[The role of endoscopy in the management of peripheral pulmonary nodules, part 2: Treatment]. / Place de l'endoscopie dans la gestion des nodules pulmonaires périphériques, partie 2 : traitement.

The management of peripheral lung nodules is challenging, requiring specialized skills and sophisticated technologies. The diagnosis now appears accessible to advanced endoscopy (see Part 1), which can also guide treatment of these nodules; this second part provides an overview of endoscopy techniques that can enhance surgical treatment through preoperative marking, and stereotactic radiotherapy treatment through fiduciary marker placement. Finally, we will discuss how, in the near future, these advanced endoscopic techniques will help to implement ablation strategy.

[Advanced bronchoscopic techniques for the diagnosis of peripheral lung nodule]. / Place de l'endoscopie dans les gestions des nodules périphériques. Partie 1 : diagnostic.

The endoscopic diagnosis of peripheral lung nodules is a challenging aspect of oncological practice. More often than not inaccessible by traditional endoscopy, these nodules necessitate multiple imagery tests, as well as diagnostic surgery for benign lesions. Even though transthoracic ultrasonography has a high diagnostic yield, a sizeable complication rate renders it suboptimal. Over recent years, a number of safe and accurate navigational bronchoscopic procedures have been developed. In this first part, we provide an overview of the bronchoscopic techniques currently applied for the excision and diagnostic analysis of peripheral lung nodules; emphasis is laid on electromagnetic navigation bronchoscopy and the association of virtual bronchoscopy planner with radial endobronchial ultrasound. We conclude by considering recent innovations, notably robotic bronchoscopy.

RADIORYTHMIC: Phase III, Opened, Randomized Study of Postoperative Radiotherapy Versus Surveillance in Stage IIb/III of Masaoka Koga Thymoma after Complete Surgical Resection.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway. PATIENTS AND METHODS: Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers. RESULTS: The first patient will be enrolled in January 2021, with results expected in 2028.

Self-expanding metallic Y-stent compared to silicone Y-stent for malignant lesions of the main carina: A single center retrospective study.

BACKGROUND: Bifurcation stents are often required in patients with malignant airway obstruction or fistulization involving the main carina. The silicone Y stent is the most used but remains challenging to place. The self-expanding metallic Y (SEM) stent appears easy to use. The objective is to report the feasibility, efficacy, and tolerance of SEM Y stent compared to silicone Y stent in patients with malignant tumors involving the main carina. PATIENTS AND METHODS: This retrospective single center study was performed between May 2004 and May 2017. All patients with malignant carina involvement treated with a bronchial Y stent were included. RESULTS: Forty silicone Y stents and 38 SEM Y stents were placed. Seven stenting placements failed in the silicone Y group but none in the SEM Y stent group (P=0.008). The median duration of the procedure was 80min (25-210) in the silicone Y group and.50min (25-110min) in the SEM Y group (P=0.001). There was no significant difference in terms of early or late complications between the 2 groups. Nine silicone Y stents (26.5%) and 7 SEM Y stents (18.4%) were removed (P=0.4). The median survival time following stent insertion was 171 days (Interquartile range (IQR): 53-379) in the silicone Y group and 104 days (IQR: 53-230) in the SEM Y group. CONCLUSION: If silicone Y stent remains the best solution for benign obstruction, SEM Y stent seems to be an easy alternative with no difference in terms of complication or ablation for malignant lesions involving the main carina.

Crizotinib-induced osteitis mimicking bone metastasis in a stage IV ALK-rearranged NSCLC patient: a case report.

BACKGROUND: Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. CASE PRESENTATION: A 31-year-old woman with stage IV ALK-rearranged NSCLC presented with back pain after 3 months of crizotinib treatment. Diagnostic work-up showed osteitis on the 4th and 5th thoracic vertebrae, anterior soft tissue infiltration and epiduritis, without any sign of infection. Spinal cord decompression, histological removal and osteosynthesis were performed. Histologic examination showed necrosis with abundant peripheral neutrophils, no microorganism nor malignant cell. Symptoms and Computarized Tomography-abnormalities rapidly diseappeared after crizotinib withdrawal and did not recur after ceritinib onset. CONCLUSIONS: This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression.

Does training respiratory physicians in clinical respiratory physiology and interpretation of pulmonary function tests improve core knowledge?

Lung function tests have a major role in respiratory medicine. Training in lung function tests is variable within the European Union. In this study, we have shown that an internship in a lung function tests laboratory significantly improved the technical and diagnostic skills of French respiratory trainees.

A Novel Method for In Vivo Imaging of Solitary Lung Nodules Using Navigational Bronchoscopy and Confocal Laser Microendoscopy.

Solitary pulmonary nodules (SPN) have become increasingly prevalent and diagnostic management remains challenging. We demonstrate a novel technique in which probe-based confocal endomicroscopy (pCLE) could be performed to microimage SPN in vivo and in real-time. Two confocal wavelengths (488 and 660 nm with methylene blue (MB)) were used for elastin network and cellular imaging, respectively using pCLE in conjunction with r-EBUS and virtual navigation. In the first case, the 1-mm Alveoflex was used to image a metastatic melanoma in a subcentimetric nodule in the right middle lobe. In the next case, a malignant 2-cm nodule in the posterior segment of the upper lobe was imaged using the smaller 0.6-mm Cholangioflex. Lastly, we present a benign case revealing confocal characteristics of a nodular lipid pneumonitis. This reports for the first time the feasibility and utility of pCLE in vivo microimaging of SPN using either the Alveoflex or Cholangioflex miniprobes in addition to 660 nm/MB imaging.

Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers.

OBJECTIVES: Procalcitonin (PCT) is widely used for the diagnosis of bacterial infections. The aim of this study was to evaluate PCT as a tumor and as a prognostic marker in patients with primary lung cancer. DESIGN AND METHODS: We retrospectively performed a PCT dosage in the frozen serum samples of 147 patients with pulmonary neoplasia for whom a test of neuron-specific enolase (NSE) had been conducted at the time of diagnosis. RESULTS: We show that a PCT serum level above 0.15 ng/mL was independently linked to the presence of a neuroendocrine component in the tumor (HR=5.809 95% CI [1.695-19.908] p: 0005). Thus, median PCT serum levels were significantly more elevated in small-cell lung cancers than in pulmonary adenocarcinomas: 0.33 ng/mL versus 0.07 ng/mL (p<0.001). However, the diagnostic value of serum PCT levels for diagnosing carcinoma with a neuroendocrine component remains low (sensitivity 63.8%; specificity 71.9%). In this series, serum PCT levels were significantly more elevated in the presence of liver metastases: 0.37 ng/mL versus 0.09 ng/mL in the absence of liver metastasis (p<0.001). In uni- and multivariate analyses, a serum PCT level above 0.15n g/mL and the presence of metastases and of sepsis at the time of diagnosis were independent factors of unfavorable prognosis. CONCLUSIONS: Serum PCT is elevated in patients with lung cancer with neuroendocrine component or with liver metastases. As a consequence, in this population, PCT has a poor specificity for bacterial infection. At diagnosis, an elevated serum PCT is an independent predictive factor of bad prognosis.

[Cost-effectiveness of lung volume reduction coil treatment in emphysema. STIC REVOLENS]. / Évaluation médico-économique de la réduction volumique endobronchique par spirales. STIC REVOLENS.

BACKGROUND: Medical therapeutic options for the treatment of emphysema remain limited. Lung volume reduction surgery is infrequently used because of its high morbi-mortality. Endobronchial lung volume reduction coil (LVRC(®), PneumRx, Mountain View, CA) treatment has been recently developed and has been shown to be feasible and associated with an acceptable safety profile, while resulting in improvements in dyspnea, exercise capacity and lung function. The objective of this study is to analyze the cost effectiveness of LVRC treatment in severe emphysema. METHODS: This prospective, multicenter study, randomized with a 1:1 ratio (LVRC vs conventional treatment) will include 100 patients who will be followed up for 1year. The primary outcome measure is the 6-month improvement of the 6-minute walk test: the percentage of patients showing an improvement of at least 54m will be compared between groups. A cost-effectiveness study will estimate the cost of LVRC treatment, the global cost of this therapeutic option and will compare the cost between patients treated by LVRC and by medical treatment alone. EXPECTED RESULTS: This study should allow validating the clinical efficacy of LVRC in severe emphysema. The cost-effectiveness study will assess the medical-economic impact of the LVRC therapeutic option.

[Endobronchial ultrasound (EBUS): the state of the art]. / Échoendoscopie endobronchique (EBUS): le point de la question.

Endobronchial ultrasound (EBUS) is a technique which allows the endoscopist to sample mediastinal and/or hilar lymph nodes for complete staging of thoracic malignancy without recourse to surgery. Originally developed at the beginning of the 21st century, EBUS has become a well developed practice within France in recent years. As the technique requires high tech, expensive and fragile equipment, it has been important to develop an approach that is appropriate for the specific features and constraints of the French health system, including access to anaesthesia, imaging modalities and costing. The first centers to adopt EBUS had to adapt quickly and develop their own practices for its use. Training seminars were carried out in order to pass on this experience. After the passage of several years, it seems helpful to give a progress report on this technique through the stages of its development, taking account of the specificities of the French system and thus to transmit this accumulated experience. In this article, the authors review the literature concerning all the essential aspects needed to apply this technique under the best conditions in the French health system.

[Clomipramine hypersensitivity with predominantly pulmonary involvement]. / DRESS syndrome avec atteinte pulmonaire prédominante sous clomipramine.

Drug hypersensitivity (DRESS syndrome) is a rare disorder with diverse systemic and visceral manifestations. Pulmonary involvement is uncommon and is mainly characterized by eosinophilic infiltration. We report a case of DRESS syndrome induced by clomipramine with predominant pulmonary involvement.

Pneumocystis jirovecii colonization and infection among non HIV-infected patients.

OBJECTIVE AND METHOD: The epidemiology of pneumocystosis has changed in the last decade with a decreased incidence in HIV infected patients, and the emerging concept of Pneumocystis colonization. The study objective was to describe Pneumocystis infection as well as colonization among non-HIV infected patients in the Rouen teaching hospital and cancer institute. A retrospective study was made of all patients with a positive respiratory sample for Pneumocystis jirovecii between January 1, 2000 and June 6, 2007. RESULTS: Fifty-four cases were reported (46 cases of pneumocystosis and eight of asymptomatic carriage) and an increasing yearly incidence over the study period was observed. Underlying diseases for pneumocystosis were haematological malignancies (n=25; 54%), organ transplantation (n=8; 17.4%), inflammatory disorders (n=6; 13%), and solid cancer (n=5; 10.8%). Sixty-five per cent of patients were under long-term steroid therapy. The overall mortality rate was 21.4%. The CD4 count for 26 patients, ranged from 18 to 1449/mm(3) (median: 107). Eight cases of asymptomatic carriage were reported with an underlying immunodepression (n=6) and pulmonary disease (n=2). DISCUSSION: The increasing incidence of pneumocystosis in immunosuppressed patients without AIDS is due to more frequent favorable conditions and progress of diagnostic tools. The clinical presentations are severe. Prophylaxis is badly codified because there is no threshold value for CD4 count. Colonization could present a warning value.

[Interstitial pneumonia after infliximab therapy for psoriasis]. / Pneumopathie interstitielle subaiguë après traitement d'un psoriasis par infliximab.

BACKGROUND: Tumour necrosis factor (TNF)-alpha inhibitors are increasingly used for treatment of severe psoriasis. Hypersensitivity pneumonia is a rare but frequently fatal side-effect of such therapy that is unknown to most dermatologists. PATIENTS AND METHODS: A 68-year-old woman was hospitalized for subacute dyspnoea, fever, dry cough and basal chest pain 3 months after beginning infliximab therapy for severe psoriasis. Blood tests revealed an inflammatory syndrome and hypoxaemia. Thoracic computed tomography showed bilateral basal interstitial infiltrates with pleural effusion. The results of bronchoalveolar lavage and of the other microbiology testing were negative. Probabilistic treatment with amoxicillin/clavulanic acid and spiramycin was ineffective. We suspected drug-induced alveolitis and began corticosteroid therapy which improved dyspnoea, gas exchange and X-ray images. DISCUSSION: Hypersensitivity pneumonia is a potential pulmonary complication of anti-TNF alpha therapy and is frequently fatal. We report the first case of interstitial pneumonia secondary to infliximab given for severe psoriasis without any other pneumotoxic agents. Clinical features include dry cough, dyspnoea, and fever of acute or subacute onset. A diagnosis of allergic alveolitis was retained after elimination of other possible causes of the patient's interstitial pneumonia. CONCLUSION: The indications for anti-TNF agents are increasing in dermatology, and it is thus vital to consider their very rare but serious complications such as hypersensitivity pneumonia.

[Confocal endomicroscopy of the lung: from the bronchus to the alveolus]. / Endomicroscopie confocale en pneumologie : de la bronche à l'alvéole.

INTRODUCTION: Fibred confocal fluorescence microscopy, also named probe based confocal laser endomicroscopy (pCLE), is a new endoscopic technique that can be applied for in-vivo microscopic imaging of both upper airways and distal lung structures during bronchoscopy. BACKGROUND: Two recent in-vivo human studies using pCLE at 488nm light excitation have described the normal fluorescence endomicroscopic features of the bronchial wall and the elastic framework of the alveolus. These studies have demonstrated that elastin, a major component of the bronchial basement membrane and of the acinar elastic framework, is the main endogenous fluorophore in the non-smoking population. In smoking subjects, the tobacco tar itself is highly fluorescent and, thereby, acts as an additional fluorophore, allowing study of the macrophage alveolitis associated with smoking. These studies have also confirmed the safety of this endoscopic procedure. VIEWPOINT: In the near future, confocal endomicroscopy of the airways should make it possible to investigate the semiology of focal and diffuse distal lung diseases, to characterize cancerous and precancerous lesions of both upper and distal airways and to study the lung microcirculation. These studies may also use exogenous molecular fluorescent probes, which will enable functional imaging of the lung structures in-vivo. CONCLUSION: Confocal endomicroscopy has the potential to explore accurately the peripheral lung in-vivo and may become a useful tool to improve endoscopic diagnosis of many lung diseases.

Relationships between lung adenocarcinoma and gender, age, smoking and occupational risk factors: A case-case study.

BACKGROUND: The hypothesis that some risk factors for lung cancer may have more specific associations with particular histologic types remains controversial. The aim of this study was to investigate possible associations between adenocarcinoma and gender, age, smoking characteristics and selected occupational carcinogens in relation to other histologic types. METHODS: This study included all histologically confirmed lung cancer cases diagnosed consecutively in two French University hospitals from 1997 to 2006. All medical data were obtained by face-to-face patient interviews. Occupational carcinogen exposures of each patient were assessed by an industrial hygienist. Relationships between risk factors and adenocarcinoma were analyzed by case-case comparisons using unconditional logistic regressions (ULRs). RESULTS: A total of 1493 subjects were enrolled in this study, comprising 1303 men (87.3%), 67 nonsmokers (4.5%) and 489 adenocarcinomas (32.7%). Using ULR, no associations were observed between adenocarcinoma and age, gender or smoking characteristics except for a negative relationship with smoking duration (p<0.0001). Significant associations were observed between ADC and exposure to welding fumes and silica in the whole population and with polycyclic aromatic hydrocarbons in ever smokers. CONCLUSION: This study demonstrated that some risk factors, such as duration of smoking and certain occupational exposures but not gender or age, have a more important influence on the incidence of lung ADC than on other histologic types. As the distribution of histologic types may reflect underlying biological mechanisms, these findings also suggest that lung carcinogenesis pathways should be studied in relation to smoking duration and other lung cancer risk factors.

Human in vivo fluorescence microimaging of the alveolar ducts and sacs during bronchoscopy.

The aim of the present study was to assess fibred confocal fluorescence microscopy (FCFM) as a tool for imaging the alveolar respiratory system in vivo during bronchoscopy. A 488-nm excitation wavelength FCFM device was used in 41 healthy subjects including 17 active smokers. After topical anaesthesia, the 1.4-mm miniprobe was introduced into the bronchoscope working channel and advanced distally to the alveoli. Morphometric and cellular analyses were performed on selected frames harbouring a minimal compression effect. In vivo acinar microimaging was obtained from each lung segment except for the apical and posterior segments of both upper lobes. Reproducible patterns, corresponding to the elastic framework of the axial and peripheral interstitial systems, were recorded from 192 separate acini. The mean+/-sd thickness of the acinar elastic fibres was 10+/-2.7 microm. Alveolar mouth diameters (mean+/-sd 278+/-53 microm) were normally distributed but appeared smaller in the right upper lobe and right medial basal segment. Lobular microvessels (median diameter 90 microm) were equally distributed throughout the lungs. Alveolar macrophages were not detectable in nonsmokers, whereas a specific tobacco-tar-induced fluorescence was observed in smoking subjects, providing fine details of the alveolar walls and macrophages. A strong correlation was found between the number of cigarettes smoked per day and the amount of large and mobile macrophages observed in vivo, as well as with the intensity of the macrophage alveolitis. Fibred confocal fluorescence microscopy enables accurate exploration of the peripheral lung in vivo in both smokers and nonsmokers.

[Aspergillosis and sarcoidosis]. / Aspergillose et sarcoïdose.

INTRODUCTION: Diffuse fibrosing sarcoidosis represents an important predisposing factor for infection by Aspergillus sp. The clinical features and specific complications are illustrated by 3 case reports. BACKGROUND: Patients with chronic fibrosing sarcoidosis and cystic changes or cavitation in the upper lobes are the most prone to aspergillosis. Aspergilloma is the most common form and can be difficult to distinguish from chronic necrotising aspergillosis. Sarcoidosis with aspergillosis is associated with an increased incidence of respiratory failure and fatal haemoptysis. The 3 cases presented in this paper also illustrate the poor efficacy of oral antifungal drugs and bronchial embolisation. Surgery is often necessary but may be difficult on account of the extent of the lesions and poor respiratory function. VIEWPOINT: In the future the use of new drugs such as voriconazole and posaconazole may improve the prognosis of this complication. CONCLUSION: Aspergillosis represents a frequent complication of diffuse fibrosing sarcoidosis which warrants early detection and treatment on account of its poor prognosis.

Double stenting of oesophagus and airways in palliative treatment of patients with oesophageal cancer is efficient but associated with a high morbidity.

BACKGROUND: Double stenting of oesophagus and airways may be required in palliative treatment of patients with locally advanced oesophageal cancer. AIM: To assess feasibility, efficacy and complications occurring in patients with locally advanced oesophageal cancer receiving both oesophagus and airways stenting. METHODS: In one single centre between 1997 and 2005, among 180 patients with locally advanced oesophageal cancer treated by the palliative placement of a self-expanding metal stent, patients requiring double stenting of oesophagus and airways were identified. Clinical efficacy, complications and survival were retrospectively collected. RESULTS: Fifteen patients (8.3% of 180) required a double stenting at follow-up. Symptomatic efficacy of oesophagus and airways stenting was 86.7% for dysphagia and 100% for dyspnoea. Median survival after the second stent insertion was 99 days. Life-threatening early complications occurred in three patients after double stenting (20%), including two deaths following oesophageal perforation and massive haemoptysis, respectively. Procedure-related mortality was 13.3%. CONCLUSIONS: Double stenting of oesophagus and airways is feasible in patients with locally advanced oesophageal cancer, with a relevant clinical efficacy. However, early major complications including procedure-related death may occur in as many as 20% of patients. This treatment should be reserved to very selected patients with severe symptoms and end-stage disease.