Philippe Astoul

Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM. To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in ∼10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patients performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.

The French National Mesothelioma Surveillance Program

Objectives: The French National Mesothelioma Surveillance Program (NMSP) was established in 1998 by the National Institute for Health Surveillance (InVS). Its objectives are to estimate the trends in mesothelioma incidence and the proportion attributable to occupational asbestos exposure, to help improve its pathology diagnosis, to assess its compensation as an occupational disease, and to contribute to research. Methods: The NMSP records incident pleural tumours in 21 French districts that cover a population of approximately 16 million people (a quarter of the French population). A standardised procedure of pathological and clinical diagnosis ascertainment is used. Lifetime exposure to asbestos and to other factors (man made mineral fibres, ionising radiation, SV40 virus) is reconstructed, and a case-control study was also conducted. The proportion of mesothelioma compensated as an occupational disease was assessed. Results: Depending on the hypothesis, the estimated number of incident cases in 1998 ranged from 660 to 761 (women: 127 to 146; men: 533 to 615). Among men, the industries with the highest risks of mesothelioma are construction and ship repair, asbestos industry, and manufacture of metal construction materials; the occupations at highest risk are plumbers, pipe-fitters, and sheet-metal workers. The attributable risk fraction for occupational asbestos exposure in men was 83.2% (95% CI 76.8 to 89.6). The initial pathologist’s diagnosis was confirmed in 67% of cases, ruled out in 13%, and left uncertain in the others; for half of the latter, the clinical findings supported a mesothelioma diagnosis. In all, 62% applied for designation of an occupational disease, and 91% of these were receiving workers’ compensation. Conclusions: The NMSP is a large scale epidemiological surveillance system with several original aspects, providing important information to improve the knowledge of malignant pleural mesothelioma, such as monitoring the evolution of its incidence, of high risk occupations and economic sectors, and improving pathology techniques.

ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax

Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research. The European Respiratory Societys Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence. Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach. In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required. A European Task Force reviews scientific evidence and suggests future research for primary spontaneous pneumothorax http://ow.ly/MWhuF

Narrow Band Imaging Applied to Pleuroscopy for the Assessment of Vascular Patterns of the Pleura

Background: Narrow band imaging (NBI), which enhances blood vessels, is a new endoscopic technology for diagnosing malignancies, but it has not been investigated for pleuroscopy. Objectives: To evaluate the efficacy of NBI applied to pleuroscopy for detecting malignant lesions by assessing vascular patterns of the pleura. Methods: From May 2006 to September 2008, 45 patients with undiagnosed pleural ef-fusion underwent pleuroscopy using a pleura-videoscope with white light (WL) and NBI under local anesthesia. For this prospective study, 73 biopsy specimens were obtained from sites where images under both WL and NBI were recorded and classified regarding vascular patterns. Results: Of the 73 lesions, WL showed blood vessels in 32 lesions, and NBI in 52 lesions (WL vs. NBI; p = 0.0014). The accuracy, sensitivity and specificity in the detection of irregular vascular patterns, e.g. blood vessels with irregular caliber or punctate vessels indicating malignant lesions, were 60.3, 76.5 and 55.4% in WL, and 80.8, 85.3 and 76.9% in NBI, respectively, resulting in a significant increase in NBI (p = 0.0106 for accuracy and p = 0.0494 for specificity). For flat lesions, NBI revealed a higher accuracy rate (90.6%) in the detection of irregular vascular patterns indicating malignant lesions. Conclusion: Our study demonstrated that NBI applied to pleuroscopy displayed blood vessels significantly better than WL. NBI was useful to detect irregular vascular patterns suggesting malignant lesions, especially for flat lesions. Therefore, NBI was considered useful in the selection of optimal biopsy sites by assessing vascular patterns.

Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma

Objectives To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. Methods A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. Results A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI −33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. Conclusions Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

Mesothelioma and Asbestos-Related Pleural Diseases

At present, the use of asbestos is not regulated at a worldwide scale. Moreover, there is a latency period between asbestos exposure and the manifestations of asbestos-related diseases. Consequently, pulmonologists are still dealing with consequences of asbestos exposure, which mainly occur at the pleural surface. The aim of this review is to provide an overview of asbestos-related pleural diseases. We summarized the most relevant data for the diagnosis and the management of benign asbestos pleural effusions, pleural plaques, diffuse pleural thickening and rounded atelectasis. Special attention is dedicated to malignant pleural mesothelioma, given the challenging issues of this disease, the recent advances in its management and the dynamism of research in this area.

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

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.

Gefitinib (ZD1839, Iressa®) in non-small-cell lung cancer : a review of clinical trials from a daily practice perspective

Gefitinib (ZD1839) is the most widely studied targeting agent in the area of non‐small‐cell lung cancer (NSCLC). Gefitinib is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor. In order to assess the role of gefitinib in the management of NSCLC patients, we systematically reviewed published clinical trials from a daily practice perspective. A systematic research was made in the international medical literature. Gefitinib demonstrated a good tolerance and an encouraging efficacy in pretreated NSCLC patients in preclinical studies. These results were then confirmed in two phase II trials (IDEAL 1 and 2) involving more than 400 patients mostly pretreated with a platinum‐containing regimen and docetaxel. All these results were reinforced by those of retrospective studies on patients enrolled in a compassionate use programme. Thus, two phase III trials in chemo‐naive patients were initiated (INTACT 1 and 2). Unfortunately, the use of gefitinib with standard combination chemotherapy provided no survival benefit nor response rate or progression‐free survival improvement over placebo. Furthermore, we also reviewed the results of studies interested in the characterization of predictive clinical or biological markers for response to gefitinib and discussed the results obtained with other EGFR inhibitors. The efficacy of gefitinib in the first‐line setting of each stage of NSCLC has to be further studied through clinical trials. Furthermore, translational studies characterizing the molecular features involved in the response to anti‐EGFR‐targeted therapies are needed.

Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005.

The evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980–2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (−3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998–2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980–1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.

Malignant pleural mesothelioma: from the bench to the bedside

Optimal management of malignant pleural mesothelioma (MPM), which is mainly based on patient characteristics and clinical stage, is not clearly defined yet, although detailed, practical guidelines for these patients have been proposed by some scientific societies. Translational research, in the field of this disease, is currently in progress and different molecular oncogenic pathways leading to the growth and progression of MPM have been characterized with recent pharmaceutical developments. However, further in-depth analysis still needs to be done for a more advanced deciphering of the step-by-step process leading from early increased mesothelial cell proliferation to invasive mesothelioma, from which we are expecting the development of definitively effective therapy. Thus, this review is an overview of the recent advances in the biology of MPM and their potential therapeutic applications in the field of MPM diagnosis and treatment.