The aim of the present systematic review was to assess the effectiveness and safety of real time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with suspected or known bronchopulmonary carcinoma, as well as in other clinical indications presented by lymphatic adenopathies.A systematic review was carried out in November 2007 and updated in April 2008 using the main databases. Inclusion and exclusion criteria were applied to the papers retrieved.A total of 20 publications were included. Of these, 14 were original studies that investigated the clinical usefulness of the technique in visualising and staging lymph nodes in patients with suspected or established lung cancer. Sensitivity ranged 85-100% and negative predictive value ranged 11-97.4%. Three studies assessed the clinical usefulness of the technique in the diagnosis of sarcoidosis. EBUS-TBNA was diagnostic in 88-93% of patients. One retrospective study evaluated the use of EBUS-TBNA in the diagnosis of lymphoma. None of the studies included in the present review reported important complications.Endobronchial ultrasound-guided transbronchial needle aspiration is a safe and highly accurate procedure for the examination and staging of mediastinal and hilar lymph nodes in patients with known or suspected lung malignancy. The evidence is promising for sarcoidosis but is not sufficient for lymphoma.

The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a metaanalysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/ index.html). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9-3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9-1.1). The metaanalysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-OR m2/m2 : 1.9, 95% confidence interval: 1.4-2.7; Pooled OR m2m2 : 2.0, 95% confidence interval:1.3-3.1; OR m1m2 or [infi]m2m2 : 1.3, 95% confidence interval: 1.1-1.6). The association was present for the CYP1A1 (exon 7) polymorphism (OR Val/Val : 2.2, 95% confidence interval: 1.1-4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer. Genet Med 2008:10(6):369-384. Key Words: GSTM1, CYP1A1, oral and pharyngeal cancers, epidemiology, meta-analysis and pooled analysis Glutathione S-transferasesThe Glutathione S-transferases (GSTs) comprise a family of phase II detoxifying enzymes that catalyze a large number of reactions taking place between the cytosolic glutathione and compounds containing an electrophilic center. 1 These enzymes are involved in the elimination of xenobiotics and endogenous products of oxidative stress formed as a result of aerobic metabolism, exposure to ionizing radiation or any other process that causes cellular damage. Substrates for GSTs include acetaldehyde and several polyaromatic hydrocarbons (PAHs) found in tobacco smoke. The main steps for GST catalysis includes the formation of a complex with the cytosolic glutathione and the ionization of the sulfydryl group of this enzyme bound to glutathione to yield a highly reactive thiolate anion through hydrogen bonding with the adjacent hydroxyl

Stage III non-small cell lung cancer (NSCLC) includes a highly heterogeneous group of patients with differences in the extent and localization of disease. Many aspects of stage III disease are controversial. The data supporting treatment approaches are often subject to a number of limitations, due to the heterogeneous patient populations involved in the trials. Furthermore, the definition of stage III disease has changed over time, and early studies were frequently inadequately powered to detect small differences in therapeutic outcome, were not randomized, or had a limited follow-up times. Major improvements in therapy, including the use of more active chemotherapy agents and refinements in radiation and surgical techniques, also limit the interpretation of earlier clinical trials. Lastly, improvements in pretreatment staging have led to reclassification of patients with relatively minimal metastatic disease as stage IV rather than stage III, leading to an apparent increase in the overall survival of both stage III and IV patients. Median overall stage III NSCLC survival ranges from 9 to 34 months. Higher survival rates are observed in younger Caucasian women with good performance status, adenocarcinoma, mutations, stage IIIA, and in patients with multidisciplinary-team-based diagnoses.

The understanding of the benefit risk profile, and relative effectiveness of a new medicinal product, are initially established in a circumscribed patient population through clinical trials. There may be uncertainties associated with the new medicinal product that cannot be, or do not need to be resolved before launch. Postlicensing or postlaunch evidence generation (PLEG) is a term for evidence generated after the licensure or launch of a medicinal product to address these remaining uncertainties. PLEG is thus part of the continuum of evidence development for a medicinal product, complementing earlier evidence, facilitating further elucidation of a product's benefit/risk profile, value proposition, and/or exploring broader aspects of disease management and provision of healthcare. PLEG plays a role in regulatory decision making, not only in the European Union but also in other jurisdictions including the USA and Japan. PLEG is also relevant for downstream decision‐making by health technology assessment bodies and payers. PLEG comprises studies of different designs, based on data collected in observational or experimental settings. Experience to date in the European Union has indicated a need for improvements in PLEG. Improvements in design and research efficiency of PLEG could be addressed through more systematic pursuance of Scientific Advice on PLEG with single or multiple decision makers. To date, limited information has been available on the rationale, process or timing for seeking PLEG advice from regulators or health technology assessment bodies. This article sets out to address these issues and to encourage further uptake of PLEG advice.

Currently, there is no universal agreement on galactosaemia screening, fundamentally because of the risk-benefit uncertainties. We conducted two exhaustive systematic searches in the main electronic databases (PubMed, Embase, Cochrane, etc.) to recover relevant information about the disease and screening test/s in order to support decision making in Spain. All of the 45 studies identified that covered disease issues were retrospective case series or cross-sectional analysis (level-4 evidence). Studies consistently found that the majority of patients presented characteristic symptomatology before diagnosis. Long term disabilities were not significantly correlated with age of diagnosis, onset of dietary restriction or strict diet compliance. The five studies that provided accuracy data used different cut-off points and verification tests, and thus differed in their definitions of a positive case (level-3b evidence). The estimated sensitivity was 100 % and the specificity 99.9 %. The false-positive rate ranged from 0.0005 % to 0.25 %, and the PPV from 0 % to 64.3 %. The comparative clinical effectiveness in relation to not screening or implementation of other programs is unknown. In summary, existing evidence remains insufficient to establish the appropriateness of newborn screening for galactosaemia screening, although health benefits could be expected if early diagnosis and treatment is achieved. If screening is implemented in Spain, it would be important that a pilot programme be implemented to assess false positive rate and ensure that early diagnosis is not delayed.