The Value of Intraoperative Examination of Axillary Sentinel Nodes in Carcinoma of the Breast.

Abstract Axillary sentinel lymph node biopsy (SLNB) has become the standard of care for T1-2, N-0, M-0 carcinoma of the breast. However, the accuracy of frozen section in the intra-operative examination of sentinel nodes (SN) remains controversial. The senior author has championed the use of the intraoperative examination of SN by frozen section ex-amination from the inception of its use, and we present our experience with frozen section examination of SN, confirming that this technique is both practical and highly accurate. Materials & Methods: Between 2000 and 2007, 236 SLNB procedures were performed that were read as “fro-zen section negative.” SN were identified by 1% lymphazurin blue dye only. The identification of SN in these 236 women was 100%. Each SN specimen was prosected by the senior author; a dedicated surgical pathology technician prepared the frozen sections. Nodes were dissected from the specimen individually and cut at 2.5 to 3.0 mm. intervals. Each of these sections was then cut at three levels. The frozen sections were read by the attending pathologist assigned to frozen sections for that day, not by a dedicated breast pathologist. During the period of the study, 14 different attending pathologists read the slides, with 6 pathologists each reading more than 20 cases. Others read from 1 to14 cases. Results: In this group of 236 cases, 11 patients had positive nodes on subsequent examination of the H&E slides; thus, the false negative rate of intraoperative frozen section was 4.7%, i.e., the frozen section was read as negative but the paraffin sections were posi-tive for metastasis. Therefore, the sensitivity of the negative frozen section was \u3e95%. Nine of the 11 false positives were micrometastases, less than 2 mm diameter, one was considered a macrometastasis, with two areas in one node measuring 2.0 and 2.1 mm each, and one was a sub-micrometastasis. The following variables were compared for significance: Pathologist, nuclear grade, histologic grade, margins, lymphovascular invasion, tumor type (ductal vs lobular), ER & PR values. The only significant variables were lymphovascular invasion (p=.019) and presence of in situ ductal carcinoma (p=.001). Only one of the false negatives was a purely lobular carcinoma (1/11). Discussion: Our data confirm the high accuracy of intraoperative examination of SN, \u3e95%, even without a dedicated breast pathologist reviewing the sections. The missed metastases are likely to be micrometastases, and the likelihood of missing a macrometastasis is \u3c1%. In patients with large primary tumors, presence of in situ ductal carcinoma or if lymphovascular invasion is associated with the tumor, special care should be taken to review these cases more thoroughly since these characteristics of tumors seem to make them more likely than others to have micrometastases to the axillary nodes over-looked

Direct Evidence of the Role of Hybridization in the X-Ray Magnetic Circular Dichroism of a-Ce

We present an x-ray magnetic circular dichroism (XMCD) study of a [Ce(10 Å)/Fe(30 Å)] multilayer performed at the Ce-M4,5 absorption edges. In this system the Ce-4f electrons are strongly hybridized with the valence band. XMCD experiments show that they carry an ordered magnetic moment. The differences of the shape of the XMCD signals of a typical g-like compound (CeCuSi) and of the Ce/ Fe multilayer highlight the role of hybridization in determining the ground state of cerium atoms in the multilayer, which results in a mixing of J = 5/2 and J = 7/2 coupled states

Characterization of defect structures in nanocrystalline materials by X-ray line profile analysis

X-ray line profile analysis is a powerful alternative tool for determining dislocation densities, dislocation type, crystallite and subgrain size and size-distributions, and planar defects, especially the frequency of twin boundaries and stacking faults. The method is especially useful in the case of submicron grain size or nanocrystalline materials, where X-ray line broadening is a well pronounced effect, and the observation of defects with very large density is often not easy by transmission electron microscopy. The fundamentals of X-ray line broadening are summarized in terms of the different qualitative breadth methods, and the more sophisticated and more quantitative whole pattern fitting procedures. The efficiency and practical use of X-ray line profile analysis is shown by discussing its applications to metallic, ceramic, diamond-like and polymer nanomaterials

Nanocrystalline materials studied by powder diffraction line profile analysis

X-ray powder diffraction is a powerful tool for characterising the microstructure of crystalline materials in terms of size and strain. It is widely applied for nanocrystalline materials, especially since other methods, in particular electron microscopy is, on the one hand tedious and time consuming, on the other hand, due to the often metastable states of nanomaterials it might change their microstructures. It is attempted to overview the applications of microstructure characterization by powder diffraction on nanocrystalline metals, alloys, ceramics and carbon base materials. Whenever opportunity is given, the data provided by the X-ray method are compared and discussed together with results of electron microscopy. Since the topic is vast we do not try to cover the entire field

Regulated Expression of CCL21 in the Prostate Tumor Microenvironment Inhibits Tumor Growth and Metastasis in an Orthotopic Model of Prostate Cancer

Currently there are no curative therapies available for patients with metastatic prostate cancer. Thus, novel therapies are needed to treat this patient population. Immunotherapy represents one promising approach for the elimination of occult metastatic tumors. However, the prostate tumor microenvironment (TME) represents a hostile environment capable of suppressing anti-tumor immunity and effector cell function. In view of this immunosuppressive activity, we engineered murine prostate cancer cells with regulated expression (tet-on) of CCL21. Prostate tumor cells implanted orthotopically produced primary prostate tumors with predictable metastatic disease in draining lymph nodes and distant organs. Expression of CCL21 in the prostate TME enhanced survival, inhibited tumor growth and decreased the frequency of local (draining lymph node) and distant metastasis. Therefore, these studies provide a strong rationale for further evaluation of CCL21 in tumor immunity and its use in cancer immunotherapy

Cryptic Disc Structures Resembling Ediacaran Discoidal Fossils from the Lower Silurian Hellefjord Schist, Arctic Norway

The Hellefjord Schist, a volcaniclastic psammite-pelite formation in the Caledonides of Arctic Norway contains discoidal impressions and apparent tube casts that share morphological and taphonomic similarities to Neoproterozoic stem-holdfast forms. U-Pb zircon geochronology on the host metasediment indicates it was deposited between 437 ± 2 and 439 ± 3 Ma, but also indicates that an inferred basal conglomerate to this formation must be part of an older stratigraphic element, as it is cross-cut by a 546 ± 4 Ma pegmatite. These results confirm that the Hellefjord Schist is separated from underlying older Proterozoic rocks by a thrust. It has previously been argued that the Cambrian Substrate Revolution destroyed the ecological niches that the Neoproterozoic frond-holdfasts organisms occupied. However, the discovery of these fossils in Silurian rocks demonstrates that the environment and substrate must have been similar enough to Neoproterozoic settings that frond-holdfast bodyplans were still ecologically viable some hundred million years later

X-linked cataract and Nance-Horan syndrome are allelic disorders

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication–triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved