Lete I.,Araba University Hospital |
Chabbert-Buffet N.,University Pierre and Marie Curie |
Jamin C.,boulevard Haussmann |
Lello S.,Gynecology Unit |
And 3 more authors.
European Journal of Contraception and Reproductive Health Care | Year: 2015
Objective Since its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E2) (estradiol valerate [E2V]/dienogest [DNG] and E2/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers.Methods A literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill.Results The haemostatic impact of E2 pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E2V/DNG were generally not statistically significant. E2/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG.Conclusion E2/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed. Chinese Abstract 50,(VTE)EE/LNG/DRSP2(COCs)E2[E2V] /[DNG]/[NOMAC]MEDLINE/PubMed////////// © 2015 © 2015 The European Society of Contraception and Reproductive Health.
Stelloo E.,Leiden University |
Bosse T.,Leiden University |
Nout R.A.,Leiden University |
Mackay H.J.,University of Toronto |
And 11 more authors.
Modern Pathology | Year: 2015
This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment.
PubMed | Cancer Research UK Research Institute, The Royal Marsden NHS Foundation Trust, Kingston Hospital and Gynecology Unit
Type: Comparative Study | Journal: European radiology | Year: 2016
To compare sensitivity and specificity of endovaginal versus external-array coil T2-W and T2-W+DWI for detecting and staging small cervical tumours.Optimised endovaginal and external array coil MRI at 3.0-T was done prospectively in 48 consecutive patients with stage Ia/Ib1 cervical cancer. Sensitivity/specificity for detecting tumour and parametrial extension against histopathology for a reading radiologist were determined on coronal T2-W and T2W+DW images. An independent radiologist also scored T2-W images without and with addition of DWI for the external-array and endovaginal coils on separate occasions >2 weeks apart. Cohens kappa assessed inter- and intra-observer agreement.Median tumour volume in 19/38 cases positive on subsequent histology was 1.75 cm(3). Sensitivity, specificity, PPV, NPV were: reading radiologist 91.3 %, 89.5 %, 91.3 %, 89.5 %, respectively; independent radiologist T2-W 82.6 %, 73.7 %, 79.1 %, 77.8 % for endovaginal, 73.9 %, 89.5 %, 89.5 %, 73.9 % for external-array coil. Adding DWI improved sensitivity and specificity of endovaginal imaging (78.2 %, 89.5 %); adding DWI to external-array imaging improved specificity (94.7 %) but reduced sensitivity (66.7 %). Inter- and intra-observer agreement on T2-W+DWI was good (kappa=0.67 and 0.62, respectively).Endovaginal coil T2-W MRI is more sensitive than external-array coil for detecting tumours <2 cm(3); adding DWI improves specificity of endovaginal imaging but reduces sensitivity of external-array imaging. Endovaginal more accurate than external-array T2-W MRI for detecting small cervical cancers. Addition of DWI improves sensitivity and specificity of endovaginal T2-W imaging. Addition of DWI substantially reduces sensitivity of external-array T2-W imaging.
PubMed | Oxford Genetics, St. Mary's University, Leiden University, University of Groningen and 4 more.
Type: Journal Article | Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | Year: 2016
Studies in early-stage, predominantly low- and intermediate-risk endometrial cancer have demonstrated that L1 cell adhesion molecule (L1CAM) overexpression identifies patients at increased risk of recurrence, yet its prognostic significance in high-risk endometrial cancer is unclear. To evaluate this, its frequency, and the relationship of L1CAM with the established endometrial cancer biomarker p53, we analyzed the expression of both markers by immunohistochemistry in a pilot series of 116 endometrial cancers (86 endometrioid, 30 non-endometrioid subtype) with high-risk features (such as high tumor grade and deep myometrial invasion) and correlated results with clinical outcome. We used The Cancer Genome Atlas (TCGA) endometrial cancer series to validate our findings. Using the previously reported cutoff of 10% positive staining, 51/116 (44%) tumors were classified as L1CAM-positive, with no significant association between L1CAM positivity and the rate of distant metastasis (P=0.195). However, increasing the threshold for L1CAM positivity to 50% resulted in a reduction of the frequency of L1CAM-positive tumors to 24% (28/116), and a significant association with the rate of distant metastasis (P=0.018). L1CAM expression was strongly associated with mutant p53 in the high-risk and TCGA series (P<0.001), although a substantial fraction (36% of endometrioid, 10% of non-endometrioid morphology) of p53-mutant endometrial cancers displayed <10% L1CAM positivity. Moreover, 30% of p53-wild-type non-endometrioid endometrial cancers demonstrated diffuse L1CAM staining, suggesting p53-independent mechanisms of L1CAM overexpression. In conclusion, the previously proposed threshold for L1CAM positivity of >10% does not predict prognosis in high-risk endometrial cancer, whereas an alternative threshold (>50%) does. L1CAM expression is strongly, but not universally, associated with mutant p53, and may be strong enough for clinical implementation as prognostic marker in combination with p53. The high frequency of L1CAM expression in high-risk endometrial cancers suggests that it may also be a promising therapeutic target in this tumor subset.
Martinelli I.,anchi Bonomi Hemophilia And Thrombosis Center |
Ruggenenti P.,Mario Negri Institute for Pharmacological Research |
Ruggenenti P.,Nephrology Unit |
Cetin I.,University of Milan |
And 14 more authors.
Blood | Year: 2012
To assess whether antithrombotic prophylaxis with low-molecular-weight heparin effectively prevents recurrence of late pregnancy complications, 135 women with previous history of preeclampsia, hemolytic anemia, elevated liver enzymes and low platelet count syndrome, intrauterine fetal death, fetal growth restriction, or placental abruption who had been referred within the 12th gestational week were randomized to medical surveillance alone (n = 68) or combined to open-label nadroparin (3800 IU daily subcutaneous injections) treatment (n = 67) in the setting of a randomized, parallel-group, superiority trial, run in Italy from April 2007 to April 2010. Primary outcome was a composite end point of late-pregnancy complications. Analysis was by intention to treat. The study was stopped for futility at the time of the first planned interim analysis. Among the 128 women eventually available for final analyses, 13 of the 63 (21%) randomized to nadroparin compared with 12 of the 65 (18%) on medical surveillance alone progressed to the primary end point. The absolute event risk difference between treatment arms (2.2; -1.6 to 16.0) was not statistically significant (P = .76). Thus, nadroparin did not prevent late-pregnancy complications in women at risk of recurrence. This finding challenges the role of antithrombotic prophylaxis with low-molecular-weight heparin in the prevention of recurrent late pregnancy complications The trial was registered at http://ricerca-clinica.agenziafarmaco.it as EudraCT 2006-004205-26. © 2012 by The American Society of Hematology.
Philip C.-A.,Center Leon Berard |
Pautier P.,Gynecology Unit |
Duffaud F.,Marseille University Hospital Center |
Ray-Coquard I.,Center Leon Berard
Current Oncology Reports | Year: 2014
High-grade undifferentiated sarcomas (HGUS) are rare malignancies accounting for 6 % of all uterine sarcomas and have a very poor outcome. Histological classification of HGUS is currently debated as a subgroup with uniform nucleoli, and frequently YWHAE–FAM22 transcript has been described, constituting a potential target for new therapies. In localized HGUS, surgery involving total hysterectomy and bilateral oophorectomy is recommended. Adjuvant radiotherapy has recently been suggested in a retrospective study to decrease local recurrence and improve survival versus observation in localized HGUS. In metastatic or recurrent disease, chemotherapy with doxorubicin with or without ifosfamide constitutes the standard of care. Gemcitabine plus docetaxel also seems to be an interesting alternative. Targeted therapies such as pazopanib are now available for soft tissue sarcomas and so could be proposed for uterine sarcoma patients after first- or second-line chemotherapy in the metastatic phase. Further investigations are needed to determine their indications and targets. A European Organisation for Research and Treatment of Cancer (EORTC) randomized trial testing maintenance therapy with cabozantinib after first-line chemotherapy in HGUS is ongoing. © 2014, Springer Science+Business Media New York.
Della Pepa C.,Gynecology Unit |
Banerjee S.,Gynecology Unit
OncoTargets and Therapy | Year: 2014
Targeting angiogenesis is proving to be a successful approach in the management of ovarian cancer. The vascular endothelial growth factor inhibitor, bevacizumab, is the first angiogenesis inhibitor to have shown a significant progression-free survival advantage in the Phase III setting. There is now evidence supporting the use of bevacizumab in combination with chemotherapy for first-line and relapsed (platinum-sensitive and resistant) ovarian cancer. In this review, we summarize the positive Phase III trial (OCEANS [Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum Sensitive Recurrent Disease]) that led to European Medicines Agency approval of bevacizumab in platinum-sensitive first relapse and discuss the best use of the drug in this disease. © 2014 Della Pepa and Banerjee.
Leary A.,Gynecology Unit |
Petrella M.C.,Gynecology Unit |
Pautier P.,Gynecology Unit |
Duvillard P.,Gynecology Unit |
And 6 more authors.
Gynecologic Oncology | Year: 2014
Background Most borderline ovarian tumors (BOTs) are cured with surgery. However BOTs with invasive implants have a poor prognosis with a mortality of 20-40%. The benefit of adjuvant chemotherapy (CT) in this setting remains poorly defined. Methods Retrospective study of serous BOT + invasive implants treated with adjuvant CT. Results 36 patients were referred with serous BOTs + invasive implants and treated with surgery and platinum-based CT between 06/1982 and 02/2011. 83% were stage III/IV. Tumors demonstrated microinvasion, micropapillary pattern or desmoplastic implants in 53%, 47% and 67% of cases, respectively. 8% had fertility-sparing surgery. Taking into account initial and completion surgeries, R0 was achieved in 84% (27/32) (NA, N = 4). The majority (72%) received a combination of platinum + taxane. 11% of patients experienced a G3/G4 toxicity. 13 of 36 (36%) patients relapsed at a median of 27.3 months after diagnosis of invasive implants. Among 12 patients with histologically confirmed relapse, 8 patients progressed with invasive disease in the form of carcinoma or invasive implants. 5 year PFS/OS were 67%/96%. Neither microinvasion, micropapillary pattern, nor desmoplastic implants predicted relapse. In cases with evaluable disease, an objective response to chemotherapy was observed in 4 of 6 patients. Conclusion This is the largest study of BOT with invasive implants treated with surgery and adjuvant platinum-based CT. Treatment was well tolerated and the invasive relapse rate was 22% (8/36). Although numbers are small, the objective responses suggest a possible role for adjuvant CT in BOTs with invasive implants. © 2013 Elsevier Inc.
Cagnacci A.,Gynecology Unit |
Cannoletta M.,Gynecology Unit |
Caretto S.,Gynecology Unit |
Zanin R.,Gynecology Unit |
And 2 more authors.
Menopause | Year: 2011
Objective: Vasomotor symptoms may increase the risk for cardiovascular diseases through still elusive mechanisms. Increased cortisol release may favor atherosclerosis. In this study, we tested whether vasomotor and psychological symptoms are associated with an increase in cortisol levels. Methods: A cross-sectional investigation on women in early menopause enrolled consecutively between January and June 2009 was conducted. This study was set at a menopause outpatient service at University Hospital. Participants included 85 healthy women who were 6 months to 5 years postmenopause. The 24-hour urinary cortisol level and Greene Climacteric Scale scores were evaluated. Anthropometric parameters and fasting blood samples for the determination of high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, glucose, and insulin levels were measured. Body mass index, waist-to-hip ratio, and homeostatic model assessment of insulin resistance were calculated. The relation between Greene Climacteric Scale scores and 24-hour urinary cortisol level and between 24-hour urinary cortisol level and lipid levels or insulin resistance was determined. Results: The Greene Climacteric Scale score for climacteric symptoms (coefficient of regression [CR], 1.343; 95% CI, 0.441-2.246) and body mass index (CR, 4.469; 95% CI, 1.259-7.678) explained 32.5% and 10.3%, respectively, of the variance in 24-hour urinary cortisol level (r = 0.428; P = 0.0003). Twenty-four-hour urinary cortisol level was inversely related to HDL-cholesterol level (CR, -0.065; 95% CI, -0.114 to -0.017; r = 0.283; P = 0.009) and was related to waist girth (CR, 0.685; 95% CI, 0.306-1.063) and homeostatic model assessment of insulin resistance (CR, 0.097; 95% CI, 0.032-0.162; r = 0.510; P = 0.0001). Conclusions: In early postmenopausal women, the Greene Climacteric Scale score is associated with increased 24-hour urinary cortisol level. Increased cortisol level is associated with known risk factors for cardiovascular disease, such as insulin resistance and decreased HDL-cholesterol level. © 2011 by The North American Menopause Society.
PubMed | Gynecology Unit, Institut Universitaire de France, University of Québec and Laval University
Type: Journal Article | Journal: Adipocyte | Year: 2016
To assess the ability of CT-derived measurements including adipose tissue attenuation and area to predict fat cell hypertrophy and related cardiometabolic risk.Abdominal adipose tissue areas and radiologic attenuation were assessed using 4 CT images in 241 women (age: 47years, BMI: 26.5kg/m(2)). Fat cell weight was measured in paired VAT and SAT samples. Fasting plasma lipids, glucose and insulin levels were measured.Adipose tissue attenuation was negatively correlated with SAT (r=-0.46) and VAT (r=-0.67) fat cell weight in the corresponding depot (p<0.0001 for both). Women with visceral adipocyte hypertrophy had higher total-, VLDL-, LDL- and HDL-triglyceride and apoB levels as well as a higher cholesterol/HDL-cholesterol ratio, fasting glucose and insulin levels compared to women with smaller visceral adipocytes. Adjustment for VAT area minimized these differences while subsequent adjustment for attenuation eliminated all differences, with the exception of fasting glycaemia. In SAT, adjustment for VAT area and attenuation eliminated all adipocyte hypertrophy-related alterations except for fasting hyperglycaemia.CT-derived adipose tissue attenuation and area both contribute to explain variation in the cardiometabolic risk profile associated with the same biological parameter: visceral fat cell hypertrophy.