Cirugía radioguiada de las lesiones no palpables de mama (ROLL): ¿cómo lo hacemos? / No disponible

El objetivo de este trabajo es describir la técnica ROLL tal como nosotros la venimos aplicando, aprendida durante estancias realizadas en el Instituto Europeo de Oncología de Milán. S e describen los aspectos más importantes que tenemos en cuenta en las distintas fases: diagnóstica, pre-quirúrgica, quirúrgica y de cuidados postoperatorios. El procedimiento ROLL es una técnica multidisciplinar sencilla y reproducible que permite conseguir resultados óptimos y una tasa baja de reintervenciones, así como un buen resultado estético cuando se adquiere la suficiente experiencia(AU)

The aim of this paper is to describe the ROLL technique as we perform after having it learned during stays at the European Institute of Oncology in Milan. We describe the most important aspects that we consider in the different phases such as diagnostic, pre-surgical, surgical and postoperative care. The ROLL procedure is a multidisciplinary technique, simple and reproducible, that allows optimum results with a low rate of reintervention and a good cosmetic result when sufficient experience is gained(AU)

Ganglio centinela en cáncer de mama: ¿histológico o molecular? Estudio diagnóstico comparativo multicéntrico español. Grupo de Estudios Senológicos / Nodisponible

Introducción: La biopsia del ganglio centinela (GC) estáaceptada como el procedimiento estándar para la cirugía conservadorade la axila en el cáncer de mama, pero la gran variabilidadexistente en los protocolos de estudio anatomopatológicoshan impedido una correcta estandarizacióndiagnóstica.Objetivo: Comparar los resultados de un nuevo métodomolecular (“One-step-Nucleic-Acid-Amplification”, OSNA)con los resultados de los procedimientos habituales y evaluar sies posible la implementación del OSNA como procedimientode elección para el diagnóstico intraoperatorio.Material y métodos: Se estudió una serie de 181 GC procedentesde seis hospitales. De cada ganglio, se realizaron seccionesde 2 mm de espesor hasta agotar el ganglio. Se incluyerontodas las secciones de manera alternativa “a” y “c” paraestudio histológico, y “b” y “d” para OSNA.Resultados: Se obtuvo un nivel de concordancia entre elprocedimiento histológico y el molecular del 99,45%.Conclusiones: El estudio multicéntrico demuestra que elOSNA es un procedimiento altamente sensible, específico yreproducible y que permite la estandarización del diagnósticointraoperatorio del GC en cáncer de mama(AU)

Background: The biopsy of the sentinel node (SN) hasbeen established as the standard procedure for conservativeaxillary surgery but its adequate diagnostic standardization hasnot yet been achieved since the protocols for histopathologicstudy have been highly variable.Objective: Our goal is to compare the results of this newmethod with the results of conventional histological tests, toevaluate the feasibility of this procedure for the intra-operativestudy of SN in breast cancer surgery and to evaluate it as away to standardize the sentinel node procedure.Material and methods: The study included 181 cases. Parallel,2 mm-thick sections were performed to drain the lymphnode which were then processed alternately for histologicalanalysis (“a” and “c”) and the others (“b” and d”) following theOSNA procedure.Results: A concordance level of 99.45% was found betweenthe histological and the molecular procedure.Conclusions: Our multicentric OSNA assay for sentinelnode in breast cancer demonstrates that this is a highly sensitive,specific and reproducible technique that allows the standardizationof the diagnostic procedure, a needed and up tonow unresolved question(AU)

Expression and regulation of insulin and the glucose transporter GLUT8 in the testes of diabetic rats.

Diabetes induces several malfunctions in male germ cells. The aim of this study was to analyze the levels and localization of the glucose transporter GLUT8 and insulin in the testes of rats induced to a diabetic status by a single dose of streptozotocin. One month after inducing diabetes, the GLUT8 immunoreactivity in diabetic rats was mainly located associated to the acrosomic system of spermatids, and at low levels in Leydig cells. Neither the immunohistochemical localization of this transporter nor its levels showed any difference when compared to control rats. Furthermore, it was observed that control rat testes expressed insulin, which was diffusely located in the cytoplasm of both Leydig cells and early elongated spermatids and concentrated in a cytoplasmic compartment in the more mature spermatids. Testicular insulin levels measured by western blot were reduced by more than half in diabetic rats, although the distribution of the hormone was unchanged. These results indicate that i) insulin is produced by testicular cells, ii) insulin is depleted by streptozotocin-induced diabetes, and iii) that insulin depletion and hyperglycemia do not regulate the expression of GLUT8 in testes. These results also suggest that testicular production of insulin could play a role in regulating spermatogenesis and/or glucose metabolism in these organs.

Ensembl 2009.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases, and other information for chordate, selected model organism and disease vector genomes. As of release 51 (November 2008), Ensembl fully supports 45 species, and three additional species have preliminary support. New species in the past year include orangutan and six additional low coverage mammalian genomes. Major additions and improvements to Ensembl since our previous report include a major redesign of our website; generation of multiple genome alignments and ancestral sequences using the new Enredo-Pecan-Ortheus pipeline and development of our software infrastructure, particularly to support the Ensembl Genomes project (http://www.ensemblgenomes.org/).

Experiencia en CMA en un servicio de cirugía de un hospital comarcal / No disponible

No disponible

Ensembl 2008.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Utilidad de la resonancia magnética en la evaluación local del cáncer de mama: impacto en el cambio de actitud terapéutica en una serie prospectiva de 338 pacientes / No disponible

Introducción: la estadificación del cáncer de mama implicareunir información no sólo sobre el tamaño del tumor principal,sino también sobre la presencia de multifocalidad, multicentricidad,bilateralidad, componente intraductal extenso oextensión al complejo areola-pezón. El objetivo de nuestro estudioes validar la técnica en nuestro entorno asistencial y evaluarel impacto que la RM de mama con contraste ha tenido sobre338 pacientes consecutivas con diagnóstico de cáncer demama en el proceso de la toma de decisión del modelo de tratamiento.Como objetivo secundario se plantea la correlaciónde los hallazgos de la RM con los hallazgos histopatológicos.Material y métodos: estudiamos con RM a 338 pacientesconsecutivas con diagnóstico de cáncer de mama antes de decidircuál era el abordaje terapéutico más adecuado. La intenciónterapéutica se registró antes y después de cada estudio deRM. Se calculó la sensibilidad, la especificidad, el valor predictivopositivo y el valor predictivo negativo de la RM para lesionesadicionales, así como el coeficiente de correlación linealde Pearson para el diámetro del tumor índice o principal.Resultados: en 145 pacientes (42%) se identificaron 164lesiones adicionales, de las cuales 87 (53%) fueron malignas,28 (17%) fueron benignas, 35 (21,3%) se catalogaron comoprobablemente benignas, en 6 (3,6%) no se alcanzó un diagnósticofinal y 8 (4,9%) no quedaron incluidas en la pieza quirúrgicao bien desaparecieron tras la quimioterapia neoadyuvante.Estos hallazgos implicaron un cambio en la actitudterapéutica en 82 pacientes (24,2%). Este cambio se confirmócon los resultados de la anatomía patológica como correcto en69 paciente (20,4%) y como incorrecto o innecesario en 13pacientes (3,8%). El coeficiente de correlación de Pearson resultóser fuertemente positivo (r = 0,784) cuando se compararonlos resultados de la RM y la anatomía patológica...(AU)

Background: breast cancer staging implies gathering informationnot only on the size of the main tumour, but also onmultifocality, multicentricity, bilaterality, presence of an extensiveintraductal component and extension to the nipple-areolarcomplex. The objective of our study is to demonstrate thatbreast magnetic resonance (MR) is the modality of choice inthe staging of breast cancer patients due to the fact that it addsinformation capable of modifying the therapeutic approach inthese patients. A secondary objective is to validate our resultsin our clinical environment.Material and methods: 338 consecutive patients with abreast cancer diagnosis were studied with breast MR beforedeciding the most appropiate therapeutic approach. Therapeuticintention was registered before and after each MRstudy. Sensibility, specificity, postive predictive value (PPV)and negative predictive value (NPV) of MR for additional lesionswas calculated and Pearson's linear correlation coefficientwas calculated for the index lesion diameter.Results: 164 additional lesions were found in 145 patients(42%) of which 87 (53%) were malignant, 28 (17%) were benign,35 (21,3%) were probable benign, 6 (3,6%) had no diagnosisand 8 (4,9%) were not included in the surgical specimenor else dissappeared after neoadjuvant chemotherapy. Thesefindings implied change in therapeutic approach in 82 patients(24,2%). These change was pathologically validated ascorrect in 69 patients (20,4%) and as unnecessary or incorrectin 13 patients (3,8%). Pearson's linear correlation coefficientwas strongly positive (r = 0,784) when MR and pathology resultswere compared. Sensibility, specificity, PPV and NPV ofMR for additional lesions was 90,6, 55,2, 75,7 and 79,5%respectively...(AU)

Estudio por congelación del ganglio centinela en carcinoma de mama / No disponible

A pesar de que el estudio del ganglio centinela constituyeya un procedimiento de rutina en la estadificación del cáncerde mama, todavía no existe consenso acerca de cuál es el protocolomás eficiente para su estudio histopatológico.El objetivo fundamental de este estudio es describir nuestroprotocolo para el estudio histopatológico del ganglio centinela(GC), comparando los resultados del mismo cuando se realizaintraoperatoriamente o diferido y justificar la inclusión de la citoqueratinacomo parte necesaria del protocolo.La serie incluye 85 casos de los cuales 42 se estudiaron intraoperatoriamente,de los cuales el 45,2% mostró positividadpara células tumorales. De los 43 restantes, estudiados en diferido,mostró positividad para células tumorales el 34,8%. En10 de los 85 casos (28,5%), el diagnóstico sólo pudo realizarsesobre los cortes teñidos con citoqueratina (CK). No se observarondiferencias estadísticamente significativas entre losresultados de los grupos intraoperatorio y diferido.En conclusión, nuestros resultados apoyan este protocolocomo un método sensible y específico que permite realizar eltratamiento quirúrgico del cáncer de mama y su estadificaciónen un solo tiempo(AU)

In spite that the Sentinel Node (SN) procedure is admittedfor routine breast cancer staging, there is still no agreementon the most efficient histopathological protocol to evaluate it.The main aim of this study is to describe our histopathologicalwork up comparing intraoperative and deferred protocols,and to emphasize the use of Cytokeratin Immunostain asa desirable part of it.Out of 85 cases in our series, 42 were studied by intraoperativeprocedure and 45.2% of them showed positive tumourcells. Of the 43 remaining cases, studied by deferred procedure,34.8% were positive for tumour cells. In 10 out of 85 cases(28.5%) the diagnosis was reached by cytokeratin immunostain.There were not statistically significant differencesbetween the intraoperative and the deferred groups.We conclude that the results make our method is sensibleand specific enough to allow one step surgical treatment andstaging of breast cancer(AU)

Síndrome antifosfolípido en pacientes con bacteriemia por Salmonella enteritidis / Antiphospholipid syndrome in a patient with Salmonella enteritidis bacteremia

No disponible

Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas.

The classification of peripheral T-cell lymphomas (PTCL) is still a matter of debate. To establish a molecular classification of PTCL, we analysed 59 primary nodal T-cell lymphomas using cDNA microarrays, including 56 PTCL and three T-lymphoblastic lymphoma (T-LBL). The expression profiles could discriminate angioimmunoblastic lymphoma, anaplastic large-cell lymphoma and T-LBL. In contrast, cases belonging to the broad category of 'PTCL, unspecified' (PTCL-U) did not share a single molecular profile. Using a multiclass predictor, we could separate PTCL-U into three molecular subgroups called U1, U2 and U3. The U1 gene expression signature included genes known to be associated with poor outcome in other tumors, such as CCND2. The U2 subgroup was associated with overexpression of genes involved in T-cell activation and apoptosis, including NFKB1 and BCL-2. The U3 subgroup was mainly defined by overexpression of genes involved in the IFN/JAK/STAT pathway. It comprised a majority of histiocyte-rich PTCL samples. Gene Ontology annotations revealed different functional profile for each subgroup. These results suggest the existence of distinct subtypes of PTCL-U with specific molecular profiles, and thus provide a basis to improve their classification and to develop new therapeutic targets.

[Study of the sentinel node in breast cancer using lymphoscintigraphy and a fast method for cytokeratin]. / Estudio del ganglio centinela en el cáncer de mama mediante linfogammagrafía y citoqueratina por congelación.

INTRODUCTION: Histopathological examination of the axillary sentinel node (SN) is becoming a routine procedure in the surgical phase of infiltrating ductal carcinoma of the breast (IDC). The SN exam may yield false negative cases mainly due to identification failure of the SN but some of the false negative cases may be the result of the pathological examination procedure applied. MATERIAL AND METHODS: Sixty two (62) cases of clinically staged N0 IDC of the breast by TNM nomenclature were assigned to breast surgery along with conventional axillary node dissection. The identification technique included lymphoscintigraphy and intraoperative gamma-detecting probe after peritumoral injection of 99mTc-labeled colloids.The histological study of SN was performed with paired 4 microm slices and staining with hematoxylin-eosin and with a fast method of cytokeratins for freezing. RESULTS: In only two of the 62 patients, it was not possible to identify the SN. Eighteen of the remaining 60 had SN involvement by metastasis, having no metastases in the other nodes of the axillary dissection in 6 of them. Ten of those were micrometastasis (size of metastasis= or <0.2 cm). In two out of these last 10 cases, diagnosis of the micrometastasis was only possible using slices stained with CK. There were no false negative results. CONCLUSIONS: The lymphoscintigraphy, after peritumoral injection of small volumes and low dose of the tracer, makes it possible to obtain excellent results in the intraoperative detection of the SN in breast cancer. The study of this SN with a fast method for CK decreases the number of false negative results of the technique.

Estudio del ganglio centinela en el cáncer de mama mediante linfogammagrafía y citoqueratina por congelación / Study of the sentinel node in breast cancer using lymphoscintigraphy and a fast method for cytokeratin

Introducción: El estudio histológico del ganglio centinela axilar (GC) está estableciéndose como un procedimiento habitual en la cirugía del carcinoma infiltrante de mama. Los falsos negativos descritos son imputables tanto a la identificación del verdadero ganglio centinela como al protocolo aplicado para el estudio de dicho ganglio. Material y métodos: Estudiamos 62 enfermas de carcinoma infiltrante de mama, clínicamente N0 (TNM), subsidiarias de exéresis tumoral y vaciamiento axilar. En todas se practicó linfogammagrafía y detección intraoperatoria tras la administración peritumoral de 99mTc-nanocoloide de albúmina. El estudio histológico del GC se efectuó realizando pares de cortes de 4 y tinción mediante hematoxilina-eosina (H/E) y técnica rápida de citoqueratinas (CK) por congelación. Resultados: Del total de 62 enfermas, en dos no fue posible detectar el GC. De las 60 restantes, 18 presentaban metástasis en el GC, sin observarse afectación de otros ganglios en 6 de ellas. Diez de estas enfermas mostraron la presencia de micrometástasis exclusivamente (depósito tumoral 2 mm).En dos de estos diez últimos casos, el diagnóstico de las micrometástasis sólo fue posible a partir de los cortes teñidos con CK. No se obtuvo ningún resultado falso negativo. Conclusiones: La linfogammagrafía, previa inyección peritumoral de volúmenes pequeños y dosis bajas del radiotrazador, permite obtener excelentes resultados en la localización intraoperatoria del GC en el cáncer de mama. Su posterior estudio mediante CK rápida permite disminuir el número de falsos negativos de la técnica (AU)

Flow cytometry analysis of gamma-radiation-induced Epstein-Barr virus reactivation in lymphocytes.

Epstein-Barr virus (EBV), a member of the gamma-herpesvirus family, is involved in the development of several diseases, and the infection is believed to persist for life in latent form. Ionizing radiation at clinically relevant doses may increase the amount of virus reactivation in B cells, and the combination of radiation with stress could amplify EBV reactivation. In vitro experiments were performed on several cell lines, including EBV-positive Burkitt lymphoma cells. The presence of the immediate-early protein ZEBRA, which is a hallmark of EBV reactivation, was evaluated using flow cytometry, which enabled us to measure the percentage of ZEBRA-positive cells. The process was studied previously in the EBV-positive Burkitt lymphoma cell line B95-8. Forty-eight hours after irradiation alone, 13.6 and 19.9% ZEBRA-positive cells were observed at 2 and 4 Gy, respectively, compared to the basal level of 1.85%. Thus irradiation induces EBV reactivation. The addition of a glucocorticoid (the final effector of the stress response) had no effect on EBV reactivation in our model. However, the combination of radiation and treatment with a glucocorticoid (dexamethasone) increased the expression of ZEBRA in B95-8 cells (15.8 and 28.75% of the cells was positive at 24 and 48 h after gamma irradiation, respectively). Thus the combination of gamma radiation and a glucocorticoid may play an important role in EBV reactivation.

The bacterial nucleoside N(6)-methyldeoxyadenosine induces the differentiation of mammalian tumor cells.

Contrary to bacterial DNA, mammalian DNA contains very little if any N(6)-methyldeoxyadenosine (MDA). The possible biological effect of this nucleoside on eukaryotic cells has been studied on different tumor cell lines. Addition of MDA to C6.9 glioma cells triggers a differentiation process and the expression of the oligodendroglial marker 2',3'-cyclic nucleotide 3'phosphorylase (CNP). The biological effects of N(6)-methyldeoxyadenosine were not restricted to C6.9 glioma cells since differentiation was also observed on pheochromocytoma and teratocarcinoma cell lines and on dysembryoplastic neuroepithelial tumor cells. The precise mechanism by which MDA induces cell differentiation remains unclear, but is related to cell cycle modifications. These data point out the potential interest of N(6)-methyldeoxyadenosine as a novel antitumoral and differentiation agent. They also raise the intriguing question of the loss of adenine methylation in mammalian DNA. Furthermore, the finding that a methylated nucleoside found in bacterial DNA induces a biological process might have implications in gene therapy approaches when plasmid DNAs are injected into humans.

Effects of selenium supplementation on malignant lymphoproliferative pathologies associated with OF1 mouse ageing.

Low plasma selenium (Se) levels have been shown to correlate with increased cancer incidence in humans and in mice. This study was undertaken to investigate the ability of Se to decrease mortality rate and tumor production in ageing mice. Se (2.5 ppm) given as sodium selenite in drinking water to 8 months old OF1 mice, for 4 consecutive months, reduced significantly the mortality of mice with 6% and 50% mortality rate for Se and control groups, respectively. In addition 80% of control deaths resulted from a lymphoid cell neoplasma, while no one of Se supplemented mice produced tumor. Evaluation of parameters of free radical metabolism showed highly significant reduction of the antioxidant defence system in the liver of cancer mice, with a 78% decrease in GSH-Px activity, a 65% decrease in superoxide dismutase (SOD) activity, a 75% decrease in the GSH/GSSG ratio and a 62% decrease of plasma Se level, as compared to healthy old mice. Nevertheless in the conditions of our experiment, Se didn't really improve the endogenous antioxidant status of ageing mice.