Evaldo Marchi

Evidence that mesothelial cells regulate the acute inflammatory response in talc pleurodesis

Intrapleural instillation of talc is used to produce pleurodesis in cases of recurrent malignant pleural effusions. The mechanisms by which pleurodesis is produced remain unknown but may involve either injury or activation of the mesothelium. The aim of the current study was to assess the inflammatory response of pleural mesothelial cells to talc in an experimental model in rabbits. A group of 10 rabbits were injected intrapleurally with talc (200 mg·kg-1) and undiluted pleural fluid was collected after 6, 24 or 48 h for measurement of interleukin (IL)-8, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β1. Samples of pleura were studied to assess the inflammatory infiltrate and mesothelial cell viability. The pleural fluid IL-8 concentration peaked at 6 h, whereas VEGF and TGF-β1 concentrations increased steadily over 48 h. Immunohistochemistry for cytokeratin showed a preserved layer of mesothelial cells despite the intense inflammatory pleural reaction. In conclusion, it is proposed that the mesothelial cell, although injured by the talc, may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.

Management of Malignancy-Associated Pleural Effusion

Management of recurrent malignant pleural effusion, a common complication of malignancy, poses a challenge to clinicians. Although almost one century has elapsed since the introduction of the pleurodesis procedure, the ideal approach and best agent are still to be defined. Optimally, pleurodesis should be done at the bedside with a minimally invasive procedure, and suitable agents to achieve pleural symphysis should be inexpensive, available worldwide and free of adverse effects. To date, no substance completely fulfills these requirements.Silver nitrate should be considered for pleurodesis because of its low cost and ease of handling. Although talc has been used most frequently to induce pleurodesis, reports of death due to acute respiratory failure have raised concerns about the safety of this agent. Tetracycline, an effective alternative used in the past, is no longer commercially available. This agent has been substituted with derivatives of tetracycline, such as minocycline and doxycycline with success rates similar to those with tetracycline. Several antineoplastic agents have been injected into the pleural space with the aim of producing pleural symphysis, the most representative of this group being bleomycin.Recent knowledge of the molecular mechanisms involved in pleural inflammation has brought into focus new substances, such as transforming growth factor β and vascular endothelial growth factor, which may be used as pleurodesis agents in the future. Nevertheless, more studies are necessary to better define the potential of these substances in the induction of pleural symphysis.Ideally, a sclerosing agent should be cost-effective, available worldwide and easily administered. Talc will probably stand as the preferred agent to be used for pleurodesis in malignant pleural effusion because of its efficacy, easy manipulation and handling. However, further investigation is necessary to minimize adverse effects related to talc.

Transmediastinal migration of Kirschner wire

The authors describe a case of transmediastinal migration, and lodging into the right lung, of a Kirschner wire used to fix a fracture of the left clavicle. The medical literature reports cases of intrathoracic migration of Kirschner wire; however, a transmediastinal migration has not been previously described. A small right thoracotomy was performed and the wire was removed without complications. We discuss aspects of this uncommon finding and alert physicians for the potential risks of the migration of metallic pins used to fixate boney structures within the chest.

Inflammation and clinical repercussions of pleurodesis induced by intrapleural talc administration

Although reports on pleurodesis date back to the beginning of the 20th century, the search for the ideal sclerosing agent is ongoing. Several agents have been studied and used, but talc continues to be the most popular. However, potentially harmful systemic side effects have been associated with talc pleurodesis. In this article we discuss the likely mechanisms of pleural inflammation and pleurodesis with emphasis on the systemic response due to the instillation of talc into the pleural space.

Improvements in the 6-Min Walk Test and Spirometry Following Thoracentesis for Symptomatic Pleural Effusions

BACKGROUND Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. METHODS Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV(1) were analyzed before and 48 h after the removal of large pleural effusions. RESULTS The mean fluid removed was 1,564 ± 695 mL. After the procedure, values of FVC, FEV(1), and 6-min walk distance increased (P < .001), whereas dyspnea decreased (P < .001). Statistical correlations (P < .001) between 6-min walk distance and FVC (r = 0.725) and between 6-min walk distance and FEV(1) (r = 0.661) were observed. Correlations also were observed between the deltas (prethoracentesis × postthoracentesis) of the 6-min walk test and the percentage of FVC (r = 0.450) and of FEV(1) (r = 0.472) divided by the volume of fluid removed (P < .05). CONCLUSION In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities.

Monoclonal anti-vascular endothelial growth factor antibody reduces fluid volume in an experimental model of inflammatory pleural effusion.

Background and objective:  Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti‐VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation.

Talc pleurodesis: Evidence of systemic Inflammatory response to small size talc particles *

The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles.

Acute inflammatory response secondary to intrapleural administration of two types of talc

Intrapleural instillation of talc has been used in the treatment of recurrent pleural effusions but can, in rare instances, result in respiratory failure. Side-effects seem to be related to composition, size and inflammatory power of talc particles. The aim of this study was to evaluate the inflammatory response to intrapleural injection of talc containing small particles (ST) or talc containing particles of mixed size (MT). 100 rabbits received intrapleural talc, 50 with ST (median 6.41 μm) and 50 with MT (median 21.15 μm); the control group was composed of 35 rabbits. Cells, lactate dehydrogenase, C-reactive protein (CRP), interleukin (IL)-8 and vascular endothelial growth factor were evaluated in serum and bronchoalveolar lavage at 6, 24, 48, 72 and 96 h. Lung histology and the presence of talc were also analysed. Statistics were performed using ANOVA and an unpaired t-test. Most of the parameters showed greater levels in the animals injected with talc than in the controls, suggesting a systemic and pulmonary response. Higher serum levels of CRP and IL-8 were observed in the animals injected with ST. Talc particles were observed in both lungs with no differences between groups. Lung cell infiltrate was more evident in the ST group. In conclusion, talc with larger particles should be the preferred choice in clinical practice in order to induce safer pleurodesis.

Pleurodesis Induced by Talc or Silver Nitrate: Evaluation of Collagen and Elastic Fibers in Pleural Remodeling

This study evaluated the extracellular matrix (collagen and elastic fibers) in pleurodesis induced by intrapleural talc (TL) or silver nitrate (SN). Study subjects were 420 rabbits divided into two groups and sacrificed from 15 min to 12 months after the injection of the sclerosing agents at intervals previously defined. Pleural adhesions and fibrosis were graded (0–4), and the collagen and elastin were quantified. The maximum score of the pleural adhesions was observed two months after TL (2.80 ± 0.99) and 15 days after SN (3.75 ± 0.25). More intense pleural adhesions were observed in the SN group from day 5 (p < 0.05). Pleural thickness and pleural fibrosis were, in general, significantly higher after SN (p < 0.05). Increased deposition of collagen and elastin was observed in both groups but was more evident in the SN group. In the TL group, a linear correlation was observed between pleural adhesions and fibrosis (r = 0.775), between pleural adhesions and collagen (r = 0.779), and between fibrosis and collagen (r = 0.709). In the SN group, these correlations were acceptable (r = 0.605, 0.665, and 0.663). The elastin presented a correlation of 0.707 (p < 0.001) in the TL group and of 0.564 (p < 0.001) in the SN group. In conclusion, intrapleural 0.5% silver nitrate and talc (400 mg/kg) are effective in the induction of pleurodesis. However, the intensity of adhesions and the richness of collagen after SN, in combination with the early onset of tissue remodeling, demonstrate the local superiority of this agent. Considering the easy availability and instillation, the low cost, and the absence of important side effects, silver nitrate might be considered as a sclerosing agent to induce pleurodesis in humans.

Proinflammatory and Antiinflammatory Cytokine Levels in Complicated and Noncomplicated Parapneumonic Pleural Effusions

OBJECTIVES This study aimed to evaluate a panel of proinflammatory and antiinflammatory cytokines in noncomplicated and complicated parapneumonic pleural effusions and to correlate their levels with pleural fluid biochemical parameters. METHODS Serum and pleural effusion were collected from 60 patients with noncomplicated (n = 26) or complicated (n = 34) parapneumonic effusions and assayed for cytologic, biochemical, and proinflammatory and antiinflammatory cytokines. Student t test was used to compare serum and pleural fluid values, Spearman correlation to analyze the relationship between pleural fluid cytokines and biochemical parameters, and accuracy of pleural fluid cytokine levels to determine the optimal cutoff value for identification of complicated effusions. Corrections for multiple comparisons were applied and a P value < .05 was accepted as significant. RESULTS Serum and pleural fluid cytokine levels of IL-8, vascular endothelial growth factor (VEGF), IL-10, and tumor necrosis factor (TNF) soluble receptor (sR) II were similar between groups. In contrast, complicated effusions had higher levels of pleural fluid IL-1β, IL-1 receptor antagonist (ra), and TNF sRI. Negative correlations were found between pleural fluid glucose with IL-1β and TNF sRI and positive correlations between lactic dehydrogenate (LDH) with IL-1β, IL-8, and VEGF. Pleural fluid levels of IL-1β, IL-1ra, and TNF sRI were more accurate than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. CONCLUSIONS Both proinflammatory and antiinflammatory cytokine levels in pleural fluid are elevated in complicated in comparison with noncomplicated parapneumonic pleural effusions, and they correlate with both pleural fluid glucose and LDH levels. IL-1β, IL-1ra, and TNF sRI had higher sensitivity and specificity than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions.