RESUMEN
Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.
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Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Modelos Teóricos , Axila/patología , Axila/cirugía , Calibración , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Biopsia del Ganglio Linfático CentinelaRESUMEN
The success of cytology in screening programs for cervical cancer is highly dependent on the smear quality. Interdisciplinary projects which evaluate the smear quality and the results of collection devices could be helpful for an improvement and a successful example for quality improvement is presented here. An average of 83% technically adequate and representative smears was documented for 12 million conventional PAP smears; however only an average of 68% technically adequate and representative smears was found for the group of least successful smear takers of all laboratories. This indicates a potential for improvement. Following an interdisciplinary project on smear quality improvement the average rate of representative smears increased from 69 to 83% and in another project this rate remained stable at 86%. Based on 158,411 conventional smears, representative smears were achieved in 92% using Cervex-Brush®, 86% using Szalay Spatula and 82% Cytobrush methods. The combinations of Cytobrush with the Ayre wooden spatula, cotton wool swab or Szalay Spatula achieved 97%, 94% and 92% representative smears, respectively.
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Detección Precoz del Cáncer/normas , Motivación , Prueba de Papanicolaou , Garantía de la Calidad de Atención de Salud/normas , Mejoramiento de la Calidad/normas , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Frotis Vaginal/normas , Austria , Diseño de Equipo , Femenino , Adhesión a Directriz , Humanos , Valor Predictivo de las Pruebas , Control de Calidad , Frotis Vaginal/instrumentaciónRESUMEN
OBJECTIVE: The intraluminal thrombus (ILT) present in the majority of abdominal aortic aneurysms (AAAs) plays an important role in aneurysm wall weakening. Studying the age-dependent elastic properties of the ILT and the thrombus-covered wall provides a better understanding of the potential effect of ILT on AAA remodelling. MATERIALS AND METHODS: A total of 43 AAA samples (mean age 67 ± 6 years) including ILT and AAA wall was harvested. Biaxial extension tests on the three individual ILT layers and the thrombus-covered wall were performed. Histological investigations of the thrombi were performed to determine four different age phases, and to correlate with the change in the mechanical properties. A three-dimensional material model was fitted to the experimental data. RESULTS: The luminal layers of the ILT exhibit anisotropic stress responses, whereas the medial and the abluminal layers are isotropic materials. The stresses at failure in the equibiaxial protocol continuously decrease from the luminal to the abluminal side, whereby cracks, mainly oriented along the longitudinal direction, can be observed in the ruptured luminal layers. The thrombi in the third and fourth phases contribute to wall weakening and to an increase of the mechanical anisotropy of their covered walls. The material models for the thrombi and the thrombus-covered walls are in excellent agreement with the experimental data. CONCLUSION: Our results suggest that thrombus age might be a potential predictor for the strength of the wall underneath the ILT and AAA rupture.
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Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/patología , Rotura de la Aorta/etiología , Modelos Cardiovasculares , Trombosis/patología , Anciano , Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/cirugía , Rotura de la Aorta/patología , Fenómenos Biomecánicos , Elasticidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Estrés Mecánico , Trombosis/complicaciones , Trombosis/cirugía , Factores de TiempoAsunto(s)
Adenocarcinoma , Unión Esofagogástrica , Recurrencia Local de Neoplasia , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Adenocarcinoma/patología , Unión Esofagogástrica/patología , Neoplasias Gástricas/patología , Receptor ErbB-2/metabolismo , Recurrencia Local de Neoplasia/epidemiología , Incidencia , Neoplasias Esofágicas/patologíaRESUMEN
Practice and accuracy of immunohistochemistry is known to vary highly. Reliability of HER-2 immunohistochemistry is critical because of its role in patient selection for therapeutical options in breast cancer. Therefore reliability of HER-2 immunohistochemistry in pathology laboratories in Austria was assessed. Ten tissue specimens of invasive ductal breast carcinomas and three cell line samples were tested. Presence/absence of gene amplification was determined by FISH to be used as a gold standard. Laboratories were asked to stain and assess slides using their routine immunohistochemical staining protocol. Overall the study consisted of 311 tests on tissue specimens and 142 on cell lines. In all cases manual scoring was performed. Participation was voluntary and was 94%. Overall sensitivity was 90.5% and specificity 99.2%. Overscoring including true false positive results were found in 6.7% and 6.3% in tissue specimens and cell lines, respectively. False negative determinations were obtained in 1.9% and 2.8% of tissue specimens and cell lines, respectively. HercepTest showed slightly higher reliability in comparison with individualized staining methods. By manual scoring inaccurate scoring affected 12.3% of test results and 62% of the laboratories. In conclusion participation rate and accuracy of HER-immunohistochemistry was high all over the country. Manually performed scoring demonstrated some limitations.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Inmunohistoquímica/normas , Receptor ErbB-2/metabolismo , Austria , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Línea Celular Tumoral , Reacciones Falso Negativas , Femenino , Humanos , Inmunohistoquímica/métodos , Garantía de la Calidad de Atención de Salud , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIM: The aim of the present study was to evaluate the risk of axillary non-sentinel lymph-node metastases (ALN) in breast cancer patients presenting macrometastasis (Mac-m) in the sentinel lymph node (SN). MATERIALS AND METHODS: A retrospective series of 1464 breast cancers from patients who underwent ALN dissection following the diagnosis of Mac-m in the sentinel node (SN) was studied. In all the cases the MAC-m linear size was evaluated and correlated with presence or absence of non-SN ALN metastases. RESULTS: Non-SN metastases were detected in 644∖1464 cases (43.98%). The risk of further axillary metastases ranged from 20.2% (37/183) in cases with Mac-m between 2 and 2.9 mm, to 65.3% (262/401) in cases with Mac-m measuring > 10 mm. The risk of non-SN ALN metastases showed a 3% increase, parallel to each mm increment in SN metastasis size. The data evaluated with the receiver operating characteristic (ROC) curve showed that the Mac-m could be subdivided according to a new cut-off of 7 mm. pT1 tumours, with Mac-m < 7 mm had a risk of non-SN ALN metastases of <30%. Furthermore 109/127 of these (85.8%) had 3 or less non-SN ALN -metastases. CONCLUSIONS: The present data give a detailed description on the risk of non-SN ALN involvement, that may be useful in the evaluation of breast cancer patients. It is suggested that a Mac-m size of <7 mm is related to a low residual axillary disease burden in breast cancer patients with small (pT1) tumours.
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Neoplasias de la Mama/patología , Metástasis Linfática/patología , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Axila , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Cytokeratin immunohistochemistry (IHC) reveals a higher rate of occult lymph node metastases among lobular carcinomas than among ductal breast cancers. IHC is widely used but is seldom recommended for the evaluation of sentinel lymph nodes in breast cancer patients. OBJECTIVE: To assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes of patients with invasive lobular carcinoma. METHODS: The value of IHC, the types of metastasis found by this method, and the involvement of non-sentinel lymph nodes were analysed in a multi-institutional cohort of 449 patients with lobular breast carcinoma, staged by sentinel lymph node biopsy and routine assessment of the sentinel lymph nodes by IHC when multilevel haematoxylin and eosin staining revealed no metastasis. RESULTS: 189 patients (42%) had some type of sentinel node involvement, the frequency of this increasing with increasing tumour size. IHC was needed for identification of 65 of these cases: 17 of 19 isolated tumour cells, 40 of 64 micrometastases, and 8 of 106 larger metastases were detected by this means. Non-sentinel-node involvement was noted in 66 of 161 cases undergoing axillary dissection. Although isolated tumour cells were not associated with further lymph node involvement, sentinel node positivity detected by IHC was associated with further nodal metastases in 12 of 50 cases (0.24), a proportion that is higher than previously reported for breast cancer in general. CONCLUSIONS: IHC is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Carcinoma Lobular/patología , Queratinas/análisis , Axila , Neoplasias de la Mama/química , Carcinoma Lobular/química , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica/métodos , Metástasis Linfática , Pronóstico , Sensibilidad y Especificidad , Biopsia del Ganglio Linfático CentinelaRESUMEN
Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100% agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Carcinoma/patología , Inmunohistoquímica/métodos , Metástasis de la Neoplasia/diagnóstico , Femenino , Humanos , Variaciones Dependientes del Observador , Patología Clínica/métodos , Patología Clínica/normasRESUMEN
The mechanical behavior of the entire anulus fibrosus is determined essentially by the tensile properties of its lamellae, their fiber orientations, and the regional variation of these quantities. Corresponding data are rare in the literature. The paper deals with an in vitro study of single lamellar anulus lamellae and aims to determine (i) their tensile response and regional variation, and (ii) the orientation of lamellar collagen fibers and their regional variation. Fresh human body-disc-body units (L1-L2, n=11) from cadavers were cut midsagittally producing two hemidisc units. One hemidisc was used for the preparation of single lamellar anulus specimens for tensile testing, while the other one was used for the investigation of the lamellar fiber orientation. Single lamellar anulus specimens with adjacent bone fragments were isolated from four anatomical regions: superficial and deep lamellae (3.9+/-0.21 mm, mean +/- SD, apart from the outer boundary surface of the anulus fibrosus) at ventro-lateral and dorsal positions. The specimens underwent cyclic uniaxial tensile tests at three different strain rates in 0.15 mol/l NaCl solution at 37 degrees C, whereby the lamellar fiber direction was aligned with the load axis. For the characterization of the tensile behavior three moduli were calculated: E(low) (0-0.1 MPa), E(medium) (0.1-0.5 MPa) and E(high) (0.5-1 MPa). Additionally, specimens were tested with the load axis transverse to the fiber direction. From the second hemidisc fiber angles with respect to the horizontal plane were determined photogrammetrically from images taken at six circumferential positions from ventral to dorsal and at three depth levels. Tensile moduli along the fiber direction were in the range of 28-78 MPa (regional mean values). Superficial lamellae have larger E(medium) (p=0.017) and E(high) (p=0.012) than internal lamellae, and the mean value of superficial lamellae is about three times higher than that of deep lamellae. Tensile moduli of ventro-lateral lamellae do not differ significantly from the tensile moduli of dorsal lamellae, and E(low) is generally indifferent with respect to the anatomical region. Tensile moduli transverse to the fiber direction were about two orders of magnitude smaller (0.22+/-0.2 MPa, mean +/- SD, n=5). Tensile properties are not correlated significantly with donor age. Only small viscoelastic effects were observed. The regional variation of lamellar fiber angle phi is described appropriately by a regression line |phi|=23.2 + 0.130 x alpha (r(2)=0.55, p<0.001), where alpha is the polar angle associated with the circumferential position. The single anulus lamella may be seen as the elementary structural unit of the anulus fibrosus, and exhibits marked anisotropy and distinct regional variation of tensile properties and fiber angles. These features must be considered for appropriate physical and numerical modeling of the anulus fibrosus.
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Disco Intervertebral/fisiología , Vértebras Lumbares/fisiología , Modelos Biológicos , Anisotropía , Cadáver , Elasticidad , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Estrés Mecánico , Resistencia a la Tracción/fisiología , ViscosidadRESUMEN
Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.
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Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela/métodos , Femenino , Humanos , Metástasis de la Neoplasia/patología , Variaciones Dependientes del Observador , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Sensibilidad y Especificidad , Biopsia del Ganglio Linfático Centinela/normasRESUMEN
Pseudomelanosis coli is characterized by pigment deposition in the lamina propria and caused by increased epithelial apoptosis. Pseudomelanosis coli is absent in colonic neoplasia. The aim of our studies was to investigate this phenomenon in more detail. Apoptotic fragments of epithelial cells and their distribution, cell proliferation (Ki-67, MIB 1 immunostaining), macrophages (CD68 immunostaining), Bcl-2 expression and apoptosis [terminal-deoxynucleotidyl-transferase mediated dUTP fluorescein nick end labeling (TUNEL) assay] were studied in adenomas arising in normal and melanotic colonic mucosa, in normal colonic mucosa and colonic mucosa with pseudomelanosis alone. In adenomas, we found 7.0 apoptotic bodies per 100 epithelial cells in the epithelial layer and only 0.2 apoptotic bodies per high power field (HPF) in the lamina propria. In contrast, in melanotic mucosa 1.7 apoptotic bodies per 100 epithelial cells in the epithelial layer and 2.5 per HPF in the lamina propria were found. Our results show that apoptotic fragments remain in the neoplastic (adenomatous) epithelium and do not reach (at least in higher amounts) the lamina propria. They can, therefore, not contribute to the development of pseudomelanosis in these lesions. However, macrophages are diminished in adenomas. Proliferation (Ki-67) and also Bcl-2 expression are highly increased in adenomas. The pathway of mucosal macrophages is also discussed.
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Adenoma/patología , Apoptosis , Neoplasias del Colon/patología , Mucosa Intestinal/patología , Adenoma/inmunología , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Neoplasias del Colon/inmunología , Colorantes , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Mucosa Intestinal/inmunología , Antígeno Ki-67/análisis , Macrófagos/inmunología , Melanosis/patología , Proteínas Proto-Oncogénicas c-bcl-2/análisisRESUMEN
We describe an insulinoma of the pancreas in a 56-year-old patient, which showed insular-ductular differentiation in its liver metastasis. Although the primary tumor was uniformly endocrine in nature with insulin production, the metastasis contained two distinct cell types in organoid arrangement. One cell type was insulin-positive and was arranged in islet-like structures; the other was insulin-negative but distinctly pan-cytokeratin and cytokeratin 7 positive and arranged in ducts. In the primary tumor and the metastasis, the tumor cells were surrounded by a desmoplastic stroma. As to the histogenesis of the tumor and its metastasis, we discuss the following possibilities: (1) the tumor cells might derive from a common stem cell that matures into two phenotypically different cell lines, resembling the situation in embryogenesis and (2) one tumor cell type originates from the other by transdifferentiation (metaplasia). We conclude that the parallel occurrence of endocrine and ductal differentiation supports the concept that, under certain conditions, islet cells and ductular cells may also originate from islets and that mixed endocrine/exocrine pancreatic tumors do not necessarily arise from totipotent duct cells but might also have a primary endocrine cell origin.
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Carcinoma Ductal Pancreático/secundario , Transformación Celular Neoplásica/patología , Insulinoma/secundario , Neoplasias Hepáticas/secundario , Células Madre Neoplásicas/patología , Neoplasias Pancreáticas/patología , Biomarcadores de Tumor/análisis , Carcinoma Ductal Pancreático/química , Humanos , Insulina/análisis , Insulinoma/química , Insulinoma/cirugía , Queratina-7 , Queratinas/análisis , Neoplasias Hepáticas/química , Masculino , Persona de Mediana Edad , Páncreas/química , Páncreas/patología , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/cirugíaRESUMEN
To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.
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Neoplasias de la Mama/metabolismo , Inmunohistoquímica/normas , Receptores de Estrógenos/metabolismo , Coloración y Etiquetado/normas , Unión Europea , Femenino , Humanos , Control de Calidad , Reproducibilidad de los ResultadosRESUMEN
AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.
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Neoplasias de la Mama/patología , Práctica Profesional/estadística & datos numéricos , Biopsia del Ganglio Linfático Centinela/normas , Biomarcadores de Tumor/análisis , Femenino , Encuestas de Atención de la Salud , Humanos , Inmunohistoquímica , Cuidados Intraoperatorios/métodos , Cuidados Intraoperatorios/normas , Metástasis Linfática , Guías de Práctica Clínica como Asunto , Biopsia del Ganglio Linfático Centinela/métodos , Encuestas y CuestionariosRESUMEN
Ionizing radiation at very low doses frequently has a stimulating or hormetic effect on the growth of organisms. Irradiation of seed before planting can stimulate early plant growth, leading to advanced maturity and increased yield. The unreliability of this response has limited its application. However, the technique has been extensively studied and now is practiced on a large scale on some farms in certain countries. Our research has addressed various factors that may determine the stimulation response with the goal of developing an ability to predict the occurrence of increased economic yield. In this paper, we discuss several of these factors in light of our data and data from other field studies in Canada. A hormesis response was observed for most species studied, but varied among cultivars and among seed lots within a cultivar. Seed condition may be the underlying factor in these effects. The response was most frequently evident at very early stages of growth and was often masked in subsequent growth. This suggests that the hormesis phenomenon in seeds may be quite common and is not reliably manifest in advanced maturity or yield increases because of environmental effects. Storage time after irradiation must be minimized to gain the greatest response. There is little evidence to suggest that the photon energy or dose rate of the radiation source is an important factor.
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Semillas/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Grano Comestible , Semillas/crecimiento & desarrollo , VerdurasRESUMEN
INTRODUCTION: Thrombus ages, defined as four relative age phases, are related to different compositions of the intraluminal thrombus (ILT) in the abdominal aortic aneurysm (AAA) (Tong et al., 2011b). Experimental studies indicate a correlation between the relative thrombus age and the strength of the thrombus-covered wall. METHODS: On 32 AAA samples we performed peeling tests with the aim to dissect the material (i) through the ILT thickness, (ii) within the individual ILT layers and (iii) within the aneurysm wall underneath the thrombus by using two extension rates (1mm/min, 1mm/s). Histological investigations and mass fraction analysis were performed to characterize the dissected morphology, to determine the relative thrombus age, and to quantify dry weight percentages of elastin and collagen in the AAA wall. RESULTS: A remarkably lower dissection energy was needed to dissect within the individual ILT layers and through the thicknesses of old thrombi. With increasing ILT age the dissection energy of the underlying intima-media composite continuously decreased and the anisotropic dissection properties for that composite vanished. The quantified dissection properties were rate dependent for both tissue types (ILT and wall). Histology showed that single fibrin fibers or smaller protein clots within the ILT generate smooth dissected surfaces during the peeling. There was a notable decrease in mass fraction of elastin within the thrombus-covered intima-media composite with ILT age, whereas no significant change was found for that of collagen. CONCLUSIONS: These findings suggest that intraluminal thrombus aging leads to a higher propensity of dissection for the ILT and the intima-media composite of the aneurysmal wall.
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Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/patología , Disección Aórtica/patología , Endotelio Vascular/patología , Trombosis/patología , Anciano , Anciano de 80 o más Años , Aorta Abdominal/anatomía & histología , Colágeno/análisis , Elastina/análisis , Fibrina/análisis , Humanos , Persona de Mediana Edad , PresiónRESUMEN
OBJECTIVES: To date, no reliable markers are available to predict response to or to assess prognosis after preoperative systemic chemotherapy (PST) in patients with locally advanced breast cancer. Previous studies demonstrated that elevated levels of soluble E-cadherin (sE-cadherin), a product of proteolytic cleavage of cell surface E-cadherin, are associated with higher risk for metastatic disease and poor prognosis in various tumor types. We, therefore, hypothesized that serum sE-cadherin levels measured before PST may correlate with pathological response. DESIGN AND METHODS: In a retrospective analysis, sE-cadherin levels were measured in sera of 108 female patients with histologically proven breast cancer before initiation of PST by using a commercially available quantitative sandwich enzyme immunoassay technique. Patients received a median number of 4 (range 3-6) cycles of anthracyline-based chemotherapy. The median patient age was 51.5 (range 21-71) years. Tumor size was measured clinically and translated into the tumor-node-metastasis (TNM)-system before the start of chemotherapy. Histopathological response in surgically removed specimens was evaluated using a modified Sinn regression score. In univariate analyses the correlations between levels of sE-cadherin and pathological response to PST were calculated. RESULTS: The histopathological regression scores correlated significantly with tumor grading (p=0.045), clinical lymph node status before PST (p=0.031) and sE-cadherin levels (p=0.039). No correlation was seen between histopathological regression scores and hormone receptor and menopausal status as well as Her2-neu status. CONCLUSION: sE-cadherin may be a marker predicting response to PST for patients with breast cancer. Our findings warrant further evaluation of sE-cadherin in a prospective trial.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Cadherinas/genética , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Adulto , Anciano , Análisis de Varianza , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Cadherinas/sangre , Carcinoma Ductal de Mama/sangre , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/sangre , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/genética , Quimioterapia Adyuvante , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Valor Predictivo de las Pruebas , Pronóstico , Proteolisis , Receptor ErbB-2/sangre , Receptor ErbB-2/genética , Estudios Retrospectivos , Solubilidad , Carga TumoralRESUMEN
INTRODUCTION: In recognition of the advances and evidence based changes in clinical practice that have occurred in recent years and taking into account the knowledge and experience accumulated through the voluntary breast unit certification programme, Eusoma has produced this up-dated and revised guidelines on the requirements of a Specialist Breast Centre (BC). METHODS: The content of these guidelines is based on evidence from the recent relevant peer reviewed literature and the consensus of a multidisciplinary team of European experts. The guidelines define the requirements for each breast service and for the specialists who work in specialist Breast Centres. RESULTS: The guidelines identify the minimum requirements needed to set up a BC, these being an integrated Breast Centre, dealing with a sufficient number of cases to allow effective working and continuing expertise, dedicated specialists working with a multidisciplinary approach, providing all services throughout the patients pathway and data collection and audit. It is essential that the BC also guarantees the continuity of care for patients with advanced (metastatic) disease offering treatments according to multidisciplinary competencies and a high quality palliative care service. The BC must ensure that comprehensive support and expertise may be needed, not only through the core BC team, but also ensure that all other medical and paramedical expertise that may be necessary depending on the individual case are freely available, referring the patient to the specific care provider depending on the problem. CONCLUSIONS: Applying minimum requirements and quality indicators is essential to improve organisation, performance and outcome in breast care. Efficacy and compliance have to be constantly monitored to evaluate the quality of patient care and to allow appropriate corrective actions leading to improvements in patient care.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Instituciones Oncológicas/organización & administración , Atención Dirigida al Paciente/organización & administración , Acreditación , Comunicación , Detección Precoz del Cáncer , Educación Médica Continua/legislación & jurisprudencia , Educación Médica Continua/organización & administración , Femenino , Humanos , Comunicación Interdisciplinaria , Grupo de Atención al Paciente/legislación & jurisprudencia , Grupo de Atención al Paciente/organización & administración , Relaciones Médico-PacienteRESUMEN
Sentinel lymph node (SN) biopsy offers the possibility of selective axillary treatment for breast cancer patients, but there are only limited means for the selective treatment of SN-positive patients. Eight predictive models assessing the risk of non-SN involvement in patients with SN metastasis were tested in a multi-institutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected non-SN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models, including tumour size, type, grade, oestrogen receptor positivity, rate of lymphovascular invasion, proportion of micrometastatic cases and the presence of extracapsular extension of SN metastasis. There were also significant differences in the proportion of cases classified as having low risk of non-SN metastasis. Despite these differences, there were practically no such differences in the sensitivities, specificities and false reassurance rates of the predictive tools. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN-positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.
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Neoplasias de la Mama/patología , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Anciano , Neoplasias de la Mama/cirugía , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Biopsia del Ganglio Linfático CentinelaRESUMEN
The assessment of morphologic changes in atherosclerotic lesions during interventional procedures such as transluminal balloon angioplasty is an issue of highest clinical importance. We propose a methodology that allows realistic 3D morphomechanical modeling of the vessel, the plaque and the lumen at different stages of in vitro angioplasty. We elaborate on a novel device designed to guide angioplasty under controlled experimental conditions. The device allows to reproduce in vivo conditions as good as possible, i.e. axial in situ pre-stretch, 100mmHg intraluminal pressure, 37 degrees C Tyrode solution, balloon inflation without external constraints using a high-pressure syringe and contrast medium. With a standard 1.5T MR-system we accomplish multi-spectral images at different stages of the angioplasty experiment. After MR image acquisition the specimen is used for histopathological analysis and biomechanical tests. A segmentation process is used to generate NURBS-based 3D geometric models of the individual vessel and plaque components at different balloon pressures. Tissue components are segmented automatically using generalized gradient vector flow active contours. We investigated 10 human femoral arteries. The effects of balloon compression on the individual artery components is particularly described for two obstructed arteries with an intact collagenous cap, a pronounced lipid pool and with calcification. In both arteries we observe a significant increase in lumen area after angioplasty. Dissection between intima and media and reduction of the lipid pool are primary mechanisms of dilatation. This methodology provides a basis for studying plaque biomechanics under supra-physiological loading conditions. It has the potential to improve and validate finite element models of atherosclerotic plaques which may allow a better prediction of angioplasty procedures.