Lisa Barroilhet

PET/CT and MRI in the imaging assessment of cervical cancer.

Imaging plays a central role in the evaluation of patients with cervical cancer and helps guide treatment decisions. The purpose of this pictorial review is to describe magnetic resonance (MR) imaging and positron emission tomography (PET)/computed tomography (CT) assessment of cervical cancer, including indications for imaging, important findings that may result in management change, as well as limitations of both modalities. The International Federation of Gynecology and Obstetrics cervical cancer staging system does not officially include imaging; however, the organization endorses the use of MR imaging and PET/CT in the management of patients with cervical cancer where these modalities are available. MR imaging provides the best visualization of the primary tumor and extent of soft tissue disease. PET/CT is recommended for assessment of nodal involvement, as well as distant metastases. Both MR imaging and PET/CT are used to follow patients post-treatment to assess for recurrence. This review focuses on the current MR imaging and PET/CT protocols, the utility of these modalities in assessing primary tumors and recurrences, with emphasis on imaging findings which change management and on imaging pitfalls to avoid. It is important to be familiar with the MR imaging and PET/CT appearance of the primary tumor and metastasis, as well as the imaging pitfalls, so that an accurate assessment of disease burden is made prior to treatment.

Robotic surgery for early stage cervical cancer: Evolution and current trends.

The management of early stage cervical cancer often includes surgery in the form of radical hysterectomy, radical trachelectomy, or radical parametrectomy. Surgical techniques have evolved to include minimal invasive approaches, and more recently, to include robotic assisted techniques. This review highlights the evolution of surgical management of early cervical cancer and specifically explores robotic assisted radical hysterectomy, radical trachelectomy, radical parametrectomy, and the role of neoadjuvant chemotherapy. J. Surg. Oncol. 2015;112:772–781.

Site-specific factors for cancer of the corpus uteri from SEER registries: Collaborative stage data collection system, version 1 and version 2

Uterine cancer is the fourth leading cancer among US women. Changes in uterine cancer staging were made from the American Joint Committee on Cancer (AJCC) 6th to 7th edition staging manuals, and 8 site‐specific factors (SSFs) and 3 histologic schemas were introduced. Carcinomas account for 95% of cases and are the focus of this report.

Alternatively-Activated Macrophages Upregulate Mesothelial Expression of P-Selectin to Enhance Adhesion of Ovarian Cancer Cells

Peritoneal metastasis of high-grade serous ovarian cancer (HGSOC) occurs when tumor cells suspended in ascites adhere to mesothelial cells. Despite the strong relationship between metastatic burden and prognosis in HGSOC, there are currently no therapies specifically targeting the metastatic process. We utilized a coculture model and multivariate analysis to examine how interactions between tumor cells, mesothelial cells, and alternatively-activated macrophages (AAM) influence the adhesion of tumor cells to mesothelial cells. We found that AAM-secreted MIP-1β activates CCR5/PI3K signaling in mesothelial cells, resulting in expression of P-selectin on the mesothelial cell surface. Tumor cells attached to this de novo P-selectin through CD24, resulting in increased tumor cell adhesion in static conditions and rolling underflow. C57/BL6 mice treated with MIP-1β exhibited increased P-selectin expression on mesothelial cells lining peritoneal tissues, which enhanced CaOV3 adhesion ex vivo and ID8 adhesion in vivo Analysis of samples from patients with HGSOC confirmed increased MIP-1β and P-selectin, suggesting that this novel multicellular mechanism could be targeted to slow or stop metastasis in HGSOC by repurposing anti-CCR5 and P-selectin therapies developed for other indications.Significance: This study reports novel insights on the peritoneal dissemination occurring during progression of ovarian cancer and has potential for therapeutic intervention.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3560/F1.large.jpg Cancer Res; 78(13); 3560-73. ©2018 AACR.

The Feasibility and Safety of Adopting Single-Incision Laparoscopic Surgery into Gynecologic Oncology Practice

STUDY OBJECTIVE To determine the complications associated with single-incision laparoscopy in gynecologic oncology surgery. DESIGN A retrospective cohort (Canadian Task Force classification II-3). SETTING A single academic institution. PATIENTS One hundred fifteen consecutive patients undergoing single-incision laparoscopy with suspected gynecologic oncology conditions. INTERVENTIONS Single-incision laparoscopy. MEASUREMENTS AND MAIN RESULTS One hundred fifteen patients underwent single-incision laparoscopy. The mean age was 55.3 ± 13.1 years. For procedures completed via single-incision laparoscopy (102/115 [88.7%]), the mean operative time was 130.7 ± 55.5 minutes. The average blood loss was 63 ± 111 mL. The conversion to open rate was 13 of 115 (12.17%). The conversion rate of the 55 patients with benign conditions was lower (2/55 [3.64%]) compared with the 60 patients with malignant conditions (11/60 [18.33%]). The hernia rate was 2 of 115 (1.80%), 1 of which was a recurrent hernia. The median time for follow-up was 30 days (range, 5-653 days). CONCLUSION Single-incision laparoscopy provides a feasible, safe, and promising minimally invasive modality for treating gynecologic oncology patients.

Oxidative stress via inhibition of the mitochondrial electron transport and Nrf-2-mediated anti-oxidative response regulate the cytotoxic activity of plumbagin

Plumbagin, an anti-cancer agent, is toxic to cells of multiple species. We investigated if plumbagin targets conserved biochemical processes. Plumbagin induced DNA damage and apoptosis in cells of diverse mutational background with comparable potency. A 3–5 fold increase in intracellular oxygen radicals occurred in response to plumbagin. Neutralization of the reactive oxygen species by N-acetylcysteine blocked apoptosis, indicating a central role for oxidative stress in plumbagin-mediated cell death. Plumbagin docks in the ubiquinone binding sites (Q0 and Qi) of mitochondrial complexes I–III, the major sites for oxygen radicals. Plumbagin decreased oxygen consumption rate, ATP production and optical redox ratio (NAD(P)H/FAD) indicating interference with electron transport downstream of mitochondrial Complex II. Oxidative stress induced by plumbagin triggered an anti-oxidative response via activation of Nrf2. Plumbagin and the Nrf2 inhibitor, brusatol, synergized to inhibit cell proliferation. These data indicate that while inhibition of electron transport is the conserved mechanism responsible for plumbagin’s chemotoxicity, activation of Nrf2 is the resulting anti-oxidative response that allows plumbagin to serve as a chemopreventive agent. This study provides the basis for designing potent and selective plumbagin analogs that can be coupled with suitable Nrf2 inhibitors for chemotherapy or administered as single agents to induce Nrf2-mediated chemoprevention.

Indeterminate Adnexal Cysts at US: Prevalence and Characteristics of Ovarian Cancer

Purpose To assess the prevalence of indeterminate adnexal cysts in women presenting to academic medical centers for pelvic ultrasonography (US), determine the incidence of malignancy, and identify cyst and patient characteristics that are predictive of malignancy. Materials and Methods A multicenter study of US-detected adnexal cysts with appropriate follow-up (surgical pathologic examination, imaging and/or clinical examination) was conducted from January 2008 to June 2012. Indeterminate cysts were classified as category 1 (typical benign appearing cysts >5 cm) or category 2 (cysts with avascular solid components) on the basis of a combination of definitions in the existing literature. The incidence of neoplasms and malignant tumors was calculated. Patient and cyst characteristics associated with neoplasm and malignant tumors were evaluated with the χ2 test or Fisher exact test for categorical variables and the t test for continuous variables. A backward stepwise logistic regression model was performed for two outcomes: (a) the presence of any neoplasm (benign or malignant) and (b) the presence of a malignant tumor. Results There were 1637 women with an adnexal cyst at US; 391 (mean age = 41.8 years ± 13.5.1; range = 17-91 years) had an indeterminate adnexal cyst at US. The prevalence of indeterminate adnexal cysts was 23.9% (391 of 1637; 95% confidence interval [CI]: 0.22, 0.26). Three hundred three indeterminate cysts in 280 women (mean age = 42.9 years ± 14.1; range = 17-88 years) had adequate follow-up. The incidence of ovarian neoplasms (benign and malignant) was 24.8% (75 of 303 cysts; 95% CI: 0.20, 0.30), and the incidence of malignant tumors was 3.6% (11 of 303 cysts; 95% CI: 0.02, 0.06). The proportion of ovarian neoplasms differed between category 1 and category 2 cysts (17.5% [25 of 143 cysts; 95% CI: 0.12, 0.25] vs 31.3% [50 of 160 cysts; 95% CI: 0.24, 0.39], respectively; P = .001). The proportion of malignant tumors differed between categories 1 and 2 cysts (0% [0 of 143 cysts] vs 6.9% [11 of 160 cysts; 95% CI: 0.03, 0.12]; P < .001). The presence of an avascular nodular component was a significant predictor of malignancy at stepwise logistic regression analysis (odds ratio = 2.83; P ≤ .0001; 95% CI: 1.69, 4.70). Conclusion The presence of an avascular nodular component was the most significant predictor of the presence of malignancy in indeterminate adnexal cysts. The risk of malignancy is higher with category 2 cysts than with category 1 cysts.

Neoadjuvant chemotherapy is associated with more anemia and perioperative blood transfusions than primary debulking surgery in women with advanced stage ovarian cancer

OBJECTIVE The purpose of this case-controlled study was to determine the prevalence of anemia and incidence of perioperative blood transfusions in patients undergoing treatment for advanced ovarian cancer with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS). METHODS We performed a single institution review of patients diagnosed with stage IIIB-IVB epithelial ovarian cancer between 2010 and 2013 undergoing either NACT or PDS. Anemia was defined as a hemoglobin (Hgb) concentration of ≤11.5 g/dL. Continuous variables were compared by student t-test and binary variables compared via chi square analysis. RESULTS One hundred thirty-one women were included, 66 treated with NACT and 65 treated with PDS. Average Hgb prior to surgery was lower in women who received NACT (10.7 g/dL vs 12.8 g/dL, p < 0.0001). Women treated with NACT had a decrease in mean Hgb during chemotherapy treatment (11.8 g/dL at diagnosis to 10.7 g/dL preoperatively). Seventy-seven percent of NACT patients were anemic prior to surgery compared to 15% of patients prior to PDS (p < 0.001). Mean EBL at debulking was higher in patients selected for PDS (871 mL) than NACT (544 mL); however, the perioperative transfusion rate was higher during interval debulking surgeries (NACT 77% vs PDS 56%, p = 0.01). CONCLUSION Women selected for NACT were more likely to be anemic at diagnosis and became progressively anemic during NACT. Despite less blood loss during debulking surgery, NACT patients receive more blood transfusions perioperatively than patients undergoing PDS. This represents a potential opportunity for therapeutic intervention during NACT to correct anemia prior to interval debulking surgery.

Peri-operative allogeneic blood transfusion is associated with poor overall survival in advanced epithelial ovarian Cancer; potential impact of patient blood management on Cancer outcomes

BACKGROUND Transfusion related immune modulation associated with red blood cell (RBC) transfusion is thought to result in decreased cancer survival. Results in epithelial ovarian cancer (EOC) have been mixed however most suggest worse oncologic outcomes in patients who were transfused at the time of debulking surgery. The impact of restrictive transfusion strategies on this patient population is currently not known. METHODS We conducted a retrospective study of women with EOC. The study population was divided into two groups based on whether they were transfused RBCs during the peri-operative period or not. Clinical characteristics and prognosticators were compared between groups. Overall survival was compared between groups based on transfusion status and other known prognostic factors. Cox proportional hazard modeling was used to examine the association between the prognostic factors and the study endpoint. RESULTS Sixty-six percent of women were transfused. Transfusion was associated with CA125, the use of neoadjuvant chemotherapy (NACT), surgical blood loss, and anemia. The mean pre-transfusion Hgb was 7.8 + 0.6 g/dL and 94% had a hemoglobin level greater than the transfusion threshold of 7 g/dL. RBC transfusion, suboptimal debulking, anemia, and NACT were associated with decreased survival. Only RBC transfusion and suboptimal debulking status remained significant in a multivariate model. CONCLUSIONS Peri-operative RBC transfusion compromises survival in ovarian cancer supporting the need to minimize the use of transfusion at the time of debulking surgery. Adherence to evidence-based transfusion guidelines offers an opportunity to reduce transfusion rates in this population with a resulting positive influence on survival.

MR Imaging of Cervical Cancer

Cervical cancer is a significant cause of morbidity and mortality worldwide despite advances in screening and prevention. Although cervical cancer remains clinically staged, the 2009 International Federation of Gynecology and Obstetrics committee has encouraged the use of advanced imaging modalities, including MR imaging, where available, to increase the accuracy of staging, guide treatment, and detect recurrence. Understanding the multiple roles of advanced imaging in the evaluation of cervical cancer will help radiologists provide an accurate and useful report to the referring clinicians.