Standardization of caregiver and nursing perioperative care on gynecologic oncology wards in a resource-limited setting.

INTRODUCTION: In Kampala, Uganda, there is a strong cultural practice for patients to have designated caregivers for the duration of hospitalization. At the same time, nursing support is limited. This quality improvement project aimed to standardize caregiver and nursing perioperative care on the gynecologic oncology wards at the Uganda Cancer Institute and Mulago Specialised Women and Neonatal Hospital. METHODS: We developed, implemented, and evaluated a multidisciplinary intervention involving standardization of nursing care, patient education, and family member integration from October 2019 - July 2020. Data were abstracted from medical records and patient interviews pertaining to the following outcomes: 1) pain control; 2) post-operative surgical site infections, urinary tract infections, and pneumonia; 3) nursing documentation of medication administration, pain quality, and vital sign assessments, and 4) patient and caregiver education. Descriptive statistics, Fisher's exact test, and independent samples t-test were applied. RESULTS: Data were collected from 25 patients undergoing major gynecologic procedures. Pre- (N = 14) and post- (N = 11) intervention comparison demonstrated significant increases in preoperative patient education (0% to 80%, p = 0.001) and utilization of a comprehensive postoperative order form (0% to 45.5%, p = 0.009). Increased frequency in nursing documentation of patient checks (3 to 8, p = 0.266) and intraoperative antibiotic administration (9 to 10, p = 0.180) in patient charts did not reach significance. There was no change in infection rate, pain score utilization, caregiver documentation, or preoperative medication acquisition. CONCLUSION: Our findings suggest that patient- and family-centered perioperative care can be improved through standardization of nursing care, improved education, and integration of caregivers in a nursing-limited setting.

Factors associated with publication of plenary presentations at the Society of Gynecologic Oncologists annual meeting.

OBJECTIVE: To determine the rate and factors associated with publication of plenary abstract presentations from the Society of Gynecologic Oncologists annual meeting. METHODS: Plenary presentations were reviewed from 2000 to 2005. A PubMed search was performed to identify subsequent peer-reviewed publication of these presentations. Chi-squared test and logistic regression were used for statistical analyses. RESULTS: Of 378 main, focused or express plenary presentations, 173 (45.8%) involved multiple and 205 (54.2%) single institutions. The types of study include: chart review (29.4%), cohort study (28.0%), translational (23.5%), and randomized clinical trial (6.9%). 309 (81.7%) of presentations were subsequently published. The median time from presentation to publication was 14months (range: 1-85). Studies from multiple vs. single institutions were more likely to be published (87.9% vs. 76.6%; p=0.005). In addition, randomized controlled trials were more likely to be published compared with chart review, cohort, and translation research (92.3% vs. 83.8%, 77.4%, and 74.2%; p<0.01). On multivariate analysis, multi-institutional studies (OR=2.28, 95% CI=1.28-4.04; p=0.005) and type of study (OR=1.64, 95% CI=1.19-2.26; p=0.002) were independent factors associated with publication. In addition, multi-institutional studies had longer times from presentation to publication compared with their counterparts. CONCLUSIONS: A high percentage of plenary presentations at the Society of Gynecologic Oncologists annual meeting resulted in subsequent publication. Multi-institutional studies and randomized clinical trials were more likely to be published.

Utilization of and charges for robotic versus laparoscopic versus open surgery for endometrial cancer.

BACKGROUND AND OBJECTIVES: To analyze the utilization and hospital charges associated with robotic (RS) versus laparoscopic (LS) versus open surgery (OS) in endometrial cancer patients. METHODS: Hospital discharge data were extracted from Florida Agency for Health Care Administration between October 2008 and December 2009. RESULTS: Of 2,247 patients (median age: 64 years), 29% had RS, 10% had LS, and 61% had OS. The mean length of hospital stay was 1.6, 1.8, and 3.9 days for RS, LS, and OS, respectively (P < 0.001). The median hospital charge was $51,569, $37,202, and $36,492, for RS, LS, and OS (P < 0.001), with operating room charges ($22,600, $13,684, and $11,272) accounting for the major difference. Robotic surgery utilization increased by 11% (23-34%) over time. CONCLUSIONS: In this statewide analysis of endometrial cancer patients, the utilization of robotic surgery increased and is associated with higher hospital charges compared to laparoscopic and open procedures.

Stage I noninvasive and minimally invasive uterine serous carcinoma: comprehensive staging associated with improved survival.

OBJECTIVE: The aim of this study was to determine if comprehensive surgical staging is a better predictor of outcome than incomplete staging for women with stage I noninvasive or minimally invasive (≤3 mm) uterine serous carcinoma (USC). METHODS: Retrospective chart review was used to identify patients undergoing hysterectomy at the Johns Hopkins Hospital from 1989 to 2010. Relevant clinical and pathologic data were extracted. Patients with noninvasive and minimally invasive (≤3-mm myometrial invasion) USC were identified. Stage was assigned based on the 2009 International Federation of Gynecology and Obstetrics endometrial cancer criteria. Survival curves were generated using the Kaplan-Meier method. RESULTS: We identified 63 patients with noninvasive or minimally invasive (≤3 mm) USC. Stages I, II, III, and IV disease were noted in 65% (41/63), 6% (4/63), 14% (9/63), and 14% (9/63) of the patients, respectively. Lower stage was associated with a significantly improved disease-specific survival (P = 0.001). Comprehensive staging, including total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies, was completed in 29% (12/41) of the patients with stage I disease. There were no disease-specific deaths in the comprehensive staging group. Compared with incomplete staging, comprehensive staging was associated with a significantly improved disease-specific survival (P = 0.039). CONCLUSIONS: Patients with stage I noninvasive and minimally invasive USC on comprehensive staging have an excellent prognosis. Adjuvant therapy may not benefit this patient population.

Abnormal cervical cytology in the diagnosis of uterine papillary serous carcinoma: earlier detection of a poor prognostic cancer subtype?

OBJECTIVE: Early detection of uterine papillary serous (UPSC), clear cell (CCC), and grade 3 endometrioid carcinomas (G3EC) - all poor prognostic variants of endometrial carcinoma (EC) - is of particular clinical relevance. The study objective was to assess the utility of liquid-based cytology (Pap) in the detection of high-grade EC. STUDY DESIGN: A retrospective, two-institution analysis of patients diagnosed with UPSC, CCC, or G3EC with a preoperative Pap from 1999 to 2010 was conducted. RESULTS: One hundred and one patients were evaluated; 51.5% had UPSC, 27.7% had CCC, and 20.8% had G3EC. Stage I/II disease was found in 69.3% of patients, and 46/101 patients (45.5%) had abnormal Paps. Significantly more patients with UPSC had abnormal Paps (65.7%) than those with CCC (25%) or G3EC (23.8%; p < 0.001). An abnormal Pap was the only presenting clinical finding in a significant number of asymptomatic UPSC patients (26.9%) compared with 4% of patients with CCC and G3EC (p = 0.005). On multivariate analysis, UPSC histology was the only variable associated with an abnormal Pap. CONCLUSIONS: A high incidence of abnormal cervical cytology was observed in women with high-grade EC, particularly in UPSC patients. Although hypothesis generating, a proportion of asymptomatic UPSC patients had abnormal cytology, signifying that Pap smear screening may help detect the disease before the patient develops symptoms.

Analysis of postoperative complications associated with the use of anti-adhesion sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier after cytoreductive surgery for ovarian, fallopian tube and peritoneal cancers.

OBJECTIVE: To evaluate the risk of postoperative complications related to HA-CMC use in patients undergoing optimal cytoreductive surgery for primary and recurrent ovarian, fallopian tube, and peritoneal cancers. METHODS: A single institution retrospective review identified all patients undergoing optimal (≤1 cm) cytoreductive surgery for primary or recurrent ovarian, fallopian tube, and peritoneal cancers between 1/95 and 12/08. Operative details and post-operative complications (<30 days) were extracted from the medical record. Fisher's exact test, Mann-Whitney-U, and multiple regression analyses were performed to identify factors, including HA-CMC use, associated with post-operative complications. RESULTS: Three hundred seventy-five cases were analyzed: HA-CMC was utilized in 168 debulking procedures. There was no difference in the incidence of overall morbidity for patients with HA-CMC compared to those without HA-CMC (OR 1.07; 95% CI: 0.68-1.67). On univariate analysis, application of HA-CMC increased the risk of pelvic abscess (OR 2.66; 95% CI: 1.21-5.86), particularly in the primary surgery setting (OR 4.65; 95% CI: 1.67-12.98) and in patients undergoing hysterectomy (OR 3.36; 95% CI: 1.18-9.53). After controlling for confounding factors using multiple linear regression, HA-CMC use approached statistical significance in predicting an increased risk of pelvic abscess but not major postoperative morbidity. CONCLUSIONS: HA-CMC adhesion barrier placement at the time of optimal cytoreductive surgery for ovarian, fallopian tube, and peritoneal cancer is not associated with major postoperative complications but may be associated with increased risk of pelvic abscess.

Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas.

Our previous reports demonstrated that NAC1, a BTB/POZ domain-containing nuclear protein, upregulates in recurrent ovarian serous carcinoma and participates in developing drug resistance in cancer cells. The current study applies quantitative proteomics to identify the proteins controlled by NAC1 by comparing the proteomes of SKOV3 cells with and without expression of a dominant negative NAC1 construct, N130. From the proteins that are downregulated by N130 (upregulated by NAC1), we chose to further characterize fatty acid synthase (FASN). Similar to change in protein level, the FASN transcript level in SKOV3 cells was significantly reduced by N130 induction or by NAC1 knockdown. Immunohistochemistry showed that NAC1 and FASN immunointensities in ovarian serous carcinoma tissues had a highly significant correlation (P < .0001). Moreover, we found that recurrent serous carcinomas exhibited higher FASN immunointensities than their matched primary tumors (P < .001). Multivariate analysis showed that an FASN staining score of >1 in serous carcinomas was associated with a worse overall survival time (P < .01). Finally, C93, a new FASN inhibitor, induced massive apoptosis in carboplatin/paclitaxel resistant ovarian cancer cells. In conclusion, we show that NAC1 is essential for FASN expression in ovarian serous carcinomas and the expression of FASN significantly correlates with tumor recurrence and disease aggressiveness. The dependence of drug resistant tumor cells on FASN suggests a potential application of FASN-based therapeutics for recurrent ovarian cancer patients.

Trophoblastic neoplasms express fatty acid synthase, which may be a therapeutic target via its inhibitor C93.

Fatty acid synthase (FASN) is an emerging tumor-associated marker and a promising antitumor therapeutic target. In this study, we analyzed the expression of FASN in normal and molar placentas, as well as gestational trophoblastic neoplasia, and assessed the effects of a new FASN inhibitor, C93, on cellular proliferation and apoptosis in choriocarcinoma cells. Using a FASN-specific monoclonal antibody, we found that FASN immunoreactivity was detected in the cytotrophoblast and intermediate (extravillous) trophoblast of normal and molar placentas, as well as in placental site nodules. All choriocarcinomas (n = 33), 90% of epithelioid trophoblastic tumors (n = 20), and 60% of placental site trophoblastic tumors (n = 10) exhibited FASN positivity. FASN expression was further confirmed in vitro by Western blot and real-time PCR. Treatment of JEG3 and JAR cells with C93 induced significant apoptosis through the caspase-3/caspase-9/poly(ADP)ribose polymerase pathway. Cell cycle progression was not affected by the inhibitor. In summary, the data indicate that FASN is expressed in the majority of gestational trophoblastic neoplasias, and is essential for choriocarcinoma cells to survive and escape from apoptosis. FASN inhibitors such as C93 warrant further investigation as targeted therapeutic agents for metastatic and chemoresistant gestational trophoblastic neoplasia.

Cytoreductive surgery for advanced and recurrent endometrial cancer: a review of the literature.

There is no standard approach to managing women with advanced or recurrent endometrial cancer; however, there is increasing evidence to support a role for cytoreductive surgery in these women to improve survival outcome. The existing literature is limited by the inherent biases of retrospective studies, as well as small numbers of patients in individual studies; however, the association between optimal or complete cytoreductive surgery in patients with advanced and recurrent endometrial cancer and improved overall survival has been consistent. Furthermore, there is also a strong association between the size of postoperative residual disease and survival; as such, maximal cytoreduction should be the goal in carefully selected patients with advanced or recurrent endometrial cancer who are candidates for surgical management. Additional prospective research is needed in order to further define the role of cytoreductive surgery in advanced and recurrent endometrial cancer, and to develop effective adjuvant therapy to be used postoperatively in order to improve the prognosis in these women.

Analysis of phase II studies on targeted agents and subsequent phase III trials: what are the predictors for success?

PURPOSE: To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors. METHODS: We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models. RESULTS: Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial. CONCLUSION: In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.

Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths.

OBJECTIVE: The purpose of this study was to determine factors responsible for the increasing number of deaths from corpus cancer over three time periods. STUDY DESIGN: Data were collected from the Surveillance, Epidemiology and End Results database from 1988-2001. Kaplan-Meier and Cox proportional hazards regression analyses were performed. RESULTS: Of 48,510 women with corpus cancer, there was an increase in the proportion of patients dying from advanced cancers (52.1% to 56.0% to 68.8%; P < .001), grade 3 disease (47.5% to 53.3% to 60.6%; P < .001), serous tumors (14.3% to 18.4% to 16.6%; P < .001), and sarcomas (19.1% to 20.4% to 27.2%; P < .001) over time. On multivariate analysis, older age, African American race, lack of primary staging procedures, advanced-stage, high-grade, and non-endometrioid histology were independent prognostic factors for worse survival. CONCLUSION: Our data suggest that the increase in mortality in women with corpus cancer over the last 14 years may be related to an increased rate of advanced-stage cancers and high-risk histologies.