INTRODUCTION

Large, wide-necked intracranial aneurysms are aneurysms with diameters larger than 10 mm and a neck wider than 4 mm. The incidence rate of large,wide-necked aneurysms is about 6%-10% of all intracranial aneurysms. Commonly, large,wide-necked aneurysms are seen in the cavernous and clinoid segments of the internal carotid artery (ICA),the bifurcation of the basilar artery, and the posterior cerebral artery. Clipping of craniotomy is difficult to cure. In recent years, vascular revascularization devices such as pipeline, silk, and surpass mesh stents have been successfully implanted in the treatment of medium and large aneurysms. We here retrospectively analyzed the clinical data of the treatment of giant(large), wide-necked aneurysms of the ICA with a new type of Pipeline Flex embolization device (PFED)from 2017 to 2018, to explore the safety and effectiveness of the PFED.

MATERIALS AND METHODS

Inclusion criteria

Inclusion criteria: 1) Patients with unruptured saccular aneurysm of the ICA (Hunt-Hess score < III grade, Fisher score < 2); 2) Aneurysm neck ≥ 10 mm and maximum diameter of aneurysm ≥ 5 mm; 3)Diameter of the tumor (aneurysm) bearing vessel is 2.0 mm-6.5 mm; 4) Exclusion of patients with definite cobalt chromium alloy and anticoagulant contraindications; and 5) Exclusion of unattached stents in target vessels of recurrent aneurysms.

Patients and general information

A total of 78 patients (22 males and 56 females)aged 20-78 years (mean, 52.3 years) were included in the study. There were 21 cases of hypertension, 6 cases of type II diabetes, 18 cases of oculomotor nerve compression, 19 cases of dyslipidemia, 2 cases of atrial premature beat, and 1 case after tubride(Enterprise) stent treatment. According to the location of the ICA segment aneurysms (28 cases of cavernous sinus segment, 21 cases of clinoid process segment, 18 cases of ophthalmic artery segment, 9 cases of posterior communicating segment, 2 cases of bilateral cavernous sinus segment), the average height of the aneurysm was 12.6 ± 1.92 mm, the average width of the aneurysm neck was 5.8 ± 1.97 mm, and the average ratio of body to neck was 0.46 ± 0.21. In the balloon occlusion test, the range of cerebral blood flow measured by the balloon occlusion experiment combined with single photon emission tomography was 75%-90% in 16 cases, 90%-95% in 37 cases, and 95% in 25 cases.

Embolization technique and treatment process

The clopidogrel (75 mg/d) and enteric-coated aspirin (100 mg/d) were given to patients orally for 3 days. Patients underwent bilateral femoral artery angiography under local anesthesia, and the next BOT test used to assess the affected side of the ICA occlusion after blood flow compensation. After hyperform balloon occlusion, the compensation of cerebral blood flow measured by SPECT was good,and the BOT test was negative. After general anesthesia, the 6F Chaperon guiding catheter was placed near the petrosal segment of the right ICA. The proper working angle was selected after the 5S DSA 3D rotational angiography of the affected side of the ICA was performed. A 0.029-in endopipe microcatheter was used under the guidance of the microguide wire to superselect the affected middle cerebral artery segment in the road map. (The tip of the microcatheter can be molded for 20 s if necessary.)Then the Pipeline Flex embolization device was imported. We brought the Pipeline stent distal to the tip of the microcatheter, coincidence of the proximal portion of the development segment of the transport guide wire and the distal development label of the microcatheter. We fixed the guide wire and slowly retracted it until the microcatheter overlapped with the distal end of the stent. After fixing the microcatheter,we pushed the delivery guide wire for about 10 mm.We fixed the delivery guide wire and continued to slowly withdraw the microcatheter and completely release the distal end of the stent and increase the metal density at the neck of the aneurysm. We alternately pushed the wire and withdrew the microcatheter. We made the distal marking of the microcatheter coincide with the mark point of the delivery guide wire. Cerebral angiography was performed immediately after complete stent release to observe the change of the pattern of blood flow into the aneurysm. DynaCT reconstruction was performed to assess whether the stent was well-adhered to the artery wall. Three-dimensional reconstruction of the stent using DynaCT to see if the stent was completely released and no stent stenosis Tirofiban hydrochloride was continuously pumped into the micropump within 24 h of the operation (5-6 mL/h).

Curative effect and prognosis

All patients were followed up for 3-18 months,average of about 9.25 months. Efficacy evaluation: 1)Total occlusion of the neck of the aneurysm; 2)Incomplete occlusion of aneurysm, residual neck of aneurysm; 3) Failure of sent to adhere to the vascular wall when it was opened; and 4) Lack of significant blood flow guidance. Prognosis evaluation: 1)Ischemic complication; 2) Delayed rupture of aneurysm; 3) Transient ischemic attack (TIA); 4)Hemorrhage intracranial; 5) Thrombotic stroke 6.Embolism and thrombosis; 7) Retroperitoneal hemorrhage; and 8) Visual field defect.

Statistical analysis

A 46-year-old female patient was admitted to hospital for 3 days with a headache and binocular vision (A 46-year-old female patient with three days history of headache and visual impairment before hospitalization). She had a history of hypertension and lumbar compression fractures. A physical examination reported the following: lucid, fluent speech, drooping of the right eyelid, normal limb muscle strength, and muscle tension. A magnetic resonance plain scan and contrast-enhanced examination indicated something occupying the right parasellar region; magnetic resonance angiography was performed to facilitate the diagnosis of aneurysm of the right ICA. Digital subtraction angiography(DSA) resulted in the diagnosis of a giant,wide-necked aneurysm in the cavernous segment of the right ICA (Figure 1A and 1B). The size of the aneurysm was determined using three-dimensional reconstruction (Figure 1C) and found to be 14. 8 ×11.9 mm. The width of the aneurysm neck was 6.2 mm.After general anesthesia and general heparinization,synchro guide wire and a stent catheter were selected to M3 segment of right middle cerebral artery (to the third segment of the right middle cerebral artery). The Pipeline Flex embolization device was slowly released and allowed to unfold. Postoperative follow-up DSA and 3D reconstruction showed that the Pipeline Flex embolization device adhered to the artery wall well,which delayed imaging of the aneurysm (the way of blood flow in the aneurysm changes, and contrast blood flow in the aneurysm changes, and contrast agent is partially retained in the aneurysm) (Figure 1D). One year after the operation, these aneurysms were re-examined using DSA. Blood was directed to the distal end of the artery and did not pass through the aneurysm (Figure 1F). MRI imaging prompted intra-aneurysm thrombosis (Figure 1G and 1H).

Figure 1. (A-G) Images of the treatment process of carotid cavernous segment aneurysms. (A) The anteroposterior position of digital subtraction angiography of the right ICA. (B) Lateral view of digital subtraction angiography of the right ICA. (C) Three-dimensional reconstruction of the aneurysm. (D) Positioning of the Pipeline Flex embolization device. (E) Three-dimensional reconstruction of the Pipeline Flex embolization device. (F) DSA examination after operation, showing that blood is directed to the distal end of the artery and does not pass through the aneurysm. (G) T1-weighted MRI shows a mixed and high signal. (H) Contrast-enhanced MRI in the aneurysm shows thrombosis.

RESULTS

Patient follow-up

地下开采过程中岩石物理力学性质的测量通常是比较困难的，而对岩石物理力学性质的影响因素又多种多样，容易造成结果的不确定性，因此对岩石物理力学性质的研究，采用较多的是岩石弹性波速测量及声发射观测等声学方法，主要分为2种[8]：

The Pipeline Flex embolization device (PFED) was a major breakthrough in endovascular treatment of large, wide-necked aneurysms. It reflects the philosophy of treatment from aneurysm embolism to vascular reconstruction. It differs from the traditional endovascular therapy. PFED can provide a physiologically appropriate treatment for aneurysms.It is the only clinical treatment for giant aneurysms of the internal carotid artery approved by the Food and Drug Administration (FDA) (in the United States).Changes in hemodynamics of aneurysms through the dense meshwork structure of stents (1,2), reduction of blood flow into the aneurysm sac, and stillness of local blood flow, all promote the formation of stable aneurysm thrombosis and endothelialization in the neck of the aneurysm. Due to the existence of a difference in pressure between artery-bearing aneurysms and the branch vessels, the branch vessels can be kept unobstructed after operation, which prevents local cerebral infarction caused by occlusion of perforating vessels. This can help achieve the optimal treatment of large intracranial aneurysms.

Side effects and complications

Table 1 compares the serious neurological adverse events in the Pipeline Flex embolization device group,giving the cumulative incidence at 180 days, 1 year,and 540 days. Results of the analysis of the data from our two centers indicate that Pipeline Flex embolization device can cause such neurological complications as hemorrhagic complications and ischemic complication. We compared these three time nodes, showing the increased probability of ischemic events than hemorrhagic events (7.7% vs. 6.4%),especially for the rate of ischemic stroke (2.6%increase to 6.4%), showing a correlation between patients who failed to take aspirin on time.

Table 1 Neurological complication of the Pipeline Flex embolization device at 180 to 540 days.

Complications 180 days 1 year 540 days Number of patients 9 (11.5%) 13 (16.7%) 15 (19.2%)Headache with dizziness 4 (5.1%) 5 (6.4%) 5 (6.4%)Intracranial hemorrhage 3 (3.8%) 3 (3.8%) 4 (5.1%)Ischemic stroke 2 (2.6%) 4 (5.1%) 5 (6.4%)Cerebral hematoma 0 (0.0%) 0 (0.0%) 1 (0.13%)Thrombotic stroke 0 (0.0%) 1 (0.13%) 1 (0.13%)

DISCUSSION

卡车司机群体规模庞大且年龄段分布较广，主要原因是卡车司机是众多职业中收入较高但门槛相对较低的。相对于其它行业，卡车司机这一职业虽然较为辛苦，但是收入水平相对较高。收入在5000～10000元区间的卡车司机占比达50%以上。虽然准入门槛相对较低，对学历要求不高，但还是不断有大学生涌入新物流行业。

Follow-up was performed through clinical check-up and radiological imaging with MRI and DSA. A total of 78 patients were examined. Among them, initial follow-up imaging and clinical evaluation was carried out in all patients at 3 to 18 months (mean,9.25 ± 1.2 months) after the procedure. Here, 66 cases were treated with the Pipeline Flex embolization device alone; 10 patients were treated with a pipeline stent-assisted coil embolization in; and 2 patients were treated with two pipeline stents. Angiography was performed immediately after complete stent release.Changes in the pattern of blood flow injection into the aneurysm were observed. Intra-aneurysm contrast agent retention and Dyna CT reconstruction showed that the pipeline stent was well adhered to the artery wall. Total occlusion of the neck of the aneurysm was observed in 67 patients, (Raymondl grade I; mRS score 0; 85.9%). Recurrence of the aneurysm due to the residual neck of the aneurysm took place in 8 patients (Raymondl grade II; mRS score 1; 10.3%).Delayed ischemia was observed in 1 patient (mRS score >2; 0.13%). The stent failed to adhere to the vascular wall in 1 patient. Mild stent stenosis was observed in 1 patient.

The close mesh structure of pipeline can reduce the oscillatory wall shear stress and improve vascular endothelial remodeling. It also has good adherence to the wall and high occlusive rate of aneurysms in the early stage of treatment. In one study based on the rat aneurysm model by Aquarius et al. (3), the average number of malapposed struts was lower for the occluded aneurysm group (4.4000200 ± 00021.9) than in the nonoccluded aneurysm group (7.7000200 ±00022.6, P0002<0002.01). The average distance between malapposed struts and the parent artery wall was lower for the occluded aneurysm group than for the nonoccluded aneurysm group, showing that wall apposition is more important than pore density for aneurysm occlusion. The study published by King et al. (4) also showed the prolonged (long time) healing of aneurysms to be related to the parent artery and the blood shunt in the body of the aneurysm. Studies of the use of a Pipeline in an observational registry show that 85.5% of the aneurysm patients received PFED therapy for 1092 patients (1221 intracranial aneurysms) with 3% patients treated with PFED therapy. The PFED adhered tightly to the vascular wall and hemodynamic changes stabilized.

There is still no clear method of predicting the efficacy of the PFED. There were significant individual differences between occlusion time and occlusion extent of aneurysms. Unlike with the tamponade spring coil placed inside the aneurysm,anticoagulation therapy is usually necessary after PFED placement, and excessive anticoagulant therapy often leads to complications (5,6). Brinjikji et al. (7)Meta-analysis of vascular remodeling devices showed that postoperative subarachnoid hemorrhage and cerebral parenchymal hemorrhage were estimated at 2%-4%. Griessenauer et al. (8) found there to be no significant association between aneurysm occlusion,retreatment, and packing density when cases were divided into high (>22%), moderate (12%-22%), and low (<12%) packing density categories. Aneurysm size remains the most important predictor of aneurysm recanalization and retreatment after stent-assisted coiling. The indications for the use of the PFED are giant, wide-necked aneurysms (9,10). The aneurysm recurrence rate was not closely associated with aneurysm size, so the PFED is safe for this type of aneurysm. This result also shows that the PFED has better therapeutic effects than normal coil embolism.Due to preliminary application of the PFED in clinical treatment, further prospective research on the PFED is essential.

公司对发展有信心，甚至财政危机也未能阻止其在俄罗斯的发展。俄罗斯工业及商贸部称，经济过程(包括汇率的波动)赋予那些在俄罗斯生产的国际板材生产者以进口商没有的优势。许多欧洲和中国的进口商因无力提供理想的价格和质量与当地的生产商竞争，在2017年中离开了俄罗斯市场。预期境内产品将占有95%的MDF市场份额。

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