Surgical and Systemic Treatment of Hereditary Breast Cancer: A Mini-Review With a Focus on BRCA1 and BRCA2 Mutations.

Hereditary breast cancer accounts for 5%-10% of breast cancer cases. The majority of familial cases have been linked to germline mutations in BRCA1 and BRCA2 genes, though other high penetrance susceptibility genes have also been identified through genomic testing advances. Optimal surgical treatment for these patients, who are of a younger age, has several challenges as it usually involves aggressive therapeutic and risk reducing interventions. At the same time, the therapeutic armamentarium for BRCA1/2 mutation carriers apart from platinum salts, has been enriched with the addition of poly-ADP ribose polymerase (PARP) inhibitors with promising outcomes. In this review we provide a succinct and comprehensive overview of the surgical and systemic treatment options for patients with BRCA1/2 mutation related breast cancer and an update on the most recent systemic treatment advances.

Discordance in glycemic categories and regression to normality at baseline in 10,000 people in a Type 2 diabetes prevention trial.

The world diabetes population quadrupled between 1980 and 2014 to 422 million and the enormous impact of Type 2 diabetes is recognised by the recent creation of national Type 2 diabetes prevention programmes. There is uncertainty about how to correctly risk stratify people for entry into prevention programmes, how combinations of multiple 'at high risk' glycemic categories predict outcome, and how the large recently defined 'at risk' population based on an elevated glycosylated haemoglobin (HbA1c) should be managed. We identified all 141,973 people at highest risk of diabetes in our population, and screened 10,000 of these with paired fasting plasma glucose and HbA1c for randomisation into a very large Type 2 diabetes prevention trial. Baseline discordance rate between highest risk categories was 45.6%, and 21.3-37.0% of highest risk glycaemic categories regressed to normality between paired baseline measurements (median 40 days apart). Accurate risk stratification using both fasting plasma glucose and HbA1c data, the use of paired baseline data, and awareness of diagnostic imprecision at diagnostic thresholds would avoid substantial overestimation of the true risk of Type 2 diabetes and the potential benefits (or otherwise) of intervention, in high risk subjects entering prevention trials and programmes.

The Routine Use of Cholangiography for Laparoscopic Cholecystectomy in the Modern Era.

BACKGROUND AND OBJECTIVES: The use of routine versus selective intra-operative cholangiogram (IOC) for laparoscopic cholecystectomy (LC) remains an area of debate. In this study, we investigated the routine use of IOC in a single center, to determine whether it confers a reduced risk of common bile duct (CBD) injury and improved patient outcomes. We also identified several preoperative predictive factors for CBD stone detection on IOC to investigate the feasibility of a predictive model. METHODS: We identified 1005 LCs with routine IOC over a 2-year period at the Norfolk and Norwich University Hospital from October 1, 2013, to September 30, 2015. Outcomes measured included CBD stone detection on IOC, CBD injury, complication rates, readmission rate, and mortality. We also calculated sensitivity, specificity, and likelihood ratios for detection of CBD stones on IOC from preoperative biochemistry and radiological investigations. RESULTS: We identified a CBD stone detection rate of 10.1% and a readmission rate of 0.03%, with no reported CBD injuries and 1 reported mortality. Of the preoperative predictive factors investigated, the most specific for CBD stone detection on IOC was bilirubin at 89%. The most sensitive was preoperative MRCP at 77%. DISCUSSION: This study demonstrates that routine IOC is an effective method of detecting CBD stones and CBD injuries, resulting in improved patient outcomes and economic benefits for health services. We have also identified several predictive factors for CBD stones on IOC.

The importance of "His" story.

A 73-year-old previously healthy man presented with a 3-day history of rigours, abdominal pain, diarrhoea, haemoptysis and myalgia. He had not been abroad recently, but reported being a farmer and having had a recent rat infestation. Laboratory investigations revealed acute kidney failure, deranged liver function tests, raised C reactive protein and a chest CT revealed bilateral ground-glass opacities. This presentation was consistent with icteric leptospirosis which was confirmed by serological testing. Following haemofiltration and the administration of antibiotics the patient made an excellent recovery from his leptospirosis.

Alternative population sampling frames produced important differences in estimates of association: a case-control study of vasculitis.

OBJECTIVE: A common population sampling frame in countries with universal health care is health service registers. We have evaluated the use of such a register, in the United Kingdom, against a commercially available database claiming large population coverage, an alternative that offers ease of access and flexibility of use. STUDY DESIGN AND SETTING: A case-control study of vasculitis, which recruited cases from secondary care clinics in Scotland, compared two alternative sampling frames for population controls, namely the registers of National Health Service (NHS) primary care practices and a commercially available database. The characteristics of controls recruited from both sources were compared in addition to separate case-control comparison using logistic regression. RESULTS: A total of 166 of 189 cases participated (88% participation rate), while both the commercial database and NHS Central Register (NHSCR) controls achieved a participation rate of 24% among persons assumed to have received the invitation. On several measures, the NHSCR patients reported poorer health than the commercial database controls: low scores on the physical component score of the Short Form 36 (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3-4.1), chronic widespread pain (OR: 2.3; CI: 1.1-4.7), and high levels of fatigue (OR: 2.0; CI: 1.3-3.1). These had an important influence on the estimates of association with case status with one association (pain) showing a strong and significant association using commercial database controls, which was absent with NHSCR controls. CONCLUSION: There are important differences in self-reported measures of health and quality of life using controls from two alternative population sampling frames. It emphasizes the importance of methodological rigor and prior assessment in choosing sampling frames for case-control studies.