Intrapleural administration of pemetrexed: a pharmacokinetic study in an animal model.

BACKGROUND: Pemetrexed is a key drug for the treatment of malignant pleural mesothelioma. The intrapleural administration of pemetrexed might increase its efficacy and decrease its toxicity in comparison with intravenous administration. The aim of this study was to assess in an animal model the pharmacokinetics of pemetrexed administered intrapleurally compared with intravenously. METHODS: Thirty Wistar rats were randomly assigned to four groups defined by route (intravenous or intrapleural) and dose (10 or 100 mg/kg) of pemetrexed. After pemetrexed administration, serial plasma pemetrexed concentrations were analyzed by high performance liquid chromatography to determine the maximum plasma concentration (C(max)), the area under the plasma concentration-time curve (AUC), and the total body clearance (CL). RESULTS: The C(max) was significantly lower after intrapleural versus intravenous administration of 10 mg/kg pemetrexed (14.36 microg/ml versus 29.83 microg/ml; p = 0.008) or 100 mg/kg pemetrexed (70.64 microg/ml versus 218.64 microg/ml; p = 0.001). At either dose, the AUC and the CL did not significantly differ according to the route of administration. CONCLUSIONS: While intravenous and intrapleural administration of pemetrexed yielded similar AUC and CL, the intrapleural route yielded a significantly lower C(max). As Cmax is a determinant of pemetrexed toxicity, intrapleural administration might offer a means of widening the effective therapeutic index of the drug by improving tolerability. Future studies are needed to confirm this hypothesis in malignant pleural mesothelioma patients.

Distribution of breath sound images in patients with pneumothoraces compared to healthy subjects. Diagnostic yield of vibration response imaging technology.

BACKGROUND: Vibration response imaging (VRI) is a new technology that provides a radiation-free dynamic lung image from the vibrations produced by airflow. The vibration energy from the respiratory cycle can be quantified for any lung region. This is obtained by integrating the energy profiles from 42 acoustic sensors placed on the patient's back. OBJECTIVE: The aim of this study was to evaluate whether a physician trained in interpreting acoustic images can accurately distinguish between normal and abnormal breath sound distribution in patients with pneumothoraces compared to healthy controls. METHODS: In total, 14 patients with spontaneous or iatrogenic pneumothoraces and 15 healthy volunteers were enrolled in the study. VRI recordings and physical examination were obtained in all cases. Chest radiographs (CXRs) were reviewed in patients with pneumothoraces. Dynamic images recorded during one complete respiratory cycle were analyzed for each subject. RESULTS: The VRI images of patients with pneumothoraces demonstrated a reduction in the vibration response on the affected side which correlated with the CXR. Sensitivity was 100%, specificity was 87% and positive predictive value and negative predictive value were 86 and 100%, respectively. CONCLUSIONS: This study demonstrates that VRI can be safely used to assess patients with pneumothoraces. Moreover, the analysis of breath sound distribution images obtained noninvasively can distinguish between patients with a normal chest examination from those with pneumothoraces.

Redo medical thoracoscopy is feasible in patients with pleural diseases - a series.

Previous pleural endoscopy is considered to be a relative contraindication to further medical thoracoscopy. We reviewed our experience in patients undergoing more than one thoracoscopy irrespective of the primary indication. From January 2001 to December 2006, patient baseline characteristics, endoscopic appearance and technique, volume of pleural fluid and final histological diagnosis were collated in all patients undergoing more than one thoracoscopy. The endpoints were morbidity and mortality related to the procedures, to compare the length of procedure time between pleural endoscopies in individual patients and the degree of difficulty of the second or subsequent thoracoscopic procedure. During this period, 29 patients underwent 'redo' thoracoscopy resulting in a total of 61 procedures (rate of 'redo' thoracoscopy; 9.1%). The mean time between thoracoscopies was 5.3+/-3.8 months. Although pleural adhesions were more common at the time of the subsequent procedure, it did not result in failure to induce a pneumothorax or perform the procedure. There was no difference in the duration of procedure between the primary and subsequent thoracoscopy (P=0.46), as well as no complications directly attributed to the repeat pleural endoscopy. Repeat medical thoracoscopy is technically feasible in patients with pleural disease without an associated increased morbidity and mortality.

Accuracy of pleural biopsy using thoracoscopy for the diagnosis of histologic subtype in patients with malignant pleural mesothelioma.

BACKGROUND: Promising results with trimodality therapy combining surgery, chemotherapy, and radiotherapy have been obtained in the management of patients with malignant pleural mesothelioma (MPM). However, the histologic subtype has to be taken into account because of its influence on prognosis. The aim of the current study was to analyze retrospectively the accuracy, sensitivity, and specificity of preoperative thoracoscopy for diagnosis of the histologic subtype of MPM. METHODS: The histologic reports from all consecutive patients undergoing 'intent-to-treat' surgery from 3 institutions as well as the initial pathologic diagnosis obtained using thoracoscopy were reviewed and compared after institutional review board approval. All cases of MPM were confirmed by a panel of pathologists. RESULTS: Ninety-five patients were included in the current study. Of these 95 patients, 75 underwent extrapleural pneumonectomy, 9 patients underwent pleurectomy/decortication, and 11 patients underwent pleurectomy. Of the 95 patients with a final diagnosis of MPM, 80 (84.2%) were classified as having epithelial and 15 (15.8%) as having biphasic subtype. Among the 87 patients classified as having MPM of epithelial subtype after the initial thoracoscopy, 75 cases (86.2%) were confirmed to be a true histologic diagnosis and 12 cases (13.8%) were found to be of biphasic subtype at final diagnosis. One patient with a biphasic subtype at initial thoracoscopy was found to have MPM of epithelial subtype after surgery. The sensitivity and specificity values of an epithelial subtype diagnosis after thoracoscopy were 94% and 20%, respectively, with a positive predictive value of 86% and a negative predictive value of 37%. Conversely, the sensitivity and specificity values of a biphasic subtype diagnosis after thoracoscopy were 20% and 98%, respectively, with a positive predictive value of 75% and a negative predictive value of 87%. CONCLUSIONS: Pleural biopsy performed using thoracoscopy is considered to be the cornerstone of the diagnosis and pleural staging of MPM. However, this procedure appears to be less efficient in diagnosing the histologic subtype as either epithelial or biphasic.

Video-assisted thoracoscopic management of recurrent primary spontaneous pneumothorax after prior talc pleurodesis: a feasible, safe and efficient treatment option.

OBJECTIVE: To assess the role of video-assisted thoracoscopic surgery (VATS) in the management of a recurrent primary spontaneous pneumothorax after a prior talc pleurodesis. METHODS: From 1996 to 2002, we retrospectively reviewed all patients who were treated for a recurrent primary spontaneous pneumothorax after a previous talc pleurodesis. Data on the talc procedure and the recurrent pneumothorax, delay between both, and operative features were studied. Conversion rate to a thoracotomy and postoperative complications as well as long-term outcome were reported. RESULTS: We collected 39 patients (28 male) with a median age of 25 years (15-41 years). The initial procedure consisted of thoracoscopic talc poudrage in all cases. The median delay between the talc procedure and the recurrence was 23 months [10 days-13 years]. Size of recurrence involved 10-80% of the hemithorax. The VATS procedure was successfully achieved in 27 patients (69%) while 12 required conversion to a thoracotomy. The main cause for conversion was the presence of dense pleural adhesion at the mediastinal part of the pleural cavity. Postoperative morbidity was limited to pleural complications in the VATS group (n=6, 22%). Median follow-up was 26 months [10-38 months]. One patient treated by VATS developed a partial recurrent pneumothorax at 12 months with a favorable outcome without further surgery. CONCLUSIONS: Feasibility, safety and efficacy of VATS for management of recurrent primary spontaneous pneumothorax following thoracoscopic talc poudrage are strongly suggested.

Distribution of calibrated talc after intrapleural administration: an experimental study in rats.

STUDY OBJECTIVE: Many reports have shown that talc is the most effective and least expensive agent for the creation of a pleural symphysis. However, its use still remains controversial due to severe acute respiratory side effects possibly related to the systemic dissemination of talc particles. The purpose of this study was to assess the distribution of calibrated talc after intrapleural administration in rats. MATERIAL AMD METHODS: Thirty-seven Wistar male rats were randomly assigned to undergo pleurodesis by talc slurry (33 rats) or by simple chest tube drainage (control group; 4 rats). Forty milligrams of calibrated talc suspended in 1 mL sterile saline solution was injected into rats in the treated group. The animals were randomly assigned for autopsy at 24 or 72 h after pleural injection. Lungs, parietal pleura, diaphragm, liver, kidneys, spleen, pericardium, brain, and blood were assessed by polarized light for birefringent talc particle detection and counting. RESULTS: No deaths were observed. The autopsies showed no pleurodesis at 24 and 72 h. Despite high doses of talc (extrapolated from the dose of 10 g in a 70-kg adult man), few talc particles were found in the liver of two rats, in the spleen of one rat, and only one particle of talc was observed at the brain surface of the rat studied by scanning electron microscopy. No particles were found in the other organs, in particular in the contralateral lung and blood, contrasting with previously published results using noncalibrated talc particles. CONCLUSIONS: The lack of systemic dispersion of talc particles, with the packaging talc we currently use in our clinical practice, is probably due to the size of the talc particles, which are larger than the other talc preparations. Calibrated talc is required in case of intrapleural administration for pleurodesis to avoid systemic dissemination and potential secondary acute respiratory failures.