The clinical use of metallic expandable intravascular stents has resulted in improved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-bisphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine bisphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular bisphosphonate layer on metal alloy surfaces (steel, nitinol, and cobaltchromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Adinducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal͞media ratio 1.68 ؎ 0.27 and 3.4 ؎ 0.35; Ad-iNOS vs. control, P < 0.01). It is concluded that effective gene vector delivery from metallic stent surfaces can be achieved by using this approach.gene therapy ͉ local delivery ͉ restenosis T he use of balloon expandable metallic stents has resulted in improved therapeutic outcomes for coronary artery disease (1). However, stent angioplasty is complicated in many patients by reobstruction due to the formation of a neointima in the stented arterial segment, a disease process known as in-stent restenosis (2). The mechanisms responsible for instent restenosis involve proliferation and migration of medial smooth muscle cells (SMCs) and an associated increase in extracellular matrix components (2). The use of polymercoated drug-eluting stents has markedly decreased the incidence of in-stent restenosis observed with unmodified metal stents (3). However, both experimental (4) and clinical (5) studies indicate a number of concerns about this approach, because polymer coatings on stents cause a more pronounced inf lammatory response than metal surfaces (6), thus delaying rather than preventing restenosis (7,8).Polymer-coated gene-delivery stents have been demonstrated in animal studies to be effective for both reporter (9-13) and therapeutic (14, 15) vector delivery. Nevertheless, their use is problematic because of harmful properties of the polymer coatings (6, 7). Therefore, the present experiments investigated gene deli...
Objective. To assess the performance of sonography in evaluating small indeterminate liver lesions detected on computed tomography in patients with cancer. Methods. Radiology database review from January 1, 1998, to August 4, 2000, identified 76 patients with 124 indeterminate hepatic lesions smaller than 1.5 cm on computed tomography who had abdominal sonography within 3 months. Sonographic reports and images were reviewed to assess whether lesions were referenced or specifically sought and to verify lesion correspondence, detection, and characterization. The validity of sonographic characterization was determined by histopathologic examination or follow-up imaging (mean time to follow up, 17 months; range, 6.5-38.8 months). Results. Sixty (48%) of 124 indeterminate lesions were evident on sonography. Detection improved when lesions were specifically sought and lesion size was greater than 0.5 cm. Forty (66%) of 61 lesions were detected when the radiologist referenced the preceding computed tomography versus 20 (32%) of 63 lesions when the computed tomographic findings were not referenced (P = .0004). Fifty-one (67%) of 76 lesions measuring 0.6 to 1.5 cm were detected on sonography versus 9 (19%) of 48 lesions measuring 0.1 to 0.5 cm. Lesion size (P < .0001) and body habitus (P = .02) were significant factors influencing lesion detection. Sonography characterized 56 (93%) of 60 detected lesions (33 cysts, 18 solid lesions/metastases, and 5 hemangiomas). Sonographic diagnoses were supported in 42 (93%) of 45 lesions by follow-up imaging (37 of 40) or histopathologic examination (5 of 5). Conclusions. Sonography may be useful in cancer patients with average body habitus to characterize small (0.6-to 1.5-cm) indeterminate liver lesions detected on computed tomography. Key words: cancer; liver lesions; metastases.Received November 19, 2002, Abbreviations CT, computed tomography; MRI, magnetic resonance imaging mall liver lesions (<1.5 cm) detected during routine computed tomography (CT) of the abdomen are frequent, estimated as present on abdominal CT in up to 17% of outpatients.1 Schwartz et al 2 evaluated indeterminate and small hepatic lesions (<1.0 cm) found in CT examinations of 378 patients with cancer and found that, despite a nonspecific imaging appearance, 12% of such lesions represented metastases on the basis of interval growth on follow-up. Computed tomography has become the principal examination for initial staging and follow-up of malignancies; however, difficulty in characterizing small hepatic lesions by CT has long been understood.3 Some authors have advocated sonography to characterize such small hepatic lesions.
In patients with recurrent ovarian carcinoma considered for secondary cytoreductive surgery, preoperative CT can be helpful in identifying the extent of the disease and can be used as an adjunct to treatment planning and management decisions.
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