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Background/purpose: This study was designed to evaluate the response and toxicity of sorafenib alone or when combined with carboplatin and paclitaxel in patients with platinum-sensitive, recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (EOC)., Methods: Patients with recurrent platinum-sensitive EOC with no more than 2 prior courses of chemotherapy were randomized to single-agent sorafenib 400 mg twice daily or combination sorafenib 400 mg bid (days 2-19) with IV carboplatin (AUC 6) and IV paclitaxel 175 mg/m(2) (S+C/T) every 3 weeks. Single agent sorafenib could cross over to combination upon progression., Results: Patients were initially randomized to either arm, however, due to poor accrual, sorafenib arm was prematurely closed. A total of 13 patients were evaluable for response to sorafenib and 23 patients were evaluable for response to S+C/T. Objective response rate (RR) was 15 % for patients on sorafenib vs. 61 % for patients on S+C/T (p = 0.014); stable disease was seen in 62 % and 35 %, respectively. Clinical benefit rate (CBR) at 4 months (mos.) was 69 % for S and 65 % for S+C/T. The median progression free survival was 5.6 months on sorafenib vs. 16.8 months on S+C/T (p = 0.012) and there was no significant difference of overall survival between two arms (p = 0.974) with median overall survival 25.6 months under sorafenib vs. 25.9 months on S+C/T. Patients remained on trial for a median of 7.8 cycles on sorafenib and 5.4 cycles on S+C/T., Conclusion: Sorafenib, alone or in combination with carboplatin and paclitaxel, has activity in patients with platinum-sensitive EOC. Sorafenib in combination with carboplatin and paclitaxel improved RR and PFS; however, there were increased grade and frequencies of toxicities.

Background: Despite recent efforts to educate multiple sclerosis (MS) health-care providers about the importance of pelvic floor disorders (urinary, bowel, and sexual dysfunction), no data are currently available to assess outcomes of these efforts in terms of patient satisfaction., Methods: As part of the fall 2010 North American Research Committee on Multiple Sclerosis survey, we conducted a prospective, survey-based cohort study (N = 14,268) to evaluate patient satisfaction with the current evaluation and treatment of pelvic floor disorders. Patients were queried about 1) bother from bladder, bowel, or sexual symptoms; 2) whether they had been evaluated by a health-care provider for pelvic floor issues in the last 12 months; and 3) satisfaction with the evaluation and treatment they received, on a 5-point Likert scale. Patients were also asked whether these treatments had affected their quality of life (7-point Likert scale)., Results: A total of 9397 responses were received (response rate of 65.9%); respondents were primarily white (89%) and female (77.4%). Moderate-to-severe pelvic floor symptoms were reported by one-third of patients (bladder, 41%; bowel, 30%; sexual, 42%). Most respondents had been asked about bladder (61%) or bowel (50%) issues by their health-care providers, but only 20% had been queried about sexual dysfunction. Most respondents were moderately to very satisfied with the management of their bladder and bowel disorders but significantly less satisfied with that of sexual dysfunction., Conclusions: While MS patients are generally satisfied with current management of bladder and bowel dysfunction, improvement is needed in that of sexual dysfunction.

Aims: The aim of this study was to assess acute and subacacute gastrointestinal toxicity after fractionated stereotactic ablative radiotherapy (SABR) in women having recurrent gynecological cancers in the upper abdomen., Materials & Methods: In total, 34 women underwent upper abdominal SABR (24 Gy/three divided 8 Gy consecutive daily doses) using a robotic Cyberknife® (Accuray, CA, USA) platform. Volumes of the duodenum receiving 10% increments of the prescription dose were associated to post-therapy gastrointestinal toxicities using binary logistic regression analyses., Results: Median clinical follow-up was 10 months. In total, 14 (41%) of the 34 women manifested grade 2 or higher post-therapy gastrointestinal adverse events. The duodenal volume, receiving 80% of a 24-Gy dose, was significantly associated with gastrointestinal toxicity (p = 0.03). However, in a multivariate analysis, only patient age at SABR adjusted the odds of experiencing gastrointestinal toxicity (p = 0.02)., Conclusion: The duodenal volume receiving 80% of 24 Gy dose may be associated with gastrointestinal toxicity from upper abdominal SABR.

Aim: To determine agreement of cardiac anomalies between maternal fetal medicine (MFM) physicians and pediatric cardiologists (PC) in fetuses with single umbilical artery (SUA)., Methods: A retrospective review of all fetuses with SUA between 1999 and 2008. Subjects were studied by MFM and PC, delivered at our institution, and had confirmation of SUA and cardiac anomaly by antenatal and neonatal PC follow-up. Subjects were divided into four groups: isolated SUA, SUA and isolated cardiac anomaly, SUA and multiple anomalies without heart anomalies, and SUA and multiple malformations including cardiac anomaly., Results: 39,942 cases were studied between 1999 and 2008. In 376 of 39,942 cases (0.94%), SUA was diagnosed. Only 182 (48.4%) met inclusion criteria. Cardiac anomalies were found in 21% (38/182). Agreement between MFM physicians and PC in all groups combined was 94% (171/182) (95% CI [89.2, 96.8]). MFM physicians overdiagnosed cardiac anomalies in 4.4% (8/182). MFM physicians and PC failed to antenatally diagnose cardiac anomaly in the same two cases., Conclusions: Good agreement was noted between MFM physicians and PC in our institution. Studies performed antenatally by MFM physicians and PC are less likely to uncover the entire spectrum of cardiac abnormalities and thus neonatal follow-up is suggested.

Objectives: To examine whether adjuvant therapy after primary surgery for treatment of early-stage uterine leiomyosarcoma (LMS) improves recurrence and survival rates., Methods: A multisite, retrospective study of women diagnosed with stage I-II high grade LMS from 1990-2010 was performed. All patients (pts) underwent primary surgery followed by observation (OBS), radiotherapy (RT), or chemotherapy (CT) postoperatively., Results: One hundred eight patients were identified with long-term follow-up; 94 pts (87.0%) had stage I and 14 (13.0%) had stage II disease. The mean patient age was 55.4 years and mean BMI was 28.0. Thirty-four (31.5%) patients underwent OBS, 35 (32.4%) received RT, and 39 (36.1%) received chemotherapy. After a median follow-up of 41.8 months, a recurrence was diagnosed in 70.8%. Recurrence was evident in 25/34 (73.5%) OBS, 23/35 (65.7%) RT, and 28/39 (71.8%) of CT cohorts and was not different based on treatment (p=0.413). However, extra-pelvic recurrences were significantly higher in the RT (95.2%) than in the OBS (60%) or CT (64.3%) cohorts (p=0.012). Additionally, recurrences were more likely to be successfully treated or palliated in those who initially received CT (p=0.031). On multivariate analysis, stage (p<0.001) and chemotherapy (p=0.045) were associated with overall survival., Conclusions: Women with early-stage, high grade uterine LMS experience high recurrence rates and poor survival outcomes, irrespective of adjuvant therapy. These rates are higher than previously reported in the literature. Although women treated with CT had similar recurrence rates as those treated with OBS or RT, treatment with adjuvant chemotherapy may decrease the risk of extra-pelvic recurrence and improve survival., (© 2013.)

Background: Sexual dysfunction (SD) is a common complaint in female and male patients with multiple sclerosis (MS) and can arise at anytime during the course of the disease even in patients with low disability. Increasing neurological and physical impairment, psychological factors, and medication side effects are thought to increase rates of SD., Objective: To determine the prevalence of various SD symptoms among MS patients, their impact on patient self-reported sexual activity and satisfaction (SAS), and to examine the rates at which symptomatic patients utilize therapies for their complaints., Methods: Results from the Spring, 2006 North American Research Committee on Multiple Sclerosis (NARCOMS) Project were reviewed. Participants were asked to answer the Multiple Sclerosis Intimacy and Sexuality Questionaire-19 (MSISQ-19) and to indicate which symptomatic therapy they used to alleviate SD. Symptoms were grouped as severe (they impacted SAS always or almost always), moderate (occasionally), and mild (never or almost never). Primary end point was the prevalence of SD symptoms and their impact on patient SAS., Results: Of 17,883 surveys mailed, 9861 (55.1%) responses were returned. Of these, 6739 (68.3%) answered the questions on sexuality. Respondents were primarily female (76.7%), Caucasian (87.8%), with average age of 38.4 (±9.6), and time since diagnosis of 13.9 years (±9.3). 38.6% of male subjects and 34.8% of female subjects experienced at least 5 different types of severe symptoms. Also, 14.3% of males and 12.9% of females complained of at least 10 severe symptoms that affected their SAS. The most common severe symptoms were shared by both sexes: too long to achieve orgasm/climax (37.8%), inadequate lubrication/difficult erection (36.5%), less intense or pleasure with orgasm/climax (35.2%), lack of interest or desire (32.1%), problems moving the body (29.1%), less feeling or numbness in genitals (28.8%), feeling less confident (25.5%), and body less attractive (24.8%). The severe symptoms positively correlated with time since diagnosis, Patient Determined Disease Steps Score, bladder disability score, and spasticity score. Few patients with at least one severe symptom used therapies to improve their SD (vibrators 19.1%, phosphodiesterase-5 enzyme inhibitors 14.2%, other medications 0.6%, counseling 4.1%, penile device 1.0%, intracorporeal therapy 0.7%, sex surgery 0.5%, and clitoral device 0.3%)., Conclusion: SD in patients with MS is multifactorial and very similar in men and women. Despite increasing therapeutic options, many patients with MS do not seek treatment for their SD complaints. It is very important for the physicians caring for patients with MS to initiate discussion of potential SD to allow earlier diagnosis and treatment., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: The primary objective was to examine the safety and feasibility of robotic-assisted laparoscopy in a cohort of women treated surgically for stage III and IV endometriosis. The secondary objective was to explore whether the stage of endometriosis affected surgical outcome., Methods: In this cohort study, 43 women with severe endometriosis were treated with robot-assisted laparoscopic hysterectomy with unilateral or bilateral salpingooophorectomy for stage III (n = 19) or stage IV (n = 24) disease., Results: Histopathologic evaluation confirmed endometriosis in all patients, and fibroids were also shown in 12 patients. The median actual operative time was 145 min (range, 67-325 min), and the median blood loss was 100 mL (range, 20 - 400 mL). All but one of the procedures were completed successfully robotically. The length of hospital stay was 1 d for 95% of patients (41 of 43), and 2 patients had prolonged stays of 4 d and 5 d, respectively. One patient was readmitted for a vaginal cuff abscess; this represented the only complication identified in this series., Conclusions: Robot-assisted laparoscopic surgery appears to be a reasonably safe and feasible method for the definitive surgical management of women with severe endometriosis.

Objective: The objective of this study was to determine the patterns of recurrence of stage IB-IIA endometrioid endometrial adenocarcinoma (EMCA) with lymphovascular invasion (LVSI)., Methods: A multicenter retrospective study of 1988 International Federation of Gynecology and Obstetrics stage IB-IIA EMCA patients with LVSI treated with surgery with or without radiation was conducted. Those with papillary serous or clear cell histologies and women treated with chemotherapy were excluded. Data regarding surgical-pathologic factors, treatment, and outcome were collected. Data were analyzed using χ test, Kaplan-Meier estimates, and Cox multivariate proportional hazards models., Results: From 1997 to 2008, we identified 131 patients with LVSI who met entry criteria among 5 institutions. Median age was 67 years (25%-75%: 60-75 years), and median follow-up was 4.25 years (25%-75%: 3-10 years). Following surgery, 45 patients were observed (Obs), and 86 patients received adjuvant radiation. We observed 30 total relapses 30/131 (23%): 11/45 (24%) in the Obs group and 19/86 (22%) in the adjuvant radiation group. Recurrence rates were similar between staged and unstaged patients: 24% (20/84) and 21% (10/47), respectively. Among Obs patients, 82% of relapses were local, whereas in patients treated with adjuvant radiation, 84% were distant. Relapses were significantly associated with invasion of the lower uterine segment (LUS) (P = 0.035). Both cancer-related survival and overall survival (OS) were not significantly impacted by adjuvant radiation, because of distant failure rates. Adjuvant radiation significantly improved pelvic control (P = 0.007). In a multivariate analysis, OS correlated with LUS invasion (P = 0.008) and was borderline-associated with stage (P = 0.06), whereas age (P = 0.12), grade (P = 0.31), myometrial invasion (P = 0.99), and radiation treatment (P = 0.23) were not., Conclusions: Overall recurrence rates for stage IB-IIA EMCA patients with LVSI are high (23%). Although adjuvant radiation therapy improved pelvic control, it did not impact recurrence rates, cancer-related survival, and OS, likely secondary to distant failures. The role of systemic therapy with or without radiotherapy for early-stage EMCA with LVSI should be evaluated, particularly in patients with high-grade tumors or involvement of the LUS.

Background: Obesity increases the risk of endometrial cancer (EC) and obese EC patients have the highest risk of death among all obesity-associated cancers. However, only two lifestyle interventions targeting this high-risk population have been conducted. In one trial, food disinhibition, as determined by the Three-Factor Eating Questionnaire, decreased post-intervention compared to baseline, suggesting an increase in emotional eating and, potentially, an increase in food related reward. Therefore, we evaluated appetitive behavior using functional magnetic resonance imaging (fMRI) and a visual food task in 8 obese, Stage I/II EC patients before and after a lifestyle intervention (Survivors in Uterine Cancer Empowered by Exercise and a Healthy Diet, SUCCEED), which aimed to improve nutritional and exercise behaviors over 16 group sessions in 6 months using social cognitive theory., Results: Congruent to findings in the general obese population, we found that obese EC patients, at baseline, had increased activation in response to high- vs. low-calorie food cues after eating a meal in brain regions associated with food reward (insula, cingulate gyrus; precentral gyrus; whole brain cluster corrected, p < 0.05). At 6 months post-intervention compared to baseline, we observed decreased activation for the high-calorie vs. non-food contrast, post-meal, in regions involved in food reward and motivation (posterior cingulate, cingulate gyrus, lateral globus pallidus, thalamus; claustrum; whole brain cluster corrected, p < 0.05)., Conclusions: Our preliminary results suggest behavioral lifestyle interventions may help to reduce high-calorie food reward in obese EC survivors who are at a high-risk of death. To our knowledge, this is the first study to demonstrate such changes.

Objective: The majority of endometrial cancer survivors (ECS) are obese and at risk for premature death. The purpose of this study was to evaluate an intervention for ECS to promote weight loss and a healthy lifestyle., Methods: Early stage overweight and obese (body mass index ≥ 25) ECS (N=75) were randomized to a 6-month lifestyle intervention (LI) or usual care (UC). The LI group received education and counseling for six months (10 weekly followed by 6 bi-weekly sessions). Weight change at 12 months was the primary endpoint. Secondary outcomes included fruit/vegetable servings/day and physical activity (PA). Multiple imputations were used for missing data and mixed models were used to analyze changes from baseline., Results: Adherence was 84% and follow-up data were available from 92% of participants at 6 months and 79% at 12 months. Mean [95% CI] difference in weight change between LI and UC groups at 6 months was -4.4 kg [-5.3, -3.5], p<0.001 and at 12 months was -4.6 kg [-5.8, -3.5], p<0.001. Mean [95% CI] difference in PA minutes between groups at 6 months was 100 [6, 194], p=0.038 and at 12 months was 89 [14, 163], p=0.020. Mean difference in kilocalories consumed was -217.8 (p<0.001) at 6 months and -187.2 (p<0.001) at 12 months. Mean [95% CI] difference in fruit and vegetable servings was 0.91 servings/day at 6 months and 0.92 at 12 months (p<0.001)., Conclusions: Behavior change and weight loss are achievable in overweight and obese ECS, however, the clinical implications of these changes are unknown and require a larger trial with longer follow-up., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective. To evaluate the surgical outcomes of robotic-assisted sacrocolpopexy (RASCP) before and after the incorporation of hands-on training for urology and gynecology residents. Study Design. Forty-one patients underwent RASCP between December 2008 and March 2010 with one surgeon. RASCP was performed in the context of surgical repair of complex pelvic organ prolapse and/or stress urinary incontinence. The first 20 cases (group I) were performed exclusively by the attending surgeon. In the last 21 cases (group II), the urology resident performed a 50% or more of the RASCP while the gynecology resident performed the supracervical hysterectomy. The primary outcome measure was vaginal vault support at 24 weeks postoperatively based on pelvic organ prolapse quantification (POP-Q). Results. Mean ± SD operative time for the entire surgery including RASCP was 282.3 ± 51.3 min and median EBL was 83.1 ± 50.4 mL. Patient demographics and stage of disease did not differ between groups. Procedure time, PACU time, blood loss, and intraoperative complications were similar between groups. Follow-up POP-Q evaluations demonstrated significant correction of all points on vaginal examination for both groups (P < 0.001). Conclusions. Incorporation of resident training during RASCP allows teaching of robotic surgery techniques in an effective manner without prolonging operative time or affecting the overall surgical outcome.

Background: The objective of this study was to compare the incidence of hand-foot syndrome (HFS) in patients who received pyridoxine versus placebo during pegylated liposomal doxorubicin (PLD) chemotherapy for recurrent ovarian, breast, or endometrial cancer., Methods: Patients received PLD 40 mg/m(2) for a maximum of 6 cycles. Patients were assigned randomly to receive pyridoxine 100 mg twice daily (Group A) or placebo (Group B) and received standard HFS education. Patients completed the Functional Assessment of Cancer Therapy quality-of-life (QOL) questionnaire. The incidence of HFS as measured by common toxicity criteria was compared between groups. Analyses were conducted according to an intent-to-treat basis. Chi-square tests or Fisher exact tests were used., Results: Thirty-four patients were enrolled (18 in Group A and 16 in Group B), and 5 patients were unevaluable for HFS assessment. Overall, 15 of 29 patients (52%) had HFS (all grades), and 10 of 29 patients (35%) had grade 2/3 events. Eight of 15 patients in Group A (53%) and 7 of 14 patients in Group B (50%) had HFS (P = .857). For grade 2/3 events, there was no difference between groups: Six of 15 events (40%) occurred in Group A, and 4 of 14 events (29%) occurred in Group B (P = .70). There was no difference in QOL scores between patients who had grade 2/3 HFS and patients who had grade 0/1 HFS. QOL analysis revealed that all patients had elevated social well being., Conclusions: Pyridoxine as administered in the current study did not prevent HFS in patients who received PLD. It is possible that QOL is not compromised in patients with HFS because they may have increased social well being while coping with their disease., (© 2010 American Cancer Society.)

Objective: Clinical assessment of androgen action and its correlation to testosterone levels in women has been challenging. The current gold standard for measuring biologically active testosterone (T) is serum free T by equilibrium dialysis. Alternative methods are desirable due to the cost, complexity, and limited availability of the equilibrium dialysis method. Salivary testing has been proposed as a possible substitute for serum testing. This study compared salivary versus serum measurements of total T (TT), bioavailable T (BT; consisting of free T [FT] and albumin-bound T), and FT from samples collected simultaneously in women who were either receiving transdermal T patch supplementation (300 microg/d) or a placebo patch., Methods: Naturally and surgically postmenopausal women receiving concomitant hormone therapy were recruited to participate in a 24- to 52-week phase III trial of a 300 microg/day transdermal T patch for the treatment of hypoactive sexual desire disorder., Results: Initial analysis demonstrated high correlations between TT, BT, and FT levels (r = 0.776-0.855). However, there was no correlation with salivary T levels for any of the serum T subtypes (r = 0.170-0.261). After log transformation, salivary T correlated modestly with BT (r = 0.436, P < 0.001), FT (r = 0.452, P < 0.001), and TT (r = 0.438, P < 0.001)., Conclusions: Although salivary testing of T concentrations is an appealing alternative because it is inexpensive and noninvasive, our results do not support the routine use of salivary T levels in postmenopausal women.

Background: The objective was to examine whether rates of disease recurrence, treatment-related adverse effects, and survival differed between obese or morbidly obese and nonobese patients., Methods: Data from patients who participated in a randomized trial of surgery with or without adjuvant radiation therapy were retrospectively reviewed. RESULTS.: Body mass index (BMI) data were available for 380 patients, of whom 24% were overweight (BMI, 25-29.9), 41% were obese (BMI, 30-39.9), and 12% were morbidly obese (BMI, > or =40). BMI did not significantly differ based on age, performance status, histology, tumor grade, myometrial invasion, or lymphovascular-space involvement. BMI > 30 was more common in African Americans (73%) than non-African Americans (50%). Patients with a BMI > or = 40 compared with BMI < 30 (hazards ratio [HR], 0.42; 95% confidence interval [CI], 0.09-1.84; P = .246) did not have lower recurrence rates. Compared with BMI < 30, there was no significant difference in survival in patients with BMI 30-39.9 (HR, 1.48; 95% CI, 0.82-2.70; P = .196); however, there was evidence for decreased survival in patients with BMI > or = 40 (HR, 2.77; 95% CI, 1.21-6.36; P = .016). Unadjusted and adjusted BMI hazards ratios for African Americans versus non-African Americans in the current study differed, thus suggesting a confounding effect of BMI on race. Eight (67%) of 12 deaths among 45 morbidly obese patients were from noncancerous causes. For patients who received adjuvant radiation therapy, increased BMI was significantly associated with less gastrointestinal (R, -0.22; P = .003) and more cutaneous (R, 0.17; P = .019) toxicities., Conclusions: In the current study, obesity was associated with higher mortality from causes other than endometrial cancer but not disease recurrence. Increased BMI was also associated with more cutaneous and less gastrointestinal toxicity in patients who received adjuvant radiation therapy. Future recommendations include lifestyle intervention trials to improve survival in obese endometrial cancer patients., (Copyright 2006 American Cancer Society.)