Search

RATIONALE: Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation. OBJECTIVES: To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM. METHODS: A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively. MEASUREMENTS AND MAIN RESULTS: SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance. CONCLUSIONS: In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance. [ABSTRACT FROM AUTHOR]

Abstract Background Plasma transforming growth factor β1 (TGFβ1 ) levels are elevated in patients with lung cancer. As TGFβ1 is mainly found in platelets and as nonmalignant pulmonary diseases (NMPD) are frequently associated with lung cancer, we investigated the potential contribution of platelet degranulation and/or of a concomitant NMPD to the increased plasma levels of TGFβ1 reported in patients with lung cancer. Materials and Methods Blood samples were collected in duplicate from 30 healthy subjects, 14 patients suffering from NMPD and 37 patients with lung cancer. The platelet count was determined and the samples were processed to obtain plasma. One sample was collected in EDTA (EDTA plasma) and the other in a mixture inhibiting platelet degranulation (PIM plasma). TGFβ1 concentrations and β-thromboglobulin (βTG) levels, an index of platelet degranulation, were measured in both plasma samples. Results TGFβ1 and βTG plasma levels measured in PIM plasma were lower than those obtained in EDTA plasma. With respect to PIM plasma, both TGFβ1 and βTG levels were higher in patients with lung cancer than those with NMPD and in healthy individuals. In patients with NMPD, only TGFβ1 levels were increased as compared to healthy controls, βTG levels being similar. Conclusion Methods for collecting and processing blood samples are critical in determining reliable circulating TGFβ1 levels. Increased TGFβ1 plasma levels observed in patients with lung cancer are related, at least partly, to concomitant NMPD and also to platelet degranulation as proved by increased βTG levels. [ABSTRACT FROM AUTHOR]

Boerhaave syndrome or spontaneous rupture of the oesophagus is a severe condition commonly misdiagnosed or unrecognized. Prognosis is poor even if the diagnosis is made promptly. We describe a case of Boerhaave syndrome diagnosed after the development of pneumomediastinum and cardiac arrest. Unfortunately, the patient died 48 hours after admission to the Intensive Care Unit. This entity requires a multidisciplinary management approach which may include conservative, surgical or endoscopic procedures., Learning Points: Boerhaave syndrome is a diagnostic and therapeutic challenge, and rapid diagnosis and management are crucial.A thoraco-abdominal CT scan with oesophageal opacification is the gold standard investigation.A multidisciplinary and individualized approach is needed in the management of this condition., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interest, (© EFIM 2019.)

Measles is a highly contagious viral disease and one of the biggest causes of morbidity and mortality in the world. Transmission occurs from person to person through direct contact or by aerosolization of pharyngeal secretions. It can be responsible for severe respiratory and neurological complications. The diagnosis is clinical, confirmed by serology, PCR or culture of the measles virus. Treatment is symptomatic and prevention is based on a well conducted vaccination. In severe cases, the use of vitamin A is recommended by the World Health Organization, at least in chidren. Antivirals (ribavirin) have not been shown to be effective in clinical practice. We present a severe respiratory form of measles, affecting a young immunocompetent adult.

Introduction: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor., Methods: Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease., Results: Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung., Conclusion: The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed., Trial Registration: ClinicalTrials.gov NCT00339586.

Introduction: To assess the safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with stage IB-III MAGE-A3-positive non-small-cell lung cancer (NSCLC) who were or were not undergoing standard cisplatin/vinorelbine chemotherapy., Methods: This open, prospective, multicenter, parallel-group phase I study (NCT00455572) enrolled patients with resected (cohorts 1-3) or unresectable (cohort 4) MAGE-A3-positive NSCLC. MAGE-A3 immunotherapeutic (300 μg recombinant MAGE-A3 formulated with AS15) was administered (eight doses, 3 weeks apart) concurrent with (cohort 1), after (cohort 2), or without (cohort 3) standard-adjuvant chemotherapy, or after standard radiotherapy and/or chemotherapy (cohort 4)., Results: Sixty-seven patients received greater than or equal to 1 dose of MAGE-A3 immunotherapeutic. Grade 3/4 adverse events (AEs) were reported for 16 out of 19 (84%), 2 out of 18 (11%), 5 out of 18 (28%), and 1 out of 12 (8%) patients in cohorts 1, 2, 3, and 4, respectively. Many grade 3/4 AEs in cohort 1 (e.g., neutropenia) were typical of chemotherapy. Six patients, including three in cohort 1, reported study treatment-related grade 3/4 AEs (injection-site reactions or musculoskeletal/back pain, which resolved within 5 days). One patient (in cohort 4) died, but this and the other serious adverse events were not study treatment related. MAGE-A3-specific antibody responses to immunotherapy were induced in all patients evaluated in all cohorts. MAGE-A3-specific CD4 T-cell responses to immunotherapy were detected in 4 out of 11 (36%), 4 out of 15 (27%), 2 out of 8 (25%), and 5 out of 6 (83%) evaluated patients in cohorts 1, 2, 3, and 4, respectively; and CD8 T-cell responses were only detected in four patients., Conclusion: In resected and unresectable NSCLC patients and irrespective of whether standard chemotherapy was concurrent or not, MAGE-A3 immunotherapeutic is well tolerated and induces MAGE-A3-specific immune responses.

The incidence of non tuberculosis mycobacterial (NTM) pulmonary diseases is increasing. Patients with NTM disease usually suffer prolonged periods of clinical illness prior to diagnosis. An etiological treatment, initiated by a well informed clinician and based on presumptive evidence, can be successful in a significant proportion of cases.

Purpose: Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC., Patients and Methods: A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m(2) intravenously (IV) on days 1 to 3 or topotecan 1.5 mg/m(2) IV on days 1 to 5. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival (PFS), and safety., Results: Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan (HR, 0.802; P = .018). ORR was 31.1% with amrubicin and 16.9% with topotecan (odds ratio, 2.223; P < .001). Grade ≥ 3 treatment-emergent adverse events in the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004), thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001), respectively. NQO1 polymorphisms did not influence safety outcomes., Conclusion: Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC. OS did not differ significantly between treatment groups, although an improvement in OS was noted in patients with refractory disease treated with amrubicin., (© 2014 by American Society of Clinical Oncology.)

Non-small cell lung cancer (NSCLC) is common. Approximately one out of every five patients with NSCLC has locally advanced disease that is surgically unresectable. For these patients, the disease has a poor prognosis characterized by a high rate of local disease progression or recurrence despite attempts at chemo- and radiation therapy. The purpose of this review is to describe the heterogeneity of this group of patients, to clarify the terms of the combination of chemotherapy and radiotherapy and to clarify the efficacy of modern radiotherapy techniques to increase local control.

Background: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study examined the effect of clinical covariates on biomarkers levels and their diagnostic and prognostic value., Methods: Five hundred ninety-four participants were enrolled in a multicenter study, including 106 patients with mesothelioma and 488 control subjects. Multiple linear regression analyses were used to identify which covariates were independently associated with SM and MPF levels. The effect of these covariates on the diagnostic accuracy was evaluated with receiver operating characteristics curve analysis. In patients with mesothelioma, survival analysis was performed with Cox regression., Results: SM and MPF levels were independently associated with age, glomerular filtration rate (GFR), and BMI in control subjects and with GFR and tumor stage in patients with mesothelioma. The diagnostic accuracy of SM and MPF was significantly affected by the distribution of these covariates in the study population. The patients with mesothelioma were best discriminated from the control subjects with either the youngest age, the highest GFR, or the largest BMI. Furthermore, the control subjects were significantly better differentiated from stage II to IV than from stage I mesothelioma. MPF, not SM, was an independent negative prognostic factor, but only if adjusted for the biomarker-associated covariates., Conclusions: SM and MPF levels were affected by the same clinical covariates, which also had a significant impact on their diagnostic and prognostic value. To improve the interpretation of biomarker results, age, GFR, and BMI should be routinely recorded. Approaches to account for these covariates require further validation, as does the prognostic value of SM and MPF.

Advanced non-small-cell lung cancers are diseases of late diagnosis with bad prognosis. Conventional chemotherapies are not very efficient. Over the last years, many research works have been performed in this way to improve prognosis. Targeted therapies seem promising. They were notably developed against epithelial growth factor receptors and tumoral angiogenesis. We report here the clinical history of a patient with an advanced non-small-cell lung cancer presenting an exceptional response to small-molecule tyrosine kinase inhibitors.

Infiltrative lung lesions are not always linked to infectious processes or cancers. An interesting entity, the OP (Organizing Pneumonia) or COP (Cryptogenic Organizing Pneumonia)--formerly BOOP (Bronchiolitis Obliterans Organizing Pneumonia)--is discussed through observations repor. ted in this article. We provide some keys to allow the astute observer to target this often curable disease.