Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci.

Pleiotropic Analysis of Lung Cancer and Blood Triglycerides.

Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.

High performance of F-fluorodeoxyglucose positron emission tomography and contrast-enhanced CT in a rapid outpatient diagnostic program for patients with suspected lung cancer.

Background: The diagnostic evaluation of patients presenting with possible lung cancer is often complex and time consuming. A rapid outpatient diagnostic program (RODP) including (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contrast-enhanced computed tomography (CT) as a routine diagnostic tool may improve timeliness, however the diagnostic performance of such a combined approach of RODP remains unclear.

Objectives: We evaluated timeliness of care and diagnostic performance of FDG-PET and contrast-enhanced CT (FDG-PET/CT) in an RODP for all patients referred with a chest X-ray suspicious of lung cancer.

The faster the better?—A systematic review on distress in the diagnostic phase of suspected cancer, and the influence of rapid diagnostic pathways.

Objective: To perform a systematic review of articles published in the last 25 years on prevalence and course of distress and quality of life surrounding the diagnostic process of suspected cancer, and the influence of rapid diagnostic programs.

Methods: Twenty-three articles were identified via Pubmed, PsycINFO, and reference lists of articles. Except for three randomized clinical trials and one case control study all studies were uncontrolled cohort studies.

EBUS and EUS guided fine needle aspirations for molecular diagnostic analysis in lung cancer.

In daily clinical practice the diagnosis of lung cancer is often based on cytological specimens. These cytological samples are increasingly obtained by ultrasound-guided techniques with fine needle aspirations. Recent developments have shown that transesophageal ultrasound guided fine needle aspiration (EUS-FNA) and endobronchial ultrasound guided transbronchial fine needle aspiration (EBUS-TBNA) are minimally invasive diagnostic and staging procedures that have shown to be highly sensitive and accurate.

Increased risk of lung cancer in individuals with a family history of the disease: a pooled analysis from the International Lung Cancer Consortium.

Background And Methods: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium.

Differences in metabolism between adeno- and squamous cell non-small cell lung carcinomas: spatial distribution and prognostic value of GLUT1 and MCT4.

Background: Hypoxia leads to changes in tumor cell metabolism such as increased glycolysis. In this study, we examined the spatial distribution of the glycolysis and hypoxia related markers glucose transporter 1 (GLUT1) and monocarboxylate transporter 4 (MCT4) expression in relation to the vasculature in stage I, II and resectable stage IIIA NSCLC. Furthermore, associations of these markers with survival were investigated.

Timeliness of lung cancer diagnosis and treatment in a rapid outpatient diagnostic program with combined 18FDG-PET and contrast enhanced CT scanning.

Introduction: Delays in the diagnosis of lung cancer are under debate and may affect outcome. The objectives of this study were to compare various delays in a rapid outpatient diagnostic program (RODP) for suspected lung cancer patients with those described in literature and with guideline recommendations, to investigate the effects of referral route and symptoms on delays, and to establish whether delays were related to disease stage and outcome.

Methods: A retrospective chart study was conducted of all patients with suspected lung cancer, referred to the RODP of our tertiary care university clinic between 1999 and 2009.

EUS-FNA for the detection of left adrenal metastasis in patients with lung cancer.

In patients with lung cancer, enlarged or (18)Fluoro-deoxyglucose positron emission tomography ((18)FDG-PET) positive left adrenal glands are suspected for distant metastases and require tissue confirmation for a definitive assessment. The aim of this study was to assess the sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for left adrenal metastases in lung cancer patients with a suspect adrenal gland based on imaging. EUS-FNA findings of patients with (suspected) lung cancer and CT enlarged or (18)FDG-PET positive left adrenal glands were retrospectively evaluated.

A brief retrospective report on the feasibility of epidermal growth factor receptor and KRAS mutation analysis in transesophageal ultrasound- and endobronchial ultrasound-guided fine needle cytological aspirates.

Introduction: Molecular testing for epidermal growth factor receptor (EGFR) and KRAS mutations is of increasing clinical importance in daily practice. In this study, we aimed to investigate the yield and applicability of molecular testing for KRAS and EGFR mutations in cytologic specimens obtained by EUS or endobronchial ultrasound (EBUS)-guided fine needle aspiration (FNA).

Methods: We selected all patients with an EUS- or EBUS-guided FNA positive for lung adenocarcinoma from the database of our tertiary care center for endosonography.

Clinical aspects and treatment of primary tracheal malignancies.

Conclusions: Selecting patients that are candidates for surgical treatment is important in the work-up of patients with tracheal cancer. Toward this goal, centralization of care concerning tracheal tumors is advised. Centralization may increase long-term survival and decrease operative morbidity and mortality even further.

Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium.

Background: Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies.

Methods: Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled.

The role of (18)F-FDG PET in the differentiation between lung metastases and synchronous second primary lung tumours.

Purpose: In lung cancer patients with multiple lesions, the differentiation between metastases and second primary tumours has significant therapeutic and prognostic implications. The aim of this retrospective study was to investigate the potential of (18)F-FDG PET to discriminate metastatic disease from second primary lung tumours.

Methods: Of 1,396 patients evaluated by the thoracic oncology group between January 2004 and April 2009 at the Radboud University Nijmegen Medical Centre, patients with a synchronous second primary lung cancer were selected.

Non-invasive mechanical ventilation for diagnostic bronchoscopy using a new face mask: an observational feasibility study.

Purpose: Bronchoscopy is an indispensable tool for invasive pulmonary evaluation with high diagnostic yield and low incidence of major complications. However, hypoxemia increases the risk of complications, in particular after bronchoalveolar lavage. Non-invasive positive pressure ventilation may prevent hypoxemia associated with bronchoalveolar lavage.

Circulating DNA is a non-invasive prognostic factor for survival in non-small cell lung cancer.

Introduction: Circulating plasma DNA is present in a considerably higher concentration in lung cancer patients than in controls. Conflicting data are reported about circulating DNA as a prognostic factor. The aim of this study was to prospectively analyse the relationship of circulating plasma DNA with overall survival (OS) of previously untreated non-small cell lung cancer (NSCLC) patients.

The PI3-K/AKT-pathway and radiation resistance mechanisms in non-small cell lung cancer.

The phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (AKT) pathway is associated with all three major radiation resistance mechanisms: intrinsic radiosensitivity, tumor cell proliferation, and hypoxia. In cell signaling cascades, the PI3-K/AKT signaling pathway is a key regulator of normal and cancerous growth and cell fate decisions by processes such as proliferation, invasion, apoptosis, and induction of hypoxia-related proteins. Activation of this pathway can be the result of stimulation of receptor tyrosine kinases such as epidermal growth factor receptor or vascular endothelial growth factor receptor or from mutations or amplification of PI3-K or AKT itself which are frequently found in non-small cell lung cancer (NSCLC).

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.

Undertreatment of tracheal carcinoma: multidisciplinary audit of epidemiologic data.

National epidemiologic data were examined to determine the eligibility for curative therapy in tracheal carcinoma. An expert audit of primary tracheal carcinomas registered from 2000 to 2005 with the Netherlands Cancer Registry (NCR) included blinded patient data and radiographic review to assess diagnosis and resectability. Actual treatment was compared with the opinions of a multidisciplinary panel (Radboud panel) and a second reviewer.

Prognostic value of different metabolic measurements with fluorine-18 fluorodeoxyglucose positron emission tomography in resectable non-small cell lung cancer: a two-center study.

Introduction: Standard uptake value (SUV) is a quantitative measure for the preferential uptake of a radiopharmaceutical in a tumor compared with the homogeneous distribution in the body. SUV can be based on the maximal value of one pixel (SUVmax) or on the mean value in a region outlined by isodensity contours. The prognostic value of different SUVs in non-small cell lung cancer (NSCLC) is not established.

Predictive and prognostic value of FDG-PET in nonsmall-cell lung cancer: a systematic review.

For several years, molecular imaging with (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has become part of the standard of care in presurgical staging of patients with nonsmall-cell lung cancer (NSCLC), focusing on the detection of malignant lesions at early stages, early detection of recurrence, and metastatic spread. Currently, there is an increasing interest in the role of FDG-PET beyond staging, such as the evaluation of biological characteristics of the tumor and prediction of prognosis in the context of treatment stratification and the early assessment of tumor response to therapy. In this systematic review, the literature on the value of the evolving applications of FDG-PET as a marker for prediction (ie, therapy response monitoring) and prognosis in NSCLC is addressed, divided in sections on the predictive value of FDG-PET in locally advanced and advanced disease, the prognostic value of FDG-PET at diagnosis, after induction treatment, and in recurrent disease.

Chemotherapy response evaluation with 18F-FDG PET in patients with non-small cell lung cancer.

Unlabelled: The aim of this prospective study was to evaluate the value of (18)F-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism.

Methods: In 51 patients, dynamic (18)F-FDG PET was performed before and at 5-8 wk into treatment.

Impaired isotonic contractility and structural abnormalities in the diaphragm of congestive heart failure rats.

Background: Metabolic alterations and decreased isometric force generation have been demonstrated in different animal models for congestive heart failure (CHF). However, as few morphological examinations have been performed on the CHF diaphragm, it is unknown if structural abnormalities comprise a substrate for diaphragm dysfunction in CHF. Therefore, we investigated CHF diaphragm isometric and isotonic contractility together with the presence of structural abnormalities.

Diaphragm single-fiber weakness and loss of myosin in congestive heart failure rats.

Diaphragm weakness commonly occurs in patients with congestive heart failure (CHF) and is an independent predictor of mortality. However, the pathophysiology of diaphragm weakness is poorly understood. We hypothesized that CHF induces diaphragm weakness at the single-fiber level by decreasing myosin content.