Multiplexed Profiling of CDK Kinase Activities in Tumor Biopsies with Fluorescent Peptide Biosensors.

Detection of disease biomarkers constitutes a major challenge for the development of personalized and predictive diagnostics as well as companion assays. Protein kinases (PKs) involved in the coordination of cell cycle progression and proliferation that are hyperactivated in human cancers constitute attractive pharmacological targets and relevant biomarkers. Although it is relatively straightforward to assess the relative abundance of PKs in a biological sample, there is not always a direct correlation with enzymatic activity, which is regulated by several posttranslational mechanisms.

Brief Report: A Multidisciplinary Initial Workup for Suspected Lung Cancer as Fast-Track Intervention to Histopathologic Diagnosis.

Guidelines for optimal timing of lung cancer diagnosis and treatment have been implemented in many countries, but the effect of fast-track interventions on the shortening of time interval is still debatable. In this study, the delay from the first specialist visit to the histopathologic diagnosis was compared between two patient cohorts: before (n = 280) and after (n = 247) implementation of a fast-track multidisciplinary diagnosis program. The cumulative incidence function curves were compared, and hazard ratio was adjusted in the Cox model.

Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series.

Background: Immune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening.

EGFR-dependent mechanisms of resistance to osimertinib determined by ctDNA NGS analysis identify patients with better outcome.

Background: Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is highly selective for subclones in patients with non-small cell lung cancer (NSCLC). Unfortunately, all patients develop resistance through EGFR-dependent or EGFR-independent pathways. Recently, circulating tumoral DNA (ctDNA) analysis has highlighted the usefulness of plasma genotyping for exploring patient survival outcomes after disease progression under osimertinib.

Complication and lung function impairment prediction using perfusion and computed tomography air trapping (CLIPPCAIR): protocol for the development and validation of a novel multivariable model for the prediction of post-resection lung function.

Background: Recent advancements in computed tomography (CT) scanning and post processing have provided new means of assessing factors affecting respiratory function. For lung cancer patients requiring resection, and especially those with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD), the ability to predict post-operative lung function is a crucial step in the lung cancer operability assessment. The primary objective of the CLIPPCAIR study is to use novel CT data to develop and validate an algorithm for the prediction of lung function remaining after pneumectomy/lobectomy.

[Granulomatous lung disease induced by kayexalate inhalation during immunotherapy for metastatic melanoma].

Introduction: When a patient treated by immune checkpoint inhibitors for metastatic melanoma presents with pulmonary symptoms, several diagnoses are possible. We report a case of acute granulomatous lung disease secondary to repeated kayexalate inhalations, and probably stimulated by immunotherapy.

Case Report: A patient treated with pembrolizumab and then ipilimumab presented with fever and acute shortness of breath.

Club Cell Loss as a Feature of Bronchiolization in ILD.

Distal airway metaplasia may precede honeycombing in progressive fibrosing interstitial lung disease (ILD). The SCGB1A1 bronchiolar-specific club cell may play a role in this aberrant regenerative process. To assess the presence of club cells in the small airways of patients suffering from ILD.

[Cancers of the external genital organs of male in Hérault: Results from the Hérault tumor register (RTH) over a period of 30 years (1987-2016)].

Aim: The objective of this study is to present the history of cancers of the external genital organs of male in Hérault using data from the Hérault tumor register (RTH) over a period of 30 years.

Patients And Methods: Using the RTH database, we studied the development of testicular germ cell tumors (TGCT) and penile cancer (PC) over 30 years, from 1987 to 2016. We analyzed the incidence and mortality data for these tumors.

Combination of tissue and liquid biopsy molecular profiling to detect transformation to small cell lung carcinoma during osimertinib treatment.

Background: Histological transformation of advanced non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of the mechanisms of resistance to third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib. This acquired TKI resistance is linked to the high degree of tumor heterogeneity and adaptive cellular signaling pathways, including epidermal growth factor receptor ()-dependent pathways, observed in NSCLC.

Methods: Here, we investigated a series of paired pre- and post-histological transformation biopsies obtained from three patients initially having a NSCLC with an mutation treated with first-generation TKI, who then received osimertinib as second-line after resistance and, lastly, developed a histological transformation to SCLC.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

Background: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases.

Materials And Methods: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019.

[Renal cell carcinoma in the department of Hérault: Results over a 30 year period].

Objective: The objective of the study was to determine the specificities of renal cell carcinoma (RCC) in the department of Herault using the Herault Tumor Registry over 30 years.

Methods: Data of this study were obtained from the Herault cancer database. We analysed the evolution of RCC from 1987 to 2016, including the incidence, mortality, cancer pathology and staging at the moment of diagnosis.

[RHESOU (Registry in HErault Specialized in Onco-Urology) : the first French Registry specialized in Onco-Urology. One-year experience].

Purpose: In 2016, the Herault tumor registry collected 1961cancers in urology (21.4 % from all Herault cancers this year). RHESOU was created to complete RTH' data with specific parameters in onco-urology.

Homoplasmic deleterious MT-ATP6/8 mutations in adult patients.

To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis.

Childhood pulmonary Langerhans cell histiocytosis: a comprehensive clinical-histopathological and BRAF mutation study from the French national cohort.

Childhood pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease. Its pulmonary histopathology, according to comprehensive clinical-radiological findings and BRAF mutation status, has not yet been thoroughly documented. From the 167 childhood PLCH cases entered in the French National Histiocytosis Registry (1983-2016), we retrieved lung biopsies from a consecutive retrospective series of 17 patients, diagnosed when they were 2 weeks to 16 years old (median, 9.

Poor Concordance between Sequential Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy in the Diagnosis of Diffuse Interstitial Lung Diseases.

The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)-versus surgical lung biopsy (SLB) as the current gold standard-in interstitial lung disease (ILD) cases requiring histology remains controversial. To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA.

Can early neurological improvement after mechanical thrombectomy be used as a surrogate for final stroke outcome?

Background And Purpose: We aimed to identify the best definition of early neurological improvement (ENI) at 2 and 24 hours after mechanical thrombectomy (MT) and determine its ability to predict a good functional outcome at 3 months.

Methods: This retrospective analysis was based on a prospectively collected registry of patients treated by MT for ischemic stroke from May 2010 to March 2017. We included patients treated with stent-retrievers with National Institute of Health Stroke Scale (NIHSS) score before treatment and at 2 and/or 24 hours after treatment and modified Rankin Score (mRS) at 3 months.

Mechanical Thrombectomy for Tandem Occlusions of the Internal Carotid Artery-Results of a Conservative Approach for the Extracranial Lesion.

Mechanical thrombectomy (MT) is of clinical benefit for patients with extracranial-intracranial tandem lesions of anterior circulation. However, the optimal approach to the cervical lesion of the internal carotid artery (ICA) during MT has yet to be established. Data on a conservative approach for the proximal lesion during the acute phase are scarce.

SMARCA4-deficient Thoracic Sarcomas: Clinicopathologic Study of 30 Cases With an Emphasis on Their Nosology and Differential Diagnoses.

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity with an aggressive clinical course and specific genetic alterations of the BAF chromatin remodeling complex. In the present study, we reviewed the clinical and pathologic features of 30 cases of SMARCA4-DTS, discussed its main differential diagnoses and the challenging diagnostic scenarios that the average pathologist may face. In addition, we tested the specificity of the "SMARCA4-DTS immunohistochemical signature" (co-loss of SMARCA4 and SMARCA2 with overexpression of SOX2) in a large cohort of intrathoracic malignancies.

Detection of known and novel ALK fusion transcripts in lung cancer patients using next-generation sequencing approaches.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) represent a novel molecular target in a small subset of tumors. Although ALK rearrangements are usually assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), molecular approaches have recently emerged as relevant alternatives in routine laboratories. Here, we evaluated the use of two different amplicon-based next-generation sequencing (NGS) methods (AmpliSeq and ArcherFusionPlex) to detect ALK rearrangements, and compared these with IHC and FISH.

Is there a benefit of mechanical thrombectomy in patients with large stroke (DWI-ASPECTS ≤ 5)?

Background And Purpose: Whether to withhold mechanical thrombectomy when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is undetermined. Our aim was to identify markers that will help to select patients with large DWI lesions [DWI-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) ≤ 5] that may benefit from thrombectomy.

Methods: From May 2010 to November 2016, 82 acute ischaemic stroke patients with DWI-ASPECTS ≤5 (43 men, 64.

Susceptibility vessel sign on T2* magnetic resonance imaging and recanalization results of mechanical thrombectomy with stent retrievers: a multicentre cohort study.

Background And Purpose: The susceptibility vessel sign (SVS) on T2*-weighted magnetic resonance imaging has been reported in several studies as a negative predictor of early recanalization after intravenous thrombolysis. The meaning of SVS regarding the results of mechanical thrombectomy with stent retrievers was investigated.

Methods: Susceptibility vessel sign presence and length were studied in 153 acute ischaemic stroke patients (82 men; mean ± SD age 59 ± 17 years, baseline National Institutes of Health Stroke Scale score 17.

Delayed pulmonary arterial hypertension in relation to pulmonary damage score after pneumonectomy under protective ventilation: experimental study.

Objective: To characterize pulmonary hemodynamic changes in relation to lung injury at 2 time points [48 h (H48) and 168 h (H168)] after pneumonectomy under intraoperative protective ventilation in order to improve postpneumonectomy pulmonary edema (PPE) prevention.

Method: Fifteen pigs (25 ± 1.9 kg) were randomly allocated to nonsurgical (control, n = 5) and surgical (H48 and H168) groups.

Impact of preoperative marking coils on surgical and pathologic management of impalpable lung nodules.

Background: The management of occult lung lesions, particularly subsolid opacities, is a new challenge because they are difficult to localize during surgery and the number of lesions detected by computed tomography (CT) is increasing.

Methods: Between February 2008 and December 2011, preoperative CT-guided marking with coils was systematically carried out to localize presumed impalpable nodules before video-assisted thoracoscopic surgery (VATS). The procedure feasibility, reliability, and safety as well as its impact on the resection volume and on the pathologic examination strategy were examined.