Photodynamic therapy as an adjunct to surgery for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is increasingly observed in industrial countries. Despite concerted efforts and combined treatments including surgery, chemotherapy and irradiation patients eventually succumb from relentless local progression of the disease. Recent publications have demonstrated an improved response rate with the cytostatic agent pemetrexed which will be tested in a neoadjuvant setting followed by surgery. However, effective tumor control requires new loco-regional treatment modalities, eventually in combination with neoadjuvant chemotherapy. Intraoperative photodynamic therapy (PDT) of the chest cavity has been proposed as an attractive treatment concept for MPM since a selective treatment of the tumor bed following resection has the potential to improve local tumor control. It has been shown to afford tumor destruction in patients with mesothelioma but efficiency and selectivity is not yet sufficient for routine clinical application. Experimental work on MPM has shown that tumor selectivity of PDT depend on treatment conditions and can be improved by structural modification and improved targeting of the sensitizers. Refinements of PDT for mesothelioma will depend on a more detailed understanding of the pathways for preferential sensitizer accumulation within the tumor as well as on synergistic effects between PDT and chemotherapeutic agents.

Photodynamic therapy selectively enhances liposomal doxorubicin uptake in sarcoma tumors to rodent lungs.

BACKGROUND: In specific conditions, photodynamic therapy (PDT) can enhance the distribution of macromolecules across the endothelial barrier in solid tumors. It was recently postulated that tumor neovessels were more responsive to PDT than the normal vasculature. We hypothesized that Visudyne(R)-mediated PDT could selectively increase liposomal doxorubicin (Liporubicin) uptake in sarcoma tumors to rodent lungs while sparing the normal surrounding tissue. MATERIALS AND METHODS: Sarcoma tumors were generated subpleurally in the left lower lung lobe of 66 Fischer rats. Ten days following sarcoma implantation, tumors underwent different pre-treatment schemes: no PDT (controls), low-dose PDT (0.0625 mg/kg Visudyne(R), 10 J/cm(2) and 35 mW/cm(2)) and high-dose PDT (0.125 mg/kg Visudyne(R), 10 J/cm(2) and 35 mW/cm(2)). Liporubicin was then administered and allowed to circulate for 1, 3, or 6 hours. At the end of each treatment scheme, we assessed the uptake of Liporubicin in tumor and lung tissues by high-performance liquid chromatography and fluorescence microscopy. RESULTS: In all PDT-treated groups, there was a significant enhancement of Liporubicin uptake in tumors compared to controls after 3 and 6 hours of drug circulation. In addition, Liporubicin distribution within the normal lung tissue was not affected by PDT. Thus, PDT pre-treatment significantly enhanced the ratio of tumor-to-lung drug uptake compared to controls. Finally, fluorescence microscopy revealed a well-detectable Liporubicin signaling throughout PDT-treated tumors but not in controls. CONCLUSIONS: PDT is a tumor-specific enhancer of Liporubicin distribution in sarcoma lung tumors which may find a translation in clinics.

Protein contamination on Klason lignin contents in tropical grasses and legumes

The objective of this work was to evaluate the extent of protein contamination on Klason lignin (KL) in tropical grasses and legumes, and to propose an equation to estimate the protein-free content of Klason lignin (KLp). Five grass (30 samples) and 12 legume species (31 samples) were evaluated. Legumes had higher KL contents. Protein contamination was significant in both grasses and legumes, but greater in legume samples. The model to predict KLp was based on KL and crude protein (CP) contents, as follows: KLp = 0.8807KL - 0.0938KL x D - 0.00338CP (R2=0.935), in which D=0, for grasses, and D=1 for legumes.

Sclerosing hemangioma of the lung.

A well circumscribed nodular mass discovered on routine chest ray examination, in the left inferior lobe of an otherwise healthy 49-year-old male. Histopathologically the lesion corresponded to a typical so called sclerosing hemangioma. The clinical and histopathological features are described. The sclerosing hemangioma of the lung is a rare benign tumor. Its histogenesis has not been explained yet. Following the electron-microscopic and immunohistochemical researches the opinions have been still unhomogeneous. Therefore, it is concluded that is a tumor of epithelial, endothelial, mesenchymal and even mesothelial origin. This study deals with this tumor, its immunohistochemical analysis points at its epithelial character.

Resultados de la aplicación en parcelas comerciales de un programa de control integrado de plagas de manzano en Lleida

Se describen los métodos de muestreo, los umbrales de tolerancia y los métodos de control utilizados en un programa de control integrado de plagas de manzano basado en el control biológico de Panonychus ulmi Koch mediante Amblyseius andersoni Chant y en el empleo de productos selectivos cuando existen, contra el resto de las plagas, en Lleida. El programa se ha llevado a cabo en 6 fincas en las campañas 1989-90 y 1990-91. Sólo en un caso no se produjo control biológico de P. ulmi, siendo necesario un tratamiento acaricida. En general, los métodos de control del resto de las plagas han funcionado correctamente, aunque en algunos casos son tácticas conservadoras. Se discuten finalmente los distintos componentes del programa de control integrado y se señalan los objetivos del plan de trabajo futuro.

Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy.

BACKGROUND: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. in vivo. Lasers Surg. Med. 47:323-330, 2015. © 2015 Wiley Periodicals, Inc. METHODS: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). RESULTS: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. CONCLUSIONS: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. Lasers Surg. Med. 47:323-330, 2015.

Vacuum-assisted closure device for the management of infected postpneumonectomy chest cavities.

BACKGROUND: Infected postpneumonectomy chest cavities may be related to chronic postpneumonectomy empyema or arise in rare situations of necrotizing pneumonia with complete lung destruction where pneumonectomy and pleural debridement are required. We evaluated the safety and efficacy of an intrathoracic vacuum-assisted closure device (VAC) for the treatment of infected postpneumonectomy chest cavities. METHOD: A retrospective single institution review of all patients with infected postpneumonectomy chest cavities treated by VAC between 2005 and 2013. Patients underwent surgical debridement of the thoracic cavity, muscle flap closure of the bronchial stump when a fistula was present, and repeated intrathoracic VAC dressings until granulation tissue covered the entire chest cavity. After this, the cavity was obliterated by a Clagett procedure and closed. RESULTS: Twenty-one patients (14 men and 7 women) underwent VAC treatment of their infected postpneumonectomy chest cavity. Twelve patients presented with a chronic postpneumonectomy empyema (10 of them with a bronchopleural fistula) and 9 patients with an empyema occurring in the context of necrotizing pneumonia treated by pneumonectomy. In-hospital mortality was 23%. The median duration of VAC therapy was 23 days (range, 4-61 days) and the median number of VAC changes per patient was 6 (range, 2-14 days). Infection control and successful chest cavity closure was achieved in all surviving patients. One adverse VAC treatment-related event was identified (5%). CONCLUSIONS: The intrathoracic VAC application is a safe and efficient treatment of infected postpneumonectomy chest cavities and allows the preservation of chest wall integrity.

Liderazgo femenino. Un análisis de las diferencias de género en la formación y desarrollo de asociaciones de inmigrantes africanos

En el presente estudio se describen, analizan y comparan las manifestaciones del liderazgo femenino en las asociaciones de inmigrantes africanos: sus objetivos de trabajo, temáticas y formas, organización e institucionalización. Para ello se analizan en profundidad diez historias de vida, partiendo de la hipótesis de la existencia de una clara diferenciación de objetivos entre las asociaciones de hombres y mujeres africanos derivados de la desigualdad básica de las posiciones sociales entre hombres y mujeres, y muy especialmente, de las culturas de género. Los resultados obtenidos sugieren que existen mujeres inmigrantes “fuertes” (ni sumisas ni ignorantes) con capacidad de liderazgo en la asociación, pero no por unas supuestas especificidades “femeninas” sino por un proceso de aprendizaje temprano (adolescente), éxito educativo y un origen social relativamente elevado que forjan una cierta rebeldía y la asunción de una autoridad explícita. De cualquier modo, no se observan diferencias relevantes entre el liderazgo femenino y el liderazgo masculino, ya que en ambos casos se da un cierto “carisma”, la existencia de unas dotes personales que se desarrollan desde la interacción en situaciones sociales concretas.

La teoría de los códigos. Desigualdades lingüísticas en educación

Las desigualdades lingüísticas en educación constituyen un problema que puede acentuarse con el cambio de sociedad. Este artículo recupera la teoría de los códigos de Basil Bernstein desde una perspectiva culturalista para aclarar sus aspectos más polémicos y, al mismo tiempo, introducir un nuevo modelo de análisis que pone en relación el capital cultural de las familias con el nivel de desarrollo lingüístico de los adolescentes. Se observa que el nivel de estudios alcanzado por los padres adquiere una notable importancia en el desarrollo de la competencia comunicativa, especialmente en el desarrollo de las habilidades correspondientes al lenguaje escrito en los adolescentes de primer curso de Educación Secundaria Obligatoria.

Las asociaciones de inmigrantes africanos. Organización, proyección y actuaciones

El asociacionismo de personas de origen extranjero ha crecido de forma notable desde los años 90 y, especialmente, desde los 2000, influenciado por los intereses de estas personas pero también por el contexto social, político e institucional que lo ha favorecido y condicionado. Este trabajo presenta los resultados de una encuesta realizada a 206 representantes de asociaciones de inmigrantes de origen africano de las comunidades autónomas de Cataluña, Valencia y Navarra. Nuestro objetivo ha consistido en clasificar las asociaciones, estudiar su organización y funcionamiento y conocer sus ámbitos de actuación. Entre otras cuestiones, hemos observado que este asociacionismo es joven y no responde a una única forma organizativa, sino que, en función de dinámicas internas y externas, intereses de los asociados y años de vida de cada asociación, adquiere diferentes estructuras y estrategias.

La mediación intercultural en las asociaciones de inmigrantes de origen africano

El artículo analiza cómo realizan la mediación intercultural las asociaciones de inmigrantes de origen africano de tres comunidades autónomas (Cataluña, Valencia y Navarra) y qué caracteriza a sus actores. El análisis se basa en una encuesta realizada a 206 asociaciones de inmigrantes y en 30 entrevistas: 15 a directivos, 10 a administraciones y entidades que trabajan con ellas, y 5 a inmigrantes no asociados. Los resultados apuntan a que las asociaciones son espacios de convivencia, pero una parte importante de ellas carece de objetivos específicos claros en sus planteamientos de trabajo con sus usuarios y otros agentes sociales. También hemos visto que la mediación es una práctica incipiente en las asociaciones, al contrario de lo que sucede en el seno de las instituciones españolas del ámbito educativo, sanitario y familiar. Por otra parte, hemos apreciado que las asociaciones africanas desvirtúan, a menudo, el concepto de mediación considerándola simplemente como una conversación entre los suyos.

Incidence and Risk Factors of Abdominal Complications After Lung Transplantation.

BACKGROUND: Due to the underlying diseases and the need for immunosuppression, patients after lung transplantation are particularly at risk for gastrointestinal (GI) complications that may negatively influence long-term outcome. The present study assessed the incidences and impact of GI complications after lung transplantation and aimed to identify risk factors. METHODS: Retrospective analysis of all 227 consecutively performed single- and double-lung transplantations at the University hospitals of Lausanne and Geneva was performed between January 1993 and December 2010. Logistic regressions were used to test the effect of potentially influencing variables on the binary outcomes overall, severe, and surgery-requiring complications, followed by a multiple logistic regression model. RESULTS: Final analysis included 205 patients for the purpose of the present study, and 22 patients were excluded due to re-transplantation, multiorgan transplantation, or incomplete datasets. GI complications were observed in 127 patients (62 %). Gastro-esophageal reflux disease was the most commonly observed complication (22.9 %), followed by inflammatory or infectious colitis (20.5 %) and gastroparesis (10.7 %). Major GI complications (Dindo/Clavien III-V) were observed in 83 (40.5 %) patients and were fatal in 4 patients (2.0 %). Multivariate analysis identified double-lung transplantation (p = 0.012) and early (1993-1998) transplantation period (p = 0.008) as independent risk factors for developing major GI complications. Forty-three (21 %) patients required surgery such as colectomy, cholecystectomy, and fundoplication in 6.8, 6.3, and 3.9 % of the patients, respectively. Multivariate analysis identified Charlson comorbidity index of ≥3 as an independent risk factor for developing GI complications requiring surgery (p = 0.015). CONCLUSION: GI complications after lung transplantation are common. Outcome was rather encouraging in the setting of our transplant center.

Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial.

BACKGROUND: One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes. METHODS: We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m(2) cisplatin and 85 mg/m(2) docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030771. FINDINGS: From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7-22·9) in the chemoradiotherapy group and 11·6 months (8·4-15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6-50·0) with radiotherapy, compared with 26·2 months (19·9-52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. INTERPRETATION: Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi.

Thoracoscopic resection of pulmonary metastasis: Current practice and results.

NlmCategory="UNASSIGNED">Video-assisted thoracoscopic surgery (VATS) is currently a routinely performed procedure for the management of early non small cell lung cancer. The oncological results of VATS in terms of local recurrence and overall survival are equivalent or superior to those of conventional thoracotomy with lower morbidity and hospital stay. In the field of pulmonary metastasectomy, current guidelines support a thoracotomy approach in order to properly palpate the lung and detect nodules too small to be identified on standard radiological examinations (typically less than 5mm in diameter). However, the oncological and clinical significance of these millimetric nodules is not known. This has led some thoracic surgeons to rethink the approach of solitary pulmonary metastasectomy: because of improvements in thin slice helical CT-scans, some support a VATS approach for solitary pulmonary nodules without formal bimanual palpation and suggest this allows equivalent oncological results and decreased surgical morbidity.

Densidade mamográfica assimétrica: como investigar? (Revisão de literatura e apresentação de rotina de investigação)

A distribuição de tecido fibroglandular nas mamas ocorre em sua maioria de forma simétrica, e qualquer alteração nesta simetria pode ser indício de lesão oculta no parênquima. A avaliação da densidade assimétrica constitui, portanto, um dos principais desafios no dia-a-dia do radiologista, no sentido de diferenciar áreas de superposição de estruturas normais de lesões parenquimatosas verdadeiras. O conhecimento das diferentes técnicas e dos recursos que podem ser utilizados na investigação das densidades assimétricas é de grande importância, assim como o estabelecimento de protocolo de sua avaliação, para que a origem dessas densidades seja plenamente estabelecida, uma vez que elas podem representar a única manifestação de um câncer de mama oculto, clínica e radiograficamente.