Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank

This is the author accepted manuscriptData availability: All data in this project was part of the UK Biobank resource and was accessed under application number 74981. Information on how to access the UK Biobank can be found at https://www.ukbiobank.ac.uk/enable-your-research/apply-for-accessCode availability: All code used to generate results for this study can be found at the author’s Github page: https://github.com/hdg204/ProstateCancerBackground Prostate cancer is highly heritable, with >250 common variants associated in genome-wide association studies. It commonly presents with non-specific lower urinary tract symptoms that are frequently associated with benign conditions. Methods Cohort study using UK Biobank data linked to primary care records. Participants were men with a record showing a general practice consultation for a lower urinary tract symptom. The outcome measure was prostate cancer diagnosis within two years of consultation. The predictor was a genetic risk score of 269 genetic variants for prostate cancer. Results A genetic risk score (GRS) is associated with prostate cancer in symptomatic men (OR per SD increase=2.12 [1.86 to 2.41] p=3.5e-30). An integrated risk model including age and GRS applied to symptomatic men predicted prostate cancer (AUC 0.768 [0.739 to 0.796]). Prostate cancer incidence was 8.1% (6.7 to 9.7) in the highest risk quintile. In the lowest quintile, prostate cancer incidence was <1%. Conclusions This study is the first to apply GRS in primary care to improve the triage of symptomatic patients. Men with the lowest genetic risk of developing prostate cancer could safely avoid invasive investigation, whilst those identified with the greatest risk could be fast-tracked for further investigation. These results show that a GRS has potential application to improve the diagnostic pathway of symptomatic patients in primary care.Philanthropic Donatio

Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease

Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have therefore purified human biliary epithelial cells (hBECs) from human livers that were not used for liver transplantation. hBECs were tested as a cell therapy in a mouse model of biliary disease in which the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures, and fibrosis. hBECs are expandable and phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5–7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: (1) Follow-up and survivorship of patients with resected colorectal cancer; (2) Indications for liver metastasectomy; (3) Treatment of oligometastases by stereotactic body radiation therapy; (4) Treatment of borderline resectable and unresectable pancreatic cancer; (5) Transarterial chemoembolization in hepatocellular carcinoma; (6) Infectious complications of antineoplastic agents