Faculty Bibliography

BACKGROUND AND PURPOSE: Concurrent temporary inflation of a nondetachable balloon in the parent artery has been reported to be useful during endovascular coiling of complex, wide-neck aneurysms, facilitating truer coil reconstruction of the native vessel. Nevertheless, there exists concern that adjunctive use of balloon assistance may lead to increased adverse events during aneurysm coiling. MATERIALS AND METHODS: A literature search of all of the unassisted and balloon-remodeling studies published between 1997 and 2006 was conducted with application of strict selection criteria based on the reporting of complication incidence and outcome. The final cohort was analyzed to determine rates and clinical outcomes of iatrogenic aneurysm rupture and thromboembolism. Additional data were collected on the degree of initial and follow-up aneurysm occlusion rates. RESULTS: A total of 83 potential studies (4973 patients) were identified, from which 23 articles reporting results for 867 traditional-unassisted and 273 balloon-assisted coiled aneurysms met inclusion criteria for the analysis of thromboembolic complications, and 21 articles with 993 routinely coiled and 170 balloon-remodeled aneurysms were eligible for iatrogenic perforation analysis. No statistically significant difference was found in the rates of thromboembolism. Iatrogenic perforation rates were also comparable, though the overall numbers were too few for meaningful statistical analysis. Both initial and follow-up aneurysm occlusion rates were higher in balloon-assisted cases. CONCLUSION: This largest-to-date literature review and meta-analysis did not demonstrate a higher incidence of thromboembolic events or iatrogenic rupture with the use of adjunctive balloon remodeling compared with unassisted coiling. Balloon remodeling appears to result in higher initial and follow-up aneurysm occlusion rates

OBJECTIVE: The purposes of this article are to summarize recent developments and concerns in endovascular aneurysm therapy leading to the adjunctive use of endoluminal devices, to review the published literature on stent-supported coil embolization of cerebral aneurysms, and to describe our experience with this technique in a limited subgroup of problematic complex aneurysms over a medium-term follow-up period. METHODS: Between January 2003 and June 2004, 28 individuals among 157 patients with cerebral aneurysms we evaluated were identified as harboring aneurysms with exceptionally broad necks. Out of these 28 patients, 16 were treated with a combination of stents and detachable coils, preserving the parent artery. Recorded data included patient demographics, the clinical presentation, aneurysm location and characteristics, procedural details, and clinical and angiographic outcome. RESULTS: Over an 18-month period, 16 patients with large cerebral aneurysms additionally characterized by neck sizes between 7 and 14 mm were treated, using combined coil embolization of the aneurysm with stent reconstruction of the aneurysm neck. Thirteen out of the 16 aneurysms were occluded at angiographic reevaluation between 11 and 24 months (mean angiographic follow-up, 17.5 mo). There were no treatment-related deaths or clinically evident neurological complications. Thirteen patients experienced excellent clinical outcomes, with good outcomes in two patients and a poor visual outcome in one patient (mean clinical follow-up, 29 mo). A single technical complication occurred, involving transient nonocclusive stent-associated thrombus, which was treated uneventfully with abciximab. CONCLUSION: Stent-supported coil embolization of large, complex-neck cerebral aneurysms seems to provide superior medium-term anatomic reconstruction of the parent artery compared with historic series of aneurysms treated exclusively with endosaccular coils. In the near future, increasingly sophisticated endoluminal devices offering higher coverage of the neck defect will likely enable more definitive endovascular treatment of complex cerebral aneurysms and further expand our ability to manipulate the vascular biology of the parent artery

Some 4- and 2-(nitrobenzyloxycarbonyl)-1, 2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines (4, 6, and 7) were synthesized and evaluated for their ability to exert preferential toxicity to hypoxic EMT6 mammary carcinoma cells using a colony-forming assay. Of these, the 4,5-dimethoxy-2-nitro analogue 6 (50 microM, 1-h exposure) caused greater than 3 logs of kill of hypoxic cells, with relatively minor toxicity to corresponding aerobic cells. The ability of 4-nitro (4) and 4,5-dimethoxy-2-nitro (6) analogues to reach and kill hypoxic cells of solid tumors was also demonstrated using intradermally implanted EMT6 solid tumors in mice. In addition, a possible source of toxicity to normal tissue, i. e., the activation of the 4-nitrobenzyl derivative 4 by glutathione S-transferase-catalyzed thiolysis, was essentially eliminated by replacing one of the benzylic methylene protons by a methyl group. The 4-nitro (4) and 4,5-dimethoxy-2-nitro (6) analogues also appear to be reduced more easily under acidic conditions (pH 6.0) than under neutral conditions, as measured by differential pulse polarography. Since the pH in hypoxic regions is often lower than that in adjacent aerobic regions, this property should aid in the cytotoxic action of these agents against hypoxic cells of solid tumors