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In order to determine the diagnostic and prognostic significance of low pleural glucose and pH levels, we executed a prospective study of these parameters and cytologic yield in 77 cases of malignant pleural effusions diagnosed from 116... more
In order to determine the diagnostic and prognostic significance of low pleural glucose and pH levels, we executed a prospective study of these parameters and cytologic yield in 77 cases of malignant pleural effusions diagnosed from 116 consecutive thoracoscopies. The extension of the neoplasms detected by thoracoscopy as well as the results of our attempts to carry out pleurodesis by talc were also studied. Pleural glucose levels were less than 60 mg/dl in 16 cases, and the cytologic yield was positive in 14 of these cases (87%). The glucose value rose above this level in 61 cases, and the cytology was positive in 30 cases (49%; p less than 0.006). A pH less than 7.30 was encountered in 18 cases and there were positive cytologic findings in 14 of these cases (78%). The pH was above 7.30 in 46 cases, and cytologic studies were positive in 22 cases (48%; p less than 0.03). There were ten cases in which both the glucose and pH levels were low, and the cytology was positive in 9 cases (90%), while there were 40 cases in which both the glucose and pH levels were high and cytologic yields of 20 of these cases were positive (50%; p less than 0.03). The extension of the lesions observed during thoracoscopy showed important differences as far as this related to the glucose levels (p less than 0.005), but this relationship as it concerned pH levels was even more significant (p less than 0.0002). The differences were also highly significant (p less than 0.003) when the glucose and pH were jointly considered.(ABSTRACT TRUNCATED AT 250 WORDS)
Our findings showed that p53 mRNA expression levels are upregulated in epicardial adipose tissue (EAT) from patients with heart failure (HF). This upregulation was also found in myocardium [2]. Our group have described its upregulation in... more
Our findings showed that p53 mRNA expression levels are upregulated in epicardial adipose tissue (EAT) from patients with heart failure (HF). This upregulation was also found in myocardium [2]. Our group have described its upregulation in EAT by sympathetic system. This article is protected by copyright. All rights reserved.
The fear of complications arising from the procedure is often the main quoted reason for the reluctance of many pulmonologists to perform thoracoscopy and for a decline of “medical thoracoscopy” in some countries. In addition there is a... more
The fear of complications arising from the procedure is often the main quoted reason for the reluctance of many pulmonologists to perform thoracoscopy and for a decline of “medical thoracoscopy” in some countries. In addition there is a trend to transfer pleural investigations to the thoracic surgeon in many centres around the world.
Malignant pleural effusion (MPE) is a frequent problem faced by clinicians, but tumor pleural involvement can be seen without effusion. Imaging, pleural fluid analysis, biomarkers for MPE, needle pleural biopsy and thoracoscopy. To... more
Malignant pleural effusion (MPE) is a frequent problem faced by clinicians, but tumor pleural involvement can be seen without effusion. 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). 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.
Epithelial-to-mesenchymal transition EMT is a molecular-cellular process activated during embryonic development and tissue remodelling, by which epithelial cells lose their polarity and cell contacts, acquire the expression of mesenchymal... more
Epithelial-to-mesenchymal transition EMT is a molecular-cellular process activated during embryonic development and tissue remodelling, by which epithelial cells lose their polarity and cell contacts, acquire the expression of mesenchymal markers and manifest a migratory phenotype. The progressive loss of E-cadherin is coupled with expression of non-epithelial cadherins, process known as “cadherin switching”. As tumours often mimic embryonic development, it has been postulated that EMT represents a transient event in carcinomas progession. Malignant Mesothelioma MM could represent an EMT in vivo model, because tumor cells can exhibit epithelial, sarcomatous and biphasic differentiation. Forty five patients with MM were investigated by immunohistochemical expression of cadherins E,N,P,11,p120 catenin,SPARC and caveolin in two tissue microarrays. Protein expression was scored from 0 to 3 in tumour and stroma. Data were correlated with histologic patterns, thoracoscopy findings and survival. E-P cadherins expression was observed in 79,3% of epithelial MM without evidence in mesenchymal component of mixed and sarcomatous types. N-11cadherins were detected in 20,6%, 29.4% and 17.6% of these histotypes,respectively.The mesenchymal markers were detected in 100% of sarcomatous and mixed MM and in a many samples of epithelial group. Immunohistochemical data correlated with metastatic status, multi-focal disease and poor survival, showed, in epithelial MM forms, weak or absent E-Pcadherins expression, while N-11cadherins, mesenchymal markers and P120 catenin were observed. Our results suggest that the aggressiveness of MM,could be explained by the acquisition of a mesenchymal phenotype in the context of EMT
The incidence of malignant pleural effusions has been increasing over the last few decades (mainly due to the absolute increase in several types of cancers, especially those of lung and breast origin) and they account for up to 50% of the... more
The incidence of malignant pleural effusions has been increasing over the last few decades (mainly due to the absolute increase in several types of cancers, especially those of lung and breast origin) and they account for up to 50% of the exudates in many clinical series. Although pleural malignancies are thought to present most frequently with a pleural effusion, several autopsy series, including the current one, found a pleural effusion present in little more than half of the cases of malignant pleural involvement (55% in this series). Thus, many pleural malignancies without effusion might pass unnoticed in clinical practice, especially in metastatic disease. Primary malignancies of the pleura (mesotheliomas) are associated with asbestos exposure in about two-thirds of cases, and they frequently present with chest pain, sometimes associated with a pleural effusion. Benign pleural plaques can coexist with malignant mesothelioma, and this association should be suspected when long-standing plaques change in shape or size over the years, and especially if chest pain develops in a previously asymptomatic patient. Metastatic pleural involvement is much more frequent than mesotheliomas, and its most frequent mechanism is the vascular spreading of tumour cells from distant organs to the lungs, and on to the visceral and parietal pleura. The visceral pleura was involved in up to 87% of the current metastatic cases, whereas the parietal zone in only 47% of the autopsy series. The diagnostic work-up lies in cytology, whose average yield is approximately 50%, and a biopsy technique (either by blind needle biopsy or thoracoscopy) is recommended when the effusion persists, for > 2 weeks, and the first cytology has been negative. Thoracoscopy has the additional advantage of allowing pleurodesis with talc poudrage if clear tumour lesions are found in the pleura. In cases of malignant effusion which are not sensitive to chemotherapy, pleurodesis is the treatment of choice for palliation of symptoms, and talc is the most effective agent. It can be used either in suspension ("slurry") or in dry aerosolized form ("talc poudrage"), but it seems that this last technique achieves the best effects. However, it requires thoracoscopy for a proper application, and this is its main drawback when that technique is not readily available.
As opposed to ‘video-assisted thoracoscopic surgery’ which requires general anesthesia, double-lumen tracheal intubation and single lung ventilation, medical thoracoscopy (or ‘pleuroscopy’) is frequently performed in the respiratory... more
As opposed to ‘video-assisted thoracoscopic surgery’ which requires general anesthesia, double-lumen tracheal intubation and single lung ventilation, medical thoracoscopy (or ‘pleuroscopy’) is frequently performed in the respiratory endoscopy suite using local anesthesia. It can be done by well-trained physicians, either pulmonologists or thoracic surgeons, and its main indication is related to diagnosis and treatment of pleural effusions. Also, pneumothorax can be managed in most cases using medical thoracoscopy. This article focuses in particular on technical aspects of medical thoracoscopy, including the selection and preparation of the patient, the choice of equipment, specific details of the procedure itself, and other technical details aimed at preventing complications.
Pleurodesis is intended to prevent the accumulation of fluid or air in the pleural space by creating symphysis between the visceral and parietal pleura. The main indications for this procedure are malignant effusions and pneumothorax. A... more
Pleurodesis is intended to prevent the accumulation of fluid or air in the pleural space by creating symphysis between the visceral and parietal pleura. The main indications for this procedure are malignant effusions and pneumothorax. A reexpandable lung and reasonably long expected survival are criteria that must be met before pleurodesis is attempted in a patient with malignant pleural effusion. A low pleural fluid pH (less than 7.20) is a good predictor for both the presence of a trapped lung and short expected survival. Talc appears to be the sclerosing agent of choice in cases of cancer, whereas video-assisted thoracic surgery techniques are preferable for the treatment of pneumothorax, especially in young patients. To improve results and prevent complications, application of the right technique is crucial, especially with regard to size of drainage and rate of suction. In addition, recent research suggests that prevention of a systemic activation of coagulation with prophylactic heparin should be taken into account in patients who are undergoing pleurodesis for palliative treatment of malignant effusion.
Realizamos un estudio prospectivo para conocer la evolucion de los defectos de perfusion a los 6 meses tras un tromboembolismo pulmonar (TEP), identificar aquellos factores asociados con su evolucion y evaluar la incidencia de... more
Realizamos un estudio prospectivo para conocer la evolucion de los defectos de perfusion a los 6 meses tras un tromboembolismo pulmonar (TEP), identificar aquellos factores asociados con su evolucion y evaluar la incidencia de recurrencias subclinicas. Se incluyeron a 70 pacientes diagnosticados de TEP. Se practico una gammagrafia pulmonar de perfusion a los 6 meses del episodio agudo de TEP. Los resultados se compararon con los defectos iniciales. Se buscaron relaciones significativas entre los distintos perfiles evolutivos y diferentes factores, tales como la edad, el sexo, el tratamiento anticoagulante y los antecedentes personales. Los defectos gammagraficos persistieron identicos al episodio inicial en 15 de los 70 pacientes (21%), disminuyeron en 37 (53%) y desaparecieron en su totalidad en 16 (23%). Se hallaron nuevos defectos en 2 casos. Existio una relacion significativa entre la evolucion gammagrafica favorable y el cumplimiento del tratamiento anticoagulante (p = 0,0024). Otras relaciones con significacion estadistica fueron el perfil evolutivo favorable y el antecedente de intervencion quirurgica en el episodio agudo (p = 0,004) y el perfil evolutivo desfavorable con el antecedente de enfermedad tromboembolica venosa (ETV) previa (p = 0,004).
To assess the validity of enlarged mediastinal nodes as markers of involvement for staging in non-small cell lung cancer, we studied the records of 167 consecutive patients who underwent thoracotomy for this disease in the last 4 yr in... more
To assess the validity of enlarged mediastinal nodes as markers of involvement for staging in non-small cell lung cancer, we studied the records of 167 consecutive patients who underwent thoracotomy for this disease in the last 4 yr in our center. Careful search for both hilar (N1) and ipsilateral mediastinal nodes (N2) was done in every case. All nodes found at thoracotomy (regardless of their size) were either removed or sampled and then sent to the pathology department for examination. We found enlarged nodes (larger than 10 mm) in 131 of the 167 patients included in the study (72%). Of these patients, 58 had enlarged nodes at the hilar level (presumably N1 disease, 38%), and 73 were considered as presumably N2 at thoracotomy, before pathologic examination (62%). Only 12 of 58 patients with presumably N1 disease had true neoplastic involvement at this level (21%), whereas there was true N2 disease in only 18 of 73 patients with enlarged mediastinal nodes (25%). The positive predictive value for N2 in epidermoid carcinoma was 23%, and it was even lower with adenocarcinoma (18%). We conclude that open surgery with careful sampling is the method of choice for evaluation of mediastinal nodes in non-small cell lung cancer if evidence of malignant involvement cannot be proven histologically before thoracotomy.
Introduction: - Chemical pleurodesis is a therapeutic option for symptomatic patients with MPE and a life expectancy > 2-3 months. Contradictory data exists about prognostic factors associated with survival in these patients. Aim: - To... more
Introduction: - Chemical pleurodesis is a therapeutic option for symptomatic patients with MPE and a life expectancy > 2-3 months. Contradictory data exists about prognostic factors associated with survival in these patients. Aim: - To analyze the variables associated with survival in patients with MPE undergoing TPP. Population and methods: - Prospective and multicenter (11 hospitals in Spain) study of patients with MPE undergoing TPP. Inclusion criteria: > 18 years old, pleural effusion (PE) that required drainage and pleurodesis because of dyspnea, pleural malignancy proved by cytology and/or histology and signed informed consent. Survival was considered since the date of pleurodesis until death or the date of last visit. Variables studied: Age, gender, Karnofsky performance status (KPS), mesothelioma as primary tumor, high risk-non high risk tumor 1 , hematic PE, pleural pH and glucose level. Kaplan-Meier curves (KMC) and log-rank were used to analyze survival. Results: - 324 cases were included. The median survival time was 9.2 months. The KMC of variables that showed statistical difference are shown in Figure 1. Conclusion: - The KPS ≥ 80, pleural pH ≥ 7.20 and pleural glucose level > 60 mg/dl were factors associated with better survival. 1. Heffner J, et al. Pleural fluid pH as a predictor of survival for patients with malignant pleural effusions. Chest. 2000; 117: 79-86.
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... more
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.
Bei einer Pleurodese wird versucht, durch Induktion ausgedehnter Verklebungen zwischen der viszeralen und parietalen Pleura den Pleuraspalt zu verschließen. Auf diese Weise soll Rezidiven eines Pleuraergusses (in den meisten Fällen... more
Bei einer Pleurodese wird versucht, durch Induktion ausgedehnter Verklebungen zwischen der viszeralen und parietalen Pleura den Pleuraspalt zu verschließen. Auf diese Weise soll Rezidiven eines Pleuraergusses (in den meisten Fällen maligne) oder einem Pneumothorax vorgebeugt werden. Die erfolgreiche Pleurodese setzt die dichte und vollständige Apposition der beiden Pleurablätter voraus. Allerdings gibt es - neben diesem mechanischen Aspekt - zahlreiche biologische Mechanismen, die den meisten derzeit verwendeten sklerosierenden Substanzen gemeinsam zu sein scheinen. Nach intrapleuraler Applikation der sklerosierenden Substanz werden im Pleuraspalt eine diffuse Entzündung, ein Ungleichgewicht zwischen Koagulation und Fibrinolyse (zugunsten der Bildung von Fibrinadhäsionen), die Rekrutierung und anschließende Proliferation von Fibroblasten und eine Kollagenbildung beobachtet. Primäre Zielstruktur der sklerosierenden Substanzen ist die Mesothelauskleidung der Pleura, die auch für den gesamten Pleurodese-Prozess eine zentrale Rolle spielt, beispielsweise durch Freisetzung verschiedener Mediatoren wie Interleukin-8, transformierender Wachstumsfaktor-β und basischer Fibroblastenwachstumsfaktor. Bei hoher Tumorlast sind nur noch wenige normale Mesothelzellen vorhanden, so dass die Reaktion auf die sklerosierende Substanz geringer ausfällt, was das Versagen der Pleurodese zur Folge hat. Darüber hinaus kann auch der Tumortyp in der Pleurahöhle den Erfolg der Pleurodese beeinflussen (diffuse maligne Mesotheliome und metastasierte Bronchialkarzinome sind mit einem schlechteren Ansprechen verbunden). Es besteht allgemeines Einvernehmen darüber, dass Talkum die besten Ergebnisse erzielt. Erste experimentelle Studien weisen darüber hinaus darauf hin, dass Talkum eine Apoptose in Tumorzellen induzieren und die Angiogenese hemmen kann und auch dadurch zu einer besseren Kontrolle maligner Pleuraergüsse beiträgt. Bedenken bestehen hinsichtlich von Komplikationen (möglicherweise bei Talkum, aber auch bei anderen Substanzen) im Zusammenhang mit systemischen Entzündungsprozessen und einer möglichen Aktivierung der Gerinnungskaskade. Um eine extrapleurale Verteilung des Talkums zu verhindern, wird grobkörniger Talkumpuder empfohlen. Darüber hinaus wird während des stationären Aufenthalts (unmittelbar vor und nach dem Pleurodese-Eingriff ) die prophylaktische Gabe von subkutanem Heparin empfohlen, auch wenn dies - in einem gewissen Maß - die zur Pleurodese führenden Mechanismen beeinträchtigen könnte, weswegen eine sorgfältige klinische Abwägung erforderlich ist.
... 1-1/1, Seleccionar todos Título: ¿Cuándo y cómo drenar un derrame pleural? Autores: Porcel, JM; Rodríguez Panadero, F. Revista: Medicina clínica, 2002; 118(7) Página(s): 265-267 ISSN: 00257753. © UCM 2010, Biblioteca de la Universidad... more
... 1-1/1, Seleccionar todos Título: ¿Cuándo y cómo drenar un derrame pleural? Autores: Porcel, JM; Rodríguez Panadero, F. Revista: Medicina clínica, 2002; 118(7) Página(s): 265-267 ISSN: 00257753. © UCM 2010, Biblioteca de la Universidad Complutense. ...
Diffuse pleural inflammation and fibrin deposition following the instillation of the sclerosing agent is considered necessary for a successful pleural symphysis. We hypothesized that an impairment in fibrin formation or an increased... more
Diffuse pleural inflammation and fibrin deposition following the instillation of the sclerosing agent is considered necessary for a successful pleural symphysis. We hypothesized that an impairment in fibrin formation or an increased endopleural fibrinolysis would lead to failure of pleurodesis. To investigate changes in the pleural coagulation/fibrinolysis balance, we studied 75 consecutive patients who underwent thoracoscopy. Fifty-four of these patients with malignant pleural effusions and four with a benign recurrent effusion underwent thoracoscopic talc pleurodesis. Another four patients with malignancy and 13 with benign effusions had no talc poudrage performed and were included as a control group. Serial determinations of thrombin-antithrombin III complex (TAT), plasminogen activator inhibitor (PAI), and D-dimer were made in pleural fluid samples taken at the beginning of thoracoscopy (baseline), immediately after thoracoscopic biopsies had been done (postbiopsy), 3 h after thoracoscopy--either with talc poudrage or without--and 24 and 48 h after the procedure, as well as in cases of recurrence of effusions (farline). Successful pleurodesis was obtained in 42 of 52 patients who could be evaluated (81%), and failure was seen in 10. Strong activation of coagulation and production of PAI was observed in all groups, including the control (no talc) group. Fibrinolytic activity (as expressed by D-dimer levels) showed a clear decline 24 h after talc poudrage in patients with a good outcome of pleurodesis, as oppossed to those with bad results and to the control group, and returned to the baseline by 15 d. We conclude that increased pleural fibrinolytic activity is associated with failure of pleurodesis, despite significant inhibitory activity of PAI in all groups.

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