O-IDS). Median age (63.0 vs 66.2 years) did not differ between the 2 groups (p = .1). Of the total patients, 91% were optimally cytoreduced (57% R0 and 34% R1), and R0 rate was not influenced by surgical modality (52% O-IDS vs 63% R-IDS, p = .4). Progression-free survival (PFS) and overall survival (OS) did not differ between patients undergoing O-IDS and those undergoing R-IDS (PFS 15.4 vs 16.7 months, p = .7; OS 38.2 vs 35.6 months, p = .7). Cytoreduction to R0 improved both PFS and OS independent of surgical approach. Subgroup analysis showed that, specifically in patients undergoing R-IDS, receiving >6 total cycles of chemotherapy was independently associated with both decreased PFS (hazard ratio 3.85; 95% confidence interval, 1.52-9.73) and OS (hazard ratio 3.97; 95% confidence interval, 1.08-14.59). When analyzed separately, neither NACT nor adjuvant cycle numbers had any effect on survival. CONCLUSION: In this retrospective study of patients with advanced EOC undergoing IDS after NACT, the use of robot-assisted surgery did not affect debulking success or oncologic survival indices. Receiving >6 total cycles of chemotherapy before IDS was associated with a decrease in both PFS and OS in patients undergoing R-IDS in this cohort and warrants further investigation.

Accuracy of preoperative cross-sectional imaging in cervical cancer patients undergoing primary radical surgery.

OBJECTIVE: We aim to describe the false negative (FN) and false positive (FP) rates of preoperative cross-sectional imaging (PCI) prior to radical surgery for cervical cancer. METHODS: A retrospective cohort study of patients who underwent radical hysterectomy for early-stage cervical cancer from January 2010 until December 2017 at a single tertiary care center was performed. Patients were included if they underwent preoperative PCI and radical surgery. Patient demographics and clinicopathologic information were recorded from medical record review. Descriptive statistics were used. RESULTS: Overall, 106 patients met inclusion criteria. Eighty-four percent (89/106) of patients had no suspicion for metastatic disease on PCI, while 16% (17/106) had suspicion for metastatic disease. Of the 89 without suspicion for metastatic disease on PCI, 16% (14/89) had a false negative study with metastatic disease identified on final surgical pathology. False negative rates by modality were 16% (11/70) for PET/CT and 6% (2/33) for diagnostic CT. Of the 17 cases with suspicion for metastatic disease on imaging, 53% (9/17) were false positive studies with no metastatic disease identified histologically. False positive rates by modality were 7% (5/70) for PET/CT and 12% (4/33) for diagnostic CT. CONCLUSION: PCI is a tool to help identify patients who are optimal candidates for radical surgery. In this sample, the false negative rate was 16%, and false positive rate was 53% for PCI among women who underwent primary radical surgery. Further study is needed to explore preoperative testing that may more accurately identify optimal surgical candidates.

Paraneoplastic cerebellar degeneration heralding recurrence of fallopian tube adenocarcinoma: A case report and literature review.

•Paraneoplastic cerebellar degeneration in recurrence of fallopian tube cancer.•Describes the initial symptoms of paraneoplastic cerebellar degeneration.•Identify a diagnosis that can lead to rapid irreversible deterioration.•Describe management and outcomes of paraneoplastic cerebellar degeneration.

The Role of Obesity in the Development and Management of Gynecologic Cancer.

IMPORTANCE: Endometrial cancer is the most common gynecologic malignancy, with an estimated 54,000 new cases and 10,000 deaths in the United States in 2015. The obesity epidemic directly contributes to the escalating prevalence of chronic diseases, including obesity-related cancers. Patient body weight and nutritional status markedly impact perioperative oncologic care, chemotherapy administration, recurrence risk, and survivorship goals. OBJECTIVES: The objective of this review is to explore the association between obesity and the development, treatment, and survival outcomes of gynecologic cancers. EVIDENCE ACQUISITION: A systematic literature review was performed utilizing PubMed and ClinicalTrials.gov. CONCLUSIONS AND RELEVANCE: Caring for obese women with gynecologic cancers presents unique challenges. A coordinated multidisciplinary and system effort is required to address the prevention and treatment of obesity, as the sequela of this disease is a clear risk factor for the development of gynecologic malignancy and other comorbidities. Health care providers must be ready to address this worldwide health problem.

Clinical characteristics of CNS metastases from primary gynecologic cancers.

The development of brain and central nervous system (CNS) metastases from primary gynecologic cancers is an extremely uncommon but deadly process. Through this retrospective case series of patients treated at a single institution from 2004 to 2018, we aim to explore potential clinical patterns of this phenomenon with respect to primary tumor type, histology, and symptomatology. A total of 42 patients were identified with CNS metastases, with 24 patients having endometrial cancer, 9 patients with ovarian cancer, 5 patients with cervical cancer, and 4 patients with gestational trophoblastic neoplasia (GTN). The two most common presenting complaints were headache and ataxia. Most patients (67%) presented with more than one lesion on imaging and the frontal lobe was most likely to be involved. The median age of diagnosis for both primary cancer and CNS metastasis were significantly younger in the GTN group when compared to other cancers. Meningeal involvement was more prevalent in patients with cervical cancer. Over 83% of endometrial cancer patients in this cohort had type II histologies, a significantly higher percentage than that in the general population. While the rarity of CNS metastases in primary gynecologic malignancies precludes routine screening, patients diagnosed with more aggressive histologic subtypes of endometrial and uterine cancers may benefit from a lowered threshold of brain imaging in the context of new onset neurological symptoms.

Reversal of obesity-driven aggressiveness of endometrial cancer by metformin.

BACKGROUND: Obesity and diabetes are associated with increased risk and worse outcomes for endometrial cancer. Metformin is a widely prescribed generic drug for the treatment of type II diabetes and metabolic syndrome and may also have anti-tumorigenic effects. Thus, we assessed the metabolic anti-tumorigenic effects of metformin in (1) human endometrial cancer cell lines under varying glucose concentrations, and (2) a novel genetically engineered mouse model of endometrioid endometrial cancer under obese and lean conditions. METHODS: The effects of metformin on cytotoxicity, apoptosis, cell cycle progression, and the AMPK/mTOR/S6 and MAPK pathways were assessed in ECC-1 and Ishikawa cells under low, normal and high glucose conditions. The impact of metformin treatment on tumor growth under obese and lean conditions was evaluated using a novel LKB1fl/fl p53fl/fl mouse model of endometrial cancer. Global, untargeted metabolomics was used to identify (1) obesity-associated differences between endometrial tumors and (2) the obesity-dependent effects of metformin in the endometrial tumors. RESULTS: Hypoglycemic conditions significantly enhanced the sensitivity of the cells to metformin in regards to its anti-proliferative and apoptotic effects, as compared to hyperglycemic and normal glucose conditions. Metformin inhibited tumor growth in both the obese and lean mice, which metformin-induced inhibition of tumor progression in obese mice was significantly greater than in lean mice. Metabolomic profiling in endometrial cancer tissues revealed significant differences between obese- and lean-mice. Enhanced energy metabolism was seen in obese- versus lean-mice as evidenced by increases in glycolytic and oxidative phosphorylation intermediates. In addition, dramatic increases in lipid biosynthesis and lipid peroxidation were found in the obese- versus lean-mice, whereas metformin obviously reversed the obesity-driven upregulation of lipid and protein biosynthesis in the obese mice. CONCLUSIONS: The obese state promoted tumor aggressiveness in the LKB1fl/fl p53fl/fl mouse model, accompanied by increases in energy metabolism, lipid biosynthesis, and markers of lipid peroxidation. Metformin had increased efficacy against endometrial cancer in obese versus lean mice and reversed the detrimental metabolic effects of obesity in the endometrial tumors. Taken together, it is likely that the unique metabolic milieu underlies metformin's improved efficacy in treating endometrial cancer which develop in an obese host environment.

Physical Activity: Impact on Survival in Gynecologic Cancer.

IMPORTANCE: Physical activity has many important health benefits. There is also growing evidence that physical activity plays a role in the prevention and prognosis of multiple cancers, including gynecologic malignancies. Despite the many benefits of physical activity, the number of individuals meeting physical activity recommendations remains low. OBJECTIVE: To examine the role that physical activity plays in the prevention, treatment, and prognosis of gynecologic malignancies and to review the feasibility of physical activity interventions among gynecologic cancer survivors. EVIDENCE ACQUISITION: A PubMed search was performed using relevant terms to identify journal articles related to the proposed subject. The websites of multiple national and international organizations were also used to obtain up-to-date guidelines and recommendations. RESULTS: Physical activity appears to decrease the risk of ovarian, endometrial, and cervical cancer, with the strongest evidence of this association seen in endometrial cancer. Although the literature is scarce, participation in physical activity is feasible during active treatment for gynecologic cancers and may decrease symptom burden and increase chemotherapy completion rates. Gynecologic cancer survivors are motivated to increase physical activity, and lifestyle intervention programs are feasible and well received among this population. CONCLUSIONS AND RELEVANCE: Health care providers caring for women with gynecologic malignancies must counsel patients regarding the importance of physical activity. This should include a discussion of the health benefits and, specifically, the cancer-related benefits. A personalized approach to physical activity intervention is essential.

Malignant Brenner tumor of the ovary: Case series and review of treatment strategies.

Malignant Brenner tumor (MBTs) is a rare histological subtype of epithelial ovarian cancer, accounting for <0.05% of all ovarian neoplasms. As such, current evidence on the treatment of MBTs is predominantly limited to case studies and small case series. To add to existing literature, we performed a retrospective review of 10 cases of MBT diagnosed and treated at a single institution between 1999 and 2018. For the 10 cases included in our cohort, the median age was 64 and the median tumor stage was IIa/IIb. All patients underwent either a primary or interval debulking surgery and achieved an R0 resection per classifications set by the Union for International Cancer Control (UICC). Lymph node dissections were performed on 6 patients and found no evidence of positive nodal disease. 7 patients received platinum-based adjuvant chemotherapy and experienced a median progression-free survival (PFS) of 37 months. Recurrent disease was varied in terms of locoregional versus distant spread, and these patients had largely suboptimal responses to salvage chemotherapy with doxorubicin, gemcitabine, and eribulin. Sites of metastatic disease included the liver, lungs, bone, and brain. While there is no consensus for the optimal treatment of this rare disease, MBTs seem to respond well to adjuvant platinum-taxane treatment after complete surgical resection, consistent with the current management approach of other epithelial ovarian cancers. Recurrent disease is considerably more difficult to manage, and clinicians may consider a wider avenue of treatment options to include hormonal, biologic, and radiation therapies.

Cost-effectiveness of opportunistic salpingectomy vs tubal ligation at the time of cesarean delivery.

BACKGROUND: Removal of the fallopian tubes at the time of hysterectomy or interval sterilization has become routine practice to prevent ovarian cancer. While emerging as a strategy, uptake of this procedure at the time of cesarean delivery for pregnant women seeking permanent sterilization has not been widely adopted due to perceptions of increased morbidity and operative difficulty with a lack of available data in this setting. OBJECTIVE: We sought to conduct a cost-effectiveness analysis comparing strategies for long-term sterilization and ovarian cancer risk reduction at the time of cesarean delivery, including bilateral tubal ligation, opportunistic salpingectomy, and long-acting reversible contraception. STUDY DESIGN: A decision-analytic and cost-effectiveness model was constructed for pregnant women undergoing cesarean delivery who desired permanent sterilization in the US population, comparing 3 strategies: (1) bilateral tubal ligation, (2) bilateral opportunistic salpingectomy, and (3) postpartum long-acting reversible contraception. This theoretic cohort consisted of 110,000 pregnant women desiring permanent sterilization at the time of cesarean delivery and ovarian cancer prevention at an average of 35 years who were monitored for an additional 40 years based on an average US female life expectancy of 75 years. The primary outcome measure was the incremental cost-effectiveness ratio. Effectiveness was measured as quality-adjusted life years. Secondary outcomes included: the number of ovarian cancer cases and deaths, procedure-related complications, and unintended and ectopic pregnancies. The 1-, 2-, and 3-way and Monte Carlo probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set at $100,000. RESULTS: Both bilateral tubal ligation and bilateral opportunistic salpingectomy with cesarean delivery have favorable cost-effectiveness ratios. In the base case analysis, salpingectomy was more cost-effective with an incremental cost-effectiveness ratio of $23,189 per quality-adjusted life year compared to tubal ligation. Long-acting reversible contraception after cesarean was not cost-effective (ie, dominated). Although salpingectomy and tubal ligation were both cost-effective over a wide range of cost and risk estimates, the incremental cost-effectiveness ratio analysis was highly sensitive to the uncertainty around the estimates of salpingectomy cancer risk reduction, risk of perioperative complications, and cost. Monte Carlo probabilistic sensitivity analysis estimated that tubal ligation had a 49% chance of being the preferred strategy over salpingectomy. If the true salpingectomy risk of perioperative complications is >2% higher than tubal ligation or if the cancer risk reduction of salpingectomy is <52%, then tubal ligation is the preferred, more cost-effective strategy. CONCLUSION: Bilateral tubal ligation and bilateral opportunistic salpingectomy with cesarean delivery are both cost-effective strategies for permanent sterilization and ovarian cancer risk reduction. Although salpingectomy and tubal ligation are both reasonable strategies for cesarean patients seeking permanent sterilization and cancer risk reduction, threshold analyses indicate that the risks and benefits of salpingectomy with cesarean delivery need to be better defined before a preferred strategy can be determined.

Current First-line Therapy for Ovarian Cancer: A Comprehensive Review.

IMPORTANCE: Ovarian, fallopian tube, and primary peritoneal cancers constitute the deadliest gynecologic malignancies. After primary cytoreductive surgery, there are several standard first-line cytotoxic treatments for providers to consider. Newer molecular targeted therapies are becoming more common and may have a role as first-line therapy in the future. OBJECTIVE: This article provides an evidence-based review of all approved standard therapies for first-line treatment of advanced-stage, high-grade serous ovarian cancer. Treatment schedules, dose modifications, and drug substitutions are reviewed. Ongoing trials and pending approvals for newer molecular therapies are discussed. EVIDENCE ACQUISITION: A comprehensive primary literature review was performed using MEDLINE, the Cochrane Collaborative Database, and PubMed. Guidelines from the National Comprehensive Cancer Network and the Society for Gynecologic Oncology were also reviewed. RESULTS: Seven different approved first-line regimens for high-grade serous ovarian cancer are available based on literature review. These vary in route of administration, dose intensity, drug combinations, and treatment schedules. Molecular targeted therapies, including antiangiogenic drugs and poly(ADP-ribose) polymerase inhibitors, have also been studied in multiple randomized controlled trials in the first-line setting. CONCLUSIONS AND RELEVANCE: Cytotoxic regimens remain the foundation of first-line treatment for high-grade serous ovarian cancer. Choosing which regimen is best for a patient depends on both patient and disease factors. Molecular therapies in first-line treatment are a promising and exciting possibility, with regulatory approval pending.

ONC201 demonstrates anti-tumorigenic and anti-metastatic activity in uterine serous carcinoma in vitro.

Uterine serous carcinoma (USC) represents an aggressive histologic subtype of endometrial cancer. It is associated with a poor prognosis, and improved therapies for women battling USCs are greatly needed. ONC201 is an orally bioavailable, first-in-class small molecule that induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) independent of p53. ONC201 has demonstrated anti-tumorigenic activity in pre-clinical models of solid tumors through induction of apoptosis and inactivation of the AKT/MAPK pathways. Recent phase I and II clinical trials have shown that ONC201 is well tolerated and may have single agent activity in high grade glioma patients among others. We sought to determine the effects of ONC201 on cell proliferation in USC and identify the mechanisms by which ONC201 inhibits cell growth in this disease. ONC201 inhibited cell proliferation in a dose-dependent manner in ARK1, ARK2 and SPEC-2 cell lines. The anti-proliferative activity of ONC201 in ARK1 and SPEC-2 cells was associated with induction apoptosis independent of p53 via both a TRAIL mediated apoptotic pathway and a mitochondrial apoptosis pathway. Treatment with ONC201 resulted in significant reduction in adhesion and invasion as well as inhibition of the AKT and MAPK pathways. In addition, ONC201 markedly potentiated the anti-tumorigenic effects of paclitaxel in USC cells. Our results suggest that ONC201 has significant anti-proliferative and anti-metastatic effects in USC cells through both induction of apoptosis and inhibition of the AKT and MAPK pathways. ONC201 and paclitaxel are a promising therapeutic combination in USC cells. Thus, ONC201 should be evaluated as a single agent and as a therapeutic partner with paclitaxel in future clinical trials of USC.

Topiramate exhibits anti-tumorigenic and metastatic effects in ovarian cancer cells.

Ovarian cancer is one of the leading causes of cancer related deaths among women worldwide, with an overall 5-year survival of only 30-40%. Carbonic anhydrases are up-regulated in many types of cancer and play an important role in tumor progression and metastasis. Carbonic anhydrase 9 has been implicated as a potential anti-tumorigenic target. Topiramate (TPM) is a potent inhibitor of carbonic anhydrase isozymes, including carbonic anhydrase 9, and has been shown to have anti-tumorigenic activity in several cancer types. Our goal was to evaluate the effect of TPM on cell proliferation and to identify possible mechanisms by which TPM inhibits cell growth in ovarian cancer. TPM significantly inhibited ovarian cancer cell proliferation and induced cell cycle G1 arrest, cellular stress and apoptosis through the AKT/mTOR and MAPK pathways. TPM also exerted anti-metastatic effects by decreasing the adhesion and invasion of ovarian cancer cells and affecting the expression of critical regulators of the epithelial-mesenchymal transition (EMT). Our findings demonstrate that TPM has anti-tumorigenic effects in ovarian cancer and is worthy of further exploration in clinical trials.

Erratum: Atorvastatin exhibits anti-tumorigenic and anti-metastatic effects in ovarian cancer in vitro.

[This corrects the article on p. 2478 in vol. 7, PMID: 29312801.].

Novasoy and genistein inhibit endometrial cancer cell proliferation through disruption of the AKT/mTOR and MAPK signaling pathways.

OBJECTIVES: Excess estrogen states, such as those generated by obesity, have long been associated with the development of type I endometrial cancers. Epidemiological studies have linked consumption of isoflavones with a decreased incidence of endometrial malignancy. Thus, our goal was to assess the effect of the isoflavones, novasoy and genistein, on cell proliferation, cell cycle, apoptosis, progesterone receptor (PR) and estrogen receptor-alpha (ERα) expression and the AKT/mTOR and MAPK pathways in endometrial cancer cells. METHODS: The endometrial cancer cell lines ECC-1 and RL-95-2 were used. Cell proliferation was assessed with MTT assay after exposure to novasoy and genistein at varying concentrations. Cell cycle progression was analyzed by flow cytometry. Apoptosis was assessed by flow cytometery for annexin V expression and ELISA for caspase-3 activity. Expression of ERα, PR and hTERT mRNA were evaluated using real time RT-PCR. Western immunoblotting was performed to evaluate the effects of novasoy and genistein on the AKT/mTOR and MAPK signaling pathways. RESULTS: Novasoy and genistein inhibited cell growth in a dose-dependent manner in both cell lines through induction of cell cycle G2 arrest and apoptosis. Treatment with novasoy and genistein decreased hTERT expression in a dose-dependent manner. Genistein decreased ERα mRNA expression while increasing PR expression. Genistein induced phosphorylation of p42/44 in a dose dependent manner in both cell lines but reduced phosphorylation of S6 in only the RL-95-2 cells. CONCLUSIONS: Novasoy and genistein inhibited cell proliferation through varying pathways in different cell lines but included decreased ERα expression and subsequent alteration in the expression of proteins upstream and downstream of the AKT/mTOR and MAPK pathways. Thus, isoflavones may be a promising therapeutic agent in the treatment and prevention of endometrial cancer.

Impact of Trainee Involvement in Cervical Excision Procedures: Does Trainee Involvement Impact Quality?

OBJECTIVE: Cervical excision procedures are essential to the care of cervical dysplasia and malignancy. We sought to determine whether learner involvement in cervical excision procedures affects the quality of excision specimen. MATERIALS AND METHODS: A retrospective cohort study of cervical cancer patients diagnosed from July 1, 2000, to July 1, 2015, was performed. We included patients who had (1) a cervical excision procedure, either loop electrosurgical excision procedure or cold knife cone, and (2) pathologic information available. Primary outcome was the margin status of the specimen; secondary outcome was the size of the excision specimen including both width and depth. The exposure of interest was trainee participation, defined as resident physicians under the supervision of either a gynecologist or gynecologic oncologist. Descriptive statistics and general linear models were used for analysis. RESULTS: Ninety-four patients were identified. Overall, 58% (n = 54) of procedures were performed with trainee involvement. There was no difference in age, body mass index, or specimen width between trainee-performed and nontrainee-performed excisions. There was no significant difference in the status of margins with or without a trainee [44/57 (77%) and 29/37 (78%), respectively, p = .89]. There was a statistically significant difference in median specimen depth between trainee-performed and nontrainee-performed cases (15.4 mm vs 12 mm, p < .02). When adjusting for age, body mass index, excision type, indication, presence of trainee, and type of supervising physician, only the indication and type of excision were associated with greater depth of excision, (p < .01). CONCLUSIONS: Trainee involvement in cervical excision procedures does not alter the quality of excision specimen.