Survivin is a negative prognostic factor in malignant pleural effusion.

BACKGROUND: Survivin is a well-known member of the inhibitor of apoptosis family, and has been related to increased tumour aggressivity, both in tissue and in pleural fluid. OBJECTIVES: In patients with malignant pleural effusion, we sought to investigate the changes in pleural fluid survivin concentrations induced by talc instillation into the pleural space. Those changes were also examined in relation to pleurodesis outcome and patient survival. METHODS: We investigated 84 patients with malignant pleural effusion who underwent talc pleurodesis. Of them, 32 had breast cancer, 25 lung cancer and 27 had mesothelioma. Serial samples of pleural fluid were obtained before thoracoscopy (baseline) and 24 hours thereafter. RESULTS: Survivin levels were successfully quantified in all pleural fluid samples, and they were significantly higher in samples obtained after thoracoscopic talc poudrage compared with baseline (P < .001). Patients with higher pleural fluid survivin levels at baseline had a significantly poorer pleurodesis outcome (P = .004). A 30 pg/mL cut-off for baseline survivin in pleural fluid predicted failure of pleurodesis with a 54% sensitivity and 79% specificity (P = .009). Moreover, median postpleurodesis survival of patients with baseline survivin levels ≥30 pg/mL was 4 months (range: 0.1-38), compared with 13 months (range: 0.1-259) in patients below that cut-off (P < .001). CONCLUSION: Elevated pleural fluid survivin concentrations are useful to predict failure of pleurodesis and are associated with shorter survival in patients with malignant pleural effusion.

Stent-induced tracheal stenosis can be predicted by IL-8 expression in rabbits.

BACKGROUND: Bare metal stents may cause complications like fibrous encapsulation, granulation and tracheal stenosis. We investigated the behaviour of three commercially available stents in vivo (rabbits) and in vitro (coculture of those stents with epithelial and fibroblast cell lines). Also, we investigated whether development of tracheal stenosis could be predicted by any biological marker. MATERIALS AND METHODS: The tracheae of 30 rabbits were implanted with either nitinol stents, with or without paclitaxel elution, or a cobalt-based stent. An additional ten rabbits underwent mock implantation (controls). Serial peripheral venous blood samples were taken throughout the study, and several cytokines measured. Animals were euthanized on day 90, with immediate tracheal endoscopy and lavage performed, then necropsy. RESULTS: Rabbits with cobalt-based stent exhibited more inflammation and the highest stenosis incidence, with reduced survival. Both in vivo and in vitro, this stent induced higher IL-8 levels than nitinol stents. Most important, the presence of stent-induced tracheal stenosis was closely associated to increase in IL-8 expression in blood just 1 day after tracheal stent implantation: a 1·19-fold increase vs. baseline had 83% sensitivity, 83% specificity, 77% positive predictive value, 88% negative predictive value and 83% accuracy to predict development of stenosis. CONCLUSIONS: The cobalt-based stent had the highest incidence of tracheal inflammation and stenosis. On the other hand, the paclitaxel-eluting nitinol stent did not prevent those complications and provoked a marked reaction compared with the bare nitinol stent. Early increase in IL-8 expression in blood after stent implantation could predict development of tracheal stenosis in rabbits.

Stents traqueales metálicos autoexpandibles. Estudio comparativo de 3 tipos diferentes de stents en un modelo animal / Tracheal Self-Expandable Metallic Stents: A Comparative Study of Three Different Stents in a Rabbit Model

Introducción: El objetivo de este estudio es evaluar l8mm frea reactividad traqueal tras la implantación de distintos stents metálicos autoexpandibles (SMAE). Material y métodos: Se utilizaron 40 conejos hembra de raza neozelandesa, que se dividieron en 4 grupos. En 3 grupos se implantaron SMAE: de acero (SA), de nitinol (NiTi) o stents liberadores de nitinol (SLF). El cuarto grupo fue el grupo de control (sin stent). Los stents se implantaron por vía percutánea bajo control fluoroscópico. Los animales se evaluaron mediante tomografía axial computarizada (TAC) multicorte y las tráqueas se extirparon para su estudio anatomopatológico (EAP). Los datos de la TAC y el EAP se analizaron estadísticamente y se correlacionaron. Resultados: El grupo que recibió SLF presentaba la mayor longitud de estenosis (20,51 ± 14,0nte a 5,84 ± 12,43 y 6,57 ± 6,54 mm en los grupos NiTi y SA, día 30; p < 0,05) y el mayor índice de formación de granulomas evidenciados mediante TAC (50% de los casos). El grupo al que se implantaron stents NiTi mostró el menor grado de estenosis (2,86 ± 6,91% frente a 11,28 ± 13,98 y 15,54 ± 25,95% en los grupos SLF y SA; p<0,05). En el estudio AP, el grupo SA presentó reactividad proliferativa intensa en comparación con los otros 2 grupos. En el grupo SLF se observó una respuesta destructiva en el 70% de animales, mientras que el stent NiTi fue el que menos reacción provocó. La TAC resultó ser superior para detectar el engrosamiento (correlación positiva de un 68,9%; p < 0,001) que para la observación de granulomas (n.s.). Conclusiones: El grupo SA desarrolló granulomas y estenosis significativas. El stent NiTi fue el que menos reacción indujo, mientras que el SLN provocó lesiones importantes que podrían estar relacionadas con la dosis de fármaco. Por consiguiente, este tipo de SLF no se recomienda para el tratamiento de la estenosis traqueobronquial

Introduction: The objective of this study was to assess tracheal reactivity after the deployment of different self-expandable metal stents (SEMS). Material and methods: Forty female New Zealand rabbits were divided into four groups. Three groups received three different SEMS: steel (ST), nitinol (NiTi), or nitinol drug-eluting stent (DES); the fourth group was the control group (no stent). Stents were deployed percutaneously under fluoroscopic guidance. Animals were assessed by multi-slice, computed tomography (CT) scans, and tracheas were collected for anatomical pathology (AP) study. Data from CT and AP were statistically analyzed and correlated. Results: The DES group had the longest stenosis (20.51 ± 14.08 mm vs. 5.84 ± 12.43 and 6.57 ± 6.54 mm in NiTi and ST, respectively, day 30; P < .05), and higher granuloma formation on CT (50% of cases). The NiTi group showed the lowest grade of stenosis (2.86 ± 6.91% vs. 11.28 ± 13.98 and 15.54 ± 25.95% in DES and ST, respectively; P<.05). The AP study revealed that the ST group developed intense proliferative reactivity compared to the other groups. In the DES group, a destructive response was observed in 70% of the animals, while the NiTi was the least reactive stent. CT was more effective in detecting wall thickening (positive correlation of 68.9%; P < .001) than granuloma (not significant). Conclusions: The ST group developed granulomas and significant stenosis. NiTi was the least reactive stent, while DES caused significant lesions that may be related to drug dosage. This type of DES stent is therefore not recommended for the treatment of tracheobronchial stenosis

Tracheal Self-Expandable Metallic Stents: A Comparative Study of Three Different Stents in a Rabbit Model.

INTRODUCTION: The objective of this study was to assess tracheal reactivity after the deployment of different self-expandable metal stents (SEMS). MATERIAL AND METHODS: Forty female New Zealand rabbits were divided into four groups. Three groups received three different SEMS: steel (ST), nitinol (NiTi), or nitinol drug-eluting stent (DES); the fourth group was the control group (no stent). Stents were deployed percutaneously under fluoroscopic guidance. Animals were assessed by multi-slice, computed tomography (CT) scans, and tracheas were collected for anatomical pathology (AP) study. Data from CT and AP were statistically analyzed and correlated. RESULTS: The DES group had the longest stenosis (20.51±14.08mm vs. 5.84±12.43 and 6.57±6.54mm in NiTi and ST, respectively, day 30; P<.05), and higher granuloma formation on CT (50% of cases). The NiTi group showed the lowest grade of stenosis (2.86±6.91% vs. 11.28±13.98 and 15.54±25.95% in DES and ST, respectively; P<.05). The AP study revealed that the ST group developed intense proliferative reactivity compared to the other groups. In the DES group, a destructive response was observed in 70% of the animals, while the NiTi was the least reactive stent. CT was more effective in detecting wall thickening (positive correlation of 68.9%; P<.001) than granuloma (not significant). CONCLUSIONS: The ST group developed granulomas and significant stenosis. NiTi was the least reactive stent, while DES caused significant lesions that may be related to drug dosage. This type of DES stent is therefore not recommended for the treatment of tracheobronchial stenosis.

Diagnóstico y tratamiento del mesotelioma pleural maligno / Diagnosis and Treatment of Malignant Pleural Mesothelioma

El diagnóstico del mesotelioma pleural maligno presenta 3 importantes retos: es necesario distinguir entre hiperplasia mesotelial benigna y mesotelioma, entre mesotelioma maligno (con subtipos) y carcinoma metastásico, y también se requiere demostrar la invasión de estructuras vecinas a la pleura. Para aclarar los 2 primeros aspectos hay que basarse en un panel de anticuerpos monoclonales con adecuado estudio inmunohistoquímico -realizado por manos muy expertas- y para el tercero hay que apoyarse en biopsias suficientemente amplias y profundas, y la toracoscopia es la técnica de elección. La biopsia con aguja guiada con técnicas de imagen en tiempo real puede ser de gran ayuda cuando existe marcado engrosamiento nodular difuso y derrame pequeño o ausente. Dadas las dificultades de un diagnóstico precoz, es infrecuente que se consiga un tratamiento curativo mediante cirugía radical (pleuroneumonectomía), por lo que en los últimos años está ganando adeptos la liberación de masa tumoral mediante pleurectomía/decorticación, con asociación de quimio y radioterapia a las técnicas quirúrgicas (terapia multimodal). En los casos en que la cirugía no es factible se plantea la quimioterapia (combinando pemetrexed y compuestos de platino en la mayoría de los casos), con pleurodesis o colocación de un catéter pleural tunelizado si se requiere el control del derrame pleural, y se reserva la radioterapia para el tratamiento del dolor asociado a infiltración de la pared torácica o cualquier otra estructura vecina. En todo caso, es esencial un completo tratamiento de soporte para el control del dolor (que adquiere particular protagonismo en esta neoplasia) en unidades especializadas

There are three major challenges in the diagnosis of malignant pleural mesothelioma: mesothelioma must be distinguished from benign mesothelial hyperplasia; malignant mesothelioma (and its subtypes) must be distinguished from metastatic carcinoma; and invasion of structures adjacent to the pleura must be demonstrated. The basis for clarifying the first two aspects is determination of a panel of monoclonal antibodies with appropriate immunohistochemical evaluation performed by highly qualified experts. Clarification of the third aspect requires sufficiently abundant, deep biopsy material, for which thoracoscopy is the technique of choice. Video-assisted needle biopsy with real-time imaging can be of great assistance when there is diffuse nodal thickening and scant or absent effusion. Given the difficulties of reaching an early diagnosis, cure is not generally achieved with radical surgery (pleuropneumonectomy), so liberation of the tumor mass with pleurectomy/decortication combined with chemo- or radiation therapy (multimodal treatment) has been gaining followers in recent years. In cases in which surgery is not feasible, chemotherapy (a combination of pemetrexed and platinum-derived compounds, in most cases) with pleurodesis or a tunneled pleural drainage catheter, if control of pleural effusion is required, can be considered. Radiation therapy is reserved for treatment of pain associated with infiltration of the chest wall or any other neighboring structure. In any case, comprehensive support treatment for pain control in specialist units is essential: this acquires particular significance in this type of malignancy

Diagnosis and treatment of malignant pleural mesothelioma.

There are three major challenges in the diagnosis of malignant pleural mesothelioma: mesothelioma must be distinguished from benign mesothelial hyperplasia; malignant mesothelioma (and its subtypes) must be distinguished from metastatic carcinoma; and invasion of structures adjacent to the pleura must be demonstrated. The basis for clarifying the first two aspects is determination of a panel of monoclonal antibodies with appropriate immunohistochemical evaluation performed by highly qualified experts. Clarification of the third aspect requires sufficiently abundant, deep biopsy material, for which thoracoscopy is the technique of choice. Video-assisted needle biopsy with real-time imaging can be of great assistance when there is diffuse nodal thickening and scant or absent effusion. Given the difficulties of reaching an early diagnosis, cure is not generally achieved with radical surgery (pleuropneumonectomy), so liberation of the tumor mass with pleurectomy/decortication combined with chemo- or radiation therapy (multimodal treatment) has been gaining followers in recent years. In cases in which surgery is not feasible, chemotherapy (a combination of pemetrexed and platinum-derived compounds, in most cases) with pleurodesis or a tunneled pleural drainage catheter, if control of pleural effusion is required, can be considered. Radiation therapy is reserved for treatment of pain associated with infiltration of the chest wall or any other neighboring structure. In any case, comprehensive support treatment for pain control in specialist units is essential: this acquires particular significance in this type of malignancy.

Normativa sobre el diagnóstico y tratamiento del derrame pleural. Actualización / Recommendations of Diagnosis and Treatment of Pleural Effusion. Update

A pesar de los múltiples avances diagnósticos o terapéuticos de la medicina de los últimos años, el derrame pleural (DP) continúa siendo una de las enfermedades que con frecuencia tiene que abordar el especialista de aparato respiratorio o el cirujano torácico. El presente texto no tiene como objetivo realizar una revisión exhaustiva sobre las enfermedades que pueden producir DP, su diagnóstico o su tratamiento, sino constituir una actualización de los conocimientos publicados en los últimos años. Teniendo en cuenta la vocación eminentemente práctica de esta normativa, se ha concedido más extensión a las enfermedades que presentan una mayor incidencia o prevalencia, aunque no hemos renunciado a un ligero recordatorio de otras menos frecuentes. Entre los mayores avances destacan los conocimientos sobre la utilidad de la ecografía torácica, los fibrinolíticos y los agentes pleurodésicos, o la utilización de nuevas técnicas de drenaje pleural, como los tubos torácicos finos o los catéteres tunelizados. La actualización periódica de las normativas favorece la potencial incorporación de nuevas técnicas en el estudio de la enfermedad pleural

Although during the last few years there have been several important changes in the diagnostic or therapeutic methods, pleural effusion is still one of the diseases that the respiratory specialist have to evaluate frequently. The aim of this paper is to update the knowledge about pleural effusions, rather than to review the causes of pleural diseases exhaustively. These recommendations have a longer extension for the subjects with a direct clinical usefulness, but a slight update of other pleural diseases has been also included. Among the main scientific advantages are included the thoracic ultrasonography, the intrapleural fibrinolytics, the pleurodesis agents, or the new pleural drainages techniques

MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD.

Lung adenocarcinoma and chronic obstructive pulmonary disease (COPD) are pulmonary diseases that share common aetiological factors (tobacco smoking) and probable dysregulated pathways. MicroRNAs (miRNAs) play an essential role in regulating numerous physiological and pathological processes. The purpose of this study was to assess global miRNA expression patterns in patients with COPD and/or adenocarcinoma to elucidate distinct regulatory networks involved in the pathogenesis of these two smoking-related diseases. Expression of 381 miRNAs was quantified by TaqMan Human MicroRNA A Array v2.0 in bronchoalveolar lavage fluid samples from 87 patients classified into four groups: COPD, adenocarcinoma, adenocarcinoma with COPD, and control (neither COPD nor adenocarcinoma). 11 differentially expressed miRNAs were randomly selected for validation in an independent cohort of 40 patients. Distinct miRNA expression profiles were identified and validated for each pathological group, involving 66 differentially expressed miRNAs. Four miRNA clusters (the mir-17-92 cluster and its paralogues, mir-106a-363 and mir-106b-25; and the miR-192-194 cluster) were upregulated in patients with adenocarcinoma and one miRNA cluster (miR-132-212) was upregulated in patients with COPD. These results contribute to unravelling miRNA-controlled networks involved in the pathogenesis of adenocarcinoma and COPD, and provide new tools of potential use as biomarkers for diagnosis and/or therapeutic purposes.

Recommendations of diagnosis and treatment of pleural effusion. Update.

Although during the last few years there have been several important changes in the diagnostic or therapeutic methods, pleural effusion is still one of the diseases that the respiratory specialist have to evaluate frequently. The aim of this paper is to update the knowledge about pleural effusions, rather than to review the causes of pleural diseases exhaustively. These recommendations have a longer extension for the subjects with a direct clinical usefulness, but a slight update of other pleural diseases has been also included. Among the main scientific advantages are included the thoracic ultrasonography, the intrapleural fibrinolytics, the pleurodesis agents, or the new pleural drainages techniques.

Current and future options for the diagnosis of malignant pleural effusion.

INTRODUCTION: Malignant pleural effusion (MPE) is a frequent problem faced by clinicians, but tumor pleural involvement can be seen without effusion. AREAS COVERED: Imaging, pleural fluid analysis, biomarkers for MPE, needle pleural biopsy and thoracoscopy. To prepare this review, we performed a search using keywords: 'diagnosis' + 'malignant' + 'pleural' + 'effusion' (all fields) in PubMed, and found 4106 articles overall (until 16 January 2013, 881 in the last 5 years). EXPERT OPINION: Ultrasound techniques will stay as valuable tools for pleural effusions. Biomarkers in pleural fluid do not currently provide an acceptable yield for MPE. In subjects with past history of asbestos exposure, some serum or plasma markers (soluble mesothelin, fibulin) might help in selecting cases for close follow-up, to detect mesothelioma early. Needle pleural biopsy is justified only if used with image-techniques (ultrasound or CT) guidance, and thoracoscopy is better for both diagnosis and immediate palliative treatment (pleurodesis). Animal models of MPE and 'spheroids' are promising for research involving both pathophysiology and therapy. Considering the possibility of direct pleural delivery of nanotechnology-developed compounds-fit to both diagnosis and therapy purposes ('theranostics')-MPE and mesothelioma in particular are likely to benefit sooner than later from this exciting perspective.

Small particle-size talc is associated with poor outcome and increased inflammation in thoracoscopic pleurodesis.

RATIONALE: Talc is very effective for pleurodesis, but there is concern about complications, especially acute respiratory distress syndrome. OBJECTIVES: It was the aim of this study to investigate if talc with a high concentration of small particles induces greater production of cytokines, and if pleural tumor burden has any influence on the local production and spillover of cytokines to the systemic circulation and eventual complications. METHODS: We investigated 227 consecutive patients with malignant effusion submitted to talc pleurodesis. One hundred and three patients received 'small-particle talc' (ST; containing about 50% particles <10 µm) and 124 received 'large-particle talc' (with <20% particles <10 µm). Serial samples of both pleural fluid and blood were taken before and 3, 24, 48 and 72 h after thoracoscopy. Also, mesothelial cells were stimulated with both types of talc in vitro. MEASUREMENTS AND RESULTS: Interleukin-8, tumor necrosis factor-α, vascular endothelial growth factor, basic fibroblast growth factor and thrombin-antithrombin complex were measured in all samples. Early death (<7 days after talc) occurred in 8 of 103 patients in the ST and in 1 of 124 in the 'large-particle talc' group (p = 0.007). Patients who received ST had significantly higher proinflammatory cytokines in pleural fluid and serum after talc application, and also in supernatants of the in vitro study. Pleural tumor burden correlated positively with proinflammatory cytokines in serum, suggesting that advanced tumor states induce stronger systemic reactions after talc application. CONCLUSIONS: ST provokes a strong inflammatory reaction in both pleural space and serum, which is associated with a higher rate of early deaths observed in patients receiving it.

Determination of inflammatory biomarkers in patients with COPD: a comparison of different assays.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory pulmonary disorder with systemic inflammatory manifestations that are mediated by circulating acute-phase reactants. This study compared an enzyme-linked immunosorbent assay (ELISA) to a nephelometric technique for the measurement of serum C-reactive protein (CRP) and serum amyloid A (SAA) and investigated how the choice of assay influenced the estimation of inflammation in patients with stable COPD. METHODS: CRP and SAA concentrations measured by ELISA and nephelometry in 88 patients with COPD and 45 control subjects were used to evaluate the performance of these methods in a clinical setting. RESULTS: With both assays, the concentrations of CRP and SAA were higher in COPD patients than in controls after adjustment for age and sex. There was a moderate correlation between the values measured by ELISA and those measured by nephelometry (logCRP: r = 0.55, p < 0.001; logSAA: r = 0.40, p < 0.001). However, the concentrations of biomarkers determined by nephelometry were significantly higher than those obtained with ELISA for CRP (mean difference = 2.7 (9.4) mg/L) and SAA (mean difference = 0.31 (14.3) mg/L). CONCLUSION: Although the serum CRP and SAA concentrations measured by ELISA and nephelometry correlated well in COPD patients, the ELISA values tended to be lower for CRP and SAA when compared with nephelometric measurements. International standardization of commercial kits is required before the predictive validity of inflammatory markers for patients with COPD can be effectively assessed in clinical practice.

Mechanisms of pleurodesis.

Pleurodesis aims to obliterate the pleural space by producing extensive adhesion of the visceral and parietal pleura, in order to control relapse of either pleural effusions (mostly malignant) or pneumothorax. A tight and complete apposition between the two pleural layers is a necessary condition to obtain a successful pleurodesis, but--besides this mechanical aspect--there are many biological mechanisms that appear to be common to most of the sclerosing agents currently used. Following intrapleural application of the sclerosing agent, diffuse inflammation, pleural coagulation-fibrinolysis imbalance (favoring the formation of fibrin adhesions), recruitment and subsequent proliferation of fibroblasts, and collagen production are findings in the pleural space. The pleural mesothelial lining is the primary target for the sclerosant and plays a pivotal role in the whole pleurodesis process, including the release of several mediators like interleukin-8, transforming growth factor-ß and basic fibroblast growth factor. When the tumor burden is high, normal mesothelial cells are scarce, and consequently the response to the sclerosing agent is decreased, leading to failure of pleurodesis. Also, the type of tumor in the pleural cavity may also affect the outcome of pleurodesis (diffuse malignant mesothelioma and metastatic lung carcinomas have a poorer response). There is general agreement that talc obtains the best results, and there are also preliminary experimental studies suggesting that it can induce apoptosis in tumor cells and inhibit angiogenesis, thus contributing to a better control of the malignant pleural effusion. There is concern about complications (possibly associated with talc but other agents as well) related to systemic inflammation and possible activation of the coagulation cascade. In order to prevent extrapleural talc dissemination, large-particle talc is recommended. Although it could--to some degree--interfere with the mechanisms leading to pleurodesis and a carefully balanced clinical decision has therefore to be made, prophylactic treatment with subcutaneous heparin is recommended during hospitalization (immediately before and after the pleurodesis procedure).

Management of malignant pleural effusions.

PURPOSE OF REVIEW: Malignant pleural effusions (MPEs) are one of the most common problems faced by clinicians and, since there is no optimum treatment available, they deserve efforts aimed to improve their management. RECENT FINDINGS: We have reviewed the most recent articles regarding treatment of MPE, with special emphasis on pleurodesis and indwelling pleural catheter placement. Although iodopovidone, silver nitrate and doxycycline are useful, talc continues to be the most effective agent available for pleurodesis. Use of calibrated talc with large particle size is now firmly established, in order to prevent complications. Indwelling pleural catheters are gaining general acceptance, and they are currently a valid option for patients with lung entrapment or those who have a previous failed pleurodesis. Advances in translational medicine related to this topic are also described. SUMMARY: The above results may contribute to improve significantly management of patients with malignant pleural effusions, especially those with advanced disease who are not suitable for pleurodesis procedures.

Tumor type influences the effectiveness of pleurodesis in malignant effusions.

Pleurodesis is commonly indicated for symptom relief in patients with malignant pleural effusions. A number of factors may influence pleurodesis outcome, but whether tumor type is one of them is a matter of debate. This study investigates the impact of tumor type on the efficacy of bedside doxycycline and thoracoscopic talc poudrage pleurodesis in order to determine which patients may benefit most from these procedures. A retrospective study of 138 and 450 doxycycline and talc poudrage pleurodesis procedures, respectively, evaluated their overall successes and failures, according to primary tumor types. In addition, a logistic regression model addressed whether the pleurodesis outcome in different tumor types was influenced by or attributable to pleural tumor burden. In the talc group, patients with lung cancer and mesothelioma had significantly lower complete response rates (63 and 61%, respectively) as compared with breast (77%) and other metastatic effusions (74%, p = 0.012). In the doxycycline group, the data followed the same trend in that complete response rates were lower in patients with lung carcinomas (31%) than in those with breast cancer (54%) or metastases from other primary sites (74%, p = 0.001). The regression analysis showed pleural burden and tumor type as independent predictors of pleurodesis failure in the talc group. The tumor type involving the pleural surfaces influences the success of a pleurodesis, regardless of the sclerosing agent used. Malignant effusions due to mesothelioma and lung cancer are particularly prone to a failed procedure.

The use of pleural fluid sCD44v6/std ratio for distinguishing mesothelioma from other pleural malignancies.

OBJECTIVE: Differentiating metastatic adenocarcinoma from malignant pleural mesothelioma is often a challenging task. Spliced forms of CD44, such as exon v6 (CD44v6), have been implicated in tumor metastasis. We examined the diagnostic performance of soluble (s) CD44v6 and CD44 standard (sCD44std) as biomarkers for nonmesothelioma pleural malignancies in a retrospective series. METHODS: The pleural fluid from 161 patients with pleural effusion (33 mesotheliomas, 104 nonmesothelioma malignancies, and 24 benign conditions) was analyzed for sCD44v6 and sCD44std levels using an enzyme-linked immunosorbent assay kit. The ability of sCD44v6 and sCD44std levels and the sCD44v6/std ratio for distinguishing mesothelioma from nonmesothelioma malignancy were examined. RESULTS: Median pleural fluid concentrations of sCD44v6 but not sCD44std were significantly higher in patients with nonmesothelioma malignancy (101.5 ng/mL) than in those with mesothelioma (38 ng/mL, p < 0.0001). Fluids from metastatic squamous cell carcinomas exhibited particularly high sCD44v6 levels (388 ng/mL). A cutoff value of 100 ng/mL had the highest accuracy for distinguishing mesothelioma from nonmesothelioma malignancy (sensitivity 53% and specificity 88%) or metastatic adenocarcinoma (sensitivity 60% and specificity 88%). An sCD44v6/std ratio of more than 0.34 discriminated between adenocarcinoma and mesothelioma with a sensitivity of 60%, a specificity of 93%, a likelihood ratio positive of 9.97, and an area under the curve of 0.87 (95% confidence interval: 0.80-0.94). CONCLUSIONS: The pleural fluid sCD44v6/std ratio may be a new diagnostic marker in the differential diagnosis between primary mesothelioma and other pleural malignancies. Values greater than 0.34 predict nonmesothelioma malignancy and may be a help in determining whether an invasive thoracoscopy is necessary.

Endobronchial administration of tranexamic Acid for controlling pulmonary bleeding: a pilot study.

BACKGROUND: Tranexamic acid (TA) is a synthetic antifibrinolytic substance used for short-term control of bleeding. However, control of pulmonary bleeding with endobronchial administration of TA in more than 2 cases has not been attempted earlier. OBJECTIVE: We tested the feasibility of endobronchial administration of TA for controlling pulmonary bleeding. METHODS: This was a 2-year prospective observational trial of endobronchial TA in consecutive patients presenting with hemoptysis to our bronchoscopy unit. Patients were initially treated according to the recommendations of the Spanish National Guidelines using ice-cold saline and adrenaline. Endobronchial administration of TA was attempted in patients with uncontrolled hemoptysis before proceeding with further interventions (balloon occlusion or embolization). RESULTS: Forty-eight patients (37 male; mean age: 64±13 y) were treated with endobronchial TA. The causes of bleeding were divided into iatrogenic (n=28) and noniatrogenic (n=20). Among patients with noniatrogenic bleeding, malignancies (11 patients) and bronchiectasis (10 patients) were the most frequent causes of hemoptysis. In this patient group, endobronchial TA successfully controlled the bleeding in 11 subjects (39.2%). Nonresponders to endobronchial TA suffered more frequently from bronchiectasis (58.3% vs. 18.8%, P=0.039) and less frequently from malignancies (16.7% vs. 56.3%, P=0.040) as compared with responders. All patients with iatrogenic bleeding were treated successfully with endobronchial TA. No subject in either of the patient groups suffered from thrombotic events or other adverse events related to endobronchial TA administration. CONCLUSIONS: Patients with acute pulmonary bleeding may benefit from endobronchial instillation of TA. Further double-blinded controlled studies are necessary to confirm our results.

High levels of tumor markers in pleural fluid correlate with poor survival in patients with adenocarcinomatous or squamous malignant effusions.

BACKGROUND: The aim of this study was to determine whether several pleural fluid (PF) tumor markers, either alone or in combination, could be used to predict survival time of patients with malignant pleural effusion secondary to adenocarcinoma or squamous cell carcinoma. METHODS: A total of 224 patients with confirmed metastatic pleural malignancies due to adenocarcinoma or squamous cell carcinoma were enrolled. PF tumor markers were determined either by electrochemiluminescence immunoassay (CEA, CA 15-3, CYFRA 21-1) or microparticle enzyme immunoassay (CA 125) technologies. Cutoff points that predicted death during the first month after diagnoses, with a specificity of 60%, were selected for each marker, using receiver operating characteristic analysis. RESULTS: In patients with adenocarcinomatous or squamous malignant effusion, the combination of PF CA 125>or=1000 U/mL and CYFRA 21-1>or=100 ng/mL predicted a lower survival (4 vs. 11.7 months, p=0.03; and 0.3 vs. 8.4 months, p=0.003 respectively). This tumor marker combination remained as an independent predictor of poor outcome when adjusted for age and tumor type. CONCLUSION: High PF tumor marker levels identify a subgroup of patients with a shorter median survival.