A novel pleural-bladder pump for the management of recurrent malignant pleural effusions: a feasibility animal study.

BACKGROUND: Recurrent malignant pleural effusions (MPE) are common and associated with significant morbidity in cancer patients. A new pump connecting the pleural cavity and the bladder may have application for the management of recurrent MPE. In a pre-clinical study, we investigated the utility of this pump in healthy pigs. METHODS: A novel pump system (Pleurapump® system) was inserted into four pigs under general anaesthesia. A tunnelled-pleural catheter was connected to a subcutaneously implanted pump while the urinary bladder was connected by percutaneous technique. Animals were ventilated mechanically and pump functioning was tested using a range of ventilation parameters and spontaneous breathing. Fluid was added to the pleural space to mimic pleural effusion and to assess the effectiveness of the pump at removing fluid to the bladder. RESULTS: The 'pleurapump' system successfully transported fluid from the pleural cavity to the bladder. Pressure variations caused by respiration and variations in the amount of fluid in the pleural cavity had no impact on the pumping. Pumping stopped when the pleural cavity was drained. CONCLUSION: This pump can be implanted into pigs and successfully removed fluid from the pleural cavity to the bladder and may represent a new treatment for management of recurrent MPE. Evaluation in humans is planned.

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.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

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.

Temporary endobronchial embolization with silicone spigots for moderate hemoptysis: a retrospective study.

BACKGROUND: The management of airway bleeding is generally performed in an emergency to prevent hypoxemia and lung flooding. When the bleeding arises from peripheral lesions that are not visible endoscopically, bronchoscopic options have limited curative intents. Endobronchial embolization using silicone spigots (EESS) is a novel approach. OBJECTIVES: We analyzed the efficacy and safety of EESS in a retrospective study. METHODS: We retrospectively reviewed charts of patients referred to our center for moderate hemoptysis (MH) who underwent EESS. Successful management is defined as immediate bleeding cessation. RESULTS: From December 2008 to January 2012, 9 patients were treated with EESS in our endoscopy unit. The MH originated from the left upper lobe in 4 cases, the right upper lobe in 3 cases and the right middle lobe and left lower lobe in 1 case each. Thirteen spigots were inserted. The success rate was 78%. Of the 9 patients, 7 were referred to interventional radiology for bronchial artery embolization, with a success rate of 86%, and 2 were referred for thoracic surgery. One patient had EESS as definitive treatment; the silicone spigots were bronchoscopically removed after a median of 4 days in 6 of the remaining 8 patients. Only 2 patients had hemoptysis recurrence after a median follow-up of 107 days (ranging from 13 to 1,017 days). None of the patients died from hemoptysis. CONCLUSION: EESS is an original, temporary technique that requires only a flexible bronchoscope and biopsy forceps for placement and removal. EESS ensures airway protection while waiting for definitive management.

Short-term safety of thoracoscopic talc pleurodesis for recurrent primary spontaneous pneumothorax: a prospective European multicentre study.

The safety of talc pleurodesis is under dispute following reports of talc-induced acute respiratory distress syndrome (ARDS) and death. We investigated the safety of large-particle talc for thoracoscopic pleurodesis to prevent recurrence of primary spontaneous pneumothorax (PSP). 418 patients with recurrent PSP were enrolled between 2002 and 2008 in nine centres in Europe and South Africa. The main exclusion criteria were infection, heart disease and coagulation disorders. Serious adverse events (ARDS, death or other) were recorded up to 30 days after the procedure. Oxygen saturation, supplemental oxygen use and temperature were recorded daily at baseline and after thoracoscopic pleurodesis (2 g graded talc). During the 30-day observation period following talc poudrage, no ARDS (95% CI 0.0-0.9%), intensive care unit admission or death were recorded. Seven patients presented with minor complications (1.7%, 95% CI 0.7-3.4%). After pleurodesis, mean body temperature increased by 0.41°C (95% CI 0.33-0.48°C; p<0.001) at day 1 and returned to baseline value at day 5. Pleural drains were removed after day 4 in 80% of patients. Serious adverse events, including ARDS or death, did not occur in this large, multicentre cohort. Thoracoscopic talc poudrage using larger particle talc to prevent recurrence of PSPS can be considered safe.

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.

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 approximately 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. Patient's 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.

Feasibility of short term drainage for diagnostic thoracoscopy.

BACKGROUND AND AIM: Thoracoscopy is a diagnostic tool superior to other available techniques for the assessment of pleural effusions. There are numerous publications that describe the technique in detail but there is very little published on the optimal time of chest drain removal post procedure. Our aim was to retrospectively study all cases of diagnostic thoracoscopy and to ascertain the time of chest drain removal, length of hospital stay and associated complications. METHODS: All patients who underwent thoracoscopy during a 6-year period were identified from a computerised database. Patients who received talc for pleurodesis were excluded as they required longer drainage time. A review of the remaining patients' charts and radiology was performed to ascertain the predefined outcomes. RESULTS: 124 patients had a diagnostic thoracoscopy. The time to chest drain removal was documented as less than four hours, four to 24 hours, 24 to 48 hours and greater than 48 hours in 66 (53.2%), 29 (23.4%), 12 (9.7%) and 17 (13.7%) of patients respectively. The median length of stay for all patients was one day (interquartile range, 1-4 days). There was a statistically significant difference in overall length of hospital stay between the early (<4 hours) and late (>48 hours) chest drain removal groups, p=0.0028. The overall complication rate was 15.9%. There was no statistical difference in complication rates between the two groups. CONCLUSION: This retrospective series demonstrates that early chest drain removal post diagnostic thoracoscopy is possible and safe. This is likely to confer economic benefits.

[Trans-vocal cord prostheses - preliminary experience treating benign laryngotracheal stenosis in adults]. / Sténoses laryngotrachéales bénignes de l'adulte : place des prothèses transcordales. Expérience préliminaire.

INTRODUCTION: Benign laryngotracheal stenosis is a rare pathology with multiple etiologies, the management of which is complex. This is because of the configuration and proximity of the larynx and the difficulty with surgical approaches, which are potentially mutilating, especially for the management of a benign disease. When surgery is challenging, iterative dilatations of the stricture or the fashioning of a definitive tracheotomy are therapeutic alternatives. Advances in rigid bronchoscopy and the evolution of prosthetic silicone material allow a new approach in the management of benign laryngotracheal stenosis, by placing flexible silicone prostheses which cover all the stenosis from the arytenoids to the trachea. This preliminary work aims to evaluate the feasibility, effectiveness, tolerance and complications of the implementation of this type of prosthesis. PATIENTS AND METHODS: This is a retrospective single-centre study which analyzed the records of patients with symptomatic benign laryngotracheal stenosis who underwent placement of a transcordial prosthesis over a period of three years. The prosthesis used, inserted under general anesthesia during a rigid tube interventional bronchoscopy, was either a straight silicone prosthesis or a Montgomery T-tube for those with a pre-existing tracheotomy. RESULTS: Six patients were included. Five are still alive, one patient died from a cause unrelated to the placement of the prosthesis. Four have no tracheostomy and two now have no transcordal prosthesis. The data collected on tolerance found, for three patients, two cases of minor aspiration and one case of transient cough. All patients had whispered voice dysphonia. We did not observe prosthesis migration or obstruction. CONCLUSION: These preliminary results are encouraging. Transcordal prostheses in benign laryngotracheal stenosis have a complementary or alternative role compared to surgery with a palliative or even curative objective.

[Management of a tracheal adenoid cystic medico-surgical carcinoma]. / Prise en charge médico-chirurgicale d'un carcinome adénoïde kystique trachéal : l'union fait la force.

Adenoid cystic carcinoma or cylindroma is a rare tumor of the trachea which arises from mucous secreting cells. Its evolution and growth are slow but it is often fatal in the absence of radical treatment. The latter relies on a surgical sleeve resection of the pathological area, with a tracheo-tracheal anastomosis. Therapeutic bronchoscopy plays a crucial role in the clinical improvement of patients before surgery which will be performed under better conditions. For inoperable patients, radiotherapy has proved its efficacy, unlike conventional chemotherapy. The finding of biomarkers expressed by tumor cells could lead to target therapies. This case report illustrates the efficient combination of therapeutic bronchoscopy and surgery for the treatment of adenoid cystic carcinoma affecting central airways.

[Other thoracic cancers. Malignant pleural mesothelioma: biology and diagnosis]. / Mésothéliome pleural malin: biologie et diagnostic.

Malignant pleural mesothelioma (MPM) is a serious issue worldwide because of its increasing incidence and poor prognosis despite real recent improvements in the disease management. Most of the patients are diagnosed late in the course of the disease when radical treatment is no more an option. Therefore an earlier diagnosis of MPM is needed to significantly increase the survival of patients. Some soluble markers, including soluble mesothelin and osteopontin, have been previously proposed for MPM diagnosis but none has been validated yet. Soluble mesothelin, assessed in blood and in pleural effusion, seems to be the most promising candidate. However, even if it has a good diagnostic and prognostic value, it is quite specific for the epithelioid subtype, the most frequent one of mesothelioma, thus limiting its usefulness in practice. Despite sometimes a good sensitivity, other potential markers as osteopontin are of little interest for MPM diagnosis because of a low specificity. In conclusion, the present data do not justify the use of biology for MPM diagnosis in routine yet but rather suggest a need for a continuing evaluation of soluble mesothelin in clinical studies and the search for other potential tumor markers.

[Blue rubber bleb naevus syndrome involving the pleura]. / Syndrome de Bean (« blue rubber bleb naevus syndrome ¼) avec localisation pleurale.

Bean's syndrome ('blue rubber bleb nevus syndrome') is a rare disease characterized by venous malformations involving various organs. Most often these lesions are localized to the skin and the digestive system. Gastro-intestinal bleeding is the most frequent presentation. Though other organs can be affected, chest localizations are infrequent and pleural localization is exceptional. We report the case of an asbestos-exposed patient with Bean's syndrome with characteristic skin lesions, smoker, hospitalized for the investigation of a hemorrhagic pleural effusion. A medical thoracoscopy revealed pleural lesions similar to the cutaneous lesions and compatible with a pleural localization of the disease. This is the first documented case of this disease involving the pleura. A review of the literature was carried out on account of this clinical case.

[Pleural mesothelioma: impact of the staging for the therapeutic strategy]. / Mésothéliome pleural : conséquences de la stadification sur la stratégie thérapeutique.

Realistic improvement has been recently done for the treatment of malignant pleural mesothelioma. Besides new findings for the epidemiology of the disease, medico-social impact for patients, the knowledge of biological parameters for diagnosis, prognosis and future therapeutic targets as well, the early diagnosis of the disease mainly based on more extended practice of thoracoscopy allows in association with new imaging techniques a careful staging of the disease and consequently new therapeutic implications. Indeed if new balistic assessment of the disease improves the efficacy of radiotherapy and new combined chemotherapy have shown antitumoral responses, surgical strategy takes part in the armamenterium for this disease and combined with others therapeutic modalities seems to be a raisonnable approach despite the lack of prospective, comparative, randomized study and the drawback of current staging. However, the most important point is the multidisciplinary concertation induced by the management of this disease which represents a "model" in thoracic oncology.

[Severe cutaneous toxicity after Pemetrexed as second line treatment for a refractory non small cell lung cancer]. / Toxicité cutanée grave après pemetrexed en traitement de deuxième ligne pour un cancer bronchique.

INTRODUCTION: Pemetrexed is a chemotherapeutic drug with good tolerance, used as first line treatment for malignant pleural mesothelioma in association with cisplatin, and alone as second line treatment in resistant or relapsing non-small cell lung cancer (NSCLC). However, cutaneous toxicity has been described, principally as a rash. Cutaneous toxicity of all grades has been observed in up to 14%, and grade 3 or 4 toxicity in 0.8-1.3% of cases. CASE REPORT: We report the case of an 85 year old man treated for NSCLC presenting 15 days after administration of the second cycle of pemetrexed with cutaneous lesions including erythema, bullae, and desquamation, associated with deterioration in his general condition; a skin reaction corresponding to Lyell's syndrome. Treatment with steroids and gammaglobulins led to local resolution and improvement in his general condition. CONCLUSION: Cutaneous toxicity from pemetrexed should be recognised on account of its potential severity. The appearance of skin lesions is an indication for careful follow-up for evidence of Lyell's syndrome for which intensive management is needed.

[Role of DNA microarrays in the diagnosis of pleural exudates: a feasibility study]. / Apport des puces à ADN dans le diagnostic étiologique des pleurésies: étude de faisabilité

INTRODUCTION: Establishing the cause of exudative pleural effusions is sometimes difficult, especially in the context of possible malignant pleural mesothelioma (MPM). Therefore, the development of new biological tools is necessary. The aim of this study was to determine the feasibility and the diagnostic contribution of genomic analysis of cells contained in pleural fluid, using DNA microarray techniques. METHODS: Patients with pleural effusion requiring diagnostic thoracocentesis were eligible to participate in the study. Five hundred mls of pleural fluid were then collected. RNA was extracted from pleural fluid cells and its integrity was assessed. Gene expression was studied using pangenomic DNA microarrays. RESULTS: Seventeen patients were included (4 MPM, 8 secondary malignant pleurisies, 5 benign pleurisies). Three patients offered fully exploitable samples. Taking into account the results of control experiments, gene expression study from pleural fluid was reproducible. The comparison of samples showed significant differences in gene expression. Samples from 14 patients were not exploitable because of RNA degradation. CONCLUSIONS: Gene expression study of cells from pleural fluid is feasible but remains difficult, essentially in relationship with RNA weakness.

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.

[Clinical types of thoracic cancer. Pleural mesothelioma]. / Formes cliniques des cancers thoraciques. Mésothéliome pleural.

Malignant pleural mesothelioma (MPM) is a rare aggressive tumour, but the worldwide incidence is increasing on account of the extensive use of asbestos in the recent past. This is the principal aetiological factor and evidence of exposure should be sought in every case under investigation. Interest in this disease has increased for several reasons: the increase in incidence in the last twenty years, the heavy exposure of several groups of workers, claims for compensation for industrial disease and other medico-legal aspects, the question of environmental exposure with no threshold and the great media interest in the subject (3 million internet pages devoted to mesothelioma). Medical interest in this disease has evolved from almost total fatalism to a real interest in active management with acceptable surgery, new cytotoxic drugs and effective combinations, biological therapies, new modalities of radiotherapy and, above all, the development of multidisciplinary strategies to set up prospective randomised comparative trials which have been largely absent in this field.

[Hypersensitivity to carboplatin. An effect of generic drugs?]. / Hypersensibilité au carboplatine: un rôle pour les génériques?

INTRODUCTION: Carboplatin is a chemotherapeutic agent used frequently in thoracic medicine on account of its relatively good tolerance. Nevertheless hypersensitivity reactions have been described. CASE REPORTS: We report the cases of 2 patients, treated for undifferentiated bronchial carcinoma and carcinoma of the breast, presenting with hypersensitivity reactions to carboplatin developing after 6 and 8 courses respectively. The first patient presented with an irritant maculo-papular rash and the second with severe hypotension and bronchospasm. Neither of these reactions was fatal. Both of these reactions occurred when generic carboplatin was substituted for the propriety preparation. CONCLUSION: Hypersensitivity reactions to carboplatin should be recognised by respiratory physicians on account of their potential seriousness and their occurrence after several courses of treatment. This takes on particular importance at a time when plans for domiciliary treatment of patients are being considered. In addition a national survey of hypersensitivity to carboplatin should be considered by the regional drug safety centres.