Systematic review and meta-analysis of the influence of circumferential resection margin involvement on survival in patients with operable oesophageal cancer.

BACKGROUND: The prognostic role and definition of circumferential resection margin (CRM) involvement in operable oesophageal cancer remain controversial. The College of American Pathologists (CAP) and Royal College of Pathologists (RCP) define CRM involvement as tumour found at the cut resection margin and within 1 mm of the cut margin respectively. This systematic review and meta-analysis was performed to determine the influence of CRM involvement on survival in operable oesophageal cancer. METHODS: PubMed, MEDLINE and the Cochrane Library (January 1990 to June 2012) were searched for studies correlating CRM involvement with 5-year mortality. Statistical analysis of dichotomous variables was performed using the odds ratio (OR) as the summary statistic. RESULTS: Fourteen studies involving 2433 patients with oesophageal cancer who had undergone potentially curative oesophagectomy were analysed. Rates of CRM involvement were 15·3 per cent (173 of 1133) and 36·5 per cent (889 of 2433) according to the CAP and RCP criteria respectively. Overall 5-year mortality rates were significantly higher in patients with CRM involvement compared with CRM-negative patients according to both CAP (OR 4·02, 95 per cent confidence interval (c.i.) 2·25 to 7·20; P < 0·001) and RCP (OR 2·52, 1·96 to 3·25; P < 0·001) criteria. CRM involvement between 0·1 and 1 mm was associated with a significantly higher 5-year mortality rate than CRM-negative status (involvement more than 1 mm from CRM) (OR 2·05, 95 per cent c.i. 1·41 to 2·99; P < 0·001). CONCLUSION: CRM involvement is an important predictor of poor prognosis. CAP criteria differentiate a higher-risk group than RCP criteria, but overlook a patient group with similar poor outcomes.

BRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 years.

BACKGROUND: Triple-negative (TN) tumours are the predominant breast cancer subtype in BRCA1 mutation carriers. Recently, it was proposed that all individuals below 50 years of age with TN breast cancer should be offered BRCA testing. We have evaluated the BRCA1 mutation frequency and the implications for clinical practice of undertaking genetic testing in women with TN breast cancer. METHODS: We undertook BRCA1 mutation analysis in 308 individuals with TN breast cancer, 159 individuals from unselected series of breast cancer and 149 individuals from series ascertained on the basis of young age and/or family history. RESULTS: BRCA1 mutations were present in 45 out of 308 individuals. Individuals with TN cancer <50 years had >10% likelihood of carrying a BRCA1 mutation in both the unselected (11 out of 58, 19%) and selected (26 out of 111, 23%) series. However, over a third would not have been offered testing using existing criteria. We estimate that testing all individuals with TN breast cancer <50 years would generate an extra 1200 tests annually in England. CONCLUSION: Women with TN breast cancer diagnosed below 50 years have >10% likelihood of carrying a BRCA1 mutation and are therefore eligible for testing in most centres. However, implementation may place short-term logistical and financial burdens on genetic services.

Assay of AHF concentrates and standards: failure to eliminate variability with a monographed assay.

Previous calibration studies have shown a high interlaboratory variability in the potency of the proposed Office of Biologics (National Center for Drugs and Biologics, US-FDA) AHF standard relative to the 2nd International Standard for Factor VIII (Factor VIII:C) (WHO 73/552). This led to the formation of an Industry Collaborative Study group whose objective was to reduce the assay variability. The group, in collaboration with the Office of Biologics and the National Institute for Biological Standards and Control (UK), designed a study based on a monographed one-stage assay protocol, which specified all materials, assay methods, equipment, dilution technique, reagents, assay order, and calculation methodology. All participants received common reagents and samples, with the exception of substrate plasma. It was felt that substrate plasma could not be a common reagent in a monographed assay. However, each laboratory prepared substrate plasma according to the protocol. All data were analyzed by an independent statistical staff. Preparations assayed included two 10-donor plasma pools, the 2nd International Standard for Factor VIII (WHO 73/552), the proposed OoB Lot A internal standard, the participants' own house standards, and commercial AHF concentrate material. The results show a statistically insignificant reduction in the interlaboratory variability, but intralaboratory consistency was generally maintained. The study shows that monographing an assay for Factor VIII.