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1.
Mol Cancer ; 17(1): 148, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309369

RESUMO

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Mesotelioma/sangue , Mesotelioma/patologia , Neovascularização Patológica/sangue , Neoplasias Pleurais/sangue , Neoplasias Pleurais/patologia , Biomarcadores Tumorais , Fator Neurotrófico Derivado do Encéfalo/genética , Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Mesotelioma/genética , Mesotelioma/mortalidade , Mesotelioma Maligno , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurais/genética , Neoplasias Pleurais/mortalidade , Prognóstico , RNA Mensageiro/genética , Curva ROC
2.
BMC Cancer ; 18(1): 372, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29614983

RESUMO

BACKGROUND: Active smoking at the time of diagnosis of a first head & neck (H&N) or lung cancer is associated with a worse cancer outcome and increased mortality. However, the compared characteristics of active vs. former smokers at cancer diagnosis are poorly known. METHODS: In 371 subjects with a first H&N or lung cancer, we assessed: 1) socio-demographic features; 2) lifelong types of smoking; 3) alcohol use disorder identification test (AUDIT); 4) cannabis abuse screening test (CAST); and 5) Mini International Neuropsychiatric Interview (MINI). Using a multivariable regression model, we compared the profile of current smokers and past smokers. RESULTS: Current smokers more frequently exhibited H&N cancer (OR 3.91; 95% CI [2.00-6.51]; p <  0.0001) and ever smoking of hand-rolled cigarettes (OR 2.2; 95% CI [1.25-3.88]; p = 0.007). Among subjects with lung cancer (n = 177), current smoking was primarily associated with ever smoking of hand-rolled cigarettes (OR 2.88; 95% CI [1.32-6.30]; p = 0.008) and negatively associated with age (OR 0.92; 95% CI [0.89-0.96]; p <  0.001). Among subjects with H&N cancer (n = 163), current smokers exhibited a significantly greater AUDIT score (OR = 1.08; 95% CI [1.01-1.16]; p = 0.03). CONCLUSION: At the time of diagnosis of the first lung or H&N cancer, current smoking is highly associated with previous type of smoking and alcohol drinking patterns. TRIAL REGISTRATION: NCT01647425 ; Registration date: July 23, 2012.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Fumantes , Fumar , Idoso , Estudos Transversais , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Fatores de Tempo
3.
World J Surg ; 42(4): 1171-1179, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28948336

RESUMO

BACKGROUND: Liver and lungs are the two most frequent sites of metastatic spread of colorectal cancer (CRC). Complete resection of liver and/or lung metastases is the only chance of cure, and several studies have reported an improved survival after an aggressive treatment. Nevertheless, CRC liver metastases (CLM) have been recognized as a pejorative factor for patients undergoing pulmonary metastasectomy. We report our experience with patients successively operated on for CRC hepatic and pulmonary metastasis (CPM) and seek to identify prognostic factors. METHODS: All consecutive patients who had resection of CPM and CLM between 2001 and 2014 were enrolled in the study. Clinicopathological and survival data were retrospectively analysed. RESULTS: Forty-six patients underwent resections of both CLM and CPM. Hepatic resection preceded pulmonary resection in most cases (91.3%). The median intervals between the resection of the primary tumour and the hepatic recurrence and between hepatic and pulmonary recurrences were 12 months [0-72] and 21.5 months [1-84], respectively. The mortality rate following CPM resection was 4.3%. After a median follow-up of 41.5 months [0-126], 35 patients recurred of whom 14 (40%) and 11(31.4%) could benefit from repeated resection of recurrent CLM and CPM, respectively. The median and 5-year overall survivals (OS) were 53 months and 49%, respectively. No prognostic factor was identified. CONCLUSION: An aggressive management of CLM and CPM, including repeated resections, may provide a long-term survival comparable to survival of patients with unique metastasectomy. The absence of prognostic factor may reflect the highly selected pattern of the eligible patients.


Assuntos
Neoplasias Colorretais/cirurgia , Hepatectomia/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/cirurgia , Metastasectomia/mortalidade , Pneumonectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/secundário , Pulmão/cirurgia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
4.
Eur Respir J ; 42(5): 1357-64, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23520312

RESUMO

There are no international guidelines for an appropriate and cost-effective follow-up for resected nonsmall cell lung cancer (NSCLC). We retrospectively reviewed the outcome of NSCLC patients after curative surgery. Follow-up included physical examination and chest radiography every 3 months, and chest computed tomography (CT) scan, bronchoscopy, abdominal ultrasound, brain CT scan and bone scan every 6 months for 3 years, then every year over the following 2 years. Prognostic factors and costs were analysed. Median overall survival following surgery for NSCLC in 162 patients was 38.5 months. Recurrence occurred in 85 (52.5%) patients including 41 (48%) symptomatic subjects. Disease-free survival was similar between patients with asymptomatic recurrence versus symptomatic patients (11.4 versus 12 months; p=0.41). Recurrence was detected by physical examination or chest radiography in 47 (55.3%) patients. Curative-intent therapy was provided in 18 (41%) out of 44 patients with asymptomatic recurrence and in four (10%) out of 41 symptomatic cases (p=0.001). Median overall survival from time of recurrence was higher in asymptomatic patients than in symptomatic patients (15.5 versus 7.2 months; p=0.001). The cost per year of life gained was USD32 700 (€22 397). An extensive follow-up, with acceptable cost, may improve the outcome of patients with resected NSCLC through detection of asymptomatic recurrences; however, validation by prospective studies is required.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/economia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Análise Custo-Benefício , Intervalo Livre de Doença , Feminino , Seguimentos , Custos de Cuidados de Saúde , Humanos , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Radiografia Torácica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia
5.
BMC Cancer ; 13: 324, 2013 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-23816056

RESUMO

BACKGROUND: Malignant pleural effusions (MPE) are a common and fatal complication in cancers including lung or breast cancers, or malignant pleural mesothelioma (MPM). MPE animal models and immunotherapy trials in MPM patients previously suggested defects of the cellular immunity in MPE. However only few observational studies of the immune response were done in MPM patients, using questionable control groups (transudate…). METHODS: We compared T cell populations evaluated by flow cytometry from blood and pleural effusion of untreated patients with MPM (n = 58), pleural metastasis of adenocarcinoma (n = 30) or with benign pleural lesions associated with asbestos exposure (n = 23). Blood and pleural fluid were also obtained from healthy subjects, providing normal values for T cell populations. RESULTS: Blood CD4+ or CD8+ T cells percentages were similar in all groups of patients or healthy subjects. Whereas pleural fluid from healthy controls contained mainly CD8+ T cells, benign or malignant pleural effusions included mainly CD4+ T cells. Effector memory T cells were the main T cell subpopulation in pleural fluid from healthy subjects. In contrast, there was a striking and selective recruitment of central memory CD4+ T cells in MPE, but not of effector cells CD8+ T cells or NK cells in the pleural fluid as one would expect in order to obtain an efficient immune response. CONCLUSIONS: Comparing for the first time MPE to pleural fluid from healthy subjects, we found a local defect in recruiting effector CD8+ T cells, which may be involved in the escape of tumor cells from immune response. Further studies are needed to characterize which subtypes of effector CD8+ T cells are involved, opening prospects for cell therapy in MPE and MPM.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Exsudatos e Transudatos/imunologia , Mesotelioma/imunologia , Derrame Pleural Maligno/imunologia , Neoplasias Pleurais/imunologia , Idoso , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Feminino , Citometria de Fluxo , Humanos , Memória Imunológica/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Derrame Pleural/imunologia , Derrame Pleural/patologia , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia
6.
Sci Adv ; 8(45): eadd3854, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36351013

RESUMO

Robust and accurate acceleration tracking remains a challenge in many fields. For geophysics and economic geology, precise gravity mapping requires onboard sensors combined with accurate positioning and navigation systems. Cold atom-based quantum inertial sensors can potentially provide these high-precision instruments. However, current scalar instruments require precise alignment with vector quantities. Here, we present the first hybrid three-axis accelerometer exploiting the quantum advantage to measure the full acceleration vector by combining three orthogonal atom interferometer measurements with a classical navigation-grade accelerometer triad. Its ultralow bias permits tracking the acceleration vector over long time scales, yielding a 50-fold improvement in stability (6 × 10-8 g) over our classical accelerometers. We record the acceleration vector at a high data rate (1 kHz), with absolute magnitude accuracy below 10 µg, and pointing accuracy of 4 µrad. This paves the way toward future strapdown applications with quantum sensors and highlights their potential as future inertial navigation units.

7.
Am J Respir Crit Care Med ; 179(10): 950-4, 2009 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19201924

RESUMO

RATIONALE: Previous data suggested that serum levels of soluble mesothelin (SM) are related to tumor size and may have prognostic significance in malignant pleural mesothelioma (MPM). OBJECTIVES: We tested the hypothesis that this marker could also be useful for monitoring response to treatment. METHODS: Serial measurements of SM were determined in 40 patients diagnosed with MPM and subjected to gene-transfer therapy using intrapleural infusion of an adenoviral vector expressing human IFN-beta or conventional treatment (mainly chemotherapy). MEASUREMENTS AND MAIN RESULTS: In patients with baseline SM levels greater than 1 nM/L and disease progression after therapy, SM levels increased by 2.1 nM/L at two, 5.2 nM/L at four and 1.3 nM/L at 6 months. Patients with initial SM below 1 nM/L had a similar but more moderate increase of SM over time. Patients who responded to treatment or were considered stable had an initial small decrease of SM followed by a return to baseline values after 6 months of follow-up. In patients with baseline SM levels greater than 1 nM/L, increasing levels were associated with a significantly shorter median survival than in patients with stable or decreasing SM levels (4.4 vs. 27.7 months; P = 0.012). CONCLUSIONS: Increasing serum levels of SM were associated with disease progression and worse outcome, whereas stable or decreasing values suggested response to treatment. If confirmed in larger series, SM could be used to monitor patients with malignant pleural mesothelioma under treatment.


Assuntos
Biomarcadores Tumorais/sangue , Mesotelioma/sangue , Neoplasias Pleurais/sangue , Idoso , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/patologia , Feminino , Terapia Genética/métodos , Humanos , Interferon beta/biossíntese , Interferon beta/genética , Masculino , Mesotelioma/genética , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Pleurais/genética , Neoplasias Pleurais/terapia , Prognóstico , Resultado do Tratamento
8.
Ann Endocrinol (Paris) ; 80(1): 21-25, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29555080

RESUMO

The purpose of this study was to analyse the characteristics of 6 patients managed in a university hospital between 1996 and 2016 for non-islet cell tumor hypoglycemia (NICTH), a form of hypoglycaemia due to the paraneoplastic secretion of IGF-2 or its related substances. RESULTS: Three of these 6 patients (50%), aged over 69 years, including 2 with acromegaloid phenotype, presented with a pleural solitary fibrous tumor (SFT), with median diameter 20 cm (interquartile range, 12.5-20.5) with a low median SUV (3.3 g/mL (QR, 2-7.5)) on 18F-FDG PET. The other 3 patients presented respectively neuroendocrine carcinoma (NEC) of the palate (70-year-old woman), retroperitoneal myxofibrosarcoma (66-year-old man) and meningeal hemangiopericytoma (36-year-old woman). All 3 were inoperable and did not respond to any therapy other than glucose solution. Corticosteroid therapy was effective in the 3 SFTs and the NEC. One of the SFTs recurred 10 years later with asymptomatic hypoglycemia, which resolved after reintervention. Median (IQR) blood glucose levels of the 6 patients was 0.4g/L (QR, 0.31-0.41), with hypoinsulinemia at 0.7mIU/L (QR 0.7-2.0), undetectable GH, low IGF-1, normal IGF-2 level in 5/6 cases, a high IGF-2:IGF-1 ratio at 26.9 (QR, 20.8-37.8), hypokalemia and hypomagnesemia. CONCLUSION: NICTH is a rare syndrome, which should be considered in the presence of hypoinsulinemic hypoglycemia with low GH and IGF-1, and a IGF-2:IGF-1 ratio>10. Corticosteroid therapy was effective in elderly subjects, particularly with solitary fibrous tumor, which was generally operable. Hemangiopericytoma and myxofibrosarcoma had poor prognosis in younger patients.


Assuntos
Hipoglicemia/etiologia , Tumores Neuroendócrinos/complicações , Tumor Fibroso Solitário Pleural/complicações , Adulto , Idoso , Glicemia/análise , Feminino , Fibroma , Fibrossarcoma/sangue , Fibrossarcoma/complicações , Hemangiopericitoma/sangue , Hemangiopericitoma/complicações , Hospitais Universitários , Hormônio do Crescimento Humano/sangue , Humanos , Hipoglicemia/sangue , Hipoglicemia/tratamento farmacológico , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II/análise , Magnésio/sangue , Masculino , Neoplasias Meníngeas/sangue , Neoplasias Meníngeas/complicações , Tumores Neuroendócrinos/sangue , Potássio/sangue , Prognóstico , Neoplasias Retroperitoneais/sangue , Neoplasias Retroperitoneais/complicações , Tumor Fibroso Solitário Pleural/sangue
9.
Nat Commun ; 10(1): 1333, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30902996

RESUMO

Malignant pleural mesothelioma (MPM) is recognized as heterogeneous based both on histology and molecular profiling. Histology addresses inter-tumor and intra-tumor heterogeneity in MPM and describes three major types: epithelioid, sarcomatoid and biphasic, a combination of the former two types. Molecular profiling studies have not addressed intra-tumor heterogeneity in MPM to date. Here, we use a deconvolution approach and show that molecular gradients shed new light on the intra-tumor heterogeneity of MPM, leading to a reconsideration of MPM molecular classifications. We show that each tumor can be decomposed as a combination of epithelioid-like and sarcomatoid-like components whose proportions are highly associated with the prognosis. Moreover, we show that this more subtle way of characterizing MPM heterogeneity provides a better understanding of the underlying oncogenic pathways and the related epigenetic regulation and immune and stromal contexts. We discuss the implications of these findings for guiding therapeutic strategies, particularly immunotherapies and targeted therapies.


Assuntos
Heterogeneidade Genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mesotelioma/genética , Mesotelioma/patologia , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Análise por Conglomerados , Epigênese Genética/efeitos dos fármacos , Feminino , Heterogeneidade Genética/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/imunologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/imunologia , Prognóstico , Adulto Jovem
10.
Clin Cancer Res ; 13(10): 2928-35, 2007 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-17504993

RESUMO

PURPOSE: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment. We compared diagnostic and prognostic values of mesothelin and osteopontin in 172 patients suspected of malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic asbestos-exposed subjects. EXPERIMENTAL DESIGN: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos-exposed healthy subjects. Results were correlated with patient's diagnosis and survival. RESULTS: Serum osteopontin level was higher in MPM patients compared with healthy asbestos-exposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients. CONCLUSIONS: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnostic marker. Both molecules have a potential value as prognostic markers.


Assuntos
Glicoproteínas de Membrana/sangue , Mesotelioma/diagnóstico , Osteopontina/sangue , Neoplasias Pleurais/diagnóstico , Idoso , Líquido Extracelular/química , Feminino , Proteínas Ligadas por GPI , Humanos , Masculino , Mesotelina , Mesotelioma/mortalidade , Pessoa de Meia-Idade , Pleura/química , Neoplasias Pleurais/mortalidade , Prognóstico , Análise de Sobrevida
11.
Eur J Cardiothorac Surg ; 52(4): 698-703, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29156014

RESUMO

OBJECTIVES: Adrenal oligometastatic non-small-cell lung cancer is rare, and surgical management remains controversial. METHODS: We performed a multicentre, retrospective study from January 2004 to December 2014. The main objective was to evaluate survival in patients who had undergone adrenalectomy after resection of primary lung cancer. Secondary objectives were to determine prognostic, survival and recurrence factors. RESULTS: Fifty-nine patients were included. Forty-six patients (78%) were men. The median age was 58 years [39-75 years]. Twenty-six cases (44%) showed synchronous presentation, and 33 cases (56%) had a metachronous presentation. The median time to onset of metastasis was 18.3 months [6-105 months]. The 5-year overall survival rate was 59%; the median survival time was 77 months [0.6-123 months]. A recurrence was observed in 70% of the population. Mediastinal lymph node invasion (P = 0.035) is a detrimental prognostic factor of survival. CONCLUSIONS: After exhaustive staging, patients with adrenal oligometastatic non-small-cell lung cancer benefit from bifocal surgery.


Assuntos
Neoplasias das Glândulas Suprarrenais/secundário , Adrenalectomia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias/métodos , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Intervalo Livre de Doença , Feminino , França/epidemiologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências
12.
J Invest Dermatol ; 126(9): 2057-64, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16778803

RESUMO

CCR5 is one of the major inflammatory chemokine receptors with potential therapeutical applications in humans. However, the redundancy of chemokines and their receptors, and the species specificity of chemokine receptor antagonists pose challenges to understanding of the role they play in pharmacological situations. To address this question, we used a humanized severe combined immunodeficient mouse model grafted with human skin and autologous leukocytes, and evaluated the effect of a blocking antibody against human CCR5, on CCL5-induced cutaneous leukocyte recruitment in vivo. At baseline, CCL5 induced a significant recruitment of T cells mainly of the memory phenotype, of monocytes/macrophages, eosinophils, and IFN-gamma(+) but not IL-4(+) and IL-5(+) cells. In vivo, anti-CCR5 antibody was able to almost completely inhibit the recruitment of monocytes/macrophages and T-helper (Th)1-type cells to inhibit partially the attraction of memory T cells, but had no effect on eosinophil infiltration, although all these cell types express other CCL5 binding chemokine receptors than CCR5. These results indicate that the in vivo environment regulates target cell specificity of CCL5 leading to differential cell recruitment, suggesting that antagonizing CCR5 receptor may be of therapeutic value in diseases such as acquired immuno deficiency syndrome, where CCL5/CCR5, monocytes, and Th1-type cells play a predominant role.


Assuntos
Movimento Celular/imunologia , Quimiocinas CC/imunologia , Imunoterapia/métodos , Receptores CCR5/imunologia , Transplante de Pele/imunologia , Células Th1/imunologia , Animais , Anticorpos/farmacologia , Quimiocina CCL5 , Modelos Animais de Doenças , Eosinófilos/citologia , Eosinófilos/imunologia , Humanos , Memória Imunológica , Interferon gama/metabolismo , Macrófagos/citologia , Macrófagos/imunologia , Camundongos , Camundongos SCID , Monócitos/citologia , Monócitos/imunologia , Mutação , Receptores CCR5/genética , Células Th1/citologia , Células Th1/metabolismo , Células Th2/citologia , Células Th2/imunologia , Transplante Heterólogo/imunologia
13.
Chest ; 130(2): 412-8, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16899839

RESUMO

STUDY OBJECTIVES: To determine whether nonoperative management can be applied to iatrogenic postintubation tracheobronchial rupture (TBR). DESIGN: Prospective cohort study. PATIENTS AND INTERVENTIONS: Thirty consecutive patients with TBR complicating intubation between June 1993 and December 2005 entered the study. Patients not receiving mechanical ventilation at time of diagnosis were treated nonsurgically. Patients receiving mechanical ventilation who were judged operable underwent surgical repair, while nonoperable candidates had their TBR bridged by endotracheal tubes. RESULTS: Fifteen patients not requiring mechanical ventilation underwent simple conservative management. TBR length measured 3.85 +/- 1.46 cm (mean +/- SD). Eight TBRs showed full-thickness rupture with frank anterior intraluminal protrusion of the esophagus. In three patients, transient noninvasive positive pressure ventilatory support (NIV) was necessary. All lesions healed without sequelae. Two patients receiving mechanical ventilation underwent surgical repair and died. Thirteen patients receiving mechanical ventilation were considered at high surgical risk, and TBR bridging was attempted as salvage therapy. Complete bridging was achieved in five patients by simply advancing the endotracheal tube distal to the injury. Separate bilateral mainstem endobronchial intubation was necessary in six patients whose TBRs were too close to the carina. Nine of 13 patients (69%) treated with nonoperative therapy completely recovered. CONCLUSION: We conclude that conservative nonoperative therapy should be considered in patients with postintubation TBR who are breathing spontaneously, or when extubation is scheduled within 24 h from the time of diagnosis, or when continued ventilation is required to treat an underlying respiratory status. Surgical repair should be reserved for cases in which NIV or bridging the lesion is technically not feasible.


Assuntos
Brônquios/lesões , Broncopatias/terapia , Drenagem/métodos , Intubação Intratraqueal/efeitos adversos , Toracotomia/métodos , Traqueia/lesões , Doenças da Traqueia/terapia , Adulto , Idoso , Broncopatias/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ruptura , Doenças da Traqueia/etiologia , Resultado do Tratamento
14.
Eur J Cardiothorac Surg ; 29(6): 880-5, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16675257

RESUMO

OBJECTIVE: To investigate on the feasibility, safety, and effectiveness of a new bioabsorbable material for lung staple-line reinforcement. METHODS: This prospective open trial included 66 patients (mean age of 56+/-17 years) who underwent various types of lung resection using staplers with knitted calcium alginate sleeves for buttressing (FOREseal, Laboratoires Brothier, Nanterre, France) at three academic centers: 29 lobectomies, 22 emphysema surgeries, 15 wedge resections or lung biopsies. Intraoperative air leakage was assessed at a mean respiratory peak pressure of 30 cmH2O, and rated as grade 1, 2, or 3. Persistent air leakage in the postoperative course, as well as any relevant event, was assessed daily. The follow-up period was of 6 months. RESULTS: No technical problem linked to the device occurred. Hemostasis of the cutting edges was completed in all patients. Fifty-six percent of the patients had no intraoperative air leak and 27.3% had grade 1 leaks. Mean postoperative air leaks and thoracic drainage times were 1.9+/-2.3 days and 6+/-5.3 days, respectively. In-hospital mortality was nil. There was no empyema. Mean hospital stay was 9.1+/-6.6 days. At follow-up, one patient underwent lung transplantation, and pathology of the explanted specimen showed the absence of device-related foreign-body inflammation. One patient complained from metalloptysis, and another one, with a metastatic invasive aspergillosis, developed an infectious recurrence that required reoperation. CONCLUSIONS: FOREseal is an ergonomic, safe, and promising new material instead of nonabsorbable materials and xenomaterials for staple-line reinforcement. A randomized comparative study is now in progress.


Assuntos
Implantes Absorvíveis , Pneumonectomia/métodos , Grampeamento Cirúrgico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alginatos , Feminino , Seguimentos , Ácido Glucurônico , Hemostasia Cirúrgica , Ácidos Hexurônicos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/instrumentação , Pneumotórax/etiologia , Pneumotórax/prevenção & controle , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida/métodos
15.
Lung Cancer ; 101: 59-67, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27794409

RESUMO

OBJECTIVES: The receptor tyrosine kinase MET is essential to embryonic development and organ regeneration. Its deregulation is associated with tumorigenesis. While MET gene amplification and mutations leading to MET self-activation concern only a few patients, a high MET level has been found in about half of the non-small cell lung cancers (NSCLCs) tested. How this affects MET activation in tumors is unclear. Also uncertain is the prognostic value, in cancer, of a phenomenon well described in cell models: MET shedding, i.e. its cleavage by membrane proteases leading to release of a soluble fragment into the medium. MATERIALS AND METHODS: A prospective cohort of 39 NSCLC patients was constituted at diagnosis or soon after. Normal tissues, tumor tissues, and blood samples were obtained. This allowed, for the same patient, synchronous determination of (i) the MET level in the tumor, (ii) receptor phosphorylation, and (iii) the concentration of soluble MET fragment (sMET) in the serum. RESULTS: After confirming the adequacy of an ELISA for measuring the serum level of sMET, we found no correlation between this level and the concentration of MET in tumors, as evaluated by immunohistochemistry and western blotting. Nevertheless, all but one tumor displaying a high MET level also displayed receptor phosphorylation, restricted to a small number of tumor cells. CONCLUSION: Our results thus demonstrate that the serum level of sMET is not indicative of the amount of MET present in the tumor cells and cannot be used as a biomarker for therapeutic purposes. However, MET scoring of tumor biopsies could be a first step prior to determination of MET receptor activation in high-MET tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-met/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/sangue , Linhagem Celular Tumoral , Feminino , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Fosforilação , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Proteólise , Proteínas Proto-Oncogênicas c-met/sangue
16.
Ann Thorac Surg ; 99(5): 1810-1, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25952216

RESUMO

Tracheal necrosis is a rare life-threatening phenomenon that most often occurs after thyroid operations or prolonged intubation. Conservative treatment can be one choice in extensive tracheal necrosis. We report the case of a 59-year-old man, with tracheal necrosis that developed after pharyngolaryngectomy, that we treated conservatively using hyperbaric oxygen therapy and antibiotic therapy. The follow-up was assured by tracheobronchoscopy. A year after his discharge, the trachea was totally healed.


Assuntos
Laringectomia/efeitos adversos , Faringectomia/efeitos adversos , Traqueia/patologia , Antibacterianos/uso terapêutico , Humanos , Oxigenoterapia Hiperbárica , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/terapia
17.
Ann Thorac Surg ; 99(6): 2237-45, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25912746

RESUMO

In the surgical multimodal management of malignant pleural mesothelioma, it seems crucial to proceed with an efficient local adjuvant treatment to kill residual tumor cells. Intrapleural photodynamic therapy has recently emerged as a potential candidate in this goal. In this review, we analyzed and classified 16 articles in which patients with malignant pleural mesothelioma received intrapleural photodynamic therapy after maximal surgical resection. The toxicity, effect on survival, and development of the technique were assessed. After two decades of clinical studies, intrapleural photodynamic therapy after surgical resection became a safe treatment that significantly improved the survival of patients.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Fotoquimioterapia/tendências , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias Pleurais/tratamento farmacológico , Humanos , Injeções , Mesotelioma Maligno , Fotoquimioterapia/métodos , Cavidade Pleural
19.
Interact Cardiovasc Thorac Surg ; 19(5): 816-23, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25035439

RESUMO

OBJECTIVES: General anaesthesia (GA) carries high risks of ventilator dependency with increased morbidity and mortality in patients with severe respiratory disease. It also presents an ethical dilemma if surgery remains the only treatment option for patients with advanced terminal chronic respiratory disease. Thoracic epidural anaesthesia for awake thoracic surgery (TEATS) in high-risk patients with dyspnoea at rest could avoid ventilator dependency and speed up recovery even in patients with severe dyspnoea. This retrospective observational study analysed indications, management and outcome of patients contraindicated to GA undergoing awake thoracic surgery with thoracic epidural anaesthesia. METHODS: From 716 patients requiring thoracic surgery, nine were contraindicated to GA. Eight patients [American Society of Anesthesiologists (ASA) 4] had a maximum grade four of the modified Medical Research Council dyspnea scale (MMRC). Two patients (ASA 3, grade 1 MMRC and ASA 4, grade 4 MMRC) refused GA. RESULTS: Patients (female : male ratio 1.25 : 1, age 19-76 years) had the following chronic respiratory diseases: pulmonary fibrosis (n = 2), pulmonary metastases (n = 3), chronic obstructive pulmonary disease (n = 1), alveolitis (n = 1) and myopathy (n = 2). Surgical indications were: thoracotomy (n = 6) for pleurectomy to treat recurring pneumothorax (n = 3), pleurostomy (n = 1), emphysema surgery (n = 1), lung biopsy (n = 1) and thoracoscopy (n = 3) for pleural/lung biopsy (n = 2), pneumothorax (n = 1). Lidocaine 20 mg/ml or ropivacaine 7.5 mg/ml was titrated to achieve an anaesthesia level T2-T12. No patient required GA [time of surgery: 46-128 min, mean = 76 min, standard deviation (SD) = 23 min]. Seven patients had light sedation with TCI propofol, remifentanyl or both and remained responsive. Fifty percent of patients received phenylephrine or ephedrine to maintain arterial pressure. Two patients went into hypercapnia, which was reversed with assisted mask ventilation. One patient suffered acute respiratory distress 7 days postoperatively and died of intestinal bleeding on Day 25. There were no postoperative complications in other patients. Excluding Patient 9 always remaining in a medical intensive care unit (ICU), the mean postoperative ICU stay in thoracic surgery was 4.4 days (SD 5.2). Hospital discharge was between 5 and 40 days after surgery. CONCLUSIONS: TEATS with/without sedation was an alternative to GA for thoracotomy/thoracoscopy in severely dyspnoeic patients (MMRC grade 4, ASA 4) without postoperative sequelae.


Assuntos
Anestesia Epidural/métodos , Anestesia Geral , Dispneia/complicações , Doenças Torácicas/cirurgia , Procedimentos Cirúrgicos Torácicos/métodos , Vigília/fisiologia , Adulto , Idoso , Contraindicações , Dispneia/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Doenças Torácicas/complicações , Doenças Torácicas/diagnóstico , Vértebras Torácicas , Resultado do Tratamento , Adulto Jovem
20.
Eur J Cardiothorac Surg ; 45(4): 652-9; discussion 659, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24062351

RESUMO

OBJECTIVES: Nutritional assessment is not included yet as a major recommendation in lung cancer guidelines. The purpose of this study was thus to assess the influence on surgical outcome of the nutritional status of patients with primary lung cancer undergoing lobectomy. METHODS: We queried Epithor, the national clinical database of the French Society of Thoracic and Cardiovascular Surgery, and identified a retrospective cohort of 19 635 patients having undergone lobectomy for a primary lung cancer in the years 2005-11. Their nutritional status was categorized according to the WHO definition: underweight (BMI < 18.5): 857 patients (4.4%), normal (18.5 ≤ BMI < 25): 9391 patients (47.8%), overweight (25 ≤ BMI < 30): 6721 patients (34.2%), obese (BMI ≥ 30): 2666 patients (13.6%). Operative mortality, pulmonary, cardiovascular, infectious and surgical complications rates were collected and analysed for these various BMI groups. RESULTS: In the normal-weight category, operative mortality, pulmonary, surgical, cardiovascular and infectious complications rates were 2.7, 14.6, 13.8, 5.5 and 4.1%, respectively. When compared with that of normal BMI patients, adjusted operative mortality was significantly lower in overweight (2.3%; odd ratio (OR): 0.72 [95% confidence interval (CI): 0.59-0.89]; P = 0.002) and obese patients (1.9%, OR: 0.54 [95% CI: 0.40-0.74]; P < 0.001), and significantly higher in underweight patients (4.1%, OR: 1.89 [95% CI: 1.30-2.75]; P = 0.001). Underweight patients experienced significantly more pulmonary (21.1%; P < 0.001), surgical (23.2%; P < 0.001) and infectious (5.1%; P = 0.05) complications (P < 0.0001). Among surgical complications, prolonged air leaks (17.6%; P < 0.001) and bronchial stump dehiscence (1.5%; P = 0.001) were significantly more frequent in underweight patients than in normal BMI patients. Obesity was not associated with increased incidence of postoperative complications, except for arrhythmia (5.6%; P < 0.05), deep venous thrombosis and pulmonary embolism (1.5%; P = 0.005). Moreover, a statistical protective effect of obesity was observed regarding surgical complications (7.1%; P < 0.001). CONCLUSIONS: Despite having an increased risk of some postoperative cardiovascular complications, obese patients should undergo surgical standard of care therapy for appropriately stage-specific lung cancer. In underweight patients, in addition to preoperative rehabilitation including a nutritional program, attention should be given to aggressive prophylactic respiratory therapy in the perioperative period, and specific intraoperative actions to prevent prolonged air leaks and bronchial stump dehiscence.


Assuntos
Índice de Massa Corporal , Neoplasias Pulmonares/cirurgia , Estado Nutricional , Pneumonectomia/métodos , Idoso , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
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