We hypothesized that IFN-A would enhance the apoptotic activity of bortezomib on melanoma cells. Combined treatment with bortezomib and IFN-A induced synergistic apoptosis in melanoma and other solid tumor cell lines. Apoptosis was associated with processing of procaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cleavage of Bid and poly(ADP-ribose) polymerase. Bortezomib plus IFN-A was effective at inducing apoptosis in melanoma cells that overexpressed Bcl-2 or Mcl-1, suggesting that this treatment combination can overcome mitochondrial pathways of cell survival and resistance to apoptosis. The proapoptotic effects of this treatment combination were abrogated by a caspase-8 inhibitor, led to increased association of Fas and FADD before the onset of cell death, and were significantly reduced in cells transfected with a dominant-negative FADD construct or small interfering RNA targeting Fas. These data suggest that bortezomib and IFN-A act through the extrinsic pathway of apoptosis via FADD-induced caspase-8 activation to initiate cell death. Finally, bortezomib and IFN-A displayed statistically significant antitumor activity compared with either agent alone in both the B16 murine model of melanoma and in athymic mice bearing human A375 xenografts. These data support the future clinical development of bortezomib and IFN-A for malignant melanoma. [Cancer Res 2008;68(20):8351-60]

In our experience, the rate of gastrojejunostomy stenosis following Roux-en-Y gastric bypass is 6.8%. Endoscopic balloon dilation is a safe and effective therapy for stomal stenosis with a high success rate. It should be considered an appropriate intervention with a low risk for reoperation.

A conservative estimate by both population and workload analysis, disregarding aging of the population, lifestyle choices of future VSN, and increasing demand for services, indicates a shortage of VSN in the future. Unless the Balanced Budget Act of 1997 is revised by Congress, the cost to train the additional VS workforce remains a significant barrier.

Objective Abdominal aortic aneurysm (AAA) wall stiffness has been suggested to be an important factor in the overall rupture risk assessment compared to anatomical measure; we hypothesize that AAA diameter will have no correlation to AAA wall stiffness. The aim of this study is to 1) determine MRE-derived aortic wall stiffness in AAA patients and its correlation to AAA diameter; 2) determine correlation between AAA stiffness and amount of thrombus and calcium; and 3) compare the AAA stiffness measurements against age matched healthy subjects. Methods In-vivo abdominal aortic MRE was performed on 36 subjects (24 patients with AAA measuring 3-10 cm and 12 healthy volunteers) aged 36-78 years old after obtaining written informed consent under the approval of the institutional review board. MRE images were processed to obtain spatial stiffness maps of the aorta. AAA diameter, amount of thrombus and calcium score were reported by experienced interventional radiologists. Spearman correlation, Wilcoxon signed rank test and Mann-Whitney test were performed to determine the correlation between AAA stiffness and diameter, and also to determine significant difference in stiffness measurements between AAA patients and healthy subjects. Results No significant correlation (P>.1) was found between AAA stiffness and diameter or amount of thrombus or calcium score. AAA stiffness (mean:13.97±4.2kPa) is significantly (P≤.02) higher than remote normal aorta in AAA (mean:8.87±2.2kPa) patients and in normal subjects (mean:7.1±1.9kPa). Conclusion Our results suggest that AAA wall stiffness may provide additional information independent of AAA diameter, which may contribute to our understanding of AAA pathophysiology, biomechanics, and risk for rupture.

Endovascular interventions for TASC II B and C lesions are associated with restenosis/occlusion rates that are at least as good as those of open femoropopliteal bypass surgery from historical, previously published series. Furthermore, overall assisted-patency rates are excellent, although low preoperative ABIs continue to be associated with worse outcomes.

TEVAR for traumatic aortic transection is feasible, with good initial success. Repair can be delayed in selected cases. Continued surveillance is necessary to ensure good long-term outcomes in these young patients. Care must be taken when performing TEVAR for this off-label indication because these devices are designed for the larger aortic diameters of aneurysm patients.

After EVAR, a 6-month CT after a normal 1-month CT result does not identify any clinically significant findings warranting intervention and can be omitted safely from the follow-up schedule.

Three thoracic endograft devices have concluded their phase II trials for release in the United States. The Gore TAG endoprosthesis (W. L. Gore and Associates, Flagstaff, Ariz) was the first to enter clinical trials for the treatment of thoracic aortic aneurysms, confirming its safety and efficacy as well as its short-term advantages over open surgical repair. In March 2005, it became the first endograft to gain United States Food and Drug Administration approval for general use. Follow-up in the Gore TAG pivotal trial demonstrates that aneurysm-related mortality is improved compared with open surgical repair, with similar overall mortality and reintervention rates.