Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent.

Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3-6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3'-dione were found altered in PRE, and their levels returned to those of a baseline control group 3-6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods.

Evaluation of an enhanced recovery after lung surgery (ERALS) program in lung cancer lobectomy: An eight-year experience / Evaluación de un programa de rehabilitación multimodal en lobectomía por cáncer de pulmón: experiencia de 8 años

Introduction: Enhanced recovery after lung surgery (ERALS) protocols have proven useful in reducing postoperative stay (POS) and postoperative complications (POC). We studied the performance of an ERALS program for lung cancer lobectomy in our institution, aiming to identify which factors are associated with a reduction of POC and POS. Methods: Analytic retrospective observational study conducted in a tertiary care teaching hospital involving patients submitted to lobectomy for lung cancer and included in an ERALS program. Univariable and multivariable analysis were employed to identify factors associated with increased risk of POC and prolonged POS. Results: A total 624 patients were enrolled in the ERALS program. The median POS was 4 days (range 1–63), with 2.9% of ICU postoperative admission. A videothoracoscopic approach was used in 66.6% of cases, and 174 patients (27.9%) experienced at least one POC. Perioperative mortality rate was 0.8% (5 cases). Mobilization to chair in the first 24h after surgery was achieved in 82.5% of cases, with 46.5% of patients achieving ambulation in the first 24h. Absence of mobilization to chair and preoperative FEV1% less than 60% predicted, were identified as independent risk factors for POC, while thoracotomy approach and the presence of POC predicted prolonged POS. Conclusions: We observed a reduction in ICU admissions and POS contemporaneous with the use of an ERALS program in our institution. We demonstrated that early mobilization and videothoracoscopic approach are modifiable independent predictors of reduced POC and POS, respectively. (AU)

Introducción: Los programas de recuperación intensificada en cirugía de pulmón (por sus siglas en inglés, ERALS) han demostrado ser útiles para reducir la estancia hospitalaria y las complicaciones postoperatorias. Estudiamos los resultados de la aplicación de un programa ERALS para lobectomía por cáncer en nuestro centro con la intención de identificar aquellos factores que se relacionan con la reducción de las complicaciones y la estancia. Métodos: Estudio observacional retrospectivo en pacientes sometidos a lobectomía por cáncer de pulmón e incluidos en un programa ERALS. Se empleó análisis univariable y multivariable para identificar los factores de riesgo de complicaciones y estancia prolongada. Resultados: Un total de 624 pacientes se inscribieron en el programa ERALS. La estancia postoperatoria mediana fue de 4 días (1-63), con una tasa de ingreso en la UCI del 2,9%. El abordaje videotoracoscópico fue empleado en el 66,6% de los casos, y la tasa de complicaciones postoperatorias fue del 27,9%, con una tasa de mortalidad del 0,8% (5 casos). La no movilización en las primeras 24h, y el FEV1% inferior al 60% del previsto, se identificaron como factores de riesgo de complicaciones; mientras que el abordaje mediante toracotomía y la presencia de complicaciones predijeron la estancia prolongada. Conclusiones: Observamos una reducción en la estancia hospitalaria y en los ingresos postoperatorios en la UCI concomitante a la puesta en marcha de un programa ERALS en nuestro centro. La movilización precoz y el abordaje quirúrgico videotoracoscópico demostraron ser predictores independientes y modificables para la reducción de las complicaciones y para la duración de la estancia, respectivamente. (AU)

Surgical Risk Following Anatomic Lung Resection in Thoracic Surgery: A Prediction Model Derived from a Spanish Multicenter Database. / Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica.

INTRODUCTION: The aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). METHODS: Data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. RESULTS: The incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. CONCLUSIONS: The risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection.

Spanish Video-Assisted Thoracic Surgery Group: Method, Auditing, and Initial Results From a National Prospective Cohort of Patients Receiving Anatomical Lung Resections / Grupo Español de Cirugía Torácica Videoasistida: Método, Auditoría y Resultados Iniciales de una Cohorte Nacional Prospectiva de Pacientes Tratados con Resección Pulmonar Anatómica

INTRODUCTION: Our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). METHODS: We conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for "90-day mortality" and "Grade IIIb-V complications". RESULTS: The series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR = 0.61 (p = 0.081), 90-day mortality OR = 0.46 (p = 0.051). CONCLUSIONS: More than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort

INTRODUCCIÓN: Nuestro estudio buscó conocer el grado de implementación actual de la cirugía toracoscópica asistida por video (VATS, por sus siglas en inglés) para las resecciones pulmonares anatómicas en España. Presentamos nuestros resultados iniciales y describimos los sistemas de auditoría desarrollados por el grupo español de VATS (GEVATS). MÉTODOS: Realizamos un estudio de cohortes prospectivo multicéntrico que incluyó pacientes que fueron tratados con resecciones pulmonares anatómicas entre el 20/12/2016 y el 20/03/2018. Los controles de calidad principales consistieron en determinar la tasa de reclutamiento de cada centro y la precisión de los datos perioperatorios recolectados en base a seis variables clave. Se analizaron las implicaciones de una baja tasa de reclutamiento para "mortalidad a los 90 días" y "complicaciones de grado IIIb-V". RESULTADOS: La serie estaba compuesta por 3533 casos (1917 VATS; 54,3%) en 33 servicios. La mediana de la tasa de reclutamiento de los centros fue del 99% (p25-p75: 76-100%), con una tasa de reclutamiento global del 83% y una precisión de los datos del 98%. No pudimos demostrar una asociación significativa entre la tasa de reclutamiento y el riesgo de morbi-mortalidad, pero se encontró una tendencia en el análisis no ajustado para aquellos centros con tasas de reclutamiento inferiores al 80% (usando los centros con tasas de 95-100% como referencia): OR = 0,61 para el grado IIIb-V (p = 0,081), OR = 0,46 para la mortalidad a los 90 días (p = 0,051). CONCLUSIONES: Más de la mitad de las resecciones pulmonares anatómicas en España se realizan a través de VATS. Según nuestros resultados, la tasa de reclutamiento del centro y sus posibles implicaciones debido al sesgo de selección, deberían recibir más atención por parte de los principales estudios multicéntricos voluntarios de nuestra especialidad. La alta representatividad y la confiabilidad de los datos de GEVATS constituyen un punto de partida fundamental para esta cohorte nacional

Tratamiento del aspergiloma pulmonar en paciente de alto riesgo quirúrgico: cavernostomía / Cavernostomy in the Treatment of Pulmonary Aspergilloma in a High Surgical Risk Patient

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Spanish Video-Assisted Thoracic Surgery Group: Method, Auditing, and Initial Results From a National Prospective Cohort of Patients Receiving Anatomical Lung Resections.

INTRODUCTION: Our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). METHODS: We conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for "90-day mortality" and "Grade IIIb-V complications". RESULTS: The series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). CONCLUSIONS: More than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort.

Evaluation of lung parenchyma, blood vessels, and peripheral blood lymphocytes as a potential source of acute phase reactants in patients with COPD.

Background: Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments. Methods: Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry. Results: A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P<0.001, respectively; 8-fold higher for SAA2, P<0.001) and peripheral blood leukocytes (16-fold higher for SAA1, 439-fold higher for SAA2, and 5-fold higher for SAA4; P<0.001). No correlation between plasma levels of inflammatory markers and their expression in the lung and peripheral blood leukocytes was observed. Conclusions: The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny.

Cigarette Smoke Decreases the Maturation of Lung Myeloid Dendritic Cells.

BACKGROUND: Conflicting data exist on the role of pulmonary dendritic cells (DCs) and their maturation in patients with chronic obstructive pulmonary disease (COPD). Herein, we investigated whether disease severity and smoking status could affect the distribution and maturation of DCs in lung tissues of patients undergoing elective pneumectomy or lobectomy for suspected primary lung cancer. MATERIALS AND METHODS: A total of 75 consecutive patients were included. Spirometry testing was used to identify COPD. Lung parenchyma sections anatomically distant from the primary lesion were examined. We used flow cytometry to identify different DCs subtypes-including BDCA1-positive myeloid DCs (mDCs), BDCA3-positive mDCs, and plasmacytoid DCs (pDCs)-and determine their maturation markers (CD40, CD80, CD83, and CD86) in all participants. We also identified follicular DCs (fDCs), Langerhans DCs (LDCs), and pDCs in 42 patients by immunohistochemistry. RESULTS: COPD was diagnosed in 43 patients (16 current smokers and 27 former smokers), whereas the remaining 32 subjects were classified as non-COPD (11 current smokers, 13 former smokers, and 8 never smokers). The number and maturation of DCs did not differ significantly between COPD and non-COPD patients. However, the results of flow cytometry indicated that maturation markers CD40 and CD83 of BDCA1-positive mDCs were significantly decreased in smokers than in non-smokers (P = 0.023 and 0.013, respectively). Immunohistochemistry also revealed a lower number of LDCs in COPD patients than in non-COPD subjects. CONCLUSIONS: Cigarette smoke, rather than airflow limitation, is the main determinant of impaired DCs maturation in the lung.

The Spanish Society of Pulmonology and Thoracic Surgery Lung Cancer Cooperative Group-II registry. A descriptive study.

INTRODUCTION AND OBJECTIVES: The seventh edition of the TNM classification, together with undeniable advantages, has limitations. The International Association for the Study of Lung Cancer (IASLC) Staging Committee has designed an international prospective study to improve this classification. A group of thoracic surgeons and pulmonologists was established in the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) Oncology area, and created a registry of new lung cancer (LC) cases to participate in this project. The aim of this paper is to describe the main characteristics of the patients included. MATERIALS AND METHODS: Prospective, observational, multicentre, multiregional data collection (epidemiological, clinical, therapeutic and, especially, anatomical extension) study, according to the IASLC protocol, to analyse its prognostic value. RESULTS: Two thousand, four hundred and nineteen patients (83.6% men) from 28 hospitals were included. Ninety-six percent of the men and 54% of the women were smokers or ex-smokers. Chest/abdominal computed tomography (CT) scanning was performed in over 90% and positron emission tomography (PET)/CT scanning in 51.5% of cases. Among the 1035 patients who underwent surgery, 77% had early stages (ia to iib), and 61.6% of those treated using other methods had stage iv. Respiratory comorbidity was higher in men (47.9% versus 21.4%). The most common histological subtype was adenocarcinoma (34%), especially in non-smoking women (69.5%). CONCLUSIONS: The proportion of women and adenocarcinomas, as well as those resected at an early stage, increased among LC cases in Spain.