Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (>75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P<0.001). Using specific thresholds, patients with ⩾25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P<0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease

Potentials of Plasma NGAL and MIC-1 as Biomarker(s) in the Diagnosis of Lethal Pancreatic Cancer

Pancreatic cancer (PC) is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s) is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL) and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1) are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91) and compared it with those in healthy control (HC) individuals (n = 24) and patients with chronic pancreatitis (CP, n = 23). The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (± standard deviation, SD) plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2), 219.2 U/mL (7.8) and 4.5 ng/mL (4.1), respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81%) but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively). For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively). CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage 1/2) pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml). Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029). Overall, MIC-1 in combination with CA19-9 improved the diagnostic accuracy of differentiating PC from CP and HCs

A national cross-sectional study among drug-users in France: epidemiology of HCV and highlight on practical and statistical aspects of the design

<p>Abstract</p> <p>Background</p> <p>Epidemiology of HCV infection among drug users (DUs) has been widely studied. Prevalence and sociobehavioural data among DUs are therefore available in most countries but no study has taken into account in the sampling weights one important aspect of the way of life of DUs, namely that they can use one or more specialized services during the study period. In 2004–2005, we conducted a national seroepidemiologic survey of DUs, based on a random sampling design using the Generalised Weight Share Method (GWSM) and on blood testing.</p> <p>Methods</p> <p>A cross-sectional multicenter survey was done among DUs having injected or snorted drugs at least once in their life. We conducted a two stage random survey of DUs selected to represent the diversity of drug use. The fact that DUs can use more than one structure during the study period has an impact on their inclusion probabilities. To calculate a correct sampling weight, we used the GWSM. A sociobehavioral questionnaire was administered by interviewers. Selected DUs were asked to self-collect a fingerprick blood sample on blotting paper.</p> <p>Results</p> <p>Of all DUs selected, 1462 (75%) accepted to participate. HCV seroprevalence was 59.8% [95% CI: 50.7–68.3]. Of DUs under 30 years, 28% were HCV seropositive. Of HCV-infected DUs, 27% were unaware of their status. In the month prior to interview, 13% of DUs shared a syringe, 38% other injection parapharnelia and 81% shared a crack pipe. In multivariate analysis, factors independently associated with HCV seropositivity were age over 30, HIV seropositivity, having ever injected drugs, opiate substitution treatment (OST), crack use, and precarious housing.</p> <p>Conclusion</p> <p>This is the first time that blood testing combined to GWSM is applied to a DUs population, which improve the estimate of HCV prevalence. HCV seroprevalence is high, indeed by the youngest DUs. And a large proportion of DUs are not aware of their status. Our multivariate analysis identifies risk factors such as crack consumption and unstable housing.</p

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research