Comprehensive ethoxymer characterization of complex alcohol ethoxy sulphate products by mixed-mode high-performance liquid chromatography coupled to charged aerosol detection.

The present work describes a simultaneous mixed-mode high performance liquid chromatography (HPLC) method combined with a universal and non-selective-response detector for the complete ethoxymer profiling of alcohol ethoxy sulphate mixtures. The optimized HPLC methodology combines the dual hydrophilic (HILIC) and reversed-phase selectivity of a surfactant-type column in order to render a comprehensive and simultaneous separation of more than 50 endogenous ethoxymers in a single analysis. Furthermore, an accurate quantitation of every single analyte was achieved using a final universal charged aerosol detector (CAD) including specific mathematical processing tools. Results obtained helped describing a complete alkyl chain and ethoxymer distribution of the investigated AES samples. Method validation evidences provided reliability of the individual ethoxymer contributions determined with the proposed HPLC-CAD methodology. Regarding accuracy including independent nuclear magnetic resonance (NMR) experiments, an excellent correlation was found between the structural information provided by a COSY NMR spectrum and the CAD results regarding the mono/polyethoxylated and the non-ethoxylated/ethoxylated distribution. Additional calculations including the average molecular weight and the degree of ethoxylation for the reference AES sample showed minimum differences (relative error < 1 %) between the two considered techniques. An outstanding precision and linearity along the working concentration range (r2>0.999) was also observed. The individual limit of detection for the target sulphate ethoxymers was determined to be in the low ppm range. Further validated distribution profiles for a large number of AES samples demonstrated the applicability of the optimized HPLC-CAD methodology to routine surfactant screenings. Therefore, the hereby developed methodology provided extensive information regarding the detailed individual ethoxymer profile of AES formulations, which can be extremely useful for the surfactant industry in order to gain information on specific synthesis routes and/or detergency properties.

Pseudoprogresión tumoral en el tratamiento inmunoterápico con nivolumab en el cáncer de pulmón / Tumor pseudoprogression during nivolumab immunotherapy for lung cancer

OBJETIVOS: La inmunoterapia es un nuevo tratamiento en estadios avanzados del cáncer de pulmón de célula no pequeña (CPCNP) que modula la respuesta inmunitaria frente a células malignas. Un reto para el radiólogo es la valoración del fenómeno de la pseudoprogresión, en la que se observa un aumento o aparición de lesiones por infiltración de células inflamatorias, con posterior disminución o desaparición de estas, hecho que traduce en realidad la respuesta al tratamiento. El objetivo fue determinar la frecuencia de pseudoprogresión en pacientes con CPCNP en estadios avanzados tratados con nivolumab. PACIENTES Y MÉTODOS: Se incluyeron 56 pacientes con CPCNP en estado avanzado tratados con nivolumab en segunda línea o posterior. Se analizaron las tomografías computarizadas (TC) realizadas durante el período de tratamiento. Se consideró pseudoprogresión tumoral al aumento o aparición de lesiones con posterior disminución o desaparición en una TC de control realizada a las 4-8 semanas. Se realizó un análisis descriptivo. RESULTADOS: No se pudo valorar la existencia de pseudoprogresión en 15 pacientes porque no se disponía de al menos dos TC (por cambio de tratamiento o fallecimiento). Se observó pseudoprogresión tumoral en un 12,2% (5/41) de los pacientes, en la mayoría de los casos antes de las 12 semanas del inicio del tratamiento (en el 4. ° ciclo). Un 40% (2/5) de los pacientes con pseudoprogresión presentó un segundo episodio, que se produjo de forma tardía, a partir de las 12 semanas del inicio del tratamiento. CONCLUSIÓN: Se observó pseudoprogresión tumoral en un 12,2% de los pacientes con CPCNP tratados con nivolumab. El aumento o aparición de lesiones debe valorarse evolutivamente para evitar diagnosticar erróneamente progresión de la enfermedad

OBJECTIVES: Immunotherapy is a new treatment in advanced lung cancer that works by modulating the immune response against malignant cells. One aspect that is challenging for radiologists in the evaluation of the response to immunotherapy is the phenomenon of pseudoprogression, in which the infiltration of inflammatory cells causes lesions to increase in size or new lesions to appear and then decrease in size or disappear. Pseudoprogression actually represents a response to treatment. We aimed to determine the frequency of pseudoprogression in patients with advanced stages of lung cancer treated with nivolumab. PATIENTS AND METHODS: We included 56 patients with advanced stages of lung cancer treated with nivolumab as a second-line or later treatment. We analyzed CT studies done while patients were undergoing nivolumab treatment. Tumor pseudoprogression was defined as an increase in the size of lesions or appearance of new lesions followed by a decrease in size or disappearance of these lesions on follow-up CT studies 4 to 8 weeks later. We did a descriptive analysis. RESULTS: In 15 patients, it was impossible to evaluate possible pseudoprogression because a second CT study was unavailable due to change of treatment or death. Tumor pseudoprogression was observed in 5 (12.2%) of the 41 patients, in most cases within 12 weeks of treatment initiation (in the fourth cycle). A second episode of pseudoprogression occurred in 2 (40%) of the 5 patients with an initial episode; the second episode occurred more than 12 weeks after treatment initiation. CONCLUSION: Tumor pseudoprogression occurred in 12.2% of patients with advanced stage lung cancer treated with nivolumab. An increase in lesion size or the appearance of new lesions must be assessed over time to avoid mistaking pseudoprogression for true progression of disease

Detección del foco epileptógeno mediante dos nuevos métodos de procesamiento de imágenes SPECT y PET cerebral: PET-Analysis y PISCOM / Detection of epileptogenic focus with two new methods of processing of SPECT and PET cerebral images: PET-Analysis and PISCOM

La neuroimagen funcional de la PET con 18F-FDG y la SPECT de perfusión son exploraciones cada vez más imprescindibles para la localización prequirúrgica del foco epileptógeno. Presentamos el caso de un paciente varón de 18 años con crisis epilépticas refractarias a tratamiento antiepiléptico. La RM mostró displasia en córtex insular posterior derecho. El SISCOM detectó un aumento focal de captación en cíngulo frontoparietal izquierdo y en la PET-FDG se visualizaba una distribución normal del radiotrazador. Se realizó resección insular posterior derecha, cuyo resultado anatomopatológico fue ganglioglioma grado I de la clasificación de la OMS. El paciente mostró una evolución posquirúrgica favorable, encontrándose libre de crisis desde hace 5 años (Engel I). Un análisis retrospectivo de este caso con 2 nuevos métodos de procesamiento de imágenes: PET-Analysis y PISCOM, permitió localizar correctamente el foco epileptógeno en córtex insular posterior derecho

Functional neuroimaging with positron emission tomography with 18F-fluorodeoxyglucose (PET-18F-FDG) and perfusion single photon emission computerized tomography (SPECT) are increasingly more essential for presurgically locating the epileptogenic focus. We present the case of an 18-year-old male with epileptic seizures refractory to antiepileptic treatment. Magnetic resonance (MR) showed dysplasia in the posterior right insular cortex. Subtraction of ictal SPECT co-registered to MR (SICOM) detected a focal increase of uptake in the left fronto-parietal cingulate and PET-FDG showed normal distribution of the radiotracer. The posterior right insula was resected with histopathological results of grade I ganglioglioma according to the World Health Organization classification. The patient made favourable post-surgical progress, and remains seizure-free after 5 years (Engel I). Retrospective analysis of this case with two new image processing methods (PET analysis and PET interictal subtracted ictal SPECT coregistered with MR [PISCOM]) correctly localized the epileptogenic focus in the posterior right insular cortex

Tumor pseudoprogression during nivolumab immunotherapy for lung cancer. / Pseudoprogresión tumoral en el tratamiento inmunoterápico con nivolumab en el cáncer de pulmón.

OBJECTIVES: Immunotherapy is a new treatment in advanced lung cancer that works by modulating the immune response against malignant cells. One aspect that is challenging for radiologists in the evaluation of the response to immunotherapy is the phenomenon of pseudoprogression, in which the infiltration of inflammatory cells causes lesions to increase in size or new lesions to appear and then decrease in size or disappear. Pseudoprogression actually represents a response to treatment. We aimed to determine the frequency of pseudoprogression in patients with advanced stages of lung cancer treated with nivolumab. PATIENTS AND METHODS: We included 56 patients with advanced stages of lung cancer treated with nivolumab as a second-line or later treatment. We analyzed CT studies done while patients were undergoing nivolumab treatment. Tumor pseudoprogression was defined as an increase in the size of lesions or appearance of new lesions followed by a decrease in size or disappearance of these lesions on follow-up CT studies 4 to 8 weeks later. We did a descriptive analysis. RESULTS: In 15 patients, it was impossible to evaluate possible pseudoprogression because a second CT study was unavailable due to change of treatment or death. Tumor pseudoprogression was observed in 5 (12.2%) of the 41 patients, in most cases within 12 weeks of treatment initiation (in the fourth cycle). A second episode of pseudoprogression occurred in 2 (40%) of the 5 patients with an initial episode; the second episode occurred more than 12 weeks after treatment initiation. CONCLUSION: Tumor pseudoprogression occurred in 12.2% of patients with advanced stage lung cancer treated with nivolumab. An increase in lesion size or the appearance of new lesions must be assessed over time to avoid mistaking pseudoprogression for true progression of disease.

Guidelines for the assembly of hydrogen-bonded macrocycles.

The formation of well-defined, discrete self-assembled architectures relies on the interplay between non-covalent interactions and cooperative phenomena. In particular, chelate or intramolecular cooperativity is responsible for the assembly of closed, cyclic structures in competition with open, linear oligomers, and it can be enhanced in several ways to increase the stability of a given cycle size. In this article, we review the work of several researchers on the synthesis of hydrogen-bonded macrocycles from ditopic molecules and analyze the main factors, often interrelated, that influence the equilibrium between ring and chain species. Emphasis will be set on the diverse features that can increase cyclization fidelity, including monomer geometry, template effects, conformational effects, intramolecular interactions and H-bonding pattern.

Detection of epileptogenic focus with two new methods of processing of SPECT and PET cerebral images: PET-Analysis and PISCOM. / Detección del foco epileptógeno mediante dos nuevos métodos de procesamiento de imágenes SPECT y PET cerebral: PET-Analysis y PISCOM.

Functional neuroimaging with positron emission tomography with 18F-fluorodeoxyglucose (PET-18F-FDG) and perfusion single photon emission computerized tomography (SPECT) are increasingly more essential for presurgically locating the epileptogenic focus. We present the case of an 18-year-old male with epileptic seizures refractory to antiepileptic treatment. Magnetic resonance (MR) showed dysplasia in the posterior right insular cortex. Subtraction of ictal SPECT co-registered to MR (SICOM) detected a focal increase of uptake in the left fronto-parietal cingulate and PET-FDG showed normal distribution of the radiotracer. The posterior right insula was resected with histopathological results of grade I ganglioglioma according to the World Health Organization classification. The patient made favourable post-surgical progress, and remains seizure-free after 5 years (Engel I). Retrospective analysis of this case with two new image processing methods (PET analysis and PET interictal subtracted ictal SPECT coregistered with MR [PISCOM]) correctly localized the epileptogenic focus in the posterior right insular cortex.

Análisis de la prueba de evaluación clínica objetiva estructurada (ECOE) de sexto curso en la Facultad de Medicina de la Universidad Miguel Hernández de Elche / Analysis of the objective structured clinical examination (OSCE) of the sixth year in the School of Medicine of the Miguel Hernández University of Elche

INTRODUCCIÓN: La prueba evaluación clínica objetiva y estructurada (ECOE) es un método de evaluación de la competencia clínica con evidencia de validez, objetividad y confiabilidad. En este estudio nos propusimos analizar la prueba ECOE de los estudiantes de sexto del grado de medicina. MATERIAL Y MÉTODOS: Estudio transversal de la prueba ECOE realizada en la Facultad de Medicina de la Universidad Miguel Hernández de Elche en junio de 2016. RESULTADOS: En la prueba participaron 116 alumnos. Había 7 (35%) estaciones de paciente estandarizado, 5 (25%) estaciones de informe, 4 (20%) estaciones de maniquí/procedimiento y 4 (20%) estaciones de tipo examen oral estructurado. La mediana de la puntuación de los alumnos fue de 7,14 (recorrido intercuartílico: 6,90-7,43). La mediana de la puntuación de los alumnos del primer día por la mañana fue de 7,10, del primer día por tarde fue superior (7,14) y la del segundo día por la mañana también lo fue (7,24; p = 0,1). La estación con menor puntuación fue la de informe (6,41) y la estación con mayor puntuación fue la de maniquí/procedimiento (7,88) (p < 0,001). Dentro de las estaciones de paciente estandarizado (mediana = 7,12), los resultados de los alumnos fueron mejores en las que el paciente era un facultativo en formación (7,52) que en las que el paciente era un actor (6,82) (p < 0,001). El área competencial con mejor puntuación fue la de los aspectos éticos legales y profesionalismo (8,56), seguida de las habilidades de comunicación (7,79). CONCLUSIONES: El análisis de la prueba ECOE ha permitido comprender su naturaleza y las oportunidades de mejora que ofrece con vistas a futuras pruebas

INTRODUCTION: The objective structured clinical examination (OSCE) is a method of evaluating clinical competence with evidence of validity, objectivity, and reliability. In this study an analysis is presented of the OSCE by sixth-year medical students. MATERIAL AND METHODS: Cross-sectional study of the OSCE carried out in the School of Medicine of the Universidad Miguel Hernández de Elche in June 2016. RESULTS: The test involved 116 sixth-year students. The test consisted of 7(35%) standardised patient stations, 5 (25%) reporting stations, 4 (20%) mannequin/procedure stations, and 4 (20%) structured oral exam-type stations. The median student score was 7.14 (interquartile range: 6.90-7.43). The median score for the students on the first day in the morning was 7.10. On the first day in the afternoon it was higher (7.14) and also higher (7.24) on the second day in the morning, but with no statistically significant differences. The station with the lowest score was the report station (6.41), and the station with the highest score was the mannequin/procedure station (7.88) (P < .001). In the standardised patient stations (score: 7.12), the results of the students were better in those where the patient was a doctor in training (7.52) than in those where the patient was an actor (6.82) (P < .001). The highest-ranking of competence was legal ethics and professionalism (8.56), followed by communication skills (7.79) (P < .001). CONCLUSIONS: The analysis of the OSCE has led to understanding the nature of the test and the opportunities of improvement that it offers for future tests

Correlación de la captación de 18F-FDG de la PET/TC con el Ki67 de la inmunohistoquímica en el cáncer epitelial de ovario pretratamiento / Correlation of 18F-FDG uptake on PET/CT with Ki67 immunohistochemistry in pre-treatment epithelial ovarian cancer

Objetivo. El Standardized uptake value (SUV) y los parámetros volumétricos volumen metabólico tumoral (MTV) y glicolisis total de la lesión (TLG) de la 18F-FDG PET/TC son útiles para determinar el pronóstico preoperatorio y postratamiento del cáncer epitelial de ovario (CEO). El Ki67 es otro marcador pronóstico en el CEO asociado con la agresividad tumoral. El objetivo fue estudiar la asociación entre los parámetros de la 18F-FDG PET/TC y el Ki67 en el CEO pretratamiento para determinar si la PET/TC puede predecir la agresividad tumoral de forma no invasiva. Material y métodos. Se realizó una PET/TC a 18 pacientes con sospecha o recién diagnóstico de CEO. Se obtuvo el SUV máximo (SUVmax), SUV medio (SUVmean) y el MTV y la TLG corporal (wbMTV y wbTLG, respectivamente), con un dintel del 30%-40% del SUVmax. Se estimó el índice de Ki67 (medio y máximo) en muestras del tejido tumoral, y se correlacionó con los parámetros de la PET. Resultados. La edad media fue 57,0 años (desviación estándar 13,6 años). Se observó una moderada correlación entre el Ki67 medio y el SUVmax (r=0.392), SUVmean 30% (r=0.437) y SUVmean 40% (r=0.443), así como entre el Ki67 máximo y el SUVmax (r=0.360), SUVmean 30% (r=0.362) y SUVmean 40% (r=0.319). La correlación fue más débil, e inversamente negativa, entre el Ki67 medio y máximo y los parámetros volumétricos de la PET. No hubo diferencias estadísticamente significativas entre las correlaciones. Conclusiones. SUVmax y SUVmean se correlacionaron moderadamente con el Ki67 mientras que los parámetros volumétricos mostraron una correlación débil. SUVmax y SUVmean podrían utilizarse para predecir la agresividad tumoral en el CEO pretratamiento (AU)

Objective. Standardised uptake value (SUV) and volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are useful criteria for disease prognosis in pre-operative and post-treatment epithelial ovarian cancer (EOC). Ki67 is another prognostic biomarker in EOC, associated with tumour aggressiveness. The aim of this study is to evaluate the association between 18F-FDG PET/CT measurements and Ki67 in pre-treatment EOC to determine if PET/CT parameters could non-invasively predict tumour aggressiveness. Material and methods. A pre-treatment PET/CT was performed on 18 patients with suspected or newly diagnosed EOC. Maximum SUV (SUVmax), mean SUV (SUVmean), whole-body MTV (wbMTV), and whole-body TLG (wbTLG) with a threshold of 30% and 40% of the SUVmax were obtained. Furthermore, Ki67 index (mean and hotspot) was estimated in tumour tissue specimens. Immunohistochemical findings were correlated with PET parameters. Results. The mean age was 57.0 years old (standard deviation 13.6 years). A moderate correlation was observed between mean Ki67 index and SUVmax (r=0.392), SUVmean 30% (r=0.437), and SUVmean 40% (r=0.443), and also between hotspot Ki67 index and SUVmax (r=0.360), SUVmean 30% (r=0.362) and SUVmean 40% (r=0.319). There was a weaker correlation, which was inversely negative, between mean and hotspot Ki67 and volumetric PET parameters. However, no statistical significant differences were found for any correlations. Conclusions. SUVmax and SUVmean were moderately correlated with Ki67 index, whereas volumetric PET parameters overall, showed a weaker correlation. Thus, SUVmax and SUVmean could be used to assess tumour aggressiveness in pre-treatment EOC (AU)

Correlation of 18F-FDG uptake on PET/CT with Ki67 immunohistochemistry in pre-treatment epithelial ovarian cancer. / Correlación de la captación de 18F-FDG de la PET/TC con el Ki67 de la inmunohistoquímica en el cáncer epitelial de ovario pretratamiento.

OBJECTIVE: Standardised uptake value (SUV) and volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are useful criteria for disease prognosis in pre-operative and post-treatment epithelial ovarian cancer (EOC). Ki67 is another prognostic biomarker in EOC, associated with tumour aggressiveness. The aim of this study is to evaluate the association between 18F-FDG PET/CT measurements and Ki67 in pre-treatment EOC to determine if PET/CT parameters could non-invasively predict tumour aggressiveness. MATERIAL AND METHODS: A pre-treatment PET/CT was performed on 18 patients with suspected or newly diagnosed EOC. Maximum SUV (SUVmax), mean SUV (SUVmean), whole-body MTV (wbMTV), and whole-body TLG (wbTLG) with a threshold of 30% and 40% of the SUVmax were obtained. Furthermore, Ki67 index (mean and hotspot) was estimated in tumour tissue specimens. Immunohistochemical findings were correlated with PET parameters. RESULTS: The mean age was 57.0 years old (standard deviation 13.6 years). A moderate correlation was observed between mean Ki67 index and SUVmax (r=0.392), SUVmean 30% (r=0.437), and SUVmean 40% (r=0.443), and also between hotspot Ki67 index and SUVmax (r=0.360), SUVmean 30% (r=0.362) and SUVmean 40% (r=0.319). There was a weaker correlation, which was inversely negative, between mean and hotspot Ki67 and volumetric PET parameters. However, no statistical significant differences were found for any correlations. CONCLUSIONS: SUVmax and SUVmean were moderately correlated with Ki67 index, whereas volumetric PET parameters overall, showed a weaker correlation. Thus, SUVmax and SUVmean could be used to assess tumour aggressiveness in pre-treatment EOC.

Dye-conjugated complementary lipophilic nucleosides as useful probes to study association processes by fluorescence resonance energy transfer.

Modern supramolecular chemistry relies on the combination of diverse analytical techniques that can provide complementary information on complex self-assembly landscapes. Among them, resonance energy transfer, monitored by fluorescence emission spectroscopy, arises as a sensitive and convenient phenomenon to report binding intermolecular interactions. The use of molecular probes labelled with suitable complementary energy-transfer pairs can provide valuable information about the thermodynamics, kinetics and self-sorting characteristics of a particular self-assembled system. The objective of this work is to generate a set of nucleoside FRET probes that can be reliably employed to prove and analyse quantitatively H-bonding interactions between complementary Watson-Crick pairs. We first describe the preparation of a set of lipophilic nucleosides that are linked to a π-conjugated functional fragment. The bases include guanosine and 2-aminoadenosine as purine heterocycles, and cytidine and uridine as complementary pyrimidine bases. The π-conjugated moiety comprises either a short phenylene-ethynylene oligomer, a bithiophene, or a BODIPY dye. We then demonstrate that the last two chromophores constitute an energy donor-acceptor couple and that donor emission quenching can be related to the ratio of molecules bound to the complementary acceptor pair. Hence, fluorescence spectroscopy in combination with resonance energy transfer, is shown here to be a useful tool to study and quantify the association and self-sorting events between complementary and non-complementary nucleosides in apolar aromatic solvents, where the binding strength is considerably high, and sensitive techniques that employ low concentrations are demanded.

18F-FDG PET/CT and sentinel lymph node biopsy in the staging of patients with cervical and endometrial cancer. Role of dual-time-point imaging / PET/TC con 18F-FDG y biopsia del ganglio centinela en la estadificación de pacientes con cáncer de cérvix y endometrio. Utilidad de la imagen dual-time-point

Objective. Definitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual-time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference. Material and methods. A prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results. Results. In the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found. Conclusions. PET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes (AU)

Objetivo. La estadificación definitiva del cáncer de cérvix (CC) y de endometrio (CE) tiene lugar tras la cirugía. Nuestro objetivo fue evaluar la utilidad de la PET/TC para la detección de metástasis ganglionares en el CC y en el CE con imagen dual-time-point (DPI), considerando como gold standard la histopatología del ganglio centinela (GC) y la linfadenectomía. Material y métodos. Diecisiete pacientes con CC inicial y 13 con CE de alto riesgo fueron incluidas prospectivamente. Preoperatoriamente se realizó una PET/TC, RM, detección del GC y linfadenectomía en los casos indicados. Se comparó la PET/TC con la histopatología. Resultados. En el estudio anatomopatológico, 4 pacientes con CC y 4 con CE tuvieron metástasis ganglionares. La PET/TC mostró ganglios hipermetabólicos en una paciente con CC y en 5 con CE. Cuatro de ellas tenían metástasis, una detectada en el GC. Cuatro pacientes con PET/TC negativa presentaron micrometástasis en el GC, una paciente con ganglios adicionales infiltrados. La sensibilidad, especificidad, valor predictivo positivo y negativo y la exactitud diagnóstica de la PET/TC para detectar metástasis ganglionares fueron 20,0; 100,0; 100,0; 87,9 y 88,2% para el CC, y 57,1; 88,9; 66,7; 84,2 y 80,0% para el CE. La DPI mostró un índice de retención superior en ganglios infiltrados respecto a los inflamatorios, sin hallar diferencias estadísticamente significativas. Conclusiones. La PET/TC tiene baja sensibilidad para estadificar el CC y CE por la incapacidad de detectar micrometástasis y, por tanto, no sustituye la detección del GC. Aunque no hubo diferencias estadísticamente significativas, la DPI podría ayudar a diferenciar ganglios inflamatorios de tumorales (AU)

18F-FDG PET/CT and sentinel lymph node biopsy in the staging of patients with cervical and endometrial cancer. Role of dual-time-point imaging.

OBJECTIVE: Definitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual-time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference. MATERIAL AND METHODS: A prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results. RESULTS: In the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found. CONCLUSIONS: PET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes.

Prognostic value of 18F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer / Valor pronóstico de los parámetros volumétricos de la 18F-FDG PET/TC en el cáncer epitelial de ovario recurrente

Objective. Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of 18F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. Material and methods. Twenty-six patients with EOC who underwent a total of 31 18F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. Results. Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. Conclusion. Volumetric parameters wbMTV and wbTLG 50% measured by 18F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC (AU)

Objetivo. El metabolic tumour volume (MTV) y la total lesion glycolysis (TLG) obtenidos de la 18F-FDG PET/TC son biomarcadores pronósticos emergentes en varias neoplasias. Estos parámetros volumétricos junto con el SUVmax son útiles para determinar el pronóstico preoperatorio y post-tratamiento de las pacientes con cáncer epitelial de ovario (CEO). El objetivo fue determinar la utilidad de los parámetros de la 18F-FDG PET/TC para predecir la supervivenvia de las pacientes con CEO recurrente. Material y métodos. Se incluyeron retrospectivamente 26 pacientes con CEO a las que se les realizó 31 estudios 18F-FDG PET/TC por sospecha de recidiva. Se obtuvo el valor del SUVmax, whole-body MTV (wbMTV) y whole-body TLG (wbTLG) con un umbral del 40% y 50% del SUVmax. Se estimó la correlación entre los parámetros PET y el intervalo libre de progresión (ILP) y se realizó análisis de supervivencia segun factores pronósticos. Resultados. El subtipo histológico más frecuente fue cáncer seroso (76,9%). La mediana del ILP fue 12,5 meses (rango 10,7-20,6 meses). Se observó correlación inversa moderada entre los parámetros volumétricos e ILP, sin evidenciar correlación significativa con SUVmax. La correlación fue más fuerte para primeras recidivas. Las curvas de supervivencia mostraron correlación entre wbMTV 40%, wbMTV 50% y wbTLG 50% con ILP. SUVmax y wbTLG 40% no fueron predictores de ILP de forma estadísticamente significativa. Conclusión. Los parámetros wbMTV y wbTLG 50% de la 18F-FDG PET/TC podrían utilizarse como factores pronósticos ofreciendo una valiosa información para individualizar el tratamiento de las pacientes con CEO recurrente (AU)

Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer.

OBJECTIVE: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. MATERIAL AND METHODS: Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. RESULTS: Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. CONCLUSION: Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC.

Cribado mediante angiogammagrafía previo a la realización de gammagrafía con leucocitos 99mTc-HMPAO en el diagnóstico de infección de prótesis articulares / Screening with angiographic images prior to 99mTc-HMPAO labelled leukocyte scintigraphy in the diagnosis of periprosthetic infection

Objetivo. Analizar la utilidad de la fase angiogammagráfica de la gammagrafía ósea en 3 fases como posible método de cribado en el diagnóstico de infección de prótesis de cadera y de rodilla, previa a la realización de la gammagrafía con leucocitos marcados. Material y métodos. Se analizaron prospectivamente 120 pacientes (70 mujeres y 50 hombres) con edad media de 71 ± 11 años y sospecha clínica de infección de prótesis de cadera (n = 63) o rodilla (n = 57), a los que se realizó gammagrafía ósea en 3 fases (angiogammagrafía, fase vascular y fase ósea) y gammagrafía con leucocitos marcados con 99mTc-HMPAO. El diagnóstico definitivo se realizó mediante estudio microbiológico o seguimiento clínico mínimo de 12 meses. Resultados. Se estableció el diagnóstico de infección de la prótesis articular en 18/120 pacientes: 10 pacientes con prótesis de cadera y 8 pacientes con prótesis de rodilla. La angiogammagrafía fue positiva en 15/18 pacientes infectados y en 21/102 pacientes no infectados, mostrando una sensibilidad del 83%, una especificidad del 79% y un valor predictivo negativo del 97%. La gammagrafía con leucocitos marcados mostró una sensibilidad y una especificidad del 72 y del 95%, respectivamente. Si se realizara la gammagrafía con leucocitos marcados exclusivamente a los pacientes con angiogammagrafía positiva, se reduciría un 70% de gammagrafías con leucocitos practicadas. No hubo ningún caso de infección con gammagrafía con leucocitos marcados positiva y angiogammagrafía negativa. Conclusiones. La angiogammagrafía es una buena técnica de cribado de infección de prótesis articulares de cadera y rodilla, disminuyendo significativamente el número de gammagrafías con leucocitos marcados, sin afectar la sensibilidad de la técnica (AU)

Aim. To evaluate the impact of the angioscintigrapy of the three phase bone scan as screening method to rule out infection of the hip and knee prosthesis prior to performing the 99mTc-HMPAO leukocyte scintigraphy. Material and methods. A total of 120 (70 women, 50 men; mean age 71 ± 11 years) with clinical suspicion of hip (n = 63) or knee (n = 57) infection of the prosthesis and clinical suspicion of infection were evaluated prospectively. All patients underwent three-phase bone scan (angioscintigraphy, vascular and bone phase) and 99mTc-HMPAO-labelled white blood cell scintigraphy. Final diagnosis of infection was made by microbiological documentation or clinical follow-up for at least 12 months. Results. Eighteen out of 120 patients were diagnosed of infection of hip prosthesis (n = 10) or knee prosthesis (n = 8). The angioscintigraphy was positive in 15/18 infected cases and in 21/102 of the non-infected cases with a sensitivity of 83%, specificity of 79% and negative predictive value of 97%. Sensitivity and specificity of 99mTc-HMPAO leukocyte scintigraphy were 72% and 95%, respectively. If the leukocyte labeled scintigraphies had been used exclusively for patients with positive angioscintigraphy, this would have saved up to 70% of the 99mTc-HMPAO leukocyte scintigraphies performed. There were no cases of infection with positive labeled leukocyte scintigraphy and negative angioscintigraphy. Conclusion. Angioscintigraphy (blood flow phase of bone scan) is a useful technique for screening for hip and knee joint prosthesis infection, significantly reducing the need for 99mTc-HMPAO leukocyte scintigraphy without affecting the sensitivity of the technique (AU)

[Screening with angiographic images prior to (99m)Tc-HMPAO labelled leukocyte scintigraphy in the diagnosis of periprosthetic infection]. / Cribado mediante angiogammagrafía previo a la realización de gammagrafía con leucocitos (99m)Tc-HMPAO en el diagnóstico de infección de prótesis articulares.

AIM: To evaluate the impact of the angioscintigrapy of the three phase bone scan as screening method to rule out infection of the hip and knee prosthesis prior to performing the (99m)Tc-HMPAO leukocyte scintigraphy. MATERIAL AND METHODS: A total of 120 (70 women, 50 men; mean age 71±11years) with clinical suspicion of hip (n=63) or knee (n=57) infection of the prosthesis and clinical suspicion of infection were evaluated prospectively. All patients underwent three-phase bone scan (angioscintigraphy, vascular and bone phase) and (99m)Tc-HMPAO-labelled white blood cell scintigraphy. Final diagnosis of infection was made by microbiological documentation or clinical follow-up for at least 12months. RESULTS: Eighteen out of 120 patients were diagnosed of infection of hip prosthesis (n=10) or knee prosthesis (n=8). The angioscintigraphy was positive in 15/18 infected cases and in 21/102 of the non-infected cases with a sensitivity of 83%, specificity of 79% and negative predictive value of 97%. Sensitivity and specificity of (99m)Tc-HMPAO leukocyte scintigraphy were 72% and 95%, respectively. If the leukocyte labeled scintigraphies had been used exclusively for patients with positive angioscintigraphy, this would have saved up to 70% of the (99m)Tc-HMPAO leukocyte scintigraphies performed. There were no cases of infection with positive labeled leukocyte scintigraphy and negative angioscintigraphy. CONCLUSION: Angioscintigraphy (blood flow phase of bone scan) is a useful technique for screening for hip and knee joint prosthesis infection, significantly reducing the need for (99m)Tc-HMPAO leukocyte scintigraphy without affecting the sensitivity of the technique.

Emergence of structure through protein-protein interactions and pH changes in dually predicted coiled-coil and disordered regions of centrosomal proteins.

Human centrosomal proteins show a significant, 3.5 fold, bias to be both unstructured and coiled-coils with respect to generic human proteins, based on results from state of the art bioinformatics tools. We hypothesize that this bias means that these proteins adopt an ensemble of disordered and partially helical conformations, with the latter becoming stabilized when these proteins form complexes. Characterization of the structural properties of 13 peptides from 10 different centrosomal proteins ranging in size from 20 to 61 residues by biophysical methods led us to confirm our hypothesis in most cases. Interestingly, the secondary structure adopted by most of these peptides becomes stabilized at acidic pH and it is concentration dependent. For two of them, PIK3R1(453-513) and BRCA1(1253-1273), we observed not only the stabilization of helical structure through self-association, but also the presence of ß-structures linked to the formation of high molecular weight oligomers. These oligomers are the predominant forms detected by CD, but unobservable by liquid state NMR. BRCA1(1397-1424) and MAP3K11(396-441) populate helical structures that can also self-associate at pH3 through oligomeric species. Four peptides, derived from three proteins, namely CCNA2(103-123), BRCA1(1253-1273), BRCA1(1397-1424) and PIK3R1(453-513), can form intermolecular associations that are concomitant with alpha or beta structure stabilization. The self-phosphorylation previously described for the kinase NEK2 did not lead to any stabilization in the peptide's structure of NEK2(303-333), NEK2(341-361), and NEK2(410-430). Based on these results, obtained from a series of peptides derived from a significant number of different centrosomal proteins, we propose that conformational polymorphism, modulated by intermolecular interactions is a general property of centrosomal proteins.

The added value of a portable gamma camera for intraoperative detection of sentinel lymph node in squamous cell carcinoma of the oral cavity: A case report / El valor añadido de la gammacámara portátil en la detección intraoperatoria del ganglio centinela en el carcinoma escamoso de la cavidad oral: caso clínico

The use of sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity is still subject to debate although some studies have reported its feasibility. The main reason for this debate is probably due to the high false-negative rate for floor-of-mouth tumors per se. We report the case of a 54-year-old man with a T1N0 floor-of-mouth squamous cell carcinoma who underwent the sentinel lymph node procedure. Lymphoscintigraphy and SPECT/CT imaging were performed for lymphatic mapping with a conventional gamma camera. Sentinel lymph nodes were identified at right Ib, left IIa and Ia levels. However, these sentinel lymph nodes were difficult to detect intraoperatively with a gamma probe owing to the activity originating from the injection site. The use of a portable gamma camera made it possible to localize and excise all the sentinel lymph nodes. This case demonstrates the usefulness of this tool to improve sentinel lymph node detecting in floorof- mouth tumors, especially those close to the injection area (AU)

La biopsia del ganglio centinela en el carcinoma escamoso de la cavidad oral es un tema controvertido aunque varios estudios hayan demostrado su viabilidad, probablemente por la elevada tasa de falsos negativos en los tumores del suelo de la boca. Presentamos el caso de un hombre de 54 a˜nos con carcinoma escamoso del suelo de la boca T1N0 que se sometió al procedimiento del ganglio centinela. Se realizaron imágenes linfogammagráficas y de SPECT/TC con una gammacámara convencional. Se identificaron ganglios centinela en los niveles Ibderecho, IIa izquierdo y Ia, siendo difíciles de localizar intraoperatoriamente con una gammasonda dada la actividad procedente del lugar de inyección. Usando una gammacámara portátil se pudieron localizar y resecar todos los ganglios centinela. Este caso muestra la utilidad de esta herramienta para mejorar la detección del ganglio centinela en los tumores del suelo de la boca, especialmente en aquellos próximos al área de inyección (AU)

The added value of a portable gamma camera for intraoperative detection of sentinel lymph node in squamous cell carcinoma of the oral cavity: A case report.

The use of sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity is still subject to debate although some studies have reported its feasibility. The main reason for this debate is probably due to the high false-negative rate for floor-of-mouth tumors per se. We report the case of a 54-year-old man with a T1N0 floor-of-mouth squamous cell carcinoma who underwent the sentinel lymph node procedure. Lymphoscintigraphy and SPECT/CT imaging were performed for lymphatic mapping with a conventional gamma camera. Sentinel lymph nodes were identified at right Ib, left IIa and Ia levels. However, these sentinel lymph nodes were difficult to detect intraoperatively with a gamma probe owing to the activity originating from the injection site. The use of a portable gamma camera made it possible to localize and excise all the sentinel lymph nodes. This case demonstrates the usefulness of this tool to improve sentinel lymph node detecting in floor-of-mouth tumors, especially those close to the injection area.