Vergote I.,University Hospitals |
Trope C.G.,Norwegian Radium Hospital |
Amant F.,University Hospitals |
Kristensen G.B.,Norwegian Radium Hospital |
And 14 more authors.
New England Journal of Medicine | Year: 2010
BACKGROUND: Primary debulking surgery before initiation of chemotherapy has been the standard of care for patients with advanced ovarian cancer. METHODS: We randomly assigned patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (so-called interval debulking surgery). RESULTS: Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval [CI], 0.84 to 1.13; P = 0.01 for non-inferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival. CONCLUSIONS: Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636). Copyright © 2010 Massachusetts Medical Society. All rights reserved.
Caronia D.,Human Genotyping Unit CeGen |
Martin M.,Hospital Universitario Gregorio Maranon |
Sastre J.,Hospital Universitario San Carlos |
De La Torre J.,Hospital Universitario San Carlos |
And 8 more authors.
Clinical Cancer Research | Year: 2011
Purpose: Hand-foot syndrome (HFS) is one of the most relevant dose-limiting adverse effects of capecitabine, an oral prodrug of 5-fluorouracil used in the standard treatment of breast and colorectal cancer. We investigated the association between grade 3 HFS and genetic variations in genes involved in capecitabine metabolism. Experimental Design: We genotyped a total of 13 polymorphisms in the carboxylesterase 2 (CES2) gene, the cytidine deaminase (CDD) gene, the thymidine phosphorylase (TP) gene, the thymidylate synthase (TS) gene, and the dihydropyrimidine dehydrogenase (DPD) gene in 130 patients treated with capecitabine. We correlated these polymorphisms with susceptibility to HFS. Results: We found an association of HFS appearance with rs532545 located in the promoter region of CDD (OR=2.02, 95% CI=1.02-3.99, P=0.039). Because we found no association between the rs532545 genotype and CDD mRNA expression in Epstein-Barr virus lymphoblastoid cells, we explored additional genetic variations across the CDD promoter. We found an insertion, rs3215400, in linkage disequilibrium with rs532545 (D′ = 0.92), which was more clearly associated with HFS (OR = 0.51, 95% CI = 0.27-0.95, P = 0.028) in patients and with total CDD gene expression (P = 0.004) in lymphoblastoid cells. In silico analysis suggested that this insertion might create a binding site for the transcriptional regulator E2F. Using a SNaPshot assay in lymphoblastoid cells, we observed a 5.7-fold increased allele-specific mRNA expression from the deleted allele. Conclusions: The deleted allele of rs3215400 shows an increased allele-specific expression and is significantly associated with an increased risk of capecitabine-induced HFS. ©2011 AACR.
Dumontet C.,French Institute of Health and Medical Research |
Krajewska M.,Sanford Burnham Institute for Medical Research |
Treilleux I.,French Institute of Health and Medical Research |
Mackey J.R.,Cross Cancer Institute |
And 4 more authors.
Clinical Cancer Research | Year: 2010
Purpose: There are currently no validated factors predictive of response to taxanes in patients with breast cancer. We analyzed specimens from patients included in the Breast Cancer International Research Group (BCIRG) 001 trial, a randomized study which showed the superiority of docetaxel/doxorubicin/ cyclophosphamide over fluorouracil/doxorubicin/cyclophosphamide as adjuvant therapy for nodepositive operable breast cancer in terms of disease-free survival (DFS) and overall survival (OS). Experimental Design: Immunohistochemical assessment of biological markers included histologic grade, tumor size, estrogen and progesterone receptors, lymph node status, HER2, MUC1, Ki-67/MIB-1, p53, Bcl-2, Bax, Bcl-XL, BAG-1, β-tubulin isotypes II, III and IV, τ protein, and detyrosinated α tubulin. Associations between selected parameters and survival were tested through univariate analyses, then completed with multivariate analyses and a bootstrap resampling technique. Results: In univariate analysis histologic grade, tumor size, number of involved nodes, estrogen and progesterone receptor status, p53, Ki-67, tubulin III, and τ protein were associated both with DFS and with OS. In multivariate analysis estrogen and progesterone receptors, tumor size, number of involved nodes, and Ki-67 protein were associated both with DFS and with OS, whereas τ protein levels were correlated with DFS and tubulin III and P53 were correlated with OS. No interaction was observed between Ki-67 and treatment allocation. Conclusions: We conclude that the expression in primary tumors of Ki-67 and p53 protein, as well as of the microtubule-related parameters ô protein and tubulin III, are independent prognostic factors in patients receiving adjuvant chemotherapy for node-positive breast cancer but are not predictive of benefit from docetaxel-containing adjuvant chemotherapy. ©2010 AACR.
Rodriguez A.,Eli Lilly and Company |
Calle A.,Hospital Universitario San Carlos |
Vazquez L.,Hospital Universitario Marques Of Valdecilla |
Chacon F.,Eli Lilly and Company |
And 2 more authors.
Diabetic Medicine | Year: 2011
Aims To assess blood glucose control and quality of health care provided to non-insulin-treated patients with Type2 diabetes mellitus in routine clinical practice in Spain. Methods In this observational, retrospective, cross-sectional study, patients were grouped as either having good or suboptimal blood glucose control according to International Diabetes Federation or American Diabetes Association HbA1c goals. Clinical and socio-demographic data and compliance with the main standard level of care recommendations of the International Diabetes Federation were recorded during a routine visit. Correlates of glucose control were analysed by logistic regression. Results Many patients were grouped as having suboptimal control under International Diabetes Federation (61.9%) or American Diabetes Association (45.0%) criteria. The mean number of accomplished International Diabetes Federation recommendations (7.3 out of 11) was higher for endocrinologists (than for internists or primary care physicians), and significantly more patients under their care were in the good glucose control group (than with primary care physicians). More recommendations were associated with blood glucose control using International Diabetes Federation than American Diabetes Association criteria, demanding higher quality of health care for achieving stricter goals. Some recommendations were poorly observed, particularly those concerning patients' education on diabetes, the prompt prescription of effective treatments and monitoring of complications. Diabetes complications were associated with being in the suboptimal control group. Patients' education on diabetes and HbA1c monitoring were associated with being in the good control group. Conclusions These results demonstrate the need for improvement in the management of patients with non-insulin-treated Type2 diabetes in actual clinical practice in Spain. Such improvement would entail a stricter adherence to International Diabetes Federation recommendations. © 2011 Eli Lilly and Company. Diabetic Medicine © 2011 Diabetes UK.
Garcia-Albea Ristol E.,Hospital Universitario Principe Of Asturias |
Garcia-Albea Martin J.,Hospital Universitario San Carlos
Revista de Neurologia | Year: 2010
Introduction. The neurosciences developed at a swift pace throughout the 19th century. In Spain, following the intellectual poverty of the absolutist rule of King Ferdinand, medicine took on a new flourishing lease of life in the last third of the century under the leadership of its most distinguished proponent, Santiago Ramón y Cajal. In April 1903, and in spite of the country's multiple political and social ups and downs, Madrid organised a great medical convention (14th International Congress of Medicine) that gathered together the foremost figures in the neurosciences. Development. This work attempts to describe the situation in which neurology found itself at that time, as well as the socio-political context, and to highlight the most important contributions that were made in our specialty. Conclusions. A whole medical generation from around the world enthusiastically took part and 1681 communications and papers were presented, many of which dealt with neurological topics. Special mention should be made of the presentations by Cajal, who described the histological structure of the optic thalamus, and by Pavlov, who gave details of his theory of conditioned reflexes for the very first time. © 2010 Revista de Neurología.
Trimbos B.,Leiden University |
Timmers P.,Medisch Centrum Rijnmond Zuid |
Timmers P.,Data Center |
Pecorelli S.,University of Brescia |
And 5 more authors.
Journal of the National Cancer Institute | Year: 2010
A long-term follow-up analysis of the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm (ACTION) from the European Organization for Research and Treatment of Cancer was undertaken to determine whether the original results with a median follow-up of 5.5 years could be verified after longer follow-up with more events. In the ACTION trial, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation (no further treatment). The original analysis found that adjuvant chemotherapy improved recurrence-free survival but not overall survival and found in a subgroup analysis that completeness of surgical staging was an independent prognostic factor, with better recurrence-free and overall survival among those with complete (optimal) surgical staging. After a median follow-up of 10.1 years, we analyzed the more mature data from the ACTION trial and found support for most of the main conclusions of the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy (hazard ratio of death = 1.89, 95% confidence interval = 0.99 to 3.60; overall two-sided log-rank test P =. 05). More cancer-specific deaths were observed among nonoptimally staged patients (40 [27%] of the 147 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) than among optimally staged patients (seven [9%] of the 75 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) (two-sided χ2 test for heterogeneity, P =. 06). Thus, completeness of surgical staging in patients with early ovarian cancer was found to be statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy appeared to be restricted to patients with nonoptimal surgical staging. © 2010 The Author. Published by Oxford University Press.
Lopez-Campos J.L.,Hospital Universitario Virgen Del Rocio |
Lopez-Campos J.L.,Institute Salud Carlos III |
Soriano J.B.,Fundacion Caubet Cimera Balearic Islands |
Calle M.,Hospital Universitario San Carlos
Chest | Year: 2013
Background: We aimed to evaluate the availability and practice of spirometry, training of technicians, and spirometer features and maintenance in Spain in both primary care (PC) and secondary care (SC) centers. Methods: We used a nationwide, cross-sectional, 36-item telephone survey of health-care centers in Spain to target the technician in charge of conducting spirometries in PC and SC centers where outpatient respiratory patients are routinely evaluated. The questions surveyed for resources, training, spirometer use, bronchodilator tests, and spirometer features and maintenance. Results: Of a total of 1,259 centers screened, 605 PC centers (21.2% of the PC centers in Spain) and 200 SC centers (24.9% of the SC centers in Spain) were surveyed. The response rate was 85.4% for PC centers and 75.1% for SC centers. All together, 19% of screened centers did not have a spirometer or were not using it. The number of spirometers per center and spirometries conducted per week was higher in SC centers than in PC centers (P < .001). Most centers received training for conducting spirometries, but this was periodically done in < 40%. Most centers used two inhalations of salbutamol for the bronchodilator test, but the international criteria of a positive test was considered only in 55.8% of PC and 52.8% of SC centers. Calibration of the spirometer was never done in 10.5% of PC and 3.1% of SC centers. Conclusions: This survey maps for the fi rst time, to our knowledge, the current situation of spirometry in Spain, identifying bottlenecks and suggesting future directions applicable in both PC and SC centers and elsewhere. © 2013 American College of Chest Physicians.
Prosthesis/annulus discongruence assessed by three-dimensional transoesophageal echocardiography: A predictor of significant paravalvular aortic regurgitation after transcatheter aortic valve implantation
Santos N.,Hospital Universitario San Carlos |
De Agustin J.A.,Hospital Universitario San Carlos |
Almeria C.,Hospital Universitario San Carlos |
Goncalves A.,Hospital Universitario San Carlos |
And 7 more authors.
European Heart Journal Cardiovascular Imaging | Year: 2012
Aims: Paravalvular aortic regurgitation (AR) is common after transcatheter aortic valve implantation (TAVI). This study aimed to assess the prosthesis/aortic annulus discongruence by three-dimensional (3D) transoesophageal (TOE) planimetry of aortic annulus and its impact on the occurrence of significant AR after TAVI. Methods and results: We included 33 patients who underwent TAVI with a balloon expandable device for severe aortic stenosis. To appraise the prosthesis/annulus discongruence, we defined a 'mismatch index' expressed as: annulus area - prosthesis area. The aortic annulus area was planimetered with 3D TOE, and approximated by circular area formula (π r2) using annulus diameter obtained by two-dimensional (2D) TOE. After TAVI, 13 patients (39.3) developed significant AR (<2/4). The occurrence of significant AR was associated to the 3D planimetered annulus area (P 0.04), and the 'mismatch index' obtained through 3D planimetered annulus area (P 0.03), but not to 'mismatch index' derived of 2D annulus diameter. In multivariate analysis, 'mismatch index' for 3D planimetered annulus area was the only independent predictor of significant AR (odds ratio: 10.614; 95 CI: 1.044-17.21; P 0.04). The area under the receiver operating characteristic curve for the 'mismatch index' by the 3D planimetered annulus area was 0.76 (95 CI: 0.54-0.92), whereas for 'mismatch index' obtained by the 2D circular area was 0.36 (95 CI: 0.17-0.55). Using the 3D planimetered annulus area as the reference parameter to decide the prosthetic size, the choice would have been different in 21 patients (63). Conclusion: Three-dimensional TOE planimetry of aortic annulus improves the assessment of prosthesis/annulus discongruence and predicts the appearance of significant AR after TAVI. © The Author 2012.
De Agustin J.A.,Hospital Universitario San Carlos |
Marcos-Alberca P.,Hospital Universitario San Carlos |
Fernandez-Golfin C.,Hospital Universitario San Carlos |
Goncalves A.,Hospital Universitario San Carlos |
And 7 more authors.
Journal of the American Society of Echocardiography | Year: 2012
Background: The two-dimensional (2D) proximal isovelocity surface area (PISA) method has some technical limitations, mainly the geometric assumptions of PISA shape required to calculate effective regurgitant orifice area (EROA). Recently developed single-beat, real-time three-dimensional (3D) color Doppler imaging allows direct measurement of PISA without geometric assumptions. The aim of this study was to validate this novel method in patients with chronic mitral regurgitation (MR). Methods: Thirty-three patients were included, 25 (75.7%) with degenerative MR and eight (24.2%) with functional MR. EROA and regurgitant volume were assessed using transthoracic 2D and 3D PISA methods. The quantitative Doppler method and 3D transesophageal echocardiographic planimetry of EROA were used as reference methods. Results: Both EROA and regurgitant volume assessed using the 3D PISA method had better correlations with the reference methods than conventional 2D PISA. A consistent significant underestimation of EROA and regurgitant volume using 2D PISA was observed, particularly in the assessment of eccentric jets. On the basis of 3D transesophageal echocardiographic planimetry of EROA, 14 patients had severe MR (EROA ≥ 0.4 cm2). Of these 14 patients, 42.8% (6 of 14) were underestimated as having nonsevere MR (EROA ≤ 0.4 cm2) by the 2D PISA method. In contrast, the 3D PISA method had 92.9% (13 of 14) agreement with 3D transesophageal planimetry in classifying severe MR. Good intraobserver and interobserver agreement for 3D PISA measurements was observed, with intraclass correlation coefficients of 0.96 and 0.92, respectively. Conclusions: Direct measurement of PISA without geometric assumptions using single-beat, real-time 3D color Doppler echocardiography is feasible in the clinical setting. MR quantification using this methodology is more accurate than the conventional 2D PISA method. © 2012 American Society of Echocardiography.
Vivas D.,Hospital Universitario San Carlos |
Bernardo E.,Hospital Universitario San Carlos |
Palacios-Rubio J.,Hospital Universitario San Carlos |
Fernandez-Ortiz A.,Hospital Universitario San Carlos
Current Treatment Options in Cardiovascular Medicine | Year: 2013
Opinion statement: Evidences on hyperglycemia management in patients with acute coronary syndrome (ACS) are scarce and controversial. While approaches such as infusion of glucose, insulin, and potassium (GIK therapy) have not demonstrated any improvement in outcome, glycemic control by means of either continuous insulin infusion or subcutaneous on-demand boluses may be useful only when glycaemia is successfully controlled. Nevertheless, results from several studies are controversial and there is no consensus on glycaemia target values. Concerning oral antidiabetic treatment, previous reports stated an increase in heart attacks throughout their chronic use, however no studies have addressed the effects of either starting or continuing oral antidiabetics during ACS setting. Therefore, there is not enough evidence to strongly recommend any specific therapy to manage hyperglycemia in an ACS patient other than trying to keep glycaemia within reasonable levels (usually defined by consensus), and there is evidence discouraging the use of GIK therapy since no beneficial effect has been observed. © 2012 Springer Science+Business Media New York.