Endometrial Cancer Surgery With or Without Concomitant Stress Urinary Incontinence Surgery.

OBJECTIVE: To compare quality of life (QOL) among patients with endometrial intraepithelial neoplasia or early-stage endometrial cancer and stress urinary incontinence (SUI) who chose to have concomitant surgery with cancer surgery alone. METHODS: A multicenter, prospective cohort study was conducted across eight U.S. sites. Potentially eligible patients were screened for SUI symptoms. Those who screened positive were offered referral to urogynecology and incontinence treatment, including concomitant surgery. Participants were categorized into two groups: 1) concomitant cancer and SUI surgery or 2) cancer surgery alone. The primary outcome was cancer-related QOL as measured by the FACT-En (Functional Assessment of Cancer Therapy-Endometrial) (range 0-100; higher score indicates better QOL). The FACT-En and questionnaires assessing urinary symptom-specific severity and effects were assessed before surgery and 6 weeks, 6 months, and 12 months after surgery. Adjusted median regression accounting for clustering was used to examine the relationship between SUI treatment group and FACT-En scores. RESULTS: Of 1,322 (53.1%) patients, 702 screened positive for SUI with 532 analyzed; 110 (21%) chose concomitant cancer and SUI surgery, and 422 (79%) chose cancer surgery alone. FACT-En scores increased for both the concomitant SUI surgery and cancer surgery-only groups from the preoperative to the postoperative period. After adjustment for timepoint and preoperative covariates, the median change in FACT-En score (postoperative-preoperative) was 1.2 points higher (95% CI -1.3 to 3.6) for the concomitant SUI surgery group compared with the cancer surgery-only group across the postoperative period. Median time until surgery (22 days vs 16 days; P <.001), estimated blood loss (150 mL vs 72.5 mL; P <.001), and operative time (185.5 minutes vs 152 minutes; P <.001) were all greater for the concomitant cancer and SUI surgery group compared with the cancer-only group, respectively. CONCLUSION: Concomitant surgery did not result in improved QOL compared with cancer surgery alone for endometrial intraepithelial neoplasia and patients with early-stage endometrial cancer with SUI. However, FACT-En scores were improved in both groups.

Utilization of an Alternative Docetaxel-based Intraperitoneal Chemotherapy Regimen in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma: A Continued Need for Ovarian Cancer Patients.

OBJECTIVE: The objective of this study was to report the tolerability and toxicity of a regimen consisting of intravenous (IV) docetaxel and intraperitoneal (IP) cisplatin and paclitaxel with granulocyte colony-stimulating factor support. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients with surgical stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma treated with an outpatient IP chemotherapy regimen consisting of docetaxel 75 mg/m IV and cisplatin 75 mg/m IP day 1 followed by paclitaxel 60 mg/m IP day 8 every 21 days. Grade 3 and 4 toxicity, dose delays and reductions, port complications, and tolerability are reported. Outcomes, including response rate, progression-free survival (PFS), overall survival (OS) are also reported. RESULTS: A total of 60 patients received this IP regimen. Most common toxicities included neutropenia (47%), gastrointestinal (28%), and anemia (25%). Most patients (85%) experienced no IP port complications. Dose delay or reduction was required in 30% of patients. Two-thirds completed all prescribed cycles, with 80% of total planned cycles completed. Complete response was achieved for 88%, and 43% are currently without evidence of disease. Median PFS for all patients was 25.5 months (95% confidence interval [CI], 20.4-30.5 mo) while OS for all patients was 56.8 months (95% CI, 47.7-65.9 mo). For the 44 patients with stage III disease, median PFS was 22.1 months (95% CI, 16.3-28.0 mo), while median OS was 56.8 months (95% CI, 47.3-66.3 mo). CONCLUSIONS: This docetaxel-based IP chemotherapy regimen demonstrates an improved tolerability profile compared with GOG172. Additional evaluations on alternative IP regimens remain warranted. Short follow-up time limits survival assessment, but results are encouraging.

Vulvar Cancer as a Result of GATA2 Deficiency, a Rare Genetic Immunodeficiency Syndrome.

BACKGROUND: Vulvar cancer has become more prevalent, and its causes include chronic dermatoses and human papillomavirus (HPV)-mediated disease. Younger immunocompromised women can also be affected. We describe a case of vulvar carcinoma as a result of GATA2 deficiency. CASE: A 19-year-old woman presented to our gynecologic oncology clinic for management of a large vulvar mass. She was diagnosed with stage IB vulvar carcinoma after vulvectomy. GATA2 deficiency was the contributing factor causing vulvar carcinoma. CONCLUSION: GATA2 deficiency causes immunodeficiency in young women, and patients with early-onset HPV-related disease, a family or personal history of leukemia, recurrent infection, or immune irregularities should be screened. Health care providers for these women are often obstetrician-gynecologists, who can provide diagnosis, treatment, referral, and prevention of HPV-related diseases.

A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer.

Background: The glycolytic nature of cancer cells presents a potential treatment target that may be addressed by a ketogenic diet (KD). Objective: We hypothesized that a KD would improve body composition and lower serum insulin and insulin-like growth factor-I (IGF-I) in women with ovarian or endometrial cancer. Methods: In this randomized controlled trial, women with ovarian or endometrial cancer [age: ≥19 y; body mass index (kg/m2): ≥18.5] were randomly assigned to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS; high-fiber, low-fat). Body composition (DXA) and fasting serum insulin, IGF-I, and ß-hydroxybutyrate were obtained at baseline and at 12 wk; urinary ketones were also measured throughout the intervention. We assessed differences between the diets with ANCOVA and independent t tests. We used correlation analyses to estimate associations between changes in serum analytes and body composition. Results: After 12 wk, the KD (compared with ACS) group had lower adjusted total (35.3 compared with 38.0 kg, P < 0.05) and android (3.0 compared with 3.3 kg, P < 0.05) fat mass. Percentage of change in visceral fat was greater in the KD group (compared with the ACS group; -21.2% compared with -4.6%, P < 0.05). Adjusted total lean mass did not differ between the groups. The KD (compared with ACS) group had lower adjusted fasting serum insulin (7.6 compared with 11.2 µU/mL, P < 0.01). There was a significant inverse association between the changes in serum ß-hydroxybutyrate and IGF-I concentrations (r = -0.57; P < 0.0001). Conclusions: In women with ovarian or endometrial cancer, a KD results in selective loss of fat mass and retention of lean mass. Visceral fat mass and fasting serum insulin also are reduced by the KD, perhaps owing to enhanced insulin sensitivity. Elevated serum ß-hydroxybutyrate may reflect a metabolic environment inhospitable to cancer proliferation. This trial was registered at www.clinicaltrials.gov as NCT03171506.

Molecular Response to Neoadjuvant Chemotherapy in High-Grade Serous Ovarian Carcinoma.

While high-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants [by DNA next-generation sequencing (NGS) using a 50 gene Ion Torrent panel] and gene expression (using the NanoString PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n = 14) to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted, whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways.Implications: Gene expression profiles at the time of interval debulking provide additional genetic information that could help impact treatment decisions after NACT; although, continued collection and analysis of matched tumor and cfDNA from multiple time points are needed to determine the role of cfDNA in the management of HGSOC. Mol Cancer Res; 16(5); 813-24. ©2018 AACR.

Lay Patient Navigators' Perspectives of Barriers, Facilitators and Training Needs in Initiating Advance Care Planning Conversations With Older Patients With Cancer.

CONTEXT: Respecting Choices is an evidence-based model of facilitating advance care planning (ACP) conversations between health-care professionals and patients. However, the effectiveness of whether lay patient navigators can successfully initiate Respecting Choices ACP conversations is unknown. As part of a large demonstration project (Patient Care Connect [PCC]), a cohort of lay patient navigators underwent Respecting Choices training and were tasked to initiate ACP conversations with Medicare beneficiaries diagnosed with cancer. OBJECTIVES: This article explores PCC lay navigators' perceived barriers and facilitators in initiating Respecting Choices ACP conversations with older patients with cancer in order to inform implementation enhancements to lay navigator-facilitated ACP. METHODS: Twenty-six lay navigators from 11 PCC cancer centers in 4 states (Alabama, George, Tennessee, and Florida) completed in-depth, one-on-one semistructured interviews between June 2015 and August 2015. Data were analyzed using a thematic analysis approach. RESULTS: This evaluation identifies 3 levels-patient, lay navigator, and organizational factors in addition to training needs that influence ACP implementation. Key facilitators included physician buy-in, patient readiness, and navigators' prior experience with end-of-life decision-making. Lay navigators' perceived challenges to initiating ACP conversations included timing of the conversation and social and personal taboos about discussing dying. CONCLUSION: Our results suggest that further training and health system support are needed for lay navigators playing a vital role in improving the implementation of ACP among older patients with cancer. The lived expertise of lay navigators along with flexible longitudinal relationships with patients and caregivers may uniquely position this workforce to promote ACP.

Values and worries of ovarian cancer patients.

INTRODUCTION: Older women with ovarian cancer (OC) are less likely to receive guideline concordant treatment. Differences in values and worries about treatment may explain why. METHODS: Women with OC in 2013-2015 were surveyed about values and worries at the time of initial treatment. Existing values (11 item, e.g., maintaining quality of life) and worries (12 items, e.g., treatment side effects) scales were adapted based on OC literature. Responses were very/somewhat/a little/not at all important or worried. Principal Component Analyses (PCA) identified groups of values and worries that best explained scales' variation. We examined proportions reporting very/somewhat important/worried on ≥1 item in each component by age (older ≥65years, younger <65years). RESULTS: Of 170 respondents, 42.3% were older. PCA components for values were: functional well-being (3 survey items, proportion of variance explained [PoVE] 26.3%), length of life and sexual functioning (3 items, PoVE 20.1%), attitudes (3 items, PoVE 14.2%), and not becoming a burden (2 items, PoVE 13.7%). PCA components for worries were: economic (4 items, PoVE 27.2%), uncertainty (6 items, PoVE 26.0%), and family impact (2 items, PoVE 16.3%). Older women were less likely to indicate very/somewhat worried to ≥1 item in the economic (51.4% vs 72.4%, p=0.006), uncertainty (80.6% vs. 98.0%, p=0.001), and family impact component (55.6% vs. 70.4%, p=0.03). No other age differences were found. CONCLUSIONS: While worry during OC treatment decision-making may differ across age groups, values do not. Research should assess how differences in worry might affect OC medical decision-making for older and younger women.

Implementation and Impact of Patient Lay Navigator-Led Advance Care Planning Conversations.

CONTEXT: Advance care planning (ACP) improves alignment between patient preferences for life-sustaining treatment and care received at end of life (EOL). OBJECTIVES: To evaluate implementation of lay navigator-led ACP. METHODS: A convergent, parallel mixed-methods design was used to evaluate implementation of navigator-led ACP across 12 cancer centers. Data collection included 1) electronic navigation records, 2) navigator surveys (n = 45), 3) claims-based patient outcomes (n = 820), and 4) semistructured navigator interviews (n = 26). Outcomes of interest included 1) the number of ACP conversations completed, 2) navigator self-efficacy, 3) patient resource utilization, hospice use, and chemotherapy at EOL, and 4) navigator-perceived barriers and facilitators to ACP. RESULTS: From June 1, 2014 to December 31, 2015, 50 navigators completed Respecting Choices® First Steps ACP Facilitator training. Navigators approached 18% of patients (1319/8704); 481 completed; 472 in process; 366 declined. Navigators were more likely to approach African American patients than Caucasian patients (20% vs. 14%, P < 0.001). Significant increases in ACP self-efficacy were observed after training. The mean score for feeling prepared to conduct ACP conversations increased from 5.6/10 to 7.5/10 (P < 0.001). In comparison with patients declining ACP participation (n = 171), decedents in their final 30 days of life who engaged in ACP (n = 437) had fewer hospitalizations (46% vs. 56%, P = 0.02). Key facilitators of successful implementation included physician buy-in, patient readiness, and prior ACP experience; barriers included space limitations, identifying the "right" time to start conversations, and personal discomfort discussing EOL. CONCLUSION: A navigator-led ACP program was feasible and may be associated with lower rates of resource utilization near EOL.

IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

BACKGROUND: Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8+ T cell response in the omentum and peritoneal cavity. RESULTS: All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8+ T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with sterile phosphate buffer solution. CONCLUSION: Our pilot study demonstrates that an interleukin-12-expressing oncolytic herpes simplex virus effectively kills both murine and human ovarian cancer cell lines and promotes tumor antigen-specific CD8+ T-cell responses in the peritoneal cavity and omentum, leading to reduced peritoneal metastasis and improved survival in a mouse model.

Patient-centered support in the survivorship care transition: Outcomes from the Patient-Owned Survivorship Care Plan Intervention.

BACKGROUND: To the authors' knowledge, few studies to date have evaluated the effects of survivorship care planning on the care transition process from specialty cancer care to self-management and primary care, patient experience, or health outcomes. The Patient-owned Survivorship Transition Care for Activated, Empowered survivors (POSTCARE) is a single coaching encounter based on the Chronic Care Model that uses motivational interviewing techniques to engage survivors of breast cancer. The current study examined the effects of the POSTCARE intervention on patient outcomes and care coordination. METHODS: A total of 79 survivors of American Joint Commision on Cancer TNM System stage 0 to IIIB breast cancer were randomized to POSTCARE (40 patients) or usual care (39 patients). Patient outcomes were assessed using the 36-Item Short Form Health Survey (SF-36), Social/Role Activities Limitations, Self-Efficacy for Managing Chronic Disease 6-Item Scale, the Patient Activation Measure-Short Form, and Patient Health Questionnaire depression scale at baseline and at 3-month follow-up. Care coordination was assessed using confirmed primary care physician visits and reported discussion of the survivorship care plan at the 3-month follow-up. Logistic and linear regression analyses were conducted to examine the effect of POSTCARE on selected outcomes. RESULTS: Participants in the intervention group versus those receiving usual care demonstrated significantly higher self-reported health (F-statistic (3,71), 3.63; P =.017) and lower social role limitations (F (3,70), 3.82; P =.014) and a trend toward greater self-efficacy (F (3,69), 2.51; P = .07). Three quality-of-life domains reached clinically meaningful improvement at the 3-month follow-up, including physical role (P =.0009), bodily pain (P =.03), and emotional role (P =.04). CONCLUSIONS: The POSTCARE intervention appeared to have a positive impact on patient outcomes and demonstrated promise as a strategy with which to improve survivors' experience, care coordination, and health outcomes. Cancer 2016;122:3232-42. © 2016 American Cancer Society.

Improved outcomes with dose-dense paclitaxel-based neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma.

OBJECTIVE: We compared tolerability, toxicity, response, and interval debulking surgery (IDS) outcomes between patients who received weekly dose-dense paclitaxel (DDP) and every three-week platinum to standard every three-week taxane plus platinum neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC). METHODS: We conducted a retrospective study of patients receiving NACT at our center between June 1, 2012 and July 31, 2015. Patients with stage III/IV EOC who received at least one cycle of DDP (weekly paclitaxel plus every three-week carboplatin) or standard taxane (every three-week paclitaxel or docetaxel plus carboplatin) therapy were included. Abstracted data included demographics, tolerability, grade 3/4 toxicity, response, and IDS outcomes. Fisher's exact and student t-test were used for statistical significance. RESULTS: Twenty-one patients received DDP and 40 received standard taxane. Tolerability was comparable. More patients receiving DDP experienced grade 3 or 4 toxicity when considered in aggregate (86% vs. 40%; p=0.001). Pathologic complete response (pCR) was achieved in 14% of DDP patients versus 3% of standard (p=0.11). 48% of patients in the DDP group were debulked to no residual disease (NRD) versus 28% in the standard group (p=0.16). CONCLUSIONS: While associated with an increase in severe toxicity compared to standard three-week taxane, DDP appears to facilitate higher rates of pCR and NRD for patients receiving NACT in this preliminary study. These results warrant further investigation of DDP for patients with advanced EOC and assessment of impact on long-term survival outcomes.

Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients.

BACKGROUND: To compare the efficacy of chemotherapy (C) combined with bevacizumab (Bev) versus Bev alone in recurrent, heavily pretreated epithelial ovarian cancer (EOC). METHODS: A multicenter analysis of patients treated from 2004 to 2011 was performed. Demographic, treatment, response, and adverse event information were obtained. Progression-free (PFS) and overall survival (OS) were analyzed. RESULTS: Of 277 patients (median age: 58years), the majority had Stage III and IV (86%) disease, and 72% had serous histology. 244 (88%) were treated with C+Bev and 33 (12%) with Bev. Corresponding median progression-free survival (PFS) was 8.7 and 6.7months, and median overall survival (OS) was 14.3 and 10.5months, respectively. The chemotherapeutic agents combined with Bev and the median OS include: pegylated liposomal doxorubicin (n=19, OS of 20.4months), taxanes (n=55, OS of 20.2months), gemcitabine (n=106, OS of 14.1months), topotecan (n=43, OS of 13months), and cyclophosphamide (n=21, OS of 13months). There was no significant difference in toxicities between the C+Bev vs. Bev alone group. CONCLUSION: This retrospective analysis supports that combination chemotherapy and bevacizumab prolongs PFS and OS compared with bevacizumab alone.

Combination therapy with paclitaxel, carboplatin and megestrol acetate for the management of advanced stage or recurrent carcinoma of the endometrium: a phase II study.

OBJECTIVE: To determine overall survival (OS), progression-free interval (PFI), and toxicity in patients with advanced stage or recurrent endometrial cancer (EMCA) treated with combination paclitaxel, carboplatin and megestrol acetate. STUDY DESIGN: Patients with stage III/IV or recurrent EMCA were enrolled between October 2004 and April 2008 and received paclitaxel (175 mg/m2) and carboplatin (AUC 6) every 21 days for 6 cycles and megestrol acetate 40 mg orally 4 times daily for up to 5 years. Dose reductions were based on grade 3/4 hematologic toxicity. Survival was calculated from time of study enrollment. RESULTS: A total of 28 patients were evaluable: 21 (75%) patients with stage III/IV disease and 7 (25%) with recurrent disease. Three patients with recurrence received prior radiation. Mean PFI was 40.2 months (29.7-50.6). Mean OS was 50.1 months (41.5-58.7). After a median 40.4 months (range, 5.6-68.4) of follow-up, 13 patients (46%) had no evidence of disease, 4 were alive with disease, and 10 were dead of disease. One patient died without evidence of disease. Twenty-three patients (82%) completed 6 cycles of chemotherapy. Ten patients experienced a dose reduction. Myelosuppression was common, with 22 patients (78%) experiencing grade 3/4 neutropenia and 6 patients (21%) experiencing grade 3/4 anemia. Three patients had a deep vein thrombosis. One patient experienced a pulmonary thromboembolus. CONCLUSION: Combination therapy with paclitaxel, carboplatin and megestrol acetate demonstrates activity. Myelosuppression is common but can be managed with colony-stimulating factors. The addition of hormonal therapy to cytotoxic chemotherapy may improve survival.

Comparison of operative risks associated with radical hysterectomy in pregnant and nonpregnant women.

OBJECTIVE: To compare the operative data and complications of radical hysterectomy performed on pregnant women versus nonpregnant women. STUDY DESIGN: Following institutional review board approval, we reviewed our surgical databases to identify pregnant women who had undergone a radical hysterectomy for cervical carcinoma from 1992-2005 (n = 7). A nonpregnant control group (n = 35) of women undergoing radical hysterectomy during the study interval were identified and matched for age, year of surgery, and surgeon. Pertinent operative and outcome data were abstracted and compared. RESULTS: Of the 7 women who had undergone a radical hysterectomy during pregnancy, 4 had a cesarean radical hysterectomy at a mean gestational age of 35.4 weeks (range, 32.3-38 weeks) and 3 had a radical hysterectomy with a previable fetus in situ at a mean gestational age of 14.2 weeks. Demographics were similar between groups. Transfusion rates were significantly higher among pregnant women (57%) as compared to nonpregnant controls (9%) (p = 0.0009). The overall incidence of operative complications was similar between the pregnant women (43%) and nonpregnant controls (40%) (p = NS). CONCLUSION: Radical hysterectomy performed in pregnant women was associated with higher blood loss and increased need for transfusion as compared to nonpregnant controls. No differences were observed in regards to other operative surgical complications between the two groups.

Vulvar histoplasmosis as a rare cause of genital ulceration.

BACKGROUND: Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum and primarily presents with pulmonary symptoms. Immunocompromised individuals are at high risk for contracting disseminated histoplasmosis, which can be fatal if left untreated. CASE: We present a case involving a 50-year-old woman with acquired immunodeficiency syndrome with an ulcerated vulvar lesion concerning for carcinoma. Extensive workup revealed disseminated histoplasmosis without pulmonary manifestations. She was treated with an extended course of an antifungal agent. Her vulvar lesion resolved. CONCLUSION: Vulvar histoplasmosis is a rare etiology of vulvar pathology but one that should be considered in immunocompromised patients.

Incidence of port site hernias and/or dehiscence in robotic-assisted procedures in gynecologic oncology patients.

OBJECTIVES: The incidence of port site hernia and/or dehiscence using bladeless trocars is 0-1.2%. Robotic surgery uses additional port sites and increases manipulation of instruments, raising the concern for more complications. We sought to characterize the incidence of port site complications following robotic surgery when fascia was not routinely closed. METHODS: Robotically-assisted (RA) procedures performed for suspected gynecologic malignancy between 1/2006 and 12/2011 were retrospectively reviewed. Bladeless 12 mm and 8mm robotic trocars were used. Fascial closure was not routinely performed except after specimen removal through the port site. The decision to close the fascia remained at the discretion of the surgeon. RESULTS: Data from 842 procedures were included. Mean patient age was 55.6 years. Mean Body Mass Index was 33.6 kg/m(2). RA-total laparoscopic hysterectomy (TLH)± unilateral or bilateral salpingo-oophorectomy (BSO)± lymphadenectomy (LND) accounted for 91.6% of procedures. Final pathology confirmed malignancy in 58.6% of cases, primarily endometrial cancer. In 35 cases, the specimen was removed through the port site; fascia was closed in 54.3% of them and no port site hernias or dehiscences occurred. Only one patient underwent a RA-TLH/BSO/LND for endometrial adenocarcinoma and had a port site dehiscence of the 8mm trocar site. No port site hernias occurred. CONCLUSION: Port site hernias and dehiscences are rare in RA gynecologic oncology procedures. When bladeless dilating trocars are used, routine closure of even up to a 12 mm port site is unnecessary, even in cases requiring removal of the specimen through the trocar sites.

The effect of the APPRISE mandate on use of erythropoiesis-stimulating agents and transfusion rates in patients with ovarian cancer receiving chemotherapy.

OBJECTIVE: Erythropoiesis-stimulating agents (ESAs) support chemotherapy-induced anemia in patients with epithelial ovarian cancer (EOC). In response to research demonstrating that ESAs increase tumor growth and shorten survival, the Food and Drug Administration mandated the new APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) guidelines for consenting patients before ESAs administration. We sought to quantify the change in ESA and red blood cell (RBC) transfusion use after the APPRISE mandate was instituted. METHODS/MATERIALS: After institutional review board approval, a retrospective chart review compared patients with EOC undergoing chemotherapy before and after the APPRISE mandate. Abstracted data included patient demographics, chemotherapy treatment status and regimen, and number of patients requiring ESAs or RBCs. A cost savings analysis was also performed. RESULTS: Eighty-four patients who underwent 367 cycles of chemotherapy after the APPRISE guidelines were compared with a matched set of 88 patients receiving 613 cycles of chemotherapy before the APPRISE guidelines. There were no statistically significant differences between the groups. Most patients had advanced stage disease and received primary taxane-/platinum-based chemotherapy. Of 88 patients, 45 (51%) in the pre-APPRISE group received a total of 196 ESA injections compared with 0 patients in the post-APPRISE group. Red blood cell transfusion in the post-APPRISE group was similar to that in the pre-APPRISE group (8.3% vs 14.8%, P = 0.28). Omission of ESAs in the post-APPRISE group resulted in a roughly $700,000 savings in billable charges. CONCLUSIONS: In our institution, the APPRISE guidelines have resulted in complete cessation of the use of ESAs in patients with primary or recurrent EOC, resulting in considerable cost savings. Importantly, RBC transfusion rates did not significantly increase after the guidelines were imposed.

Smoothened antagonists reverse taxane resistance in ovarian cancer.

The hedgehog pathway has been implicated in the formation and maintenance of a variety of malignancies, including ovarian cancer; however, it is unknown whether hedgehog signaling is involved in ovarian cancer chemoresistance. The goal of this study was to determine the effects of antagonizing the hedgehog receptor, Smoothened (Smo), on chemotherapy response in ovarian cancer. Expression of hedgehog pathway members was assessed in three pairs of parental and chemotherapy-resistant ovarian cancer cell lines (A2780ip2/A2780cp20, SKOV3ip1/SKOV3TRip2, HeyA8/HeyA8MDR) using quantitative PCR and Western blot analysis. Cell lines were exposed to increasing concentrations of two different Smo antagonists (cyclopamine, LDE225) alone and in combination with carboplatin or paclitaxel. Selective knockdown of Smo, Gli1, or Gli2 was achieved using siRNA constructs. Cell viability was assessed by MTT assay. A2780cp20 and SKOV3TRip2 orthotopic xenografts were treated with vehicle, LDE225, paclitaxel, or combination therapy. Chemoresistant cell lines showed higher expression (>2-fold, P < 0.05) of hedgehog signaling components compared with their respective parental lines. Smo antagonists sensitized chemotherapy-resistant cell lines to paclitaxel, but not to carboplatin. LDE225 treatment also increased sensitivity of ALDH-positive cells to paclitaxel. A2780cp20 and SKOV3TRip2 xenografts treated with combined LDE225 and paclitaxel had significantly less tumor burden than those treated with vehicle or either agent alone. Increased taxane sensitivity seems to be mediated by a decrease in P-glycoprotein (MDR1) expression. Selective knockdown of Smo, Gli1, or Gli2 all increased taxane sensitivity. Smo antagonists reverse taxane resistance in chemoresistant ovarian cancer models, suggesting combined anti-hedgehog and chemotherapies could provide a useful therapeutic strategy for ovarian cancer.

Stem cell pathways contribute to clinical chemoresistance in ovarian cancer.

PURPOSE: Within heterogeneous tumors, subpopulations often labeled cancer stem cells (CSC) have been identified that have enhanced tumorigenicity and chemoresistance in ex vivo models. However, whether these populations are more capable of surviving chemotherapy in de novo tumors is unknown. EXPERIMENTAL DESIGN: We examined 45 matched primary/recurrent tumor pairs of high-grade ovarian adenocarcinomas for expression of CSC markers ALDH1A1, CD44, and CD133 using immunohistochemistry. Tumors collected immediately after completion of primary therapy were then laser capture microdissected and subjected to a quantitative PCR array examining stem cell biology pathways (Hedgehog, Notch, TGF-ß, and Wnt). Select genes of interest were validated as important targets using siRNA-mediated downregulation. RESULTS: Primary samples were composed of low densities of ALDH1A1, CD44, and CD133. Tumors collected immediately after primary therapy were more densely composed of each marker, whereas samples collected at first recurrence, before initiating secondary therapy, were composed of similar percentages of each marker as their primary tumor. In tumors collected from recurrent platinum-resistant patients, only CD133 was significantly increased. Of stem cell pathway members examined, 14% were significantly overexpressed in recurrent compared with matched primary tumors. Knockdown of genes of interest, including endoglin/CD105 and the hedgehog mediators Gli1 and Gli2, led to decreased ovarian cancer cell viability, with Gli2 showing a novel contribution to cisplatin resistance. CONCLUSIONS: These data indicate that ovarian tumors are enriched with CSCs and stem cell pathway mediators, especially at the completion of primary therapy. This suggests that stem cell subpopulations contribute to tumor chemoresistance and ultimately recurrent disease.

Cervical conization and the risk of preterm delivery.

The current body of literature concerning cervical conization and its effect on subsequent pregnancy outcome is conflicting. Depending on the type of conization procedure that is examined and the quality of the control group, the results and conclusions vary widely. Because treatment for cervical intraepithelial neoplasia is commonplace among women of reproductive age, it is imperative that practitioners have an understanding of the issues surrounding the treatment. Therefore, this review will summarize the published literature that addresses excisional procedures of the uterine cervix and the risk of preterm delivery in subsequent pregnancies and provide reasonable treatment recommendations for women with cervical abnormalities and a desire for future fertility.