Comparing risk stratification criteria for predicting lymphatic dissemination in endometrial cancer.

OBJECTIVE: To compare two published risk stratification models (Milwaukee Model vs. Mayo Criteria) to predict lymphatic dissemination (LD) in endometrioid endometrial cancer (EC). METHODS: Patients with stage I-III EC undergoing surgery from 1/1/2004-9/30/2013 were retrospectively reviewed and classified as low-risk vs at-risk for LD using two independent risk models. LD was defined as positive nodes at surgery or lymph node recurrence within 2 years of surgery after negative lymph node dissection (LND) or when LND was not performed. False positive (FP) and false negative (FN) rates for each risk model were calculated. RESULTS: Among 1103 patients, 81 (7.3%) had LD (72 positive LN and 9 LN recurrences), and most (90.2%) had stage I EC. The Milwaukee Model yielded a low at-risk rate for LD (38.1%) but a high FN rate (13.6%, 95% CI 7.0-23.0). The traditional Mayo Criteria using a cut-off of 2 cm for tumor diameter (TD) had a higher at-risk rate for LD (69.5%) but a FN rate of 0% (95% CI, 0-4.5). Modifying the Mayo Criteria using a TD cutoff of ≤3 cm identified fewer women at-risk (56.8% vs. 69.5%) and had a lower FP rate (53.6% vs. 67.1%), but had a higher FN rate (3.7%, 95% CI, 0.8-10.4). CONCLUSIONS: The Milwaukee Model had the lowest at-risk rate of LD but an unacceptable FN rate. Modifying the Mayo Criteria by increasing the TD cutoff from the traditional ≤2 cm to ≤3 cm would spare an estimated 13.5% of patients LND, but the accompanying FN rate is unacceptably high. The traditional Mayo Criteria for low-risk EC remains the most sensitive in determining which patients LND can be omitted.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Randomized comparison of a reduced-visit prenatal care model enhanced with remote monitoring.

BACKGROUND: Standard prenatal care, consisting of 12-14 visits per pregnancy, is expensive and resource intensive, with limited evidence supporting the structure, rhythm, or components of care. Some studies suggest a reduced-frequency prenatal care model is as safe as the standard model of care for low-risk pregnant women, but evidence is limited. We developed and evaluated an innovative, technology-enhanced, reduced prenatal visit model (OB Nest). OBJECTIVE: To evaluate the acceptability and effectiveness of OB Nest, a reduced-frequency prenatal care model enhanced with remote home monitoring devices and nursing support. STUDY DESIGN: A single-center randomized controlled trial, composed of pregnant women, aged 18-36 years, recruited from an outpatient obstetric tertiary academic center in the Midwest United States. OB Nest care consisted of 8 onsite appointments with an obstetric provider; 6 virtual visits consisting of phone or online communication with an assigned nurse, supplemented with fetal Doppler and sphygmomanometer home monitoring devices; and access to an online community of pregnant women. Usual care consisted of 12 prescheduled prenatal clinic appointments with obstetric providers. Acceptability of OB Nest was measured by validated surveys of patient satisfaction with care at 36 weeks; perception of stress at 14, 24, and 36 weeks; and perceived quality of care at 36 weeks of gestation. Effectiveness was analyzed by comparing adherence to the American College of Obstetricians and Gynecologists recommended routine prenatal and ancillary services, maternal and fetal safety outcomes, and healthcare utilization. RESULTS: Three hundred pregnant women at <13 weeks of gestation were recruited and randomized to OB Nest or usual care (150 in each arm) using a minimization algorithm. Demographic characteristics were similar between groups. Compared to usual care, patients in OB Nest had higher satisfaction on a 100-point validated modified Littlefield and Adams Satisfaction scale (OB Nest = 93.9% vs usual care = 78.9%, P < .01). Pregnancy-related stress, measured, on a 0-2 point PreNatal Maternal Stress validated scale, with higher scores indicating higher levels of stress, was lower among OB Nest participants at 14 weeks (OB Nest = 0.32 vs usual care = 0.41, P < .01) and at 36 weeks of gestation (OB Nest = 0.34 vs usual care = 0.40, P < .03). There was no statistical difference in perceived quality of care. Adherence to the provision of American College of Obstetricians and Gynecologists prenatal services was similar in both arms. Maternal and fetal clinical outcomes were similar between groups. Total reported nursing time was higher in OB Nest (OB Nest = 171.2 minutes vs usual care = 108.2 minutes, 95% confidence interval, 48.7-77.4). CONCLUSION: OB Nest is an innovative, acceptable, and effective reduced-frequency prenatal care model. Compared to routine prenatal care, OB Nest resulted in higher patient satisfaction and lower prenatal stress, while reducing the number of appointments with clinicians and maintaining care standards for pregnant women. This program is a step toward evidence-driven prenatal care that improves patient satisfaction.

Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy.

OBJECTIVE: We studied the long-term risk of depressive and anxiety symptoms in women who underwent bilateral oophorectomy before menopause. DESIGN: We conducted a cohort study among all women residing in Olmsted County, MN, who underwent bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the bilateral oophorectomy cohort was matched by age with a referent woman from the same population who had not undergone an oophorectomy. In total, we studied 666 women with bilateral oophorectomy and 673 referent women. Women were followed for a median of 24 years, and depressive and anxiety symptoms were assessed using a structured questionnaire via a direct or proxy telephone interview performed from 2001 through 2006. RESULTS: Women who underwent bilateral oophorectomy before the onset of menopause had an increased risk of depressive symptoms diagnosed by a physician (hazard ratio = 1.54, 95% CI: 1.04-2.26, adjusted for age, education, and type of interview) and of anxiety symptoms (adjusted hazard ratio = 2.29, 95% CI: 1.33-3.95) compared with referent women. The findings remained consistent after excluding depressive or anxiety symptoms that first occurred within 10 years after oophorectomy. The associations were greater with younger age at oophorectomy but did not vary across indications for the oophorectomy. In addition, treatment with estrogen to age 50 years in women who underwent bilateral oophorectomy at younger ages did not modify the risk. CONCLUSIONS: Bilateral oophorectomy performed before the onset of menopause is associated with an increased long-term risk of depressive and anxiety symptoms.

Adequate pelvic lymphadenectomy and survival of women with early-stage epithelial ovarian cancer.

OBJECTIVE: To examine the trends and survival for women with early-stage epithelial ovarian cancer who underwent adequate lymphadenectomy during surgical treatment. METHODS: This is a retrospective observational study examining the Surveillance, Epidemiology, End Results program between 1988 and 2013. We evaluated 21,537 cases of stage I-II epithelial ovarian cancer including serous (n=7,466), clear cell (n=6,903), mucinous (n=4,066), and endometrioid (n=3,102) histology. A time-trend analysis of the proportion of patients who underwent adequate pelvic lymphadenectomy (≥8 per Gynecologic Oncology Group [GOG] criteria, ≥12 per Collaborative Group Report [CGR] criteria for bladder cancer, and >22 per Mayo criteria for endometrial cancer) and a survival analysis associated with adequate pelvic lymphadenectomy were performed. RESULTS: There were significant increases in the proportion of women who underwent adequate lymphadenectomy: GOG criteria 3.6% to 28.6% (1988-2010); CGR criteria 2.4% to 22.4% (1988-2013); and Mayo criteria 0.7% to 9.5% (1988-2013) (all, p<0.05). On multivariable analysis, adequate lymphadenectomy was independently associated with improved cause-specific survival compared to inadequate lymphadenectomy: GOG criteria, adjusted-hazard ratio (HR)=0.75, CGR criteria, adjusted-HR=0.77, and Mayo criteria, adjusted-HR=0.85 (all, p<0.05). Compared to inadequate lymphadenectomy, adequate lymphadenectomy was significantly associated with improved cause-specific survival for serous (HR range=0.67-0.73), endometrioid (HR range=0.59-0.61), and clear cell types (HR range=0.66-0.73) (all, p<0.05) but not in mucinous type (HR range=0.80-0.91; p>0.05). CONCLUSION: Quality of lymphadenectomy during the surgical treatment for early-stage epithelial ovarian cancer has significantly improved. Adequate lymphadenectomy is associated with a 15%-25% reduction in ovarian cancer mortality compared to inadequate lymphadenectomy.

OB Nest: Reimagining Low-Risk Prenatal Care.

Using a human-centered design method, our team sought to envision a new model of care for women experiencing low-risk pregnancy. This model, called OB Nest, aimed to demedicalize the experience of pregnancy by providing a supportive and empowering experience that fits within patients' daily lives. To explore this topic, we invited women to use self-monitoring tools, a text-based smartphone application to communicate with their care team, and moderated online communities to connect with other pregnant women. Through observations of tool use and patient- and care team-provided feedback, we found that self-measurement and access to a fetal heart monitor provided women with confidence and joy in the progress of their pregnancies while shifting their position to being an active participant in their care. The smartphone application gave women direct access to their care team, provided continuity, and removed hurdles in establishing communication. The online community platform was a space where women in the same obstetric clinic could share nonmedical questions and advice with one another. This created a sense of community, leveraged the knowledge of women, and provided a venue beyond the clinic visit for information exchange. These findings were integrated into the design of the Mayo Clinic OB Nest model. This model redistributes care based on the individual needs of patients by providing self-measurement tools and continuous flexible access to their care team. By enabling women to meaningfully participate in their care, there is potential for cost savings and improved patient satisfaction.

Intrapartum factors associated with neonatal hypoxic ischemic encephalopathy: a case-controlled study.

BACKGROUND: Neonatal encephalopathy (NE) affects 2-4/1000 live births with outcomes ranging from negligible neurological deficits to severe neuromuscular dysfunction, cerebral palsy and death. Hypoxic ischemic encephalopathy (HIE) is the sub cohort of NE that appears to be driven by intrapartum events. Our objective was to identify antepartum and intrapartum factors associated with the development of neonatal HIE. METHODS: Hospital databases were searched using relevant diagnosis codes to identify infants with neonatal encephalopathy. Cases were infants with encephalopathy and evidence of intrapartum hypoxia. For each hypoxic ischemic encephalopathy case, four controls were randomly selected from all deliveries that occurred within 6 months of the case. RESULTS: Twenty-six cases met criteria for hypoxic ischemic encephalopathy between 2002 and 2014. In multivariate analysis, meconium-stained amniotic fluid (aOR 12.4, 95% CI 2.1-144.8, p = 0.002), prolonged second stage of labor (aOR 9.5, 95% CI 1.0-135.3, p = 0.042), and the occurrence of a sentinel or acute event (aOR 74.9, 95% CI 11.9-infinity, p < 0.001) were significantly associated with hypoxic ischemic encephalopathy. The presence of a category 3 fetal heart rate tracing in any of the four 15-min segments during the hour prior to delivery (28.0% versus 4.0%, p = 0.002) was more common among hypoxic ischemic encephalopathy cases. CONCLUSION: Prolonged second stage of labor and the presence of meconium-stained amniotic fluid are risk factors for the development of HIE. Close scrutiny should be paid to labors that develop these features especially in the presence of an abnormal fetal heart tracing. Acute events also account for a substantial number of HIE cases and health systems should develop programs that can optimize the response to these emergencies.

Clinical Utility of Preoperative Computed Tomography in Patients With Endometrial Cancer.

OBJECTIVE: The aim of this study was to determine the clinical utility of routine preoperative pelvic and abdominal computed tomography (CT) examinations in patients with endometrial cancer (EC). METHODS: We retrospectively reviewed records from patients with EC who underwent a preoperative endometrial biopsy and had surgery at our institution from January 1999 through December 2008. In the subset with an abdominal CT scan obtained within 3 months before surgery, we evaluated the clinical utility of the CT scan. RESULTS: Overall, 224 patients (18%) had a preoperative endometrial biopsy and an available CT scan. Gross intra-abdominal disease was observed in 10% and 20% of patients with preoperative diagnosis of endometrioid G3 and type II EC, respectively, whereas less than 5% of patients had a preoperative diagnosis of hyperplasia or low-grade EC. When examining retroperitoneal findings, we observed that a negative CT scan of the pelvis did not exclude the presence of pelvic node metastasis. Alternately, a negative CT scan in the para-aortic area generally reduced the probability of finding para-aortic dissemination but with an overall low sensitivity (42%). However, the sensitivity for para-aortic dissemination was as high as 67% in patients with G3 endometrioid cancer. In the case of negative para-aortic nodes in the CT scan, the risk of para-aortic node metastases decreased from 18.8% to 7.5% in patients with endometrioid G3 EC. Up to 15% of patients with endometrioid G3 cancer had clinically relevant incidental findings that necessitated medical or surgical intervention. CONCLUSIONS: In patients with endometrioid G3 and type II EC diagnosed by the preoperative biopsy, CT scans may help guide the operative plan by facilitating preoperative identification of gross intra-abdominal disease and enlarged positive para-aortic nodes that are not detectable during physical examinations. In addition, CT may reveal other clinically relevant incidental findings.

Primary brain metastases of endometrial cancer: A report of 18 cases and review of the literature.

OBJECTIVE: To present a series of brain metastases from endometrial cancer (EC) and describe a comprehensive review of the literature. METHODS: We retrospectively reviewed medical records of 1) patients with cerebral dissemination of EC treated at Mayo Clinic from 1984 to 2001 and 2) all patients referred for treatment of primary brain metastases after primary treatment for EC elsewhere. We also reviewed published case reports and case series describing cerebral spread of EC. RESULTS: Among the 1632 patients treated at Mayo, 14 (0.86%) had primary brain dissemination; 4 additional referral cases were identified (total, 18 patients). In 2 cases (11.1%), diagnosis of brain metastases was made at presentation of EC; in the others, median time to development of brain metastasis was 5 (range, 1-57) months. Median survival was 57 (range, 7-118) months in patients with single cerebral metastases and no extracerebral involvement (n=6); for the remaining 12 patients, median survival was 4 (range, 0-28) months. Among the 6 patients with single brain metastases, complete surgical excision was possible in 5; in that group, the overall survival was 64 (range, 12-118) months. We identified 98 cases of brain metastases of EC in the literature: 58 were primary cerebral metastases. Overall survival after brain dissemination was significantly higher in patients with a single metastasis without other localization and receiving multimodal treatment including surgery and whole-brain radiotherapy. CONCLUSIONS: Single primary brain metastases without extracerebral spread seem to have a relatively favorable prognosis. Aggressive multimodal treatment may include surgery and brain radiation.

Molecular classification of high grade endometrioid and clear cell ovarian cancer using TCGA gene expression signatures.

BACKGROUND: It is unclear whether the transcriptional subtypes of high grade serous ovarian cancer (HGSOC) apply to high grade clear cell (HGCCOC) or high grade endometrioid ovarian cancer (HGEOC). We aim to delineate transcriptional profiles of HGCCOCs and HGEOCs. METHODS: We used Agilent microarrays to determine gene expression profiles of 276 well annotated ovarian cancers (OCs) including 37 HGCCOCs and 66 HGEOCs. We excluded low grade OCs as these are known to be distinct molecular entities. We applied the prespecified TCGA and CLOVAR gene signatures using consensus non-negative matrix factorization (NMF). RESULTS: We confirm the presence of four TCGA transcriptional subtypes and their significant prognostic relevance (p<0.001) across all three histological subtypes (HGSOC, HGCCOC and HGEOCs). However, we also demonstrate that 22/37 (59%) HGCCOCs and 30/67 (45%) HGEOCs form 2 additional separate clusters with distinct gene signatures. Importantly, of the HGCCOC and HGEOCs that clustered separately 62% and 65% were early stage (FIGO I/II), respectively. These finding were confirmed using the reduced CLOVAR gene set for classification where most early stage HGCCOCs and HGEOCs formed a distinct cluster of their own. When restricting the analysis to the four TCGA signatures (ssGSEA or NMF with CLOVAR genes) most early stage HGCCOCs and HGEOC were assigned to the differentiated subtype. CONCLUSIONS: Using transcriptional profiling the current study suggests that HGCCOCs and HGEOCs of advanced stage group together with HGSOCs. However, HGCCOCs and HGEOCs of early disease stages may have distinct transcriptional signatures similar to those seen in their low grade counterparts.

Incorporating robotic-assisted surgery for endometrial cancer staging: Analysis of morbidity and costs.

OBJECTIVE: To evaluate how the introduction of robotic-assisted surgery affects treatment-related morbidity and cost of endometrial cancer (EC) staging. METHODS: We retrospectively reviewed the records of consecutive patients with stage I-III EC undergoing surgical staging between 2007 and 2012 at our institution. Costs (from surgery to 30days after surgery) were set based on the Medicare cost-to-charge ratio for each year and inflated to 2014 values. Inverse probability weighting (IPW) was used to decrease the allocation bias when comparing outcomes between surgical groups. RESULTS: We focused our analysis on the 251 EC patients who had robotic-assisted surgery and the 384 who had open staging. During the study period, the use of robotic-assisted surgery increased and open staging decreased (P<0.001). Correcting group imbalances by using IPW methodology, we observed that patients undergoing robotic-assisted staging had a significantly lower postoperative complication rate, lower blood transfusion rate, longer median operating time, shorter median length of stay, and lower readmission rate than patients undergoing open staging (all P<0.001). Overall 30-day costs were similar between the 2 groups, with robotic-assisted surgery having significantly higher median operating room costs ($2820 difference; P<0.001) but lower median room and board costs ($2929 difference; P<0.001) than open surgery. Increasing experience with robotic-assisted staging was significantly associated with a decrease in median operating time (P=0.002) and length of stay (P=0.003). CONCLUSIONS: The implementation of robotic-assisted surgery for EC staging improves patient outcomes. It provides women the benefits of minimally invasive surgery without increasing costs and potentially improves patient turnover.

Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

BACKGROUND: The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. OBJECTIVE: The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. STUDY DESIGN: This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. RESULTS: During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43). For low-risk pregnancies, there was no significant difference in the levels for any of the measured indices over the study period (P = .61, P = .41, and P = .34 for the Modified Adverse Outcomes Index, Modified Weighted Adverse Outcomes Index, and Modified Severity Index, respectively). Among the high-risk pregnancies, the monthly Modified Weighted Adverse Outcomes Index decreased by 4.2 ± 1.8 (P = .03). The monthly Modified Severity Index decreased by 53.9 ± 17.7 points from the pre- to the postintervention periods (P = .01) and was < 50% of the predicted Modified Severity Index had the intervention not been implemented. The cesarean delivery rate was increasing prior to the intervention, but the rate was stable after the intervention, and the absolute rate did not differ between the pre- and the postintervention periods (28.4% vs 30.0%, P = .20). CONCLUSION: Overall and for high-risk pregnancies, the implementation of the labor and delivery care bundle had a positive impact on the Modified Weighted Adverse Outcomes Index and Modified Severity Index but not the Modified Adverse Outcomes Index.

Implementation of a new prenatal care model to reduce office visits and increase connectivity and continuity of care: protocol for a mixed-methods study.

BACKGROUND: Most low-risk pregnant women receive the standard model of prenatal care with frequent office visits. Research suggests that a reduced schedule of visits among low-risk women could be implemented without increasing adverse maternal or fetal outcomes, but patient satisfaction with these models varies. We aim to determine the effectiveness and feasibility of a new prenatal care model (OB Nest) that enhances a reduced visit model by adding virtual connections that improve continuity of care and patient-directed access to care. METHODS AND DESIGN: This mixed-methods study uses a hybrid effectiveness-implementation design in a single center randomized controlled trial (RCT). Embedding process evaluation in an experimental design like an RCT allows researchers to answer both "Did it work?" and "How or why did it work (or not work)?" when studying complex interventions, as well as providing knowledge for translation into practice after the study. The RE-AIM framework was used to ensure attention to evaluating program components in terms of sustainable adoption and implementation. Low-risk patients recruited from the Obstetrics Division at Mayo Clinic (Rochester, MN) will be randomized to OB Nest or usual care. OB Nest patients will be assigned to a dedicated nursing team, scheduled for 8 pre-planned office visits with a physician or midwife and 6 telephone or online nurse visits (compared to 12 pre-planned physician or midwife office visits in the usual care group), and provided fetal heart rate and blood pressure home monitoring equipment and information on joining an online care community. Quantitative methods will include patient surveys and medical record abstraction. The primary quantitative outcome is patient-reported satisfaction. Other outcomes include fidelity to items on the American Congress of Obstetricians and Gynecologists standards of care list, health care utilization (e.g. numbers of antenatal office visits), and maternal and fetal outcomes (e.g. gestational age at delivery), as well as validated patient-reported measures of pregnancy-related stress and perceived quality of care. Quantitative analysis will be performed according to the intention to treat principle. Qualitative methods will include interviews and focus groups with providers, staff, and patients, and will explore satisfaction, intervention adoption, and implementation feasibility. We will use methods of qualitative thematic analysis at three stages. Mixed methods analysis will involve the use of qualitative data to lend insight to quantitative findings. DISCUSSION: This study will make important contributions to the literature on reduced visit models by evaluating a novel prenatal care model with components to increase patient connectedness (even with fewer pre-scheduled office visits), as demonstrated on a range of patient-important outcomes. The use of a hybrid effectiveness-implementation approach, as well as attention to patient and provider perspectives on program components and implementation, may uncover important information that can inform long-term feasibility and potentially speed future translation. TRIAL REGISTRATION: Trial registration identifier: NCT02082275 Submitted: March 6, 2014.

Incisional Recurrences After Endometrial Cancer Surgery.

AIM: The aim of the present study was to estimate the incisional recurrence (IR) rate after endometrial cancer (EC) staging surgery and analyze characteristics of affected patients. PATIENTS AND METHODS: We retrospectively searched for patients with EC at 2 institutions and analyzed the occurrence of IR after open, laparoscopic, or robotic surgery. Additionally, a review of the literature was performed. RESULTS: Out of 2,636 patients with EC, 1,732 (65.7%), 461 (17.5%), and 443 (16.8%) had open, laparoscopic, and robotic surgery, respectively. Only 3 patients (0.11%) had IR, all after open surgery. Additionally, 38 cases of IR were identified from the literature. Patients with non-isolated IR had worse overall survival than patients with isolated IR (p=0.04). Among this latter group, combined treatments may be associated with improved survival outcome. CONCLUSION: IR after EC surgery is rare and may occur after minimally-invasive or open operations. Combination of local and systemic treatments may provide favorable outcomes for patients with isolated IR.

Robotic radical hysterectomy in early stage cervical cancer: A systematic review and meta-analysis.

OBJECTIVE: To compare intraoperative and short-term postoperative outcomes of robotic radical hysterectomy (RRH) to laparoscopic and open approaches in the treatment of early stage cervical cancer. METHODS: A search of MEDLINE, EMBASE (using Ovid interface) and SCOPUS databases was conducted from database inception through February 15, 2014. We included studies comparing surgical approaches to radical hysterectomy (robotic vs. laparoscopic or abdominal, or both) in women with stages IA1-IIA cervical cancer. Intraoperative outcomes included estimated blood loss (EBL), operative time, number of pelvic lymph nodes harvested and intraoperative complications. Postoperative outcomes were hospital stay and surgical morbidity. The random effects model was used to pool weighted mean differences (WMDs) and odds ratios (OR). RESULTS: Twenty six nonrandomized studies were included (10 RRH vs abdominal radical hysterectomy [ARH], 9 RRH vs laparoscopic radical hysterectomy [LRH] and 7 compared all 3 approaches) enrolling 4013 women (1013 RRH, 710 LRH and 2290 ARH). RRH was associated with less EBL (WMD=384.3, 95% CI=233.7, 534.8) and shorter hospital stay (WMD=3.55, 95% CI=2.10, 5.00) than ARH. RRH was also associated with lower odds of febrile morbidity (OR=0.43, 95% CI=0.20-0.89), blood transfusion (OR=0.12, 95% CI 0.06, 0.25) and wound-related complications (OR=0.31, 95% CI=0.13, 0.73) vs. ARH. RRH was comparable to LRH in all intra- and postoperative outcomes. CONCLUSION: Current evidence suggests that RRH may be superior to ARH with lower EBL, shorter hospital stay, less febrile morbidity and wound-related complications. RRH and LRH appear equivalent in intraoperative and short-term postoperative outcomes and thus the choice of approach can be tailored to the choice of patient and surgeon.

Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer.

Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confidence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions.

Efficacy of contemporary chemotherapy in stage IIIC endometrial cancer: a histologic dichotomy.

BACKGROUND: Treatment failures in stage IIIC endometrial carcinoma (EC) are predominantly due to occult extrapelvic metastases (EPM). The impact of chemotherapy on occult EPM was investigated according to grade (G), G1/2EC vs G3EC. METHODS: All surgical-stage IIIC EC cases from January 1, 1999, through December 31, 2008, from Mayo Clinic were included. Patient-, disease-, and treatment-specific risk factors were assessed for association with overall survival, cause-specific survival, and extrapelvic disease-free survival (DFS) using Cox proportional hazards regression. RESULTS: 109 cases met criteria, with 92 (84%) having systematic lymphadenectomy (>10 pelvic and >5 paraaortic lymph nodes resected). In patients with documented recurrence sites, occult EPM accounted for 88%. Among G1/2EC cases (n=48), the sole independent predictor of extrapelvic DFS was grade 2 histology (hazard ratio [HR], 0.28; 95% CI, 0.08-0.91; P=.03) while receipt of adjuvant chemotherapy approached significance (HR 0.13; 95% CI, 0.02, 1.01; P=.0511). The 5-year extrapelvic DFS with and without adjuvant chemotherapy was 93% and 54%, respectively (log-rank, P=.02). Among G3EC (n=61), the sole independent predictor of extrapelvic DFS was lymphovascular space involvement (HR, 2.63; 95% CI, 1.16-5.97; P=.02). Adjuvant chemotherapy did not affect occult EPM in G3EC; the 5-year extrapelvic DFS for G3EC with and without adjuvant chemotherapy was 43% and 42%, respectively (log-rank, P=.91). CONCLUSIONS: Chemotherapy improves extrapelvic DFS for stage IIIC G1/2EC but not stage IIIC G3EC. Future efforts should focus on prospectively assessing the impact of chemotherapy on DFS in G3EC and developing innovative phase I and II trials of novel systemic therapies for advanced G3EC.

Comparison of current staging systems and a novel staging system for uterine leiomyosarcoma.

OBJECTIVES: Uterine leiomyosarcoma (LMS) was traditionally staged by modified 1988 International Federation of Gynecology and Obstetrics (FIGO) staging criteria for endometrial adenocarcinoma. Contemporary methods of staging include the 2009 FIGO system for uterine LMS and the 2010 American Joint Committee on Cancer (AJCC) soft tissue sarcoma system. The aim of this study was to compare the accuracy of these 3 staging systems and a novel system in predicting disease-specific survival for patients with uterine LMS. METHODS: Patients, evaluated at our institution with uterine LMS from 1976 to 2009, were identified. Stage was assigned retrospectively based on operative and pathology reports. Staging systems performance was compared using confidence indices. RESULTS: We identified 244 patients with uterine LMS with sufficient information to be staged by all 3 systems. For each staging method, lower stage was associated with significantly improved disease-specific survival, P < 0.001. Patients with 2010 AJCC stage IA disease (low-grade, ≤5 cm) experienced no disease-specific deaths. We created a novel staging system, which used size and grade to stratify patients with disease confined to the uterus and/or cervix and combined the remaining patients with extrauterine disease as stage IV. Based on confidence index, the 2010 AJCC system and our novel system provided more accurate prognostic information than either of the 2 FIGO systems. CONCLUSIONS: Uterine LMS remains a clinically aggressive malignancy. Size and grade provided accurate prognostic information for patients with disease confined to the uterus and/or cervix. Patients with small, low-grade uterine LMS do not benefit from adjuvant therapy.