Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results.

PURPOSE: Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. METHODS: Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. RESULTS: 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8-538.5, P=.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. CONCLUSIONS: Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.

Pruebas de coagulación preoperatorias en pacientes pediátricos: relevancia clínica y consecuencias hemorrágicas de los resultados anómalos / Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results

Objetivo: Las pruebas de evaluación de la coagulación en niños siguen realizándose con frecuencia en muchos países, para evaluar el riesgo de hemorragia. El objetivo de este estudio fue valorar el manejo de la prolongación inesperada del tiempo de tromboplastina parcial activada (APTT) y el tiempo de protrombina (PT) en niños previa a la cirugía electiva, y el riesgo hemorrágico perioperatorio. Métodos: Se incluyó a los niños con APTT y/o PT prolongados que acudieron a consulta de anestesia preoperatoria desde enero del 2013 a diciembre del 2018. Se agrupó a los pacientes en función de si habían sido derivados a Hematología o habían sido programados para cirugía sin pruebas adicionales. El resultado primario fue comparar las complicaciones hemorrágicas perioperatorias. Resultados: Se evaluó para elegibilidad a 1.835 niños. Presentaron resultados anormales 102 de ellos (5,6%) y el 45% fue derivado a Hematología previo a la cirugía. Los trastornos hemorrágicos significativos estuvieron asociados a a una historia hemorrágica (personal y/o familiar) positiva, odds ratio de 51 (IC 95% de 4,8 a 538,5, p = 0,0011). No se encontró diferencia en términos de resultados de hemorragia perioperatoria entre los grupos. Se observó un coste adicional de 181 € por paciente y una mediana de demora preoperatoria de 43 días en los pacientes derivados a Hematología. Conclusiones: Nuestros resultados sugieren que la derivación a Hematología tiene un valor limitado en niños asintomáticos con APTT y/o PT prolongados. Las complicaciones hemorrágicas fueron similares entre los pacientes derivados y los no derivados a Hematología. Una historia familiar positiva de hemorragia puede ayudar a identificar a los pacientes con mayor riesgo de sangrado, por lo que debería guiar la petición de los análisis de coagulación y la derivación a Hematología. Esfuerzos adicionales son necesarios para estandarizar las herramientas preoperatorias de evaluación hemorrágica en niños.(AU)

Purpose: Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. Methods: Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. Results: 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8 to 538.5, P = 0.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. Conclusions: Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.(AU)

Dedicated breast PET value to evaluate BI-RADS 4 breast lesions.

PURPOSE: To evaluate the diagnostic value of dedicated breast PET (dbPET) parallel imaging in mammographically or sonographically detected BI-RADS 4 (Breast Imaging Reporting And Data Systems) lesions. MATERIALS AND METHODS: After institutional review board and patient approvals, 50 consecutive women with 60 BI-RADS 4 breast lesions were prospectively included in the study. All patients underwent Magnetic Resonance Imaging (MRI) and dbPET before biopsy and fusion of both MRI and dbPET images was performed to better locate corresponding lesions. Final findings were compared with histological results. Sensitivity and specificity for dbPET were determined along with their respective 95%-confidence intervals. RESULTS: Histopathology examination revealed 18 malignant lesions (7 in situ and 11 invasive carcinomas) and 42 benign entities. The dedicated breast PET reported no evidence of malignancy in 41 patients, 9 of them with histological diagnosis of neoplasm. Besides, dbPET showed increased metabolically activity in 10 benign lesions and in 9 breast cancers. Two invasive carcinomas were located less than 1 cm from the pectoral muscle, which can explain that they were missed by dbPET because they were outside the field of view (FOV). There were other 6 false negative results, which corresponded to a 0.1 cm invasive lobular carcinoma and 5 in situ carcinomas. Sensitivity and specificity of dbPET were 50% and 76%, respectively. CONCLUSIONS: Our analysis does not allow the recommendation of dbPET for diagnosis of malignancy in BI-RADS 4 mammographic or US abnormalities, mainly due to its high false-negative rate for the detection of in situ carcinomas (85.7%). However, considering the lesions greater than 0.1 cm and included in the FOV, dbPET depicted all invasive carcinomas.

HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The role of high in normal-1 (HIN-1) as a potential biomarker in combating this disease is being described for the first time in this study. A combination of O6-methylguanine DNA methyltransferase (MGMT) and HIN-1 methylation could be a possible biomarker in therapy choice. Interestingly, survival data shows a similar trend for the methylation of MGMT and for unmethylation of HIN-1 and vice versa. Eighty-eight paraffin-embedded brain tumors were analyzed to screen methylation rates of different genes and evaluate the association between genes methylation and clinicopathologic variables. Our study is the first of its kind to indicate that MGMT and HIN-1 methylation status are inverted (97.7% of methylated ones) and could be new markers in the study of GBM prognosis, especially in the therapy selection.

Estudios simulados de PET FDG para la evaluación de diferentes métodos de cuantificación de SUV / Simulated FDG-PET studies for the assessment of SUV quantification methods

Objetivo. estudiar en detalle la precisión y la repetitividad de tres métodos de uso común en la estimación del SUV de nódulos pulmonares solitarios. Material y métodos. hemos diseñado una metodología de trabajo basada en la simulación de adquisiciones de estudios PET-FDG a partir de modelos antropomórficos de actividad, que incluyen nódulos pulmonares de diferente tamaño y valor de SUV conocido. Esta metodología nos permite comparar el SUV estimado a partir de la imagen PET con el SUV teórico. La actividad del tumor fue estimada mediante tres métodos conocidos: SUVmax, SUVmean y SUV50. Resultados. nuestros resultados muestran que, por un lado SUVmax sobreestima la actividad en el tumor, mientras SUV50 subestima el valor de actividad de manera muy significa. En cambio, la cuantificación de SUV50 mostró un buen acuerdo con los valores de SUV teóricos o simulados, y únicamente mostró una ligera subestimación para lesiones muy pequeñas. Por otro lado, SUVmean mostró un mejor comportamiento que SUV50 en términos de repetitividad, proporcionando variabilidades por debajo del 5% para todos los tamaños de lesión y para dosis inyectadas tan bajas como 111 MBq. Conclusiones. nuestros hallazgos mostraron que SUV50 proporciona el mejor comportamiento para estimar la actividad en nódulos pulmonares, pero SUVmean mostró mejores resultados en términos de repetitividad (AU)

Aim. To study in detail the accuracy and repeatability of three commonly used methods for SUV estimation in solitary pulmonary nodules. Material and methods. We have designed a realistic framework based on simulated FDG-PET acquisitions from an anthropomorphic activity model that included solitary pulmonary nodules (different sizes) of well-known SUV. This framework enables us to compare the SUV values obtained from the reconstructed PET images with the real SUV values. Three commonly used methods (SUVmax, SUVmean and SUV50) were used to estimate the tumor activity. Results. Our results showed the tumor activity was overestimated using SUVmax and clearly subestimated using SUVmean. Instead, the quantification of SUV50 showed great agreement with the simulated tumor activity and only slight subestimation was found for very small lesions. On the other hand, SUVmean showed better performance than SUV50 in terms of repeatability, providing variabilities below 5% for all tumor sizes and for injected doses as low as 111 MBq. Conclusions. Our findings showed that SUV50 provided better performance for estimating accurately tumor SUV values in pulmonary nodules, but SUVmean showed better results in terms of repeatability (AU)

Simulated FDG-PET studies for the assessment of SUV quantification methods.

AIM: To study in detail the accuracy and repeatability of three commonly used methods for SUV estimation in solitary pulmonary nodules. MATERIAL AND METHODS: We have designed a realistic framework based on simulated FDG-PET acquisitions from an anthropomorphic activity model that included solitary pulmonary nodules (different sizes) of well-known SUV. This framework enables us to compare the SUV values obtained from the reconstructed PET images with the real SUV values. Three commonly used methods (SUVmax, SUVmean and SUV50) were used to estimate the tumor activity. RESULTS: Our results showed the tumor activity was overestimated using SUVmax and clearly subestimated using SUVmean. Instead, the quantification of SUV50 showed great agreement with the simulated tumor activity and only slight subestimation was found for very small lesions. On the other hand, SUVmean showed better performance than SUV50 in terms of repeatability, providing variabilities below 5% for all tumor sizes and for injected doses as low as 111 MBq. CONCLUSIONS: Our findings showed that SUV50 provided better performance for estimating accurately tumor SUV values in pulmonary nodules, but SUVmean showed better results in terms of repeatability.

The performance of a hybrid analytical-Monte Carlo system response matrix in pinhole SPECT reconstruction.

It is well-known that in pinhole SPECT (single-photon-emission computed tomography), iterative reconstruction methods including accurate estimations of the system response matrix can lead to submillimeter spatial resolution. There are two different methods for obtaining the system response matrix: those that model the system analytically using an approach including an experimental characterization of the detector response, and those that make use of Monte Carlo simulations. Methods based on analytical approaches are faster and handle the statistical noise better than those based on Monte Carlo simulations, but they require tedious experimental measurements of the detector response. One suggested approach for avoiding an experimental characterization, circumventing the problem of statistical noise introduced by Monte Carlo simulations, is to perform an analytical computation of the system response matrix combined with a Monte Carlo characterization of the detector response. Our findings showed that this approach can achieve high spatial resolution similar to that obtained when the system response matrix computation includes an experimental characterization. Furthermore, we have shown that using simulated detector responses has the advantage of yielding a precise estimate of the shift between the point of entry of the photon beam into the detector and the point of interaction inside the detector. Considering this, it was possible to slightly improve the spatial resolution in the edge of the field of view.

Preliminary experience with small animal SPECT imaging on clinical gamma cameras.

The traditional lack of techniques suitable for in vivo imaging has induced a great interest in molecular imaging for preclinical research. Nevertheless, its use spreads slowly due to the difficulties in justifying the high cost of the current dedicated preclinical scanners. An alternative for lowering the costs is to repurpose old clinical gamma cameras to be used for preclinical imaging. In this paper we assess the performance of a portable device, that is, working coupled to a single-head clinical gamma camera, and we present our preliminary experience in several small animal applications. Our findings, based on phantom experiments and animal studies, provided an image quality, in terms of contrast-noise trade-off, comparable to dedicated preclinical pinhole-based scanners. We feel that our portable device offers an opportunity for recycling the widespread availability of clinical gamma cameras in nuclear medicine departments to be used in small animal SPECT imaging and we hope that it can contribute to spreading the use of preclinical imaging within institutions on tight budgets.

Only in patients with hormone-dependent breast infiltrating ductal carcinomas, CA15.3 serum levels are inversely correlated with the immunohistochemical expression of Bcl2.

OBJECTIVE: To study possible association between serum CA15.3 levels and immunohistochemical expression of Bcl2 in women affected by infiltrating ductal breast carcinomas. MATERIALS AND METHODS: Two hundred and fifty consecutives women with breast infiltrating ductal carcinomas, aged between 37 and 83 years were included in this study. Serum CA15.3 was determined by electro-chemoluminescence assay (ECLIA-Elecsys 170 Roche). Immunohistochemical staining on tissue sections of 4-5 microns was done by the EnVision method with a heat-induced antigen retrieval step. Antibody used for Bcl2 was (124, Dako, dilution 1/150). Bcl2 expression was assessed as negative (-), weak positive (+) or strong positive (++). RESULTS: In the study group, serum CA15.3 concentrations ranged between 1 and 1743 U/ml, with 25, 50 and 75 percentiles of 12.7, 17.6 and 24.3 U/ml respectively. Serum CA15.3 concentrations were higher in Bcl2 negative cases than in Bcl2 + and Bcl2 ++. We found statistically significant differences between subgroups Bcl2 negative and Bcl2 ++ (p=0.044), between Bcl2 + Bcl2 ++ (p=0.039) and between Bcl2 ++ and Bcl2 -/+ (p=0.013). When we considered 25 U/mL as the threshold of positivity, antigen values>25 U/ml were more frequent in tumors Bcl2- than in Bcl2 ++ (20/52 vs 29/170, p=0.001). The same behavior was observed when comparing the subgroups -/+ with ++ (p=0.001). A very important aspect of our work was that this CA15.3 behavior in relation to the immunohistochemical expression of Bcl2 was maintained in hormone-dependent tumors (ER+), but not in hormone-independent ones. CONCLUSIONS: The results led us to the following consideration: In women affected by infiltrating ductal breast carcinomas, serum levels of CA15.3 associated inversely, both qualitatively and quantitatively, with the immunohistochemical expression of Bcl2, but this fact exists only in hormone-dependent tumors.

[Spanish Society of Anaesthesia (SEDAR) guidelines for pre-anaesthesia checking procedures]. / Directrices de procedimientos de comprobación y validación («chequeo¼) previos a la anestesia de la Sociedad Española de Anestesiología.

We present this document as a guide to preparing a specific institutional pre-anaesthesia checklist, as recommended in the Helsinki declaration on patient safety in anaesthesiology. Also, the recently recommended WHO "safe surgery check-list" includes a check-list for anaesthesia. A working group was established in accordance with the charter of the Spanish Society of Anaesthesiology and Resuscitation (Sociedad Española de Anestesiología y Reanimación [SEDAR]). The new patient safety culture introduced into medicine, and the recommendations of European anaesthesia societies has led us to design and update protocols in order to improve results in this important part of our speciality. We have prepared these recommendations or guidelines using, as examples, updates of pre-anaesthesia check-lists by other American (ASA), British, or Canadian societies of anaesthesia. With that aim, we enlisted the help of anaesthesia ventilator experts and the participation and advice of experienced anaesthesiologists from all parts of Spain. After various corrections and modifications, the document was available at www.sedar.es, so that any anaesthesiologist could propose any correction, or give their opinion. Finally, these guidelines have been approved by the SEDAR Board of Directors, before it was sent for publication in this journal. The aims of this document are to provide: a guideline applicable to all anaesthesia machines, a descriptive pre-anaesthesia check-list that include everything necessary for the anaesthesia procedure, and a resumed check-list to be available in all the anaesthesia machines or other equivalent, but prepared for each institution, which should include anaesthetic equipment and drugs. So, in order to ensure the aims and requirements of the European Board of Anaesthesiology, the European Society of Anaesthesiology, and the WHO are met, each institution should have a protocol for checking equipment and drugs. These guidelines are applicable to any anaesthesia equipment, enabling every institution to develop their own checking protocols, adapted to their anaesthesia machines and their procedures. With the consent of the SEDAR, this group will collaborate with anaesthesia machines providers in order to develop specific checklists for each of their models that will be available at www.sedar.es.

Directrices de procedimientos de comprobación y validación («chequeo») previos a la anestesia de la Sociedad Española de Anestesiología / Spanish Society of Anaesthesia (SEDAR) guidelines for pre-anaesthesia checking procedures

Este documento que presentamos pretende servir de guía para la elaboración por cada centro de una lista de chequeo previo a la anestesia o pre-anestesia, tal y como recomienda la reciente declaración de Helsinki sobre seguridad del paciente en anestesia. Además, la reciente implantación del «check-list quirúrgico de la OMS» (safe surgery check-list) incluye un epígrafe de chequeo de anestesia. El grupo de trabajo se constituyó con este fin según los estatutos de la Sociedad Española de Anestesiología, Reanimación y Tratamiento del Dolor (SEDAR). La nueva cultura de seguridad del paciente que se está implantando en la práctica médica y las recomendaciones de las sociedades europeas de anestesia nos obligan a actualizar y realizar protocolos que mejoren los resultados en este aspecto fundamental de nuestra especialidad. Tomando como ejemplo las actualizaciones de las listas de comprobación de diferentes asociaciones de anestesiólogos como la americana, británica o canadiense, hemos elaborado esta propuesta. Para ello hemos contado con la ayuda de expertos en respiradores y la colaboración y consejos de anestesiólogos expertos de todas las comunidades autónomas. Después de sucesivas correcciones, fue publicada en la página web de la SEDAR para que cualquier anestesiólogo pudiera aportar sus correcciones o su opinión. Finamente el documento ha sido aprobado por la junta directiva de la SEDAR, antes de ser enviado para su publicación en esta revista. Los objetivos de este documento son: proporcionar unas directrices o recomendaciones de comprobación aplicables a todos los sistemas de anestesia, realizar un listado descriptivo de comprobación que incluya todos los elementos necesarios para el procedimiento anestésico y aportar un listado con los elementos del chequeo en forma de esquema para disponer de él en cada equipo de anestesia o de otro similar realizado por cada centro, que incluya respirador, monitores, material auxiliar y fármacos. Por tanto, para cumplir con las recomendaciones de seguridad del paciente del European Board of Anaesthesiology (EBA), European Society of Anaesthesiology (ESA) y de la OMS, cada centro debe elaborar una lista de comprobación y verificación (en adelante «chequeo») previo a la anestesia. Este documento proporciona unas directrices aplicables a todos los sistemas de anestesia de tal manera que cada departamento pueda desarrollar sus propios protocolos de comprobación, adaptados a sus equipos de anestesia y a sus procedimientos de trabajo. De acuerdo con la directiva de la SEDAR, este grupo de trabajo colaborará con los fabricantes de equipos de anestesia para desarrollar listas de comprobación específicas de cada uno de sus modelos para que estén disponibles en www.sedar.es(AU)

We present this document as a guide to preparing a specific institutional pre-anaesthesia checklist, as recommended in the Helsinki declaration on patient safety in anaesthesiology. Also, the recently recommended WHO "safe surgery check-list" includes a check-list for anaesthesia. A working group was established in accordance with the charter of the Spanish Society of Anaesthesiology and Resuscitation (Sociedad Española de Anestesiología y Reanimación [SEDAR]). The new patient safety culture introduced into medicine, and the recommendations of European anaesthesia societies has led us to design and update protocols in order to improve results in this important part of our speciality. We have prepared these recommendations or guidelines using, as examples, updates of pre-anaesthesia check-lists by other American (ASA), British, or Canadian societies of anaesthesia. With that aim, we enlisted the help of anaesthesia ventilator experts and the participation and advice of experienced anaesthesiologists from all parts of Spain. After various corrections and modifications, the document was available at www.sedar.es, so that any anaesthesiologist could propose any correction, or give their opinion. Finally, these guidelines have been approved by the SEDAR Board of Directors, before it was sent for publication in this journal. The aims of this document are to provide: a guideline applicable to all anaesthesia machines, a descriptive pre-anaesthesia check-list that include everything necessary for the anaesthesia procedure, and a resumed check-list to be available in all the anaesthesia machines or other equivalent, but prepared for each institution, which should include anaesthetic equipment and drugs. So, in order to ensure the aims and requirements of the European Board of Anaesthesiology, the European Society of Anaesthesiology, and the WHO are met, each institution should have a protocol for checking equipment and drugs. These guidelines are applicable to any anaesthesia equipment, enabling every institution to develop their own checking protocols, adapted to their anaesthesia machines and their procedures. With the consent of the SEDAR, this group will collaborate with anaesthesia machines providers in order to develop specific checklists for each of their models that will be available at www.sedar.es(AU)

Breast carcinomas with hyperprolactinemia at the time of diagnosis-clinico-biological association.

AIM: To analyse association between preoperative hyperprolactinemia serum levels and clinical and biological features of breast tumors. METHODS: Serum levels of prolactin were measured in 253 women with invasive breast cancer. Clinical and biological parameters analysed were age, size, lymph node involvement, distant metastasis and immunohistochemical expression of estrogen receptor, progesterone receptor, androgen receptor, bcl-2, p53 and Ki67. RESULTS: In ductal carcinomas hyperprolactinemia were associated with high age (p = 0.017), and with bcl-2 + + + expression (p = 0.017). Furthermore, serum prolactin values were significantly higher in bcl-2 +++ cases vs negative (p = 0.029); the same happened when we considered the positivity threshold of 25 ng/mL (p = 0.015). CONCLUSION: Is possible to detect in 6% of infiltrating ductal breast carcinomas hyperprolactinemia (>25 ng/mL), being associated only with increasing age, but not with other clinical or biological factors; and 2) the most surprising data was the association between prolactinemia (qualitative (>25 ng/mL) and quantitative) and intense bcl-2 tissue expression, which suggests that, probably, this (prolactinemia) is not a sign of worse prognosis and evolution.

[The immunohistochemical expression of cyclin B1 is associated with higher SUV in 18F-FDG-PET in non-small cell lung cancer patients. Initial results]. / La expresión inmunohistoquímica de ciclina B1 conlleva mayores valores de SUV en la 18F-FDG-PET de pacientes con carcinomas no microcíticos de pulmón. Primeros resultados.

AIM: to study the expression of cyclin B1 and its possible relationship with the maximum SUV in FDG-PET and MIB1 expression in patients with NSCLC. MATERIALS AND METHODS: 49 patients (15 adenocarcinomas, 27 squamous cell carcinomas and 7 bronchoalveolar carcinomas) were included in this study; the immunohistochemical expression of cyclin B1 was determined using the tissue-array technique. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: cyclin B1 expression was detected in 40 out of 45 cases. The SUV values were higher (p=0.04) in the cyclin B1+ cases than in the negative cases (16.4+/-8.1 vs 10.9+/-6.2). Cyclin B1 expression and SUV values were not correlated with the clinical stage. The expression of cyclin B1+ correlated positively (p<0.0001) with that of MIB1. After univariate analysis, only the cellular proliferation was a prognostic factor (p=0.037). CONCLUSIONS: our results suggest that there is a direct correlation between cyclin B1 expression and max-SUV values in the PET of NSCLC patients. When the association of cyclin B1 with positive MIB1 is also considered, our results support the role of cell proliferation in FDG uptake by the tumour.

La expresión inmunohistoquímica de ciclina B1 conlleva mayores valores de SUV en la 18F-FDG-PET de pacientes con carcinomas no microcíticos de pulmón. Primeros resultados / The immunohistochemical expression of cyclin B1 is associated with higher SUV in 18F-FDG-PET in non-sma ll cell lung cancer patients. Initial results

Objetivo: estudiar la posible correlación entre la expresión de ciclina B1, proliferación celular y la SUV máxima-18F-FDG-PET en pacientes con carcinomas no microcíticos pulmonares. Material y metodo: se incluyó a 49 pacientes (15 adenocarcinomas, 27 carcinomas escamosos y 7 carcinomas broncoalveolares) y se realizó la expresión inmunohistoquímica de ciclina B1 mediante tissue-arrays. Asimismo, analizamos la proliferación celular (MIB-1). El PET se realizó 60 min después de la administración intravenosa (i.v.) de 350-518 MBq de 18F-FDG en un PET (Advance, GE) y adquisión en 2D. Resultados: la expresión inmunohistoquímica de ciclina B1 se detectó en 40 (81,6%) casos y no se relacionó con el estadio clínico (I-II: 17/21 frente a III-IV: 23/28). Los valores de SUV fueron mayores (p = 0,04) en los casos positivos (16,4 ± 8,1) que en los negativos (10,9 ± 6,2) y no difirieron en función del estadio clínico. La expresión de ciclina B1 se correlacionó (p < 0,0001) con la de MIB1. Tras análisis univariable, la ciclina B1 y los valores SUV no fueron factores pronósticos, pero sí la proliferación celular (p = 0,037). Conclusiones: nuestros resultados muestran una relación directa entre la expresión de ciclina B1 y los valores max SUV en el PET de pacientes afectos de carcinomas no microcíticos de pulmón, lo cual, unido a la asociación de aquella con la positividad del MIB1, apoya el papel de la proliferación celular en la captación del radiofármaco por el tumor(AU)

Aim: to study the expression of cyclin B1 and its possible relationship with the maximum SUV in FDG-PET and MIB1 expression in patients with NSCLC. Materials and methods: 49 patients (15 adenocarcinomas, 27 squamous cell carcinomas and 7 bronchoalveolar carcinomas) were included in this study; the immunohistochemical expression of cyclin B1 was determined using the tissue-array technique. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. Results: cyclin B1 expression was detected in 40 out of 45 cases. The SUV values were higher (p = 0.04) in the cyclin B1+ cases than in the negative cases (16.4 ± 8.1 vs 10.9 ± 6.2). Cyclin B1 expression and SUV values were not correlated with the clinical stage. The expression of cyclin B1+ correlated positively (p < 0.0001) with that of MIB1. After univariate analysis, only the cellular proliferation was a prognostic factor (p = 0.037). Conclusions: our results suggest that there is a direct correlation between cyclin B1 expression and max-SUV values in the PET of NSCLC patients. When the association of cyclin B1 with positive MIB1 is also considered(AU)

[The immunohistochemical expression of cyclooxygenase 2 is inversely associated with (18)F-FDG-PET SUV values in non-small-cell lung cancers. Initial results]. / La expresión inmunohistoquímica intensa de ciclooxigenasa 2 se asocia inversamente con los valores máximos de SUV en la (18)F-FDG-PET de pacientes afectados de carcinomas no microcíticos de pulmón. Relación con otros factores biológicos.

OBJECTIVE: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. MATERIAL AND METHOD: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 +/- 1.2 vs. 12.9 vs. 17.1 +/- 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. CONCLUSIONS: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression.

La expresión inmunohistoquímica intensa de ciclooxigenasa 2 se asocia inversamente con los valores máximos de SUV en la 18F-FDG-PET de pacientes afectados de carcinomas no microcíticos de pulmón. Relación con otros factores biológicos / The immunohistochemical expression of cyclooxygenasa 2 is inversely associated with 18F-FDG-PET SUV values in non-small cell lung cancers. Initial results

Objetivo: estudiar la expresión de COX-2 y sus posibles relaciones con el valor de captación estándar (SUV, standardized uptake value, valor de captación estándar) máximo-FDG-PET y la expresión de MIB1, p16 y receptor del factor de crecimiento epidérmico (EGFR) en pacientes afectados de carcinoma no microcítico de pulmón (CPNM). Material y método: se incluyó 45 pacientes (12 adenocarcinomas y 33 carcinomas escamosos) en los que se analizó, mediante tissue-arrays, la expresión de los factores biológicos. Los valores de SUV se obtuvieron 60 min después de la administración del radiofármaco y la imagen se efectuó en un PET Advanced System (GE). Resultados: la expresión de COX-2 se apreció en 35/45 casos, y fue muy importante (> ++) en 12. Los valores de SUV fueron menores (p = 0,059) en los casos COX-2 > ++ que en los restantes (13,4 ± 1,2 frente a 12,9 frente a 17,1 ± 1,5). La expresión de COX-2 > ++ no se correlacionó con el estadio, ni tampoco lo hizo el SUV. La expresión de COX-2 > ++ se correlacionó positivamente con la de p16 (r = 0,36; p = 0,014) y negativamente con la de MIB1 (r = -0,32; p = 0,041), mientras que la SUV lo hizo positivamente con la del EGFR (r = 0,44; p = 0,004) y negativamente con la de p16 (r = -0,29; p = 0,041). Conclusiones: a) la expresión intensa (> ++) de COX-2 se constata en el 26,6% de los CPNM y es independiente del estadio clínico; b) los valores de SUV tampoco se relacionaron con el estadio y fueron menores en los tumores COX-2++ que en el resto de casos, y c) este comportamiento diferente de ambos parámetros se podría explicar por sus distintas relaciones con la proliferación celular (MIB1) y la expresión de EGFR y p16 (AU)

Objective: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. Material and method: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. Results: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 ± 1.2 vs. 12.9 vs. 17.1 ± 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. Conclusions: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression. © 2008 Elsevier España, S.L. and SEMN. All rights reserved (AU)

Reduced clinicopathological influence of hormone-dependence on breast carcinomas in women older than 70 years.

In order to evaluate the influence of hormone dependence on the features of infiltrating ductal carcinoma of the breast we have assayed the cytosolic levels of estrogen receptor (ER), progesterone receptor (PR), pS2 and cathepsin D in 53 women aged over 70 years and in 95 women aged between 55 and 70 years. Tumor size, axillary involvement, distant metastasis, histological grade, ploidy and S-phase were taken into account. Carcinomas of women aged over 70 did not show higher concentrations or higher positive results for ER and PR than those of women in the 55-70-year age group. In older patients, negativity for ER was associated only with higher S-phase fraction, while negativity for PR was not associated with any of the parameters analyzed. In the younger subgroup, negativity for ER was associated with larger tumor size, higher S-phase fraction, lymph node involvement, histological grade 3 and lower pS2 values. Negativity for PR was associated with the same parameters, as well as with a higher frequency of recurrence. Our results suggest a reduced influence of hormone dependence on the clinicopathological features of breast carcinomas in patients older than 70 years compared with women aged between 55 and 70 years.

Reduced clinicopathological influence of hormone-dependence on breast carcinomas in women older than 70 years.

In order to evaluate the influence of hormone dependence on the features of infiltrating ductal carcinoma of the breast we have assayed the cytosolic levels of estrogen receptor (ER), progesterone receptor (PR), pS2 and cathepsin D in 53 women aged over 70 years and in 95 women aged between 55 and 70 years. Tumor size, axillary involvement, distant metastasis, histological grade, ploidy and S-phase were taken into account. Carcinomas of women aged over 70 did not show higher concentrations or higher positive results for ER and PR than those of women in the 55-70-year age group. In older patients, negativity for ER was associated only with higher S-phase fraction, while negativity for PR was not associated with any of the parameters analyzed. In the younger subgroup, negativity for ER was associated with larger tumor size, higher S-phase fraction, lymph node involvement, histological grade 3 and lower pS2 values. Negativity for PR was associated with the same parameters, as well as with a higher frequency of recurrence. Our results suggest a reduced influence of hormone dependence on the clinicopathological features of breast carcinomas in patients older than 70 years compared with women aged between 55 and 70 years.

Carcinomas infiltrantes mamarios en mujeres menores de 40 años: posible interés fisiopatológico del receptor del factor de crecimiento epidérmico (EGFR) / No disponible

Objetivo: Estudiar las características clínico-biológicas delos carcinomas mamarios de pacientes con edad < 40 años ycompararlas con las de mujeres de edad comprendida entre40 y 45 años.Pacientes y método: Incluyen dos subgrupos: a) 11 mujerescon una edad < 40 años; y b) 26 con edades comprendidasentre 40 y 45 años. Hemos determinado las concentracionesde EGFR en las membranas celulares, así como las delreceptor de estrógenos, de progesterona, pS2, y catepsina Dcitosólicas. Se consideró, además, el tamaño, afectación axilar,metástasis a distancia, grado y subtipo histológico, asícomo la fase de síntesis celular (FS).Resultados: Los tumores de mujeres < 40 años mostraronmayores concentraciones de EGFR (p < 0,05) y fueron másfrecuentemente EGFR positivo (> 5 fmol/mg prot. –p <0,01– y FS > 7% –p < 0,01–). No se constataron diferenciasen el número de recidivas y muertes observadas durante el seguimiento.El patrón tisular RE negativo/EGFR-negativo seasoció significativamente a tumores en mujeres entre los 40 y45 años, mientras que el patrón RE-negativo/EGFR-positivolo hizo con los de mujeres < 40 años.Conclusiones: Nuestros resultados, sugieren que los carcinomasmamarios en mujeres < 40 años parecen cursarcon una mayor proliferación y expresión de EGFR que losde mujeres con edad comprendida entre los 40 y 45 años,asociándose a un patrón tisular RE-negativo/EGFR-positivo;son necesarios más estudios para poder precisar el valordel EGFR en la biología de los carcinomas mamarios de mujeresjóvenes(AU)

Objective: To study the clinical-biological features of infiltratingbreast carcinomas in women aged < 40 years and tocompare then with those observed in women aged 40-45years with the same malignant tumours.Material and methods: The study group included two subgroups:a) 11 women aged < 40 years; and b) 26 womenaged between 40 and 45 years. We assayed the levels of epidermalgrowth factor receptor in cell surfaces, as well as thecytosolic concentrations of estrogen receptor, progesteronereceptor, pS2 and cathepsin D. Tumor size, axillary involvement,distant metastasis, histological grade and cellular Sphase(SP) were taken account.Results: The breast carcinomas of patients aged < 40 yrs.had higher concentrations of EGFR (p < 0,05) and were moreoften EGFR positive (> 5 fmol/mg prot.; p < 0,01) and FS> 7% (p < 0,01). We did not observed any statistically differencesin the number of recurrences and deaths in both subgroupsof patients. The ER-negative/EGFR-positive pattern associatedsignificantly with the tumors of women aged between40 and 45 years, whereas the RE-negative/EGFR-negative associatedwith the tumors of patients aged less than 40 years.Conclusions: Our results suggest that the breast carcinomasin women aged < 40 yrs. show a greater proliferation andEGFR expression than those of women aged between 40 and45 yrs., being associated with ER-negative/EGFR-negativepattern. Further studies are necessary to know the EGFR rolein breast carcinomas in young women(AU)