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The present report is of two patients who, immediately after internal carotid endarterectomy, presented with unexplained hemiplegia, despite normal findings on repeated MRI scans, which secondarily evolved into homolateral subacute corticobasal syndrome (CBS), with asymmetrical hemispheric hypometabolism and evidence of dopaminergic denervation. This prompted us to propose an hypothesis of transient cerebral hypoxia arising during the surgical clamping period that might have provoked a prolonged or permanent functional lesion of the left hemisphere and basal ganglia, with no visible infarction on MRI but only synaptic rearrangement of the neural networks, thereby revealing or exacerbating a potentially preexisting silent impairment.
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Enfermedades de los Ganglios Basales/etiología , Endarterectomía Carotidea/efectos adversos , Complicaciones Posoperatorias/terapia , Anciano , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/terapia , Hemorragia Cerebral/etiología , Hemorragia Cerebral/terapia , Circulación Cerebrovascular , Imagen de Difusión por Resonancia Magnética , Dopaminérgicos/uso terapéutico , Hemiplejía/etiología , Hemiplejía/terapia , Humanos , Hipoxia Encefálica/etiología , Hipoxia Encefálica/terapia , Levodopa/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/etiología , Trastornos de la Memoria/psicología , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , Complicaciones Posoperatorias/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: The 3D modeling of human anatomy is more and more often used in medical education and in computer-augmented medicine. The lack of a 3D model of the pericardium has led us to its implementation. METHODS: The pericardium was reconstructed from a CT scan recording of a young, healthy subject. The anonymous CT scan data were blindly reviewed and interpreted by two independent radiologists. Stage one consisted in reconstructing the entire heart with the main afferent and efferent vessels. As the pericardial layers cannot be observed only with the CT scan, the second stage was to draw its reflection line following the most frequent model of pericardium defined in one of our prior studies. Afterwards, the epicardium had to be milled to finally create a pericardial sac area. RESULTS: Firstly, a model of one normal heart was reconstructed. Secondly, parietal and visceral layers of the pericardium have been achieved from the representation of their line of reflection. A short video shows recesses and sinuses and particularly, the transverse sinus crossed by a virtual object. CONCLUSIONS: The resulting model is subject to certain limits, including reproducibility linked to the operator, individual anatomical variation, and scanner resolution but it represents a pericardial pouch true to its more common anatomical morphology. It offers a very precise educational tool. It must be considered as the first step of an automatic segmentation and reconstruction process to modelize normal and pathological pericardium. This is also the first step before a 3D dynamic model, synchronized with heartbeats.
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Imagenología Tridimensional/métodos , Pericardio/anatomía & histología , Pericardio/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Variaciones Dependientes del Observador , Valores de ReferenciaRESUMEN
Objective.To optimize and ensure the safety of ultrasound brain therapy, personalized transcranial ultrasound simulations are very useful. They allow to predict the pressure field, depending on the patient skull and probe position. Most transcranial ultrasound simulations are based on numerical methods which have a long computation time and a high memory usage. The goal of this study is to develop a new semi-analytical field computation method that combines realism and computation speed.Approach.Instead of the classic ray tracing, the ultrasonic paths are computed by time of flight minimization. Then the pressure field is computed using the pencil method. This method requires a smooth and homogeneous skull model. The simulation algorithm, so-called SplineBeam, was numerically validated, by comparison with existing solvers, and experimentally validated by comparison with hydrophone measured pressure fields through anex vivohuman skull.Main results.SplineBeam simulated pressure fields were close to the experimentally measured ones, with a focus position difference of the order of the positioning error and a maximum pressure difference lower than 6.02%. In addition, for those configurations, SplineBeam computation time was lower than another simulation software, k-Wave's, by two orders of magnitude, thanks to its capacity to compute the field only at the focal spot.Significance.These results show the potential of this new method to compute fast and realistic transcranial pressure fields. The combination of this two assets makes it a promising tool for real time transcranial pressure field prediction during ultrasound brain therapy interventions.
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Cráneo , Cráneo/diagnóstico por imagen , Humanos , Factores de Tiempo , Presión , Simulación por Computador , Terapia por Ultrasonido/métodos , Algoritmos , Ultrasonografía/métodosRESUMEN
BACKGROUND: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.
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Neoplasias de la Mama , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Quimioterapia Adyuvante/métodos , Anciano , Adulto , Ganglios Linfáticos/patología , Anciano de 80 o más AñosRESUMEN
Detection of disseminated tumour cells (DTCs) in bone marrow by immunocytochemistry (ICC) includes morphological evaluation of cytokeratin immunopositive cells. The aim of this study was to disclose the prognostic significance of different morphological categories of ICC-positive cells according to treatment status and tumour subtype. Bone marrow samples (at surgery) were analysed for the presence of cytokeratin-positive DTCs by a standard immunocytochemical method. The immunopositive cells were classified into the following categories, prior to any analysis of the association between DTCs and clinical outcome: tumour cells (TC), uninterpretable cells (UIC), hematopoietic cells (HC), and questionable HC (QHC). The analysis included 747 early breast cancer patients. Median follow-up was 84 months for relapse, and 99 months for death. The categorisation of the ICC positive cells revealed TC in 13.3 % of the patients, whereas 13.1, 17.8, and 21.4 % of the cases were positive for UIC, QHC, and HC, respectively. Analysing all patients, only TC and UIC predicted systemic relapse. Separate analysis of all patients not receiving adjuvant systemic treatment (No-Adj; n = 389) showed that only QHC were associated with reduced survival (DDFS: p = 0.008; BCSS: p = 0.004, log rank) and the presence of QHC also remained significant in multivariate analysis. Primary tumour subgroup analysis (of all patients) by hormone receptors (HR) and HER2, demonstrated that only TC/UIC had prognostic impact in the HR+/HER2- patients, whereas presence of QHC was associated with unfavourable outcome only in triple negative patients (DDFS: p = 0.004; BCSS: p = 0.024). Patients with ≥3HC had improved outcome compared to those with fewer/no HC (DDFS: p = 0.005; BCSS: p = 0.009). Hence, morphological DTC subgroups may differ in clinical significance according to primary tumour subtype and treatment status. This emphasises the importance of DTC characterisation, and separate analyses of DTC categories according to tumour subtype. Hematopoietic ("false positive") cells might predict an immune-related favorable clinical outcome.
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Médula Ósea/patología , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/secundario , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidad , Carcinoma Lobular/terapia , Forma de la Célula , Estudios Transversales , Reacciones Falso Positivas , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Mastectomía Segmentaria , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: In centers for craniosynostosis surgery, the volume of activity does not necessarily reflect the quality of the treatment. OBJECTIVE: Our aim was to analyze a retrospective series of patients over a period of 6 years in a low-volume craniosynostosis surgery center, and to study indicators that reflect the quality of treatment. PATIENTS AND METHODS: The analysis included all patients who underwent a craniofacial surgery for all forms of craniosynostosis during the period 2012-2017 (annual follow-up for 4 years). Data on the type of synostosis, sex, age, weight, type of surgery, duration of surgery, blood transfusion, postinterventional care, and total length of hospital stay were collected. Medical and surgical complications were recorded using the Leeds classification. RESULTS: Overall, 42 patients (33 male; 23 cases of scaphocephaly, 13 cases of trigonocephaly, 4 cases of coronal plagiocephaly, 1 case of lambdoid plagiocephaly, and 1 case of brachycephaly) underwent craniofacial surgery with a median age of 7.4 months [4.8; 10.4] and a mean weight of 8.40 ± 1.92 kg at surgery. The median hospital stay was 7 days [6;7] with 1 day in the postinterventional care unit for 83% of patients. The global complication rate was 12% (95% CI: 4%-26%) with three minor cutaneous and two major (cardiovascular and septic) complications. CONCLUSION: Complication rates reflect the quality of care in a center that treats craniosynostosis much more than do the number of procedures, mean hospital stay, and blood transfusion rates. It is essential to define new indicators capable of measuring the quality of life linked to surgical procedures and of using them to assess the competence of a center.
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Craneosinostosis , Plagiocefalia , Humanos , Masculino , Lactante , Estudios Retrospectivos , Calidad de Vida , Craneosinostosis/cirugía , Huesos , Resultado del TratamientoRESUMEN
BACKGROUND: A registry of chronic subdural hematoma does not exist in France yet. OBJECTIVE: To present a monocentric pilot project of a French registry of surgical management of chronic subdural hematoma. METHOD: A monocentric pseudonymized formal database was created. From May 2020 to May 2021, all patients undergoing surgical evacuation of chronic subdural hematoma were entered into the database. RESULTS: One hundred and twenty four surgeries from 113 patients were entered in the database. Patients' demographic and surgical data as well as follow-up are described. CONCLUSION: A local database is easy to implement. We propose a national registry of chronic subdural hematoma management.
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Hematoma Subdural Crónico , Francia , Hematoma Subdural Crónico/cirugía , Humanos , Proyectos Piloto , Nivel de AtenciónRESUMEN
OBJECTIVE: Intracranial aneurysm (IA) is a frequent vascular malformation that can be managed by endovascular treatment (EVT) or microsurgery. A previously treated IA can recanalize, which may require further treatment. The aim of our study was to evaluate procedural complications related to IA retreatment and their risk factors. METHODS: All patients retreated for IA between 2007 and 2017 in 4 hospitals were included. We retrospectively reviewed the frequency of procedural complications of IA retreatment, defined as death or≥1-point increase in modified Rankin score 24h after the procedure. We then screened for risk factors of procedural complications by comparing the characteristics of patients with and without complications. RESULTS: During the inclusion period, 4,997 IAs were treated in our 4 institutions. Of these, 237 (4.7%) were retreated. 29 (12.2%) had≥1 procedural complication. However, severe complications, defined as death or dependency at 1 month, occurred only in 3 patients (1.3%). The only risk factor for complications was microsurgical clipping as retreatment. CONCLUSIONS: Procedural complications during IA retreatment were frequent but, in most cases, retreatment did not lead to death or severe disability. The only risk factor for complications of IA retreatment was clipping as retreatment. However, the design of the study did not allow any conclusion to be drawn as to the optimal means of aneurysm retreatment, and further studies are needed.
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Aneurisma Roto , Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma Intracraneal , Aneurisma Roto/terapia , Procedimientos Endovasculares/efectos adversos , Humanos , Aneurisma Intracraneal/cirugía , Recurrencia , Retratamiento , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Anisotropy is a good indicator of white matter fascicle macrostructure and organization but the interpretation of its changes with age remains difficult. The increase of WM fascicle fractional anisotropy with time and its relationship with WM fascicle volume have never been examined during childhood. We studied the maturation of associative WM fascicles during childhood using MR imaging-based DTI. We explored whether the fractional anisotropy increase of the main WM fascicles persists beyond the period of brain growth and is related to WM fascicle volume increase. MATERIALS AND METHODS: In a series of 25 healthy children, the fractional anisotropy and volume of 15 associative WM fascicles were calculated. Several regression linear mixed models were used to study maturation parameters (fractional anisotropy, volume, and total telencephalon volume) considered as dependent variables, while age and sex were independent variables (the variable identifying the different WM fascicles was considered as a repeated measure). RESULTS: In children older than 8 years of age, WM fascicle fractional anisotropy increased with age (P value = .045) but not its volume (P value = .7) or the telencephalon volume (P value = .16). The time course of WM fascicle fractional anisotropy and volume suggested that each WM fascicle might follow a specific pattern of maturation. CONCLUSIONS: The fractional anisotropy increase of several WM fascicles after 8 years of age may not result from an increase in WM fascicle volume. It might be the consequence of other developmental processes such as myelination.
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Encéfalo/crecimiento & desarrollo , Sustancia Blanca/crecimiento & desarrollo , Anisotropía , Niño , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Essentials The role of coagulation factor V (encoded by F5) in cancer pathogenesis is unknown. The clinical significance of tumor-expressed F5 was evaluated in breast cancer patient cohorts. F5 was expressed in human breast tumors, and the expression was higher than in normal tissue. High F5 expression was associated with aggressive tumors, but also with survival in breast cancer. SUMMARY: Background Tumor expression of certain coagulation factors has been linked to cancer progression. Single nucleotide polymorphisms (SNPs) in F5 (encoding the FV protein) have been found to be associated with breast cancer; however, the role of coagulation factor V (FV) in cancer pathogenesis remains undiscovered. Objectives We aimed to investigate the clinical significance of FV and the regulatory role of F5 gene variants in breast cancer. Patients/Methods A Scandinavian 503-sample breast cancer cohort and three public breast cancer datasets (GOBO, TCGA and KM plotter) were used to determine associations between F5 gene expression (tumor-specific), circulating FV, F5 SNPs, clinical characteristics and breast cancer survival. Immunohistochemistry (IHC) was used to detect FV antigen in tumors. Results F5 expression was 2-fold higher in breast tumors compared with normal tissue, and the presence of FV antigen in breast tumors was confirmed by IHC staining. F5 expression was increased in patients with hormone receptor negative tumors, triple negative tumors, HER2-enriched and basal-like tumors. In patients with basal tumors, high expression of F5 was associated with improved overall survival (hazard ratio, HR = 0.52, 95% confidence interval, 0.31-0.86). SNPs in F5 were associated with tumor size and luminal A tumors. The rs6427202-rs9332542 C-G haplotype, previously associated with breast cancer, displayed a cis-regulatory effect on F5 expression in tumors and plasma FV antigen levels. In silico mining supported this regulatory function. Conclusions FV was a possible marker of aggressive breast cancer, yet also a predictor of favorable outcome. Evaluation of FV expression may be clinically useful for prognosis and treatment decisions in aggressive breast cancer.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Factor V/genética , Polimorfismo de Nucleótido Simple , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Estudios Transversales , Bases de Datos Genéticas , Femenino , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Metástasis Linfática , Clasificación del Tumor , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Pronóstico , Neoplasias de la Mama Triple Negativas/sangre , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología , Carga Tumoral , Regulación hacia ArribaRESUMEN
BACKGROUND: The optimization of the management for elderly glioblastoma patients is crucial given the demographics of aging in many countries. We report the outcomes for a "real-life" patient cohort (i.e. unselected) comprising consecutive glioblastoma patients aged 70 years or more, treated with different radiotherapy +/- temozolomide regimens. METHODS: From 2003 to 2016, 104 patients ≥ 70 years of age, consecutively treated by radiotherapy for glioblastoma, were included in this study. All patients were diagnosed with IDH-wild type glioblastoma according to pathological criteria. RESULTS: Our patient cohort comprised 51 female patients (49%) and 53 male. The median cohort age was 75 years (70-88), and the median Karnofsky performance status (KPS) was 70 (30-100). Five (5%) patients underwent macroscopic complete resection, 9 (9%) had partial resection, and 90 (86%), a stereotactic biopsy. The MGMT promoter was methylated in 33/73 cases (45%). Fifty-two (50%), 38 (36%), and 14 (14%) patients were categorized with RPA scores of III, IV, and I-II. Thirty-three (32%) patients received normofractionated radiotherapy (60 Gy, 30 sessions) with temozolomide (Stupp), 37 (35%) received hypofractionated radiotherapy (median dose 40 Gy, 15 sessions) with temozolomide (HFRT + TMZ), and 34 (33%) HFRT alone. Patients receiving only HFRT were significantly older, with lower KPSs. The median overall survival (OS; all patients) was 5.2 months. OS rates at 12, 18, and 24 months, were 19%, 12%, and 5%, respectively, with no statistical differences between patients receiving Stupp or HFRT + TMZ (P = 0.22). In contrast, patients receiving HFRT alone manifested a significantly shorter survival time (3.9 months vs. 5.9 months, P = 0.018). In multivariate analyses, the prognostic factors for OS were: i) the type of surgery (HR: 0.47 [0.26-0.86], P = 0.014), ii) RPA class (HR: 2.15 [1.17-3.95], P = 0.014), and iii) temozolomide use irrespective of radiotherapy schedule (HR: 0.54 [0.33-0.88], P < 0.02). MGMT promoter methylation was neither a prognostic nor a predictive factor. CONCLUSIONS: These outcomes agree with the literature in terms of optimal surgery and the use of HFRT as a standard treatment for elderly GBM patients. Our study emphasizes the potential benefit of using temozolomide with radiotherapy in a real-life cohort of elderly GBM patients, irrespective of their MGMT status.
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Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/terapia , Quimioradioterapia , Dacarbazina/análogos & derivados , Glioblastoma/terapia , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/patología , Dacarbazina/uso terapéutico , Femenino , Estudios de Seguimiento , Glioblastoma/patología , Humanos , Masculino , Pronóstico , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Tasa de Supervivencia , TemozolomidaRESUMEN
Aromatase inhibitors improve relapse-free survival in early breast cancer, but there is concern about possible detrimental effects on bone mineral density (BMD) and plasma lipids. This paper presents the results of a 2-year study evaluating the effects of exemestane versus placebo on BMD, bone markers, plasma lipids and coagulation factors, including a 1-year follow-up after termination of treatment in 147 patients. During treatment, the mean annual rate of loss of BMD in the lumbar spine was 2.17% in the exemestane group versus 1.84% in the placebo group (n.s.) and 2.72% versus 1.48%, respectively, in the femoral neck (P=0.024). A loss of BMD above that expected in both arms of this study could be due to low vitamin D status (88% of all patients had vitamin D levels <30 ng/ml). The changes observed with exemestane were partially reversed during a 1-year follow-up, with no significant difference between the two arms. Similarly, the moderate decrease in high-density lipoprotein (HDL)-cholesterol was reversed. The bone marker values decreased, although a difference at 6 months of follow-up was still recorded, in particular for the markers of bone synthesis.
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Androstadienos/efectos adversos , Inhibidores de la Aromatasa/efectos adversos , Densidad Ósea/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Biomarcadores/metabolismo , Factores de Coagulación Sanguínea/metabolismo , Remodelación Ósea , Huesos/metabolismo , Neoplasias de la Mama/metabolismo , Femenino , Estudios de Seguimiento , Hormonas Esteroides Gonadales/sangre , Homocisteína/sangre , Humanos , Lípidos/sangre , Persona de Mediana Edad , Posmenopausia , Vitamina D/sangre , Privación de TratamientoRESUMEN
PURPOSE: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer. PATIENTS AND METHODS: BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months. RESULTS: ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P =.011) and lymph node involvement (P <.001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P <.001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS. CONCLUSION: ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.
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Médula Ósea/patología , Neoplasias de la Mama/patología , Biopsia con Aguja , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Análisis Multivariante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Pronóstico , Tasa de SupervivenciaRESUMEN
Although SERMs are currently being evaluated and are approved for breast cancer prevention in several countries, aromatase inhibitors and inactivators may represent interesting options in this setting. The encouraging results revealing these drugs to be superior to conventional therapy in metastatic breast cancer confirm their therapy efficacy and suggest that they may also have a role in adjuvant therapy and even for breast cancer prevention. Secondly, whereas the bulk of "high-risk" breast cancer patients with confirmed founder mutations in the BRCA1 or BRCA2 genes develop their cancers earlier in life (during the premenopausal period), 75-80% of all breast cancers, in general, develop in postmenopausal women. Thus, in considering prevention of breast cancer in moderate-risk groups, strategies for prevention in postmenopausal women may play an important role. Also, among high-risk patients who have not developed breast cancer by the time of the menopause, aromatase inhibition could be a feasible option. Considering the potential hazards of long-term use of SERMs, switching to an aromatase inhibitor or inactivator in this setting may be beneficial. Finally, the observation that postmenopausal estrogen levels are related to subsequent risk of breast cancer in the general population underlines the potential for estrogen suppression as a preventive strategy. Results from ongoing studies examining the toxicity of aromatase inhibitors and inactivators in postmenopausal women will set the stage for future trials that explore them as preventive treatment options.
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Inhibidores de la Aromatasa , Neoplasias de la Mama/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Anticarcinógenos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Menopausia , Receptores de Estrógenos/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéuticoRESUMEN
INTRODUCTION: Central nervous system tumors (CNST) are the most lethal of solid tumors in childhood cancer. PATIENTS AND METHODS: We report incidence and survival data for all CNST (International Classification of Diseases for Oncology third edition, category III or Xa) recorded in children under 15 years of age by the Auvergne-Limousin cancer registry for the period 1986-2009. RESULTS: Annual incidence of all CNST was 3.27 per 100,000 and the male to female ratio was 0.95. Over 45.0% of CNST were glial. Astrocytomas (36.2%) showed the highest incidence for each age group except between 1 and 4 years where embryonal tumors were more common. For all CNST, no significant variation in incidence over time was observed for the evaluated period of 23 years (annual percent change: -0.4%, 95% CI, [-2.8-2.1]). Globally, 5 years overall survival was 67% [59-73] and had increased by more than 16% between 1986-1999 and 2000-2009, mainly due to better survival for astrocytomas, other gliomas, ependymomas and choroid plexus tumors (P=0.01). CONCLUSION: We report that the incidence of CNST in Auvergne-Limousin is similar to that in the literature and did not increase between 1986 and 2009. In addition, 5 years overall survival increased after 1999, especially for surgically treatable tumors.
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Astrocitoma/epidemiología , Neoplasias del Sistema Nervioso Central/epidemiología , Ependimoma/epidemiología , Glioma/epidemiología , Adolescente , Astrocitoma/diagnóstico , Neoplasias del Sistema Nervioso Central/diagnóstico , Niño , Preescolar , Ependimoma/diagnóstico , Femenino , Glioma/diagnóstico , Humanos , Incidencia , Masculino , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/epidemiología , Sistema de RegistrosRESUMEN
Endothelin is a novel, potent, endogenous vasoconstrictor derived predominantly from endothelium and macrophages. Release of endothelin-1 (ET-1) into biological fluids was determined by radioimmunoassay in pigs undergoing either a hemorrhagic (3 h) or superior mesenteric artery (SMA) occlusion (5 h) shock followed by reperfusion (90 min) or a control group which was observed for 8 h. After surgery, there was a significant increase in ET-1 in jugular and carotid plasma, lymph, and ascitic fluid in all three models. The portal plasma ET-1 level was significantly increased (p < .05, assessed by the Spearman rank coefficient rho) in both shock models, but no significant increase was noted in the control group. In the SMA occlusion shock model, four pigs died within 30 min of reperfusion, and these animals had a much higher level of portal ET-1 (22.3 +/- 5.5 fmol/mL) than the two pigs that were alive by the end of the observation period (11.5 +/- 1.3 fmol/mL). Reperfusion in the SMA occlusion shock model induced a critical form of circulatory shock characterized by hypotension, decreased cardiac output, and decreased left and right ventricular stroke work index, and death occurred usually within 90 min. Reperfusion of the shed blood in the hemorrhagic shock model almost normalized the hemodynamic derangements caused by the hypovolemia (with the exception of RVSWI), and the portal plasma and ascitic ET-1 levels decreased. These results indicate that ET-1 is released from the gut in response to both general hypoperfusion and selective intestinal ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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Endotelinas/metabolismo , Hemodinámica , Arteria Mesentérica Superior/fisiología , Choque Hemorrágico/fisiopatología , Choque/fisiopatología , Animales , Presión Sanguínea , Gasto Cardíaco , Endotelinas/sangre , Femenino , Frecuencia Cardíaca , Masculino , Consumo de Oxígeno , Arteria Pulmonar/fisiología , Arteria Pulmonar/fisiopatología , Choque/sangre , Choque Hemorrágico/sangre , Volumen Sistólico , Porcinos , Factores de Tiempo , Resistencia Vascular , Función Ventricular IzquierdaRESUMEN
Ischemia and reperfusion of the gut may be an important etiological factor in the development of multiple organ failure. We have used a hemorrhagic and a superior mesenteric artery (SMA) occlusion shock model in pigs to estimate the effect of ischemia and reperfusion on intestinal morphology, mucosal permeability, and the occurrence of bacterial or endotoxin translocation. Mucosal ulceration and necrosis were found in the SMA shock model, while the morphological changes were less pronounced in the hemorrhagic shock model. Scanning electron microscopy showed shrinkage of the villi and plugging of the colonic crypts in both shock models. Enterocyte cell kinetics was investigated using 5-bromo-2'-deoksyuridine (BrdU) incorporation and immunovisualization by anti-BrdU antibodies. Cell renewal was almost completely lost from the jejunum to the rectum in both shock models. Intramucosal pH was measured using a tonometer placed in the terminal ileum. Segments of intestinal mucosa were mounted in Ussing chambers, and permeability was measured using radiolabeled probe molecules of differing molecular weights. Augmented molecular flux of inulin (M(r) 5.000) and mannitol (M(r) 182) and loss of short circuit current (Isc) and transepithelial potential difference (PD) were found in mucosae from both shock models. Endotoxin was demonstrated in the ascitic fluid in both shock models; 9.5 (2.7-14.3) (median and 95% confidence interval) EU/mL in the SMA occlusion model and 16.0 (4.9-29.4) EU/mL in the hemorrhagic shock model), but the levels were not significantly higher than in the control model 6.5 (4.3-34.0) EU/mL.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Endotoxinas/farmacocinética , Hemodinámica , Mucosa Intestinal/irrigación sanguínea , Isquemia/fisiopatología , Choque Hemorrágico/fisiopatología , Choque/fisiopatología , Animales , Bacterias/aislamiento & purificación , Presión Sanguínea , División Celular , Femenino , Frecuencia Cardíaca , Absorción Intestinal , Mucosa Intestinal/patología , Mucosa Intestinal/fisiopatología , Intestino Grueso/ultraestructura , Intestino Delgado/ultraestructura , Isquemia/microbiología , Isquemia/patología , Masculino , Arteria Mesentérica Superior , Microscopía Electrónica de Rastreo , Permeabilidad , Arteria Pulmonar/fisiopatología , Valores de Referencia , Reperfusión , Choque/microbiología , Choque/patología , Choque Hemorrágico/microbiología , Choque Hemorrágico/patología , PorcinosRESUMEN
In this study, we have established a pig model that can combine extensive hemodynamic monitoring with simultaneous repetitive (serial) blood sampling for the study of multiple variables related to the hemostatic system. Sixteen healthy young pigs were studied to evaluate the influence of continuous endotoxin infusion on hemodynamic patterns and activation of coagulation and fibrinolysis. The chief aim of the study was to investigate the applicability of analytical methods primarily developed for use with human plasma samples in quantification of factors and reaction products of the porcine coagulation and fibrinolytic systems, and further, to use these methods to study the longitudinal changes in the plasma levels of these hemostatic variables as a consequence of endotoxin infusion. We found that acute, controlled endotoxemia induced a hemodynamic state of shock and reduced pulmonary gas exchange. Simultaneously, a gradual increase in peripheral blood mononuclear cell tissue factor activity was demonstrated, and increased maximally 5.5-fold 4 hours after onset of endotoxin infusion. Thrombin-antithrombin complexes increased in plasma to maximum levels after 3 hours, accompanied by an ethanol gelation test that was regularly positive after 1 to 2 hours, and fibrin monomer levels that gradually increased maximally 3.8-fold after 6 hours. These changes were followed by gradual decreases of both fibrinogen and factor VII levels, mainly due to consumption. Plasma levels of tissue type plasminogen activator activity peaked at 1.5 hours (11.3-fold increase), whereas the peak of plasminogen activator inhibitor-1 activity (14-fold increase at 4.5 hours) was delayed compared to tissue plasminogen activator and completely extinguished plasma tissue plasminogen activator activity. The sequential activation of coagulation and fibrinolysis established a procoagulant state favoring disseminated intravascular coagulation and microthrombus formation, potentially leading to multiple organ dysfunction.
Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Endotoxemia/fisiopatología , Fibrinólisis/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Animales , Antifibrinolíticos/metabolismo , Factores de Coagulación Sanguínea/efectos de los fármacos , Factores de Coagulación Sanguínea/metabolismo , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Endotoxemia/metabolismo , Endotoxinas/administración & dosificación , Endotoxinas/farmacología , Recuento de Leucocitos/efectos de los fármacos , Recuento de Plaquetas/efectos de los fármacos , Porcinos , Resistencia Vascular/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: The logistics of diagnosis and treatment in a hospital with slightly above 400 new cases of breast cancer per year is analysed. MATERIALS AND METHODS: The patient flow from referral, through the diagnostic procedures and through surgical treatment is described. RESULTS AND CONCLUSIONS: The basic principle of the diagnostic assessment is the triple diagnostic procedure including mammography supplemented by ultrasonography, fine needle aspiration cytology and clinical examination. The radiologist and pathologist are working together in the breast diagnostic centre and are thus able to give a "single visit diagnosis" in most cases. The surgeon sees the patient either the same day or the next. A "consensus meeting" held each week with representatives for all specialities present has an important function in quality assurance and education. If one or more of the triple diagnostic components reach conclusion level "suspicious lesion", surgery is indicated. In hospital management is based on day surgery for all biopsies, wide excisions with or without sentinel node and some ablatio simplex mammae. For wide excision and ablation with complete axillary node clearance, the patients are transferred from the day surgery unit to a patient hotel after 3-4 hours of observation and stay till the drain can be removed. Only in rare case of high cardiopulmonary risk, beds in ordinary wards are used. This is a highly cost efficient logistic saving the hospital approximately 400,000 EUR a year compared to ordinary in hospital treatment.