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.

[Tumour sequencing: Evolutions and revolutions]. / Séquençage des tumeurs : évolutions et révolutions.

For some years now, we have entered the genomic age of tumour genotyping from a medical point of view. Technological breakthroughs in both biology and information science now allow a genomic analysis of cancers in everyday medical practice with, in some case, a major impact on patient care not only for the choice of therapy (i.e. EGFR mutations in lung adenocarcinoma), but also for diagnosis and monitoring of the disease. Tumour genotyping is performed from formalin-fixed paraffin-embedded tissues used for diagnosis of cancer. However, new approaches have emerged, with for example the more and more spread use of "liquid biopsies". Genotyping of a gene panel implicated in carcinogenesis is now routinely performed in some cancer types, with the help of high-throughput sequencers, and it is likely that improvement of these machines will make tumour genotyping easier and more accessible in the near future. Nevertheless, the current challenge is not anymore detection of molecular alterations, but their relevant interpretation, so as to be the most useful in patient care.

Electron microscopy approach for the visualization of the epithelial and endothelial glycocalyx.

This study presents a methodological approach for the visualization of the glycocalyx by electron microscopy. The glycocalyx is a three dimensional network mainly composed of glycolipids, glycoproteins and proteoglycans associated with the plasma membrane. Since less than a decade, the epithelial and endothelial glycocalyx proved to play an important role in physiology and pathology, increasing its research interest especially in vascular functions. Therefore, visualization of the glycocalyx requires reliable techniques and its preservation remains challenging due to its fragile and dynamic organization, which is highly sensitive to the different process steps for electron microscopy sampling. In this study, chemical fixation was performed by perfusion as a good alternative to conventional fixation. Additional lanthanum nitrate in the fixative enhances staining of the glycocalyx in transmission electron microscopy bright field and improves its visualization by detecting the elastic scattered electrons, thus providing a chemical contrast.

[Thymomectomy by minimally invasive surgery. Comparative study videosurgery versus robot-assisted surgery]. / Traitement des thymomes par chirurgie mini-invasive. Étude comparative vidéochirurgie versus voie robot-assistée.

OBJECTIVES: To report the results of minimally invasive surgery in patients with stage I or II thymoma in the Masaoka classification. The reference technique is partial or complete thymectomy by sternotonomy. METHODS: A retrospective single-center study of a prospective database including all cases of thymoma operated from April 2009 to February 2015 by minimally invasive techniques: either videosurgery (VATS) or robot-assisted surgery (RATS). The surgical technique, type of resection, length of hospital stay, postoperative complications and recurrences were analysed. RESULTS: Our series consisted of 22 patients (15 women and 7 men). The average age was 53 years. Myasthenia gravis was present in 12 patients. Eight patients were operated on by VATS and 14 patiens by RATS. There were no conversions to sternotomy and no perioperative deaths. The mean operating time was 92min for VATS and 137min for RATS (P<0.001). The average hospital stay was 5 days. The mean weight of the specimen for the VATS group was 13.2 and 45.7mg for the RATS group. Twelve patients were classified Masaoka stage I and 10 were stage II. According to the WHO classification there were 7 patients type A, 5 type AB, 4 type B1, 4 type B2 4 and 2 type B3. As proposed by the Group ITMIG-IASLC in 2015 all patients corresponded to group I. The mean follow-up period was 36 months. We noted 3 major perioperative complications according to the Clavien-Dindo classification: one pneumonia, one phrenic nerve paralysis and one recurrent laryngeal nerve palsy. We observed one case of local recurrence at 22 months. Following surgery 4 patients were treated with radiotherapy and 2 patients with chemotherapy. CONCLUSIONS: The minimally invasive route is safe, relatively atraumatic and may be incorporated in the therapeutic arsenal for the treatment of Masaoka stage I and II thymoma as an alternative to conventional sternotomy. RATS and VATS are two minimally invasive techniques and the results in the short and medium term are acceptable. The clinical advantages of one over the other are sifficult to establish. RATS could handle larger and more complex lesions in view of the weight and size of the operating instrument.

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.