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Sera F.,Molecular and Nutritional Epidemiology Unit | Ferrari P.,International Agency for Research on Cancer
PLoS ONE | Year: 2015

In a multicenter study, the overall relationship between exposure and the risk of cancer can be broken down into a within-center component, which reflects the individual level association, and a between-center relationship, which captures the association at the aggregate level. A piecewise exponential proportional hazards model with random effects was used to evaluate the association between dietary fiber intake and colorectal cancer (CRC) risk in the EPIC study. During an average follow-up of 11.0 years, 4,517 CRC events occurred among study participants recruited in 28 centers from ten European countries. Models were adjusted by relevant confounding factors. Heterogeneity among centers was modelled with random effects. Linear regression calibration was used to account for errors in dietary questionnaire (DQ) measurements. Risk ratio estimates for a 10 g/day increment in dietary fiber were equal to 0.90 (95%CI: 0.85, 0.96) and 0.85 (0.64, 1.14), at the individual and aggregate levels, respectively, while calibrated estimates were 0.85 (0.76, 0.94), and 0.87 (0.65, 1.15), respectively. In multicenter studies, over a straightforward ecological analysis, random effects models allow information at the individual and ecologic levels to be captured, while controlling for confounding at both levels of evidence. © 2015 Sera, Ferrari. Source


Papadia C.,University College London | Papadia C.,University of Parma | Kelly P.,Queen Mary, University of London | Kelly P.,University of Zambia | And 7 more authors.
Clinical Nutrition | Year: 2010

Background & aims: Studies have shown that the circulating citrulline concentration is decreased in patients with proximal small bowel villous atrophy from coeliac disease and more so in patients with extensive damage to the intestinal mucosa, but there have been few data on HIV enteritis and tropical enteropathy (TE). Our primary aim was to correlate serum citrulline with the degree of reduction of the enterocyte mass in HIV-infected patients with TE. Methods: Postabsorptive fasting serum citrulline was measured in 150 TE pts, 44 of whom had HIV infection, using reverse phase, high performance liquid chromatography. Absorptive capacity and permeability were measured after intrajejunal instillation of 4 sugars (5 g lactulose, 1 g l-rhamnose, 0.5 g d-xylose, 0.2 g 3-O methyl Dglucose) with assay by thin-layer chromatography. Morphometric analysis was carried out on jejunal biopsies. Results: In HIV positive patients, the median serum citrulline was significantly lower (median 19, interquartile range (IQR) 17-24 μmol/L) than in HIV negative patients (median 27, IQR 23-33 μmol/L; p < 0.001). There were statistically significant correlations (p < 0.005) between citrulline and: crypt depth; villous height/crypt depth ratio; Shenk-Klipstein score; and xylose absoption, only in the HIV positive. Conclusions: Serum citrulline concentration appears to be a quantitative biomarker of small bowel mass integrity in HIV positive enteropathy and desrves assessment as a surrogate for monitoring anti-retroviral therapy. © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. Source


Fucini C.,Section of General and Oncological Surgery | Messerini L.,University of Florence | Saieva C.,Molecular and Nutritional Epidemiology Unit | Orzalesi L.,Section of General and Oncological Surgery | And 2 more authors.
Colorectal Disease | Year: 2012

Aim The expression of pro-apoptotic (Bax) and anti-apoptotic (mutated p53, Bcl-2, Bclxl) proteins was determined retrospectively using immunohistochemistry in pre-treatment biopsy samples from patients with rectal cancer treated with or without preoperative chemoradiation to investigate their role as prognostic markers and indicators of radiochemosensitivity. Method Biopsy samples from 67 patients operated for stage II/III rectal cancer and enrolled in an active follow-up programme were examined 8-10years after surgery. Thirty-three had been treated with immediate surgery followed, in selected cases, by adjuvant postoperative chemoradiation. Thirty-four had preoperative chemoradiation. Immunohistochemical staining was carried out using an automated immunostainer on sections of paraffin-embedded tissue. Results Independent prognostic factors for rectal cancer death were pN status (hazard ratio 3.82; 95% CI 1.67-8.73) and a high level of Bclxl positivity (hazard ratio 4.75; 95% CI 2.10-10.72) according to multivariate regression analysis by stepwise selection. Bax expression was associated with downstaging and higher survival in irradiated patients (P=0.0004). Conclusion Pretreatment evaluation of apoptotic Bax and anti-apoptotic Bclxl factors in biopsy samples of stage II/III rectal cancers may be helpful in selecting tumours that will respond to chemoradiation or in identifying patients who will have limited benefit from chemoradiation and should therefore be selected for a more aggressive systemic regimen. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland. Source


Cecchi M.,Careggi Hospital | Vaiani M.,Careggi Hospital | Ceroti M.,Molecular and Nutritional Epidemiology Unit | Banfi R.,Careggi Hospital
International Journal of Clinical Pharmacy | Year: 2013

Background Recurrent glioblastoma is nearly always fatal, with median survival rates of approximately 12-14 months. Previous phase II clinical trials showed promising results with bevacizumab, alone or in combination with irinotecan, in patients with recurrent glioblastoma. Objective To assess whether the survival of patients with recurrent glioblastoma receiving bevacizumab alone or with irinotecan in everyday practice is comparable to that reported in clinical trials. Setting This was a retrospective observational study conducted at a single hospital in Italy. Method Patients with recurrent glioblastoma who had received bevacizumab alone or with irinotecan from January 2009 to September 2011 were included in our study. Main outcome measure Progression-free survival (PFS) and overall survival (OS), and rates of PFS and OS at 6 months. Results Median PFS was 5.1 months in the bevacizumab group (n = 9) and 15.4 months in the bevacizumab + irinotecan group (n = 10), with 6-month PFS rates of 45 and 69 %, respectively. Median OS was 6.8 months for bevacizumab alone and 11.1 months for bevacizumab + irinotecan, with 6-month OS rates of 100 and 90 %, respectively. Conclusion Although the number of patients included is not sufficient to allow a conclusive statement about the place of bevacizumab in the treatment of recurrent glioblastoma, the data appear promising, and are consistent with the results of clinical trials. © 2013 Springer Science+Business Media Dordrecht. Source


Chan S.S.M.,University of East Anglia | Chan S.S.M.,Norwich University | Luben R.,University of Cambridge | Olsen A.,Danish Cancer Society | And 23 more authors.
American Journal of Gastroenterology | Year: 2013

OBJECTIVES:Obesity is associated with a proinflammatory state that may be involved in the etiology of inflammatory bowel disease (IBD), for which there are plausible biological mechanisms. Our aim was to perform the first prospective cohort study investigating if there is an association between obesity and the development of incident IBD.METHODS:A total of 300,724 participants were recruited into the European Prospective Investigation into Cancer and Nutrition study. At recruitment, anthropometric measurements of height and weight plus physical activity and total energy intake from validated questionnaires were recorded. The cohort was monitored identifying participants who developed either Crohn's disease (CD) or ulcerative colitis (UC). Each case was matched with four controls and conditional logistic regression used to calculate odds ratios (ORs) for body mass index (BMI) adjusted for smoking, energy intake, and physical activity.RESULTS:In the cohort, 177 participants developed incident UC and 75 participants developed incident CD. There were no associations with the four higher categories of BMI compared with a normal BMI for UC (P trend =0.36) or CD (P trend =0.83). The lack of associations was consistent when BMI was analyzed as a continuous or binary variable (BMI 18.5<25.0 vs. ≥25 kg/m 2). Physical activity and total energy intake, factors that influence BMI, did not show any association with UC (physical activity, P trend =0.79; total energy intake, P trend =0.18) or CD (physical activity, P trend =0.42; total energy, P trend =0.11).CONCLUSIONS:Obesity as measured by BMI is not associated with the development of incident UC or CD. Alternative measures of obesity are required to further investigate the role of obesity in the development of incident IBD. © 2013 by the American College of Gastroenterology. Source

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