Clinical study of adjuvant photodynamic therapy to reduce restenosis following femoral angioplasty.

BACKGROUND: Photodynamic therapy (PDT) reduces neointimal hyperplasia and negative remodelling following balloon injury in small and large animal models. This clinical study investigated the role of adjuvant PDT following femoral percutaneous transluminal angioplasty (PTA). METHODS: Eight PTAs in seven patients (two women) with a median age of 70 (range 59-86) years were performed with adjuvant PDT. All patients had previously undergone conventional angioplasty at the same site which resulted in symptomatic restenosis or occlusion between 2 and 6 months. Each was sensitized with oral 5-aminolaevulinic acid 60 mg/kg, 5-7 h before the procedure. Following a second femoral angioplasty, up to 50 J/cm2 red light (635 nm) was delivered to the angioplasty site via a laser fibre within the angioplasty balloon. Patients were kept in subdued light overnight and discharged the following day. Outcome was assessed by duplex imaging at 24 h, 1, 3 and 6 months and by intravenous digital subtraction angiography at 6 months. A peak systolic velocity ratio (PSVR) of more than 2.0 at the angioplasty site was taken to represent restenosis. RESULTS: All patients tolerated the procedure well without adverse complications or death. All were rendered asymptomatic which was sustained throughout the study interval. All vessels remained patent and no lesion attained the duplex definition of restenosis. Median (interquartile range) PSVR across stenotic segments was 4.7 (3.7-5.7) before angioplasty, 1.1 (0.9-1.3) at 24 h and 1.4 (1.0-1.8) at 6 months after intervention (P = 0.04 compared with preoperative value). CONCLUSION: This pilot study suggests that endovascular PDT is safe and may reduce restenosis follow- ing angioplasty. The data justify a randomized controlled trial.

Intra-arterial photodynamic therapy using 5-ALA in a swine model.

OBJECTIVES: To test the hypothesis that intravascular light could be delivered via a balloon catheter for arterial photodynamic therapy (PDT). DESIGN: Pig non-injury model. MATERIALS: Clinical catheter equipment. METHODS: Large White pigs (15-20 micrograms) were photosensitised with 5-aminolaevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) at a concentration of 120 mg/kg. Arterial biopsies were taken at intervals between 30 mins and 24 h and frozen sections analysed using a CCD camera to give a temporal profile of fluorescence in each arterial layer. PDT was given to normal arterial segments via a 4 mm transparent PTA balloon inflated so as to occlude flow, but not distend the artery. Animals were culled at 3 and 14 days and the above segments harvested. RESULTS: Fluorescence peaked in the adventitia, intima and medial layers at 1.5, 4 and 6 h respectively. PDT at all time points produced VSMC depletion compared with controls. The degree of depletion mirrored the fluorescence profile of PpIX. CONCLUSIONS: PDT can be delivered via a standard PTA balloon with a transparent channel. This depletes the VSMC population within the arterial wall without complications. Intra-arterial PDT is therefore a potential therapy to reduce the incidence of restenosis post-angioplasty.

Duplex scanning and effect of multisegmental arterial disease on its accuracy in lower limb arteries.

AIM: To assess the accuracy of duplex in assessment of peripheral arterial disease and determine the effect of multisegmental disease on the accuracy duplex as opposed to single lesion. PATIENTS AND METHODS: One hundred and seventy-seven lower limbs were examined in 90 patients who presented with lower limb arterial disease, (59 male, 31 female, median age 68 years--81 with intermittent claudication, eight rest pain, one ulceration). Patients were examined with duplex US, and arteriography (IA DSA). Two radiologists and two technologists were involved in this double-blind study. Patients were classified into five groups; groups with single stenotic lesions, single occlusions, multiple stenotic lesions or occlusions, and multiple mixed disease. Duplex accuracy was determined in each group. RESULTS: Duplex was able to differentiate between normal and disease arterial segment with a sensitivity of 92%, specificity 99%, PPV 91%, and NPV 100% and Kappa 0.87. Sixty-six limbs were found to have single lesions, and 68 multisegmental disease. Duplex showed accuracy with a sensitivity of 87%, and specificity of 99%, for single stenotic lesion and 95%, 96% respectively for multisegmental. For single occlusions duplex accuracy showed sensitivity 92% and specificity 100%, and for multisegmental occlusions, sensitivity 97%, and specificity 99%. For mixed multisegmental pathology (stenosis and occlusion), sensitivity 94% and specificity 97%. CONCLUSION: Duplex is an accurate tool in diagnosis of lower limb arterial disease and multisegmental pathology does not adversely effect this accuracy.

Comparison of duplex imaging and arteriography in the evaluation of lower limb arteries.

BACKGROUND: The aim of this study was to assess the accuracy of duplex imaging, compared with arteriography, in detecting arterial disease distal to the renal arteries. METHODS: Some 177 legs were studied in 90 patients (59 men, 31 women; median age 68 years) with peripheral arterial disease. Each patient had conventional intra-arterial angiography and duplex ultrasonography. Each leg was divided into 17 arterial segments, and the disease in each segment was quantified by measuring the peak systolic velocity ratio across any arterial lesion that was identified. RESULTS: Compared with angiography, duplex imaging was able to detect arterial disease with an overall sensitivity of 92 per cent, specificity of 99 per cent, positive predictive value 91 per cent and negative predictive value 100 per cent, and with a kappa value of 0.87 (95 per cent confidence interval (c.i.) 0.81-0.93). Duplex was able to determine the length of the arterial lesion with a sensitivity of 89 per cent and a specificity of 98 per cent with a kappa value of 0.88 (95 per cent c.i. 0.86-0.90). When the surgeon's final management decision concerning each vascular lesion was used as the reference, duplex and arteriography were equivalent, with an accuracy of 84 per cent and 85 per cent respectively in identifying the management used. CONCLUSION: Duplex ultrasonography is reliable in detecting arterial lesions in peripheral arteries and could be used routinely in the initial evaluation of patients with lower limb arterial disease.

Thrombosis and restenosis after peripheral angioplasty: does acute 111indium-platelet accumulation predict angioplasty outcome?

OBJECTIVES: Use of platelet deposition to predict failure following angioplasty. DESIGN: Prospective study of angioplasty patients in a 9 months surveillance period. MATERIALS: Thirty-eight successful angioplasty patients. METHODS: Autologous 111indium-labelled platelets were re-injected immediately after angioplasty. Gamma camera and probe measures of radioactivity were obtained daily for 2-4 days and compared to a reference site to obtain a radioactivity ratio. Patient follow up was with duplex and arteriography from day 0 to 9 months or at angioplasty failure. RESULTS: Thirty-one patients remained asymptomatic; two developed acute occlusion and five developed restenosis. Platelet accumulation (increased mean radioactivity ratio) occurred at all angioplasty sites and was significantly higher after acute occlusion (camera: 2.93 and probe: 1.93) compared to asymptomatic patients (camera: 1.25 and probe: 1.15) and restenotic patients (camera: 1.31 and probe: 1.23). Radioactivity ratio was not different in patients who later developed restenosis. CONCLUSION: 111Indium platelet radioactivity effectively detected acute angioplasty reocclusions, but was unable to predict subsequent angioplasty restenosis.

Accidental intra-arterial drug injection successfully treated with Iloprost.

A 35-year-old drug abuser inadvertently injected adulterated heroin into her left femoral artery and presented with critical ischaemia of her left leg. Treatment with intravenous Iloprost, a stable prostacyclin analogue, combined with Heparin, produced a dramatic improvement in her circulation within 4 h.

Real-time color duplex scanning after sclerotherapy of the greater saphenous vein.

A color real-time duplex scanner was used to scan the greater saphenous vein in 89 limbs of 55 patients to study the efficacy of prior greater saphenous vein sclerotherapy. The greater saphenous vein was insonated from the saphenofemoral junction to the knee to evaluate both reflux to a standardized 30 mm Hg Valsalva maneuver and evidence of greater saphenous vein obliteration by sclerotherapy. These data were correlated with the number of sclerosing injections used (mean, 1.8; range, 1 to 6), time from the last injection (mean, 27.5 mo.; range, 3 to 55 mo), and concentration of injectant used (0.5% to 3% sodium tetradecyl sulfate). Fifty-one of 89 injected limbs (57%) demonstrated reflux through the saphenofemoral junction, and reflux down the more distal greater saphenous vein was found in 67 of 89 injected limbs (75%). Greater saphenous vein obliteration was noted in only 18 of 89 injected limbs (20%); two were totally obliterated, and 16 were partially obliterated. The greater saphenous vein was obliterated in 6% below a refluxing saphenofemoral junction and in 40% below a nonrefluxing junction. A greater saphenous vein obliteration rate of 9% was found with a refluxing greater saphenous vein, and 50% in a nonrefluxing greater saphenous vein. Femoral vein reflux was identified in 11 of the 110 limbs (10%) and in every case was associated with both saphenofemoral junction and greater saphenous vein reflux. We noted a trend toward more successful results with more concentrated injectate (3% sodium tetradecyl sulfate). Fifty percent of patients reported improvement in symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Mastectomy and breast reconstruction preserving the nipple.

Total mastectomy and immediate reconstruction using the latissimus dorsi myocutaneous flap with nipple preservation has been performed in 87 women. The palpable tumours were all more than 3 cm from the nipple. No recurrence in the preserved nipple was seen in 63 women who underwent the procedure for tumour recurrence after previous radiotherapy. Nipple recurrence occurred in 3 out of 24 women (12%) where the indication was multifocal disease and no radiotherapy was given. This non-irradiated group should either not have the nipple preserved or should undergo postoperative electron field therapy to the nipple-areolar complex.

Monitoring cerebral perfusion during carotid endarterectomy.

Transcranial pulsed Doppler ultrasound was used to monitor blood velocity in the middle cerebral artery (MCA) of two patients during ipsilateral carotid endarterectomy. In the first patient the ultrasound data demonstrated a non-functioning shunt which was corrected by repositioning the distal end of the shunt. In the second patient MCA blood velocity data demonstrated that clamping of the external carotid artery would have resulted in complete cessation of MCA flow throughout endarterectomy. These cases illustrate the benefit that this technique offers to the individual patient undergoing carotid surgery.

Effect of carotid endarterectomy on cerebral blood flow and its response to hypercapnia.

Cerebral blood flow (CBF) was measured in 14 patients before carotid endarterectomy, 3 h after surgery and 2 days postoperatively using the intravenous xenon-133 technique. In 11 of the patients CBF was remeasured at 6 months and in 8 patients CBF and the response to hypercapnia (5 per cent CO2 in air) was measured pre-operatively and 6 months following surgery. All operations were performed using an intraluminal Javid shunt and internal carotid artery (ICA) 'stump' pressure was recorded. CBF measured at 3 h after endarterectomy revealed a postoperative cerebral hyperperfusion with significantly increased flows in both hemispheres. There was a significant correlation between carotid cross clamping time and ipsilateral hemispheric CBF increase which implied an ischaemic aetiology for the hyperperfusion and supported the routine use of an intraluminal shunt in carotid endarterectomy. Six months after surgery, CBF had returned to its preoperative value but reactivity to CO2 was significantly improved, which suggested that the operation had increased cerebral reserve.

Reduced response of cerebral blood flow to hypercapnia: restoration by extracranial-intracranial bypass.

Cerebral blood flow, estimated by the xenon clearance technique, has been used to study eight patients before and after extracranial-intracranial (EC-IC) bypass surgery. Response of cerebral blood flow to hypercapnia was also measured to estimate cerebral reactivity, an indicator of cerebral vasodilator reserve capacity. Measurements in all patients were repeated 3 months after surgery. Resting cerebral blood flow was not increased by the operation but cerebral reactivity in the ipsilateral hemisphere was significantly increased in all patients (P = 0.002). Reactivity also increased in the contralateral hemisphere in six of the eight patients (P = 0.065). The response of cerebral blood flow to hypercapnia may prove useful in the selection of symptomatic patients with carotid occlusions or inaccessible stenoses for revascularization by EC-IC bypass.

Transcranial Doppler assessment of cerebral collateral during carotid endarterectomy.

Sixteen patients (mean age 59 +/- 9 years) who were to undergo carotid endarterectomy were examined pre- and peroperatively using pulsed Doppler-shifted ultrasound; blood velocities in the middle cerebral artery were measured before and during common carotid compression in the conscious patient, and before and during measurement of carotid stump pressures at surgery in the anaesthetized patient. Measurements at endarterectomy showed a significant difference in middle cerebral artery blood velocities from patients with stump pressures of greater and less than 50 mmHg (t = 4.0, P less than 0.005). A threshold of 10 cm s-1 distinguished between stump pressures of greater and less than 50 mmHg in 15 of the 16 patients. Pre-operative blood velocity measurements during carotid compression did not correlate with those taken peroperatively at carotid clamping.

Outpatient varicose vein surgery under local anaesthesia.

Local anaesthesia has been used for 186 varicose vein operations performed in a day surgical unit. The long saphenous vein was stripped in 87 legs using a femoral nerve block. All patients went home on the day of operation and none required readmission. Complications were minimal and included six wound infections, six episodes of thrombophlebitis and one case of saphenous neuritis; 35 patients had minor residual varices at 6 weeks of which 29 required injection sclerotherapy. The technique has been shown to be both safe and acceptable to patients, and reduced the waiting time for surgery to a mean of 3.1 months during the period studied.

Monitoring middle cerebral artery blood velocity during carotid endarterectomy.

Transcranial pulsed Doppler ultrasound and spectral analysis were used to monitor blood velocities in the middle cerebral artery of nineteen patients (mean age 61 +/- 9 years) during carotid endarterectomy. A Javid shunt was used in all patients. The intensity weighted mean Doppler frequency for each spectral sweep (at 5 ms intervals) was time-averaged over the cardiac cycle to obtain a mean value for blood velocity in the middle cerebral artery. The range of such values found in the 19 patients was: 12-38 cm s-1 after anaesthesia (baseline); 12-69 cm s-1 during diathermy; 0-30 cm s-1 during carotid clamping; 16-32 cm s-1 during shunting and 18-60 cm s-1 in the recovery room. The average change in middle cerebral artery blood velocity from baseline values showed significant increases during diathermy (P less than 0.005), shunting (P less than 0.05) and in the recovery room (P less than 0.005). Clamping of the internal carotid artery showed a significant decrease in middle cerebral artery blood velocities of all patients (P less than 0.005), three of whom showed no flow in the middle cerebral artery during clamping. Abnormally high amplitude Doppler signals at the commencement of shunting were detected in 17 of the 19 patients. Such Doppler signals are consistent with turbulent blood flow or the introduction of micro-air bubbles by the shunt. Backbleeding in the internal carotid artery before insertion of the shunt was associated with diminished flow in the ipsilateral middle cerebral artery of ten patients, oscillatory forward/reverse flow in three patients and cessation of flow in the remaining six patients.