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.

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.

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.

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.

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.

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.

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.

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.

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.

Incidence of and risk factors for postoperative ileus in women undergoing primary staging and debulking for epithelial ovarian carcinoma.

OBJECTIVE: Thorough primary cytoreduction for epithelial ovarian carcinoma (EOC) improves survival. The incidence of postoperative ileus (POI) in these patients may be underreported because of varying POI definitions and the evolving, increasingly complex contemporary surgical approach to EOC. We sought to determine the current incidence of POI and its risk factors in women undergoing debulking and staging for EOC. METHODS: We retrospectively identified the records of women who underwent primary staging and cytoreduction for EOC between 2003 and 2008. POI was defined as a surgeon's diagnosis of POI, return to nothing-by-mouth status, or reinsertion of a nasogastric tube. Perioperative patient characteristics and process-of-care variables were analyzed. Univariate analyses were used to identify POI risk factors; variables with P ≤.20 were included in multivariate analysis. RESULTS: Among 587 women identified, the overall incidence of POI was 30.3% (25.9% without bowel resection, 38.5% with bowel resection; P=.002). Preoperative thrombocytosis, involvement of bowel mesentery with carcinoma, and perioperative red blood cell transfusion were independently associated with increased POI. Postoperative ibuprofen use was associated with decreased POI risk. Women with POI had a longer length of stay (median, 11 vs 6 days) and increased time to recovery of the upper (7.5 vs 4 days) and lower (4 vs 3 days) gastrointestinal tract (P<.001 for each). CONCLUSIONS: The rate of POI is substantial among women undergoing staging and cytoreduction for EOC and is associated with increased length of stay. Modifiable risk factors may include transfusion and postoperative ibuprofen use. Alternative interventions to decrease POI are needed.

Randomized clinical trial of imiquimod: an adjunct to treating cervical dysplasia.

OBJECTIVES: Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. Imiquimod is a topical medication that enhances the immune response to HPV-induced genital warts. This study evaluated cervical application of imiquimod as an adjunct to standard treatment for cervical dysplasia. STUDY DESIGN: Fifty-six patients were randomized to standard excisional/ablative treatment vs applications of imiquimod followed by standard treatment. The primary endpoint was dysplasia recurrence within 2 years. RESULTS: There were no differences in dysplasia recurrence between the 2 groups. Treatment was well tolerated, with side effects being mild but significantly worse in women receiving imiquimod for, chills, fatigue, fever, headache, myalgias, and vaginal discharge. CONCLUSION: This trial does not support the hypothesis that imiquimod, as used in this trial, has an impact on recurrence of cervical dysplasia, but the adequacy of findings are limited by sample size. The trial does support the feasibility and acceptability of the use of imiquimod on the cervix.

Recognizing and treating ovarian cancer.

Ovarian cancer is the fifth-leading cause of cancer-related death among women and is the deadliest gynecologic cancer. The mortality rate associated with this disease is attributed in part to the fact that it is often not diagnosed until its later stages. Although no definitive screening test for this form of cancer yet exists, a recent consensus statement offers guidance to help physicians identify women who may have the disease. This article describes the importance of and means for early diagnosis of ovarian cancer, reviews treatments, and discusses the role of both the primary care physician and the gynecologic oncologist with regard to this disease.

The impact of surgical guidelines and periodic quality assessment on the staging of endometrial cancer.

OBJECTIVE: To determine the impact of surgical guidelines and transparent periodic assessment of surgical quality on endometrial cancer (EC) staging by gynecologic oncologists in a single institution and to identify process-of-care, patient-specific, and disease-specific risk factors that influence surgical quality. METHODS: In January 2004, a prospective treatment algorithm was implemented for EC at our institution. The number of nodes harvested was a surrogate, and staging quality from 2004 to 2008 (quality assessment [QA] interval) was compared with the previous 5 years (pre-QA interval). Since 2004, low-risk cases based on frozen section examination had not undergone lymphadenectomy and were excluded. Independent patient-specific, disease-specific, and surgery-related risk factors influencing lymphadenectomy quality during both intervals were identified with multivariable logistic regression analysis. RESULTS: Pelvic and para-aortic lymph node dissection (LND) in surgical EC management before QA (n=420) were 77.9% and 48.8% vs 89.3% and 83.4% during the QA (n=561) (P<.001). The median number of pelvic and para-aortic nodes harvested in LND was 29 and 10 before QA vs 34 and 16 during the QA interval (P<.001). With acceptance of stringent criteria for defining systematic LND (mean node count-1 SD) during the QA, systematic pelvic (≥22 nodes) and para-aortic (≥10 nodes) LNDs occurred in 57.4% and 25.7% of cases before QA vs 77.9% and 70.7% during the QA interval (P<.001). In patients with LND, rates of systematic pelvic and para-aortic LND were 73.7% and 53.0% before vs 87.2% and 84.8% after QA (P<.001). Multivariable logistic regression analysis showed independent factors influencing systematic pelvic and para-aortic LND (P<.01): surgeon and stage during the pre-QA interval vs surgical approach; intraoperative ascites; body mass index; surgeon; patient age; and myometrial invasion after QA implementation. CONCLUSION: Inclusion of detailed surgical guidelines and transparent periodic assessment of surgical quality translated to dramatic improvement in quality of surgical EC staging. This implementation was associated with a transition to more patient-specific risk factors influencing systematic LND. Although surgical quality metrics were markedly enhanced during QA, persistent variability observed among surgeons and the change in surgical approach render continuous QA and improvement obligatory.

Magnetic resonance-guided focused ultrasound of uterine leiomyomas: review of a 12-month outcome of 130 clinical patients.

PURPOSE: To assess 12-month outcomes and safety of clinical magnetic resonance (MR)-guided focused ultrasound (US) treatments of uterine leiomyomas. MATERIALS AND METHODS: Between March 2005 and December 2009, 150 women with symptomatic uterine leiomyomas were clinically treated with MR-guided focused US at a single institution; 130 patients completed treatment and agreed to have their data used for research purposes. Patients were followed through retrospective review of medical records and phone interviews conducted at 3-, 6-, and 12-month intervals after treatment to assess additional procedures and symptom relief. Outcome measures and treatment complications were analyzed for possible correlations with the appearance of the tumors on T2-weighted imaging. RESULTS: The cumulative incidence of additional tumor-related treatments 12 months after MR-guided focused US was 7.4% by the Kaplan-Meier method. At 3-, 6-, and 12-month follow-up, 86% (90 of 105), 93% (92 of 99), and 88% (78 of 89) of patients reported relief of symptoms, respectively. No statistically significant correlation between tumor appearance on T2-weighted imaging and 12-month outcome was found. Treatment-related complications were observed in 17 patients (13.1%): 16 patients had minor complications and one had a major complication (deep vein thrombosis). All complications were resolved within the 12-month follow-up period. CONCLUSIONS: MR-guided focused US is a noninvasive treatment option that can be used to effectively and safely treat uterine leiomyomas and delivers significant and lasting symptom relief for at least 12 months. The incidence of additional treatment during this time period is comparable with those in previous reports of uterine artery embolization.

Understanding cellular leiomyomas: a case-control study.

OBJECTIVE: Reports exist in which cellular leiomyomas (CLs) appear to have clinical characteristics or genetic profiles similar to leiomyosarcomas. This study aimed to determine whether most CLs differ clinically from typical uterine leiomyomas (ULs). STUDY DESIGN: A case-control study was conducted with women who underwent surgical procedures between January 1989 and December 2008 and who were diagnosed with a CL (n = 99). Control subjects, who were matched in a 2:1 ratio, were women with a diagnosis of UL (n = 198). Hospital and ambulatory records were reviewed. RESULTS: In multivariable logistic regression analyses, women with CLs were more likely to have surgery for the indication of enlarging leiomyoma and less likely to have concomitant endometriosis or adenomyosis. Uteri that contained CLs were also more likely to have larger and fewer leiomyomas when compared with control subjects. CONCLUSION: CLs have a distinct clinical phenotype compared with ULs and have some characteristics in common with leiomyosarcomas.

Stage IV ovarian cancer: disease site-specific rationale for postoperative treatment.

OBJECTIVES: We aimed to define the site-specific patterns of treatment failure in stage IV ovarian cancer. METHODS: Data from all consecutive Mayo Clinic patients with stage IV epithelial ovarian cancer, from 1994 through 2003, were collected and analyzed. Statistical analyses included the chi(2) test and Kaplan-Meier curves with log-rank tests. RESULTS: Review of our patient database identified 109 patients with stage IV ovarian cancer: mean age, 62 years (range, 36-83 years); 5-year overall survival, 15%. Most patients (74%) had intraperitoneal disease at the time of relapse, 36% had pleural effusion, and 49% had extraperitoneal metastases. At the time of death 75% had intraperitoneal localizations, 51% had pleural effusion, and 46% had extraperitoneal metastases. Patients with pleural effusion were more likely to have pleural disease at relapse and at last follow-up. Extrapleural disease at the time of diagnosis predicted extrapleural disease at relapse and at last follow-up. Most patients classified as having stage IV disease by pleural cytology only, as opposed to all other patients, had intraperitoneal disease at relapse (88% vs 58.7%, P=.001) and last follow-up (88.5% vs 59.6%, P=.001). Patients having stage IV disease by pleural cytology only had survival benefit when disease was optimally debulked in the abdomen and pelvis (median survival, 3.1 years vs 1.3 years; P=.001). Patients with multiple unresectable liver metastases had poor prognosis (median survival, 1.2 years) owing to progression of liver disease. CONCLUSIONS: Clinical trials for stage IV ovarian cancer should reflect the site-specific risks for recurrence according to disease location at diagnosis.