Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Structural evolution of the Pico del Águila anticline (External Sierras, southern Pyrenees) derived from sandbox, numerical and 3D structural modelling techniques

This paper reports on the integration of different modelling techniques to construct a unified conceptual model of structural evolution of the Pico del Águila anticline (External Sierras, southern Pyrenees, Spain). The structure is a well-known example of a detachment fold, which exhibits a N-S structural trend, perpendicular to the general structural trend of the southern Pyrenees (mainly E-W). Based on field observations of an unevenly distributed Triassic décollement, analogue modelling shows how to generate orogen-perpendicular structures which may result in transverse anticlines. The models show how contrasts between high and low friction patches in the basal décollement led to the formation of structures at high angle, centered over the high friction areas. Numerical models investigate the effect of a complex mechanical stratigraphy, characterized by an interlayering of competent and incompetent layers, plus syn-kinematic sedimentation in the fold growth. Based on field data and seismic interpretations, a 3D reconstruction and sequential geomechanical restoration of the Pico del Águila anticline suggests the coexistence of multiple folding mechanisms occurring simultaneously in different units and structural domains of the fold, leading to a complex strain pattern that can not be assessed by simplistic kinematic 2D approaches. By integrating the models with previous data in the region, the benefits and drawbacks of each modelling technique are discussed and an integrated model of structural evolution for the Pico del Águila anticline is presented. This enables a better comprehension of the structure as well as of the processes that drove the evolution of the N-S detachment anticlines in the external Sierras of the southern Pyrenees

Initial Medical Attention on Patients with Early-Stage Non-Small Cell Lung Cancer

Detection of early stage non-small cell lung cancer (NSCLC) is commonly believed to be incidental. Understanding the reasons that caused initial detection of these patients is important for early diagnosis. However, these reasons are not well studied.We retrospectively reviewed medical records of patients diagnosed with stage I or II NSCLC between 2000 and 2009 at UT MD Anderson Cancer Center. Information on suggestive LC-symptoms or other reasons that caused detection were extracted from patients' medical records. We applied univariate and multivariate analyses to evaluate the association of suggestive LC-symptoms with tumor size and patient survival.Of the 1396 early stage LC patients, 733 (52.5%) presented with suggestive LC-symptoms as chief complaint. 347 (24.9%) and 287 (20.6%) were diagnosed because of regular check-ups and evaluations for other diseases, respectively. The proportion of suggestive LC-symptom-caused detection had a linear relationship with the tumor size (correlation 0.96; with p<.0001). After age, gender, race, smoking status, therapy, and stage adjustment, the symptom-caused detection showed no significant difference in overall and LC-specific survival when compared with the other (non-symptom-caused) detection.Symptoms suggestive of LC are the number one reason that led to detection in early NSCLC. They were also associated with tumor size at diagnosis, suggesting early stage LC patients are developing symptoms. Presence of symptoms in early stages did not compromise survival. A symptom-based alerting system or guidelines may be worth of further study to benefit NSCLC high risk individuals

Bacterial and fungal microflora in surgically removed lung cancer samples

<p>Abstract</p> <p>Background</p> <p>Clinical and experimental data suggest an association between the presence of bacterial and/or fungal infection and the development of different types of cancer, independently of chemotherapy-induced leukopenia. This has also been postulated for the development of lung cancer, however the prevalence and the exact species of the bacteria and fungi implicated, have not yet been described.</p> <p>Aim</p> <p>To determine the presence of bacterial and fungal microflora in surgically extracted samples of patients with lung cancer.</p> <p>Materials and methods</p> <p>In this single-center prospective, observational study, tissue samples were surgically extracted from 32 consecutive patients with lung cancer, and reverse-transcription polymerase chain reaction (RT-PCR) was used to identify the presence of bacteria and fungi strains.</p> <p>Results</p> <p>The analysis of the electrophoresis data pointed out diversity between the samples and the strains that were identified. Mycoplasma strains were identified in all samples. Strains that appeared more often were Staphylococcus epidermidis, Streptococcus mitis and Bacillus strains, followed in descending frequency by Chlamydia, Candida, Listeria, and Haemophilus influenza. In individual patients Legionella pneumophila and Candida tropicalis were detected.</p> <p>Conclusions</p> <p>A diversity of pathogens could be identified in surgically extracted tissue samples of patients with lung cancer, with mycoplasma strains being present in all samples. These results point to an etiologic role for chronic infection in lung carcinogenesis. Confirmation of these observations and additional studies are needed to further characterize the etiologic role of inflammation in lung carcinogenesis.</p

Do diagnostic delays in cancer matter?

background: The United Kingdom has poorer cancer outcomes than many other countries due partly to delays in diagnosing symptomatic cancer, leading to more advanced stage at diagnosis. Delays can occur at the level of patients, primary care, systems and secondary care. There is considerable potential for interventions to minimise delays and lead to earlier-stage diagnosis. methods: Scoping review of the published studies, with a focus on methodological issues. results: Trial data in this area are lacking and observational studies often show no association or negative ones. This review offers methodological explanations for these counter-intuitive findings. conclusion: While diagnostic delays do matter, their importance is uncertain and must be determined through more sophisticated methods

Non-small-cell lung cancer in a French department, (1982–1997): management and outcome

Addition of chemotherapy to the treatment of non-small-cell lung cancer (NSCLC) resulted in a modest but clear improvement in the survival of selected patients. To ascertain if this translates to improved survival in the whole population of patients, we conducted a retrospective population-based study of a sample of 1738 patients diagnosed with primary NSCLC in a French department between 1982 and 1997. The proportion of women, metastatic cases and adenocarcinoma changed significantly over time, as did their management: use of chemotherapy alone increased from 9.7 to 28.1% (P<0.0001), while the use of radiotherapy alone decreased from 32.2 to 9.4% (P<0.0001). The 5-year survival probability was 15.7 % for all patients and 32.6% for those with resectable disease. The 1- and 2-year survival probabilities were 38.2 and 15.6% in locally advanced disease, and were, respectively, 16.8 and 5.2% in metastatic disease. Disease extent and histological subtype were significant independent prognostic factors. Survival of resectable disease was longer among patients treated with surgery or surgery plus chemotherapy, while better outcomes for locally advanced disease were associated with radiation plus chemotherapy. In metastastic disease, patients treated by classical agent without platin or palliative care only had the shortest survival. Despite changes in treatment in accordance with the state-of-the-art, overall survival did not improve over time. It is not unlikely that more patients with bad PS were diagnosed during the latter end of the study period. This could at least partially explain the absence of detection of an overall improvement in survival

DNA Methylation Changes in Atypical Adenomatous Hyperplasia, Adenocarcinoma In Situ, and Lung Adenocarcinoma

BACKGROUND:Aberrant DNA methylation is common in lung adenocarcinoma, but its timing in the phases of tumor development is largely unknown. Delineating when abnormal DNA methylation arises may provide insight into the natural history of lung adenocarcinoma and the role that DNA methylation alterations play in tumor formation. METHODOLOGY/PRINCIPAL FINDINGS:We used MethyLight, a sensitive real-time PCR-based quantitative method, to analyze DNA methylation levels at 15 CpG islands that are frequently methylated in lung adenocarcinoma and that we had flagged as potential markers for non-invasive detection. We also used two repeat probes as indicators of global DNA hypomethylation. We examined DNA methylation in 249 tissue samples from 93 subjects, spanning the putative spectrum of peripheral lung adenocarcinoma development: histologically normal adjacent non-tumor lung, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS, formerly known as bronchioloalveolar carcinoma), and invasive lung adenocarcinoma. Comparison of DNA methylation levels between the lesion types suggests that DNA hypermethylation of distinct loci occurs at different time points during the development of lung adenocarcinoma. DNA methylation at CDKN2A ex2 and PTPRN2 is already significantly elevated in AAH, while CpG islands at 2C35, EYA4, HOXA1, HOXA11, NEUROD1, NEUROD2 and TMEFF2 are significantly hypermethylated in AIS. In contrast, hypermethylation at CDH13, CDX2, OPCML, RASSF1, SFRP1 and TWIST1 and global DNA hypomethylation appear to be present predominantly in invasive cancer. CONCLUSIONS/SIGNIFICANCE:The gradual increase in DNA methylation seen for numerous loci in progressively more transformed lesions supports the model in which AAH and AIS are sequential stages in the development of lung adenocarcinoma. The demarcation of DNA methylation changes characteristic for AAH, AIS and adenocarcinoma begins to lay out a possible roadmap for aberrant DNA methylation events in tumor development. In addition, it identifies which DNA methylation changes might be used as molecular markers for the detection of preinvasive lesions

Previous Lung Diseases and Lung Cancer Risk: A Systematic Review and Meta-Analysis

In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.Relevant studies were identified through MEDLINE searches. Using random effects models, summary effects of specific previous conditions were evaluated separately and combined. Stratified analyses were conducted based on smoking status, gender, control sources and continent.A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies). The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22-1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI=1.49, 2.08), (from 30 studies). Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR=1.22, 0.97-1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer