Cancer survival in England and Wales at the end of the 20th century

Survival has risen steadily since the 1970s for most cancers in adults in England and Wales, but persistent inequalities exist between those living in affluent and deprived areas. These differences are not seen for children. For many of the common adult cancers, these inequalities in survival (the 'deprivation gap') became more marked in the 1990s. This volume presents extended analyses of survival for adults diagnosed during the 14 years 1986-1999 and followed up to 2001, including trends in overall survival in England and Wales and trends in the deprivation gap in survival. The analyses include individual tumour data for 2.2 million cancer patients. This article outlines the structure of the supplement - an article for each of the 20 most common cancers in adults, followed by an expert commentary from one of the leading UK clinicians specialising in malignancies of that organ or system. The available data, quality control and methods of analysis are described here, rather than repeated in each of the 20 articles. We open the discussion between clinicians and epidemiologists on how to interpret the observed trends and inequalities in cancer survival, and we highlight some of the most important contrasts in these very different points of view. Survival improved substantially for adult cancer patients in England and Wales up to the end of the 20th century. Although socioeconomic inequalities in survival are remarkably persistent, the overall patterns suggest that these inequalities are largely avoidable

Serum Apolipoproteins C-I and C-III Are Reduced in Stomach Cancer Patients: Results from MALDI-Based Peptidome and Immuno-Based Clinical Assays

Finding new peptide biomarkers for stomach cancer in human sera that can be implemented into a clinically practicable prediction method for monitoring of stomach cancer. We studied the serum peptidome from two different biorepositories. We first employed a C8-reverse phase liquid chromatography approach for sample purification, followed by mass-spectrometry analysis. These were applied onto serum samples from cancer-free controls and stomach cancer patients at various clinical stages. We then created a bioinformatics analysis pipeline and identified peptide signature discriminating stomach adenocarcinoma patients from cancer-free controls. Matrix Assisted Laser Desorption/Ionization–Time of Flight (MALDI-TOF) results from 103 samples revealed 9 signature peptides; with prediction accuracy of 89% in the training set and 88% in the validation set. Three of the discriminating peptides discovered were fragments of Apolipoproteins C-I and C-III (apoC-I and C-III); we further quantified their serum levels, as well as CA19-9 and CRP, employing quantitative commercial-clinical assays in 142 samples. ApoC-I and apoC-III quantitative results correlated with the MS results. We then employed apoB-100-normalized apoC-I and apoC-III, CA19-9 and CRP levels to generate rules set for stomach cancer prediction. For training, we used sera from one repository, and for validation, we used sera from the second repository. Prediction accuracies of 88.4% and 74.4% were obtained in the training and validation sets, respectively. Serum levels of apoC-I and apoC-III combined with other clinical parameters can serve as a basis for the formulation of a diagnostic score for stomach cancer patients

Development of a context model to prioritize drug safety alerts in CPOE systems

Background: Computerized physician order entry systems (CPOE) can reduce the number of medication errors and adverse drug events (ADEs) in healthcare institutions. Unfortunately, they tend to produce a large number of partly irrelevant alerts, in turn leading to alert overload and causing alert fatigue. The objective of this work is to identify factors that can be used to prioritize and present alerts depending on the 'context' of a clinical situation. Methods: We used a combination of literature searches and expert interviews to identify and validate the possible context factors. The internal validation of the context factors was performed by calculating the inter-rater agreement of two researcher's classification of 33 relevant articles. Results: We developed a context model containing 20 factors. We grouped these context factors into three categories: characteristics of the patient or case (e. g. clinical status of the patient); characteristics of the organizational unit or user (e. g. professional experience of the user); and alert characteristics (e. g. severity of the effect). The internal validation resulted in nearly perfect agreement (Cohen's Kappa value of 0.97). Conclusion: To our knowledge, this is the first structured attempt to develop a comprehensive context model for prioritizing drug safety alerts in CPOE systems. The outcome of this work can be used to develop future tailored drug safety alerting in CPOE systems

Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

<p>Abstract</p> <p>Background</p> <p>Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.</p> <p>Methods</p> <p>To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.</p> <p>Results</p> <p>For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.</p> <p>Conclusions</p> <p>Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.</p

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era