Reduction of blood transfusion need with aprotinin in orthopedic surgery. Spanish Study Group on the Use of Aprotinin in Hip Arthroplasty (GEEEAAC)

Aprotinin is a protease inhibitor of interest for its antifibrinolytic effect of reducing perioperative bleeding in certain types of surgery, with wide use in heart surgery, liver transplantation and vascular surgery. The application of aprotinin during orthopedic surgery has recently been suggested. Such use is controversial, as there is lack of consensus as to the type of patient for whom aprotinin administration would be indicated, the surgical procedure during which it would be most effective (hip or knee arthroplasty, spinal arthrodesis, major tumor or septic surgery), the doses to administer, its safety and its real efficacy for conserving homologous blood. That is to say, there is no agreement as to the cost/benefit relation of aprotinin for the various types of orthopedic surgery. This critical review of the literature leads to the conclusion that aprotinin is a promising drug for use in orthopedic surgery, given that published studies have established the benefit in blood product savings and decreased blood loss during surgery.     

Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma

Recent studies in mouse models of cancer have shown that exercise improves tumor vascular function, thereby improving chemotherapy delivery and efficacy. However, the mechanisms underlying this improvement remain unclear and the effect of exercise on Ewing sarcoma (ES), a pediatric bone and soft tissue cancer, is unknown. The effect of exercise on tumor vascular hyperpermeability, which inversely correlates with drug delivery to the tumor, has also not been evaluated. We hypothesized that exercise improves chemotherapy efficacy by enhancing its delivery through improving tumor vascular permeability. We treated ES‐bearing mice with doxorubicin with or without moderate treadmill exercise. Exercise did not significantly alter ES tumor vessel morphology. However, compared to control mice, tumors of exercised mice had significantly reduced hyperpermeability, significantly decreased hypoxia, and higher doxorubicin penetration. Compared to doxorubicin alone, doxorubicin plus exercise inhibited tumor growth more efficiently. We evaluated endothelial cell sphingosine‐1‐phosphate receptors 1 and 2 (S1PR1 and S1PR2) as potential mediators of the improved vascular permeability and increased function afforded by exercise. Relative to tumors from control mice, vessels in tumors from exercised mice had increased S1PR1 and decreased S1PR2 expression. Our results support a model in which exercise remodels ES vasculature to reduce vessel hyperpermeability, potentially via modulation of S1PR1 and S1PR2, thereby improving doxorubicin delivery and inhibiting tumor growth more than doxorubicin alone does. Our data suggest moderate aerobic exercise should be tested in clinical trials as a potentially useful adjuvant to standard chemotherapy for patients with ES.     

Characterization of breast cancer subtypes by quantitative assessment of biological parameters: relationship with clinicopathological characteristics, biological features and prognosis

Objectives

Gene expression analysis has identified several breast cancer subtypes, including luminal, epidermal growth factor receptor-2 positive (HER2+), and basal-like. To determine if our proposed molecular taxonomy correlates with biological and clinical behavior. This is based on four biological markers: estrogen and progesterone receptors (ER and PR, respectively), HER2 and the epidermal growth factor receptor-1 (HER1), all of them being determined by quantitative assays.

Study design

The biological parameters were examined by enzyme immunoassay, radioligand-binding assay or ELISA, in tumors from 787 patients with invasive breast cancer. Patients were prospectively evaluated over a median follow-up period of 50 months. Subtype definitions were as follows: luminal (ER+), HER2+ (HER2+, ER−, PgR−) and basal-like (HER2−, ER−, PgR−). In addition, we divided basal tumors into two groups based on their HER1 status.

Results

A 55.8% of tumors were of luminal type, 11.9% basal-like HER1+, 10.7 basal-like HER1−, and the remainder 21.6% HER2+. Both HER2+ and basal-like subtypes were more frequent in younger and premenopausal women, showing a higher percentage of cases of poorly differentiated tumors and higher S-phase fraction, when compared with those of luminal subtype. Multivariate analysis demonstrated that the subtype of tumor was related to both relapse and overall survival, being those of luminal subtype associated with the best prognosis.

Conclusions

Through the classification of breast tumors in four groups, according to their ER, PgR, HER2 and HER1 status, it is possible to obtain a major division of breast tumors associated with significant differences in biological features and clinical behavior.     

Mandibulofacial dysostosis, acral anomalies and frontonasal dysplasia: a new form of acrofacial dysostosis

We describe a stillborn female with acrofacial dysostosis and frontonasal dysplasia. She had protrusion of the forehead, with marked hypertelorism and absence of the nose but with the rhinencephalon present. Autopsy showed wide cranial sutures, severe hydrocephalus with separation of the right and left hemispheres of the brain, preservation of the olfactory bulb and first and second cranial nerves. The child also had small kidneys bilaterally, rectal atresia and an absent anus with rectovaginal fistula. These clinical findings suggest a new form of acrofacial dysostosis.     

Physical principles, methodology, consistency, and safety in Doppler assessment of the fetal-placental circulation

Introduction of Doppler ultrasound in obstetrical practice has changed both management and understanding of several diseases that put at risk women and them fetuses. To establish necessary basics and correctly apply this technique, this review will focus in physical principles, acquisition methods, consistency, and safety issues of Doppler ultrasound, in order to improve precision, accuracy and interpretation of this methodology.