Chemical pleurodesis - a review of mechanisms involved in pleural space obliteration.

Chemical pleurodesis is a therapeutic procedure applied to create the symphysis between the parietal and visceral pleura by intrapleural administration of various chemical agents (e.g. talk, tetracycline, iodopovidone, etc.). The two major clinical conditions treated with chemical pleurodesis are recurrent pleural effusion (PE) and recurrent spontaneous pneumothorax. Although the history of chemical pleurodesis began over a century ago, detailed data on the mechanisms of action of sclerosing agents are highly incomplete. The following article aims to present the state of knowledge on this subject.It is believed that mesothelial cells are the main structural axis of pleurodesis. In response to sclerosing agents they secrete a variety of mediators including chemokines such as interleukin 8 (IL-8) and monocyte chemoattractant protein (MCP-1), as well as growth factors - vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and transforming growth factor- ß (TGF-ß). Numerous data suggest that intact mesothelial cells and the above cytokines play a crucial role in the initiation and maintenance of different pathways of pleural inflammation and pleural space obliteration.It seems that the process of pleurodesis is largely nonspecific to the sclerosant and involves the same ultimate pathways including activation of pleural cells, coagulation cascade, fibrin chain formation, fibroblast proliferation and production of collagen and extracellular matrix components. Of these processes, the coagulation cascade with decreased fibrinolytic activity and increased fibrinogenesis probably plays a pivotal role, at least during the early response to sclerosant administration.A better understanding of various pathways involved in pleurodesis may be a prerequisite for more effective and safe use of various sclerosants and for the development of new, perhaps more personalized therapeutic approaches.

Pneumothorax-Time for New Guidelines?

Pneumothorax is a common pathology, but optimal management strategies are not yet defined. There are significant differences in international guidelines and therefore variation in clinical practice.There is increasing interest in pneumothorax research, particularly primary spontaneous pneumothorax (PSP), with evidence of lung abnormalities in this group without clinically apparent lung disease and recently completed clinical trials aiming to optimize management. The most robust evidence base is that of the equivalence of needle aspiration and chest tube insertion for initial management of PSP; although, patients with secondary spontaneous pneumothorax may also benefit. A convincing case for surgical intervention or thoracoscopy and talc poudrage to prevent recurrence at first episode in PSP has yet to be made. Clinicians should be vigilant for PSP being the first manifestation of a systemic disease, and should have a low threshold for onward referral. Time to change guidelines? First, chest tube drainage and hospitalization without recurrence prevention should no longer be standard treatment, as this has no advantage over the less invasive manual aspiration, which moreover can be performed on an outpatient basis in an important number of patients. The results of recent trials in conservative and ambulatory management are eagerly awaited. Second, shared decision-making should become more important with the well-informed patient, who may want to avoid a 1 in 3 recurrence rate and therefore will have the possibility to choose treatment including recurrence prevention even after the first episode of PSP. Third, surgical research should urgently make clear if the current practice of resection of emphysema-like changes is routinely necessary, alongside pleurodesis. Future studies should utilize risk stratification by clinical and radiological parameters (e.g., high-resolution computed tomography scanning and digital air leak monitoring) to predict short- and long-term outcomes, and hence personalize management.

[Transbronchial cryobiopsies: an alternative for surgical lung biopsy]. / Transbronchiale cryobiopsie.

Cryobiopsy is an endobronchial technique to obtain peripheral lung biopsies with the use of a flexible bronchoscopic cryo probe. This technique can be used to diagnose diffuse lung diseases when histological evidence is required. This new technique was used for the first time in 2009 and in 2014 we introduced this new method in the Netherlands at the CWZ in Nijmegen. This piece outlines our experiences with Transbronchial lung cryobiopsy (TBLC).

The optimization of the diagnostic work-up in patients with suspected obstructive lung disease.

BACKGROUND: Pulmonary function testing is a key procedure in the work-up of patients who are suspected of having asthma and chronic obstructive lung disease (COPD). Therein, clinical visits and pulmonary function tests (PFTs) are the major contributors to the overall financial costs.The aim of this study was to assess whether a specific diagnostic test protocol contributes to the optimization of the work-up of patients who are suspected of having asthma and COPD. METHODS: A prospective, single-blind, and randomized controlled study was performed. In the control group (CG), all of the PFTs that were ordered by the lung specialist were carried out. In the experimental group (EG), specific PFTs were selected according to our protocol. The primary end point was the total cost of achieving a final diagnosis. RESULTS: One hundred and seventy-nine patients were included into this study: 86 in the CG and 93 in the EG. The mean number of tests to diagnosis was 3.8 in the CG versus 2.9 in the EG (P < 0.001). The mean number of redundant PFTs before diagnosis was 1.2 in the CG versus 0.08 in the EG (P < 0.001). The number of patients who required an additional outpatient visit to complete diagnosis was higher in the CG in comparison to the EG (P = 0.02). The mean cost of work-up per diagnosis was €227 in the CG versus €181 in the EG (P < 0.001). CONCLUSIONS: In this group of patients with suspected obstructive lung disease, protocol-driven, PFT-based selection is more cost-effective than test selection at the discretion of lung physicians.

Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study.

BACKGROUND: Talc is the most effective chemical pleurodesis agent for patients with malignant pleural effusion. However, concerns have arisen about the safety of intrapleural application of talc, after reports of development of acute respiratory distress syndrome in 1-9% of treated patients. Our aim was to establish whether use of large-particle-size talc is safe in patients with malignant pleural effusion. METHODS: We did a multicentre, open-label, prospective cohort study of 558 patients with malignant pleural effusion who underwent thoracoscopy and talc poudrage with 4 g of calibrated French large-particle talc in 13 European hospitals, and one in South Africa. The primary endpoint was the occurrence of acute respiratory distress syndrome after talc pleurodesis. FINDINGS: No patients developed acute respiratory distress syndrome (frequency 0%, one-sided 95% CI 0-0.54%). 11 (2%) patients died within 30 days. Additionally, seven patients had non-fatal post-thoracoscopy complications (1.2%), including one case of respiratory failure due to unexplained bilateral pneumothorax. INTERPRETATION: Use of large-particle talc for pleurodesis in malignant pleural effusion is safe, and not associated with the development of acute respiratory distress syndrome.

Learning curve of conventional transbronchial needle aspiration in pulmonologists experienced in bronchoscopy.

BACKGROUND: Despite its proven efficacy, transbronchial needle aspiration (TBNA) remains an underutilized technique for sampling enlarged mediastinal lymph nodes in the staging of lung cancer. Previous investigators have reported on TBNA experience, but without mentioning individual learning curves related to lymph node size in pulmonologists experienced in bronchoscopy. OBJECTIVES: The aim of this study was to evaluate the TBNA learning curve in a group of pulmonologists already experienced in bronchoscopy, and to relate their yields to lymph node size and location. METHODS: Data on TBNA yield and related lymph node size were collected retrospectively for five individual pulmonologists. RESULTS: The diagnostic yield of five pulmonologists who started to perform TBNA was evaluated over the first 32 months. TBNA was performed on 138 lymph nodes in 119 patients. The overall diagnostic yield was 77% (range 67-91%). The average diagnostic yield increased from 77% at the start of the learning curve to 82% after 32 months of experience. It was related to lymph node size, but not to lymph node location. The average lymph node size was 22 mm. CONCLUSIONS: Satisfactory results were obtained immediately after introduction of TBNA in the bronchoscopy workup. There is no significant TBNA learning curve. The diagnostic yield was related to lymph node size but not to lymph node location.

A prospective study of the timing and cost-effectiveness of bronchial washing during bronchoscopy for pulmonary malignant tumors.

STUDY OBJECTIVES: The value of obtaining washings during fiberoptic bronchoscopy in the workup of lung cancer is controversial. Moreover, the optimal timing of washing relative to biopsy and brushing is not known. In this study, the diagnostic yields of washings before and after biopsy and brushings were compared. The different diagnostic strategies were assessed in terms of yield and costs. DESIGN: A prospective study performed from 2001 to 2003 in a secondary care medical center. MEASUREMENTS AND RESULTS: Two hundred twenty-one patients underwent flexible bronchoscopy, and the diagnostic yield of washings before biopsy and brushing (strategy I) and after biopsy and brushing (strategy II) specimens were assessed. Using the known probabilities and costs for various bronchoscopic procedures, the expected utility of a number of diagnostic strategies was estimated. Patients (147 men and 74 women) were included in the study in whom a definite cytologic or histologic diagnosis of pulmonary malignancy had been made. The diagnostic yield of strategy I was 72% for visible tumors and 36% for nonvisible tumors. For strategy II, the diagnostic yield was 74% for visible tumors and in 42% for nonvisible tumors. The comparison of strategies I and II for both visible and nonvisible tumors revealed that 176 cases were concordant (80%); in 19 cases (9%) the cytologic analysis of washings in strategy I was positive for malignancy and negative in strategy II. In 26 cases (12%) washings in strategy II were positive and negative in strategy I (p = 0.37). An analysis of the diagnostic yield of both washings in visible tumors and nonvisible tumors showed no significant difference. In 13 patients, a diagnosis of malignancy was established only by washings (6%). Confining the laboratory investigations of washings or brush samples to those cases in which the initial findings of the biopsies are negative (the two-stage procedure) is more cost-effective than examining all biopsy, brushing, and washing specimens. In patients with visible tumors, brushing or washing in addition to biopsy is equally cost-effective; in patients with nonvisible tumors, biopsy combined with washing is the preferred option. CONCLUSIONS: No difference in the diagnostic yield could be demonstrated for washings before or after biopsies and brushings. Although the additional diagnostic yield of washing and brushing during bronchoscopy is relatively low, it is cost-effective to use these procedures in the diagnostic workup of patients who are clinically suspected of having a pulmonary malignancy.

Diagnosing peripheral lung cancer: the additional value of the Ras-association domain family 1A gene methylation and Kirsten rat sarcoma 2 viral oncogene homolog mutation analyses in washings in nondiagnostic bronchoscopy.

BACKGROUND: The diagnostic yield of bronchoscopy in patients with endoscopically nonvisible (peripheral) tumors varies from 40% to 56%. Increasingly, molecular markers in bronchial washings are being investigated to improve the diagnostic yield. The aim of this study was to analyze the diagnostic value of the Ras association domain family 1A gene (RASSF1A) methylation analysis in washings in nondiagnostic bronchoscopy in the analysis of patients with suspected lung cancer who had peripheral tumors. Furthermore, the additional diagnostic value of Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations with RASSF1 methylation was analyzed. METHODS: From a prospectively collected series, 129 patients with lung cancer and 28 control subjects were analyzed retrospectively regarding the methylation status of the promoter region of the RASSF1A gene by quantitative methylation-specific polymerase chain reaction and KRAS point mutations by using the sensitive Point-EXACCT method. RESULTS: A total of 40% of the lung cancer patients had peripheral tumors, and 17 patients had a nondiagnostic bronchoscopy. In these patients, RASSF1A methylation was detected in the washings of four patients (24%), and KRAS mutations were detected in the washings of two patients (12%). In total, 29% of the false-negative or doubtful cytology results were accompanied by RASSF1A methylation or KRAS mutation results that were highly suggestive of malignancy. The proportion of RASSF1A methylation was significantly higher in central and larger tumors. No relevant RASSF1A methylation was detected in control samples. CONCLUSIONS: Our data suggest that the molecular analysis of two biomarkers in nondiagnostic bronchial washings may better guide diagnostic procedures in patients with suspected lung cancer.

Diagnostic value of histology compared with cytology in transbronchial aspiration samples obtained by histology needle.

OBJECTIVE: Results from endoscopic needle aspiration [transbronchial needle aspiration (TBNA), esophageal ultrasound-guided fine needle aspiration, real-time endobronchial ultrasound] mainly rely on cytology. We performed a retrospective study to evaluate the possible advantage of obtaining histologic samples during TBNA in the diagnostic assessment of mediastinal lymph node enlargement. MATERIALS AND METHODS: In a retrospective study 2 pathologists evaluated all TBNAs from patients with mediastinal lymph node enlargement in whom representative histologic and cytologic material was obtained, using only a histology needle. Cytology was reviewed before histology in a randomized, blinded fashion. Afterward, the results were related to the diagnosis made in the actual workup of the patient. RESULTS: A total of 50 TBNAs were reviewed. In 86% (43 of 50), both pathologists made the same diagnosis on both specimens, or a difference in cytology and/or histology specimens did not alter the eventual treatment. In 14% (7 of 50) of all TBNAs, histology revealed a diagnosis according to at least 1 pathologist, which altered patient treatment. CONCLUSIONS: Histologic material can reveal additional diagnostic information compared with sole cytologic examination in 14% of representative TBNA samples in patients with mediastinal lymph node enlargement. A discrepancy between cytologic and histologic TBNA results should prompt further investigation.

Diagnostic yield of transbronchial histology needle aspiration in patients with mediastinal lymph node enlargement.

BACKGROUND: Transbronchial needle aspiration (TBNA) is a safe, minimally invasive technique to assess the mediastinal spread of lung cancer. Excellent results have been published by experts. However, little information is available about the diagnostic yield of TBNA with the histology needle in a non-expert center. OBJECTIVES: The aim of this study is to assess the diagnostic yield of histology TBNA in the workup of suspected lung cancer. METHODS: In a non-university teaching hospital, TBNA data from patients diagnosed with lung cancer between June 1998 and July 2000 were analyzed retrospectively. TBNA had been performed by six different bronchoscopists in patients eligible for surgery with accessible N2 and N3 lymph nodes on computed tomography of the chest during the workup of an undefined mass. Cytology and histology specimens were obtained with the same 19-gauge needle. TBNA results were considered to be diagnostic if cytologic or histologic examination revealed a malignant lesion or non-malignant lymphoid cells. However, TBNA outcome was called non-diagnostic if no representative cells were obtained. RESULTS: From a group of 264 consecutive lung cancer patients, 106 (40%) patients were eligible for TBNA. In 79%, TBNA was diagnostic in cytology and/or histology specimens. Malignancy was demonstrated in 59% (63/106). In only 32/106 patients (30%), a histologic core of tissue could be sampled. In 87.5% of these patients (28/32), TBNA was diagnostic. For cytology only, this number was slightly lower (75%, 56/74). In 12 cases, diagnostic TBNA was verified by mediastinoscopy: these diagnoses were concordant. The sensitivity is 65% if all non-confirmed cases are considered false negative. Ten mediastinoscopies were avoided because TBNA demonstrated contralateral N2 (= N3) disease. The routine use of TBNA during bronchoscopy in suspected N2 disease is a cost-effective procedure, as the total additional costs of TBNA (9,540 EUR) were lower than the costs of 10 avoided mediastinoscopies (15,500 EUR). No complications were observed. CONCLUSION: The diagnostic yield of TBNA relied mainly on cytology specimens, despite the use of a histology needle. Representative histology specimens could only be obtained in 28/106 patients (26%). Since TBNA was performed in a general hospital by different bronchoscopists, this procedure is useful in the workup of lung cancer patients with enlarged lymph nodes.