An International Multicenter Review of the Malignancy Rate of Excised Papillomatous Breast Lesions.

BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.

CT of pelvic extraperitoneal spaces: an anatomical study in cadavers.

AIM: To evaluate the pelvic extraperitoneal compartments and communications with abdominal retroperitoneal spaces. MATERIAL AND METHODS: Helical computed tomography (CT) was used to image the abdomen and pelvis after injection of 800 ml of dilute (1 in 25) contrast material into prevesical, perivesical and perirectal spaces in eight embalmed cadavers. Axial images and multiplanar reconstructions were reviewed to determine flow pathways. RESULTS: The prevesical space was injected in four cadavers, the perivesical space in two and the perirectal in two. After the four prevesical space injections, communication was seen with the perivesical (four of four), perirectal (one of four) and abdominal extraperitoneal spaces (posterior pararenal space in all, anterior pararenal space in two of four, and perirenal space in three of four). After the two perivesical injections, communication was seen with the prevesical (two of two), perirectal (two of two) and abdominal extraperitoneal spaces (posterior pararenal in two of two, anterior pararenal in two of two, and perirenal space in two of two). After the two perirectal space injections, communication was seen with the prevesical (two of two), perivesical (one of two) and abdominal extraperitoneal spaces (posterior pararenal in two of two, anterior pararenal in two of two, and perirenal space in one of two). CONCLUSION: The extraperitoneal spaces of the pelvis comprise three communicating compartments: the prevesical space, the perivesical space, and the perirectal space. The perirectal space, previously thought to be separate, communicates with the perivesical and the prevesical spaces. Intercommunication occurs both between the pelvic extraperitoneal spaces and with abdominal retroperitoneal spaces.

Outcome after musculoskeletal trauma treated in a regional hospital.

BACKGROUND: Trauma remains the leading cause of death and morbidity in the under-35-year-old population. The majority of reports assessing outcome after trauma emanate from North American Level I trauma centers. We sought to examine outcome after trauma treated in an Irish regional unit. METHODS: All patients admitted over a 1-year period with an Injury Severity Score > or =9 were evaluated and 61 patients recruited to the study. Demographic data, medical history, and details of the mechanism and pattern of injury and treatment were collected. Patients' functional outcome was assessed using the Sickness Impact Profile (SIP), duration of hospital stay, and return to work. RESULTS: Significant residual disability was noted (mean SIP 13.63+/-14.60). Thirty-seven percent of patients had not returned to work despite a mean follow-up of 18.36 months. Factors associated with a poor outcome include increasing age, a blue-collar occupation, lower limb fractures, comorbid conditions, and the presence of complications. CONCLUSION: Optimizing primary care of the trauma victim may help to minimize consequent morbidity. A small group of patients suffer permanent disability, and vocational retraining opportunities should be made available to them.

Fully competent dendritic cells as inducers of T cell anergy in autoimmunity.

Mature immunologically competent dendritic cells are the most efficient antigen-presenting cells that powerfully activate T cells and initiate and sustain immune responses. Indeed, dendritic cells are able to efficiently capture antigens, express high levels of costimulatory molecules, and produce the combination of cytokines required to create a powerful immune response. They are also considered to be important in initiating autoimmune disease by efficiently presenting autoantigens to self-reactive T cells that, in this case, will mount a pathogenic autoimmune reaction. Triggering T cells is not a simple on-off procedure, as T cell receptor responds to minor changes in ligand with gradations of T cell activation and effector functions. These "misfit" peptides have been called Altered Peptide Ligands, and have been shown to have important biological significance. Here, we show that fully capable dendritic cells may present, upon natural antigen processing, a self-epitope with Altered Peptide Ligands features that can unexpectedly induce anergy in a human autoreactive T cell clone. These results indicate that presentation of a self-epitope by immunologically competent dendritic cells does not always mean "danger" and show a mechanism involved in the fine balance between activation and tolerance induction in humans.

Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk.

The tyrosine kinase Syk (relative molecular mass 72,000), which is widely expressed in haematopoietic cells, becomes associated with and activated by engagement of the B-cell antigen receptor. Furthermore, it has been implicated in signalling through the receptors for interleukin-2 (IL-2), granulocyte colony-stimulating factor (G-CSF) and Fc, the T cell receptor, as well as through receptors for several platelet agonists. A homologous kinase, ZAP-70, is crucial in signalling through the T-cell receptor and in T-cell development. Using homologous recombination in embryonic stem cells, we created mice null for the syk gene which showed petechiae in utero and died shortly after birth. Irradiated mice reconstituted with Syk-deficient fetal liver showed a block in B-cell development at the pro-B to pre-B cell transition, consistent with a key role for Syk in pre-B-cell receptor signalling. Despite the production of small numbers of immature B cells, Syk-deficient radiation chimaeras failed to accumulate mature B cells, indicating a possible role for this protein in the production or maintenance of mature B cells. In addition, whereas the development of alpha beta T cells proceeded normally, Syk-deficient mice showed impaired development of thymocytes using the V gamma 3 variable region gene (V gamma 3+ thymocytes). Finally, we show that Syk is not required for signalling through the IL-2 and G-CSF receptors.

Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav.

Crosslinking of B- or T-cell antigen receptors results in the rapid tyrosine phosphorylation of a number of proteins, including Vav, a protein expressed in cells of the haematopoietic system. Vav contains an array of structural motifs that include Src-homology domains SH2/SH3 and regions of homology to the guanine-nucleotide-exchange protein Dbl, pleckstrin and protein kinase C (refs 5-9). Using the RAG-complementation approach, we have analysed in vivo differentiation and in vitro responses of B- and T-lineage cells generated by injection of embryonic stem cells homozygous for a null mutation in the vav gene into blastocysts of RAG-1- or RAG-2-deficient mice. Here we report that antigen receptor-mediated proliferative responses of B and T cells in vitro are severely reduced in the absence of Vav. We also suggest a direct link between the low proliferative response of Vav-deficient B and T cells and the reduced number of these cells in peripheral lymphoid organs of chimaeric mice.