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.

[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.

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.

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.

[A double-faced myocarditis: Whipple's disease or sarcoidosis?]. / Une myocardite à deux visages : maladie de Whipple ou sarcoïdose?

INTRODUCTION: Whipple's disease is a systemic infection that may mimic sarcoidosis in its initial presentation. The heart involvement is not uncommon and consists generally in an endocarditis. Myocarditis is less common and is usually accompanied by impairment of heart conduction. CASE REPORT: We report a 56-year-old man with Whipple's disease associated with a myocarditis, initially diagnosed as having a sarcoidosis with cardiac injury. The contribution of the histology and molecular biology on intestinal sampling made it possible to rectify the diagnosis. CONCLUSION: The diagnosis of Whipple's disease should be considered in the presence of a systemic granulomatosis with or without heart involvement. Early diagnosis is important because of effectiveness of antibiotic therapy.

Diagnostic of mediastinal lymphadenopathy in extrathoracic cancer: A place for EBUS-TBNA in real life practice?

INTRODUCTION: Mediastinal lymphadenopathy in patients with extrathoracic malignancy is common. To obtain tissue proof of metastatic spread, EBUS-TBNA is an alternative to mediastinoscopy or thoracoscopy, but there are limited data about its diagnostic performance. The aim of this study was to determine the diagnostic accuracy of EBUS-TBNA for the evaluation of mediastinal lymphadenopathy in patients with extrathoracic cancers. METHODS: We performed a multicenter retrospective study based on an online questionnaire to collect data from January 2011 to December 2012 in all patients with proven extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases who underwent EBUS-TBNA for diagnosis. RESULTS: Hundred and eighty-five patients were included. Extrathoracic malignancies observed were urological (43), breast (35), gastrointestinal (33), head and neck (30), melanoma (11), lymphoma (6), and others (27). EBUS-TBNA confirmed malignancy in 93 patients (50.3%): concordant metastases in 67 (36.2%); new lung cancer in 25 (13.5%); and 1 unidentified cancer. The diagnostic accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were respectively 54.6%, 68.4%, 100%, 53.3%, and 100%. CONCLUSION: Mediastinoscopy remain the reference, but EBUS-TBNA may be considered as first line investigation in patients with suspected mediastinal lymph node metastases and extrathoracic malignancy. It prevented a surgical procedure in 50.3% of patients.

[Troponin dosage in a patient with asymptomatic myocarditis due to trichinellosis]. / Myocardite asymptomatique au cours d''un cas de trichinellose: intérêt du dosage de la troponine.

Human trichinellosis is a potentially severe parasitic disease occurring after ingestion of undercooked meat infected with Trichinella sp. larvae. We report the case of a patient who ate an undercooked bear meat hunted in Canada; he presented with the usual symptoms of trichinellosis (i.e, facial oedema, myalgias and fever) complicated with an asymptomatic myocarditis. Myocarditis is a rare, but potentially lethal complication of trichinellosis. Myocarditis should be screened systematically even when specific symptoms are missing; dosage of troponin serum is a simple and reliable mean for such screening.

[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.

[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.

[Acute encephalopathy after infusion of paclitaxel]. / Encéphalopathie aiguë après injection de paclitaxel.

INTRODUCTION: Paclitaxel is an anti-neoplastic agent commonly used in the treatment of primary bronchial carcinoma and tumours of the breast and ovary. Its toxicity, haematological and peripheral neuropathy, are well known. On the other hand central nervous system toxicity is rare. CASE REPORT: We report a case of acute encephalopathy, occurring eight hours after infusion of Paclitaxel, in a patient treated for adenocarcinoma of the lung. It included drowsiness, confusion and hallucinations, and resolved completely after ten days. The diagnosis of encephalopathy secondary to Paclitaxel injection was reached after exclusion of other possible aetiologies. CONCLUSIONS: Acute encephalopathy is a rare complication of intravenous Paclitaxel treatment. The pathophysiology of this toxic effect is discussed: a direct toxicity of Paclitaxel or of its solvent (polyoxethylated castor oil), and the role of a pre-existing alteration of the blood-brain barrier.

Spermidine induces autophagy by inhibiting the acetyltransferase EP300.

Several natural compounds found in health-related food items can inhibit acetyltransferases as they induce autophagy. Here we show that this applies to anacardic acid, curcumin, garcinol and spermidine, all of which reduce the acetylation level of cultured human cells as they induce signs of increased autophagic flux (such as the formation of green fluorescent protein-microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta and the depletion of sequestosome-1, p62/SQSTM1) coupled to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). We performed a screen to identify the acetyltransferases whose depletion would activate autophagy and simultaneously inhibit mTORC1. The knockdown of only two acetyltransferases (among 43 candidates) had such effects: EP300 (E1A-binding protein p300), which is a lysine acetyltranferase, and NAA20 (N(α)-acetyltransferase 20, also known as NAT5), which catalyzes the N-terminal acetylation of methionine residues. Subsequent studies validated the capacity of a pharmacological EP300 inhibitor, C646, to induce autophagy in both normal and enucleated cells (cytoplasts), underscoring the capacity of EP300 to repress autophagy by cytoplasmic (non-nuclear) effects. Notably, anacardic acid, curcumin, garcinol and spermidine all inhibited the acetyltransferase activity of recombinant EP300 protein in vitro. Altogether, these results support the idea that EP300 acts as an endogenous repressor of autophagy and that potent autophagy inducers including spermidine de facto act as EP300 inhibitors.

Developmental regulation of the serpin, protease nexin I, localization during activity-dependent polyneuronal synapse elimination in mouse skeletal muscle.

During vertebrate neuromuscular development, all muscle fibers are transiently innervated by more than one neuron. Among the numerous factors shown to potentially influence the passage from poly- to mononeuronal innervation, serine proteases and their inhibitors appear to play important roles. In this regard, protease nexin I (PNI), a potent inhibitor of the serine protease, thrombin, is highly localized to the neuromuscular junction (NMJ). In turn, thrombin is responsible for activity-dependent synapse elimination both in an in vitro model, and in vivo. In the present study, we used a monospecific anti-PNI polyclonal antibody to study the developmental kinetics of PNI expression in mouse leg skeletal muscle. By using immunoblotting, we detected PNI at embryonic day 16 (E16), as a 48-kDa band. This 48-kDa PNI band became prominent in leg muscle extracts at postnatal day 5 (P5) and remained so in extracts from adult muscle. In contrast, a higher molecular weight immunoreactive PNI band, which was sodium dodecyl sulfate- and beta-mercaptoethanol-resistant, was first detected at E16, increased at birth (P0), and then decreased at P15, i.e., after the wave of polyneuronal synapse elimination had occurred in these muscles. The results of an enzyme-linked immunosorbent assay, measuring active, complexed, and truncated PNI, correlated with Western blot data. We used immunocytochemistry to probe the localization of PNI at the NMJ and found that PNI was present in the cytoplasm of myotubes at E16, but neither then nor at birth did it colocalize with acetylcholine receptors. PNI became localized at NMJs by P5 and increased by P15, after which it remained stably concentrated there in the adult. Finally, we studied the gene expression of PNI mRNA, by using Northern blotting, and showed that PNI mRNA was present in skeletal muscle and remained stable throughout the time-course studies, suggesting that developmental regulation of muscle PNI occurs principally at the translational and/or post-translational levels. These results suggest that the localization of PNI, through a binding site or "receptor" may play an important role in differentiation and maintenance of synapse.

[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.