No abstract

Background:Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM.Methods:Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98).Results:Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be—beside histology and treatment—an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048).Conclusion:This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.

Albumin level has been shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia are. This approach in clinical settings can be used to guide the choice of oncologic treatment.

Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.

Running head: nontuberculous mycobacteria in CroatiaWord count: 2354 Correspondence Mateja Jankovic, University Hospital Centre Zagreb, Department for Respiratory Diseases, Jordanovac 104, 10 000 Zagreb, Croatia; Email: mateja.jankovic@gmail.com Key words: atypical mycobacteria, epidemiological study, geographical diversity, pulmonary nontuberculous mycobacterial disease, Jankovic, M., Samarzija, M., Sabol, I., Jakopovic, M., Katalinic Jankovic, V., Zmak, L., Ticac, B., Marusic, A., Obrovac, M., van Ingen, J., 2013. Geographical Jankovic, M., Samarzija, M., Sabol, I., Jakopovic, M., Katalinic Jankovic, V., Zmak, L., Ticac, B., Marusic, A., Obrovac, M., van Ingen, J., 2013. Geographical distribution and clinical relevance of non-tuberculous mycobacteria in Croatia. The International Journal of Tuberculosis and Lung Disease 17,[836][837][838][839][840][841]

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence. Its underdiagnosis and hence under-treatment is a general feature across all countries. This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease. A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms. Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV1% predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV1 ≥80% predicted. In recent years, an elegant series of studies has shown that “exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment”. In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation. Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy. This is an essential issue in COPD. In fact, on one hand, airflow limitation, even mild, can unduly limit the patient’s physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease. Therefore, we thought that it was worthwhile to analyze further and discuss this stage of “mild COPD”. To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with “mild” airflow limitation. The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind “mild” COPD. Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both.

Background:To investigate the clinical utility of pretreatment plasma fibrinogen levels in malignant pleural mesothelioma (MPM) patients.Methods:A retrospective multicenter study was performed in histologically proven MPM patients. All fibrinogen levels were measured at the time of diagnosis and clinical data were retrospectively collected after approval of the corresponding ethics committees.Results:In total, 176 MPM patients (mean age: 63.5 years±10.4 years, 38 females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated (⩾390 mg dl−1) plasma fibrinogen levels. When patients were grouped by median fibrinogen, patients with low level (⩽627 mg dl−1) had significantly longer overall survival (OS) (19.1 months, confidence interval (CI) 14.5–23.7 months) when compared with those with high level (OS 8.5; CI 6.2–10.7 months). In multivariate survival analyses, fibrinogen was found to be an independent prognostic factor (hazard ratio 1.81, CI 1.23–2.65). Most interestingly, fibrinogen (cutoff 75th percentile per 750 mg dl−1) proved to be a predictive biomarker indicating treatment benefit achieved by surgery within multimodality therapy (interaction term: P=0.034). Accordingly, only patients below the 75th percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months OS).Conclusions:Fibrinogen is a novel independent prognostic biomarker in MPM. Most importantly, fibrinogen predicted treatment benefit achieved by surgery within multimodality therapy.

Acquisition of immortality as a hallmark of malignant transformation is achieved by telomerase reactivation in the majority of human cancers. Point mutations in the telomerase reverse transcriptase (TERT) gene promoter were recently discovered as one fundamental driver of this process correlating with worse prognosis in several cancer types. The potential role of these mutations in human malignant pleural mesothelioma (MPM) aggressiveness was unknown far. Here we show that presence of TERT promoter mutations identifies a distinct MPM patient subgroup with extremely dismal prognosis. The respective MPM cell explants with TERT promoter mutations are characterized by a profoundly enhanced in vitro immortalization potential, reduced chromosomal instability and a specific mutation/deletion pattern compared to the wild-type counterparts. Consequently, our MPM-based results indicate a unique way of malignant transformation of TERT promoter-mutated tumors which has broad implications also for multiple other cancer types harboring this non-coding genomic alteration.Research.