SUVmax to tumor perimeter distance: a robust radiomics prognostic biomarker in resectable non-small cell lung cancer patients.

OBJECTIVE: The purpose of this study was to evaluate the prognostic value of novel geometric variables obtained from pre-treatment [18F]FDG PET/CT with respect to classical ones in patients with non-small cell lung cancer (NSCLC). METHODS: Retrospective study including stage I-III NSCLC patients with baseline [18F]FDG PET/CT. Clinical, histopathologic, and metabolic parameters were obtained. After tumor segmentation, SUV and volume-based variables, global texture, sphericity, and two novel parameters, normalized SUVpeak to centroid distance (nSCD) and normalized SUVmax to perimeter distance (nSPD), were obtained. Early recurrence (ER) and short-term mortality (STM) were used as end points. Univariate logistic regression and multivariate logistic regression with respect to ER and STM were performed. RESULTS: A cohort of 173 patients was selected. ER was detected in 49/104 of patients with recurrent disease. Additionally, 100 patients died and 53 had STM. Age, pathologic lymphovascular invasion, lymph nodal infiltration, TNM stage, nSCD, and nSPD were associated with ER, although only age (aOR = 1.06, p = 0.002), pathologic lymphovascular invasion (aOR = 3.40, p = 0.022), and nSPD (aOR = 0.02, p = 0.018) were significant independent predictors of ER in multivariate analysis. Age, lymph nodal infiltration, TNM stage, nSCD, and nSPD were predictors of STM. Age (aOR = 1.05, p = 0.006), lymph nodal infiltration (aOR = 2.72, p = 0.005), and nSPD (aOR = 0.03, p = 0.022) were significantly associated with STM in multivariate analysis. Coefficient of variation (COV) and SUVmean/SUVmax ratio did not show significant predictive value with respect to ER or STM. CONCLUSION: The geometric variables, nSCD and nSPD, are robust biomarkers of the poorest outcome prediction of patients with NSCLC with respect to classical PET variables. KEY POINTS: • In NSCLC patients, it is crucial to find prognostic parameters since TNM system alone cannot explain the variation in lung cancer survival. • Age, lymphovascular invasion, lymph nodal infiltration, and metabolic geometrical parameters were useful as prognostic parameters. • The displacement grade of the highest point of metabolic activity towards the periphery assessed by geometric variables obtained from [18F]FDG PET/CT was a robust biomarker of the poorest outcome prediction of patients with NSCLC.

Análisis del nódulo pulmonar solitario tras su resección quirúrgica en pacientes con 18F-FDG PET-TC integrado en el estudio preoperatorio / Analysis of solitary pulmonary nodule after surgical resection in patients with 18F-FDG positron emission tomography integrated computed tomography in the preoperative work-up

Introducción: Analizar las características clínico-patológicas de los pacientes operados por nódulo pulmonar solitario (NPS) y 18F-FDG PET-TC integrado tras su resección quirúrgica.Material y métodosEstudio retrospectivo sobre una base de datos prospectiva de pacientes operados entre enero-2007 y octubre-2017 por NPS sin diagnóstico preoperatorio. La variable dependiente fue el resultado anatomopatológico (benigno vs. maligno) del NPS. Las variables del estudio fueron: edad, sexo, captación en PET-TC, SUVmáx, tabaquismo, EPOC, antecedente de tumoración maligna previa, localización del tumor y tamaño en la TC.ResultadosUn total de 305 pacientes fueron incluidos en el estudio, 225 (73,8%) varones, 80 (26,2%) mujeres, edad media = 63,9 (rango 29-86 años), tamaño medio NPS = 1,68 (d.t. 0,65 cm), benignos = 46 (15,1%), malignos = 258 (84,6%), tipo de resección: cuña = 151 (49,5%), lobectomía = 141 (46,2%), segmentectomía = 12 (3,9%), exploradora = 1 (0,3%). La mortalidad postoperatoria fue del 1,9%. EPOC = 50,8% casos, cáncer previo = 172 casos (56,4%), tabaquismo = 250 casos (82%), PET positiva = 280 casos (91,8%), NPS en campos superiores = 204 casos (66,9%), SUVmáx mediana = 3,4 (rango 0-20,7). El modelo de regresión logística binaria por pasos hacia atrás mostró que la edad, SUVmáx, enfermedad maligna previa y sexo femenino fueron factores de riesgo independientes con significación estadística (p < 0,05).La sensibilidad, especificidad, el valor predictivo positivo, el valor predictivo negativo y la seguridad diagnóstica fueron 94,6%, 23,4%, 87,1%, 44% y 83,6%, respectivamente. Hubo un total de 14 casos falsos negativos (4,6%) y 36 casos falsos positivos (11,8%). (AU)

Introduction: To analyse clinicopathological characteristics of patients operated for pulmonary solitary nodule (PSN) and 18F-FDG integrated PET-CT scan after surgical resection.MethodologyRetrospective study on a prospective database of patients operated from January 2007 to October 2017 for PSN without preoperative diagnosis. Dependent variable was anatomopathological result (benign vs malignant) of PSN. Variables of the study were: age, sex, PET-CT uptake, SUVmax, smoking history, COPD, previous history of malignant disease, tumoral location, and tumour size on CT-scan.ResultsA total of 305 patients were included in this study, 225 (73.8%) men, 80 (26.2%) women, mean age = 63.9 (range 29-86 years), mean size PSN = 1.68 (s.d. .65 cm), benign = 46 (15.1%), malignant = 258 (84.6%), type of resection: pulmonary wedge = 151 (49.5%), lobectomy = 141 (46.2%), segmentectomy = 12 (3.9%), exploratory intervention = 1 (0.3%). Postoperative mortality was 1.9%. COPD = 50.8% cases, previous cancer disease = 172 cases (56.4%), smoking history = 250 cases (82.0%), positive PET = 280 cases (91.8%), PSN in upper pulmonary fields = 204 cases (66.9%), median SUVmax = 3.4 (range 0-20.7). Backward stepwise binary logistic regression model showed that age, SUVmax, previous malignant disease and female sex were independent risk factors with statistical significance (p < .05). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 94.6%, 23.4%, 87.1%, 44.0%, and 83.6% respectively. There were 14 false negative cases (4.6%) and 36 false positive cases (11.8%). (AU)

Evolutionary dynamics at the tumor edge reveal metabolic imaging biomarkers.

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET-computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.

Analysis of solitary pulmonary nodule after surgical resection in patients with 18F-FDG positron emission tomography integrated computed tomography in the preoperative work-up. / Análisis del nódulo pulmonar solitario tras su resección quirúrgica en pacientes con 18F-FDG PET-TC integrado en el estudio preoperatorio.

INTRODUCTION: To analyse clinicopathological characteristics of patients operated for pulmonary solitary nodule (PSN) and 18F-FDG integrated PET-CT scan after surgical resection. METHODOLOGY: Retrospective study on a prospective database of patients operated from January 2007 to October 2017 for PSN without preoperative diagnosis. Dependent variable was anatomopathological result (benign vs malignant) of PSN. Variables of the study were: age, sex, PET-CT uptake, SUVmax, smoking history, COPD, previous history of malignant disease, tumoral location, and tumour size on CT-scan. RESULTS: A total of 305 patients were included in this study, 225 (73.8%) men, 80 (26.2%) women, mean age = 63.9 (range 29-86 years), mean size PSN = 1.68 (s.d. .65 cm), benign = 46 (15.1%), malignant = 258 (84.6%), type of resection: pulmonary wedge = 151 (49.5%), lobectomy = 141 (46.2%), segmentectomy = 12 (3.9%), exploratory intervention = 1 (0.3%). Postoperative mortality was 1.9%. COPD = 50.8% cases, previous cancer disease = 172 cases (56.4%), smoking history = 250 cases (82.0%), positive PET = 280 cases (91.8%), PSN in upper pulmonary fields = 204 cases (66.9%), median SUVmax = 3.4 (range 0-20.7). Backward stepwise binary logistic regression model showed that age, SUVmax, previous malignant disease and female sex were independent risk factors with statistical significance (p < .05). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 94.6%, 23.4%, 87.1%, 44.0%, and 83.6% respectively. There were 14 false negative cases (4.6%) and 36 false positive cases (11.8%). CONCLUSIONS: Age, SUVmax, previous malignant disease, and female sex were independent risk factors in our study. Each case should be individually evaluated in a multidisciplinary committee, and the patient's preferences or concerns should be kept in mind in decision-making. Surgical resection of PSN is not exempt from morbidity and mortality, even in sublobar or pulmonary wedge resection.

Universal scaling laws rule explosive growth in human cancers.

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.

Segmentation in Non-Small Cell Lung Tumors Using 18F-FDG PET/CT: Tips and Rules.

The assessment of tumor parameters derived from F-FDG PET/CT in oncology provides valuable information in non-small cell lung cancer. A proper segmentation should delineate tumor with high accuracy, being the most important step to measure metabolic parameters. However, there is still no consensus about the optimal methodology. Additionally, some clinical conditions inherently tied to tumor and imaging can limit the proper tumor delineation. We present some practical cases that represent different aspects to consider during segmentation of primary non-small cell lung cancer by using F-FDG-PET/CT and some possible solutions to tackle with the most common limitations in clinical practice.

Sumario ejecutivo de las recomendaciones SEPAR de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas / Executive summary of the SEPAR recommendations for the diagnosis and treatment of non-small cell lung cancer

La Sociedad Española de Neumología y Cirugía Torácica (SEPAR), a través de las áreas de Cirugía Torácica y de Oncología Torácica, ha promovido la realización de un manual de recomendaciones para el diagnóstico y el tratamiento del cáncer de pulmón de células no pequeñas. Las elevadas incidencia y mortalidad de esta patología hacen necesaria una constante actualización de las mejores evidencias científicas para su consulta por parte de los profesionales de la salud. Para su confección se ha contado con un amplio grupo de profesionales de distintas especialidades que han elaborado una revisión integral, que se ha concretado en 4 apartados principales. En el primero se ha estudiado la prevención y el cribado de la enfermedad, incluyendo los factores de riesgo, el papel de la deshabituación tabáquica y el diagnóstico precoz mediante programas de cribado. En un segundo apartado se ha analizado la presentación clínica, los estudios de imagen y el riesgo quirúrgico, incluyendo el cardiológico y la evaluación funcional respiratoria. Un tercero trata sobre los estudios de confirmación cito-histológica y de estadificación, con un análisis de las clasificaciones TNM e histológica, métodos no invasivos y mínimamente invasivos, así como las técnicas quirúrgicas para el diagnóstico y estadificación. En un cuarto y último capítulo se han abordado aspectos del tratamiento, como el papel de las técnicas quirúrgicas, la quimioterapia, la radioterapia, el abordaje multidisciplinar por estadios y otros tratamientos dirigidos frente a dianas específicas, terminando con recomendaciones acerca del seguimiento del cáncer de pulmón y los tratamientos paliativos quirúrgicos y endoscópicos en estadios avanzados

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals. To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages

Executive summary of the SEPAR recommendations for the diagnosis and treatment of non-small cell lung cancer. / Sumario ejecutivo de las recomendaciones SEPAR de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas.

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals. To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages.

Recomendaciones SEPAR de diagnostico y tratamiento del cancer de pulmón de celulas no pequeñas / Recommendations of the Spanish Society of Pneumology and Thoracic Surgery on the diagnosis and treatment of non-small-cell lung cancer

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(18)F-FDG-PET/CT in the assessment of pulmonary solitary nodules: comparison of different analysis methods and risk variables in the prediction of malignancy.

OBJECTIVE: To compare the diagnostic performance of different metabolical, morphological and clinical criteria for correct presurgical classification of the solitary pulmonary nodule (SPN). METHODS: Fifty-five patients, with SPN were retrospectively analyzed. All patients underwent preoperative (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). Maximum diameter in CT, maximum standard uptake value (SUVmax), histopathologic result, age, smoking history and gender were obtained. Different criteria were established to classify a SPN as malignant: (I) visually detectable metabolism, (II) SUVmax >2.5 regardless of SPN diameter, (III) SUVmax threshold depending of SPN diameter, and (IV) ratio SUVmax/diameter greater than 1. For each criterion, statistical diagnostic parameters were obtained. Receiver operating characteristic (ROC) analysis was performed to select the best diagnostic SUVmax and SUVmax/diameter cutoff. Additionally, a predictive model of malignancy of the SPN was derived by multivariate logistic regression. RESULTS: Fifteen SPN (27.3%) were benign and 40 (72.7%) malignant. The mean values ± standard deviation (SD) of SPN diameter and SUVmax were 1.93±0.57 cm and 3.93±2.67 respectively. Sensitivity (Se) and specificity (Sp) of the different diagnostic criteria were (I): 97.5% and 13.1%; (II) 67.5% and 53.3%; (III) 70% and 53.3%; and (IV) 85% and 33.3%, respectively. The SUVmax cut-off value with the best diagnostic performance was 1.95 (Se: 80%; Sp: 53.3%). The predictive model had a Se of 87.5% and Sp of 46.7%. The SUVmax was independent variables to predict malignancy. CONCLUSIONS: The assessment by semiquantitative methods did not improve the Se of visual analysis. The limited Sp was independent on the method used. However, the predictive model combining SUVmax and age was the best diagnostic approach.

Heterogeneity in [18F]fluorodeoxyglucose positron emission tomography/computed tomography of non-small cell lung carcinoma and its relationship to metabolic parameters and pathologic staging.

To investigate the relationships between tumor heterogeneity, assessed by texture analysis of [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) images, metabolic parameters, and pathologic staging in patients with non-small cell lung carcinoma (NSCLC). A retrospective analysis of 38 patients with histologically confirmed NSCLC who underwent staging FDG-PET/computed tomography was performed. Tumor images were segmented using a standardized uptake value (SUV) cutoff of 2.5. Five textural features, related to the heterogeneity of gray-level distribution, were computed (energy, entropy, contrast, homogeneity, and correlation). Additionally, metabolic parameters such as SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), as well as pathologic staging, histologic subtype, and tumor diameter, were obtained. Finally, a correlation analysis was carried out. Of 38 tumors, 63.2% were epidermoid and 36.8% were adenocarcinomas. The mean ± standard deviation values of MTV and TLG were 30.47 ± 25.17 mL and 197.81 ± 251.11 g, respectively. There was a positive relationship of all metabolic parameters (SUVmax, SUVmean, MTV, and TLG) with entropy, correlation, and homogeneity and a negative relationship with energy and contrast. The T component of the pathologic TNM staging (pT) was similarly correlated with these textural parameters. Textural features associated with tumor heterogeneity were shown to be related to global metabolic parameters and pathologic staging.

Tratamiento de la eventración diafragmática en adultos mediante plicatura diafragmática asistida por videotoracoscopia. ¿Es una técnica difundida en nuestro medio? Revisión de la literatura, resultados de una encuesta nacional / Is video-assisted thoracoscopic diaphragmatic plication a widespread technique for diaphragmatic hernia in adults?: Review of the literature and results of a national survey

La plicatura diafragmática es el tratamiento más aceptado para la eventración diafragmática sintomática en adultos. La infrecuencia de esta dolencia y la escasa difusión de este procedimiento hacen que esta técnica sea excepcional en nuestro medio. Para estimar la difusión en la literatura, realizamos una revisión estructurada en lenguas inglesa y castellana a la que sumamos nuestra casuística: encontramos solo 6 series que aportan un total de 59 plicaturas diafragmáticas en adultos asistidas por toracoscopia. Ninguna en castellano. Nuestra serie sería la segunda mayor: 18 casos, con resultados satisfactorios similares a los publicados. Finalmente efectuamos una encuesta a todos los servicios españoles de cirugía torácica: ninguno tiene más de 10 casos operados por toracoscopia en los últimos 8 años (a excepción del nuestro) y la mayoría continúa utilizando la toracotomía como abordaje. En nuestra opinión muchos pacientes con eventración diafragmática sintomática podrían beneficiarse con la difusión de estas técnicas

Diaphragmatic plication is the most accepted treatment for symptomatic diaphragmatic hernia in adults. The fact that this pathology is infrequent and this procedure not been widespread means that this is an exceptional technique in our field. To estimate its use in the literature, we carried out a review in English and Spanish, to which we added our series. We found only 6 series that contribute 59 video-assisted mini-thoractomy for diaphragmatic plications in adults, and none in Spanish. Our series will be the second largest with 18 cases. Finally, we conducted a survey in all the Spanish Thoracic Surgery units in Spain: none reported more than 10 cases operated by thoracoscopy in the last 8 years (except our series) and most continue employing thoracotomy as the main approach. We believe that many patients with symptomatic diaphragmatic hernia could benefit from the use of such techniques

Valor pronóstico de la expresión del factor de crecimiento endotelial vascular A y del factor inducible por la hipoxia 1α en pacientes operados de cáncer de pulmón no microcítico / Prognostic value of the expression of vascular endothelial growth factor A and hypoxia-inducible factor 1alpha in patients undergoing surgery for non-small cell lung cancer

Fundamento y objetivo: Estudios recientes evidencian que la expresión del hypoxia-inducible factor 1α (HIF-1α, «factor inducible por la hipoxia 1α») favorece la expresión del vascular endothelial growth factor A (VEGF-A, «factor de crecimiento endotelial vascular A»), así como la proliferación celular, angiogénesis y metástasis en diferentes cánceres, incluido el cáncer de pulmón. El objetivo de este estudio fue investigar la correlación de la expresión del VEGF-A y del HIF-1α con las características clinicopatológicas y el pronóstico de pacientes operados por cáncer de pulmón no microcítico. Pacientes y método: Estudio prospectivo para analizar la expresión de VEGF-A y HIF-1α mediante reacción en cadena de la polimerasa en tiempo real en 66 pacientes operados de cáncer de pulmón no microcítico. Resultados: La edad media (DE) fue de 62,7 (9,8) años y la relación varón:mujer de 7,3:1. Según la nueva clasificación TNM de 2009, los estadios i , ii y iii incluyeron a 27 (40,9%), 21 (31,8%) y 18 (27,3%) pacientes, respectivamente. La histología fue: 47% carcinomas escamosos, 33,3% adenocarcinomas y 19,7% otros. El seguimiento medio fue de 42,3 meses, la mediana de supervivencia de 43,2 meses y la supervivencia estimada a los 5 años del 42,4%. No hubo correlación entre VEGF-A y HIF-1α (p = 0,306). La sobreexpresión de VEGF-A fue más frecuente en el estadio avanzado y cuando hubo metástasis ganglionares (p = 0,034 y p = 0,059, respectivamente). En el análisis multivariante, el descriptor T y el VEGF-A fueron factores pronóstico independientes (odds ratio [OR] 2,37, p = 0,016, y OR 2,51, p = 0,008, respectivamente), mientras que HIF-1α no mostró significación estadística (p = 0,172), con una OR 0,540. Conclusiones: La sobreexpresión de VEGF-A resultó ser un factor pronóstico independiente adverso en pacientes intervenidos de cáncer de pulmón no microcítico. Por el contrario, la sobreexpresión del HIF-1α mostró una tendencia hacia un efecto protector sobre la supervivencia, pero sin significación estadística (AU)

Background and objective Studies suggest that hypoxia-inducible factor 1α (HIF-1α) expression favours expression of vascular endothelial growth factor A (VEGF-A) involving cellular proliferation, angiogenesis, and metastasis in different cancers including lung cancer. We investigated the correlation of HIF-1α and VEGF-A with clinicopathologic parameters and clinical outcomes in surgically resected non-small cell lung cancer patients. Patients and method Prospective study to analyze the expression of VEGF-A and HIF-1α with real time-polymerase chain reaction in 66 patients operated on non-small cell lung cancer. Results Mean age was 62.7 ± 9.8 and male:female ratio was 7.3:1. According to the new 2009 TNM classification, stage i , ii , and iii included 27 (40.9%), 21 (31.8%) and 18 (27.3%) patients, respectively. Histological subtypes were: 47% squamous cell carcinoma, 33.3% adenocarcinoma, and 19.7% others. Mean follow-up time was 42.3 months. Median survival was 43.2 months and 5-year overall survival was 42.4%. There was no correlation between HIF-1α and VEGF-A (P = .306). The overexpression of VEGF-A was found more frequent in advanced stage and in lymph nodes metastasis (P = .034 and P = .059, respectively). In multivariate analysis, T descriptor and VEGF-A overexpression were independent prognostic factors (odds ratio [OR] = 2.37, P = .016, and OR = 2.51, P = .008, respectively). HIF-1α overexpression showed an OR = 0.540, but without statistical significance (P = .172). Conclusions The present study revealed that VEGF-A overexpression was an adverse independent prognostic factor. On the contrary, HIF-1α overexpression showed a tendency to a protective effect on survival of surgically treated non-small cell lung cancer patients, although without statistical significance (AU)

Is video-assisted thoracoscopic diaphragmatic plication a widespread technique for diaphragmatic hernia in adults? Review of the literature and results of a national survey.

Diaphragmatic plication is the most accepted treatment for symptomatic diaphragmatic hernia in adults. The fact that this pathology is infrequent and this procedure not been widespread means that this is an exceptional technique in our field. To estimate its use in the literature, we carried out a review in English and Spanish, to which we added our series. We found only six series that contribute 59 video-assisted mini-thoractomy for diaphragmatic plications in adults, and none in Spanish. Our series will be the second largest with 18 cases. Finally, we conducted a survey in all the Spanish Thoracic Surgery units in Spain: none reported more than 10 cases operated by thoracoscopy in the last 8 years (except our series) and most continue employing thoracotomy as the main approach. We believe that many patients with symptomatic diaphragmatic hernia could benefit from the use of such techniques.

Cirugía en el cáncer de pulmón T4 / No disponible

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Analysis of Expression of Vascular Endothelial Growth Factor A and Hypoxia Inducible Factor-1alpha in Patients Operated on Stage I Non-Small-Cell Lung Cancer.

Objectives. Recent studies show that expression of hypoxia inducible factor-1alpha (HIF-1α) favours expression of vascular endothelial growth factor A (VEGF-A), and these biomarkers are linked to cellular proliferation, angiogenesis, and metastasis in different cancers. We analyze expression of HIF-1α and VEGF-A to clinicopathologic features and survival of patients operated on stage I non-small-cell lung cancer. Methodology. Prospective study of 52 patients operated on with stage I. Expression of VEGF-A and HIF-1α was performed through real-time quantitative polymerase chain reaction (qRT-PCR). Results. Mean age was 64.7 and 86.5% of patients were male. Stage IA represented 23.1% and stage IB 76.9%. Histology classification was 42.3% adenocarcinoma, 34.6% squamous cell carcinoma, and 23.1% others. Median survival was 81.0 months and 5-year survival 67.2%. There was correlation between HIF-1α and VEGF-A (P = 0.016). Patients with overexpression of HIF-1α had a tendency to better survival with marginal statistical significance (P = 0.062). Patients with overexpression of VEGF-A had worse survival, but not statistically significant (P = 0.133). Conclusion. The present study revealed that VEGF-A showed correlation with HIF-1α. HIF-1α had a tendency to protective effect with a P value close to statistical significance. VEGF-A showed a contrary effect but without statistical significance.

[Prognostic value of the expression of vascular endothelial growth factor A and hypoxia-inducible factor 1alpha in patients undergoing surgery for non-small cell lung cancer]. / Valor pronóstico de la expresión del factor de crecimiento endotelial vascular A y del factor inducible por la hipoxia 1α en pacientes operados de cáncer de pulmón no microcítico.

BACKGROUND AND OBJECTIVE: Studies suggest that hypoxia-inducible factor 1α (HIF-1α) expression favours expression of vascular endothelial growth factor A (VEGF-A) involving cellular proliferation, angiogenesis, and metastasis in different cancers including lung cancer. We investigated the correlation of HIF-1α and VEGF-A with clinicopathologic parameters and clinical outcomes in surgically resected non-small cell lung cancer patients. PATIENTS AND METHOD: Prospective study to analyze the expression of VEGF-A and HIF-1α with real time-polymerase chain reaction in 66 patients operated on non-small cell lung cancer. RESULTS: Mean age was 62.7±9.8 and male:female ratio was 7.3:1. According to the new 2009 TNM classification, stage i, ii, and iii included 27 (40.9%), 21 (31.8%) and 18 (27.3%) patients, respectively. Histological subtypes were: 47% squamous cell carcinoma, 33.3% adenocarcinoma, and 19.7% others. Mean follow-up time was 42.3 months. Median survival was 43.2 months and 5-year overall survival was 42.4%. There was no correlation between HIF-1α and VEGF-A (P=.306). The overexpression of VEGF-A was found more frequent in advanced stage and in lymph nodes metastasis (P=.034 and P=.059, respectively). In multivariate analysis, T descriptor and VEGF-A overexpression were independent prognostic factors (odds ratio [OR]=2.37, P=.016, and OR=2.51, P=.008, respectively). HIF-1α overexpression showed an OR=0.540, but without statistical significance (P=.172). CONCLUSIONS: The present study revealed that VEGF-A overexpression was an adverse independent prognostic factor. On the contrary, HIF-1α overexpression showed a tendency to a protective effect on survival of surgically treated non-small cell lung cancer patients, although without statistical significance.

Heterogeneity in [¹8F]fluorodeoxyglucose positron emission tomography/computed tomography of non-small cell lung carcinoma and its relationship to metabolic parameters and pathologic staging.

To investigate the relationships between tumor heterogeneity, assessed by texture analysis of [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) images, metabolic parameters, and pathologic staging in patients with non-small cell lung carcinoma (NSCLC). A retrospective analysis of 38 patients with histologically confirmed NSCLC who underwent staging FDG-PET/computed tomography was performed. Tumor images were segmented using a standardized uptake value (SUV) cutoff of 2.5. Five textural features, related to the heterogeneity of gray-level distribution, were computed (energy, entropy, contrast, homogeneity, and correlation). Additionally, metabolic parameters such as SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), as well as pathologic staging, histologic subtype, and tumor diameter, were obtained. Finally, a correlation analysis was carried out. Of 38 tumors, 63.2% were epidermoid and 36.8% were adenocarcinomas. The mean ± standard deviation values of MTV and TLG were 30.47 ± 25.17 mL and 197.81 ± 251.11 g, respectively. There was a positive relationship of all metabolic parameters (SUVmax, SUVmean, MTV, and TLG) with entropy, correlation, and homogeneity and a negative relationship with energy and contrast. The T component of the pathologic TNM staging (pT) was similarly correlated with these textural parameters. Textural features associated with tumor heterogeneity were shown to be related to global metabolic parameters and pathologic staging.