Development of endovascular stent-grafts.

The very first experiences in the early 1990s with endovascular aortic stent-grafts were associated with significant numbers of complications including an inability to deploy the stent-graft, conversion to open surgery, and aneurysm rupture. By the mid-1990s, improved home-made and commercially available stent-grafts started to appear. These devices could be successfully deployed in the aorta, achieving aneurysm exclusion with low morbidity and mortality. However, follow-up results raised concerns about the longer-term durability. Gradually, too, these problems have been addressed such that, in the recent UK multi-centre randomized controlled trial of endovascular versus open aneurysm repair, aneurysm-related mortality was 3 per cent less in the endovascular group four years following surgery. Currently the indications for aortic stent-grafts are being expanded. It is now possible to maintain perfusion successfully in aortic side branches and to treat aneurysms that would have once been thought untreatable. This review paper reviews the main developments in endovascular stent-grafting and the major role played by medical engineering and technology.

The systemic fibrinolytic effect of BRL 26921 during the treatment of acute peripheral arterial occlusions.

BRL 26921 is a new acylated streptokinase-plasminogen complex which may have a more specific local thrombolytic effect than streptokinase or urokinase. 34 patients with acute peripheral arterial occlusions were given eight hourly bolus injections of 5 mg BRL 26921 for up to 72 h. Systemic fibrinolysis was observed in all patients yet in only 24% was the occluding thrombus lysed. 44% of the patients had haemorrhagic complications and 24% suffered further thrombotic events during or soon after treatment. There was no correlation between the degree of systemic fibrinolysis produced and dissolution of the thrombi. The degree of systemic fibrinolysis did not affect the complication rate. There is no evidence from this study that BRL 26921 has a specific local thrombolytic effect.

Fibrinolytic profiles in local low-dose thrombolysis with streptokinase and recombinant tissue plasminogen activator.

Fibrinolytic parameters have been monitored in 44 patients undergoing local low-dose intra-arterial thrombolysis for acute peripheral arterial ischaemia. Streptokinase (Sk), at a dose of 5,000 units/hr with 250 units/hr heparin, was used in 23 patients and recombinant tissue plasminogen activator (r-tPA) at a dose of 0.5 mg/hr was used in 21 patients. Successful lysis was seen in 18 (86%) patients following r-tPA and in 15 (65%) patients following streptokinase. There were 4 minor haematomas in each group usually at the catheter entry site. Both agents produced a systemic effect, which was still seen 12 hours post-infusion. However, that produced by r-tPA was delayed and significantly reduced compared to that produced by Sk. These results confirm the relative fibrin specificity of r-tPA. When used as a continuous low-dose intra-arterial infusion, r-tPA offers a significantly lower, potentially safer, systemic effect than conventional therapy with streptokinase.

A study of the use of the thromboxane A2 antagonist, sulotroban, in combination with streptokinase for local thrombolysis in patients with recent peripheral arterial occlusions: clinical effects, platelet function and fibrinolytic parameters.

In peripheral thrombolysis adjuvant anti-platelet therapy may help to lyse otherwise resistant thrombus, thereby increasing the number of patients successfully treated and reducing the "time to lysis". If continued after lysis it may help to prevent early rethrombosis. In this pilot study 21 patients undergoing peripheral thrombolysis with streptokinase were randomised to receive the thromboxane receptor antagonist sulotroban or placebo. The dose of sulotroban given was 2 mg/min (four patients), 4 mg/min (five patients) or 8 mg/min (four patients), eight patients received placebo. The clinical and laboratory effects of the treatment were monitored. Thrombolysis was achieved more quickly in patients receiving sulotroban, however, there was no difference between groups in the number of patients in whom recanalisation was achieved (six of eight receiving placebo and eight of 13 receiving sulotroban) or in the number of cases of early rethrombosis. During lysis there was an increase in plasma beta-thromboglobulin with similar levels being found in patients receiving sulotroban and streptokinase and those receiving streptokinase alone. No other major changes in platelet function during lysis were seen in patients receiving streptokinase alone. Sulotroban significantly reduced platelet aggregation and 14C-5HT release in response to several platelet agonists. With the thromboxane mimetic U46619 the degree of inhibition of aggregation and 14C-5HT release depended on the dose of sulotroban used. High levels of inhibition were associated with an excess of haemorrhagic complications especially in combination with a low plasma fibrinogen level. We conclude that the use of low dose sulotroban in combination with streptokinase merits further study and may hve a role in accelerating lysis.(ABSTRACT TRUNCATED AT 250 WORDS)

A bacteriological survey of amputation wound sepsis.

A retrospective survey of 100 lower limb amputations performed for ischaemia were analysed to assess the influence of preoperative bacterial isolates and the use of prophylactic antibiotics on wound sepsis. Forty-eight per cent had previously undergone a vascular procedure to attempt limb salvage and 17% were diabetics. Benzylpenicillin was given preoperatively and continued for 5 days; diabetics received metronidazole in addition. A total of 51 isolates were obtained from 30 patients preoperatively; Staphylococcus aureus and Enterobacteriaceae each accounted for over 25%. Postoperatively, 74 isolates (20 multiple) were obtained with an overall sepsis rate of 40%. Those patients with a positive preoperative culture were significantly more likely to develop wound sepsis. There was no significant difference in wound sepsis rates for diabetics. In view of the range of organisms causing postoperative infection, we recommend prophylaxis with a broad spectrum antibiotic for amputations.

ADP-induced P-selectin expression on platelets as a predictor of successful thrombolysis.

Unlike coronary thrombolysis, the role of platelet activity in the outcome of local thrombolytic therapy for peripheral ischaemia is not well understood. In the present study ten patients undergoing local pulse spray thrombolysis (PST) with recombinant tissue-type plasminogen activator (rt-PA), six patients undergoing conventional infusion thrombolysis (CT) with rt-PA and another six patients undergoing arteriography with iopamidol were studied. Venous blood samples obtained before and after the procedure were analysed using a flow cytometric technique for detection of platelet activation after labelling platelets with VH10, a monoclonal antibody against P-selectin. In the present study no significant differences were observed in P-selectin expression before and after any of the procedures, except that P-selectin expression following ADP stimulation was reduced in patients who had received conventional thrombolysis. Unexpectedly, we observed relatively greater P-selectin expression, particularly after ADP stimulation, both before and following thrombolysis in ten patients in whom thrombolysis was successful compared with six patients in whom thrombolysis was unsuccessful. ADP-induced P-selectin expression on platelets may therefore be a useful predictor of outcome of peripheral intra-arterial thrombolysis.

Lymphoscintigraphy and colour Doppler sonography in the assessment of leg oedema of unknown cause.

Oedema of the lower limbs may be associated with a number of factors, most commonly a lymphatic or venous abnormality. Generally effective treatment options are only available with venous disorders. The aim of this study is to show that a combination of duplex Doppler sonography and lymphoscintigraphy in patients with limb oedema will help to determine the aetiology and thus identify patients for whom treatment is appropriate. 32 patients presenting with unexplained oedema involving the lower limb have been studied. Each patient underwent Doppler sonography followed by lymphoscintigraphy. In 16 patients the lymphoscintigraphy was abnormal, showing absent or poorly visualized lymphatics. The Doppler study was abnormal in 17 patients, nine of whom went on to receive definitive surgical treatment. In five patients both studies were abnormal and there were six cases where both investigations were normal. It is concluded that in the great majority of referrals (82%), the combination of lymphoscintigraphy and Doppler ultrasound is a satisfactory means of assessment of patients with unexplained limb oedema.

111In platelet deposition following peripheral arterial thrombolysis.

Streptokinase (Sk) and recombinant tissue plasminogen activator (rt-PA) have widely different effects on platelet aggregation. We have therefore undertaken a prospective evaluation of the deposition of indium-111 platelets following peripheral arterial thrombolysis. Seventeen patients were studied using autologous indium-111 labelled platelets. Patients were randomly allocated to receive 0.5 mg h-1 intra-arterial rt-PA (ten patients), or 5000 units h-1 Sk and 250 units h-1 heparin intra-arterially (seven patients). Initial uptake ratios (comparing affected limb to contra-lateral limb) at 24 h were usually low for both agents (medians: Sk 1.17; rt-PA 1.20) despite previous angioplasty or extensive thrombosis. There were minimally higher uptake ratios at 48 h and 72 h following Sk (1.64-1.45), than with intra-arterial rt-PA (0.93-1.43). Overall, two patients (one from each group) failed to achieve complete lysis or incurred early rethrombosis. Both were associated with a progressive increase in uptake ratio which was not present in those patients with successful initial lysis and continued patency at 30 days (1.18-0.94-1.19). We have been unable to demonstrate any significant difference in post-lysis platelet deposition between intra-arterial streptokinase and recombinant tissue plasminogen activator in this preliminary study. However, higher platelet deposition was associated with failure to achieve complete lysis and early rethrombosis. Concurrent therapy with antiplatelet agents may therefore be indicated in these patients.

A comparison between visual and quantitative analysis in a prospective evaluation of labelled 111In leucocyte imaging in vascular infection.

In a continuing evaluation of 111In-oxine labelled leucocyte imaging in vascular surgery, we have studied 16 patients with a clinical diagnosis of possible vascular graft infection. We have evaluated both visual and semi-quantitative analysis of the images obtained and have interpreted these in the light of the subsequent clinical outcome. Full length or multifocal uptake was seen in six patients, all of whom eventually required graft excision with two limbs surviving, and one death. These patients had a significantly higher uptake ratio (median = 3.26) than those with either localized (median = 1.12; p = 0.0027) or negative images (median = 0.72; p = 0.0003). Of four patients showing localized uptake only, one required amputation for continuing sepsis. Six patients had negative images, and had normal DSA and CT scans. Uptake ratios could not distinguish between those with localized images and those with negative images. Computer generated vertical profiles aided separation of patients with presumed localized and negative images. Semi-quantitative analysis has proved to be a reliable method which should allow a more direct comparison of the efficacy of various investigative techniques and of the results of therapy, independent of intra-observer subjective bias.

Current concepts and controversies in endovascular repair of abdominal aortic aneurysms.

Endovascular aneurysm repair (EVAR) has rapidly expanded since its introduction in the early 1990s. Early experiences were understandably associated with relatively high rates of complications including conversion to open repair. Soon, perioperative morbidity and mortality results improved but these concerns were replaced by questions over the long-term effectiveness of the endovascular method highlighted by the increasing numbers of secondary interventions and even reports of aneurysm rupture. A better understanding of the behaviour of stent-grafts in the aorta and the response of aortic aneurysms to endovascular repair has been forged by observations both in vitro and in vivo. It was only relatively recently that terms such as migration and endoleak were coined. Only now that we are beginning to fully understand the causes and consequences of such problems can further developments be made. The following paper outlines some of the concepts and discusses the controversies and challenges facing clinicians involved in endovascular aneurysm surgery today.

Early results of a flexible bifurcated endovascular stent-graft (Aorfix).

AIM: First generation stent-grafts were associated with low applicability, high conversion rates due to technical failure and low durability. Second generation stent-grafts need to address these problems in order to secure endovascular aneurysm repair (EVAR) as a viable option to open repair in patients with abdominal aortic aneurysms (AAA). The early results of a second-generation stent-graft (Aorfix) for the treatment of AAA are reported. METHODS: A European multi-centre study of the Aorfix bifurcated endovascular stent-graft was performed. The Aorfix stent-grafts were inserted according to a predefined clinical protocol in 4 centres experienced in EVAR and all data was collected prospectively on a central database. RESULTS: A total of 24 patients underwent attempted aneurysm repair with the Aorfix stent-graft. There were no conversions to open repair. One technical failure resulted in insertion of another stent-graft. At 30-day follow-up there had been no secondary endovascular or open interventions. There were only 2 endoleaks, both of which were type II. CONCLUSIONS: Aorfix currently offers early results, which are at least as good as other second-generation stent-grafts. It has given satisfactory results with highly angulated proximal necks and may improve the treatment outlook for these patients. Whether the unique design features increase durability and reduce long-term complications remains to be seen.

Resting plasma fibrinolytic activity and fibrinolytic potential in peripheral vascular disease.

Reduced plasma fibrinolytic activity may be a risk factor in venous and arterial thrombotic disease. Resting plasma fibrinolytic activity and fibrinolytic potential after ten minutes of venous occlusion were compared in 100 patients with peripheral vascular disease of varying severity and 20 age-sex matched controls. The fibrinolytic assay used was the euglobulin lysis time. Resting plasma fibrinolytic activity was significantly reduced in patients with a recent arterial thrombosis (p = 0.02) and ischaemic rest pain (p = 0.008) compared with controls. Fibrinolytic potential after venous occlusion was significantly reduced also in patients with a recent arterial thrombosis (p = 0.02) and ischaemic rest pain (p = 0.05) compared with controls. There were no significant differences between patients with claudication and controls. A reduced plasma fibrinolytic activity has been confirmed in patients with peripheral vascular disease and fibrinolytic potential may be a superior method of assessment as the euglobulin lysis time after venous occlusion is independent of the fibrinogen concentration. It remains uncertain whether the finding of reduced plasma fibrinolytic activity in patients with peripheral vascular disease is cause or effect and whether the finding has prognostic significance.

Tissue and serum concentrations of amoxycillin and clavulanic acid in patients having reconstructive vascular surgery.

Fifteen patients received amoxycillin/clavulanic acid combination intravenously at anaesthetic induction as part of a three-dose schedule of antibiotic prophylaxis for vascular surgery. After 30 min, the mean serum concentration of amoxycillin was 39.9 mg/l and clavulanic acid was 9.3 mg/l. Mean amoxycillin tissue concentrations in fat, 5.1 mg/l; vein, 7.5 mg/l; and artery, 4.8 mg/l, were lower than serum values. Mean clavulanic acid concentrations were: fat, 0.7 mg/l; vein, 1.2 mg/l; and artery, 1.6 mg/l. At the end of surgery, the serum amoxycillin level was always greater than 6 mg/l and clavulanic acid greater than 2 mg/l, which were both still within the therapeutic range. Concentrations in fat had declined by the end of the surgery ranging from 0.76 to 5.2 mg/l for amoxycillin and from 0.03 to 0.6 mg/l for clavulanic acid, there being almost none detected in four cases. Serum and tissue concentrations of both compounds 30 min after injection were sufficient to inhibit the growth of 97% of pathogenic organisms recovered from the skin of 135 vascular surgical patients. In a few cases tissue levels of the compounds were below inhibitory concentrations for coliforms and anaerobes at the time of skin closure, although they were still effective against most Gram-positive organisms. Amoxycillin/clavulanic acid combination is suitable antibiotic prophylaxis for vascular surgery.

Technique of in situ saphenous vein arterial bypass: can the valves help to locate the major venous tributaries?

Ten cadaveric great saphenous vein systems have been dissected to assess the relationship between the valves and the termination of venous tributaries. Such tributaries were classified on the basis of size, competence and course, and the percentage of each of four classes terminating within 1 cm of each valve site has been assessed. Above the knee, valves were more numerous, closer together, and two-thirds of competent tributaries terminated within 1 cm of them, this relationship being weaker for other classes of tributary. Below the knee, less than 50% of any class of tributary was related to valves. Reference to the position of valves is not recommended as the sole method of locating potential arteriovenous fistulae.

Endoscopic transthoracic sympathectomy: successful in hyperhidrosis but can the indications be extended?

Endoscopic transthoracic sympathectomy (ETS) has recently become established as a successful treatment for severe palmar and axillary hyperhidrosis. In this unit the indications for ETS have been broadened to include patients with Raynaud's syndrome and critical upper limb ischaemia and this paper is primarily concerned with analysing outcome in relation to the indication for operation. In all, 68 operations have been attempted in 40 patients and complete follow-up details are available on 62 treated limbs. One operation was a technical failure because of an obliterated pleural cavity. In the hyperhidrosis group (n = 28), all the affected areas showed symptomatic improvement at a median follow-up of 17 months. In the Raynaud's group (n = 30), 28 limbs (93%) were improved to some degree at the time of discharge, but at a median follow-up of 18 months only 15 limbs (50%) remained symtomatically improved to some degree. The four upper limbs treated for critical ischaemia were improved by ETS and no amputations were necessary. Significant postoperative chest pain was noted by nine patients (23%). There were three postoperative pneumothoraces, two intercostobrachial neuralgias and one transient Horner's syndrome. The cosmetic result was reported as excellent or good by 97% of patients. As with other forms of surgical thoracic sympathectomy, excellent early results are not maintained in the longer term when ETS is used to treat Raynaud's syndrome. Nevertheless, the greater simplicity and lower morbidity of the endoscopic method suggest that it can be offered to Raynaud's sufferers with greater impunity than open sympathectomies.

Silicone rubber band treatment of rectal prolapse.

Fifty-two patients with rectal prolapse have been treated by the silicone rubber band perianal suture technique and satisfactory results have been obtained in 46 (89%). Eleven patients required reoperation to achieve this result. The procedure is a minor one, with little morbidity and no mortality. Provided that faecal impaction can be avoided in patients having this operation a successful outcome, can be expected. It is recommended especially for the frail and elderly with rectal prolapse.

A review of 155 extra-anatomic bypass grafts.

Extra-anatomic bypass grafting has been used as treatment for patients with aorto-iliac disease who were considered unfit for aortic surgery. Eighty five percent of the patients had ischaemic pain at rest or skin necrosis. One hundred and three femorofemoral (FF) grafts, 40 axillounifemoral and 12 axillobifemoral grafts were performed. Femoropopliteal extension grafts were performed in 39 cases. The three year cumulative graft patency rate was 69% for FF grafts and 48% for both types of axillofemoral (AF) graft, falling to 61% for FF grafts and 32% for AF grafts at five years. The long term patient survival rate was poor, particularly for AF grafts, 27% at five years, reflecting the poor general condition of these patients. In addition almost a quarter of AF grafts required declotting at some stage. However, worthwhile limb salvage rates were obtained with both types of grafts, 69% for FF and 72% for AF at three years and 61% for FF and 65% for AF at five years, suggesting that these grafts should be employed as a means of avoiding amputation in poor risk patients.

A modified Gritti-Stokes amputation: its place in the management of peripheral vascular disease.

A modified technique for performing the Gritti-Stokes amputation is described and the results obtained in 247 cases are presented. The mortality rate was 9.3% and healing occurred in 87% of survivors. Using this modified technique the frequently cited criticisms of non-union of the patella and painful stumps were not found to be major problems. The prosthetic problems of amputation at this level are discussed in relation to recent developments in the design of artificial limbs.

Unoperated abdominal aortic aneurysm: presentation and natural history.

The natural history of abdominal aortic aneurysm (AAA) is death from rupture unless the patient dies from another cause prior to rupture. Elective aortic grafting is the treatment of choice. Following rupture, emergency operation is the only treatment which will prolong the patient's survival. Controversy still exists as to the optimum management in poor risk patients and in those with a small aneurysm. This paper describes the presentation and natural history of 65 patients presenting with a ruptured abdominal aortic aneurysm who did not have an emergency operation, and a further 27 patients in whom the diagnosis of intact AAA was made who did not have an elective aortic replacement graft. The correct diagnosis was made at the time of admission in only 43 of the 65 patients with ruptured aneurysms. The diagnostic errors and appropriate investigations in cases of doubt are discussed. The mean time from admission to hospital to death was 8 hours. The reasons for not performing an elective operation in the 27 patients known to have AAA are given. Nine have subsequently died from rupture. There have been 7 deaths from other causes.

Role of Gritti-Stokes amputation in peripheral vascular disease.

The perigenicula lower limb amputations performed for peripheral vascular disease in Nottingham between April 1987 and September 1992 were reviewed. Of the 434 amputations, 173 were below-knee amputations (BKA), 144 Gritti-Stokes amputations (GSA) and 117 above-knee amputations (AKA). The 30-day mortality was significantly greater for AKA patients than either GSA or BKA patients. There was no difference in mortality within 30 days of amputation between GSA and BKA. Re-amputation rate to a more proximal level was significantly higher in BKA compared with GSA. Mobility after prosthetic rehabilitation was assessed using the Stanmore grading. A greater number of patients achieved mobility grade III and above in the GSA and BKA groups when compared with the AKA group, but there was no significant difference between GSA and BKA groups. At follow-up, a median of 23 months after amputation, there was a tendency for more patients to have given up using their limb prosthesis in the GSA group than either the BKA or AKA groups. However, there remained no significant difference between the BKA and GSA groups in the numbers of patients who remained successfully rehabilitated to Stanmore grade III or above. When a BKA is not possible, GSA offers a better prospect for rehabilitation compared with AKA in patients with occlusive arterial disease.