Povidon-iodine applied for the treatment of chylothorax in children

Introduction. The aim of this study is to demonstrate the experience of non-surgical treatment of congenital and acquired chylothorax in children using povidone-iodine.Material and methods. The study presents results of treatment of 10 patients with chylothorax who had chemical pleurodesis with povidone-iodine. The study covered a time period from 2016 to 2020. The congenital character of the disease was registered in 2 patients, the acquired one - in 8 patients. The main indication for surgery was ineffective conservative therapy, including the withdrawal of feeding and the administration of preparation Octreotide. The procedure consisted of intrapleural injection of 4% povidone-iodine solution into the pleural cavity with the calculated dose of 1 ml/kg and solution exposure for 4 hours. Results. The interpleural administration of povidone-iodine was effective in all patients. Complications of chemical pleurodesis were observed in 2 patients and were associated with pulmonary edema on the injection side. Lymph outflow was stopped on average in 4 days. There was one adverse episode which developed because of the lung malformation incompatible with life. Conclusions. Intrapleural administration of povidone-iodine is an effective treatment of chylothorax in children.

Study protocol of a phase 1 clinical trial establishing the safety of intrapleural administration of liposomal curcumin: curcumin as a palliative treatment for malignant pleural effusion (IPAL-MPE)

IntroductionThis is a phase 1, open-label, single-centre, uncontrolled, dose-escalation study to evaluate the feasibility, tolerability and pharmacokinetic profiles of a single dose of liposomal curcumin, administered via an existing tunnelled indwelling pleural catheter (TIPC) directly to the tumour site in individuals with diagnoses of malignant pleural effusion. Primarily, we aim to determine a maximum tolerated dose of liposomal curcumin administered via this method.Methods and analysisWe will use a 3+3 expanded cohort for predefined dose-escalation levels or until a predefined number of dose-limiting toxicities are reached. Participants will be administered a single dose of liposomal curcumin (LipoCurc, SignPath Pharma) via their existing TIPC as a sequential enrolling case series with the following dose cohorts: 100, 200 and 300 mg/m2. Primary endpoints are determination of the maximum tolerated dose within the predetermined dose range, and determination of the feasibility of intrapleural administration of liposomal curcumin via an existing TIPC. Secondary endpoints include determination of the safety and tolerability of intrapleural administration of liposomal curcumin, median overall survival, effects on quality of life and on feelings of breathlessness, and the pharmacokinetics and concentrations of curcumin from the plasma and the pleural fluid. Important inclusion criteria include age ≥18 years, an existing TIPC, a pleural biopsy or pleural fluid cytology-proven diagnosis of malignant pleural effusion and for whom no antitumour therapy of proven benefit is available or has been previously declined, eastern cooperative group performance status <2.Ethics and disseminationThe study protocol has been approved by the Southern Adelaide Local Health Network Human Research Ethics Committee (HREC) (approval number: HREC/20/SAC/11). Study results will be published in peer-reviewed journals, and presented at conferences, in field of medical oncology and respiratory medicine.Trial registration numberACTRN12620001216909.Protocol version numberV.1.0.

Thoracoscopy and chemical pleurodesis in treatment of pancreatogenic pleural effusion

Objective. To determine the opportunities of thoracoscopy and the effectiveness of induction of chemical pleurodesis by intrapleural administration of drugs for pancreatogenic pleurisy. Material and methods. We analyzed the results of surgical treatment of 17 patients with acute pancreatitis and 14 with pancreatic cysts after necrosis complicated by pancreatogenic pleural effusions, accounting for 3,7 % of all effusions. Results. Mild and moderate pleurisy was successfully suppressed in 4 cases (12.9 %) by pleural punctures. Six patients (19.4 %) with pancreatic necrosis and huge pleural effusion in case of severe conditions underwent pleural drainage. In 20 cases (64.5 %), fragmented pleurisy was treated using thoracoscopy. Pleurodesis was performed by means of insufflation of talcum powder in five cases that permitted to reduce the drainage time from 7.14 2.96 days without pleurodesis to 4.2 1.1 days (p = 0.026). Pleurodesis using application of trichloroacetic acid had no effect in three patients. Five patients received 200300 g of octreotide diluted with 40 ml of isotonic sodium chloride solution into the pleural cavity through the drainage. The drainage period reduced to 3.5 1.0 days (p = 0.018). The effect was maximally expressed in the cases with high amylase level in the pleural exudate. After that, 20 patients underwent various operations on the pancreas. Conclusions. Thoracoscopy is indicated to patients with pancreatogenic pleurisy for removal of fragments and sanation of the pleural cavity. Intraoperative pleurodesis with talcum effectively suppresses pleurisy and reduces the drainage period while application of trichloroacetic acid has no essential influence. Intrapleural administration of octreotide allows rapid reducing exudation when amylase index is high. Our study supports the effectiveness of mini-invasive procedures (videothoracoscopy combined with talcum powder pleurodesis and intrapleural administration of octreotide) to sanitize the pleural cavity, suppress pleurisy and shorten drainage periods.

Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural delivery in pleural infection patients

BackgroundPleural infection (PI) is a major global disease with an increasing incidence, and pleural fluid (PF) drainage is essential for the successful treatment. The MIST2 study demonstrated that intrapleural administration of tissue plasminogen activator (t-PA) and DNase, or t-PA alone increased the volume of drained PF. Mouse model studies have suggested that the volume increase is due to the interaction of the pleura with the t-PA via the monocyte chemoattractant protein 1 (MCP-1) pathway. We designed a study to determine the time frame of drained PF volume induction on intrapleural delivery of t-PA±DNase in humans, and to test the hypothesis that the induction is mediated by the MCP-1 pathway.MethodsData and samples from the MIST2 study were used (210 PI patients randomised to receive for 3 days either: t-PA and DNase, t-PA and placebo, DNase and placebo or double placebo). PF MCP-1 levels were measured by ELISA. One-way and two-way analysis of variance (ANOVA) with Tukey’s post hoc tests were used to estimate statistical significance. Pearson’s correlation coefficient was used to assess linear correlation.ResultsIntrapleural administration of t-PA±DNase stimulated a statistically significant rise in the volume of drained PF during the treatment period (days 1–3). No significant difference was detected between any groups during the post-treatment period (days 5–7). Intrapleural administration of t-PA increased MCP-1 PF levels during treatment; however, no statistically significant difference was detected between patients who received t-PA and those who did not. PF MCP-1 expression was not correlated to the drug given nor the volume of drained PF.ConclusionsWe conclude that the PF volume drainage increment seen with the administration of t-PA does not appear to act solely via activation of the MCP-1 pathway.

Fibrin turnover and pleural organization: bench to bedside

Recent studies have shed new light on the role of the fibrinolytic system in the pathogenesis of pleural organization, including the mechanisms by which the system regulates mesenchymal transition of mesothelial cells and how that process affects outcomes of pleural injury. The key contribution of plasminogen activator inhibitor-1 to the outcomes of pleural injury is now better understood as is its role in the regulation of intrapleural fibrinolytic therapy. In addition, the mechanisms by which fibrinolysins are processed after intrapleural administration have now been elucidated, informing new candidate diagnostics and therapeutics for pleural loculation and failed drainage. The emergence of new potential interventional targets offers the potential for the development of new and more effective therapeutic candidates.