Recent studies highlight the importance of BRAF alterations resulting in mitogen activated protein kinase (MAK/ERK) pathway activation in low-grade CNS tumors. We studied 106 low-grade CNS neoplasms in a cohort of primarily pediatric patients to identify the prevalence and clinicopathologic significance of these alterations. Polymerase chain reaction testing identified KIAA1549:BRAF fusions in 51 (48%) tumors overall, including 42 (60%) pilocytic astrocytomas, 4 (17%) unclassifiable low-grade gliomas, 4 (36%) low-grade glioneuronal/neuroepithelial tumors, 0 (of 5) pleomorphic xanthoastrocytomas, 0 (of 4) diffuse astrocytomas (World Health Organization grade II), and 1 (of 3, 33%) pilomyxoid astrocytoma. KIAA1549:BRAF gene fusions confirmed by sequencing included the previously reported ones involving exons 1–16/9–18 (49%), 1–15/9–18 (35%), and 1–16/11–18 (8%) and 2 fusions with novel breakpoints: 1–15/11–18 (6%) and 1–17/10–18 (1%). DNA sequencing identified BRAFV600E mutations in 8% of tumors. BRAFG468A mutations were absent. KIAA1549:BRAF fusions were significantly more frequent in infratentorial (57%) and optic pathway (59%) tumors versus supratentorial (19%) tumors (p = 0.001). We did not identify significantly improved progression-free survival in tumors with fusions. In summary, KIAA1549:BRAF fusions predominate in pilocytic astrocytomas but are also present in some low-grade unclassifiable gliomas and glioneuronal tumors. The prognostic and therapeutic significance of this alteration is unclear and merits further study.

Background: Between 9% and 23% of patients undergoing otherwise uncomplicated carotid endarterectomy (CEA) develop subtle cognitive decline 1 month postoperatively. The APOE-ε4 allele has been associated with worse outcome following stroke. Objective: To investigate the ability

The collection of peripheral blood progenitor cells (PBPC) by apheresis has become common in related allogeneic donors. However, the acceptability of the procedure to donors has not been documented. The purpose of this baseline case series study was to evaluate the psycho-social dimensions of apheresis from the perspective of healthy sibling donors and to explore issues surrounding fully informed consent including voluntary donation. At the first interview to discuss donation, 17 consecutive human leucocyte antigens (HLA) identical sibling donors who chose to donate PBPC were recruited to the study. They then completed both scales of the State-Trait Anxiety Inventory. The state scale was completed again immediately before first apheresis. At the end of the final apheresis, the donors were interviewed again by an independent researcher using a standardised questionnaire. All aspects of the procedure were well tolerated, including levels of anxiety and pain. Donors donated even if the relationship with their sibling was poor. However, some areas for improvement were highlighted. Eight (47%) donors were asked to donate by their sibling or another close relative, and this gave them no real volunteer status. Written information was judged important by 11 (65%) donors, but the material used was limited. The possibility of a poor outcome for the recipient was not well understood. The content of the written documentation and the management of confidentiality in terms of donor volunteer status needed to be addressed. A further study regarding the follow-up needs of donors, including those where the outcome is poor, is underway.

No abstract

The aim of this study was to determine the prevalence of deep venous thrombosis (DVT) following lower limb arthroplasty and to assess whether this adversely affected satisfaction, relief from pain, or the level of mobility as perceived by patients. Six hundred and ten consecutive recipients of primary total hip replacement (THR) or total knee replacement (TKR) underwent routine post-operative venography. The functional outcome had already been assessed at one year by using the Regional Arthroplasty Database questionnaire, the results of which were correlated to venographic records. The combined prevalence of DVT after THR and TKR in the patients, who did not receive chemical thromboprophylaxis, was 46.4%. Thrombus was identified in 57.6% of those with a TKR and in 33.5% of patients with a THR. Proximal thrombus was found in 11.0% of TKRs and in 14.8% of THRs. One year after surgery, patients who had a DVT established by venography did not report higher levels of immobility (p = 0.07), discomfort (p = 0.12) or dissatisfaction (p = 0.23) when compared to those with patent venous systems. This suggests that the prevalence of DVT following TKR/THR without chemical thromboprophylaxis is high and these findings are consistent with the literature. However, patients did not perceive thrombosis to compromise their overall outcome. This challenges the belief that DVT is associated with morbidity and calls for further comprehensive research in this area. The low morbidity of the lower limb associated with DVT in these patients does not support the use of chemical thromboprophylaxis.

No abstract

Histologic confirmation of axillary nodal metastases preoperatively avoids a sentinel node biopsy and enables a one step surgical procedure. The aim of this study was to establish the local positive predictive value of axillary ultrasound (AUS) and guided needle core biopsy (NCB) in axillary staging of breast cancer, and to identify factors influencing yield. A prospective audit of 142 consecutive patients (screening and symptomatic) presenting from 1st December 2008-31st May 2009 with breast lesions categorized R4-R5, who underwent a preoperative AUS, and proceeded to surgery was undertaken. Ultrasound-guided NCB was performed on nodes radiologically classified R3-R5. Lymph node size, number, and morphological features were documented. Yield was correlated with tumor size, grade, and histologic type. AUS/NCB was correlated with post surgical pathologic findings to determine sensitivity, specificity, positive and negative predictive value of AUS and NCB. A total of 142 patients underwent surgery, of whom 52 (37%) had lymph node metastases on histology. All had a preoperative AUS, 51 (36%) had abnormal ultrasound findings. 46 (90%) underwent axillary node NCB of which 24 (52%) were positive. The smallest tumor size associated with positive nodes at surgery was 11.5 mm. The sensitivity of AUS was 65%. Specificity was 81%, with a positive predictive value (PPV) of 67% and negative predictive (NPV) value of 80%. Sensitivity of U/S-guided NCB was 75%, with a specificity of 100%, PPV 100% and NPV 64%. Sensitivity of AUS for lobular carcinoma was 36% versus 76% for all other histologies. Sensitivity of NCB for lobular cancer was 33% versus 79% for all other histologies. The most significant factor producing discordance between preoperative AUS and definitive histologic evidence of lymph node metastasis was tumor type. Accurate preoperative lymph node staging was prejudiced by lobular histology (p< 0.0019).

No abstract