Abstract
Radiation injury to arterial occlusion is a rare and late complication of radiotherapy. Numerous adverse reactions may occur secondary to radiation therapy. A well-known side effect is radiation-induced occlusive lesions and the enhancement of normally occurring atherosclerosis. We report a case of symptomatic right iliac and femoral artery occlusion after radiation therapy for carcinoma of the testis.
Arterial occlusion owing to radiotherapy is a rare but important ischemia situation in the exposed extremity. 1 The vascular effects of radiation therapy are particularly challenging clinical problems and characteristically manifest after a long latency period. Radiation arteriopathy usually develops between 6 and 20 years after the radiotherapy. 2,3 Clinical and experimental data suggest that radiation predisposes patients to atherosclerotic change by causing endothelial damage. 4 We report a patient who presented with severe right lower limb ischemia following previous radiotherapy for testis carcinoma.
Case Report
A 60-year-old male had been treated with ionizing radiation for testis carcinoma 20 years before. He was admitted to our clinic for rest pain, numbness, and weakness of the right lower extremity. At the physical examination, no arterial pulse was detected in the affected extremity, and the ankle-brachial pressure index was 0.4. Selective lower extremity angiography demonstrated complete occlusion of the right distal external iliac artery and common and proximal superficial femoral artery occlusion, which was presumed to be the result of previous radiation therapy (Figure 1). Coronary, carotid, and upper extremity angiograms were normal. The right iliac and femoral arteries were in the field of the radiation. All other arteries were free of atherosclerosis in all angiographic images. For atherosclerotic disease, all blood parameters were normal. In the patient's history, there was no trauma or other cause of occlusion and no atheroembolic sites of origin. Echocardiographic evaluation was normal. There were no major atherosclerotic risk factors (eg, diabetes mellitus, smoking, hypertension).
Angiographic views of the right lower extremity arterial occlusion. A, Proximal site of the occlusion. B, Distal site of the occlusion.
The patient was treated surgically under general anesthesia. The patient was placed in a supine position, with a hard pillow under the right thoracolumbar region, thus elevating the body by about 10° to 15°. The femoral artery was fırst exposed. Flank incisions were used for proximal arterial bypass. The external oblique muscle was divided along its fibers, and the internal oblique and transversus muscles were transected. After the abdominal contents were retracted and protected with moist laparotomy sheets, the right common iliac artery was exposed. After an intravenous injection of 5,000 IU of heparin, proximal end-to-side anastomoses were fırst performed on side clamping. Iliofemoral bypass was performed with a polytetrafluoroethylene graft (Figure 2). The specimen from the femoral artery was sent for histopathologic examination. Immediate success was obtained, and we did not observe any vascular problems. The mean ankle-brachial pressure index after surgery was 0.96. The patient's postoperative course was uneventful. Histopathologic examination of the resected arterial sections revealed fibrotic changes in the intima media and thrombotic changes in the vessel lumen (Figure 3). The patient was discharged on the sixth postoperative day with no sign of lower extremity ischemia.
Operative view of the right lower extremity arterial reconstruction with a polytetrafluoroethylene graft.
Microscopic appearance of the resected arterial sections. A, Irradiated artery with marked residual intramural hemorrhage/fibrin deposition at the site of injury and nonocclusive luminal thrombus. Arrow indicates fibrosis (hematoxylin–eosin stain; ×40 original magnification). B, This photomicrograph demonstrates a typical pattern of marked destruction of the medial elastin (elastin van Gieson stain; ×40 original magnification). C, Intimal thickening and collagen deposition in the intimal layer and media (Masson trichrome stain; ×40 original magnification).
Discussion
Although arterial insufficiency is a rarely reported sequel to radiotherapy, it may be the cause of pain and disability in the affected extremity. Radiation-induced arterial injury can be expressed in many ways: acute thrombosis or arterial rupture in the early months of radiation arteritis, later arterial fibrosis and stenosis, and accelerated local atherosclerosis 3 to 10 years following treatment. Almost any artery can sustain damage. Presenting symptoms may include exsanguinating hemorrhage, acute arterial occlusion, claudication, transient ischemic attacks, and stroke. 5,6 Clinically and angiographically, these lesions are often indistinguishable from atherosclerosis. Symptomatic patients generally present at an earlier age with irradiation-induced disease and are less likely to have associated coronary or other vascular disease since irradiation injuries are localized to the irradiated areas. 7 We also determined occlusive disease to the irradiated areas and did not find coronary or other vascular disease in our case.
As stated by Butler and colleagues, there are three stages following irradiation. 8 The first pattern consists of intimal damage resulting in mural thrombosis and occurs within the first 5 years of the irradiation. The second pattern is evident within 10 years and is manifested by fibrotic occlusion. Periarterial fibrosis and accelerated atherosclerosis are common after approximately 20 years.
Irradiation may cause damage not only to small vessels but also to large arteries, such as the subclavian, carotid, and femoral arteries. 8 Morphologic changes in small arteries have been described by several investigators. These changes include endothelial proliferation, degeneration of the cells of the media with subsequent cystic medial necrosis, and fibrosis. Most injuries to the arteries present with late manifestations, and, for the most part, injury to the vasa vasorum is present. 9 Fonkalsrud and colleagues documented these changes by light electron microscopy. 2 Fibrosis of the arterial wall as a result of damage to the vasa vasorum leads to narrowing of the vessel lumen. Clinical and experimental evidence has demonstrated that radiotherapy can damage large vessels. 4 Irradiation damage to a large artery was first reported in humans in 1959 by Thomas and Forbus in a 21-year-old man who had received radiation for the treatment of lymphoma. 10 The irradiated arch had fibrotic changes in the intima media and adventitia with obliteration of the vasa vasora. In our case, fibrotic changes in the intima media and thrombotic changes in the obliterated vessel lumen were detected on histopathologic evaluation of the resected arterial specimens.
In conclusion, different mechanisms of injury leading to arterial occlusion have been proposed. This is a late complication with a considerable time lag between irradiation and onset of symptoms. The symptoms vary in type and severity but are consistent with peripheral arterial occlusive disease. To alleviate symptoms and prevent limb loss, reconstructive vascular surgery is advocated. The vascular supply was successfully reconstructed by right iliofemoral bypass with a synthetic graft in our case.