Journal of Surgical Oncology 49:205-207 (1992)
Upper Extremity Occlusive Arterial Disease After Radiotherapy for Breast Cancer UMUR ATABEK, MD, RICHARD K. SPENCE, MD, JAMES B. ALEXANDER, MD, MARK J. PELLO, MD, AND RUDOLPH C. CAMISHION, MD From the Department of Surgery, University of Medicine and Dentistry of New jersey, Robert wood lohnson Medical School at Camden, Carnden
Upper extremity arterial occlusive disease is a rare complication of radiation therapy for breast cancer. We present the case of a 74 year old woman who developed upper extremity ischemia 32 years after mastectomy and radiation therapy. Arteriography identified a stenotic proximal brachial artery lesion within the previous radiation field. Balloon angioplasty was unsuccessful. An axillo-brachial bypass relieved the ischemia and is still patent after 24 months. The previous literature shows that arterial bypass procedures have been uniformly successful in this circumstance. Little experience has been reported with balloon angioplasty for these lesions. 0 1992 Wiley-Liss, Inc. KEYWORDS:radiation therapy, axillo-brachial bypass, balloon angioplasty
INTRODUCTION Radiation therapy is an effective cancer treatment modality but it can also cause significant damage to normal tissues. Occlusive arterial disease of large elastic vessels is a rare long term complication of radiation therapy. In the upper extremities, radiation induced arterial disease is almost exclusively observed after treatment of women for breast cancer. A literature search revealed 24 previously reported cases. We present here another case and review the literature.
CASE REPORT A 74 year old woman presented in 1988 with pains and paresthesias of the right hand which had progressed over the previous 10 weeks. Her past history included a right radical mastectomy in 1956 with postoperative radiation therapy. Details of radiation therapy were unavailable. The upper extremity was subsequently functional although she did develop lymphedema. The lymphedema decreased noticeably over the 10 weeks of progressing symptoms. She also admitted to a 15 pack year history of cigarette smoking although she had quit in 1978. On physical examination, her blood pressure (left arm) was 110/70 with pulse 88. She had nonpitting edema of the entire right upper extremity. The right hand was cool and cyanotic with gangrenous changes at the tips of the index, middle, and ring fingers. Radial and brachial 0 1992 Wiley-Liss, Inc.
pulses were absent. No bruits or thrills were evident. Pulses in the other extremities were normal. The remainder of her physical examination revealed no other significant abnormalities. Laboratory studies showed cholesterol 153 mg/dl and triglycerides 115 mg/dl. Arteriography of the right upper extremity showed some atherosclerotic changes in the subclavian artery, a 30% stenosis of the mid-axillary artery, and a 99% stenosis of the distal axillary artery and proximal brachial artery over a 2.5 centimeter length (Fig. 1). The remainder of the brachial artery was normal. The radial, ulnar, and digital arteries were small but showed no disease. Collateral flow was poor. Percutaneous balloon angioplasty of the 30% stenosis was attempted with minimal success. A guidewire could be passed through the 99% stenosis but the angioplasty catheter could not be advanced through the lesion. Afterwards, her symptoms were not improved and the hand remained cyanotic. An axillo-brachial bypass with reverse saphenous vein graft was performed. The diseased arterial segment was located directly under the skin within the apparently radiated field and was surrounded by fibrous tissue. No arterial segment was excised. Postoperatively, the hand became pink and warm with Accepted for publication May 17, 1991. Address reprint requests to Umur Atabek, MD, Three Cooper Plaza, Suite 411, Camden, NJ 08103.
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Fig. 1 . Right upper extremity arteriogram showing 99% stenosis of distal axillary artery and proximal brachial artery.
normal brachial and radial pulses. The lymphedema became more pronounced. The gangrenous fingertips healed without difficulty. Twenty-four months postoperatively, normal distal pulses and equal brachial pressures indicated that the reconstruction was still patent. The extremity was fully functional. A compression garment met with limited success at controlling the edema.
DISCUSSION Large numbers of women with breast cancer have received radiotherapy through various combinations of chest wall, axillary, supraclavicular, and mediastinal ports. As a consequence, radiation doses were delivered to the inominate, subclavian, axillary, and brachial arteries. A literature search revealed 24 reported cases of upper extremity arterial occlusive disease attributable to radiotherapy for breast cancer [ 1-1 11. Radiation was implicated as the etiologic agent because the arterial lesions were within the radiation fields and because all patients had little evidence of other arterial disease. Two other cases of upper extremity arterial occlusive disease have been reported after radiotherapy for Hodgkin 's disease [ 12,131. Other reports have described radiation induced arterial disease in the aorta [ 14,151, carotid artery [ 16,171, coronary arteries [ 181, iliac artery [ 1,6], and femoral artery [ 11. A number of factors may contribute to the relatively
small number of reported cases. A long time interval of several years between radiation exposure and the development of significant arterial symptoms allows a large number of patients to die of their underlying cancer before symptoms become evident. In some patients, ischemic symptoms may be masked by or erroneously attributed to other postmastectomy problems affecting the upper limb such as pain, nerve root damage, limitation of motion, or lymphedema. Furthermore, many cases of radiation induced arterial injury may but go unrecognized due to mild or nonexistent symptomatology. An extensive collateral circulation in the shoulder area can maintain adequate limb perfusion even with complete subclavian or axillary artery occlusion. In all of the breast cancer associated cases, mastectomy preceeded radiotherapy: 20 patients had radical mastectomy, one had modified radical mastectomy, and four had simple mastectomy. For 13 patients who had the information available, radiation doses varied from 2,775 to greater than 5,775 rads. In one case, overlap of radiation fields was documented thus suggesting that local overdose was responsible [ 11. Quite possibly, other patients may have had unrecognized areas of field overlap. The interval from radiotherapy to diagnosis of arterial disease was quite variable, ranging from 2-42 years with a median of 12 years. Pain, either constant or claudicating, was the most common presenting symptom. Symptoms typically developed gradually over several months, although a few patients presented with acute symptoms consistent with thrombosis or arterioarterial emboli. Most of the case reports did not comment on the presence or absence of other risk factors for atherosclerosis such as tobacco smoking, hyperlipidemia, diabetes mellitus, or hypertension. For two patients who had fingertip gangrene at presentation, a bum was the initiating event. Arteriography was performed in 22 patients. The occlusive disease was located in the subclavian artery in 18 patients, the axillary artery in three patients, the upper brachial artery in one patient, and the subclavian and axillary arteries in two patients. Sixteen patients had complete occlusions and six had stenotic lesions. Six patients were specifically noted to have poor collateral flow. When noted, other large vessels away from the radiotherapy portals were relatively free of disease. Fifteen patients had arterial reconstruction performed: five carotid-brachial bypasses, three subclavian-brachial bypasses, two axillary-brachial bypasses, two subclavian-subclavian bypasses, one carotid-subclavian bypass, one axillary-axillary bypass, and one subclavianaxillary bypass. Graft material was autogenous vein in 11 patients, polytetrafluoroethylene in three, and dacron in one. The surgeons usually tried to avoid dissection within the areas affected by prior surgery and radiotherapy. The reconstructions were uniformly successful and no complications directly related to the surgery were reported.
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Only two of the reported patients experienced tissue bypass procedures are uniformly successful and tissue loss. One patient with fingertip gangrene had a left index loss is unusual. More experience is needed before the finger amputation after arterial reconstruction [9]. An- value of balloon angioplasty in the management of these other patient with a contracted, nonfunctioning, painful lesions can be assessed. hand had a primary forearm amputation performed [6]. Interestingly, in our patient, variation in the amount of REFERENCES upper extremity lymphedema reflected changes in arterial 1. Benson EP: Radiation injury to large arteries: three further perfusion pressure and lymph flow. During the 10 weeks examples with prolonged asymptomatic intervals. Radiology of progressing arterial symptoms, she noticed a consid106:195-197, 1973. erable decrease in edema. After successful revascular2. Mavor GE, Kasenally AT, Harper DR, Woodruff PWH: Thrombosis of the subclavian-axillary artery following radiotherapy for ization, the edema reaccumulated to the previous level. carcinoma of the breast. Br J Surg 60:983-985, 1973. The failure of balloon angioplasty in our patient should 3. Loeffler RK: Subclavian artery occlusion following radiation not discourage its use in future cases which appear therapy: a case history. Invest Radio1 10:391-393, 1975. 4. Budin JA, Casarella WJ, Harisiadis L: Subclavian artery occluamenable. Successful intraoperative balloon dilatation of sion following radiotherapy for carcinoma of the breast. Radiola postirradiation brachial artery stenosis has been reogy 118:169-173, 1976. ported [ 131. Nonetheless, stenoses in radiated arteries 5. Peters WR, Schlicke CP, Schmutz DD: Peripheral vascular disease following radiation therapy. Am Surg 45:70&702, 1979. may be intrinsically more difficult to dilate than those in 6. Butler MJ, Lane RHS, Webster JHH: Irradiation injury to large nonradiated vessels. As seen in our patient, these arteries arteries. Br J Surg 67:341-343, 1980. are often surrounded by significant periarterial fibrosis 7. Lemkin JA, Kurchin A: Delayed radiation effects on left subclavian artery. NY State J Med 81:943-944, 1981. which conceivably could limit distensibility . 8. Kalman PG, Lipton IH, Provan JL, Walker PM, Miles JT, Yeung The histologic characteristics of lesions induced by HP: Radiation damage to large arteries. Can J Surg 26%-91, radiation in large arteries have been described in several 1983. 9. Hughes WF, Carson CL, Laffaye HA: Subclavian artery occluanimal studies and in humans. Changes have been sion 42 years after mastectomy and radiotherapy. Am J Surg observed in all layers of the arterial wall with many of the 1471698-700, 1984. changes in the inner portions resembling those seen in 10. Kretschmer G, Niederle B, Polterauer P, Waneck R: Irratiationinduced changes in the subclavian and axillary arteries after normally occurring atherosclerosis. In radiatiated mice, radiotherapy for carcinoma of the breast. Surgery 99:658-663, Smith and Lowenthal observed fraying of the internal 1986. elastic lamina and increased ground substance [ 191. The 11. Hashmonai M, Elami A, Kuter A, Lichtig C, Torem S: Subclavian arterv occlusion after radiotheraov for carcinoma of the breast. lesions were similar to those normally seen in old mice. Cancer 61:2015-2018, 1988. In radiated dog aortas, Lindsay et al. produced athero- 12. Heidenberg WJ, Lupovitch A, Tan N: “Pulseless disease” comsclerotic lesions which were indistinguishable from the plicating Hodgkin’s disease: a case apparently caused by radiotherapy. JAMA 195194197, 1966. naturally occurring lesions in old dogs [20]. They pro13. Guthaner DF, Schmitz L: Percutaneous transluminal angioplasty posed that radiation injured the internal elastic lamina of radiation-induced arterial stenoses. Radiology 144:77-78, which was then followed by intimal fibrosis and plaque 1982. . . to the aorta and the formation. After studying radiated mesenteric vessels in 14. Thomas E, Forbus WD: Irradiation iniury lung. Arch Pathol 67:256-263, 1959. mice, Hirst et al. proposed that radiation destroys endo- 15. Marcia1 Rojas RA, Castro JR: Irradiation injury to elastic arteries thelial cells with the resultant increased permeability in the course of treatment of neoplastic disease. Ann Otolaryngol Rhino1 Laryngol 71:945-948, 1962. leading to hyaline thickening and deposition of fibrin and 16. Huvos AG, Learning RH, Moore 0s: Clinicopathologic study of collagen in the vessel wall [21]. In radiated mice, Sams the resected carotid artery: analysis of sixty-four cases. Am J Surg described fibrosis in the adventitial and periarterial 126:57&574, 1973. tissues which apparently contributed to occlusive mani- 17. Silverberg DG, Britt RH, Goffinet DR: Radiation-induced carotid artery disease. Cancer 41:13@137, 1978. festations by externally constricting the vessels [22]. 18. Annest LS, Anderson RP, Li W, Hafermann MD: Coronary artery disease following mediastinal radiation therapy. J Thorac CardioRubin and Casarett thought that radiation injury to vaso vasc Surg 85:257-263, 1983. vasorum led to ischemic damage in the arterial wall [23]. 19. Smith C, Lowenthal LA: Study of elastic arteries in irradiated Other coexisting processes may compound the radiamice of different ages. Proc SOCExp Biol Med 75:859-861, 1950. tion injury. Salivary fistulas and persistent tumor have 20. Lindsay S , Kohn HI, Dakin RL, Jew J: Aortic arteriosclerosis in the dog after localized aortic x-irradiation. Circ Res 10:51-60, been associated with postradiation rupture of the aorta 1962. and carotid artery [15-191. There is also evidence in 21. Hirst DG, Denkamp J, Travis EL: The response of mesenteric animals that radiation injury and hyperlipidemia have an blood vessels to irradiation. Radiat Res 77:259-277, 1979. additive effect on producing atherosclerotic lesions [24] 22. Sams A: Histological changes in the larger blood vessels of the hind limb of the mouse after x-irradiation. lnt J Radiat Biol although there is insufficient evidence for such an 9:165-174, 1965. 23. Rubin P, Casarett GW: “Clinical Radiation Pathology.” Philadelassociation in humans [ 17,181. phia, Saunders, 1968 pp 501-515. In summary, occlusive disease in large arteries is a rare 24. Artom C, Lofland HB, Clarkson TB: Ionizing radiation, atherocomplication of radiation therapy for breast cancer and sclerosis, and lipid metabolism in pigeons. Radiat Res 26:165117, 1965. usually presents after a lag time of several years. Arterial 1,
Upper Extremity Occlusive Arterial Disease After Radiotherapy for Breast Cancer UMUR ATABEK, MD, RICHARD K. SPENCE, MD, JAMES B. ALEXANDER, MD, MARK J. PELLO, MD, AND RUDOLPH C. CAMISHION, MD From the Department of Surgery, University of Medicine and Dentistry of New jersey, Robert wood lohnson Medical School at Camden, Carnden
Upper extremity arterial occlusive disease is a rare complication of radiation therapy for breast cancer. We present the case of a 74 year old woman who developed upper extremity ischemia 32 years after mastectomy and radiation therapy. Arteriography identified a stenotic proximal brachial artery lesion within the previous radiation field. Balloon angioplasty was unsuccessful. An axillo-brachial bypass relieved the ischemia and is still patent after 24 months. The previous literature shows that arterial bypass procedures have been uniformly successful in this circumstance. Little experience has been reported with balloon angioplasty for these lesions. 0 1992 Wiley-Liss, Inc. KEYWORDS:radiation therapy, axillo-brachial bypass, balloon angioplasty
INTRODUCTION Radiation therapy is an effective cancer treatment modality but it can also cause significant damage to normal tissues. Occlusive arterial disease of large elastic vessels is a rare long term complication of radiation therapy. In the upper extremities, radiation induced arterial disease is almost exclusively observed after treatment of women for breast cancer. A literature search revealed 24 previously reported cases. We present here another case and review the literature.
CASE REPORT A 74 year old woman presented in 1988 with pains and paresthesias of the right hand which had progressed over the previous 10 weeks. Her past history included a right radical mastectomy in 1956 with postoperative radiation therapy. Details of radiation therapy were unavailable. The upper extremity was subsequently functional although she did develop lymphedema. The lymphedema decreased noticeably over the 10 weeks of progressing symptoms. She also admitted to a 15 pack year history of cigarette smoking although she had quit in 1978. On physical examination, her blood pressure (left arm) was 110/70 with pulse 88. She had nonpitting edema of the entire right upper extremity. The right hand was cool and cyanotic with gangrenous changes at the tips of the index, middle, and ring fingers. Radial and brachial 0 1992 Wiley-Liss, Inc.
pulses were absent. No bruits or thrills were evident. Pulses in the other extremities were normal. The remainder of her physical examination revealed no other significant abnormalities. Laboratory studies showed cholesterol 153 mg/dl and triglycerides 115 mg/dl. Arteriography of the right upper extremity showed some atherosclerotic changes in the subclavian artery, a 30% stenosis of the mid-axillary artery, and a 99% stenosis of the distal axillary artery and proximal brachial artery over a 2.5 centimeter length (Fig. 1). The remainder of the brachial artery was normal. The radial, ulnar, and digital arteries were small but showed no disease. Collateral flow was poor. Percutaneous balloon angioplasty of the 30% stenosis was attempted with minimal success. A guidewire could be passed through the 99% stenosis but the angioplasty catheter could not be advanced through the lesion. Afterwards, her symptoms were not improved and the hand remained cyanotic. An axillo-brachial bypass with reverse saphenous vein graft was performed. The diseased arterial segment was located directly under the skin within the apparently radiated field and was surrounded by fibrous tissue. No arterial segment was excised. Postoperatively, the hand became pink and warm with Accepted for publication May 17, 1991. Address reprint requests to Umur Atabek, MD, Three Cooper Plaza, Suite 411, Camden, NJ 08103.
206
Atabek et al.
Fig. 1 . Right upper extremity arteriogram showing 99% stenosis of distal axillary artery and proximal brachial artery.
normal brachial and radial pulses. The lymphedema became more pronounced. The gangrenous fingertips healed without difficulty. Twenty-four months postoperatively, normal distal pulses and equal brachial pressures indicated that the reconstruction was still patent. The extremity was fully functional. A compression garment met with limited success at controlling the edema.
DISCUSSION Large numbers of women with breast cancer have received radiotherapy through various combinations of chest wall, axillary, supraclavicular, and mediastinal ports. As a consequence, radiation doses were delivered to the inominate, subclavian, axillary, and brachial arteries. A literature search revealed 24 reported cases of upper extremity arterial occlusive disease attributable to radiotherapy for breast cancer [ 1-1 11. Radiation was implicated as the etiologic agent because the arterial lesions were within the radiation fields and because all patients had little evidence of other arterial disease. Two other cases of upper extremity arterial occlusive disease have been reported after radiotherapy for Hodgkin 's disease [ 12,131. Other reports have described radiation induced arterial disease in the aorta [ 14,151, carotid artery [ 16,171, coronary arteries [ 181, iliac artery [ 1,6], and femoral artery [ 11. A number of factors may contribute to the relatively
small number of reported cases. A long time interval of several years between radiation exposure and the development of significant arterial symptoms allows a large number of patients to die of their underlying cancer before symptoms become evident. In some patients, ischemic symptoms may be masked by or erroneously attributed to other postmastectomy problems affecting the upper limb such as pain, nerve root damage, limitation of motion, or lymphedema. Furthermore, many cases of radiation induced arterial injury may but go unrecognized due to mild or nonexistent symptomatology. An extensive collateral circulation in the shoulder area can maintain adequate limb perfusion even with complete subclavian or axillary artery occlusion. In all of the breast cancer associated cases, mastectomy preceeded radiotherapy: 20 patients had radical mastectomy, one had modified radical mastectomy, and four had simple mastectomy. For 13 patients who had the information available, radiation doses varied from 2,775 to greater than 5,775 rads. In one case, overlap of radiation fields was documented thus suggesting that local overdose was responsible [ 11. Quite possibly, other patients may have had unrecognized areas of field overlap. The interval from radiotherapy to diagnosis of arterial disease was quite variable, ranging from 2-42 years with a median of 12 years. Pain, either constant or claudicating, was the most common presenting symptom. Symptoms typically developed gradually over several months, although a few patients presented with acute symptoms consistent with thrombosis or arterioarterial emboli. Most of the case reports did not comment on the presence or absence of other risk factors for atherosclerosis such as tobacco smoking, hyperlipidemia, diabetes mellitus, or hypertension. For two patients who had fingertip gangrene at presentation, a bum was the initiating event. Arteriography was performed in 22 patients. The occlusive disease was located in the subclavian artery in 18 patients, the axillary artery in three patients, the upper brachial artery in one patient, and the subclavian and axillary arteries in two patients. Sixteen patients had complete occlusions and six had stenotic lesions. Six patients were specifically noted to have poor collateral flow. When noted, other large vessels away from the radiotherapy portals were relatively free of disease. Fifteen patients had arterial reconstruction performed: five carotid-brachial bypasses, three subclavian-brachial bypasses, two axillary-brachial bypasses, two subclavian-subclavian bypasses, one carotid-subclavian bypass, one axillary-axillary bypass, and one subclavianaxillary bypass. Graft material was autogenous vein in 11 patients, polytetrafluoroethylene in three, and dacron in one. The surgeons usually tried to avoid dissection within the areas affected by prior surgery and radiotherapy. The reconstructions were uniformly successful and no complications directly related to the surgery were reported.
Upper Extremity Occlusive Arterial Disease
207
Only two of the reported patients experienced tissue bypass procedures are uniformly successful and tissue loss. One patient with fingertip gangrene had a left index loss is unusual. More experience is needed before the finger amputation after arterial reconstruction [9]. An- value of balloon angioplasty in the management of these other patient with a contracted, nonfunctioning, painful lesions can be assessed. hand had a primary forearm amputation performed [6]. Interestingly, in our patient, variation in the amount of REFERENCES upper extremity lymphedema reflected changes in arterial 1. Benson EP: Radiation injury to large arteries: three further perfusion pressure and lymph flow. During the 10 weeks examples with prolonged asymptomatic intervals. Radiology of progressing arterial symptoms, she noticed a consid106:195-197, 1973. erable decrease in edema. After successful revascular2. Mavor GE, Kasenally AT, Harper DR, Woodruff PWH: Thrombosis of the subclavian-axillary artery following radiotherapy for ization, the edema reaccumulated to the previous level. carcinoma of the breast. Br J Surg 60:983-985, 1973. The failure of balloon angioplasty in our patient should 3. Loeffler RK: Subclavian artery occlusion following radiation not discourage its use in future cases which appear therapy: a case history. Invest Radio1 10:391-393, 1975. 4. Budin JA, Casarella WJ, Harisiadis L: Subclavian artery occluamenable. Successful intraoperative balloon dilatation of sion following radiotherapy for carcinoma of the breast. Radiola postirradiation brachial artery stenosis has been reogy 118:169-173, 1976. ported [ 131. Nonetheless, stenoses in radiated arteries 5. Peters WR, Schlicke CP, Schmutz DD: Peripheral vascular disease following radiation therapy. Am Surg 45:70&702, 1979. may be intrinsically more difficult to dilate than those in 6. Butler MJ, Lane RHS, Webster JHH: Irradiation injury to large nonradiated vessels. As seen in our patient, these arteries arteries. Br J Surg 67:341-343, 1980. are often surrounded by significant periarterial fibrosis 7. Lemkin JA, Kurchin A: Delayed radiation effects on left subclavian artery. NY State J Med 81:943-944, 1981. which conceivably could limit distensibility . 8. Kalman PG, Lipton IH, Provan JL, Walker PM, Miles JT, Yeung The histologic characteristics of lesions induced by HP: Radiation damage to large arteries. Can J Surg 26%-91, radiation in large arteries have been described in several 1983. 9. Hughes WF, Carson CL, Laffaye HA: Subclavian artery occluanimal studies and in humans. Changes have been sion 42 years after mastectomy and radiotherapy. Am J Surg observed in all layers of the arterial wall with many of the 1471698-700, 1984. changes in the inner portions resembling those seen in 10. Kretschmer G, Niederle B, Polterauer P, Waneck R: Irratiationinduced changes in the subclavian and axillary arteries after normally occurring atherosclerosis. In radiatiated mice, radiotherapy for carcinoma of the breast. Surgery 99:658-663, Smith and Lowenthal observed fraying of the internal 1986. elastic lamina and increased ground substance [ 191. The 11. Hashmonai M, Elami A, Kuter A, Lichtig C, Torem S: Subclavian arterv occlusion after radiotheraov for carcinoma of the breast. lesions were similar to those normally seen in old mice. Cancer 61:2015-2018, 1988. In radiated dog aortas, Lindsay et al. produced athero- 12. Heidenberg WJ, Lupovitch A, Tan N: “Pulseless disease” comsclerotic lesions which were indistinguishable from the plicating Hodgkin’s disease: a case apparently caused by radiotherapy. JAMA 195194197, 1966. naturally occurring lesions in old dogs [20]. They pro13. Guthaner DF, Schmitz L: Percutaneous transluminal angioplasty posed that radiation injured the internal elastic lamina of radiation-induced arterial stenoses. Radiology 144:77-78, which was then followed by intimal fibrosis and plaque 1982. . . to the aorta and the formation. After studying radiated mesenteric vessels in 14. Thomas E, Forbus WD: Irradiation iniury lung. Arch Pathol 67:256-263, 1959. mice, Hirst et al. proposed that radiation destroys endo- 15. Marcia1 Rojas RA, Castro JR: Irradiation injury to elastic arteries thelial cells with the resultant increased permeability in the course of treatment of neoplastic disease. Ann Otolaryngol Rhino1 Laryngol 71:945-948, 1962. leading to hyaline thickening and deposition of fibrin and 16. Huvos AG, Learning RH, Moore 0s: Clinicopathologic study of collagen in the vessel wall [21]. In radiated mice, Sams the resected carotid artery: analysis of sixty-four cases. Am J Surg described fibrosis in the adventitial and periarterial 126:57&574, 1973. tissues which apparently contributed to occlusive mani- 17. Silverberg DG, Britt RH, Goffinet DR: Radiation-induced carotid artery disease. Cancer 41:13@137, 1978. festations by externally constricting the vessels [22]. 18. Annest LS, Anderson RP, Li W, Hafermann MD: Coronary artery disease following mediastinal radiation therapy. J Thorac CardioRubin and Casarett thought that radiation injury to vaso vasc Surg 85:257-263, 1983. vasorum led to ischemic damage in the arterial wall [23]. 19. Smith C, Lowenthal LA: Study of elastic arteries in irradiated Other coexisting processes may compound the radiamice of different ages. Proc SOCExp Biol Med 75:859-861, 1950. tion injury. Salivary fistulas and persistent tumor have 20. Lindsay S , Kohn HI, Dakin RL, Jew J: Aortic arteriosclerosis in the dog after localized aortic x-irradiation. Circ Res 10:51-60, been associated with postradiation rupture of the aorta 1962. and carotid artery [15-191. There is also evidence in 21. Hirst DG, Denkamp J, Travis EL: The response of mesenteric animals that radiation injury and hyperlipidemia have an blood vessels to irradiation. Radiat Res 77:259-277, 1979. additive effect on producing atherosclerotic lesions [24] 22. Sams A: Histological changes in the larger blood vessels of the hind limb of the mouse after x-irradiation. lnt J Radiat Biol although there is insufficient evidence for such an 9:165-174, 1965. 23. Rubin P, Casarett GW: “Clinical Radiation Pathology.” Philadelassociation in humans [ 17,181. phia, Saunders, 1968 pp 501-515. In summary, occlusive disease in large arteries is a rare 24. Artom C, Lofland HB, Clarkson TB: Ionizing radiation, atherocomplication of radiation therapy for breast cancer and sclerosis, and lipid metabolism in pigeons. Radiat Res 26:165117, 1965. usually presents after a lag time of several years. Arterial 1,
