Symptom lead times in lung and colorectal cancers: What are the benefits of symptom-based approaches to early diagnosis?

This is the final version of the article. Available from Cancer Research UK via the DOI in this record.Background: Individuals with undiagnosed lung and colorectal cancers present with non-specific symptoms in primary care more often than matched controls. Increased access to diagnostic services for patients with symptoms generates more early-stage diagnoses, but the mechanisms for this are only partially understood. Methods: We re-analysed a UK-based case-control study to estimate the Symptom Lead Time (SLT) distribution for a range of potential symptom criteria for investigation. Symptom Lead Time is the time between symptoms caused by cancer and eventual diagnosis, and is analogous to Lead Time in a screening programme. We also estimated the proportion of symptoms in lung and colorectal cancer cases that are actually caused by the cancer. Results: Mean Symptom Lead Times were between 4.1 and 6.0 months, with medians between 2.0 and 3.2 months. Symptom Lead Time did not depend on stage at diagnosis, nor which criteria for investigation are adopted. Depending on the criteria, an estimated 27-48% of symptoms in individuals with as yet undiagnosed lung cancer, and 12-32% with undiagnosed colorectal cancer are not caused by the cancer. Conclusions: In most cancer cases detected by a symptom-based programme, the symptoms are caused by cancer. These cases have a short lead time and benefit relatively little. However, in a significant minority of cases cancer detection is serendipitous. This group experiences the benefits of a standard screening programme, a substantial mean lead time and a higher probability of early-stage diagnosis.This work was supported by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme, RP-PG-0608-10045

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients

<p>Abstract</p> <p>Background</p> <p>Ser-249 TP53 mutation (249^Ser) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249^Sermutation in HCC from patients in Brazil.</p> <p>Methods</p> <p>We studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249^Sermutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR.</p> <p>Results</p> <p>249^Sermutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249^Sermutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249^Sermutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249^Sermutation (OR = 2.415, 95% CI = 1.001 – 5.824, p = 0.05). The mean size of 249^SerHCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249^Sermutation.</p> <p>Conclusion</p> <p>Our results indicate that 249^Sermutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.</p

Symptom lead times in lung and colorectal cancers: what are the benefits of symptom-based approaches to early diagnosis?

BACKGROUND: Individuals with undiagnosed lung and colorectal cancers present with non-specific symptoms in primary care more often than matched controls. Increased access to diagnostic services for patients with symptoms generates more early-stage diagnoses, but the mechanisms for this are only partially understood. METHODS: We re-analysed a UK-based case–control study to estimate the Symptom Lead Time (SLT) distribution for a range of potential symptom criteria for investigation. Symptom Lead Time is the time between symptoms caused by cancer and eventual diagnosis, and is analogous to Lead Time in a screening programme. We also estimated the proportion of symptoms in lung and colorectal cancer cases that are actually caused by the cancer. RESULTS: Mean Symptom Lead Times were between 4.1 and 6.0 months, with medians between 2.0 and 3.2 months. Symptom Lead Time did not depend on stage at diagnosis, nor which criteria for investigation are adopted. Depending on the criteria, an estimated 27–48% of symptoms in individuals with as yet undiagnosed lung cancer, and 12–32% with undiagnosed colorectal cancer are not caused by the cancer. CONCLUSIONS: In most cancer cases detected by a symptom-based programme, the symptoms are caused by cancer. These cases have a short lead time and benefit relatively little. However, in a significant minority of cases cancer detection is serendipitous. This group experiences the benefits of a standard screening programme, a substantial mean lead time and a higher probability of early-stage diagnosis

Toward a “constitution” for behavioral policy-making

Behavioral policy interventions aimed at redirecting individuals’ behavior toward optimal choices are characterized by an important issue which is often overlooked: the lack of an instrument to define what “optimal” means. If agents are subject to behavioral biases leading them to make “wrong” choices, the policy-maker can no longer rely on the revealed preferences approach (e.g., what people choose is what people prefer) for defining a welfare criterion. In this article, we reiterate the argument put forward by some scholars that choosing a suitable welfare criterion once the link between observed choices and individuals’ preferences is broken becomes a problematic task. We review the state of the art in the literature and the possible approaches proposed to overcome the problem, concluding that a solution has not yet been reached. Moreover, we argue that the lack of an established welfare criterion characterizing behavioral policy-making could pave the way to government wanting to restrict individual freedom. In the absence of any legislative constraint for the executive, stating that what individuals choose is not what they prefer in principle justifies any freedom-reducing government intervention, since choices can be arbitrarily labeled “sub-optimal” or “welfare-reducing.” To avoid this risk without turning down the potential of behavioral policy-making, we propose that an independent committee establishes ex ante procedural rules and domains where behavioral policy-making can be implemented. The article suggests some possible examples of normative provisions characterizing this constitution-type document, such as the selective identification of the only sectors where behavioral policies could be effectively applied, the periodic evaluation of policy effects, and the use of sunset clauses

The role of short chain fatty acids in appetite regulation and energy homeostasis

Over the last 20 years there has been an increasing interest in the influence of the gastrointestinal tract on appetite regulation. Much of the focus has been on the neuronal and hormonal relationship between the gastrointestinal tract and the brain. There is now mounting evidence that the colonic microbiota and their metabolic activity play a significant role in energy homeostasis. The supply of substrate to the colonic microbiota has a major impact on the microbial population and the metabolites they produce, particularly short chain fatty acids (SCFAs). SCFAs are produced when non-digestible carbohydrates, namely dietary fibres and resistant starch, undergo fermentation by the colonic microbiota. Both the consumption of fermentable carbohydrates and the administration of SCFAs have been reported to result in a wide range of health benefits including improvements in body composition, glucose homeostasis, blood lipid profiles, and reduced body weight and colon cancer risk. However, published studies tend to report the effects that fermentable carbohydrates and SCFAs have on specific tissues and metabolic processes, and fail to explain how these local effects translate into systemic effects and the mitigation of disease risk. Moreover, studies have tended to investigate SCFAs collectively and neglect to report the effects associated with individual SCFAs. Here, we bring together the recent evidence and suggest an overarching model for the effects of SCFAs on one of their beneficial aspects: appetite regulation and energy homeostasis