Completeness of reporting on prognostic factors for breast cancer: a regional survey.

BACKGROUND: Effective management of breast cancer is dependent on adequate pathological reporting of the surgical specimen. OBJECTIVE: To describe the frequency with which histopathological features of known prognostic importance are routinely recorded. STUDY POPULATION: 885 cases of invasive breast cancer diagnosed in NHS laboratories in Lancashire and Greater Manchester. METHODS: Pathology reports were reviewed for details for tumour histological type, size, and grade, the presence or absence of tumour in blood or lymphatic vascular channels, and a comment on the proximity of tumour to the lines of surgical excision. Laboratories were categorised according to their throughput of cases of breast cancer, involvement in the breast screening programme, and whether they were attached to a teaching hospital. RESULTS: Histological type, tumour size, presence or absence of tumour in vascular channels, and adequacy of excision were recorded for 843 (95%), 803 (91%), 436 (49%), and 761 (86%) cases, respectively. Non-screening and low throughput laboratories were significantly less likely to record certain histopathological features. No significant differences were observed between teaching and non-teaching hospitals. CONCLUSIONS: The substantial interlaboratory variation in the histopathological reporting of breast cancers can, in part, be related to throughput of cases and involvement in the breast screening programme.     

Targeting KIT in melanoma: A paradigm of molecular medicine and targeted therapeutics

Despite multiple clinical trials utilizing a spectrum of therapeutic modalities, melanoma remains a disease with dismal outcomes in patients with advanced disease. However, it is now clear that melanoma is not a single entity, but can be molecularly divided into subtypes that generally correspond to the anatomical location of the primary melanoma. Melanomas from acral lentiginous, mucosal, and chronic sun-damaged sites frequently harbor activating mutations and/or increased copy number in the KIT tyrosine kinase receptor gene, which are very rare in the more common cutaneous tumors. Multiple case reports and early observations from clinical trials suggest that targeting mutant KIT with tyrosine kinase inhibitors is efficacious in KIT mutant melanoma. This review recounts what is known about the role of KIT in melanocyte maturation, our current understanding of KIT genetic aberrations in melanoma, and how this knowledge is being translated into clinical oncology.     

Retroviral-mediated transfer and amplification of a functional human factor VIII gene

Hemophilia A results from a deficiency in factor VII (FVIII), a cofactor in the intrinsic pathway of blood coagulation. As an approach toward genetic therapy of this disease, we constructed a retroviral vector encoding human FVIII and a selectable and amplifiable genetic marker, human adenosine deaminase (Ada). A retrovirus packaging line was transfected with this vector and stable transformants were selected for Ada expression. Isolated transformants produced both FVIII activity in the conditioned medium and retrovirus capable of transferring the Ada selectable marker and FVIII expression to the mouse 3T3 fibroblasts. Selection of virus-producer cell lines for increasing levels of Ada expression yielded a 20-fold increase in both FVIII expression and viral titer. Similarly, selection of infected 3T3 fibroblasts for Ada gene amplification yielded a 20-fold increase in FVIII expression. The results demonstrate the feasibility of retrovirus- mediated transfer of human FVIII, and also the utility of selection for gene amplification to increase retrovirus titers in producer cell lines as well as expression levels in infected cells.     

Bleeding complications associated with cardiopulmonary bypass

Bleeding after CPB has been difficult to characterize and its treatment equally difficult to standardize. The complexity of this problem is related to the hemostatic process, the technical variations in the operative procedures, and the many uncontrolled variables associated with CPB, including the effects of anesthetic or pharmacologic agents, the nature of the priming solution, hemodilution, hypothermia, the type of oxygenator, and the use of transfused blood products. Although there are multiple and generally predictable complex changes in the hemostatic mechanism during CPB, the temporary loss of platelet function is the most common and clinically relevant. This transient platelet dysfunction occurs in all patients undergoing CPB; however, it only causes excessive bleeding in a small percentage of patients. Unfortunately, it has not yet been possible to predict which patients will develop hemorrhagic complications, although prolonged pump times are a contributing risk factor. Over the past decade there has been extensive investigation into the management of bleeding associated with CPB, provoked primarily by the increased awareness of transfusion-transmitted viral diseases and the inappropriately excessive use of homologous blood products. Several approaches to autotransfusion of shed blood and autologus blood donation have been developed to minimize perioperative homologous blood transfusion. Pharmacologic agents such as desmopressin, aprotinin, and topical fibrin glues have also been introduced to improve hemostasis during CPB. The protease inhibitor aprotinin is particularly promising in the reduction of bleeding associated with CPB when given prophylactically. Aprotinin may provide new insights into the mechanism of CPB-induced platelet dysfunction. Desmopressin is indicated only for the treatment of bleeding after CPB. The management of bleeding associated with CPB will undoubtedly     

Sacral Colpopexy Versus Transvaginal Mesh Colpopexy in Obese Patients

ObjectivesObesity can predispose women to pelvic organ prolapse and can also affect the success of pelvic organ prolapse surgery. The purpose of this study was to compare the postoperative anatomical outcomes following sacral colpopexy (SC) and transvaginal mesh colpopexy in a group of obese women with pelvic organ prolapse.MethodsWe conducted a retrospective cohort study of obese women who underwent SC (n = 56) or transvaginal mesh colpopexy (n = 35). Follow-up ranged from 6 to 12 months. Preoperative, perioperative, and postoperative variables were compared using Student t, Mann?Whitney U, and Fisher exact tests, and by analysis of covariance.ResultsThe women in the SC group had significantly higher mean apical vaginal measurements (P < 0.05), and significantly fewer stage II recurrences than women in the transvaginal mesh colpopexy group. There were no significant differences between the groups for other postoperative outcomes, including mesh erosion, recurrent prolapse symptoms, dyspareunia, and surgical satisfaction (P > 0.05).ConclusionIn these 91 obese patients with pelvic organ prolapse, SC resulted in better anatomical outcomes than transvaginal mesh colpopexy. However, the two procedures had similar outcomes with regard to recurrent symptoms and surgical satisfaction.