A multicenter prospective cohort study to evaluate feasibility of radio-frequency identification surgical guidance for nonpalpable breast lesions: design and rationale of the RFID Localizer 1 Trial.

BACKGROUND: Breast cancer screening and improving imaging techniques have led to an increase in the detection rate of early, nonpalpable breast cancers. For early breast cancer, breast conserving surgery is an effective and safe treatment. Accurate intraoperative lesion localization during breast conserving surgery is essential for adequate surgical margins while sparing surrounding healthy tissue to achieve optimal cosmesis. Preoperative wire localization and radioactive seed localization are accepted standard methods to guide surgical excision of nonpalpable breast lesions. However, these techniques present significant limitations. Radiofrequency identification (RFID) technology offers a new, nonradioactive method for localizing nonpalpable breast lesions in patients undergoing breast conserving surgery. This study aims to evaluate the feasibility of RFID surgical guidance for nonpalpable breast lesions. METHODS: This multicenter prospective cohort study was approved by the Institutional Review Board of the University Medical Center Utrecht. Written informed consent is obtained from all participants. Women with nonpalpable, histologically proven in situ or invasive breast cancer, who can undergo breast conserving surgery with RFID localization are considered eligible for participation. An RFID tag is placed under ultrasound guidance, up to 30 days preoperatively. The surgeon localizes the RFID tag with a radiofrequency reader that provides audible and visual real-time surgical guidance. The primary study outcome is the percentage of irradical excisions and reexcision rate, which will be compared to standards of the National Breast Cancer Organisation Netherlands (NABON)(≤ 15% irradical excisions of invasive carcinomas). Secondary outcomes include user acceptability/experiences, learning curve, duration and ease of the placement- and surgical procedure and adverse events. DISCUSSION: This study evaluates the feasibility of RFID surgical guidance for nonpalpable breast lesions. Results may have implications for the future localization techniques in women with nonpalpable breast cancer undergoing breast conserving surgery. TRIAL REGISTRATION: Netherlands National Trial Register, NL8019 , registered on September 12th 2019.

Predictors of acute and persisting ischemic brain lesions in patients randomized to carotid stenting or endarterectomy.

BACKGROUND AND PURPOSE: We investigated predictors for acute and persisting periprocedural ischemic brain lesions among patients with symptomatic carotid stenosis randomized to stenting or endarterectomy in the International Carotid Stenting Study. METHODS: We assessed acute lesions on diffusion-weighted imaging 1 to 3 days after treatment in 124 stenting and 107 endarterectomy patients and lesions persisting on fluid-attenuated inversion recovery after 1 month in 86 and 75 patients, respectively. RESULTS: Stenting patients had more acute (relative risk, 8.8; 95% confidence interval, 4.4-17.5; P<0.001) and persisting lesions (relative risk, 4.2; 95% confidence interval, 1.6-11.1; P=0.005) than endarterectomy patients. Acute lesion count was associated with age (by trend), male sex, and stroke as the qualifying event in stenting; high systolic blood pressure in endarterectomy; and white matter disease in both groups. The rate of conversion from acute to persisting lesions was lower in the stenting group (relative risk, 0.4; 95% confidence interval, 0.2-0.8; P=0.007), and was only predicted by acute lesion volume. CONCLUSIONS: Stenting caused more acute and persisting ischemic brain lesions than endarterectomy. However, the rate of conversion from acute to persisting lesions was lower in the stenting group, most likely attributable to lower acute lesion volumes. Clinical Trial Registration -URL: www.isrctn.org. Unique identifier: ISRCTN25337470.

Effects of carotid endarterectomy or stenting on arterial diameters in the circle of Willis.

BACKGROUND: In patients with internal carotid artery (ICA) stenosis, the circle of Willis (CoW) is the primary collateral pathway. We compared luminal diameters in the CoW before and after carotid revascularization and compared the effects of carotid endarterectomy (CEA) and stenting on these diameters. METHODS: At a single center in the International Carotid Stenting Study, 139 patients with symptomatic ICA stenosis of 50% or more were randomized to stenting (n = 81) or CEA (n = 58). The diameters of all segments of the CoW were assessed on computed tomography angiography (CTA), before and 30 days after revascularization. All evaluations were performed blinded to treatment allocation and order of CTA. RESULTS: A .10-mm increase (95% confidence interval [CI], .02-.17; 7%; P = .01) in diameter after revascularization occurred in the ipsilateral precommunicating anterior cerebral artery (A1), whereas both the ipsilateral and contralateral posterior communicating arteries decreased in diameter by .12 mm (95% CI, .04-.21; 14%; P = .01) and .08 mm (95% CI, .00-.17; 10%; P = .05), respectively. The increase in diameter of the A1 was larger after stenting (.15 mm; 95% CI, .07-.24; P = .001) than after CEA (.02 mm; 95% CI, -.11 to .15; P = .79). Only in patients treated with CEA, the diameters of the contralateral A1 and ipsilateral precommunicating posterior cerebral artery were reduced after revascularization. CONCLUSIONS: Carotid revascularization improves anterior collateralization and reduces reliance on posterior collateral pathways via the CoW. Carotid stenting and endarterectomy appear to have different early effects on collateralization.

Characteristics of ischemic brain lesions after stenting or endarterectomy for symptomatic carotid artery stenosis: results from the international carotid stenting study-magnetic resonance imaging substudy.

BACKGROUND AND PURPOSE: In a substudy of the International Carotid Stenting Study (ICSS), more patients had new ischemic brain lesions on diffusion-weighted magnetic resonance imaging (MRI) after stenting (CAS) than after endarterectomy (CEA). In the present analysis, we compared characteristics of diffusion-weighted MRI lesions. METHODS: Number, individual and total volumes, and location of new diffusion-weighted MRI lesions were compared in patients with symptomatic carotid stenosis randomized to CAS (n=124) or CEA (n=107) in the ICSS-MRI substudy. RESULTS: CAS patients had higher lesion numbers than CEA patients (1 lesion, 15% vs 8%; 2-5 lesions, 19% vs 5%; >5 lesions, 16% vs 4%). The overall risk ratio for the expected lesion count with CAS versus CEA was 8.8 (95% confidence interval, 4.4-17.5; P<0.0001) and significantly increased among patients with lower blood pressure at randomization, diabetes mellitus, stroke as the qualifying event, left-side stenosis, and if patients were treated at centers routinely using filter-type protection devices during CAS. Individual lesions were smaller in the CAS group than in the CEA group (P<0.0001). Total lesion volume per patient did not differ significantly. Lesions in the CAS group were more likely to occur in cortical areas and subjacent white matter supplied by leptomeningeal arteries than lesions in the CEA group (odds ratio, 4.2; 95% confidence interval, 1.7-10.2; P=0.002). CONCLUSIONS: Compared with patients undergoing CEA, patients treated with CAS had higher numbers of periprocedural ischemic brain lesions, and lesions were smaller and more likely to occur in cortical areas and subjacent white matter. These findings may reflect differences in underlying mechanisms of cerebral ischemia.

Cerebral perfusion affects the risk of ischemia during carotid artery stenting.

BACKGROUND: Patients with impaired perfusion in the hemisphere ipsilateral to a stenotic internal carotid artery may have a higher risk of cerebral ischemic complications than those with normal perfusion. We therefore studied whether the occurrence of new ischemic lesions after carotid artery stenting is related to cerebral perfusion. METHODS: In 45 patients with symptomatic carotid artery stenosis, CT perfusion and magnetic resonance diffusion-weighted imaging (DWI) were performed before carotid artery stenting; DWI was repeated within 2 days thereafter. Cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF) were measured with CT perfusion in the cortical flow territory of the middle cerebral artery. Hyperintense lesions on postprocedural DWI not visible on baseline DWI were considered new cerebral ischemic lesions. The relation between CBF, CBV, and MTT and new ipsilateral ischemic lesions was tested with logistic regression. RESULTS: In 11 of the 45 (24%) patients, new ischemic lesions were found in the ipsilateral hemisphere. The occurrence of these lesions was related to a lower CBF [adjusted odds ratio (aOR), 0.96; 95% confidence interval (CI), 0.92-1.00] and a longer MTT (aOR, 1.65; 95% CI, 1.02-2.66) compared with ipsilateral hemispheres without new lesions. CONCLUSIONS: Patients with impaired cerebral perfusion are more prone to develop ischemic lesions during carotid artery stenting. This suggests that in ischemic stroke during or after carotid artery stenting, embolic and hemodynamic mechanisms act in concert.

Incidental intracranial aneurysms in patients with internal carotid artery stenosis: a CT angiography study and a metaanalysis.

BACKGROUND AND PURPOSE: Smoking and hypertension are important risk factors for atherosclerotic carotid artery disease, but also for intracranial aneurysms. We studied the presence of aneurysms in a series of patients with internal carotid artery (ICA) stenosis and performed a systematic review of the literature to assess in patients with ICA stenosis the prevalence of intracranial aneurysms, gender differences in prevalence, and the size of the aneurysms found. METHODS: In a prospectively collected series of patients with symptomatic ICA stenosis >50% on CTA we assessed the proportion with intracranial aneurysms. We performed "Embase" and "Pubmed" searches for studies on patients with ICA stenosis (domain) and intracranial aneurysms (outcome measurement). We calculated overall prevalence and relative risks for gender, both with corresponding 95% confidence intervals (CI). RESULTS: We found an intracranial aneurysm in 8 of our 194 patients (4.1%; [95% CI 1.3 to 6.9]). The literature search resulted in 5 relevant and valid articles, totaling 4251 patients. The overall prevalence in all series combined was 3.2% (95% CI 2.7 to 3.7); the prevalence of aneurysms larger than 5 mm was 0.9% (95% CI 0.6 to 1.1). Women had a higher risk then men (relative risk 1.6; [59% CI 1.1 to 2.3]). CONCLUSIONS: About 1% of patients with a symptomatic ICA stenosis have an intracranial aneurysm with a higher than negligible risk of rupture, but in deciding aneurysms treatment the risk of cardiovascular diseases other than aneurismal rupture should be taken into account. The proportion of patients with aneurysms seems higher in series of patients with ICA stenosis than in the general population.

Frequency and consequences of early in-stent lesions after carotid artery stent placement.

PURPOSE: To examine the prevalence of in-stent lesions 1 month after carotid artery stent placement with multidetector computed tomography (CT) angiography and to evaluate their possible causes and their consequences during 1-year follow-up. MATERIALS AND METHODS: Sixty-nine patients with symptomatic carotid artery stenosis underwent multidetector CT angiography of the carotid arteries 1 month after carotid artery stent placement. Patients were followed-up until 1 year after stent placement, when duplex ultrasonography (US) was performed. In-stent lesions were defined as hypo- or hyperattenuating lesions at the stent wall found with multidetector CT. Significant restenosis (70%) at 1 year was defined as a peak systolic velocity of more than 300 cm/sec at duplex US. The Fisher exact test was used to assess the relationship between early in-stent lesions and ischemic events and restenosis. RESULTS: At 1 month, 14 of the 69 patients (20%) were found to have in-stent lesions. In one patient, the stent was occluded. The other 13 in-stent lesions did not result in significant lumen reduction. In the year following stent placement, no difference in ischemic events was found between patients with (14%) and those without (13%) early in-stent lesions (P = .99). There was no difference in the occurrence of restenosis at 1 year (7% vs 4%, P = .59). CONCLUSIONS: At 1 month after carotid artery stent placement, in-stent lesions are found in about one-fifth of patients. These lesions do not appear to be related to recurrent ischemic events or to restenosis at 1 year.

New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS).

BACKGROUND: The International Carotid Stenting Study (ICSS) of stenting and endarterectomy for symptomatic carotid stenosis found a higher incidence of stroke within 30 days of stenting compared with endarterectomy. We aimed to compare the rate of ischaemic brain injury detectable on MRI between the two groups. METHODS: Patients with recently symptomatic carotid artery stenosis enrolled in ICSS were randomly assigned in a 1:1 ratio to receive carotid artery stenting or endarterectomy. Of 50 centres in ICSS, seven took part in the MRI substudy. The protocol specified that MRI was done 1-7 days before treatment, 1-3 days after treatment (post-treatment scan), and 27-33 days after treatment. Scans were analysed by two or three investigators who were masked to treatment. The primary endpoint was the presence of at least one new ischaemic brain lesion on diffusion-weighted imaging (DWI) on the post-treatment scan. Analysis was per protocol. This is a substudy of a registered trial, ISRCTN 25337470. FINDINGS: 231 patients (124 in the stenting group and 107 in the endarterectomy group) had MRI before and after treatment. 62 (50%) of 124 patients in the stenting group and 18 (17%) of 107 patients in the endarterectomy group had at least one new DWI lesion detected on post-treatment scans done a median of 1 day after treatment (adjusted odds ratio [OR] 5.21, 95% CI 2.78-9.79; p<0.0001). At 1 month, there were changes on fluid-attenuated inversion recovery sequences in 28 (33%) of 86 patients in the stenting group and six (8%) of 75 in the endarterectomy group (adjusted OR 5.93, 95% CI 2.25-15.62; p=0.0003). In patients treated at a centre with a policy of using cerebral protection devices, 37 (73%) of 51 in the stenting group and eight (17%) of 46 in the endarterectomy group had at least one new DWI lesion on post-treatment scans (adjusted OR 12.20, 95% CI 4.53-32.84), whereas in those treated at a centre with a policy of unprotected stenting, 25 (34%) of 73 patients in the stenting group and ten (16%) of 61 in the endarterectomy group had new lesions on DWI (adjusted OR 2.70, 1.16-6.24; interaction p=0.019). INTERPRETATION: About three times more patients in the stenting group than in the endarterectomy group had new ischaemic lesions on DWI on post-treatment scans. The difference in clinical stroke risk in ICSS is therefore unlikely to have been caused by ascertainment bias. Protection devices did not seem to be effective in preventing cerebral ischaemia during stenting. DWI might serve as a surrogate outcome measure in future trials of carotid interventions. FUNDING: UK Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union, Netherlands Heart Foundation, and Mach-Gaensslen Foundation.