Src-Homology 2 Domain-Containing Phosphatase 2 in Resected EGFR Mutation-Positive Lung Adenocarcinoma.

INTRODUCTION: EGFR mutation-positive lung adenocarcinoma (LUAD) displays impaired phosphorylation of ERK and Src-homology 2 domain-containing phosphatase 2 (SHP2) in comparison with EGFR wild-type LUADs. We hypothesize that SHP2 expression could be predictive in patients positive with resected EGFR mutation versus patients with EGFR wild-type LUAD. METHODS: We examined resected LUAD cases from Japan and Spain. mRNA expression levels of AXL, MET, CDCP1, STAT3, YAP1, and SHP2 were analyzed by quantitative reverse transcriptase polymerase chain reaction. The activity of SHP2 inhibitors plus erlotinib were tested in EGFR-mutant cell lines and analyzed by cell viability assay, Western blot, and immunofluorescence. RESULTS: A total of 50 of 100 EGFR mutation-positive LUADs relapsed, among them, patients with higher SHP2 mRNA expression revealed shorter progression-free survival, in comparison with those having low SHP2 mRNA (hazard ratio: 1.83; 95% confidence interval: 1.05-3.23; p = 0.0329). However, SHP2 was not associated with prognosis in the remaining 167 patients with wild-type EGFR. In EGFR-mutant cell lines, the combination of SHP099 or RMC-4550 (SHP2 inhibitors) with erlotinib revealed synergism via abrogation of phosphorylated AKT (S473) and ERK1/2 (T202/Y204). Although erlotinib translocates phosphorylated SHP2 (Y542) into the nucleus, either RMC-4550 alone, or in combination with erlotinib, relocates SHP2 into the cytoplasm membrane, limiting AKT and ERK1/2 activation. CONCLUSIONS: Elevated SHP2 mRNA levels are associated with recurrence in resected EGFR mutation-positive LUADs, but not in EGFR wild-type. EGFR tyrosine kinase inhibitors can enhance SHP2 activation, hindering adjuvant therapy. SHP2 inhibitors could improve the benefit of adjuvant therapy in EGFR mutation-positive LUADs.

[The importance of dairy products for cardiovascular health: whole or low fat?] / Importancia de los alimentos lácteos en la salud cardiovascular: ¿enteros o desnatados?

The nutritional guidelines incorporate dairy products as part of a balanced and healthy diet. In almost all guidelines it is announced that dairy products have to preferably be consumed as non or low-fat version. The reason behind this recommendation is the intake of saturated fatty acids (SFA). Recently, it has been suggested that building nutritional recommendations according to the nutrient food content, leads to a limiting interpretation of the functions and properties of the consumed food. Lately, the research focus has been shifted towards the study of the food matrix, which allows assessing health effects considering all the components contained in the foods, and their impact in human health. Dairy products are the perfect example to highlight the importance of the food matrix as a determinant of the effects of nutrients on health. The potentially harmful effects of SFA on cardiometabolic health seem to be different when they are consumed within nutrient-rich foods such as yogurt, cheese or other dairy products. Epidemiological studies with large population cohorts and long term follow-up show that consumption of dairy products, especially yogurt, is not associated with an increased cardiovascular risk. Therefore, there is not enough scientific evidence to preferentially recommend the consumption of non-fat or low-fat dairy products to the general population, instead of its whole-fat version.

Las guías nutricionales incorporan los lácteos como parte de una dieta equilibrada y saludable. En la mayoría de las ocasiones se especifica que los productos lácteos sean preferentemente bajos en grasa o desnatados. La razón que subyace a esta limitación es el aporte de ácidos grasos saturados (AGS) inherente al consumo de grasa láctea.Recientemente se ha planteado que valorar los alimentos según el aporte de nutrientes que contienen de forma aislada conlleva a interpretar de forma limitante sus funciones y propiedades. El conocimiento de la matriz alimentaria permite valorar el efecto sobre la salud de los alimentos en su totalidad al considerar, todos los componentes que contiene, y la interacción tras su consumo.Los productos lácteos son un ejemplo para destacar la importancia de la matriz alimentaria como un determinante del efecto que pueden ejercer los nutrientes del alimento. Los efectos potencialmente nocivos de los AGS sobre la salud cardiometabólica parecen no ser tales cuando se consumen como parte de alimentos con matrices alimentarias ricas en nutrientes como son la leche, el yogur, el queso u otros productos lácteos.Estudios epidemiológicos de grandes cohortes poblacionales seguidas a largo plazo muestran que el consumo de productos lácteos, especialmente de yogur, no se asocia con un aumento del riesgo cardiovascular. Por tanto, no existen suficientes evidencias científicas para recomendar a la población general el consumo de productos lácteos bajos en grasa o desnatados de forma preferente, en lugar de su versión entera.

Importancia de los alimentos lácteos en la salud cardiovascular: ¿enteros o desnatados? / The importance of dairy products for cardiovascular health: whole or low fat?

Las guías nutricionales incorporan los lácteos como parte de una dieta equilibrada y saludable. En la mayoría de las ocasiones se especifica que los productos lácteos sean preferentemente bajos en grasa o desnatados. La razón que subyace a esta limitación es el aporte de ácidos grasos saturados (AGS) inherente al consumo de grasa láctea. Recientemente se ha planteado que valorar los alimentos según el aporte de nutrientes que contienen de forma aislada conlleva a interpretar de forma limitante sus funciones y propiedades. El conocimiento de la matriz alimentaria permite valorar el efecto sobre la salud de los alimentos en su totalidad al considerar, todos los componentes que contiene, y la interacción tras su consumo. Los productos lácteos son un ejemplo para destacar la importancia de la matriz alimentaria como un determinante del efecto que pueden ejercer los nutrientes del alimento. Los efectos potencialmente nocivos de los AGS sobre la salud cardiometabólica parecen no ser tales cuando se consumen como parte de alimentos con matrices alimentarias ricas en nutrientes como son la leche, el yogur, el queso u otros productos lácteos. Estudios epidemiológicos de grandes cohortes poblacionales seguidas a largo plazo muestran que el consumo de productos lácteos, especialmente de yogur, no se asocia con un aumento del riesgo cardiovascular. Por tanto, no existen suficientes evidencias científicas para recomendar a la población general el consumo de productos lácteos bajos en grasa o desnatados de forma preferente, en lugar de su versión entera

The nutritional guidelines incorporate dairy products as part of a balanced and healthy diet. In almost all guidelines it is announced that dairy products have to preferably be consumed as non or low-fat version. The reason behind this recommendation is the intake of saturated fatty acids (SFA). Recently, it has been suggested that building nutritional recommendations according to the nutrient food content, leads to a limiting interpretation of the functions and properties of the consumed food. Lately, the research focus has been shifted towards the study of the food matrix, which allows assessing health effects considering all the components contained in the foods, and their impact in human health. Dairy products are the perfect example to highlight the importance of the food matrix as a determinant of the effects of nutrients on health. The potentially harmful effects of SFA on cardiometabolic health seem to be different when they are consumed within nutrient-rich foods such as yogurt, cheese or other dairy products. Epidemiological studies with large population cohorts and long term follow-up show that consumption of dairy products, especially yogurt, is not associated with an increased cardiovascular risk. Therefore, there is not enough scientific evidence to preferentially recommend the consumption of non-fat or low-fat dairy products to the general population, instead of its whole-fat version

Role of heparin in pulmonary cell populations in an in-vitro model of acute lung injury.

BACKGROUND: In the early stages of acute respiratory distress syndrome (ARDS), pro-inflammatory mediators inhibit natural anticoagulant factors and initiate an increase in procoagulant activity. Previous studies proved the beneficial effects of heparin in pulmonary coagulopathy, which derive from its anticoagulant and anti-inflammatory activities, although it is uncertain whether heparin works. Understanding the specific effect of unfractioned heparin on cell lung populations would be of interest to increase our knowledge about heparin pathways and to treat ARDS. METHODS: In the current study, the effect of heparin was assessed in primary human alveolar macrophages (hAM), alveolar type II cells (hATII), and fibroblasts (hF) that had been injured with LPS. RESULTS: Heparin did not produce any changes in the Smad/TGFß pathway, in any of the cell types evaluated. Heparin reduced the expression of pro-inflammatory markers (TNF-α and IL-6) in hAM and deactivated the NF-kß pathway in hATII, diminishing the expression of IRAK1 and MyD88 and their effectors, IL-6, MCP-1 and IL-8. CONCLUSIONS: The current study demonstrated that heparin significantly ameliorated the cells lung injury induced by LPS through the inhibition of pro-inflammatory cytokine expression in macrophages and the NF-kß pathway in alveolar cells. Our results suggested that a local pulmonary administration of heparin through nebulization may be able to reduce inflammation in the lung; however, further studies are needed to confirm this hypothesis.

Video-Assisted Mediastinoscopic Lymphadenectomy for Staging Non-Small Cell Lung Cancer.

BACKGROUND: The aim of this study was to evaluate the results of video-assisted mediastinoscopic lymphadenectomy (VAMLA) for staging of non-small cell lung cancer (NSCLC). METHODS: This was a prospective observational study of all consecutive VAMLAs performed from January 2010 to April 2015 for staging NSCLC. For left lung cancers, extended cervical videomediastinoscopy was added to explore the subaortic and paraaortic nodes. Patients with negative VAMLA results underwent tumor resection and lymphadenectomy of the remaining nodes. Those with N2-3 disease underwent chemoradiation. The rate of unsuspected pathologic (p)N2-3 was analyzed in the global series and in the subgroups of patients according to their nodal status diagnosed by imaging and metabolic techniques. RESULTS: One hundred sixty VAMLAs were performed for staging NSCLC (138 tumors were clinical (c)N0-1 based on imaging techniques). The rate of unsuspected N2-3 disease was 18% for the whole series: 40.7% for cN1, 22.2% for cN0 and tumor size greater than or equal to 3 cm, and 6.4% for cN0 and tumor size less than 3 cm. Staging values were sensitivity, 0.96 (95% confidence interval [CI], 0.81-99.3); specificity, 1 (95% CI, 0.97-1); positive predictive value, 1 (95% CI, 0.87-1); negative predictive value, 0.99 (95% CI, 0.95-0.99); and diagnostic accuracy, 0.99 (95% CI, 0.96-0.99). The complication rate was 5.9%. CONCLUSIONS: VAMLA is a feasible and highly accurate technique. The high rate of unsuspected mediastinal node disease diagnosed by VAMLA in patients with cN1 or cN0 disease and tumor size larger than 3 cm suggests that preresection lymphadenectomies should be included in the current staging algorithms.

[The nutrients of the milk on cardiovascular health]. / Los nutrientes de la leche en la salud cardiovascular.

The incidence of milk components on cardiovascular health is reviewed. A fraction of great interest in relation to cardiovascular disease is that of minerals, especially calcium. Benefits of milk in reducing blood pressure due to bioavailable calcium, along with other mineral elements present and bioactive peptides with antihypertensive ability, ACE inhibitors (key enzyme involved in the regulation of blood pressure) have been documented. Furthermore, a positive association of diets with high levels of calcium from milk, the fecal excretion of fat--which is favored by the same--and cardiovascular markers has also been reported. The presence in the milk of the essential, linoleic, linolenic and arachidonic fatty acids, although at low levels, is particularly interesting. Moreover, in the milk fat bioactive components as conjugated linoleic acid and sphingomyelin, which could exert potential cardioprotective effects are also present. However, because it contains high levels of saturated fatty acids, milk fat products consumption has been discouraged indiscriminately. According to the evidence collected in a long series of scientific studies it can be concluded that consumption of milk/dairy balanced and low-fat could be neutral effect or be inversely associated with cardiovascular risk.

Se revisa la incidencia del conjunto de los componentes de la leche sobre la salud cardiovascular. Una fracción del máximo interés en relación con enfermedades cardiovasculares es la de elementos minerales, sobre todo el calcio. Se han documentado beneficios de la leche para reducir la presión arterial debido al calcio biodisponible, junto con otros elementos minerales presentes así como péptidos bioactivos con capacidad antihipertensiva, inhibidores de la ECA (enzima clave implicada en la regulación de la presión arterial). Por otra parte, se ha encontrado una asociación positiva de dietas con niveles altos de calcio procedente de la leche, la excreción fecal de grasa -que se favorece con las mismas- y marcadores cardiovasculares. La presencia en la leche de los ácidos grasos esenciales, linoléico, linolénico y araquidónico, aunque con niveles bajos, es particularmente interesante. Por otra parte, en la grasa de leche están presentes componentes bioactivos como el ácido linoleico conjugado y la esfingomielina, para los que se han descrito potenciales efectos cardioprotectores. Sin embargo, debido a los niveles altos que contiene de ácidos grasos saturados el consumo de productos con grasa de leche, se ha desaconsejado de forma indiscriminada. En línea con las evidencias recogidas en una larga serie de trabajos científicos se puede concluir que el consumo de leche/lácteos equilibrados o bajos en grasa puede tener efecto neutro o estar inversamente asociado al riesgo cardiovascular.

Los nutrientes de la leche en la salud cardiovascular / The nutrients of the milk on cardiovascular health

Se revisa la incidencia del conjunto de los componentes de la leche sobre la salud cardiovascular. Una fracción del máximo interés en relación con enfermedades cardiovasculares es la de elementos minerales, sobre todo el calcio. Se han documentado beneficios de la leche para reducir la presión arterial debido al calcio biodisponible, junto con otros elementos minerales presentes así como péptidos bioactivos con capacidad antihipertensiva, inhibidores de la ECA (enzima clave implicada en la regulación de la presión arterial). Por otra parte, se ha encontrado una asociación positiva de dietas con niveles altos de calcio procedente de la leche, la excreción fecal de grasa –que se favorece con las mismas– y marcadores cardiovasculares. La presencia en la leche de los ácidos grasos esenciales, linoléico, linolénico y araquidónico, aunque con niveles bajos, es particularmente interesante. Por otra parte, en la grasa de leche están presentes componentes bioactivos como el ácido linoleico conjugado y la esfingomielina, para los que se han descrito potenciales efectos cardioprotectores. Sin embargo, debido a los niveles altos que contiene de ácidos grasos saturados el consumo de productos con grasa de leche, se ha desaconsejado de forma indiscriminada. En línea con las evidencias recogidas en una larga serie de trabajos científicos se puede concluir que el consumo de leche/lácteos equilibrados o bajos en grasa puede tener efecto neutro o estar inversamente asociado al riesgo cardiovascular (AU)

The incidence of milk components on cardiovascular health is reviewed. A fraction of great interest in relation to cardiovascular disease is that of minerals, especially calcium. Benefits of milk in reducing blood pressure due to bioavailable calcium, along with other mineral elements present and bioactive peptides with antihypertensive ability, ACE inhibitors (key enzyme involved in the regulation of blood pressure) have been documented. Furthermore, a positive association of diets with high levels of calcium from milk, the fecal excretion of fat -which is favored by the same- and cardiovascular markers has also been reported. The presence in the milk of the essential, linoleic, linolenic and arachidonic fatty acids, although at low levels, is particularly interesting. Moreover, in the milk fat bioactive components as conjugated linoleic acid and sphingomyelin, which could exert potential cardioprotective effects are also present. However, because it contains high levels of saturated fatty acids, milk fat products consumption has been discouraged indiscriminately. According to the evidence collected in a long series of scientific studies it can be concluded that consumption of milk / dairy balanced and low-fat could be neutral effect or be inversely associated with cardiovascular risk (AU)

Caso inusual de síndrome de cushing

Objetivo: discutir las dificultades en el diagnóstico y manejo terapéutico de un caso poco frecuente de Síndrome de Cushing (SC). Caso Clínico: se reporta el caso de un paciente femenino, de 24 años, con hipercortisolismo y patrón bioquímico sugestivo de SC dependiente de corticotropina (ACTH). Estudios imagenológicos mostraron agrandamiento de la glándula hipófisis, extensión supraselar y una lesión lateral izquierda, sugestiva de microadenoma. Sometida a cirugía transesfenoidal en dos oportunidades, sin obtenerse la remisión del cuadro. Tomografía computarizada (TC) de tórax demostró la presencia de nódulo pulmonar único izquierdo, hipercaptante en el gammagrama con octreotido. Fue removido quirúrgicamente en forma satisfactoria produciéndose un abrupto descenso en los niveles de ACTH y cortisol pero nuevamente se incrementaron 24 horas después, permaneciendo elevados desde entonces. La inmunohistoquímica fue positiva para ACTH y cromogranina; el estudio anatomapatológico reportó tumor carcinoide típico sin invasión a ganglios linfáticos; sin embargo, la evolución clínica sugirió enfermedad residual. Se inició tratamiento con análogos de somatostatina (octreotido), el cual se ha mantenido por once meses, obteniéndose mejoría significativa del cuadro clínico y control parcial del hipercortisolismo. TC de tórax y gammagrama con octreotido recientemente practicados, revelaron pequeño foco, el cual correspondió a adenopatía mediastinal derecha. Se plantea la hipótesis de que el tumor producía simultáneamente ACTH y hormona liberadora de corticotropina (CRH, por sus siglas en inglés), explicándose de esta manera la hiperplasia hipofisaria. Conclusión: En pacientes con SC dependiente de ACTH hay que tener presente la existencia de incidentalomas que pueden confundir el diagnóstico. Considerar que la hiperplasia hipofisaria puede ser secundaria a una fuente ectópica productora de CRH y aunque en este caso no pudo realizarse inmunohistoquímica para CRH en las células tumorales, es posible suponer que dichas células secretaban conjuntamente CRH y ACTH lo cual explica la hiperplasia hipofisaria.

Objective: to discuss the diagnostic and therapeutic difficulties of a rare case of Cushing´s syndrome. Case Report: we describe a case of a 24-year-old female patient who developed symptoms compatible with hypercortisolism; the biochemical pattern was suggestive of ACTH dependent Cushin´s Syndrome. Imaging studies showed pituitary enlargement with suprasellar extension and a lesion suggestive microadenoma on the left side. Transsphenoidal surgery was performed in two occasions without remission. Subsequent explorations showed the presence of a single left lung nodule, positive to octreoscan. It was successfully operated and, a sharp decline on ACTH and cortisol levels was seen immediately after operation, increasing again 24 hours later and, remained elevated since then. Inmunohistochemestry studies were positive for ACTH and chromogranin and although the pathology was compatible with typical carcinoid, and no lymph node invasion was seen, the clinical evolution suggested the presence of residual disease. Treatment with somatostatin analogues (Octreotide) was started and has being maintained for eleven months, up to the present. A significant improvement of the clinical picture and partial control of the hypercortisolism has being obtained. Chest CT and octreoscan recently performed, revealed small focus, which corresponded to a right mediastinal adenopathy. We hypothesize that the tumor was simulta-neously producing ACTH and CRH, explaining in this way the pituitary hyperplasia. Conclusion: In patients with ACTH dependent Cushing the existence of incidentalomas could confuse the diagnosis and should be ruled out. Pituitary hyperplasia might be secondary to an ectopic CRH source. Although in our case immunohistochemostry for CRH was not performed, we assume that tumor cells secreted both, CRH and ACTH, explaining the pituitary hyperplasia.

Survival of patients with unsuspected pN2 non-small cell lung cancer after an accurate preoperative mediastinal staging.

BACKGROUND: The aim of this study is to analyze the survival of patients with non-small cell lung cancer (NSCLC) without clinical suspicion of mediastinal lymph node involvement who underwent complete resection and whose tumors were finally proven to be pathologic N2 (pN2). METHODS: This is a retrospective study of a prospective database from January 2004 to December 2010. A total of 621 patients with NSCLC were staged and operated according to the European Society of Thoracic Surgeons guidelines. After exclusions (previous induction treatment, carcinoid tumors, small cell carcinomas), 540 patients were analyzed; 406 (75%) required surgical exploration of the mediastinum and 134 (25%) underwent surgery directly. Survival analysis was performed by the Kaplan-Meier method and the log-rank test was used for comparisons. RESULTS: Thirty (5.5%) patients had unsuspected pN2 and complete resection was achieved in 27 (90%). Three- and 5-year survival rates were 87% and 81%, respectively, for patients with a true negative result of the protocol (pN0-1), and 79% and 40%, respectively, for those with a false negative result (unsuspected pN2) (p < 0.0001). CONCLUSIONS: The rate of unsuspected pN2 in patients whose tumors were staged according to the European Society of Thoracic Surgeons guidelines was low. The survival of this group of patients was better than expected. Therefore, resection of properly staged unsuspected pN2 NSCLC is reasonable and should not be avoided if complete resection can be achieved.

The pumpless extracorporeal lung membrane provides complete respiratory support during complex airway reconstructions without inducing cellular trauma or a coagulatory and inflammatory response.

OBJECTIVE: Our objective was to investigate the capacity of a pumpless extracorporeal lung membrane (iLA) (Novalung; Novalung GmbH, Hechingen, Germany) to provide adequate respiratory support and the impact on morbidity/mortality during complex airway reconstruction. METHODS: Only patients unable to be ventilated via conventional intubation were eligible for the study. A larynx mask or orotracheal tubes were placed above the airway defect and the iLA was attached via femoral vessels (arteriovenous), providing extracorporeal gas exchange, apneic hyperoxygenation, and total tubeless airway reconstruction. Haptoglobulin, plasmin-antiplasmin complex, P-selectin activation, and interleukin 6 were measured before, during, and after iLA use and 72 hours postoperatively. RESULTS: Fifteen consecutive patients (age, 42±17 years) underwent elective (n=7) or emergency (n=8) reconstruction of the airway owing to a variety of disorders or defects. The iLA was left in place for 185±61 minutes, diverted 1.70±0.48 L/min of the cardiac output, and provided an arteriovenous carbon dioxide removal and oxygen transfer of 173±94 and 144±83 mL/min, respectively. The arterial oxygen tension/inspired oxygen fraction (314±31 mm Hg), and arterial carbon dioxide tension (40±6 mm Hg) remained stable throughout the entire operations. The following procedures were performed: redo slide tracheoplasties (n=3), redo tracheoesophageal fistula repair (n=1), sleeve lobectomies (n=2), main carina reconstructions (n=7), and anastomotic stenting and myocutaneous coverages (n=2). Three patients required prolonged (9±2 days) postoperative iLA support. Two (13%) patients died during the hospital stay. The use of iLA was associated with significant (P<.05) but clinically nonrelevant and yet nonpathologic increases of haptoglobulin (hemolysis), plasmin-antiplasmin complex (coagulation activation), and P-selectin activation (platelet activation). Data normalized within 48 hours postoperatively. CONCLUSIONS: Data suggest that iLA provides complete intraoperative respiratory support in patients who cannot receive conventional intubation/ventilation without relevant effects on cellular trauma, coagulatory response, and inflammatory response.

Extended cervical mediastinoscopy: mature results of a clinical protocol for staging bronchogenic carcinoma of the left lung.

OBJECTIVE: The objective of this study is to evaluate the accuracy of extended cervical mediastinoscopy (ECM) in the staging of bronchogenic carcinoma (BC) of the left lung based on our updated experience. METHODS: From 1998 to 2003, 89 patients underwent routine ECM for staging of BC of the left lung. In 2004, routine positron emission tomography (PET) was included in our staging protocol and ECM was reserved for those with positive mediastinal or hilar PET images, large lymph nodes on computed tomography (CT) scan or central tumours. Following this protocol, from 2004 to 2010, we performed 132 selective ECM. ECM was considered positive when metastatic nodes or tumour involvement directly in the subaortic or para-aortic regions was confirmed pathologically. Patients with negative ECM underwent subsequent thoracotomy for tumour resection and systematic nodal dissection (SND). RESULTS: Two hundred and twenty-one ECMs were performed from 1998 to 2010 (89 routine and 132 selective). In the routine ECM protocol, four cases were positive and thoracotomy was contraindicated. The remaining 85 patients were operated and five had nodal disease in subaortic (LN5) or para-aortic (LN6) stations. In the selective ECM protocol (n = 188), 132 patients underwent ECM and in 19 it was positive; the remaining 113 patients underwent thoracotomy and SND found involved LN5 or LN6 in six patients; the other 56 patients underwent direct thoracotomy and four had positive LN5 or LN6. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ECM were 0.67, 1, 1, 0.94 and 0.95, respectively. The staging values of routine/selective ECM protocols were 0.44/0.65, 1/1, 1/1, 0.94/0.94 and 0.94/0.95, respectively. CONCLUSIONS: Selective ECM protocol according to CT and PET findings has high negative predictive value and accuracy. Therefore, its selective use is recommended because it saves around 30% ECM without decreasing staging values of the current protocol.

Optimal positive end-expiratory pressure during pumpless extracorporeal lung membrane support.

The aim of this study was to determine the optimal positive end-expiratory pressure (PEEP) required during extracorporeal lung membrane support (interventional lung assist [iLA]; Novalung GmbH, Hechingen, Germany). Twenty healthy pigs were initially (4 h) mechanically ventilated with a tidal volume (V(T)) of 10 mL/Kg, respiratory rate (RR) of 20 breaths/min, PEEP of 5 cm H(2)O, and fraction of inspired O(2) (FiO(2)) of 1.0. Thereafter, the iLAs were placed arteriovenously transfemorally and settings reduced to reach near static ventilation (V(T) < or = 2 mL/Kg, RR 4 breaths/min, PEEP of 5, FiO(2) 1.0). Then, animals were assigned to four study groups evaluating 5 cm H(2)O increasing levels of PEEP for 8 h. Gas exchanges with PEEP < or = 10 cm H(2)O were significantly worse than those with PEEP > 12 cm H(2)O, and this without hemodynamical imbalance. This study suggests that the iLA may provide adequate gas exchange during static ventilation only with PEEP levels > 10 cm H(2)O, and this without pulmonary or systemic hemodynamic imbalance.

Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma of the left lung.

OBJECTIVE: To evaluate the technical feasibility and the sensitivity, specificity and accuracy of extended cervical mediastinoscopy (ECM) in the staging of bronchogenic carcinoma (BC) of the left lung. METHODS: From 1998 to 2003, 89 patients underwent routine ECM for staging of BC of the left lung. In 2004, positron emission tomography (PET) was included in our staging protocol and ECM was reserved for those with positive mediastinal or hilar PET images, large lymph nodes on computed tomography (CT) scan or central tumours. From 2004 to 2007 we performed selective ECM in 67 patients. ECM was considered positive when metastatic nodes or tumour involvement directly in the subaortic or para-aortic regions was confirmed pathologically. One hundred and forty-three patients with negative ECM underwent subsequent thoracotomy for tumour resection and systematic nodal dissection. Pathological findings were reviewed and staging values were calculated. RESULTS: One hundred and fifty-six patients underwent ECM (89 routine and 67 selective). In 13, ECM was positive and thoracotomy was contraindicated. The rest of the patients were operated. We performed 88 lobectomies, 34 pneumonectomies, 6 wedge resections, 13 exploratory thoracotomies and 2 parasternal mediastinotomies. Lymphadenectomy specimens showed tumour involvement of subaortic lymph nodes in 8 patients. Complication rate was 2%: two cases of mediastinitis, one ventricular fibrillation, and one superficial surgical wound infection. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of routine/selective ECM were: 0.45/0.75, 1/1, 1/1, 0.94/0.95, 0.94/0.95, respectively. CONCLUSION: ECM is a feasible staging technique that allows ruling out subaortic and para-aortic nodal disease with high negative predictive value, accuracy and sensitivity. Its indication based on the CT and PET findings seems more advisable that its routine use to stage bronchogenic carcinoma of the left lung.

Extracorporeal lung membrane provides better lung protection than conventional treatment for severe postpneumonectomy noncardiogenic acute respiratory distress syndrome.

OBJECTIVE: We compared conventional treatment with pumpless extracorporeal lung membrane (Interventional Lung Assist [iLA] Novalung; Novalung GmbH, Hechingen, Germany) support in a pig model of postpneumonectomy severe acute respiratory distress syndrome. METHODS: Adult pigs underwent a left thoracotomy without (group I) or with a left extrapericardial pneumonectomy and radical lymphadenectomy (groups II to V). After stabilization, pigs belonging to group II were observed only, whereas in those belonging to groups III to V, a surfactant-depletion severe (Pao(2)/Fio(2) < 100) postpneumonectomy acute respiratory distress syndrome was induced. This was followed by observation (group III); treatment with conventional therapy including protective ventilation, steroids, and nitric oxide (group IV); or femoral arteriovenous iLA Novalung placement, near-static ventilation, steroids, and nitric oxide (group V). Each group included 5 animals. Primary outcome was extubation 12 hours postoperatively or postpneumonectomy acute respiratory distress syndrome. RESULTS: A severe postpneumonectomy acute respiratory distress syndrome was obtained after 9 +/- 2 alveolar lavages over 90 +/- 20 minutes. In group V pigs, the iLA Novalung device diverted 17% +/- 4% of the cardiac output, permitted an oxygen transfer and carbon dioxide removal of 298.4 +/- 173.7 mL/min and 287.7 +/- 87.3 mL/min, respectively, and static ventilation (tidal volume, 2.2 +/- 1 mL/kg; respiratory rate, 6 +/- 2.9 breaths/min). All but 1 pig belonging to group V could be extubated compared with none in groups III and IV (P < .01), and only their lungs normalized cytokine release (P < .001) and surfactant (P < .03) and displayed fewer parenchymal lesions (P < .05). CONCLUSIONS: The pumpless extracorporeal lung membrane and near-static ventilation achieved a significantly better outcome than conventional treatment in this pig model of severe postpneumonectomy acute respiratory distress syndrome, probably because the injured lungs were not forced to work and this "rest" gave them more time to heal.

Extrapulmonary ventilation for unresponsive severe acute respiratory distress syndrome after pulmonary resection.

BACKGROUND: The purpose of this study was to evaluate the feasibility of integrating an artificial, pumpless extracorporeal membrane ventilator (Novalung) to near static mechanical ventilation and its efficacy in patients with severe postresectional acute respiratory distress syndrome (ARDS) unresponsive to optimal conventional treatment. METHODS: Indications were severe postresectional and unresponsive acute respiratory distress syndrome, hemodynamic stability, and no significant peripheral arterial occlusive disease or heparin-induced thrombocytopenia. Management included placement of the arteriovenous femoral transcutaneous interventional lung-assist membrane ventilator, lung rest at minimal mechanical ventilator settings, and optimization of systemic oxygen consumption and delivery. RESULTS: Among 239 pulmonary resections performed between 2005 and 2006, 7 patients (2.9%) experienced, 4 +/- 0.8 days after 5 pneumonectomies and 2 lobectomies, a severe (Murray score, 2.9 +/- 0.3) acute respiratory distress syndrome unresponsive to 4 +/- 2 days of conventional therapy. The interventional lung-assist membrane ventilator was left in place 4.3 +/- 2.5 days, and replaced only once for massive clotting. During this time, 29% +/- 0.3% or 1.4 +/- 0.36 L/min of the cardiac output perfused the device, without hemodynamic impairment. Using a sweep gas flow of 10.7 +/- 3.8 L/min, the device allowed an extracorporeal carbon dioxide removal of 255 +/- 31 mL/min, lung(s) rest (tidal volume, 2.7 +/- 0.8 mL/kg; respiratory rate, 6 +/- 2 beats/min; fraction of inspired oxygen, 0.5 +/- 0.1), early (<24 hours) significant improvement of respiratory function, and reduction of plasmatic interleukin-6 levels (p < 0.001) and Murray score (1.25 +/- 0.1; p < 0.003). All but 1 patient (14%) who died of multiorgan failure were weaned from mechanical ventilation 8 +/- 3 days after removal of the interventional lung-assist membrane ventilator, and all of them were discharged from the hospital. CONCLUSIONS: The integration of this device to near static mechanical ventilation of the residual native lung(s) is feasible and highly effective in patients with severe and unresponsive acute respiratory distress syndrome after pulmonary resection.

Experimental safety and efficacy evaluation of an extracorporeal pumpless artificial lung in providing respiratory support through the axillary vessels.

OBJECTIVE: We sought to investigate the safety and feasibility of implanting the pumpless interventional lung assist device (Novalung; Novalung GmbH, Hechingen, Germany) to the axillary vessels either by means of direct cannulation or end-to-side graft interposition and the capability of either type of vascular access to provide respiratory support during apneic ventilation in adult pigs. METHODS: Ten pigs were ventilated for 4 hours (respiratory rate, 20-25 breaths/min; tidal volume, 10-12 mL/kg; fraction of inspired oxygen, 1.0; positive end-expiratory pressure, 5 cm H2O). Thereafter, the interventional lung assist device was surgically connected to the right axillary artery and vein by using direct cannulation (n = 5) or end-to-side ringed polytetrafluoroethylene graft interposition (n = 5), and ventilatory settings were reduced to achieve near apneic ventilation (respiratory rate, 4 breaths/min; tidal volume, 1-2 mL/kg; fraction of inspired oxygen, 1.0; positive end-expiratory pressure, 20 cm H2O). Hemodynamic and intrathoracic volumes and lung cytokine levels were measured. RESULTS: Blood flow through the interventional lung assist device was 1.7 +/- 0.4 L/min or 30% +/- 14% of the cardiac output, and the mean pressure gradient across the interventional lung assist device was 10 +/- 2 mm Hg. The interventional lung assist device allowed an O2 transfer of 225.7 +/- 70 mL/min and a CO2 removal of 261.7 +/- 28.5 mL/min. Although the amount of blood flow perfusing the interventional lung assist device was significantly higher (P < .01) with direct cannulation (2.1 +/- 0.3 L/min) compared with that seen in graft interposition (1.3 +/- 0.3 L/min), the latter allowed similar respiratory support with reduced hemodynamic instability. CONCLUSIONS: The axillary vessels are a safe and attractive cannulation site for pumpless partial respiratory support. Compared with direct cannulation, graft interposition was equally able to support the interventional lung assist device-driven gas exchange requirements during apneic ventilation with better hemodynamic stability.

Video-assisted direct closure of bronchial fistula.

Video-assisted thoracoscopic surgery is a well-established method for managing persistent air leak in spontaneous pneumothorax. We describe a case of complicated spontaneous secondary pneumothorax in a patient with bullous emphysema that was treated by video-assisted manual suture of the bronchial fistula at the end of the right upper bronchus.