Abstract. KRAS mutation status is established as a predictive biomarker of benefit from anti-EGFr therapies. Mutations are normally assessed using DNA extracted from one formalin-fixed, paraffin-embedded (FFPE) tumor block. We assessed heterogeneity of KRAS and BRAF mutation status intra-tumorally (multiple blocks from the same primary tumor). We also investigated the utility and efficiency of genotyping a 'DNA cocktail' prepared from multiple blocks.We studied 68 consenting patients in two randomized clinical trials. DNA was extracted, from ≥2 primary tumor FFPE blocks per patient. DNA was genotyped by pyrosequencing for KRAS codons 12, 13 and 61 and BRAF codon 600. In patients with heterogeneous mutation status, DNA cocktails were prepared and genotyped.Among 69 primary tumors in 68 patients, 7 (10.1%) showed intratumoral heterogeneity; 5 (7.2%) at KRAS codons 12, 13 and 2 (2.9%) at BRAF codon 600. In patients displaying heterogeneity, the relevant KRAS or BRAF mutation was also identified in 'DNA cocktail' samples when including DNA from mutant and wild-type blocks.Heterogeneity is uncommon but not insignificant. Testing DNA from a single block will wrongly assign wild-type status to 10% patients. Testing more than one block, or preferably preparation of a 'DNA cocktail' from two or more tumor blocks, improves mutation detection at minimal extra cost.

A review of sacrococcygeal teratomas diagnosed in the antenatal period in the West Midlands region over a six year interval is reported. The aim of the study was to assess the contribution of ultrasound scanning to the management of cases and to determine the outcome of prenatally diagnosed sacrococcygeal teratomas. A retrospective review of 10 cases was performed to obtain pregnancy details, ultrasound scan data and outcome information. Two fetuses were electively aborted. Perinatal mortality was 62.5% in the remaining cases with all stillbirths and neonatal deaths occurring in babies delivered preterm (at or before 34 weeks' gestation). Marked increase in tumour size (mainly vascular/solid) was observed in five of the fetuses, which was often associated with local compression effects and the development of hydrops. Eight out of 10 cases were delivered vaginally, one following aspiration of the large cystic tumour. Three of the four neonates surviving to surgery underwent successful resection of their benign tumours. As well as guiding prognosis, serial ultrasound scans may also allow the mode of delivery to be planned more effectively. The importance of a multidisciplinary team approach to these difficult cases is emphasized.

This research compared pregnant and non-pregnant women's perceptions of cognitive change and their performance on 13 sensitive memory and attention tasks (Study 1) and two complex driving simulation tasks (Study 2). The pregnant, but not the non-pregnant, women rated their cognitive abilities as worse than before, but only two performance measures from Study 1 differentiated the two groups (speed of language processing and attentional switching). Study 3 examined beliefs about pregnancy-related cognitive decline. Women and men with and without immediate experience of pregnancy rated pregnant women's cognitive abilities as slightly worse than before pregnancy. Memory ratings were worse from women and from those with immediate experience of pregnancy. It is concluded that there may be some mild effects of pregnancy on performance of some specific cognitive functions but that cultural expectations based on a stereotype of cognitive decline also contribute to pregnant women's perception of cognitive change.

Objective To assess management and outcome of pregnancies with anti-Kell in the West Midlands in Design A retrospective review of casenotes.Setting A regional referral clinic for red cell alloimmune disease and fetal medicine unit at a university hospital.Population Sixty-five pregnancies were identified in 52 Kell-sensitised women with Kell positive partners from the records of the Birmingham Blood Transfusion Centre.Methods Information from the casenotes was entered on a database and comparisons were made using the SPSS for Windows statistics package. Main outcome measuresMode of sensitisation, degree of fetal or neonatal anaemia, need for transfusion, gestation at delivery, birthweight and pregnancy outcome.Results Alloimmunisation was transfusion-related in 29 pregnancies and pregnancy-induced in 33. The cause could not be identified in three cases. There were 22 proven Kell positive fetuses, of which 18 were affected, in which alloimmunisation was pregnancy-related in 12 cases and transfusion-related in five. Antibody titres and amniotic fluid OD,,, were not helpful in management. Severe or very severe disease occurred in 50% of the affected pregnancies (9/18). There was no difference in pregnancy outcome between transfusion or pregnancy induced sensitisation.Conclusions Anti-Kell alloimmunisation is an uncommon cause of serious anaemia in a significant proportion of affected pregnancies. There appears to be no difference between that caused by pregnancy or transfusion. Estimation of fetal haemoglobin concentration by cordocentesis is recommended, as antibody titres and amniocentesis are not helpful.the UK over 13 years.

A review of sacrococcygeal teratomas diagnosed in the antenatal period in the West Midlands region over a six year interval is reported. The aim of the study was to assess the contribution of ultrasound scanning to the management of cases and to determine the outcome of prenatally diagnosed sacrococcygeal teratomas. A retrospective review of 10 cases was performed to obtain pregnancy details, ultrasound scan data and outcome information. Two fetuses were electively aborted. Perinatal mortality was 62.5% in the remaining cases with all stillbirths and neonatal deaths occurring in babies delivered preterm (at or before 34 weeks' gestation). Marked increase in tumour size (mainly vascular/solid) was observed in five of the fetuses, which was often associated with local compression effects and the development of hydrops. Eight out of 10 cases were delivered vaginally, one following aspiration of the large cystic tumour. Three of the four neonates surviving to surgery underwent successful resection of their benign tumours. As well as guiding prognosis, serial ultrasound scans may also allow the mode of delivery to be planned more effectively. The importance of a multidisciplinary team approach to these difficult cases is emphasized.