William M. Burke

Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells

Signal transducers and activators of transcription (STATs) are transcription factors activated in response to cytokines and growth factors. Constitutively active Stat3 has been shown to mediate oncogenic transformation in cultured cells and induce tumor formation in mice. An increasing number of tumor-derived cell lines as well as samples from human cancer have been reported to express constitutively active Stat3 protein. We previously demonstrated that ovarian cancer cell lines express high levels of constitutively active Stat3. In this study, we show that inhibition of the Stat3 signaling pathway using the Janus Kinase-selective inhibitor, AG490, and a dominant negative Stat3 (Stat3β) significantly suppresses the growth of ovarian and breast cancer cell lines harboring constitutively active Stat3. In the ovarian cancer cell lines, AG490 also diminished the phosphorylation of Stat3, Stat3 DNA binding activity, and the expression of Bcl-xL. Further, AG490 induced significant apoptosis in ovarian and breast cancer cell lines expressing high levels of constitutively active Stat3 but had a less profound effect on normal cells lacking constitutively active Stat3. AG490 also enhanced apoptosis induced by cisplatin in ovarian cancer cells. These results suggest that inhibition of Stat3 signaling may provide a potential therapeutic approach for treating ovarian and breast cancers.

Preliminary Experience with Robot-Assisted Laparoscopic Myomectomy

The following retrospective case series evaluated the technique and feasibility of integrating robot-assisted technology in the performance of a laparoscopic myomectomy in order to overcome the limitations of conventional laparoscopy. We attempted 35 robot-assisted laparoscopic myomectomies in a university hospital setting with a conversion rate of 8.6%. There were a total of 48 myomas removed in 31 patients with completed robot-assisted laparoscopy. The mean number of myomas removed/patient was 1.6 (range 1-5). The mean diameter of myomas removed was 7.9 +/- 3.5 cm (95% CI 6.63-9.13), with the majority greater than 5 cm. The mean myoma weight was 223.2 +/- 244.1 g (95% CI 135.8-310.6). Mean operating time was 230.8 +/- 83 minutes (95% CI 201.6-260). The average estimated blood loss was 169 +/- 198.7 mL (95% CI 99.1-238.4). One patient experienced cardiogenic shock from vasopressin, two developed postoperative infections, and one was found to have adenomatous adenomyosis instead of a leiomyoma. The median length of hospital stay was 1 day. Overall, robot-assisted laparoscopic myomectomy is a promising new technique that may overcome many of the surgical limitations of conventional laparoscopy.

Endometrioma Complicated by Tubo-Ovarian Abscess in a Woman With Bacterial Vaginosis

Background. Tubo-ovarian abscess involvement of an endometrioma has been reported in cases of patients with polymicrobial sources such as Neisseria gonorrhoeae, Chlamydia trachomatis, and obligate anaerobic bacteria; however, bacterial vaginosis (BV) predisposing to abscess formation in an endometrioma has not been reported to date. Case. Superinfection of an endometrioma was surgically diagnosed in a patient with known advanced-stage endometriosis after she presented with acute pelvic inflammatory disease symptoms and was unresponsive to antibiotic therapy. Gram-negative rods were cultured from the endometrioma. On admission, cervical, blood, and urine cultures were negative; BV was diagnosed on normal saline wet prep and gram stain. Conclusion. This case raises the possibility of BV ascension to the upper genital tract predisposing to abscess formation in endometriomas. Therefore, aggressive treatment of BV in patients with known advanced-stage endometriosis may be considered to prevent superinfected endometriomas.

Association of Hospital Volume and Quality of Care With Survival for Ovarian Cancer

OBJECTIVE To assess whether strict adherence to quality metrics by hospitals could explain the association between hospital volume and survival for ovarian cancer. METHODS We used the National Cancer Database to perform a retrospective cohort study of women with ovarian cancer from 2004 to 2013. Hospitals were stratified by annual case volume into quintiles (2 or less, 2.01-5, 5.01-9, 9.01-19.9, 20 cases or greater) and by adherence to ovarian cancer quality metrics into quartiles. Hospital-level adjusted 2- and 5-year survival rates were compared based on volume and adherence to the quality metrics. RESULTS A total of 100,725 patients at 1,268 hospitals were identified. Higher volume hospitals were more likely to adhere to the quality metrics. Both 2- and 5-year survival increased with hospital volume and with adherence to the measured quality metrics. For example, 2-year survival increased from 64.4% (95% CI 62.5-66.4%) at low-volume to 77.4% (95% CI 77.0-77.8%) at high-volume centers and from 66.5% (95% CI 65.5-67.5%) at low-quality to 77.3% (95% CI 76.8-77.7%) at high-quality hospitals (P<.001 for both). For each hospital volume category, survival increased with increasing adherence to the quality metrics. For example, in the lowest volume hospitals (two or less cases annually), adjusted 2-year survival was 61.4% (95% CI 58.4-64.5%) at hospitals with the lowest adherence to quality metrics and rose to 65.8% (95% CI 61.2-70.8%) at the hospitals with highest adherence to the quality metrics (P<.001). However, lower volume hospitals with higher quality scores still had survival that was lower than higher volume hospitals. CONCLUSION Although both hospital volume and adherence to quality metrics are associated with survival for ovarian cancer, low-volume hospitals that provide high-quality care still have survival rates that are lower than high-volume centers.

Practice Patterns, Attitudes, and Barriers to Palliative Care Consultation by Gynecologic Oncologists

PURPOSE We sought to describe practice patterns, attitudes, and barriers to the integration of palliative care services by gynecologic oncologists. METHODS Members of the Society of Gynecologic Oncology were electronically surveyed regarding their practice of incorporating palliative care services and to identify barriers for consultation. Descriptive statistics were used, and two-sample z-tests of proportions were performed to compare responses to related questions. RESULTS Of the 145 respondents, 71% were attending physicians and 58% worked at an academic medical center. The vast majority (92%) had palliative care services available for consultation at their hospital; 48% thought that palliative care services were appropriately used, 51% thought they were underused, and 1% thought they were overused. Thirty percent of respondents thought that palliative care services should be incorporated at first recurrence, whereas 42% thought palliative care should be incorporated when prognosis for life expectancy is ≤ 6 months. Most participants (75%) responded that palliative care consultation is reasonable for symptom control at any stage of disease. Respondents were most likely to consult palliative care services for pain control (53%) and other symptoms (63%). Eighty-three percent of respondents thought that communicating prognosis is the primary teams responsibility, whereas the responsibilities for pain and symptom control, resuscitation status, and goals of care discussions were split between the primary team only and both teams. The main barrier for consulting palliative care services was the concern that patients and families would feel abandoned by the primary oncologist (73%). Ninety-seven percent of respondents answered that palliative care services are useful to improve patient care. CONCLUSION The majority of gynecologic oncologists perceived palliative care as a useful collaboration that is underused. Fear of perceived abandonment by the patient and family members was identified as a significant barrier to palliative care consult.

Trends in Periodic Surveillance Testing for Early-Stage Uterine Cancer Survivors.

OBJECTIVE: To examine the use of periodic surveillance testing for early-stage endometrial cancer survivors. METHODS: We performed a population-based analysis using the Surveillance, Epidemiology, and End Results-Medicare database, which was used to identify patients with stage I–II endometrioid endometrial cancer treated from 1992 to 2011. Three surveillance periods (7–18, 19–30, 31–42 months) after hysterectomy were examined. Use of vaginal cytology and imaging were quantified. RESULTS: We identified 17,638 patients. From 1992 to 2011, the use of chest radiography decreased (46.3–34.2%) during the first surveillance period, whereas imaging with chest computed tomography (CT) (0.9–12.6%), abdominopelvic CT (11.7–24.8%), and positron emission tomography (0–2.9%) increased (P<.001 for all). The use of cytology increased from 68.5% in 1992 to 72.3% in 2007 and then decreased to 66.9% in 2011 (P=.02). The mean number of cytologic samples obtained per patient increased from 1.3 in 1992 to 1.6 in 2008 and then declined to 1.3 in 2011, whereas the mean per patient number of chest CTs (0.02–0.2), abdominopelvic CTs (0.2–0.4), and positron emission tomographies (0–0.03) rose from 1992 to 2011. In 2011, 49.3% underwent radiologic surveillance 7–18 months after diagnosis, whereas 11.9% underwent two or more radiologic assessments in combination with cytology. These findings were similar for surveillance periods 2 and 3. CONCLUSION: The use of chest radiography has decreased and use of cytology has started to decline. However, the use of more costly imaging modalities is increasing despite a lack of evidence for the efficacy of these tests for early-stage endometrial cancer survivors.

Utilization and Outcomes of Chemotherapy in Women With Intermediate-risk, Early-stage Ovarian Cancer

OBJECTIVE: To examine utilization and efficacy of chemotherapy for stage I ovarian cancer. METHODS: We conducted a retrospective cohort study using the National Cancer Data Base to identify women with stage I ovarian cancer treated from 1998 to 2012. Patients were classified into three groups based on grade and stage: stage IA or IB grade 1 (low risk); stage IA or IB grade 2 (intermediate risk); and stage IA or IB grade 3 or any stage IC (high risk). Multivariable models were developed to examine predictors of chemotherapy use and survival. RESULTS: We identified 21,758 patients including 4,196 (19.3%) low-risk, 3,777 (17.4%) intermediate-risk, and 13,785 (63.4%) high-risk women. The median follow-up of the cohort was 63.9 months. Use of chemotherapy within the groups was 15.5%, 39.5%, and 69.8%, respectively (P<.001). Among low-risk patients, chemotherapy was not associated with a change in survival (adjusted hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.85–1.42), whereas chemotherapy was associated with reduced mortality for high-risk patients (adjusted HR 0.78, 95% CI 0.71–0.85). For intermediate-risk patients (stage IA–IB grade 2), chemotherapy was associated with a 26% reduction in mortality (adjusted HR 0.74, 95% CI 0.62–0.89). The association between chemotherapy and improved survival among intermediate-risk patients remained significant when limited to patients who underwent staging lymphadenectomy (adjusted HR 0.77, 95% CI 0.62–0.97). CONCLUSION: There is widespread variation in the patterns of care for early-stage ovarian cancer. Chemotherapy was associated with improved survival for stage IA–IB grade 2 patients.

Buttock Necrosis after Uterine Artery Embolization for Delayed Hysterectomy in Placenta Percreta

Background. Morbidly adherent placenta (MAP) is increasing in incidence and is commonly associated with maternal hemorrhage and cesarean hysterectomy. Uterine artery embolization (UAE) may be utilized in the conservative management of placenta percreta to potentially reduce blood loss. The incidence of complications from UAE in the conservative management of placenta percreta is poorly described. To our knowledge, we present the first reported case of buttock necrosis in this setting. Case. A 39-year-old gravida nine para two with placenta percreta who underwent conservative management with UAE complicated by right buttock necrosis. Conclusion. While UAE may potentially decrease blood loss, it is not without risk. More studies must be performed in order to quantify those risks and determine the clinical utility of UAE.

National trends in total pelvic exenteration for gynecologic malignancies

OBJECTIVE: Total pelvic exenteration (TPE) is a radical procedure involving en bloc resection of the pelvic viscera. The procedure may be performed as primary treatment for gynecologic malignancies or as a salvage therapy in women with a pelvic recurrence. It is unclear how improvements in radiation and chemotherapy have impacted the use of TPE. We performed a population-based analysis to examine the annual rate of TPE among women with cervical and uterine cancer.

Cost of Care for the Initial Management of Ovarian Cancer

OBJECTIVE To examine the cost of care during the first year after a diagnosis of ovarian cancer, estimate the sources of cost, and explore the out-of-pocket costs. METHODS We performed a retrospective cohort study of women with ovarian cancer diagnosed from 2009 to 2012 who underwent both surgery and adjuvant chemotherapy using the Truven Health MarketScan database. This database is comprised of patients covered by commercial insurance sponsored by more than 100 employers in the United States. Medical expenditures, including physician reimbursement, for a 12-month period beginning on the date of surgery were estimated. All payments were examined, including out-of-pocket costs for patients. Payments were divided into expenditures for inpatient care, outpatient care (including chemotherapy), and outpatient drug costs. The 12-month treatment period was divided into three phases: surgery to 30 days (operative period), 1-6 months (adjuvant therapy), and 6-12 months after surgery. The primary outcome was the overall cost of care within the first year of diagnosis of ovarian cancer; secondary outcomes included assessment of factors associated with cost. RESULTS A total of 26,548 women with ovarian cancer who underwent surgery were identified. After exclusion of patients with incomplete insurance enrollment or coverage, those who did not undergo chemotherapy, and those with capitated plans, our cohort consisted of 5,031 women. The median total medical expenditures per patient during the first year after the index procedure were