Autologous Breast Reconstruction with Transverse Rectus Abdominis Musculocutaneous (TRAM) or Deep Inferior Epigastric Perforator (DIEP) Flaps: An Analysis of the 100 Most Cited Articles.

Post-mastectomy autologous reconstruction with abdominal tissue has evolved over the past 4 decades and is a common reconstructive modality today. To gain more insight into this evolution, we performed an analysis of the 100 most commonly cited articles focusing on autologous breast reconstruction with transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps. A review of the ISI Web of Knowledge database was performed. Only peer-reviewed articles in English were included for analysis. Articles were ranked by their total citations as well as citation density (citations divided by years since publication). The 100 most cited articles were analyzed by their bibliographic parameters. The 100 most cited articles were published in 12 journals. The highest ranked plastic surgery journal published almost 2/3 of the articles. All articles were published within 23 years and marked the "rising age" of autologous breast reconstruction with TRAM and DIEP flaps. The focus of clinical research changed over this time period and ranged from innovations in surgical technique to analysis of clinical outcomes, comparative analyses with other reconstructive modalities, timing of reconstruction, and preoperative diagnostic workup, as well as cost-effectiveness analyses. This literature review illustrates the dramatic change that has occurred subsequent to introduction of abdominal flaps for breast reconstruction. While the use of abdominal flaps has become widely accepted for breast reconstruction, many questions remain unanswered, thus highlighting the need for ongoing clinical investigation.

von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans.

Tumor-mediated procoagulatory activity leads to venous thromboembolism and supports metastasis in cancer patients. A prerequisite for metastasis formation is the interaction of cancer cells with endothelial cells (ECs) followed by their extravasation. Although it is known that activation of ECs and the release of the procoagulatory protein von Willebrand factor (VWF) is essential for malignancy, the underlying mechanisms remain poorly understood. We hypothesized that VWF fibers in tumor vessels promote tumor-associated thromboembolism and metastasis. Using in vitro settings, mouse models, and human tumor samples, we showed that melanoma cells activate ECs followed by the luminal release of VWF fibers and platelet aggregation in tumor microvessels. Analysis of human blood samples and tumor tissue revealed that a promoted VWF release combined with a local inhibition of proteolytic activity and protein expression of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type I repeats 13) accounts for this procoagulatory milieu. Blocking endothelial cell activation by the low-molecular-weight heparin tinzaparin was accompanied by a lack of VWF networks and inhibited tumor progression in a transgenic mouse model. Our findings implicate a mechanism wherein tumor-derived vascular endothelial growth factor-A (VEGF-A) promotes tumor progression and angiogenesis. Thus, targeting EC activation envisions new therapeutic strategies attenuating tumor-related angiogenesis and coagulation.

Ultralarge von Willebrand factor fibers mediate luminal Staphylococcus aureus adhesion to an intact endothelial cell layer under shear stress.

BACKGROUND: During pathogenesis of infective endocarditis, Staphylococcus aureus adherence often occurs without identifiable preexisting heart disease. However, molecular mechanisms mediating initial bacterial adhesion to morphologically intact endocardium are largely unknown. METHODS AND RESULTS: Perfusion of activated human endothelial cells with fluorescent bacteria under high-shear-rate conditions revealed 95% attachment of the S aureus by ultralarge von Willebrand factor (ULVWF). Flow experiments with VWF deletion mutants and heparin indicate a contribution of the A-type domains of VWF to bacterial binding. In this context, analyses of different bacterial deletion mutants suggest the involvement of wall teichoic acid but not of staphylococcal protein A. The presence of inactivated platelets and serum increased significantly ULVWF-mediated bacterial adherence. ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) caused a dose-dependent reduction of bacterial binding and a reduced length of ULVWF, but single cocci were still tethered by ULVWF at physiological levels of ADAMTS13. To further prove the role of VWF in vivo, we compared wild-type mice with VWF knockout mice. Binding of fluorescent bacteria was followed in tumor necrosis factor-α-stimulated tissue by intravital microscopy applying the dorsal skinfold chamber model. Compared with wild-type mice (n=6), we found less bacteria in postcapillary (60±6 versus 32±5 bacteria) and collecting venules (48±5 versus 18±4 bacteria; P<0.05) of VWF knockout mice (n=5). CONCLUSIONS: Our data provide the first evidence that ULVWF contributes to the initial pathogenic step of S aureus-induced endocarditis in patients with an apparently intact endothelium. An intervention reducing the ULVWF formation with heparin or ADAMTS13 suggests novel therapeutic options to prevent infective endocarditis.