African American women with advanced-stage ovarian cancer have worse outcomes regardless of treatment type.

OBJECTIVE: There has been an increase in the use of neoadjuvant chemotherapy in recent years. Our objective was to determine if African American women are more likely to receive neoadjuvant chemotherapy than primary debulking surgery, when compared to their Caucasian counterparts, and the impact of such an approach on oncologic outcomes. METHODS: A retrospective cohort study was performed using the National Cancer Database (NCDB). Women aged 18-90 years, diagnosed with stage IIIC or IV epithelial ovarian cancer between January 2010 through December 2014 were included. Women with unknown treatment or treatments outside of neoadjuvant chemotherapy or primary debulking surgery were excluded. Only women of Caucasian, African American, or Hispanic origin who received either neoadjuvant chemotherapy or primary debulking surgery were included; all other races were excluded. Descriptive statistics were computed, and continuous variables were assessed for normality. Groups were compared using ANOVA or non-parametric medians tests for continuous variables, and chi-squared tests were used for dichotomous or categorical variables. Logistic regression was used to identify predictors of treatment. A p value of 0.05 was considered statistically significant. RESULTS: A total of 19 838 women with stage IIIC and IV epithelial ovarian cancer met the inclusion criteria. A total of 14 988 (75.6%) were treated with primary debulking surgery, while 4850 women (24.4%) were treated with neoadjuvant chemotherapy. Of those treated with neoadjuvant chemotherapy, 24.5% were white, 27.0% were African American, and 22.1% were Hispanic (p=0.005), and when adjusted for confounders, being African American was a predictor of receiving neoadjuvant chemotherapy (adjusted odds ratio (aOR) 1.29, 95% CI 1.10 to 1.51). Ninety-day mortality rates were higher in African American women compared with Caucasian and Hispanic women (2.9% vs 2.0% vs 1.6%, p=0.013). There were no differences in 30-day mortality, 90-day mortality, or status at last contact in African American women, when comparing neoadjuvant chemotherapy and primary debulking surgery. In Caucasian women, outcomes were worse in women receiving neoadjuvant chemotherapy. CONCLUSIONS: Compared to other races, African American women with advanced ovarian cancer are more likely to receive neoadjuvant chemotherapy than primary debulking surgery and had a higher 90-day mortality rate. In African American women there was no difference in outcomes based on treatment type.

Adiponectin receptor agonist AdipoRon induces apoptotic cell death and suppresses proliferation in human ovarian cancer cells.

We tested the hypothesis that stimulation of adiponectin receptors with the synthetic agonist AdipoRon suppresses proliferation and induces apoptotic death in human high grade serous ovarian tumor cell lines and in ex vivo primary tumors, mediated by activation of 5' AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR). We determined the effect of AdipoRon on high grade serous ovarian tumor cells lines (OVCAR3, OVCAR4, A2780) and ex vivo primary tumor tissue. Western blotting analysis was performed to examine changes in activation of AMPK and mTOR signaling and flow cytometry was utilized to examine changes in cell cycle progression. Immunofluorescence of cleaved caspase-3 positive cells and flow cytometry of annexin V positive cells were used to determine changes in apoptotic response. The CyQUANT proliferation assay was used to assess cell proliferation. AdipoRon treatment increased AMPK phosphorylation (OVCAR3 P = 0.01; A2780 P = 0.02) but did not significantly alter mTOR activity. AdipoRon induced G1 cell cycle arrest in OVCAR3 (+ 12.1%, P = 0.03) and A2780 (+ 12.0%, P = 0.002) cells. OVCAR3 and OVCAR4 cells treated with AdipoRon underwent apoptosis based on cleaved caspase-3 and annexin V staining. AdipoRon treatment resulted in a dose dependent decrease in cell number versus vehicle treatment in OVCAR3 (-61.2%, P < 0.001), OVCAR4 (-79%, P < 0.001), and A2780 (-56.9%, P < 0.001). Ex vivo culture of primary tumors treated with AdipoRon resulted in an increase in apoptosis measured with cleaved caspase-3 immunohistochemistry. AdipoRon induces activation of AMPK and exhibits an anti-tumor effect in ovarian cancer cell lines and primary tumor via a mTOR-independent pathway.

Persistent opioid use after radiation therapy in opioid-naive cervical cancer survivors.

OBJECTIVES: Opioids are first-line therapy for cancer-related pain, but their use should be minimized in disease-free survivors. We sought to describe rates and identify predictors of persistent opioid use among previously opioid-naive cervical cancer survivors treated with radiation. METHODS: Opioid-naive cervical cancer patients treated primarily with radiation and chemosensitization at a single institution, between January 2011 and December 2015, were identified. Charts were reviewed for demographics, disease, and treatment characteristics, and opioid prescriptions. Primary outcome was persistent opioid use, defined as continued opioid prescription use, 6 months after radiation; patients recurring within 6 months were excluded. Groups were compared using χ2 or Fisher's exact test. Multivariable logistic regression identified predictors of persistent opioid use. RESULTS: A total of 96 patients were included, with a median age of 49 years (range 27-84). Most patients (59%) at diagnosis had International Federation of Gynecology and Obstetrics (FIGO) stage I or II cervical cancer. The most common histology was squamous cell carcinoma (72%) and most (94.7%) patients received radiation with chemosensitization. Rates of persistent opioid use at 3 and 6 months after treatment were 29% and 25%, respectively. Persistent users were more likely to be <40 years old, have disease outside the pelvis at diagnosis, and have had a history of substance abuse, depression or anxiety (p<0.05). In multivariable analysis, a history of substance abuse (adjusted OR 6.21, 95% CI 1.08 to 35.67) and depression or anxiety (aOR 6.28, 95% CI 1.70 to 23.30) were independently associated with persistent opioid use. CONCLUSION: Our study showed that 25% of patients with cervical cancer were still using opioids 6 months after radiation. History of substance abuse and depression or anxiety, all known risk factors for opioid misuse, were associated with persistent use. The goal in the disease-free survivor population should be opioid independence.

Minority Race Predicts Treatment by Non-gynecologic Oncologists in Women with Gynecologic Cancer.

BACKGROUND: Outcomes of women with gynecologic cancer are superior when treated by gynecologic oncologists. The National Surgical Quality Improvement Program (NSQIP) began identifying gynecologic surgeon subspecialty in 2014. We sought to identify characteristics and outcomes of women treated by general gynecologists in comparison with women treated by gynecologic oncologists. PATIENTS AND METHODS: Patients undergoing hysterectomy for gynecologic malignancy in 2014 and 2015 were abstracted from the NSQIP database. Patient characteristics, morbidities, surgeon specialty, and operative outcomes were captured. RESULTS: 7271 hysterectomies were performed for malignant disease, and 669 were performed by generalists. In comparison with generalists, gynecologic oncologists operated on patients who were older (P < 0.001), more likely to be White [odds ratio (OR) 2.1, P < 0.001], had disseminated cancer (OR 3.1, P < 0.001), had ascites (OR 2.6, P < 0.001), and were classified as American Society of Anesthesiologists (ASA) class ≥ 3 (OR 1.7, P < 0.001). Gynecologic oncologists were also more likely to have hospital readmissions (OR 1.7, P = 0.004) and perform lymph node dissections for endometrial cancer (OR 2.2, P < 0.001). On multivariable analysis, older age [adjusted OR (aOR) 1.0, P = 0.021], White race (aOR 2.0, P < 0.001), presence of disseminated cancer (aOR 2.5, P < 0.001), presence of ascites (aOR 1.8, P = 0.036), and ASA class ≥ 3 (aOR 1.6, P < 0.001) remained independent predictive factors for having a gynecologic oncology surgeon. CONCLUSIONS: The majority of gynecologic cancer cases are performed by gynecologic oncologists. Generalists are more likely to operate on minority patients and patients with fewer comorbidities. Further efforts to ensure access to specialized cancer care for all patients are needed.

Opioid use in gynecologic oncology in the age of the opioid epidemic: Part I - Effective opioid use across clinical settings, a society of gynecologic oncology evidence-based review.

As the only oncologists that provide both medical and surgical oncologic care, gynecologic oncologists encounter an exceptionally broad range of indications for prescribing opioids, from management of acute post-operative pain to chronic cancer-related pain to end-of-life care. If we are to balance opioid efficacy, safety and accessibility for our patients, we must be intimately familiar with appropriate clinical use of opioids in a range of settings, and engage in the national conversation around opioid misuse and how associated regulations and legislation may impact us and our patients. This article examines the appropriate use of opioids across the range of clinical settings encountered in gynecologic oncology.

Opioid use in gynecologic oncology in the age of the opioid epidemic: Part II - Balancing safety & accessibility.

As the only oncologists that provide both medical and surgical care, gynecologic oncologists encounter an exceptionally broad range of indications for prescribing opioids in clinical situations ranging from management of acute post-operative pain to chronic cancer-related pain to end-of-life care. While opioids are essential to the practice of gynecologic oncology, they can also have significant side effects and can be misused. Due to the explosive growth of opioid prescriptions and opioid-related overdoses and deaths during the first decade of the 21st century, there has been a recent concerted public health effort to prevent and treat opioid misuse through both legislation and education [1]. The first article in this two part series focused on appropriate use of opioids across clinical settings. This article addresses both the clinical and regulatory aspects of balancing opioid safety and accessibility for patients with gynecologic cancer.

Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome.

A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal.

Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia.

OBJECTIVE: Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. METHODS: A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. RESULTS: The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. CONCLUSIONS: Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients.

Relative Morbidity and Mortality of Panniculectomy-Combined Surgical Staging in Endometrial Cancer.

OBJECTIVE: To examine intraoperative and postoperative complication rates for surgical staging combined with panniculectomy for endometrial cancer. METHODS: A prospectively collected institutional surgical database was used to identify patients with endometrial cancer who underwent hysterectomy-based surgical staging between December 2008 and August 2014 (n = 551). The cases were grouped into surgical staging with panniculectomy (panniculectomy group, n = 11 [2.0%]), laparotomy without panniculectomy (laparotomy group, n = 208 [37.7%]), and laparoscopy (minimally invasive surgery group, n = 332 [60.3%]). Major complication and surgical wound complication rates within 30 days from surgery were compared. RESULTS: The panniculectomy group had a significantly higher body mass index compared with other approaches (panniculectomy group, laparotomy group, and minimally invasive surgery group: 60.4, 35.7, and 34.1; P < 0.001) and had a high stage I disease rate (90.9%, 61.5%, and 88.3%; P < 0.001). Mean pannus weight was 5733 g (4.4% of body weight). Intraoperative major complication rates were statistically nonsignificant across the groups (0%, 7.2%, and 4.2%; P = 0.23); however, the panniculectomy group had a significantly higher postoperative major complication rate compared with other approaches (36.4%, 16.3%, and 5.1%; P < 0.001). In multivariate analysis controlling for age, ethnicity, body habitus, medical comorbidities, and tumor factors, panniculectomy remained an independent predictor for increased risk of postoperative major complications (adjusted odds ratio, 4.37; P = 0.043). Surgical mortality rates were similar across the groups (0%, 0.5%, and 0%; P = 0.44). Among superobese patients (n = 50), intraoperative and postoperative complication rates were statistically similar across the 3 groups (all, P > 0.05). CONCLUSION: Although panniculectomy-combined surgical staging is associated with an increased risk of postoperative complications, the majority recovered uneventfully, making this approach a feasible treatment option, especially for superobese patients with endometrial cancer.