External-beam radiation therapy for improved dialysis access patency: feasibility and early safety.

Rectenwald, J. E., Pretus, H. A., Seeger, J. M., Huber, T. S., Mendenhall, N. P., Zlotecki, R. A., Palta, J. R., Li, Z. F., Hook, S. Y., Sarac, T. P., Welborn, M. B., Klingman, N. V., Abouhamze, Z. S. and Ozaki, C. K. External-Beam Radiation Therapy for Improved Dialysis Access Patency: Feasibility and Early Safety. Radiat. Res. 156, 53-60 (2001).Prosthetic dialysis access grafts fail secondary to neointimal hyperplasia at the venous anastomosis. We hypothesized that postoperative single-fraction external-beam radiation therapy to the venous anastomosis of hemodialysis grafts can be used safely in an effort to improve access patency. Dogs (n = 8) underwent placement of expanded polytetrafluoroethylene grafts from the right carotid artery to the left jugular vein. Five dogs received single-fraction external-beam photon irradiation (8 Gy) to the venous anastomosis after surgery. Controls were not irradiated. Shunt angiograms were completed 3 and 6 months postoperatively. Anastomoses, mid-graft, and the surrounding tissues were analyzed. Immunohistochemistry for smooth muscle cell alpha-actin, proliferating cellular nuclear antigen (PCNA), and apoptosis was performed. Incisions healed well, though all animals developed wound seromas. One control suffered graft thrombosis 4 months postoperatively. Angiography/histology confirmed severe neointimal hyperplasia at the venous anastomosis. The remaining seven dogs developed similar amounts of neointimal hyperplasia. PCNA studies showed no accelerated fibroproliferative response at irradiated anastomoses compared to controls. Skin incisions and soft tissues over irradiated anastomoses revealed no radiation-induced changes or increase in apoptosis. Thus we conclude that postoperative single-fraction external-beam irradiation of the venous anastomosis of a prosthetic arteriovenous graft that mimics the situation in humans is feasible and safe with regard to early wound healing.

Lipid risk factors in patients requiring arterial reconstruction.

Progressive peripheral atherosclerosis commonly leads to failure of a bypass graft. Lowering blood cholesterol retards coronary atherosclerosis and similar treatment might limit peripheral atherosclerosis. To identify lipid risk factors for peripheral atherosclerosis, 144 patients with peripheral atherosclerosis (98 with severe disease and 46 with stable claudication) and 61 age-matched control subjects were studied. Fasting lipid (cholesterol and triglycerides) and lipoprotein (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very-low-density lipoprotein [VLDL] cholesterol [C]) levels were measured. The incidence of hypertension and diabetes mellitus, amount of previous tobacco use, and location and severity of the peripheral atherosclerosis were also determined. Patients with peripheral atherosclerosis had higher VLDL-C and lower HDL-C levels than controls had, but serum cholesterol and plasma LDL-C levels were similar. Patients with peripheral atherosclerosis also had a higher incidence of diabetes mellitus and hypertension. Predictors of peripheral atherosclerosis by regression analysis were diabetes mellitus, low HDL-C levels, and tobacco use, with diabetes mellitus being the strongest variable. Peripheral atherosclerosis below the inguinal ligament was strongly predicted by low HDL-C and increased VLDL-C levels but not by increased cholesterol or LDL-C levels. Thus lipid risk factors for peripheral atherosclerosis are different, and attempts at limiting late graft failure by lowering lipid levels should be directed toward these lipoproteins.