- Email: [email protected]
Management of arterial occlusive radiation therapy
nt of arbrial occl raditibn therapy C.Andros,P.A. Schneider,R.W. Harris,L. B. Dulawa,R.W.Oblathand S.X. Sales-Cunha Saint Joseph Medical Center, Burbank, California, USA
Clinicatly significant arterial occlusive disease developed in 26 patients at between 5 months and 44 years (mean(s.d.) 10.7(12.0) years) following radiation therapy. Therapeulzic radiation was associated with lesions of the carotid artery (nine pal&~&~), subclavianartefies (seven) and the abdominal aorta and its branches (IO). Clinical presentations inclu&!d tr@miieti ischemic attack, stroke, vettebrobasilar insufficiency, carotid bruit, upper- o ischemia and renovascular hypertension. Surgery for cerebrovasculaf insu carotid endarterectomy with vein patch, interposition grafting or sub&Man-to-carotid bypass. Carotid or subclavian-to-axillary bypass was performed for upper-extremRy ischemla. A combination of endarterectomy and Dacron or saphenous vein graflzs was used for lnfrarenal reconstruction. Tunnels were placed orthotopically. Musculocutanews flaps assisted In heating selected wounds. Ureteral catheters were useful adjuncts in abdominal vascular reconstructions. There were no operative deaths. strokes or amputations. One patient had recu,Went transient ischemic attack following subclavian-to-carotid bypass. The mean(s.d.) e follow-up was 48.1(39.6) months. Patients presenting with end-organ ischemia foHowing radiation therapy can be managed successfully with aggressive surgical revasculariza~ion using a broad spectrum of reconstructive techniques. Keywords: radiation arteritis, arterial occlusion, radiotherapy
As the application of radiation therapy has expanded, ensuing complications have become recognized with increasing frequency. Although arteriosclerosis and radiation therapy are widely prevalent in technologically advanced countries, vascular injury due to radiation may be overlooked because it presents insidiously and gradually develops into a chronic ischemic syndrome. The recognized effects of radiation on normal and abnormal arteries should be included among risk factors for the development of atherosclerotic occlusive diseaselW3. The goal of the present study was to evaluate the diagnostic and management techniques used by the authors in patients with clinically significant vascular lesions associated with previous radiation therapy.
Correspondence to: Dr G. Andros, Vascular Laboratory, Saint Joseph Medical Center, 501 South Buena Vista Ave., Burbank, CA 91505-4866. USA
CARDIOVAWJLAR SURGERY APRlL 1996 VOL 4 NO 2
-._ --._.---
From the analysis of a large group of patients that developed diverse manifestations of radiation vasculopathy a series of management strategies has been devised.
Patients and methods Between January 1976 and December 1992,26 patients (eight men and 18 women) of mean(s.d.) age 67.4(7.3) (range 52-78) years were referred for the management of arterial lesions which occurred following therapeutic doses of external irradiation. Oropharyngeal, breast, prostate, cervical, vulvar, recta1 and bone neoplasms and peptic ulcer were treated. The mean(s.d.) interval between radiation therapy and clinical presentation with symptomatic arterial occlusive disease was 10.7(12.0) years. All patients received >5000 rads of external ortho- or super-voltage therapy through one or more portals. Accurate treatment protocols were available in 12 of the 26 patients. Patients whose treatment protocols were not available were generally 135
Arterial disease following radiation therapy: G. Andros et al.
those who received treatment more than 15 years before presentation and most of these patients had orthovoltage therapy. When the treatment protocols were not available, the patients and their families reported that they had received full ‘treatment doses’ because the course of therapy comprised 20-30 treatments, usually requiring 30-40 days. In many cases there was evidence of radiodermatitis and cutaneous tattooing of the radiation portals indicated that all lesions occurred within the radiated field. Pathologic vascular lesions consisted of arterial ulceration stenosis and/or occlusion.
Results Carotid artery lesions Nine patients presented with lesions involving the carotid arteries (Table 1). Six of the nine had squamous carcinoma of the oropharynx. Symptoms developed from 1 to 37 years after radiation therapy (mean 9.4(11.0) years). Six patients presented with transient
ischemic attack or stroke. Revascularization procedures included carotid endarterectomy and saphenous vein patch angioplasty (four cases), saphenous interposition graft (two), subclavian-to-external carotid artery saphenous vein bypass (one), subclavian-to-common carotid saphenous bypass and carotid endarterectomy (one), and a right-to-left carotid saphenous vein bypass graft (one). A contralateral carotid lesion was observed in only one case (patient no. 2) who was a heavy smoker treated for carcinoma of the larynx. Three additional vertebral artery stenoses were seen within the radiation portal and subjacent to the involved carotid artery. Lesions in which the carotid artery was significantly affected in atypical locations occurred in six patients (Figure 1). This included critical common carotid artery stenoses proximal to the bifurcation, and significant external carotid artery stenoses which were often isolated. In two of nine patients intraluminal thrombus was present (Figures 2 and 3). Radiation produced effects on the skin including atrophy and subcutaneous brawny induration and edema. In the case of carotid surgery in which the lesion was near the center of the
Table 1 Carotid artery lesions following radiation therapy
Sex Smoker
Type of primary tumor
Interval to symptoms b-an)
69
M
+
Lymphoma
13
73
M
+
Lww
37
3
75
F+
Epiglottis
6
4
60
Id+
Larynx
6
66
F+
Larynx
1
Patient no.
Age (years)
72
75
136
M
+
F+
Tongue
Pharynx
6
1
78
F
+
Breast
5
78
F
+
Breast
10
Angiographic findings Left internal carotid artery Occlusion Left common carotid artery severe stenosis Right internal carotid artery occlusion Left internal carotid artery severe stenosis Lel? common carotid artery aneurysm Left common carotid artery preocclusive stenosis Right internal carotid artery severe stenosis with free-floating thrombus Right external carotid artery Occlusion Left internal carotid artery severe stenosis with free-floating thrombus Left internal carotid artery severe stenosis
Treatment
Outcome (follow-up)
Left subclavian to external carotid artery saphenous graft
No further drop attacks (22 months)
Left common carotid artery to internal carotid artery saphenous interposition graft
Left hemispheric stroke (7 months)
Right proximal common carotid artery to left carotid saphenous graft Right carotid thromboendarterectomy vein pan
Relief of lightheadedness (21 months)
Comments
Radical neck dissection with musculocutaneous flap
No further right hemispheric transient ischemic attack (24 months)
Coronary artery bypass 10 years earlier
Full recovery from left hemispheric stroke (24 months)
Previous radical neck dissection with tracheostomy
No further left hemispheric transient ischemic attack (96 months) Remained symptom-free (24 months)
Previous radical neck dissection
Left carotid thromboendarterectomy patch
vein
Leff carotid thromboendarterectomy patch
vein
Right internal carotid artery severe stenosis
Right carotid thromboendarterectomy patch
with
Left common carotid artery severe stenosis in two locations severe bifurcation lesion Left carotid artery preocclusive stenosis
Left subclavian to carotid saphenous graft/let? carotid thrombcendarterectomy
Recurrent transient ischemic attacks (3 months)
Left common carotid artery to internal carotid artery saphenous interposition graff
No further left hemispheric transient ischemic attacks (3 months)
Aortobifemoral bypass 10 years earlier with re-do 6 months before carotid thromboendarterectomy
CARDIOVASCULAR SURGERY APRIL IQ96 VOL 4 NO 2
Arterialdhwe
followingradiation
ther%pyG. Andmetal.
Figure 1 A and B. Right common and internal carotid occlusion ar Id lefl : cal?otid bifurcation aneurysm (B, arrowed) and internal carotid stenosis 37 years after radiation therapy. Left vertebral occlusion (A. arrowed) and I& extel -nal carotid stenosis with post-stenotic dilatation (8. upper arrow) were also noted (patient no. 2)
radiation portal the dissection might resemble the tvpical arteriosclerotic patient; more often, however, the tissues were rigid and fibrotic. The endarterectomy cleavage plane was frequently difficult to establish and the wall of the postendarterectomy vessel appeared thickened and firm. The excised plaque also varied in consistency from firm to friable. In one patient treated with both a radical neck dissection and radiation, coverage of the vein-patched endarterectomized carotid could not be made safely without a myocutaneous flap. Carotid-carotid vein bypass was selected for patients with extensive carotid artery damage (stenosis/ aneurysm) that was deemed too long or fibrotic for endarterectomy. Saphenous vein patch angioplasty was performed routinely with carotid endarterectomy in post-radiation patients since the artery was less pliable than normal Prosthetic material was avoided becauseof concern about tissue healing with a foreign body in place in the radiation-injured area. There were no wound complications despite the fact that all incisions were within the radiation portal and no instances of secondary hemorrhage. Mean(s.d.) follow-up was 24.9(28.1) months. There were no perioperative deaths CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
or strokes. One patient (no. 8) developed recurrent transient ischemic attacks 3 months after subclaviancarotid bypass; neointimal hyperplasia at the distal anastomosis required revision. Another patient (no. 2) died 7 months after carotid interposition graft and myofascial flap, succumbing to a stroke appropriate to the grafted carotid; the status of the graft at the time of death was unknown. Subclavian-axillary
artery lesions
There were seven patients with symptomatic subclavian-axillary artery stenosis or occlusion (Table 2). All patients were women who had undergone mastectomy for breast cancer and subsequent radiation therapy from 1 to 16 years before the deveiopment of ischemic symptoms (mean 6.4(4.9)years). Clinical presentations included upper-extremity effort fatigue, discoloration and/or painful ulcerations of the fingertips. Five of the seven lesions were located on the left side. The arteriographic appearance of the lesions was either occlusion (five cases; Figure 4) or stenosis (two cases). Saphenous vein bypass grafts from either the carotid 137
Arterial disease following radiation therapy: C. Andros et al.
Figure 2 Moderate carotid bifurcation stenosis. The arrows indicate intraluminal clot adherent to an ulceration (patient no. 5)
Figure 3 Symptomatic, moderate internal carotid stenosis (lower arrow) and poorly visualized intraluminal thrombus and external carotid occlusion 6 years after treatment of laryngeal carcinoma. Note that the subjacent vertebral artery is grossly unaffected. A mid-common carotid lesion is also present (upper arrow) (patient no. 4)
(four) or the subclavian arteries (two) to the axillary or brachial arteries relieved ischemic symptoms in the six patients who underwent revascularization. Graft tunnels were orthotopic, under the clavicle and adjacent to the artery. All grafts were patent from 18 to 130 months postoperatively. Mean(s.d.) follow-up was 73.1(40.9) months. Two patients presented with arm edema associated with subclavian-axillary vein occlusion; both were documented by preoperative venography. Because there was longstanding edema they were ascribed either to previous radical mastectomy, radiation or both. There was no clinical evidence of nerve injury following radiation therapy. Lesions of the abdominal aorta and its branches
Symptomatic lesions involving the abdominal aorta and its branches were diagnosed in the ten patients between 5 months and 44 years after radiation therapy (mean 14.9(15.1) years; Table 3). Aortoiliac occlusive disease produced limb-threatening ischemia in five patients and claudication in four (Figures 5 and 6). There was one 138
Figure 4 no. 10)
Left axillary artery occlusion 1 year post-radiotherapy
(patient
CARDlOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
Arterial disease iMowing radiation therapy 6. Andfos et al.
significant renal artery stenosis (patient no. 20), and one case which presented with multiple occluded visceral branches in association with hypertension and short distance ciawdication (patient no. 21); both presented late following radiation therapy (17 and 25 years respectiveiy). Among the eight patients who underwent surgery for lower-extremity &hernia, aortobifemoral bypass (four), axillofemoral bypass (two), iliofemoral
Tabie 2
Subclavien and axillary artery lesions following radiation therapy TLpeof
Patient
bypass (one), iliopopliteal bypass (one) and femoral-topopliteal bypass (one) were performed. One patient (no. 17) underwent an iliofemoral bypass for gangrene and then presented 2 years later with contralateral disease which required iliofemoral bypass. Ureteral catheters were placed in patients undergoing abdominal vascular procedures and were found to be a useful adjunct to identify and protect the ureters during surgery within
lncervelto
IlO.
Age (years)
Sax Stir
Primary tumr
10
78
F
+
BPS&
1
Left axillary occlusion
I1
62
F
+
Breast
8
Left axillary severe stenosis
12
58
F
t
Breast
3
13
71
F
+
Breast
16
14
66
F
+
BWSt
4
15
72
F
-
Breast
9
16
60
F
+
Breast
5
Table 3
Treatment
Outcome (follow-up)
Comments
Left arm effort fat+aue
Left carotid thromboendarterectomy 12 .years earlier
outcome (foliow-up)
Comments
Left carotid to axillary vein graft Left subclavian to brachial vein Left axillary occlusion graft Right carotid to brachial vein Right axillaly severe stenosis graft Left subclavian to axillary vein Left axillary occlusion graft Left carotid to axillary vein Let? axillary occlusion graft Right subclavian occlusion Right carotid to axillary vein graft
Lesions of the abdominal aorta and branches following radiation therapy
Type of primary
Interval to symptoms Cveaf-9
Angicgraphic findings
Patient no.
Age (years)
Sex Smoker
17
71
M
-
Prostate
6
18
77
M
+
Bladder
10
19
52
M
+
Ewing’s sarcoma
35
20
56
M
+
Lymphoma
17
Left renal stenosis
21
59
M
+
Peptic ulcer disease
25
22
73
F
+
Celiac. superior mesenteric artery. bilateral renal and aortoiliac occlusive disease
Cerwx
44
23
71
F
+
Vulva
6
24
64
F
+
cervix
25
59
F
+
Cervix
26
70
F
+
Rectum
Urnor
Left external iliac artery severe stenosis Right external iliac artery normal Bilateral iliac artery severe stenosis Right superficial femoral artery occlusion
Treatment Left common iliac artery to common femoral artery Dacron bypass
Riihtcubernal iiiac artery severe stmcsis 2 years later requited iliofemoral bypass
Aortobifemoral bypass graft
Concomitant abdominal aotic aneurysmectomy
Right common femoral artq to above-knee popliteal saphenous graft Left renal bypass
Celiac. superior mesenteric artery. bilateral renal thromboendarCerectomy and aortobifemoral bypass Axillobifemoral bypass
Right iliac. common femoral artery, profunda. and superficial femoral artery occlusion Aortic occlusion
Left common iliac artery to right below-knee popliteal composite autogenous vein bypass Aortobifemoral bypass
3
Severe aortoiliac stenosis
Aortobifemoral
2
Severe aortoiliac stenosis
Medical
5 months
CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
bypass
Died foliowing rectal reman for necrotizing radition proctitis
Restpain relieved (71-I Severe cfaudicatkm resolved (I month) Moderate claudication (12 months)
139
Arterial disease following radiation therapy G. Andros et al.
the scarred retroperitoneum. One extra-anatomic bypass was required because of medical contraindications to aortic surgery. Saphenous vein was employed for all infrainguinal reconstructions. There were no operative deaths or amputations. Mean follow-up was 40.3(32.4) months. One patient died as a result of sepsis and renal failure following rectosigmoidectomy for necrotizing radiation proctitis 2 months after axillobifemoral bypass.
Figure 6 A and B. A 71 -year-old male irradiated for prostate carcinoma. The left external iliac lesions were bypassed from the common iliac artery to the common femoral artery. Note the absence of significant right external iliac disease. Right leg claudication developed 2 years later and a right external iliac artery stenosis was detected
Discussion
Figure 5 Left superficial femoral artery occlusion producing progressive rest pain 35 years after femur irradiation for Ewing’s sarcoma. Note the bone cyst in the distal femur (patient no. 19)
140
Arterial occlusive disease which occurs following radiation therapy presents with a broad spectrum of clinical manifestations. The arterial lesions observed within an irradiated field may resemble those seen in non-irradiated arteriosclerotic arteries or they may be atypical in location and/or appearance. Diverse examples have been reported involving the aortic arch, coronary arteries, vertebral and carotid arteries, subclavian and axillary arteries, visceral vessels, abdominal
CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
Arterial distlasefollowing radiation therapy: G.Ar?droset al. aorta, iliac and femoral arteries4-i3. The precise relationship between radiation therapy and subsequent arterial lesions remains a focus of investigation. Radiation therapy may be causative as a single factor, it may be contributory in synergy with an arteriosclerotic diathesis, or there could be a non-causal association. The patients in the present series exemplify all three relationships between radiation therapy and the subsequent arterial lesions. Coincidental factors in post-irradiation patients may contribute to the development of arterial lesions. Among the patients in the present series, all but two were habitual smokers. However, Silverberg and his colleagues14 were unable to detect any predisposition to radiation arteritis due to elevated serum cholesterol hyperlipidemia or other arteriosclerotic risk factors in their cases, even those patients with a short interval between radiation and carotid disease. The incidence of arterial lesions after radiation therapy was investigated by Elerding et a1.15 who detected an increased risk of carotid-related stroke in a retrospective study of 910 patients surviving at least 5 years after cervical irradiation for Hodgkin’s disease. In a prospective study of 118 patients, a high incidence of carotid lesions was detected. It was concluded that these carotid lesions were most likely the consequence of prior irradiation. Such findings are consistent with those of Moritz et al.‘” who found that 38% of patients receiving therapeutic doses of external radiation for head and neck cancer had significant carotid artery lesions uersus 6% of a control group. Some 10% of the irradiated patients had symptomatic lesions when the group was studied 28 months after high-dose radiation. The anatomic location, angiographic morphology, clinical characteristics and timing of occurrence for radiation-induced arterial lesions may also differ from that usually seen in non-irradiated arteriosclerotic vessels; this is readily apparent in the extracranial cerebrovasculature’7-‘9. Lesions have been observed to occur in the common carotid artery, either unilaterally or bilaterally, while sparing the carotid bifurcation. Angiographic manifestations include aneurysmal dilatation, deep ulceration and concomitant stenosis following cervical irradiation; carotid and vertebral arteries may both be affected. Propagating intraluminal thrombus arising on a necrotic, ulcerated carotid bifurcation accounted for strokes in two of the present patients. Isolated external carotid artery stenosis without significant bifurcation involvement may suggest a radiationassociated etiology. The subclavian-axillary artery lesions consisted of either occlusion of the mid to distal subclavian artery or ulcerated stenosis at the junction of the subclavian and axillary arteries. The severe hemodynamic effects of these lesions result from a paucity of collateral development which may be attributable to radiation effects within the treated portal. The trend towards earlier appearance of axillary-subclavian lesions (6.4
CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
years) as compared with the later manifestation of carotid (9.4 years) or aortofemoral disease (14.9 years) cannot be accounted for. Lesions of the axillary and subclavian arteries will assume greater importance as partial mastectomy and radiotherapy become the preferred therapeutic strategies for many breast cancers9’10,20*21. The patients in the present series all had breast cancer and were treated with radiation before the development of upperextremity ischemia. Surveillance of these patients for arterial lesions using non-invasive tests has been suggested16. Unusual sites of occurrence also characterize aortofemoral lesions, further implicating radiation as a causative factor. Exemplifying this relationship is atherosclerotic disease in the mid-aortic segment involving visceral vessels in the absence of other significant lesions. This pattern of occlusive disease occurred 25 years following external irradiation of the stomach for peptic ulcer disease in patient no. 2122. Likewise, sternosis or occlusion of the external iliac arteries without aortic, common iliac or femoral artery occlusive disease, particularly in the absence of risk factors suggests radiation. Stenosis or occlusion of long segments of the deep femoral artery are unusual in the absence of diabetes mellitus but this diseasegattern may also be attributable to external irradiation . Although arteriosclerotic superficial femoral drtery occlusive disease is quite common, the occlusion of this vessel in proximity to a post-irradiation bone cyst in an otherwise healthy male without any other evidence of arteriosclerotic occlusive disease, or risk factors, suggests radiation-induced arteritis. The authors’ experience indicates that anatomic tunnels for bypass grafts are usually feasible, in contrast to the frequently recommended cboicc of extraanatomic tunnels 13,L3. The preoperative insertion of ureteral catheters is a protective aid when making retroureteric tunnels in patients undergoing aortoiliofemoral bypass procedures. Tunnels should be fashioned under direct vision because periarterial fibrosis can make tissue planes difficult to dissect bluntly. However, if infection, false aneurysm formation or medical contraindications complicate the clinical course, extra-anatomic bypass may be obligatory. The surgeon should also be prepared to construer immediate or delayed myofascial-cutaneous flaps or pedicle grafts to cover the operated field, particularly after neck irradiation and radical neck dissection, The lesions of the aortofemoral segment were the latest ro occur following radiation (mean 14.9( 15.1) y-ears). Nevertheless the patient (no. 24) with the shortest time interval between therapy and the onset of symptoms of ischemia had a complete aortic occlusion. Because she was previously symptom-free and the onset of her complaints was sudden, it is postulated that the acute radiation effects including endotheliolysis and damage to the internal elastic membrane, superimposed upon
141
Arterial disease following radiation therapy G Andros et al
and pre-existing aortoiliac arteriosclerosis, resulted in an acute thrombotic occlusion. The relative lack of obvious advanced arteriosclerotic disease as discerned at the time of operation is compatible with this formulation. The authors’ experience suggests that occlusive lesions associated with radiation therapy can be managed in much the same way that atherosclerotic occlusive disease is treated in other patients. Aggressive surgical revascularization can be recommended and performed with good results.
References
10. 11. 12.
13. 14. 15. 16.
1. Colquhoun
J. Hypoplasia of the abdominal aorta following therapeutic irradiation in infancy. Radiology 1966; 86: 454-6. 2. Rotman M, Seidenberg B, Rubin I, Botstein C, Bosniak M. Aortic arch syndrome secondary to irradiation in childhood. Arch Intern Med 1969; 124: 87-90. 3. Lee DA, Sapire D, Markowitz R, Gruskin A. Radiation injury to abdominal aorta and iliac artery sustained in infancy. S Afr Med ] 1976; 50: 658-60. 4. Annest LS, Anderson RP, Wei-i L, Hafermann MD. Coronarv artery disease following mediastinal radiation therapy. I Thora; Cardiovasc Sum 1983: 85: 257-63. 5. Tenet W, Missh J, Hager D. Radiation-induced stenosis of the left main coronary artery. Cathet Cardiovasc Diagn 1986; 12: 169-71. 6. Levinson SA, Close MB, Ehrenfeld WK, Stoney RJ. Carotid artery occlusive disease following external cervical irradiation. Arch Surg 1973; 107: 395-7. Conomy JP, Kellermeyer RW. Delayed cerebrovascular consequences of therapeutic radiation. Cancer 1975; 36: 1702-8. Brant-Zawadzki M, Anderson M, DeArmond SJ, Conley FK, lahnke RW. Radiation-induced lame intracranial vessel occlusive vasculopathy. Am 1 Radio1 198uO; 134: 51-S. Kretschmer G, Niederle B, Polteraurer P, Waneck R. Irradiationinduced changes in the subclavian and axillary arteries after radiotherapy for carcinoma of the breast. Surgery 1986; 99: 658-63.
142
17. 18. 19. 20. 21. 22. 23.
Hashmonai M, Elami A, Kuten A, Lichtig C, Torem S. Subclavian artery occlusion after radiotherapy for carcinoma of the breast. Cancer 1988; 61: 2015-18. Savlov ED, Nahhas WA, May AG. Iliac and femoral arteriosclerosis following pelvic irradiation for carcinoma of the ovary: report of a case. Obstet Gynecol 1969; 34: 345-51. Poulias GE, Giannopoulous GD, Frangagis E. Selective constriction of the profunda femoris as a post-radiotherapy sequel: report of a case. Radiology 1967; 89: 127-8. McCready RA, Hyde GL, Bivins BA, Mattingly SS, Griffen WO. Radiation-induced arterial injuries. Surgery 1983; 93: 306-12. Silverberg GD, Britt RH, Goffinet DR. Radiation-induced carotid artery disease. Cancer 1978; 41: 130-7. Elerding SC, Fernandez RN, Grotta JC, Lindberg RD, Causay LC, McMurtrey MJ. Carotid artery disease following external cervical irradiation. Ann Surg 1981; 194: 609-M. Moritz MW, Higgins RF, Jacobs JR. Duplex imaging and incidence of carotid radiation injury after high-dose radiotherapy for tumors of the head and neck. Arch Surg 1990; 125: 1181-3. Jones TR, Frusha ID. Carotid revascularization after cervical irradiation. South &fed] 1986; 79: 1517-20. Loftus CM. Biller 1. Hart MN. Cornell SH. Hiratzka LF. Management of radiation-induced accelerated carotid atherosclerosis. Arch Neurol 1987; 44: 711-14. Lopez M, El-Bayar H, Hye RJ, Freischlag J. Carotid artery disease in patients with head and neck carcinoma. Am Surg 1990; 56: 778-81. Budin JA, Casarella WJ, Harisiadis L. Subclavian artery occlusion following radiotherapy for carcinoma of the breast. Radiology 1976; 118: 169-73. Harris JR, Hellman S, Kinne DW. Special report. Limited surgery and radiotherapy for early breast cancer. ?V Engl J Med 1985; 21: 1365-8. Palmer WL. Radiation therapy of peptic ulcer. In: Bockus HL. ed. Gastroenterology, vol. 1,3rd ed. Philadephia, WB Saunders, 1974: 710-19. Berqvist D, Jonsson K. Milsson M, Takolander R. Treatment of arterial lesions after radiation therapy. Surg Gynecol Obstet 1987; 165: 116-20.
Paper accepted 22 February 1995
CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
Clinicatly significant arterial occlusive disease developed in 26 patients at between 5 months and 44 years (mean(s.d.) 10.7(12.0) years) following radiation therapy. Therapeulzic radiation was associated with lesions of the carotid artery (nine pal&~&~), subclavianartefies (seven) and the abdominal aorta and its branches (IO). Clinical presentations inclu&!d tr@miieti ischemic attack, stroke, vettebrobasilar insufficiency, carotid bruit, upper- o ischemia and renovascular hypertension. Surgery for cerebrovasculaf insu carotid endarterectomy with vein patch, interposition grafting or sub&Man-to-carotid bypass. Carotid or subclavian-to-axillary bypass was performed for upper-extremRy ischemla. A combination of endarterectomy and Dacron or saphenous vein graflzs was used for lnfrarenal reconstruction. Tunnels were placed orthotopically. Musculocutanews flaps assisted In heating selected wounds. Ureteral catheters were useful adjuncts in abdominal vascular reconstructions. There were no operative deaths. strokes or amputations. One patient had recu,Went transient ischemic attack following subclavian-to-carotid bypass. The mean(s.d.) e follow-up was 48.1(39.6) months. Patients presenting with end-organ ischemia foHowing radiation therapy can be managed successfully with aggressive surgical revasculariza~ion using a broad spectrum of reconstructive techniques. Keywords: radiation arteritis, arterial occlusion, radiotherapy
As the application of radiation therapy has expanded, ensuing complications have become recognized with increasing frequency. Although arteriosclerosis and radiation therapy are widely prevalent in technologically advanced countries, vascular injury due to radiation may be overlooked because it presents insidiously and gradually develops into a chronic ischemic syndrome. The recognized effects of radiation on normal and abnormal arteries should be included among risk factors for the development of atherosclerotic occlusive diseaselW3. The goal of the present study was to evaluate the diagnostic and management techniques used by the authors in patients with clinically significant vascular lesions associated with previous radiation therapy.
Correspondence to: Dr G. Andros, Vascular Laboratory, Saint Joseph Medical Center, 501 South Buena Vista Ave., Burbank, CA 91505-4866. USA
CARDIOVAWJLAR SURGERY APRlL 1996 VOL 4 NO 2
-._ --._.---
From the analysis of a large group of patients that developed diverse manifestations of radiation vasculopathy a series of management strategies has been devised.
Patients and methods Between January 1976 and December 1992,26 patients (eight men and 18 women) of mean(s.d.) age 67.4(7.3) (range 52-78) years were referred for the management of arterial lesions which occurred following therapeutic doses of external irradiation. Oropharyngeal, breast, prostate, cervical, vulvar, recta1 and bone neoplasms and peptic ulcer were treated. The mean(s.d.) interval between radiation therapy and clinical presentation with symptomatic arterial occlusive disease was 10.7(12.0) years. All patients received >5000 rads of external ortho- or super-voltage therapy through one or more portals. Accurate treatment protocols were available in 12 of the 26 patients. Patients whose treatment protocols were not available were generally 135
Arterial disease following radiation therapy: G. Andros et al.
those who received treatment more than 15 years before presentation and most of these patients had orthovoltage therapy. When the treatment protocols were not available, the patients and their families reported that they had received full ‘treatment doses’ because the course of therapy comprised 20-30 treatments, usually requiring 30-40 days. In many cases there was evidence of radiodermatitis and cutaneous tattooing of the radiation portals indicated that all lesions occurred within the radiated field. Pathologic vascular lesions consisted of arterial ulceration stenosis and/or occlusion.
Results Carotid artery lesions Nine patients presented with lesions involving the carotid arteries (Table 1). Six of the nine had squamous carcinoma of the oropharynx. Symptoms developed from 1 to 37 years after radiation therapy (mean 9.4(11.0) years). Six patients presented with transient
ischemic attack or stroke. Revascularization procedures included carotid endarterectomy and saphenous vein patch angioplasty (four cases), saphenous interposition graft (two), subclavian-to-external carotid artery saphenous vein bypass (one), subclavian-to-common carotid saphenous bypass and carotid endarterectomy (one), and a right-to-left carotid saphenous vein bypass graft (one). A contralateral carotid lesion was observed in only one case (patient no. 2) who was a heavy smoker treated for carcinoma of the larynx. Three additional vertebral artery stenoses were seen within the radiation portal and subjacent to the involved carotid artery. Lesions in which the carotid artery was significantly affected in atypical locations occurred in six patients (Figure 1). This included critical common carotid artery stenoses proximal to the bifurcation, and significant external carotid artery stenoses which were often isolated. In two of nine patients intraluminal thrombus was present (Figures 2 and 3). Radiation produced effects on the skin including atrophy and subcutaneous brawny induration and edema. In the case of carotid surgery in which the lesion was near the center of the
Table 1 Carotid artery lesions following radiation therapy
Sex Smoker
Type of primary tumor
Interval to symptoms b-an)
69
M
+
Lymphoma
13
73
M
+
Lww
37
3
75
F+
Epiglottis
6
4
60
Id+
Larynx
6
66
F+
Larynx
1
Patient no.
Age (years)
72
75
136
M
+
F+
Tongue
Pharynx
6
1
78
F
+
Breast
5
78
F
+
Breast
10
Angiographic findings Left internal carotid artery Occlusion Left common carotid artery severe stenosis Right internal carotid artery occlusion Left internal carotid artery severe stenosis Lel? common carotid artery aneurysm Left common carotid artery preocclusive stenosis Right internal carotid artery severe stenosis with free-floating thrombus Right external carotid artery Occlusion Left internal carotid artery severe stenosis with free-floating thrombus Left internal carotid artery severe stenosis
Treatment
Outcome (follow-up)
Left subclavian to external carotid artery saphenous graft
No further drop attacks (22 months)
Left common carotid artery to internal carotid artery saphenous interposition graft
Left hemispheric stroke (7 months)
Right proximal common carotid artery to left carotid saphenous graft Right carotid thromboendarterectomy vein pan
Relief of lightheadedness (21 months)
Comments
Radical neck dissection with musculocutaneous flap
No further right hemispheric transient ischemic attack (24 months)
Coronary artery bypass 10 years earlier
Full recovery from left hemispheric stroke (24 months)
Previous radical neck dissection with tracheostomy
No further left hemispheric transient ischemic attack (96 months) Remained symptom-free (24 months)
Previous radical neck dissection
Left carotid thromboendarterectomy patch
vein
Leff carotid thromboendarterectomy patch
vein
Right internal carotid artery severe stenosis
Right carotid thromboendarterectomy patch
with
Left common carotid artery severe stenosis in two locations severe bifurcation lesion Left carotid artery preocclusive stenosis
Left subclavian to carotid saphenous graft/let? carotid thrombcendarterectomy
Recurrent transient ischemic attacks (3 months)
Left common carotid artery to internal carotid artery saphenous interposition graff
No further left hemispheric transient ischemic attacks (3 months)
Aortobifemoral bypass 10 years earlier with re-do 6 months before carotid thromboendarterectomy
CARDIOVASCULAR SURGERY APRIL IQ96 VOL 4 NO 2
Arterialdhwe
followingradiation
ther%pyG. Andmetal.
Figure 1 A and B. Right common and internal carotid occlusion ar Id lefl : cal?otid bifurcation aneurysm (B, arrowed) and internal carotid stenosis 37 years after radiation therapy. Left vertebral occlusion (A. arrowed) and I& extel -nal carotid stenosis with post-stenotic dilatation (8. upper arrow) were also noted (patient no. 2)
radiation portal the dissection might resemble the tvpical arteriosclerotic patient; more often, however, the tissues were rigid and fibrotic. The endarterectomy cleavage plane was frequently difficult to establish and the wall of the postendarterectomy vessel appeared thickened and firm. The excised plaque also varied in consistency from firm to friable. In one patient treated with both a radical neck dissection and radiation, coverage of the vein-patched endarterectomized carotid could not be made safely without a myocutaneous flap. Carotid-carotid vein bypass was selected for patients with extensive carotid artery damage (stenosis/ aneurysm) that was deemed too long or fibrotic for endarterectomy. Saphenous vein patch angioplasty was performed routinely with carotid endarterectomy in post-radiation patients since the artery was less pliable than normal Prosthetic material was avoided becauseof concern about tissue healing with a foreign body in place in the radiation-injured area. There were no wound complications despite the fact that all incisions were within the radiation portal and no instances of secondary hemorrhage. Mean(s.d.) follow-up was 24.9(28.1) months. There were no perioperative deaths CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
or strokes. One patient (no. 8) developed recurrent transient ischemic attacks 3 months after subclaviancarotid bypass; neointimal hyperplasia at the distal anastomosis required revision. Another patient (no. 2) died 7 months after carotid interposition graft and myofascial flap, succumbing to a stroke appropriate to the grafted carotid; the status of the graft at the time of death was unknown. Subclavian-axillary
artery lesions
There were seven patients with symptomatic subclavian-axillary artery stenosis or occlusion (Table 2). All patients were women who had undergone mastectomy for breast cancer and subsequent radiation therapy from 1 to 16 years before the deveiopment of ischemic symptoms (mean 6.4(4.9)years). Clinical presentations included upper-extremity effort fatigue, discoloration and/or painful ulcerations of the fingertips. Five of the seven lesions were located on the left side. The arteriographic appearance of the lesions was either occlusion (five cases; Figure 4) or stenosis (two cases). Saphenous vein bypass grafts from either the carotid 137
Arterial disease following radiation therapy: C. Andros et al.
Figure 2 Moderate carotid bifurcation stenosis. The arrows indicate intraluminal clot adherent to an ulceration (patient no. 5)
Figure 3 Symptomatic, moderate internal carotid stenosis (lower arrow) and poorly visualized intraluminal thrombus and external carotid occlusion 6 years after treatment of laryngeal carcinoma. Note that the subjacent vertebral artery is grossly unaffected. A mid-common carotid lesion is also present (upper arrow) (patient no. 4)
(four) or the subclavian arteries (two) to the axillary or brachial arteries relieved ischemic symptoms in the six patients who underwent revascularization. Graft tunnels were orthotopic, under the clavicle and adjacent to the artery. All grafts were patent from 18 to 130 months postoperatively. Mean(s.d.) follow-up was 73.1(40.9) months. Two patients presented with arm edema associated with subclavian-axillary vein occlusion; both were documented by preoperative venography. Because there was longstanding edema they were ascribed either to previous radical mastectomy, radiation or both. There was no clinical evidence of nerve injury following radiation therapy. Lesions of the abdominal aorta and its branches
Symptomatic lesions involving the abdominal aorta and its branches were diagnosed in the ten patients between 5 months and 44 years after radiation therapy (mean 14.9(15.1) years; Table 3). Aortoiliac occlusive disease produced limb-threatening ischemia in five patients and claudication in four (Figures 5 and 6). There was one 138
Figure 4 no. 10)
Left axillary artery occlusion 1 year post-radiotherapy
(patient
CARDlOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
Arterial disease iMowing radiation therapy 6. Andfos et al.
significant renal artery stenosis (patient no. 20), and one case which presented with multiple occluded visceral branches in association with hypertension and short distance ciawdication (patient no. 21); both presented late following radiation therapy (17 and 25 years respectiveiy). Among the eight patients who underwent surgery for lower-extremity &hernia, aortobifemoral bypass (four), axillofemoral bypass (two), iliofemoral
Tabie 2
Subclavien and axillary artery lesions following radiation therapy TLpeof
Patient
bypass (one), iliopopliteal bypass (one) and femoral-topopliteal bypass (one) were performed. One patient (no. 17) underwent an iliofemoral bypass for gangrene and then presented 2 years later with contralateral disease which required iliofemoral bypass. Ureteral catheters were placed in patients undergoing abdominal vascular procedures and were found to be a useful adjunct to identify and protect the ureters during surgery within
lncervelto
IlO.
Age (years)
Sax Stir
Primary tumr
10
78
F
+
BPS&
1
Left axillary occlusion
I1
62
F
+
Breast
8
Left axillary severe stenosis
12
58
F
t
Breast
3
13
71
F
+
Breast
16
14
66
F
+
BWSt
4
15
72
F
-
Breast
9
16
60
F
+
Breast
5
Table 3
Treatment
Outcome (follow-up)
Comments
Left arm effort fat+aue
Left carotid thromboendarterectomy 12 .years earlier
outcome (foliow-up)
Comments
Left carotid to axillary vein graft Left subclavian to brachial vein Left axillary occlusion graft Right carotid to brachial vein Right axillaly severe stenosis graft Left subclavian to axillary vein Left axillary occlusion graft Left carotid to axillary vein Let? axillary occlusion graft Right subclavian occlusion Right carotid to axillary vein graft
Lesions of the abdominal aorta and branches following radiation therapy
Type of primary
Interval to symptoms Cveaf-9
Angicgraphic findings
Patient no.
Age (years)
Sex Smoker
17
71
M
-
Prostate
6
18
77
M
+
Bladder
10
19
52
M
+
Ewing’s sarcoma
35
20
56
M
+
Lymphoma
17
Left renal stenosis
21
59
M
+
Peptic ulcer disease
25
22
73
F
+
Celiac. superior mesenteric artery. bilateral renal and aortoiliac occlusive disease
Cerwx
44
23
71
F
+
Vulva
6
24
64
F
+
cervix
25
59
F
+
Cervix
26
70
F
+
Rectum
Urnor
Left external iliac artery severe stenosis Right external iliac artery normal Bilateral iliac artery severe stenosis Right superficial femoral artery occlusion
Treatment Left common iliac artery to common femoral artery Dacron bypass
Riihtcubernal iiiac artery severe stmcsis 2 years later requited iliofemoral bypass
Aortobifemoral bypass graft
Concomitant abdominal aotic aneurysmectomy
Right common femoral artq to above-knee popliteal saphenous graft Left renal bypass
Celiac. superior mesenteric artery. bilateral renal thromboendarCerectomy and aortobifemoral bypass Axillobifemoral bypass
Right iliac. common femoral artery, profunda. and superficial femoral artery occlusion Aortic occlusion
Left common iliac artery to right below-knee popliteal composite autogenous vein bypass Aortobifemoral bypass
3
Severe aortoiliac stenosis
Aortobifemoral
2
Severe aortoiliac stenosis
Medical
5 months
CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
bypass
Died foliowing rectal reman for necrotizing radition proctitis
Restpain relieved (71-I Severe cfaudicatkm resolved (I month) Moderate claudication (12 months)
139
Arterial disease following radiation therapy G. Andros et al.
the scarred retroperitoneum. One extra-anatomic bypass was required because of medical contraindications to aortic surgery. Saphenous vein was employed for all infrainguinal reconstructions. There were no operative deaths or amputations. Mean follow-up was 40.3(32.4) months. One patient died as a result of sepsis and renal failure following rectosigmoidectomy for necrotizing radiation proctitis 2 months after axillobifemoral bypass.
Figure 6 A and B. A 71 -year-old male irradiated for prostate carcinoma. The left external iliac lesions were bypassed from the common iliac artery to the common femoral artery. Note the absence of significant right external iliac disease. Right leg claudication developed 2 years later and a right external iliac artery stenosis was detected
Discussion
Figure 5 Left superficial femoral artery occlusion producing progressive rest pain 35 years after femur irradiation for Ewing’s sarcoma. Note the bone cyst in the distal femur (patient no. 19)
140
Arterial occlusive disease which occurs following radiation therapy presents with a broad spectrum of clinical manifestations. The arterial lesions observed within an irradiated field may resemble those seen in non-irradiated arteriosclerotic arteries or they may be atypical in location and/or appearance. Diverse examples have been reported involving the aortic arch, coronary arteries, vertebral and carotid arteries, subclavian and axillary arteries, visceral vessels, abdominal
CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
Arterial distlasefollowing radiation therapy: G.Ar?droset al. aorta, iliac and femoral arteries4-i3. The precise relationship between radiation therapy and subsequent arterial lesions remains a focus of investigation. Radiation therapy may be causative as a single factor, it may be contributory in synergy with an arteriosclerotic diathesis, or there could be a non-causal association. The patients in the present series exemplify all three relationships between radiation therapy and the subsequent arterial lesions. Coincidental factors in post-irradiation patients may contribute to the development of arterial lesions. Among the patients in the present series, all but two were habitual smokers. However, Silverberg and his colleagues14 were unable to detect any predisposition to radiation arteritis due to elevated serum cholesterol hyperlipidemia or other arteriosclerotic risk factors in their cases, even those patients with a short interval between radiation and carotid disease. The incidence of arterial lesions after radiation therapy was investigated by Elerding et a1.15 who detected an increased risk of carotid-related stroke in a retrospective study of 910 patients surviving at least 5 years after cervical irradiation for Hodgkin’s disease. In a prospective study of 118 patients, a high incidence of carotid lesions was detected. It was concluded that these carotid lesions were most likely the consequence of prior irradiation. Such findings are consistent with those of Moritz et al.‘” who found that 38% of patients receiving therapeutic doses of external radiation for head and neck cancer had significant carotid artery lesions uersus 6% of a control group. Some 10% of the irradiated patients had symptomatic lesions when the group was studied 28 months after high-dose radiation. The anatomic location, angiographic morphology, clinical characteristics and timing of occurrence for radiation-induced arterial lesions may also differ from that usually seen in non-irradiated arteriosclerotic vessels; this is readily apparent in the extracranial cerebrovasculature’7-‘9. Lesions have been observed to occur in the common carotid artery, either unilaterally or bilaterally, while sparing the carotid bifurcation. Angiographic manifestations include aneurysmal dilatation, deep ulceration and concomitant stenosis following cervical irradiation; carotid and vertebral arteries may both be affected. Propagating intraluminal thrombus arising on a necrotic, ulcerated carotid bifurcation accounted for strokes in two of the present patients. Isolated external carotid artery stenosis without significant bifurcation involvement may suggest a radiationassociated etiology. The subclavian-axillary artery lesions consisted of either occlusion of the mid to distal subclavian artery or ulcerated stenosis at the junction of the subclavian and axillary arteries. The severe hemodynamic effects of these lesions result from a paucity of collateral development which may be attributable to radiation effects within the treated portal. The trend towards earlier appearance of axillary-subclavian lesions (6.4
CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2
years) as compared with the later manifestation of carotid (9.4 years) or aortofemoral disease (14.9 years) cannot be accounted for. Lesions of the axillary and subclavian arteries will assume greater importance as partial mastectomy and radiotherapy become the preferred therapeutic strategies for many breast cancers9’10,20*21. The patients in the present series all had breast cancer and were treated with radiation before the development of upperextremity ischemia. Surveillance of these patients for arterial lesions using non-invasive tests has been suggested16. Unusual sites of occurrence also characterize aortofemoral lesions, further implicating radiation as a causative factor. Exemplifying this relationship is atherosclerotic disease in the mid-aortic segment involving visceral vessels in the absence of other significant lesions. This pattern of occlusive disease occurred 25 years following external irradiation of the stomach for peptic ulcer disease in patient no. 2122. Likewise, sternosis or occlusion of the external iliac arteries without aortic, common iliac or femoral artery occlusive disease, particularly in the absence of risk factors suggests radiation. Stenosis or occlusion of long segments of the deep femoral artery are unusual in the absence of diabetes mellitus but this diseasegattern may also be attributable to external irradiation . Although arteriosclerotic superficial femoral drtery occlusive disease is quite common, the occlusion of this vessel in proximity to a post-irradiation bone cyst in an otherwise healthy male without any other evidence of arteriosclerotic occlusive disease, or risk factors, suggests radiation-induced arteritis. The authors’ experience indicates that anatomic tunnels for bypass grafts are usually feasible, in contrast to the frequently recommended cboicc of extraanatomic tunnels 13,L3. The preoperative insertion of ureteral catheters is a protective aid when making retroureteric tunnels in patients undergoing aortoiliofemoral bypass procedures. Tunnels should be fashioned under direct vision because periarterial fibrosis can make tissue planes difficult to dissect bluntly. However, if infection, false aneurysm formation or medical contraindications complicate the clinical course, extra-anatomic bypass may be obligatory. The surgeon should also be prepared to construer immediate or delayed myofascial-cutaneous flaps or pedicle grafts to cover the operated field, particularly after neck irradiation and radical neck dissection, The lesions of the aortofemoral segment were the latest ro occur following radiation (mean 14.9( 15.1) y-ears). Nevertheless the patient (no. 24) with the shortest time interval between therapy and the onset of symptoms of ischemia had a complete aortic occlusion. Because she was previously symptom-free and the onset of her complaints was sudden, it is postulated that the acute radiation effects including endotheliolysis and damage to the internal elastic membrane, superimposed upon
141
Arterial disease following radiation therapy G Andros et al
and pre-existing aortoiliac arteriosclerosis, resulted in an acute thrombotic occlusion. The relative lack of obvious advanced arteriosclerotic disease as discerned at the time of operation is compatible with this formulation. The authors’ experience suggests that occlusive lesions associated with radiation therapy can be managed in much the same way that atherosclerotic occlusive disease is treated in other patients. Aggressive surgical revascularization can be recommended and performed with good results.
References
10. 11. 12.
13. 14. 15. 16.
1. Colquhoun
J. Hypoplasia of the abdominal aorta following therapeutic irradiation in infancy. Radiology 1966; 86: 454-6. 2. Rotman M, Seidenberg B, Rubin I, Botstein C, Bosniak M. Aortic arch syndrome secondary to irradiation in childhood. Arch Intern Med 1969; 124: 87-90. 3. Lee DA, Sapire D, Markowitz R, Gruskin A. Radiation injury to abdominal aorta and iliac artery sustained in infancy. S Afr Med ] 1976; 50: 658-60. 4. Annest LS, Anderson RP, Wei-i L, Hafermann MD. Coronarv artery disease following mediastinal radiation therapy. I Thora; Cardiovasc Sum 1983: 85: 257-63. 5. Tenet W, Missh J, Hager D. Radiation-induced stenosis of the left main coronary artery. Cathet Cardiovasc Diagn 1986; 12: 169-71. 6. Levinson SA, Close MB, Ehrenfeld WK, Stoney RJ. Carotid artery occlusive disease following external cervical irradiation. Arch Surg 1973; 107: 395-7. Conomy JP, Kellermeyer RW. Delayed cerebrovascular consequences of therapeutic radiation. Cancer 1975; 36: 1702-8. Brant-Zawadzki M, Anderson M, DeArmond SJ, Conley FK, lahnke RW. Radiation-induced lame intracranial vessel occlusive vasculopathy. Am 1 Radio1 198uO; 134: 51-S. Kretschmer G, Niederle B, Polteraurer P, Waneck R. Irradiationinduced changes in the subclavian and axillary arteries after radiotherapy for carcinoma of the breast. Surgery 1986; 99: 658-63.
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17. 18. 19. 20. 21. 22. 23.
Hashmonai M, Elami A, Kuten A, Lichtig C, Torem S. Subclavian artery occlusion after radiotherapy for carcinoma of the breast. Cancer 1988; 61: 2015-18. Savlov ED, Nahhas WA, May AG. Iliac and femoral arteriosclerosis following pelvic irradiation for carcinoma of the ovary: report of a case. Obstet Gynecol 1969; 34: 345-51. Poulias GE, Giannopoulous GD, Frangagis E. Selective constriction of the profunda femoris as a post-radiotherapy sequel: report of a case. Radiology 1967; 89: 127-8. McCready RA, Hyde GL, Bivins BA, Mattingly SS, Griffen WO. Radiation-induced arterial injuries. Surgery 1983; 93: 306-12. Silverberg GD, Britt RH, Goffinet DR. Radiation-induced carotid artery disease. Cancer 1978; 41: 130-7. Elerding SC, Fernandez RN, Grotta JC, Lindberg RD, Causay LC, McMurtrey MJ. Carotid artery disease following external cervical irradiation. Ann Surg 1981; 194: 609-M. Moritz MW, Higgins RF, Jacobs JR. Duplex imaging and incidence of carotid radiation injury after high-dose radiotherapy for tumors of the head and neck. Arch Surg 1990; 125: 1181-3. Jones TR, Frusha ID. Carotid revascularization after cervical irradiation. South &fed] 1986; 79: 1517-20. Loftus CM. Biller 1. Hart MN. Cornell SH. Hiratzka LF. Management of radiation-induced accelerated carotid atherosclerosis. Arch Neurol 1987; 44: 711-14. Lopez M, El-Bayar H, Hye RJ, Freischlag J. Carotid artery disease in patients with head and neck carcinoma. Am Surg 1990; 56: 778-81. Budin JA, Casarella WJ, Harisiadis L. Subclavian artery occlusion following radiotherapy for carcinoma of the breast. Radiology 1976; 118: 169-73. Harris JR, Hellman S, Kinne DW. Special report. Limited surgery and radiotherapy for early breast cancer. ?V Engl J Med 1985; 21: 1365-8. Palmer WL. Radiation therapy of peptic ulcer. In: Bockus HL. ed. Gastroenterology, vol. 1,3rd ed. Philadephia, WB Saunders, 1974: 710-19. Berqvist D, Jonsson K. Milsson M, Takolander R. Treatment of arterial lesions after radiation therapy. Surg Gynecol Obstet 1987; 165: 116-20.
Paper accepted 22 February 1995
CARDIOVASCULAR SURGERY APRIL 1996 VOL 4 NO 2