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LATE ANEURYSM FORMATION IN ARTERIAL HOMOGRAFTS
LATE A N E U R Y S M F O R M A T I O N I N ARTERIAL
HOMOGRAFTS
Report of Four Cases of Femoral Aneurysm /. L. Provan, B.Sc, M.B. (Lond.),
F.R.C.S. (Eng.), London,
England
I
N the early days of reconstructive arterial surgery, before synthetic grafts were available, arterial homografts were widely used as vessel replacements or as bypasses. They gave initially good results and were easy to work with, but their disadvantages, particularly the difficulties of preparation and reconstitution and the shortage of supply, led some to abandon their use in favor of synthetic tubes, made of Dacron or Teflon, or vein autografts. It is now recognized, in addition, that degenerative changes occur in homografts, but aneurysm as a late complication of homografts used for bypassing superficial femoral artery occlusions has not been widely reported, especially in England. This paper describes four such aneurysms treated by the Surgical Unit at this hospital since 1961. CASE REPORTS CASE 1.—Male. No. AG.7513. The patient was admitted to the University College Hos pital in February, 1958, at the age of 61, with intermittent claudication in the calf of the right leg of 6 months' duration. He was able to walk about 300 yards. On examination, he was hypertensive (blood pressure, 160/100 mm. H g ) ; the right foot was colder than the left but there were no trophic changes. No pulses were palpable in this leg below the femoral artery. The left leg was normal. An arteriogram showed a complete block of the right super ficial femoral artery, which extended up the thigh for about 10 inches from the adductor hiatus. At operation on March 3, 1958, a frozen homograft was inserted as a bypass between the common femoral and popliteal arteries. An anticoagulant, Dindevan, was administered from the fourth postoperative day, and, when the patient was discharged, the right foot was warm and the dorsalis pedis and posterior tibial pulses were both palpable. He was re-admitted in May, 1959, for surgical treatment of a carcinoma of the floor of the mouth, but remained well as far as his feet were concerned, until an aneurysmal bulge, 1 cm. in diameter, in the upper end of the homograft was noted in December, 1960, 33 months after the original operation. This was observed until August, 1961, when it had increased rapidly in size, measuring 4 cm. in diameter. The overlying skin was thinned and noticeably blue in color. Both feet were warm and pink and all the peripheral pulses were palpable. He had had no claudication since the 1958 operation. An operation was performed on Sept. 15, 1961. The aneurysm was found to involve only the more anterior part of the graft, the rest of the graft being apparently normal. The sac was excised and the defect in the graft wall was closed by direct suture without Prom the Surgical Unit, University College Hospital, London, England. Received for publication Jan. 15, 1964. 282
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interference with the lumen of the graft. Anticoagulants, which had been stopped before the operation, were re-started afterward. He remained well, with all pedal pulses palpable and no pain on walking. However, when he was seen in April, 1963, the graft was noted to be diffusely aneurysmal and appeared as a pulsating mass in the muscles of the medial side of the thigh. Sudden thrombosis of the graft occurred in June, 1963, 63 months after its insertion. I n spite of heparinization and sympathectomy he developed severe rest pain and a mid-thigh ampu tation was performed in September, 1963. CASE 2.—Male. No. AG.4419. This man was admitted to the University College Hos pital in October, 1957, at the age of 57, for treatment of a tuberculous cavity in the upper lobe of the left lung. At that time he complained of pain in the calves of both legs on walking since 1951 ; this had been associated with recurrent ulcération around the right lateral malleolus for a year. The pain had become progressively more severe, so that on admission he could only walk about 50 yards, being limited mainly by the right leg. The tuberculosis responded well to drug therapy and he was transferred to the Surgical Unit in March, 1958. No pulses were palpable below the femoral artery in either leg. There was an ulcer above the right lateral malleolus, with scars of healed ulcers on the dorsum of each foot. No arteriogram was done as it was decided that the right popliteal artery should be explored to see if bypass grafting was possible. Operation was performed on March 31, 1958, at which time a 29-day-old frozen arterial homograft was inserted between the common femoral artery and the lowest part of the popliteal artery. The patient was given Dindevan from the fourth postoperative day and remained well, pain-free on walking, with palpable right popliteal and pedal pulses. How ever, the left calf began to trouble him more and he was re-admitted in October, 1959, for a similar bypass procedure to the left leg, although on this occasion a knitted Dacro"n prosthesis was used. The condition of the right leg remained unchanged until he was once again admitted to the University College Hospital in October, 1961, 43 months after insertion of the first graft, after having noticed a lump in the right groin for 2 months. On examination, there was a pulsating tumor, 3 cm. in diameter, situated halfway down the femoral triangle of the right thigh. The right foot was warm and peripheral pulses were palpable. At operation on Oct. 6, 1961, a fusiform aneurysm, involving almost the whole circum ference of the upper end of the graft was found. This was excised with a portion of normal homograft on either side and the gap was bridged with a length of saphenous vein from the same thigh. An end-to-side anastomosis was performed at the upper end and an end-to-end at the lower end. He has been regularly followed up since then and the pulses and condition of the right foot have remained unchanged since the original operation in 1958 and he is still pain-free on walking. CASE 3.—Male No. 10527. The patient was admitted to the University College Hospital in February, 1958, at the age of 57. He had developed left calf claudication in 1956 which followed a laminectomy for a lumbar disc protrusion. The claudication became severe and on admission he could walk about 25 yards only. On examination, the blood pressure was 130/90 mm. Hg. No pulses could be felt in the left leg below the femoral artery. The right leg was normal. An arteriogram showed complete occlusion of the superficial femoral artery below the origin of the profunda femoris. On March 10, 1958, an eight-day-old frozen homograft was inserted between the com mon femoral and popliteal arteries. He was given Dindevan from the fifth postoperative day and on discharge the pedal pulses were both palpable in the left foot. He remained relatively pain-free after this but in December, 1961, 45 months after insertion of the graft, he was found to have a pulsating swelling, 6 by 2.5 cm., in the upper medial aspect of the left thigh. The left foot pulses were palpable a t this time and his name was noted for urgent admission. However, 2 days later, he was admitted as an emer gency case, having developed sudden severe pain in the left leg and foot, which had gone white
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in color. On examination that day, there was no pulsation in the aneurysm, no pulses were palpable below the left femoral, and the left leg was white and cold, with no sensation in its lower two thirds. At operation early on Dec. 9, 1961, the femoral and popliteal arteries were exposed, the graft cut away at its upper end, and a woven Teflon prosthesis was inserted from the common femoral to the popliteal artery through a tunnel made with difficulty alongside the previous graft. There was negligible back bleed from the distal popliteal artery before insertion of the graft and a long clot was removed from it prior to the anastomosis. At the conclusion of the operation the popliteal artery pulsated vigorously, but no pedal pulses were felt and a mid-thigh amputation had to be performed 2 days later, when it was obvious that the limb was not going to survive. CASE 4.—Male. No. A E . 1512. This patient was admitted to the University College Hospital in February, 1957, at the age of 61. Intermittent claudication in the left leg had been first noticed in 1949. This was present after walking 200 to 300 yards in 1952, at which time a left lumbar sympathectomy was performed at another hospital. The leg felt warmer after this, but the claudication was not improved. A tenotomy of the left Achilles tendon was done in 1953, with some relief of calf pain, but in the same year he noticed pain in the right calf which, at the time of admission to the hospital, occurred after walking 80 to 100 yards. On examination at that time the blood pressure was 180/90 mm. Hg. A femoral pulse was the only one palpable in the right leg. No pulses, including the femoral, were present in the left leg. An arteriogram showed complete occlusion of the left common iliae artery from its origin from the aorta, with a complete block of the right superficial femoral artery in its lower part. There was extensive atheroma of the right common iliae artery. Operation on Aug. 1, 1957, included endarterectomy of the right common iliac artery and bypass graft from the aorta to the left femoral, with a freeze-dried homograft. His recovery after this was uneventful; the femoral popliteal, dorsalis pedis, and anastomotica magna pulses were palpable in the left leg and peroneal and weak femoral pulses in the right. He was re-admitted in January, 1958, when pulses were absent in the right leg, al though nutrition was good. A right femoro-popliteal bypass was performed on J a n . 13, 1958, with a frozen homograft. After this, popliteal and pedal pulses were present in that leg. He was given Dindevan after each operation and maintained on this as an out-patient. He remained well, with all pulses palpable in both legs, although since June, 1958, he had noticed pain in the right calf on walking uphill fast and said that the right foot felt cooler than the left. He was admitted to the University College Hospital again in February, 1962, 49 months after the second graft, after having noticed a pulsating swelling in the right thigh, which had been getting larger, for 3 weeks. On examination, there was a pulsating swelling, 3 inches in diameter, situated on the medial side of the right thigh, 3 % inches below the inguinal ligament in the line of the femoral artery. The right foot was cooler than the left; the right pedal pulses were palpable. Operation was performed on Feb. 22, 1962. There was aneurysmal dilatation of the homograft within the substance of the adductor longus and magnus muscles. I t was ex cised, with the upper and lower parts of the homograft left in position, and the continuity between these was restored with a saphenous vein graft from the same thigh. An end-to-end anastomosis was used at each end. Following this operation, weak pedal pulses have been only intermittently felt and the right foot is still cool. The nutrition and venous filling are good, however, but the patient now has claudication after activities such as lawn-mowing. Slow walking on the flat does not trouble him.
PREPARATION OF HOMOGRAFTS
The grafts in which these aneurysms developed were obtained from adults of up to 35 years of age, who had died suddenly as the result of injury, while
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in good health. Each graft was excised from the cadaver with aseptic technique within 8 hours of death. Bacteriological swabs taken from the bed of each artery were sterile after 48 hours; the policy was to discard grafts if the bed cultures grew pathogens. Immediately after removal from the body, the graft was put into sterile normal saline containing 1,000,000 units of crystalline penicillin and 1 gram of streptomycin. Further preparation of the graft was done in the operating theater where adherent fat and connective tissue were removed, de fects were repaired with fine silk, and branches ligated with silk. The graft was then kept in the penicillin-streptomycin solution for 24 hours at 4° C. The fluid was then decanted and the graft in its container was snap frozen by immersion in a mixture of solid carbon dioxide and acetone. The frozen graft was stored at -30° C. until required. Reconstitution was effected at the time of operation by placing the frozen artery in normal saline at room tem perature. It was then tested by injecting saline solution under pressure and leaks were repaired with silk sutures or ligatures. HISTOLOGY
The segments of grafts removed at the. operations for aneurysms were examined histologically and the changes were similar to those noted in the extensive account by Szilagyi and associates1 in 1957. In all 4 cases, the muscular tissue of the media had been replaced by dense fibrous tissue and, as in the older grafts described by Szilagyi, there was fragmentation of the elastic lami nae. However, in Cases 1 and 2, in whom grafts had been inserted for 33 and 43 months, respectively, when the aneurysm was excised, the elastic layers were very sparse indeed and in Case 2 the elastic was present mainly in the outer layers of the graft Avail. These 2 cases were also different from Cases 3 and 4 in that the fibrous tissue comprising the wall had a fairly marked collection of inflammatory cells, mainly eosinophils and neutrophils. Plasma cells, however, were not present. (In Cases 3 and 4 the wall of fibrous tissue was almost acellular). These changes are compatible with an antibody response against the graft by the host. There remains a tube of fibrous tissue, containing a minimal amount of elastic tissue, to carry the blood. This fibrous tissue has little active power to resist the pressure of blood within it, so that dilatation of the graft may eventu ally occur. However, this sequence of events would be expected to lead to diffuse dilatation, as in Case 4, rather than a localized aneurysm. This is discussed later. DISCUSSION
The fact that arterial homografts degenerate with time has been known for some years and the histological changes occurring in the graft wall are well documented (Nyhus 2 [1955] and Szilagyi 1 [1957] and their associates). Szilagyi and co-workers, in a survey of a large series of homografts used as aortic, iliac, or femoral replacements or bypasses, pointed out that there was a much greater tendency for the femoral grafts to fail. They related this partly to the inability of reconstructive arterial surgery to deal with the inevitable progress of the primary disease process in the distal parts of the host vascular tree, but also
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suggested that, as femoral homografts possessed more muscular walls than aortic ones, they might be expected to exert more antigenic activity and hence degenerate more quickly than their aortic counterparts, which are mainly elastic. However, although they had only one femoral aneurysm out of seventy homografts submitted for study, dilatation and tortuosity were much more marked. Twelve out of seventy homografts showed the latter changes, which were not present in any of their aortic or iliac grafts, although these did show four aneurysms. DeWeese and colleagues,3 in 1959, surveying the literature up to that time, recorded thirteen aneurysms of which only four were in femoral grafts. Two of these had thrombosed a year after insertion of the graft and the oldest graft, in the abdominal aorta, was only 3 years old when the aneurysm presented. Since then, Crawford and co-workers4 reported seven homograft aneurysms out of ninety-eight homografts and Humphries and his colleagues5 found six aneurysms in autopsies on 33 patients who had had arterial homografts of various types, of which at least two were femoral aneurysms. Aneurysm for mation or dilatation has also been noted by Crawford and associates6 and Linton, 7 while Whitman and co-workers8 and Tibbs,9 in accounts of homograft complications mentioning aneurysm formation, state that they had given up the use of homografts in favor of synthetic prostheses, presumably partly because of degeneration in homografts. More recently, Ashton and collaborators 10 have recorded aneurysm formation in four out of twenty-three femoral arterial homografts and Taylor 11 reported four aneurysms in twenty-two similar grafts. The 4 cases reported here are of interest for several reasons, but mainly because the aneurysms developed a long time after insertion of the homografts. In each case these had been functioning perfectly for over 3 years before reoperation was required. Also of interest is the fact that in 3 of the 4 cases the aneurysm was localized in its extent. Degenerative changes such as are known to occur in arterial homografts might be expected to lead to generalized dilata tion of the grafts, but this only occurred as the presenting symptom in Case 4. Case 1 developed this 21 months after a localized aneurysm was first operated upon, when the remainder of the graft had been noted to be grossly normal. The localization of three of the aneurysms suggests the possibility of a failure during preparation of the graft, such as injury at the time or failure to ligate a side branch flush with the wall of the main artery. Disease of the donor artery itself is another possibility and in this respect it is interesting that two of the homografts used (Cases 2 and 3) came from the same donor, a female of 34. There is, however, no record of any of the grafts being in any way abnormal. All four homografts were inserted in the short period between Jan. 13, 1958, and March 31, 1958, and they form part of a small series of twenty-two femoral homografts used between November, 1956, and February, 1959. The incidence of aneurysm formation in this series (4 of 22, or 18.2 per cent) is identical with that mentioned by Taylor 11 and very closely resembles that of Ashton and his associates who reported four aneurysms in twenty-three femoral homografts (17.9 per cent). In addition, Szilagyi 1 found 13 cases of similar degenerative changes, mainly dilatation, in seventy such grafts (18.5 per cent).
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Opinions seem divided as to the fate of arterial homografts. Key and coworkers12 state that they have a higher late thrombosis rate compared with synthetic prostheses, but Whitman and his associates8 believe that the longer homografts remain patent the less chance there is of late thrombosis. In these 4 cases the grafts had remained patent from a minimum of 39 to a maximum of 49 months before operation for the aneurysm was undertaken. In Case 1, the aneurysm was noted 33 months after the graft was inserted, but in the others they were only noticed 41, 45, and 48 months after grafting. In the case in which the aneurysm was observed early, urgent admission to the hospital was eventually required, as the aneurysm enlarged rapidly and it was thought that it might burst. Rupture of homograft aneurysms has most frequently been reported in aortic homografts (Barnes and colleagues13) but is obviously a possibility should it develop in femoro-popliteal grafts. However, treatment in these is likely to be undertaken sooner, because of their more superficial posi tion. The possibility of sudden thrombosis, which may necessitate amputation, as occurred in Case 3 and subsequently in Case 1, is another reason why these aneurysms should be treated as soon as possible after they are diagnosed. This may be an argument for performing follow-up angiograms on grafted patients, particularly when the graft has remained patent for a long time. The cases reported here also suggest possible lines of treatment. In only one case (Case 1) was excision of the aneurysmal sac with suture of the related remaining graft wall possible. Cases 2 and 4 required excision of a length of the graft, with replacement by autogenous saphenous vein, while in Case 3 a Teflon bypass was used but was unsuccessful, probably because of a poor distal run off. Although 2 of these 4 patients did well initially with preservation of at least part of the homograft, the state of the vessel wall, as noted histologically, suggests that it is probably better to replace completely the homograft once degenerative changes have occurred anywhere within its length. This argument is further reinforced by the eventual outcome in Case 1, in whom the graft became more aneurysmal and subsequently thrombosed. SUMMARY
In a series of 22 arterial homografts used as femoral bypasses, aneurysm formation occurred in 4 cases. This was a late complication and occurred up to 4 years after insertion of the graft. The incidence of this complication (about 18 per cent) is almost identical with that reported in other series. Treatment was by local repair of the graft wall in one case, excision of the portion of the graft bearing the aneurysm with autogenous saphenous vein re placement of the excised segment in two instances, and excision of the aneurysm with bypass of the whole graft with use of a Teflon prosthesis in the fourth case. Two grafts functioned normally at first after operations for aneurysm development. One patient required amputation after an unsuccessful attempt to restore blood flow to the leg following thrombosis of the graft. An amputation was performed at a later date on one patient in whom the graft had thrombosed 21 months after operation for the original aneurysm. The fourth patient had
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more severe claudication following operation but has, at present, an adequate foot circulation. Degenerative changes occurring in the homograft are the most likely cause of aneurysm formation but, in spite of careful preparation of the graft, local factors in the graft wall cannot be excluded. I am grateful to Professor B. S. Pilcher for allowing me to report these cases and for his help in the preparation of this paper. REFERENCES 1. Szilagyi, D. E., McDonald, E. T., Smith, E. F., and Whitcomb, J . G.: Biologic F a t e of Human Arterial Homografts, A. M. A. Arch. Surg. 75: 506, 1957. 2. Nyhus, L. M., Kanar, E. A., Moore, H. G., Schmitz, E. J., Zeek, E. K., Sauvage, L. E., and Harkins, H. N. : Experimental Vascular Grafts. IV. Arterial Homograft De generation, Am. Surgeon 2 1 : 289, 1955. 3. DeWeese, J . A., Woods, W. D., and Dale, W. A . : Failures of Homografts as Arterial Eeplacements, Surgery 46: 565, 1959. 4. Crawford, E. S., De Bakey, M. E., and Cooley, D. A. : Surgical Considerations of Peripheral Arterial Aneurysms, A. M. A. Arch. Surg. 78: 226, 1959. 5. Humphries, A. W., Hawk, W. A., de Wolfe, V. G., and Le Fevre, F . A.: Chemicopathological Observations on the F a t e of Freeze-Dried Arterial Homografts, Surgery 45: 59, 1959. 6. Crawford, E. S., De Bakey, M. E., Morris, G. C , Jr., and Garrett, E . : Evaluation of Late Failures After Eeconstructive Operations for Occlusive Lesions of the Aorta and Iliac, Femoral, and Popliteal Arteries, Surgery 47: 79, 1960. 7. Linton, E . E. (1961) : In discussion on Phillips. C. E., DeWeese, J . A., and Campeti, F . L . : Comparison of Arterial Grafts, A. M. A. Arch. Surg. 82: 38, 1961. 8. Whitman, E. J., Janes, J . M., Ivins, J . C , and Johnson, E. W., J r . : Femoral Bypass Grafts, Surgery 47: 29, 1960. 9. Tibbs, D. J . : Arterial Eeplacement and Eeconstruction. A Five Year Study, Lancet 2: 1313, 1960. 10. Ashton, F., Slaney, G., and Eains, A. G. H. : Femoro-Popliteal Arterial Obstructions. Late Eesults of Teflon Prostheses and Arterial Homografts, Brit. M. J . 2 : 1149, 1962. 11. Taylor, G. W. : Arterial Grafting for Gangrene, Ann. Eoy. Coll. Surgeons, England, 3 1 : 168, 1962. 12. Key, J . A., Bigelow, W. G., and Farber, E. P . : An Assessment of the Value of Arterial Grafting, Surgery 47: 74, 1960. 13. Barnes, W. H., Ellis, F . H., Kirklin, J . W., and Edwards, J . E . : Experiences With 165 Aortic Homografts, Surg., Gynec. & Obst. 106: 49, 1958.
HOMOGRAFTS
Report of Four Cases of Femoral Aneurysm /. L. Provan, B.Sc, M.B. (Lond.),
F.R.C.S. (Eng.), London,
England
I
N the early days of reconstructive arterial surgery, before synthetic grafts were available, arterial homografts were widely used as vessel replacements or as bypasses. They gave initially good results and were easy to work with, but their disadvantages, particularly the difficulties of preparation and reconstitution and the shortage of supply, led some to abandon their use in favor of synthetic tubes, made of Dacron or Teflon, or vein autografts. It is now recognized, in addition, that degenerative changes occur in homografts, but aneurysm as a late complication of homografts used for bypassing superficial femoral artery occlusions has not been widely reported, especially in England. This paper describes four such aneurysms treated by the Surgical Unit at this hospital since 1961. CASE REPORTS CASE 1.—Male. No. AG.7513. The patient was admitted to the University College Hos pital in February, 1958, at the age of 61, with intermittent claudication in the calf of the right leg of 6 months' duration. He was able to walk about 300 yards. On examination, he was hypertensive (blood pressure, 160/100 mm. H g ) ; the right foot was colder than the left but there were no trophic changes. No pulses were palpable in this leg below the femoral artery. The left leg was normal. An arteriogram showed a complete block of the right super ficial femoral artery, which extended up the thigh for about 10 inches from the adductor hiatus. At operation on March 3, 1958, a frozen homograft was inserted as a bypass between the common femoral and popliteal arteries. An anticoagulant, Dindevan, was administered from the fourth postoperative day, and, when the patient was discharged, the right foot was warm and the dorsalis pedis and posterior tibial pulses were both palpable. He was re-admitted in May, 1959, for surgical treatment of a carcinoma of the floor of the mouth, but remained well as far as his feet were concerned, until an aneurysmal bulge, 1 cm. in diameter, in the upper end of the homograft was noted in December, 1960, 33 months after the original operation. This was observed until August, 1961, when it had increased rapidly in size, measuring 4 cm. in diameter. The overlying skin was thinned and noticeably blue in color. Both feet were warm and pink and all the peripheral pulses were palpable. He had had no claudication since the 1958 operation. An operation was performed on Sept. 15, 1961. The aneurysm was found to involve only the more anterior part of the graft, the rest of the graft being apparently normal. The sac was excised and the defect in the graft wall was closed by direct suture without Prom the Surgical Unit, University College Hospital, London, England. Received for publication Jan. 15, 1964. 282
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interference with the lumen of the graft. Anticoagulants, which had been stopped before the operation, were re-started afterward. He remained well, with all pedal pulses palpable and no pain on walking. However, when he was seen in April, 1963, the graft was noted to be diffusely aneurysmal and appeared as a pulsating mass in the muscles of the medial side of the thigh. Sudden thrombosis of the graft occurred in June, 1963, 63 months after its insertion. I n spite of heparinization and sympathectomy he developed severe rest pain and a mid-thigh ampu tation was performed in September, 1963. CASE 2.—Male. No. AG.4419. This man was admitted to the University College Hos pital in October, 1957, at the age of 57, for treatment of a tuberculous cavity in the upper lobe of the left lung. At that time he complained of pain in the calves of both legs on walking since 1951 ; this had been associated with recurrent ulcération around the right lateral malleolus for a year. The pain had become progressively more severe, so that on admission he could only walk about 50 yards, being limited mainly by the right leg. The tuberculosis responded well to drug therapy and he was transferred to the Surgical Unit in March, 1958. No pulses were palpable below the femoral artery in either leg. There was an ulcer above the right lateral malleolus, with scars of healed ulcers on the dorsum of each foot. No arteriogram was done as it was decided that the right popliteal artery should be explored to see if bypass grafting was possible. Operation was performed on March 31, 1958, at which time a 29-day-old frozen arterial homograft was inserted between the common femoral artery and the lowest part of the popliteal artery. The patient was given Dindevan from the fourth postoperative day and remained well, pain-free on walking, with palpable right popliteal and pedal pulses. How ever, the left calf began to trouble him more and he was re-admitted in October, 1959, for a similar bypass procedure to the left leg, although on this occasion a knitted Dacro"n prosthesis was used. The condition of the right leg remained unchanged until he was once again admitted to the University College Hospital in October, 1961, 43 months after insertion of the first graft, after having noticed a lump in the right groin for 2 months. On examination, there was a pulsating tumor, 3 cm. in diameter, situated halfway down the femoral triangle of the right thigh. The right foot was warm and peripheral pulses were palpable. At operation on Oct. 6, 1961, a fusiform aneurysm, involving almost the whole circum ference of the upper end of the graft was found. This was excised with a portion of normal homograft on either side and the gap was bridged with a length of saphenous vein from the same thigh. An end-to-side anastomosis was performed at the upper end and an end-to-end at the lower end. He has been regularly followed up since then and the pulses and condition of the right foot have remained unchanged since the original operation in 1958 and he is still pain-free on walking. CASE 3.—Male No. 10527. The patient was admitted to the University College Hospital in February, 1958, at the age of 57. He had developed left calf claudication in 1956 which followed a laminectomy for a lumbar disc protrusion. The claudication became severe and on admission he could walk about 25 yards only. On examination, the blood pressure was 130/90 mm. Hg. No pulses could be felt in the left leg below the femoral artery. The right leg was normal. An arteriogram showed complete occlusion of the superficial femoral artery below the origin of the profunda femoris. On March 10, 1958, an eight-day-old frozen homograft was inserted between the com mon femoral and popliteal arteries. He was given Dindevan from the fifth postoperative day and on discharge the pedal pulses were both palpable in the left foot. He remained relatively pain-free after this but in December, 1961, 45 months after insertion of the graft, he was found to have a pulsating swelling, 6 by 2.5 cm., in the upper medial aspect of the left thigh. The left foot pulses were palpable a t this time and his name was noted for urgent admission. However, 2 days later, he was admitted as an emer gency case, having developed sudden severe pain in the left leg and foot, which had gone white
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in color. On examination that day, there was no pulsation in the aneurysm, no pulses were palpable below the left femoral, and the left leg was white and cold, with no sensation in its lower two thirds. At operation early on Dec. 9, 1961, the femoral and popliteal arteries were exposed, the graft cut away at its upper end, and a woven Teflon prosthesis was inserted from the common femoral to the popliteal artery through a tunnel made with difficulty alongside the previous graft. There was negligible back bleed from the distal popliteal artery before insertion of the graft and a long clot was removed from it prior to the anastomosis. At the conclusion of the operation the popliteal artery pulsated vigorously, but no pedal pulses were felt and a mid-thigh amputation had to be performed 2 days later, when it was obvious that the limb was not going to survive. CASE 4.—Male. No. A E . 1512. This patient was admitted to the University College Hospital in February, 1957, at the age of 61. Intermittent claudication in the left leg had been first noticed in 1949. This was present after walking 200 to 300 yards in 1952, at which time a left lumbar sympathectomy was performed at another hospital. The leg felt warmer after this, but the claudication was not improved. A tenotomy of the left Achilles tendon was done in 1953, with some relief of calf pain, but in the same year he noticed pain in the right calf which, at the time of admission to the hospital, occurred after walking 80 to 100 yards. On examination at that time the blood pressure was 180/90 mm. Hg. A femoral pulse was the only one palpable in the right leg. No pulses, including the femoral, were present in the left leg. An arteriogram showed complete occlusion of the left common iliae artery from its origin from the aorta, with a complete block of the right superficial femoral artery in its lower part. There was extensive atheroma of the right common iliae artery. Operation on Aug. 1, 1957, included endarterectomy of the right common iliac artery and bypass graft from the aorta to the left femoral, with a freeze-dried homograft. His recovery after this was uneventful; the femoral popliteal, dorsalis pedis, and anastomotica magna pulses were palpable in the left leg and peroneal and weak femoral pulses in the right. He was re-admitted in January, 1958, when pulses were absent in the right leg, al though nutrition was good. A right femoro-popliteal bypass was performed on J a n . 13, 1958, with a frozen homograft. After this, popliteal and pedal pulses were present in that leg. He was given Dindevan after each operation and maintained on this as an out-patient. He remained well, with all pulses palpable in both legs, although since June, 1958, he had noticed pain in the right calf on walking uphill fast and said that the right foot felt cooler than the left. He was admitted to the University College Hospital again in February, 1962, 49 months after the second graft, after having noticed a pulsating swelling in the right thigh, which had been getting larger, for 3 weeks. On examination, there was a pulsating swelling, 3 inches in diameter, situated on the medial side of the right thigh, 3 % inches below the inguinal ligament in the line of the femoral artery. The right foot was cooler than the left; the right pedal pulses were palpable. Operation was performed on Feb. 22, 1962. There was aneurysmal dilatation of the homograft within the substance of the adductor longus and magnus muscles. I t was ex cised, with the upper and lower parts of the homograft left in position, and the continuity between these was restored with a saphenous vein graft from the same thigh. An end-to-end anastomosis was used at each end. Following this operation, weak pedal pulses have been only intermittently felt and the right foot is still cool. The nutrition and venous filling are good, however, but the patient now has claudication after activities such as lawn-mowing. Slow walking on the flat does not trouble him.
PREPARATION OF HOMOGRAFTS
The grafts in which these aneurysms developed were obtained from adults of up to 35 years of age, who had died suddenly as the result of injury, while
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in good health. Each graft was excised from the cadaver with aseptic technique within 8 hours of death. Bacteriological swabs taken from the bed of each artery were sterile after 48 hours; the policy was to discard grafts if the bed cultures grew pathogens. Immediately after removal from the body, the graft was put into sterile normal saline containing 1,000,000 units of crystalline penicillin and 1 gram of streptomycin. Further preparation of the graft was done in the operating theater where adherent fat and connective tissue were removed, de fects were repaired with fine silk, and branches ligated with silk. The graft was then kept in the penicillin-streptomycin solution for 24 hours at 4° C. The fluid was then decanted and the graft in its container was snap frozen by immersion in a mixture of solid carbon dioxide and acetone. The frozen graft was stored at -30° C. until required. Reconstitution was effected at the time of operation by placing the frozen artery in normal saline at room tem perature. It was then tested by injecting saline solution under pressure and leaks were repaired with silk sutures or ligatures. HISTOLOGY
The segments of grafts removed at the. operations for aneurysms were examined histologically and the changes were similar to those noted in the extensive account by Szilagyi and associates1 in 1957. In all 4 cases, the muscular tissue of the media had been replaced by dense fibrous tissue and, as in the older grafts described by Szilagyi, there was fragmentation of the elastic lami nae. However, in Cases 1 and 2, in whom grafts had been inserted for 33 and 43 months, respectively, when the aneurysm was excised, the elastic layers were very sparse indeed and in Case 2 the elastic was present mainly in the outer layers of the graft Avail. These 2 cases were also different from Cases 3 and 4 in that the fibrous tissue comprising the wall had a fairly marked collection of inflammatory cells, mainly eosinophils and neutrophils. Plasma cells, however, were not present. (In Cases 3 and 4 the wall of fibrous tissue was almost acellular). These changes are compatible with an antibody response against the graft by the host. There remains a tube of fibrous tissue, containing a minimal amount of elastic tissue, to carry the blood. This fibrous tissue has little active power to resist the pressure of blood within it, so that dilatation of the graft may eventu ally occur. However, this sequence of events would be expected to lead to diffuse dilatation, as in Case 4, rather than a localized aneurysm. This is discussed later. DISCUSSION
The fact that arterial homografts degenerate with time has been known for some years and the histological changes occurring in the graft wall are well documented (Nyhus 2 [1955] and Szilagyi 1 [1957] and their associates). Szilagyi and co-workers, in a survey of a large series of homografts used as aortic, iliac, or femoral replacements or bypasses, pointed out that there was a much greater tendency for the femoral grafts to fail. They related this partly to the inability of reconstructive arterial surgery to deal with the inevitable progress of the primary disease process in the distal parts of the host vascular tree, but also
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suggested that, as femoral homografts possessed more muscular walls than aortic ones, they might be expected to exert more antigenic activity and hence degenerate more quickly than their aortic counterparts, which are mainly elastic. However, although they had only one femoral aneurysm out of seventy homografts submitted for study, dilatation and tortuosity were much more marked. Twelve out of seventy homografts showed the latter changes, which were not present in any of their aortic or iliac grafts, although these did show four aneurysms. DeWeese and colleagues,3 in 1959, surveying the literature up to that time, recorded thirteen aneurysms of which only four were in femoral grafts. Two of these had thrombosed a year after insertion of the graft and the oldest graft, in the abdominal aorta, was only 3 years old when the aneurysm presented. Since then, Crawford and co-workers4 reported seven homograft aneurysms out of ninety-eight homografts and Humphries and his colleagues5 found six aneurysms in autopsies on 33 patients who had had arterial homografts of various types, of which at least two were femoral aneurysms. Aneurysm for mation or dilatation has also been noted by Crawford and associates6 and Linton, 7 while Whitman and co-workers8 and Tibbs,9 in accounts of homograft complications mentioning aneurysm formation, state that they had given up the use of homografts in favor of synthetic prostheses, presumably partly because of degeneration in homografts. More recently, Ashton and collaborators 10 have recorded aneurysm formation in four out of twenty-three femoral arterial homografts and Taylor 11 reported four aneurysms in twenty-two similar grafts. The 4 cases reported here are of interest for several reasons, but mainly because the aneurysms developed a long time after insertion of the homografts. In each case these had been functioning perfectly for over 3 years before reoperation was required. Also of interest is the fact that in 3 of the 4 cases the aneurysm was localized in its extent. Degenerative changes such as are known to occur in arterial homografts might be expected to lead to generalized dilata tion of the grafts, but this only occurred as the presenting symptom in Case 4. Case 1 developed this 21 months after a localized aneurysm was first operated upon, when the remainder of the graft had been noted to be grossly normal. The localization of three of the aneurysms suggests the possibility of a failure during preparation of the graft, such as injury at the time or failure to ligate a side branch flush with the wall of the main artery. Disease of the donor artery itself is another possibility and in this respect it is interesting that two of the homografts used (Cases 2 and 3) came from the same donor, a female of 34. There is, however, no record of any of the grafts being in any way abnormal. All four homografts were inserted in the short period between Jan. 13, 1958, and March 31, 1958, and they form part of a small series of twenty-two femoral homografts used between November, 1956, and February, 1959. The incidence of aneurysm formation in this series (4 of 22, or 18.2 per cent) is identical with that mentioned by Taylor 11 and very closely resembles that of Ashton and his associates who reported four aneurysms in twenty-three femoral homografts (17.9 per cent). In addition, Szilagyi 1 found 13 cases of similar degenerative changes, mainly dilatation, in seventy such grafts (18.5 per cent).
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Opinions seem divided as to the fate of arterial homografts. Key and coworkers12 state that they have a higher late thrombosis rate compared with synthetic prostheses, but Whitman and his associates8 believe that the longer homografts remain patent the less chance there is of late thrombosis. In these 4 cases the grafts had remained patent from a minimum of 39 to a maximum of 49 months before operation for the aneurysm was undertaken. In Case 1, the aneurysm was noted 33 months after the graft was inserted, but in the others they were only noticed 41, 45, and 48 months after grafting. In the case in which the aneurysm was observed early, urgent admission to the hospital was eventually required, as the aneurysm enlarged rapidly and it was thought that it might burst. Rupture of homograft aneurysms has most frequently been reported in aortic homografts (Barnes and colleagues13) but is obviously a possibility should it develop in femoro-popliteal grafts. However, treatment in these is likely to be undertaken sooner, because of their more superficial posi tion. The possibility of sudden thrombosis, which may necessitate amputation, as occurred in Case 3 and subsequently in Case 1, is another reason why these aneurysms should be treated as soon as possible after they are diagnosed. This may be an argument for performing follow-up angiograms on grafted patients, particularly when the graft has remained patent for a long time. The cases reported here also suggest possible lines of treatment. In only one case (Case 1) was excision of the aneurysmal sac with suture of the related remaining graft wall possible. Cases 2 and 4 required excision of a length of the graft, with replacement by autogenous saphenous vein, while in Case 3 a Teflon bypass was used but was unsuccessful, probably because of a poor distal run off. Although 2 of these 4 patients did well initially with preservation of at least part of the homograft, the state of the vessel wall, as noted histologically, suggests that it is probably better to replace completely the homograft once degenerative changes have occurred anywhere within its length. This argument is further reinforced by the eventual outcome in Case 1, in whom the graft became more aneurysmal and subsequently thrombosed. SUMMARY
In a series of 22 arterial homografts used as femoral bypasses, aneurysm formation occurred in 4 cases. This was a late complication and occurred up to 4 years after insertion of the graft. The incidence of this complication (about 18 per cent) is almost identical with that reported in other series. Treatment was by local repair of the graft wall in one case, excision of the portion of the graft bearing the aneurysm with autogenous saphenous vein re placement of the excised segment in two instances, and excision of the aneurysm with bypass of the whole graft with use of a Teflon prosthesis in the fourth case. Two grafts functioned normally at first after operations for aneurysm development. One patient required amputation after an unsuccessful attempt to restore blood flow to the leg following thrombosis of the graft. An amputation was performed at a later date on one patient in whom the graft had thrombosed 21 months after operation for the original aneurysm. The fourth patient had
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more severe claudication following operation but has, at present, an adequate foot circulation. Degenerative changes occurring in the homograft are the most likely cause of aneurysm formation but, in spite of careful preparation of the graft, local factors in the graft wall cannot be excluded. I am grateful to Professor B. S. Pilcher for allowing me to report these cases and for his help in the preparation of this paper. REFERENCES 1. Szilagyi, D. E., McDonald, E. T., Smith, E. F., and Whitcomb, J . G.: Biologic F a t e of Human Arterial Homografts, A. M. A. Arch. Surg. 75: 506, 1957. 2. Nyhus, L. M., Kanar, E. A., Moore, H. G., Schmitz, E. J., Zeek, E. K., Sauvage, L. E., and Harkins, H. N. : Experimental Vascular Grafts. IV. Arterial Homograft De generation, Am. Surgeon 2 1 : 289, 1955. 3. DeWeese, J . A., Woods, W. D., and Dale, W. A . : Failures of Homografts as Arterial Eeplacements, Surgery 46: 565, 1959. 4. Crawford, E. S., De Bakey, M. E., and Cooley, D. A. : Surgical Considerations of Peripheral Arterial Aneurysms, A. M. A. Arch. Surg. 78: 226, 1959. 5. Humphries, A. W., Hawk, W. A., de Wolfe, V. G., and Le Fevre, F . A.: Chemicopathological Observations on the F a t e of Freeze-Dried Arterial Homografts, Surgery 45: 59, 1959. 6. Crawford, E. S., De Bakey, M. E., Morris, G. C , Jr., and Garrett, E . : Evaluation of Late Failures After Eeconstructive Operations for Occlusive Lesions of the Aorta and Iliac, Femoral, and Popliteal Arteries, Surgery 47: 79, 1960. 7. Linton, E . E. (1961) : In discussion on Phillips. C. E., DeWeese, J . A., and Campeti, F . L . : Comparison of Arterial Grafts, A. M. A. Arch. Surg. 82: 38, 1961. 8. Whitman, E. J., Janes, J . M., Ivins, J . C , and Johnson, E. W., J r . : Femoral Bypass Grafts, Surgery 47: 29, 1960. 9. Tibbs, D. J . : Arterial Eeplacement and Eeconstruction. A Five Year Study, Lancet 2: 1313, 1960. 10. Ashton, F., Slaney, G., and Eains, A. G. H. : Femoro-Popliteal Arterial Obstructions. Late Eesults of Teflon Prostheses and Arterial Homografts, Brit. M. J . 2 : 1149, 1962. 11. Taylor, G. W. : Arterial Grafting for Gangrene, Ann. Eoy. Coll. Surgeons, England, 3 1 : 168, 1962. 12. Key, J . A., Bigelow, W. G., and Farber, E. P . : An Assessment of the Value of Arterial Grafting, Surgery 47: 74, 1960. 13. Barnes, W. H., Ellis, F . H., Kirklin, J . W., and Edwards, J . E . : Experiences With 165 Aortic Homografts, Surg., Gynec. & Obst. 106: 49, 1958.