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Acute peripheral arterial occlusion associated with surgery for gynecologic cancer
GYNECOLOGIC
ONCOLOGY
25, 108-114 (1986)
Acute Peripheral Arterial Occlusion Associated with Surgery for Gynecologic Cancer PHILIP
A. TOWNSEND, M.D.,* DUANE G. HUTSON, M.D.,? JOHN LOVECCHIO, M.D.,* AND HERVY E. AVERETTE, M.D.§
*Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of South Florida, College of Medicine, Box 18, 12901 North 30th Street, Tampa, Florida 33612; fDepartment of Surgery, University of Miami, P.O. Box 016310, Miami, Florida 33101; $North Shore University Hospital, Manhasset, New York 11030; and #Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Miami, P.O. Box 016960, Miami, Florida 33101
Received May 23, 1985 Four cases are described of acute peripheral arterial occlusion associated with surgery for gynecologic cancer during the 5 years 1979to 1983at the University of Miami, Jackson Memorial Hospital Center. No such cases were recorded during the preceding 5 years. The probable underlying etiologic factors are discussed and recommendations made regarding the evaluation and management of such patients. 0 1986 Academic Press, Inc.
CASE 1
A 71-year-old woman underwent exploratory laparotomy in August 1982 for Stage IB, Grade 2, adenocarcinoma of the endometrium. The procedure included selective paraaortic and pelvic lymphadenectomy to maximally assess the extent of her disease. She demonstrated the common risk factors for aortoiliac arteriosclerosis, namely advanced age, obesity, and cigarette smoking. In the recovery room the patient complained of pain in the left lower limb, and on examination of that limb a diagnosis of proximal arterial occlusion was made. The patient was therefore returned to the operating room for left femoral arteriotomy via a vertical incision over the left femoral vessels. No flow from the left common femoral artery was observed, but good distal back flow was present. Fogarty balloon catheterization was successful in removing a fresh thrombus from the left external iliac artery. Local heparinized saline was instilled intraarterially, and the distal arterial tree was checked for the presence of thrombus by further Fogarty balloon catheterization. Good distal pulses were obtained at completion of the procedure. Intraoperative arteriography revealed a good trifurcation and runoff. Postoperatively, the patient’s pulses remained normal. Echocardiography, carried out in an attempt to find a mural thrombus, was normal, and she soon achieved normal ambulation. At subsequent follow-up the patient was asymptomatic with no evidence of lower limb insufficiency. 108 0090~8258/86$1.50 Copyright All rights
0 1986 by Academic Press, Inc. of reproduction in any form reserved.
ARTERIAL
OCCLUSION
WITH
SURGERY
109
CASE 2
A 69-year-old woman underwent a modified radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection for a Stage IA squamous cell carcinoma of the cervix with lymph/vascular permeation. On the seventh postoperative day she complained of bilateral leg pain at rest. Examination of her lower limbs revealed bilateral coldness, pallor, and absent pulses by both palpation and Doppler ultrasonic examination. A translumbar aortogram revealed complete occlusion of the abdominal aorta below the renal vessels. A presumptive diagnosis of acute aortic thrombosis with probable distal embolization was made. After consultation between the vascular surgeon and gynecologic oncologist, it was decided that the field of surgery was sufficiently sterile for an aortobifemoral graft insertion, as this would be a much more long-term, dependable solution to her arterial problem than a bilateral axillofemoral graft. Initial bilateral Fogarty balloon catheterization via common femoral arteriotomies was unsuccessful due to extensive aortoiliac arteriosclerosis, and therefore the abdomen was opened. The aorta was found to be grossly arteriosclerotic on inspection and after opening, it became clear that endarterectomy would not solve her problem. Further distal dissection revealed a saddle embolus extending down both common iliac arteries. Accordingly, after bilateral external iliac endarterectomies had been performed, an end-to-end aortobifemoral “Dacron” graft was inserted. Prior to this, arteriography revealed abrupt termination at the left trifurcation with dye extravasation probably due to trauma by the previously passed Fogarty catheter. At the end of the procedure, both dorsalis pedis and posterior tibia1 pulses were absent on the left side, but remained good on the right with warmth in both extremities. It was decided not to explore the left trifurcation as it was thought that improved viability of the left leg was unlikely to be achieved and any incisions would interfere with a subsequent below-knee amputation. On the second day after this procedure pulses detected by Doppler ultrasound had returned to the left foot, but rest pain remained and foot drop was present. In November 1982 she underwent a successful left lumbar sympathetic block for rest pain. Since then the extremity has remained viable and the foot drop has completely resolved. CASE 3
A 45year-old woman suffered a left ureterovaginal fistula after radical hysterectomy for Stage IB squamous cell carcinoma of the cervix in September 1979. Again, the patient exhibited risk factors for aortoiliac occlusive disease in the form of nonspecific ST and T wave changes on the EKG and a history of being a three-pack-a-day smoker. Six weeks following her initial surgery she underwent reimplantation of the left ureter. During mobilization of the left ureter in its pelvic course a 3-mm opening was inadvertently made in the wall of the left iliac artery. Repair was effected by the same surgeon with two interrupted 4/O Prolene sutures. In the recovery room the patient complained of pain in the left leg and examination was consistent with acute proximal arterial occlusion. Accordingly, the patient was returned to the operating room and the left external iliac artery was transected with a view to end-to-end anastomosis. After Fogarty balloon thrombectomy, extensive arteriosclerosis was found, necessitating en-
110
TOWNSEND
ET AL.
darterectomy to the aortic bifurcation until good flow was observed. Good distal pulses were felt at the end of the procedure but these disappeared to palpation in the postoperative period, although satisfactory function and temperature were observed and pulses were present to Doppler detection. During this time, the patient received intravenous Dextran 40, 1 liter/day for 3 days. She was discharged on a low cholesterol and fat diet but proceeded to develop claudication with increased ambulation, and finally rest pain 5 months after surgery. She continued her smoking habit during this time. Later an aortogram showed extensive aortoiliac occlusive disease with evidence of thombosis having developed throughout the vascular tree of the left lower limb. The limb has since remained somewhat ischemic as evidenced by claudication; however, this symptom has not been significant enough to warrant operative intervention. CASE 4
A 27-year-old woman underwent a radical hysterectomy with paraaortic and pelvic lymphadenectomy for a Stage IB squamous cell carcinoma of the cervix in April 1980. She had stopped using oral contraception five days previously. In the recovery room she complained of severe pain in the left leg, which was noticeably cold with complete absence of pulses. The right lower limb revealed normal pulses. Within the next hour, she complained of numbness and paraesthesia of the right foot which in turn showed a fall in temperature, and loss of the dorsalis pedis and posterior tibia1 pulses. Accordingly, she was returned to the operating room and explored via the previous abdominal incision with the removal of a fresh, red thrombus from the left common iliac artery by Fogarty balloon catheterization. Good distal pulses in the left lower limb were obtained after this procedure. A right external iliac arteriotomy was then performed, and arteriography revealed a cut-off in the right popliteal artery. Following this a right popliteal artery red thrombus was removed by Fogarty balloon catheterization. Repeat arteriography revealed extreme spasticity of the right lower limb arterial tree. At the end of the operation, although distal pulses were not palpable on the right side they were present to Doppler detection and temperature, and both lower limbs felt warm. Postoperatively, the patient had an uneventful course and palpable pulses returned to the right lower limb on the first postoperative day. The patient was anticoagulated by full heparinization and dipyridamole. On discharge the patient had full functional recovery with no evidence of lower limb arterial insufficiency. DISCUSSION
It is frequently impossible to differentiate between acute arterial embolism and thrombosis clinically or at operation. Arterial embolism is a complication of a preexisting cardiopathy, a proximal arterial lesion, or it is the result of a cardiovascular procedure. In a series reported by Haimovici [l] dealing with 228 patients who had 330 peripheral emboli, intracardiac thrombosis of the left side of the heart was found to be the origin of embolism in 96% of cases. The most common cardiac lesions were rheumatic heart disease, myocardial infarction, and arteriosclerotic heart disease. Acute arterial thrombosis, as distinct from
ARTERIAL
OCCLUSION
WITH
SURGERY
111
arterial embolism, may occur as a result of a number of local factors. These include intraoperative trauma, but may be a consequence of associated systemic diseases with or without disturbance of the normal coagulative and fibrinolytic mechanisms. Arteriosclerosis is the most common predisposing cause of acute thrombosis. At exploratory laparotomy the gynecologic oncologist endeavors to fully assess the extent of the patient’s tumor spread. In particular, at University of Miami/Jackson Memorial Hospital Center in recent years there has been increased employment of lymph node dissection along the iliac vessels and abdominal aorta often up to the renal vessels. This involves manipulation of these vessels with repeated minor blunt trauma, especially if the nodes are grossly involved and these involve the vessel adventitia. In addition, arteriosclerosis itself causes an adventitial reaction with fibrosis leading to an increased adherence of arteries to lymph nodes, with consequent increased manipulation to achieve dissection. It would seem reasonable to suppose such manipulative forces could disrupt atheromatous plaques leading to intimal damageand thrombus formation. Intramural hematoma is another recognized process leading to acute occlusion in this situation. Secondary arterial spasm is frequently seen after such manipulation, particularly in younger females free of arteriosclerosis as with Case 4, and can appear quite alarming especially in those females with small caliber vessels. An elegant study by Joris and Majno [2] was conducted on the effect of I-norepinephrine on the muscular arteries of the rat studied by serial electron microscopy. Endothelial damage was observed after only 15 min, exhibited by the tight folding of the internal elastic lamina which mechanically squeezed the cells. As the artery relaxed, the endothelium showed gaps, patches of thinned cytoplasm, and many adhesions between cells on opposite sides of intimal folds between which microthrombi could be seen. These adhesions were present for up to 1 day, after which they would seemingly snap and disappear. Such arterial spasm in conjunction with a systemic coagulopathy due to oral contraception could well have been the basis of the intraoperative arterial thrombosis in this patient. The majority of gynecologic oncology patients fall into those decades in which aortoiliac occlusive disease is most frequently seen. In addition, in many countries women are showing an increase in the smoking habit. We are thus seeing an increase in the field of gynecologic oncology of risk factors associated with arteriosclerosis of the coronary and peripheral arteries. The first three cases, as we have seen, are clear examples of this problem. Cronenwett et al. [3] reported on a series of 7.5 women requiring vascular reconstruction during 4 years for aortoiliac occlusive disease. They represented 40% of all patients requiring such surgery with the mean age of 57 years being the same as in males. Analysis revealed a 93% cigarette-smoking rate, and a high frequency of Type IV hyperlipoproteinemia as opposed to increased cholesterol. The oral contraceptive pill must be considered a risk factor in the younger female as in the last case presented. The need for avoiding surgery in this patient for at least 6 weeks after discontinuing the pill was considered to be secondary to the threat of tumor spread. The patient had, in fact, ceased oral contraceptive only 5 days prior to her surgery. As we have seen, she suffered intraoperative
112
TOWNSEND
ET AL.
thrombosis of nonsclerotic arteries. With the estrogen component of the pill being reduced to 50 pg or less, recent attention has been focused on the possible effects of the progestin component on the arterial system. In a number of recent studies on the subject, a consensus has evolved that pills containing progestin exhibiting androgenic activity (particularly the gonane norgestrel) depress total serum high-density lipoprotein (HDL) and HDL* levels when combined with 30 pg of estrogen, and are associated with an increased incidence of acute arterial incidents [4-71. This effect is considered by many as of prime importance in the pathogenesis of myocardial infarction and thrombotic strokes. This is perhaps the greatest disadvantage so far found with oral contraceptives in those few women so predisposed by as yet uncertain factors. The foregoing remarks underline a most important message:namely, gynecologic oncology patients demand a careful detailed preoperative clinical evaluation of their arterial tree. This should include documentation of risk factors in the verbal history. In particular, appropriate questioning is required to reveal symptoms of arterial insufficiency. For example, in Case 3 the patient volunteered a history of longstanding, three-block claudication only on being questioned after the event. A standard documentation of the peripheral pulses is mandatory and should include a search for bruit and signs of lower limb trophic changes, as well as palpating and documenting the presence and character of the pulses. Where indicated more detailed assessment must be undertaken, including the simple procedures of assessing venous filling on the dorsum of the foot, erythema of the foot on dependency after elevation, and recording the ankle-brachial index by portable Doppler ultrasound. This should help identify those patients with significant aortoiliac occlusive disease thus allowing preoperative assessment by a peripheral vascular surgical colleague. In addition, at surgery the lower limb pulses should always be felt before the abdomen is closed. In this way one can avoid hampering such a colleague in his management of these arterial complications by informing him of the state of the patient’s arterial tree before emergency vascular surgery. Preoperative EKG studies showing ST and T wave changes, as in Cases 1 and 3, and evidence of proximal arterial disease such as aortic calcification and tortuosity on chest X ray, as with Case 3, should alert the clinician to the likelihood of more peripheral vascular disease being found at the time of surgery. The question of prophylactic anticoagulation in an appropriate form to reduce acute arterial thrombosis perioperatively in patients exhibiting significant risk factors is an open one, and deserves further study. It appears logical that greatest success would be achieved by minimizing platelet aggregation at local sites in the surgical field showing intimal damage by atherosclerosis and blunt trauma. Prophylactic heparin, used in the standard form, would appear to be of little value in this respect. It has been shown for example by Weiss [8] to affect platelet response to collagen and ADP only in extremely high doses. These four patients all received heparin 5000 units subcutaneously every 12 hr commencing 6 PM the day prior to surgery. Much more promising is the use of antiplatelet agents, such as aspirin and dipyridamole. Aspirin apparently prevents the synthesis by platelets of thromboxane AZ, the main platelet aggregator in the body, by
ARTERIAL
OCCLUSION
WITH
SURGERY
113
inhibiting through acetylation the cyclooxygenase enzyme needed for the conversion of arachidonic acid to thromboxane AZ. It also inhibits vessel wall production of prostacyclin (PGIJ, another ecosanoid (arachidonic acid derivative). This substance, however, is an inhibitor of platelet aggregation; but recent advances in the study of ecosanoid metabolism have suggested a far more complex role than described above for the effects of aspirin on platelet aggregation [9,10]. Suffice it to say, however, in both laboratory and clinical experience varying doses of aspirin have always shown their effects on the side of inhibition of platelet aggregation rather than the opposite [11,12]. A number of salient features require emphasis regarding these patients .presented. All four patients exhibited risk factors for arterial problems during surgery. None of the patients had an adequate clinical evaluation of their arterial tree either by history or physical examination before the initial surgery. Only one patient had her dorsalis pedis pulses recorded as being present preoperatively. One should be more aware of the increasing frequency of patients with significant aortoiliac occlusive disease undergoing radical pelvic surgery with manipulation of their diseased arteries. As previously mentioned, there could be a case for prophylaxis in the form of an inhibitor of arterial platelet aggregation in such patients. During surgery, arteriosclerosis should be thought of and looked for. Manipulation of arteries particularly if sclerotic should be minimized. In particular a tendency to grasp arteries with dissecting forceps must be avoided. Extreme care is required when dissecting grossly involved lymph nodes or other tumors from these arteries. This can be aided by carefully dividing the adventitia and mobilizing it off the artery wall proximal and distal to the tumor site before removing the tumor and adventitia together. Of extreme importance is the need to check the lower limb pulses and temperature before closure of the abdomen. Only by incorporating the previously described clinical evaluation of the peripheral arterial system into the everyday workup of the preoperative patient, and maintaining an ever-present consciousness of the problems of arteriosclerosis in such patients, can the effects of this disease be minimized during surgery. REFERENCES I. Haimovici, H., Peripheral arterial embolism: A study of 330 unselected cases of embolism of the extremities, Angiology I, 20 (1950). 2. Joris, I., and Majno, G., Endothelial changes induced by arterial spasm, Amer. J. Pothol. 102, 346-358 (1981). 3. Cronenwett, J. L., Davis, J. T., Jr., and Gooch, J. B., et al., Aortoiliac occlusive disease in women, Surgery 88, 775-784 (1980). 4. Kay, C. R., Progestogens and arterial disease-evidence from the Royal College of General Practitioners’ study, Amer. J. Obstet. Gynecol. 142, 762-765 (1982). 5. Wynn, V., and Niththyananthan, R., The effect of progestins in combined oral contraceptives on serum lipids with special reference to high-density lipoproteins, Amer. J. Obstet. Gynecol. 142, 766-771 (1982). 6. Oster, P., Arab, L., and Kohlmeier, M., et al., Effects of estrogens and progestogens on lipid metabolism, Amer. J. Obstet. Gynecol. 142, 773-775 (1982). 7. Meade, T. W., Effects of progestogens on the cardiovascular system, Amer. J. Obstet. Gynecol. 142, 776-779 (1982). 8. Weiss, H. J., Antiplatelet therapy, N. Engl. J. Med. 298, 1344-1347 (1978).
114
TOWNSEND
ET AL.
9. Moncada, S., and Vane, J. R., Archidonic acid metabolites and the interactions between platelets and blood vessel walls, N. Engl. J. Med. 300, 1142-1147 (1979). 10. Preston, F. E., Whipps, S., and Jackson, C. A., et a/., Inhibition of prostacyclin and platelet thromboxane AZ after low-dose aspirin, N. Engl. J. Med. 304, 76-79 (1981). 11. FitzGerald, G. A., Oates, J. A., and Hawiger, J., et al. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man, J. Clin. Invesr. 71, 676-688 (1983). 12. Marcus, A. J., Aspirin as an antithrombotic medication: editorial retrospective, N. Engl. J. Med. 809, 151.5-1516 (1983).
ONCOLOGY
25, 108-114 (1986)
Acute Peripheral Arterial Occlusion Associated with Surgery for Gynecologic Cancer PHILIP
A. TOWNSEND, M.D.,* DUANE G. HUTSON, M.D.,? JOHN LOVECCHIO, M.D.,* AND HERVY E. AVERETTE, M.D.§
*Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of South Florida, College of Medicine, Box 18, 12901 North 30th Street, Tampa, Florida 33612; fDepartment of Surgery, University of Miami, P.O. Box 016310, Miami, Florida 33101; $North Shore University Hospital, Manhasset, New York 11030; and #Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Miami, P.O. Box 016960, Miami, Florida 33101
Received May 23, 1985 Four cases are described of acute peripheral arterial occlusion associated with surgery for gynecologic cancer during the 5 years 1979to 1983at the University of Miami, Jackson Memorial Hospital Center. No such cases were recorded during the preceding 5 years. The probable underlying etiologic factors are discussed and recommendations made regarding the evaluation and management of such patients. 0 1986 Academic Press, Inc.
CASE 1
A 71-year-old woman underwent exploratory laparotomy in August 1982 for Stage IB, Grade 2, adenocarcinoma of the endometrium. The procedure included selective paraaortic and pelvic lymphadenectomy to maximally assess the extent of her disease. She demonstrated the common risk factors for aortoiliac arteriosclerosis, namely advanced age, obesity, and cigarette smoking. In the recovery room the patient complained of pain in the left lower limb, and on examination of that limb a diagnosis of proximal arterial occlusion was made. The patient was therefore returned to the operating room for left femoral arteriotomy via a vertical incision over the left femoral vessels. No flow from the left common femoral artery was observed, but good distal back flow was present. Fogarty balloon catheterization was successful in removing a fresh thrombus from the left external iliac artery. Local heparinized saline was instilled intraarterially, and the distal arterial tree was checked for the presence of thrombus by further Fogarty balloon catheterization. Good distal pulses were obtained at completion of the procedure. Intraoperative arteriography revealed a good trifurcation and runoff. Postoperatively, the patient’s pulses remained normal. Echocardiography, carried out in an attempt to find a mural thrombus, was normal, and she soon achieved normal ambulation. At subsequent follow-up the patient was asymptomatic with no evidence of lower limb insufficiency. 108 0090~8258/86$1.50 Copyright All rights
0 1986 by Academic Press, Inc. of reproduction in any form reserved.
ARTERIAL
OCCLUSION
WITH
SURGERY
109
CASE 2
A 69-year-old woman underwent a modified radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection for a Stage IA squamous cell carcinoma of the cervix with lymph/vascular permeation. On the seventh postoperative day she complained of bilateral leg pain at rest. Examination of her lower limbs revealed bilateral coldness, pallor, and absent pulses by both palpation and Doppler ultrasonic examination. A translumbar aortogram revealed complete occlusion of the abdominal aorta below the renal vessels. A presumptive diagnosis of acute aortic thrombosis with probable distal embolization was made. After consultation between the vascular surgeon and gynecologic oncologist, it was decided that the field of surgery was sufficiently sterile for an aortobifemoral graft insertion, as this would be a much more long-term, dependable solution to her arterial problem than a bilateral axillofemoral graft. Initial bilateral Fogarty balloon catheterization via common femoral arteriotomies was unsuccessful due to extensive aortoiliac arteriosclerosis, and therefore the abdomen was opened. The aorta was found to be grossly arteriosclerotic on inspection and after opening, it became clear that endarterectomy would not solve her problem. Further distal dissection revealed a saddle embolus extending down both common iliac arteries. Accordingly, after bilateral external iliac endarterectomies had been performed, an end-to-end aortobifemoral “Dacron” graft was inserted. Prior to this, arteriography revealed abrupt termination at the left trifurcation with dye extravasation probably due to trauma by the previously passed Fogarty catheter. At the end of the procedure, both dorsalis pedis and posterior tibia1 pulses were absent on the left side, but remained good on the right with warmth in both extremities. It was decided not to explore the left trifurcation as it was thought that improved viability of the left leg was unlikely to be achieved and any incisions would interfere with a subsequent below-knee amputation. On the second day after this procedure pulses detected by Doppler ultrasound had returned to the left foot, but rest pain remained and foot drop was present. In November 1982 she underwent a successful left lumbar sympathetic block for rest pain. Since then the extremity has remained viable and the foot drop has completely resolved. CASE 3
A 45year-old woman suffered a left ureterovaginal fistula after radical hysterectomy for Stage IB squamous cell carcinoma of the cervix in September 1979. Again, the patient exhibited risk factors for aortoiliac occlusive disease in the form of nonspecific ST and T wave changes on the EKG and a history of being a three-pack-a-day smoker. Six weeks following her initial surgery she underwent reimplantation of the left ureter. During mobilization of the left ureter in its pelvic course a 3-mm opening was inadvertently made in the wall of the left iliac artery. Repair was effected by the same surgeon with two interrupted 4/O Prolene sutures. In the recovery room the patient complained of pain in the left leg and examination was consistent with acute proximal arterial occlusion. Accordingly, the patient was returned to the operating room and the left external iliac artery was transected with a view to end-to-end anastomosis. After Fogarty balloon thrombectomy, extensive arteriosclerosis was found, necessitating en-
110
TOWNSEND
ET AL.
darterectomy to the aortic bifurcation until good flow was observed. Good distal pulses were felt at the end of the procedure but these disappeared to palpation in the postoperative period, although satisfactory function and temperature were observed and pulses were present to Doppler detection. During this time, the patient received intravenous Dextran 40, 1 liter/day for 3 days. She was discharged on a low cholesterol and fat diet but proceeded to develop claudication with increased ambulation, and finally rest pain 5 months after surgery. She continued her smoking habit during this time. Later an aortogram showed extensive aortoiliac occlusive disease with evidence of thombosis having developed throughout the vascular tree of the left lower limb. The limb has since remained somewhat ischemic as evidenced by claudication; however, this symptom has not been significant enough to warrant operative intervention. CASE 4
A 27-year-old woman underwent a radical hysterectomy with paraaortic and pelvic lymphadenectomy for a Stage IB squamous cell carcinoma of the cervix in April 1980. She had stopped using oral contraception five days previously. In the recovery room she complained of severe pain in the left leg, which was noticeably cold with complete absence of pulses. The right lower limb revealed normal pulses. Within the next hour, she complained of numbness and paraesthesia of the right foot which in turn showed a fall in temperature, and loss of the dorsalis pedis and posterior tibia1 pulses. Accordingly, she was returned to the operating room and explored via the previous abdominal incision with the removal of a fresh, red thrombus from the left common iliac artery by Fogarty balloon catheterization. Good distal pulses in the left lower limb were obtained after this procedure. A right external iliac arteriotomy was then performed, and arteriography revealed a cut-off in the right popliteal artery. Following this a right popliteal artery red thrombus was removed by Fogarty balloon catheterization. Repeat arteriography revealed extreme spasticity of the right lower limb arterial tree. At the end of the operation, although distal pulses were not palpable on the right side they were present to Doppler detection and temperature, and both lower limbs felt warm. Postoperatively, the patient had an uneventful course and palpable pulses returned to the right lower limb on the first postoperative day. The patient was anticoagulated by full heparinization and dipyridamole. On discharge the patient had full functional recovery with no evidence of lower limb arterial insufficiency. DISCUSSION
It is frequently impossible to differentiate between acute arterial embolism and thrombosis clinically or at operation. Arterial embolism is a complication of a preexisting cardiopathy, a proximal arterial lesion, or it is the result of a cardiovascular procedure. In a series reported by Haimovici [l] dealing with 228 patients who had 330 peripheral emboli, intracardiac thrombosis of the left side of the heart was found to be the origin of embolism in 96% of cases. The most common cardiac lesions were rheumatic heart disease, myocardial infarction, and arteriosclerotic heart disease. Acute arterial thrombosis, as distinct from
ARTERIAL
OCCLUSION
WITH
SURGERY
111
arterial embolism, may occur as a result of a number of local factors. These include intraoperative trauma, but may be a consequence of associated systemic diseases with or without disturbance of the normal coagulative and fibrinolytic mechanisms. Arteriosclerosis is the most common predisposing cause of acute thrombosis. At exploratory laparotomy the gynecologic oncologist endeavors to fully assess the extent of the patient’s tumor spread. In particular, at University of Miami/Jackson Memorial Hospital Center in recent years there has been increased employment of lymph node dissection along the iliac vessels and abdominal aorta often up to the renal vessels. This involves manipulation of these vessels with repeated minor blunt trauma, especially if the nodes are grossly involved and these involve the vessel adventitia. In addition, arteriosclerosis itself causes an adventitial reaction with fibrosis leading to an increased adherence of arteries to lymph nodes, with consequent increased manipulation to achieve dissection. It would seem reasonable to suppose such manipulative forces could disrupt atheromatous plaques leading to intimal damageand thrombus formation. Intramural hematoma is another recognized process leading to acute occlusion in this situation. Secondary arterial spasm is frequently seen after such manipulation, particularly in younger females free of arteriosclerosis as with Case 4, and can appear quite alarming especially in those females with small caliber vessels. An elegant study by Joris and Majno [2] was conducted on the effect of I-norepinephrine on the muscular arteries of the rat studied by serial electron microscopy. Endothelial damage was observed after only 15 min, exhibited by the tight folding of the internal elastic lamina which mechanically squeezed the cells. As the artery relaxed, the endothelium showed gaps, patches of thinned cytoplasm, and many adhesions between cells on opposite sides of intimal folds between which microthrombi could be seen. These adhesions were present for up to 1 day, after which they would seemingly snap and disappear. Such arterial spasm in conjunction with a systemic coagulopathy due to oral contraception could well have been the basis of the intraoperative arterial thrombosis in this patient. The majority of gynecologic oncology patients fall into those decades in which aortoiliac occlusive disease is most frequently seen. In addition, in many countries women are showing an increase in the smoking habit. We are thus seeing an increase in the field of gynecologic oncology of risk factors associated with arteriosclerosis of the coronary and peripheral arteries. The first three cases, as we have seen, are clear examples of this problem. Cronenwett et al. [3] reported on a series of 7.5 women requiring vascular reconstruction during 4 years for aortoiliac occlusive disease. They represented 40% of all patients requiring such surgery with the mean age of 57 years being the same as in males. Analysis revealed a 93% cigarette-smoking rate, and a high frequency of Type IV hyperlipoproteinemia as opposed to increased cholesterol. The oral contraceptive pill must be considered a risk factor in the younger female as in the last case presented. The need for avoiding surgery in this patient for at least 6 weeks after discontinuing the pill was considered to be secondary to the threat of tumor spread. The patient had, in fact, ceased oral contraceptive only 5 days prior to her surgery. As we have seen, she suffered intraoperative
112
TOWNSEND
ET AL.
thrombosis of nonsclerotic arteries. With the estrogen component of the pill being reduced to 50 pg or less, recent attention has been focused on the possible effects of the progestin component on the arterial system. In a number of recent studies on the subject, a consensus has evolved that pills containing progestin exhibiting androgenic activity (particularly the gonane norgestrel) depress total serum high-density lipoprotein (HDL) and HDL* levels when combined with 30 pg of estrogen, and are associated with an increased incidence of acute arterial incidents [4-71. This effect is considered by many as of prime importance in the pathogenesis of myocardial infarction and thrombotic strokes. This is perhaps the greatest disadvantage so far found with oral contraceptives in those few women so predisposed by as yet uncertain factors. The foregoing remarks underline a most important message:namely, gynecologic oncology patients demand a careful detailed preoperative clinical evaluation of their arterial tree. This should include documentation of risk factors in the verbal history. In particular, appropriate questioning is required to reveal symptoms of arterial insufficiency. For example, in Case 3 the patient volunteered a history of longstanding, three-block claudication only on being questioned after the event. A standard documentation of the peripheral pulses is mandatory and should include a search for bruit and signs of lower limb trophic changes, as well as palpating and documenting the presence and character of the pulses. Where indicated more detailed assessment must be undertaken, including the simple procedures of assessing venous filling on the dorsum of the foot, erythema of the foot on dependency after elevation, and recording the ankle-brachial index by portable Doppler ultrasound. This should help identify those patients with significant aortoiliac occlusive disease thus allowing preoperative assessment by a peripheral vascular surgical colleague. In addition, at surgery the lower limb pulses should always be felt before the abdomen is closed. In this way one can avoid hampering such a colleague in his management of these arterial complications by informing him of the state of the patient’s arterial tree before emergency vascular surgery. Preoperative EKG studies showing ST and T wave changes, as in Cases 1 and 3, and evidence of proximal arterial disease such as aortic calcification and tortuosity on chest X ray, as with Case 3, should alert the clinician to the likelihood of more peripheral vascular disease being found at the time of surgery. The question of prophylactic anticoagulation in an appropriate form to reduce acute arterial thrombosis perioperatively in patients exhibiting significant risk factors is an open one, and deserves further study. It appears logical that greatest success would be achieved by minimizing platelet aggregation at local sites in the surgical field showing intimal damage by atherosclerosis and blunt trauma. Prophylactic heparin, used in the standard form, would appear to be of little value in this respect. It has been shown for example by Weiss [8] to affect platelet response to collagen and ADP only in extremely high doses. These four patients all received heparin 5000 units subcutaneously every 12 hr commencing 6 PM the day prior to surgery. Much more promising is the use of antiplatelet agents, such as aspirin and dipyridamole. Aspirin apparently prevents the synthesis by platelets of thromboxane AZ, the main platelet aggregator in the body, by
ARTERIAL
OCCLUSION
WITH
SURGERY
113
inhibiting through acetylation the cyclooxygenase enzyme needed for the conversion of arachidonic acid to thromboxane AZ. It also inhibits vessel wall production of prostacyclin (PGIJ, another ecosanoid (arachidonic acid derivative). This substance, however, is an inhibitor of platelet aggregation; but recent advances in the study of ecosanoid metabolism have suggested a far more complex role than described above for the effects of aspirin on platelet aggregation [9,10]. Suffice it to say, however, in both laboratory and clinical experience varying doses of aspirin have always shown their effects on the side of inhibition of platelet aggregation rather than the opposite [11,12]. A number of salient features require emphasis regarding these patients .presented. All four patients exhibited risk factors for arterial problems during surgery. None of the patients had an adequate clinical evaluation of their arterial tree either by history or physical examination before the initial surgery. Only one patient had her dorsalis pedis pulses recorded as being present preoperatively. One should be more aware of the increasing frequency of patients with significant aortoiliac occlusive disease undergoing radical pelvic surgery with manipulation of their diseased arteries. As previously mentioned, there could be a case for prophylaxis in the form of an inhibitor of arterial platelet aggregation in such patients. During surgery, arteriosclerosis should be thought of and looked for. Manipulation of arteries particularly if sclerotic should be minimized. In particular a tendency to grasp arteries with dissecting forceps must be avoided. Extreme care is required when dissecting grossly involved lymph nodes or other tumors from these arteries. This can be aided by carefully dividing the adventitia and mobilizing it off the artery wall proximal and distal to the tumor site before removing the tumor and adventitia together. Of extreme importance is the need to check the lower limb pulses and temperature before closure of the abdomen. Only by incorporating the previously described clinical evaluation of the peripheral arterial system into the everyday workup of the preoperative patient, and maintaining an ever-present consciousness of the problems of arteriosclerosis in such patients, can the effects of this disease be minimized during surgery. REFERENCES I. Haimovici, H., Peripheral arterial embolism: A study of 330 unselected cases of embolism of the extremities, Angiology I, 20 (1950). 2. Joris, I., and Majno, G., Endothelial changes induced by arterial spasm, Amer. J. Pothol. 102, 346-358 (1981). 3. Cronenwett, J. L., Davis, J. T., Jr., and Gooch, J. B., et al., Aortoiliac occlusive disease in women, Surgery 88, 775-784 (1980). 4. Kay, C. R., Progestogens and arterial disease-evidence from the Royal College of General Practitioners’ study, Amer. J. Obstet. Gynecol. 142, 762-765 (1982). 5. Wynn, V., and Niththyananthan, R., The effect of progestins in combined oral contraceptives on serum lipids with special reference to high-density lipoproteins, Amer. J. Obstet. Gynecol. 142, 766-771 (1982). 6. Oster, P., Arab, L., and Kohlmeier, M., et al., Effects of estrogens and progestogens on lipid metabolism, Amer. J. Obstet. Gynecol. 142, 773-775 (1982). 7. Meade, T. W., Effects of progestogens on the cardiovascular system, Amer. J. Obstet. Gynecol. 142, 776-779 (1982). 8. Weiss, H. J., Antiplatelet therapy, N. Engl. J. Med. 298, 1344-1347 (1978).
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9. Moncada, S., and Vane, J. R., Archidonic acid metabolites and the interactions between platelets and blood vessel walls, N. Engl. J. Med. 300, 1142-1147 (1979). 10. Preston, F. E., Whipps, S., and Jackson, C. A., et a/., Inhibition of prostacyclin and platelet thromboxane AZ after low-dose aspirin, N. Engl. J. Med. 304, 76-79 (1981). 11. FitzGerald, G. A., Oates, J. A., and Hawiger, J., et al. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man, J. Clin. Invesr. 71, 676-688 (1983). 12. Marcus, A. J., Aspirin as an antithrombotic medication: editorial retrospective, N. Engl. J. Med. 809, 151.5-1516 (1983).