Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Malnutrition in hospitalized geriatric patients

The incidence of hospital malnutrition has not been systematically studied in Hong Kong hospitals. This study was initiated to determine if malnutrition in geriatric patients is being under reported and to evaluate the efficacy of a modified monitoring and reporting procedure. Subjects (>65 yr) on congee or enteral diet were medically stable. In the control phase (3 months), newly admitted patients received standard hospital care and 9 out of 67 (13%) were identified as malnourished (CM). The study phase started one month after the last control subject was recruited. Plasma albumin (ALB) <28 g/l and the presence of diarrhea were used as criteria in identifying the malnourished (SM). 16 out of 51 (31%) newly admitted patients were SM. At identification, ALB levels were low (19.5 g/l) but similar between CM & SM. Prealbumin (PA) levels of the SM, however, were higher than that of the CM (0.117 vs 0.087 g/l, p<0.05). A similar trend was observed for plasma transferrin (TRF) (1.34 vs 1.03 g/l, p=0.07). Upon three weeks of nutritional intervention, PA levels were increased by 56% and 66% in the CM and SM, respectively. TRF levels were also increased significantly by 32% and 19%. These data suggest that malnutrition in geriatric patients is a serious problem. A routine but effective procedure should be enforced for early detection and intervention.link_to_subscribed_fulltex

Mitochondrial DNA is a pro-inflammatory damage-associated molecular pattern released during active IBD

The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux transporter that is highly expressed in the colon. In mice, loss of MDR1 function results in colitis with similarities to human inflammatory bowel diseases (IBD). Here, we show that MDR1 has an unexpected protective role for the mitochondria where MDR1 deficiency results in mitochondrial dysfunction with increased mitochondrial reactive oxygen species (mROS) driving the development of colitis. Exogenous induction of mROS accelerates, while inhibition attenuates colitis in vivo; these effects are amplified in MDR1 deficiency. In human IBD, MDR1 is negatively correlated to SOD2 gene expression required for mROS detoxification. To provide direct evidential support, we deleted intestinal SOD2 gene in mice and showed an increased susceptibility to colitis. We exploited the genome-wide association data sets and found many (∼5%) of IBD susceptibility genes with direct roles in regulating mitochondria homeostasis. As MDR1 primarily protects against xenotoxins via its efflux function, our findings implicate a distinct mitochondrial toxin+genetic susceptibility interaction leading to mitochondrial dysfunction, a novel pathogenic mechanism that could offer many new therapeutic opportunities for IBD