Tracked ultrasound registration for intraoperative navigation during pediatric bone tumor resections with soft tissue components: a porcine cadaver study.

PURPOSE: Resection of pediatric osteosarcoma in the extremities with soft tissue involvement presents surgical challenges due to difficult visualization and palpation of the tumor. Therefore, an adequate image-guided surgery (IGS) system is required for more accurate tumor resection. The use of a 3D model in combination with intraoperative tracked ultrasound (iUS) may enhance surgical decision making. This study evaluates the clinical feasibility of iUS as a surgical tool using a porcine cadaver model. METHODS: First, a 3D model of the porcine lower limb was created based on preoperative scans. Second, the bone surface of the tibia was automatically detected with an iUS by a sweep on the skin. The bone surface of the preoperative 3D model was then matched with the bone surface detected by the iUS. Ten artificial targets were used to calculate the target registration error (TRE). Intraoperative performance of iUS IGS was evaluated by six pediatric surgeons and two pediatric oncologic orthopedists. Finally, user experience was assessed with a post-procedural questionnaire. RESULTS: Eight registration procedures were performed with a mean TRE of 6.78 ± 1.33 mm. The surgeons agreed about the willingness for clinical implementation in their current clinical practice. They mentioned the additional clinical value of iUS in combination with the 3D model for the localization of the soft tissue components of the tumor. The concept of the proposed IGS system is considered feasible by the clinical panel, but the large TRE and degree of automation need to be addressed in further work. CONCLUSION: The participating pediatric surgeons and orthopedists were convinced of the clinical value of the interaction between the iUS and the 3D model. Further research is required to improve the surgical accuracy and degree of automation of iUS-based registration systems for the surgical management of pediatric osteosarcoma.

Antiendothelial cell antibodies in systemic lupus erythematosus: enhanced antibody binding to interleukin-1-stimulated endothelium.

IgG antiendothelial antibodies (IgG AEA), as measured by enzyme-linked immunosorbent assay, could be detected in serum samples of 38 out of 41 patients with systemic lupus erythematosus. Incubation of endothelial cells (EC) with interleukin-1 alpha (IL-1 alpha), in contrast to incubation with interferon gamma or tumor necrosis factor alpha, resulted in an enhanced IgG AEA binding. Immunoblotting revealed reactivity of AEA against a variety of EC antigens. The upregulation of IgG-AEA-binding reactivity to IL-1 alpha-stimulated EC was due to binding to antigens that were already expressed by unstimulated EC. The IgG-binding reactivity to both IL-1 alpha-stimulated and unstimulated EC was significantly higher in the serum of patients with joint or skin abnormalities as compared with patients without these manifestations. These data suggest that upregulated binding of IgG to EC induced by IL-1 alpha may play a role in immune vascular damage.

Characterization of anti-endothelial antibodies in patients with rheumatoid arthritis complicated by vasculitis.

Anti-endothelial antibodies (AEA) have been described in patients with rheumatoid arthritis (RA) complicated by vasculitis. In this study we made use of an ELISA and immunoblot technique (IBT) to further characterize AEA of the IgG class in serum of patients with rheumatoid vasculitis (RV) and to investigate the relationship between the presence of IgG-AEA and vasculitis. IgG-AEA as measured by ELISA or IBT could be detected in the serum from 20 of the 23 (87%) RV patients, in 2 out of 13 (15%) patients with RA and in one of 15 healthy donors. The IBT revealed reactivity of IgG-AEA against a total of 12 bands of endothelial antigens ranging in size from 16 to 68 kD. IgG-AEA as measured by ELISA and IBT in serum samples of patients followed longitudinally were present more frequently and in higher titres in patients with active RV as compared to patients with vasculitis in remission. A significant correlation was found between the presence of clinical signs of vasculitis and serum IgG-AEA reactivity against an endothelial membrane antigen of 44 kD. These data show that the pattern of IgG-AEA reactivity in the serum of RV patients is heterogeneous and suggest that IgG-AEA against one particular antigen is involved in the pathogenesis of RV.

Characterization of anti-endothelial cell antibodies in systemic lupus erythematosus (SLE).

IgG anti-endothelial antibodies (AEA), as measured by ELISA or immunoblotting technique could be detected in serum samples of 56 out of 64 patients with SLE (88%) and mainly occurred in monomeric form. AEA were not cell specific, because the binding reactivity was absorbed partially by both fibroblasts and peripheral blood mononuclear cells. No correlation was found between the presence of AEA and anti-nuclear antibodies. Immunoblotting revealed reactivity of AEA against endothelial antigens ranging in size from 15 to 200 kD. AEA titres were significantly higher in patients with joint or skin abnormalities, compared with patients without these abnormalities. A significant correlation was found between nephritis in SLE and the presence of AEA reactivity against endothelial membrane antigens of 38, 41 and 150 kD. These data show that the pattern of AEA reactivity in serum of SLE patients is heterogeneous, and suggest that AEA against a limited number of antigens may be involved in the pathogenesis of nephritis in SLE.

Cystathioninuria in patients with neuroblastoma.

Urinary excretion of cystathionine and dopa metabolites was analyzed in 61 patients with active neuroblastoma before, and at regular intervals during treatment. Thirty-seven patients with clinical evidence of active neuroblastoma excreted elevated levels of cystathionine before treatment was initiated; six other patients showed cystathioninuria at some time during treatment with chemo- or radiotherapy. The cause of the cystathioninuria remains unidentified. No relationship between excessive cystathionine excretion and liver impairment or liver metastases was established; nor was there evidence to support a consistent correlation with the ratio of the sum of the excretion values for vanilglycolic acid and vanilglycol to the excretion of vanilacetic acid. Our results indicate that absence of cystathioninuria correlates with an early clinical staging and thus with a favorable prognosis. Isolated cystathioninuria does occasionally occur in patients with neuroblastoma, permitting a presumptive diagnosis until later evidence can be obtained. Determination of cystathionine excretion is essential for an extensive biochemical evaluation of patients with neuroblastoma.