Geriatric factors associated with overall survival in older patients with metastatic colorectal cancer.

Advanced age in patients with colorectal cancer is a factor of poor prognosis, but little is known about geriatric factors associated with survival and chemotherapy prescription in frail elderly patients. Our research sought to investigate these factors in older patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: patients aged ≥75 years, who were treated for mCRC and have had a Comprehensive Geriatric Assessment (CGA) due to their frailty, were included in this multicenter practice study in the Loire Valley region (France). With initial patient care for mCRC as the starting point, demographic, oncological, geriatric and survival data were collected from the regional cancer database and the medical record of each patient. We analyzed overall survival and chemotherapy prescription, according to the geriatric factors of the CGA. RESULTS: 108 patients were enrolled (mean age 84.0 +/- 4.5 years; 57.4 % men), among whom 53 (49 %) received at least one line of chemotherapy. The median overall survival [95 %CI] was 8.05 [5.6-12.0] months. In univariate analysis, prescription of chemotherapy was associated with the number of severe co-morbidities, number of co-medications, G8 score, BMI, MMSE score, IADL and ADL scores, Lee index and Balducci criteria. Survival was significantly associated with chemotherapy, ADL and IADL scores, G8 score, repeated falls, number of severe co-morbidities, MMSE score, Lee index and Balducci criteria. In multivariate analysis, only the ADL score (HR [95 %CI]: 0.74 [0.55-0.99], p = 0.04), number of severe co-morbidities (HR [95 %CI]: 1.62 [1.06-2.47], p = 0.03) and repeated falls (HR [95 %CI]: 3.54 [1.70-7.39], p < 0.001) were significantly associated with survival. CONCLUSION: in frail elderly patients with mCRC, dependency, co-morbidities and repeated falls are independent factors associated with survival. As such, there could be merit in taking these into consideration before the choice of oncological treatment is made.

Advanced glycoxidation end products in commonly consumed foods.

OBJECTIVE: Advanced glycoxidation end products (AGEs), the derivatives of glucose-protein or glucose-lipid interactions, are implicated in the complications of diabetes and aging. The objective of this article was to determine the AGE content of commonly consumed foods and to evaluate the effects of various methods of food preparation on AGE production. DESIGN: Two-hundred fifty foods were tested for their content in a common AGE marker (epsilon)N-carboxymethyllysine (CML), using an enzyme-linked immunosorbent assay based on an anti-CML monoclonal antibody. Lipid and protein AGEs were represented in units of AGEs per gram of food. RESULTS: Foods of the fat group showed the highest amount of AGE content with a mean of 100+/-19 kU/g. High values were also observed for the meat and meat-substitute group, 43+/-7 kU/g. The carbohydrate group contained the lowest values of AGEs, 3.4+/-1.8 kU/g. The amount of AGEs present in all food categories was related to cooking temperature, length of cooking time, and presence of moisture. Broiling (225 degrees C) and frying (177 degrees C) resulted in the highest levels of AGEs, followed by roasting (177 degrees C) and boiling (100 degrees C). CONCLUSIONS: The results indicate that diet can be a significant environmental source of AGEs, which may constitute a chronic risk factor for cardiovascular and kidney damage.

Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy.

Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-alphabeta-actin mRNA ratio was 1.4 +/- 0.5 on H-AGE and 0.9 +/- 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 +/- 429 and 698 +/- 347 ngml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-alpha rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.