[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.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

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.

Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD. RESULTS: Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years. CONCLUSIONS: Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.

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.

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.

Divergent selection for residual feed intake in group-housed growing pigs: characteristics of physical and behavioural activity according to line and sex.

The aim of the study was to assess the impact of selection for residual feed intake (RFI) on the behavioural activity of lines divergently selected for RFI during seven generations. In all, six successive batches from the seventh generation of selection were raised in collective pens equipped with a single-place electronic feeder (SEF) from 10 weeks of age to 100 kg BW. Each batch included four groups of 12 pigs: high RFI (RFI+) castrated males, RFI+ females, low RFI (RFI-) castrated males, RFI- females. At 17 weeks of age, health criteria were evaluated using a gradient scale for increased severity of lameness, body lesions, bursae and tail biting. Individual behavioural activities were recorded by 24-h video tape on the day after health evaluation. The investigative motivation towards unfamiliar objects was quantified at 18 weeks of age. The daily individual feeding patterns were computed from SEF records during the 4 weeks surrounding 12, 17 and 22 weeks of age. All pigs spent significantly most of their time lying in diurnal (80% of total scan) and nocturnal (>89%) periods. The RFI- pigs showed a lower proportion of health problems (P<0.01) than RFI+ pigs. The RFI- pigs used the SEF less than the RFI+ pigs, in diurnal (5.3% v. 6.4% of video scans, P<0.05) and nocturnal periods (3.6% v. 4.5% of video scans, P<0.05). This was confirmed by a significantly lower daily number and duration of visits to the SEF computed from the SEF data. The feeding activity measured from the video recording was significantly correlated (R>0.34; P<0.05) with feeding patterns computed from the SEF. The RFI- pigs spent less time standing over the 24-h period (9.7% v. 12.2% of scans, i.e. 35 min/day, P<0.05). In terms of energy costs, this amounted to 14% of the line difference in terms of daily metabolizable energy intake. The castrated males used the SEF more than females, especially at night (4.7% v. 3.4% of total scans, P<0.05), whereas females displayed greater investigation of their environment (7.7±0.3% v. 6.6±0.2% of total scans, P<0.05) and the novel objects (10.7% v. 4.9% of total scans, P<0.05). In conclusion, the lower physical activity associated with reduced energy expenditure in RFI- pigs compared with RFI+ pigs contributed significantly to their improved efficiency and was not related to worsened health scores.

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.

[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.

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.

[Fluorescence endoscopy of the respiratory tract]. / Les explorations endoscopiques respiratoires en fluorescence.

Autofluorescence endoscopy has been used for more than 10 years in the diagnosis of early lung cancers and precancerous lesions of the bronchial tree. The technique has been extensively evaluated during the past decade and two recent large randomised studies have shown a 2 to 5 times increase in the detection of high grade pre-cancerous lesions compared with conventional white light endoscopy. This paper reviews the principal applications and results of the use of autofluorescence endoscopy in high risk individuals as well as innovative endoscopic approaches using the fluorescent properties of the respiratory tract.