Angiosarcomas associated with bone infarcts

OBJECTIVE: A bone infarct may occasionally dedifferentiate to osteogenic sarcoma, fibrosarcoma or malignant fibrous histiocytoma. However, the association of an angiosarcoma with a bone infarct is extremely rare. Such an association is presented in three patients. Their clinical course is compared with that of patients with bone infarcts associated with other sarcomas. DESIGN AND PATIENTS: The three patients were men with a mean age of 43 years. Cases 1 and 3 presented with a pathological fracture at the site of the angiosarcoma. Plain radiography was done in the three patients, computed tomography (CT) was performed in cases 1 and 3 and magnetic resonance imaging (MRI) in case 3. The femur was the site of the three tumors: midshaft in cases 1 and 3 and distal shaft in case 2. On the basis of the radiographic findings, and clinical examination, an open biopsy was performed for the three men, which confirmed the diagnosis of a high-grade angiosarcoma associated with a bone infarct. RESULTS: Case 1 was treated with high-above knee amputation and is still alive after 18 months from the time of operation. Segmental resection of the distal femur with adjuvant chemotherapy and local irradiation was the treatment for case 2, who is still alive with no tumor recurrence on metastatic disease 3 years from the operation. Intramedullary rodding was done for case 3 who died 6 months later. CONCLUSION: The association of an angiosarcoma with a bone infarct has been established in only five cases. Although the number of such associations is small, it seems that such an association may be prognostically more or less the same as in those cases in which a bone infarct is associated with either osteosarcoma, fibrosarcoma or malignant fibrous histiocytoma, where the survival rate is unfavorable. A cause-and-effect relationship may exist between a bone infarct and subsequent development of a bone sarcoma.     

Directional coronary atherectomy for the treatment of Palmaz-Schatz in-stent restenosis

Management of in-stent restenosis has become a significant challenge in interventional cardiology. The results of balloon angioplasty have been disappointing due to the high recurrence of restenosis at follow-up. Debulking of the restenotic tissue within the stents using directional coronary atherectomy (DCA) may offer a therapeutic advantage. We report the immediate clinical and angiographic outcomes and long-term clinical follow-up results of 45 patients (46 lesions), mean age 63+/-12 years, 73% men, with a mean reference diameter of 2.9+/-0.6 mm, treated with DCA for symptomatic Palmaz-Schatz in-stent restenosis. DCA was performed successfully in all 46 lesions and resulted in a postprocedural minimal luminal diameter of 2.7+/-0.7 mm and a residual diameter stenosis of 17+/-10%. There were no in-hospital deaths, Q-wave myocardial infarctions, or emergency coronary artery bypass surgeries. Four patients (9%) suffered a non-Q-wave myocardial infarction. Target lesion revascularization was 28.3% at a mean follow-up of 10+/-4.6 months. Kaplan-Meier event-free survival (freedom from death, myocardial infarction, and repeat target lesion revascularization) was 71.2% and 64.7% at 6 and 12 months after DCA, respectively. Thus, DCA is safe and efficacious for the treatment of Palmaz-Schatz in-stent restenosis. It results in a large postprocedural minimal luminal diameter and a low rate of both target lesion revascularization and combined major clinical events at follow-up.     

Peptide modification or blocking of CD8, resulting in weak TCR signaling, can activate CTL for Fas- but not perforin-dependent cytotoxicity or cytokine production

This study describes a form of partial agonism for a CD8+ CTL clone, S15, in which perforin-dependent killing and IFN-gamma production were lost but Fas (APO1 or CD95)-dependent cytotoxicity preserved. Cloned S15 CTL are H-2Kd restricted and specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260 (SYIPSAEKI). The presence of a photoactivatable group in the epitope permitted assessment of TCR-ligand binding by TCR photoaffinity labeling. Selective activation of Fas-dependent killing was observed for a peptide-derivative variant containing a modified photoreactive group. A similar functional response was obtained after binding of the wild-type peptide derivative upon blocking of CD8 participation in TCR-ligand binding. The epitope modification or blocking of CD8 resulted in an > or = 8-fold decrease in TCR-ligand binding. In both cases, phosphorylation of zeta-chain and ZAP-70, as well as calcium mobilization were reduced close to background levels, indicating that activation of Fas-dependent cytotoxicity required weaker TCR signaling than activation of perforin-dependent killing or IFN-gamma production. Consistent with this, we observed that depletion of the protein tyrosine kinase p56(lck) by preincubation of S15 CTL with herbimycin A severely impaired perforin- but not Fas-dependent cytotoxicity. Together with the observation that S15 CTL constitutively express Fas ligand, these results indicate that TCR signaling too weak to elicit perforin-dependent cytotoxicity or cytokine production can induce Fas-dependent cytotoxicity, possibly by translocation of preformed Fas ligand to the cell surface.     

Gaucher disease: assessment of skeletal involvement and therapeutic responses to enzyme replacement

The clinical, pathological and radiological manifestations of type 1 Gaucher disease and the role of imaging techniques such as CT, MRI and sulfur-colloid scintigraphy in the management of these patients is discussed. MRI appears to be the most valuable imaging technique for evaluating bone marrow involvement and detecting disease activity. MRI is also useful in assessing therapeutic responses to enzyme replacement therapy.