Promoter methylation changes in ALOX12 and AIRE1: novel epigenetic markers for atherosclerosis.

BACKGROUND: Atherosclerosis is the main cause of cardiovascular diseases such as ischemic stroke and coronary heart disease. Gene-specific promoter methylation changes have been suggested as one of the causes underlying the development of atherosclerosis. We aimed to identify and validate specific genes that are differentially expressed through promoter methylation in atherosclerotic plaques. We performed the present study in four steps: (1) profiling and identification of gene-specific promoter methylation changes in atherosclerotic tissues; (2) validation of the promoter methylation changes of genes in plaques by comparison with non-plaque intima; (3) evaluation of promoter methylation status of the genes in vascular cellular components composing atherosclerotic plaques; and (4) evaluation of promoter methylation differences in genes among monocytes, T cells, and B cells isolated from the blood of ischemic stroke patients. RESULTS: Upon profiling, AIRE1, ALOX12, FANK1, NETO1, and SERHL2 were found to have displayed changes in promoter methylation. Of these, AIRE1 and ALOX12 displayed higher methylation levels in plaques than in non-plaque intima, but lower than those in the buffy coat of blood. Between inflammatory cells, the three genes were significantly less methylated in monocytes than in T and B cells. In the vascular cells, AIRE1 methylation was lower in endothelial and smooth muscle cells. ALOX12 methylation was higher in endothelial, but lower in smooth muscle cells. Immunofluorescence staining showed that co-localization of ALOX12 and AIRE1 was more frequent in CD14(+)-monocytes than in CD4(+)-T cell in plaque than in non-plaque intima. CONCLUSIONS: Promoter methylation changes in AIRE1 and ALOX12 occur in atherosclerosis and can be considered as novel epigenetic markers.

Clinical outcomes of carotid endarterectomy in patients with carotid artery tandem lesions.

BACKGROUND AND PURPOSE: When carotid artery tandem lesions are present, the benefits of carotid endarterectomy (CEA) to reduce recurrent stroke remain uncertain. The present retrospective cohort study aimed to determine the clinical outcomes of CEA for carotid artery tandem stenosis that was diagnosed by contrast-enhanced magnetic resonance angiography. METHODS: Six hundred forty-seven consecutive patients underwent CEA between January 2001 and December 2010. Tandem stenosis, defined as a significant carotid bifurcation stenosis and identifiable stenosis of ≥50% of any downstream distal cerebral artery, was identified in 92 patients (14.2%) by contrast-enhanced magnetic resonance angiography. Patients with and without tandem stenosis were compared in terms of CEA outcomes. The primary end point was the composite of any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years after CEA. RESULTS: Tandem stenosis did not associate with ipsilateral stroke during postoperative follow-up. The 2 groups did not differ in terms of estimated 4-year primary end point rates (8.7% versus 3.8%; P=0.07) or ipsilateral stroke-free (P=0.56), any stroke-free (P=0.89), or overall survival (P=0.41) rates. CONCLUSIONS: After diagnosis by contrast-enhanced magnetic resonance angiography, patients with and without tandem stenosis had similar rates of stroke and death.

Preoperative magnetic resonance angiography as a predictive test for cerebral ischemia during carotid endarterectomy.

BACKGROUND: To evaluate whether the preoperative magnetic resonance angiography (MRA) can predict the risk of cerebral ischemia associated with the carotid endarterectomy (CEA). METHODS: Between January 2004 and December 2010, 382 consecutive patients (mean age: 56.6 years; range: 45-78 years) were identified to have undergone preoperative MRA and the CEA under regional anesthesia. It was determined that the patient needs shunting during the CEA by intraoperative monitoring of patient's neurology. All patients were divided into two subgroups: shunt group or no-shunt group. Imaging findings on preoperative MRA were correlated to shunting using univariate and multivariate logistic regression analyses combined with patient's demographic and clinical features to identify predictors of cerebral ischemia during the CEA. RESULTS: In 37 of 382 CEA cases (9.7%), shunting had been performed intraoperatively because the patient had a neurologic deficit. At multivariate analysis, preoperative MRA findings such as the absence of patent communicating arteries (odds ratio [OR], 5.56; 95% confidence interval [CI], 3.05-9.69; p = 0.013) and the increase of intracranial arteries which were not patent in the contralateral hemisphere (OR, 4.277; 95% CI, 2.575 to 7.104; p < 0.0001) were significantly associated with shunting. CONCLUSIONS: Preoperative MRA is valuable when predicting cerebral ischemia leading to an inevitable shunting during CEA. Therefore, if there are preoperative MRA findings such as multiple occlusive intracranial arteries in the contralateral hemisphere or the absence of patent communicating arteries, it is recommended that CEA be performed under general anesthesia with routine shunting to avoid a serious shunt-related complication.

Ten-year comparative analysis of bovine pericardium and autogenous vein for patch angioplasty in patients undergoing carotid endarterectomy.

BACKGROUND: To evaluate early and late clinical outcomes of carotid endarterectomy (CEA) with bovine pericardium patch in comparison with autogenous vein. METHODS: During a 10-year period, 456 CEAs were performed using patch closure of the arteriotomy with bovine pericardium (252 cases) and autogenous vein (204 cases). Retrospectively, surgical outcomes were evaluated and compared regarding CEA-related parameters, early and late mortality and morbidity rates, and the incidence of restenosis and aneurysmal dilatation between patients with bovine pericardium patch closure and those with autogenous vein closure. RESULTS: The two groups were comparable regarding basic demographics, clinical data, and anatomic data, except the incidence of coronary or peripheral arterial diseases. In patients with bovine pericardium patch closure, the total operating time and carotid clamping duration were statistically significantly shorter than in those with autogenous vein closure (P < 0.01). During the early postoperative period, 10 major (stroke and death) complications (2.2%) occurred without statistically significant difference between the two groups. The incidence of early minor postoperative complications was less with bovine pericardium patch closure (5.6% vs. 10.8%; P < 0.05). With a mean follow-up of 62 months for bovine pericardium patch closure and 67 months for autogenous vein closure, the incidence of restenosis was similar, but aneurysmal dilatation was higher in patients with autogenous vein closure with a statistically significant difference (0% vs. 2.0%; P < 0.05). CONCLUSION: CEA with bovine pericardium patch angioplasty showed excellent early and late clinical outcomes. Our results demonstrated bovine pericardium to be a suitable patch material for routine use in CEA.

Carotid endarterectomy for symptomatic complete occlusion of the internal carotid artery.

We described 9 consecutive patients who underwent operative carotid artery exploration with attempted carotid endarterectomy (CEA) for symptomatic internal carotid artery (ICA) occlusion. Indications for this surgery based on vascular imaging included segmental occlusion of the proximal ICA and also extensive occlusion of the distal ICA in selected patients in whom color-flow duplex ultrasound showed a poorly echogenic or anechoic thrombus with a flow void, suggestive of an acute thrombus. CEA was performed successfully to restore blood flow in all 9 patients:CEA in 5 and CEA with Fogarty thrombectomy in 4. Postoperative magnetic resonance (MR) angiography confirmed that revascularization had been successful in all 9 patients, and MR imaging displayed improved perfusion in 4 patients. Despite the lack of a generalized efficacy of surgical revascularization for symptomatic ICA occlusion, our study demonstrated that preoperative vascular imaging allows the selection of patients who may benefit from CEA.

Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging.

OBJECTIVE: There is hope that molecular imaging can identify vulnerable atherosclerotic plaques. However, there is a paucity of clinical translational data to guide the future development of this field. Here, we cross-correlate cathepsin-B or matrix metalloproteinase-2/-9 molecular optical imaging data of human atheromata or emboli with conventional imaging data, clinical data, and histopathologic data. METHODS AND RESULTS: Fifty-two patients undergoing carotid endarterectomy (41 atheromata) or carotid stenting (15 captured emboli) were studied with protease-activatable imaging probes. We show that protease-related fluorescent signal in carotid atheromata or in emboli closely reflects the pathophysiologic alterations of plaque inflammation and statin-mediated therapeutic effects on plaque inflammation. Inflammation-related fluorescent signal was observed in the carotid bifurcation area and around ulcero-hemorrhagic lesions. Pathologically proven unstable plaques had high cathepsin-B-related fluorescent signal. The distribution patterns of the mean cathepsin-B imaging signals showed a difference between the symptomatic vs asymptomatic plaque groups. However, the degree of carotid stenosis or ultrasonographic echodensity was weakly correlated with the inflammatory proteolytic enzyme-related signal, suggesting that molecular imaging yields complimentary new information not available to conventional imaging. CONCLUSIONS: These results could justify and facilitate clinical trials to evaluate the use of protease-sensing molecular optical imaging in human atherosclerosis patients.

Sarcoma of the abdominal aorta involving marginal arteries of the small intestine: a case report.

Primary sarcoma of the aorta is extremely rare. In the past, the disease was commonly diagnosed on autopsy. However, now it is possible to make a diagnosis preoperatively using various imaging studies such as computed tomographic scanning and magnetic resonance imaging. The authors have experienced one case of abdominal aortic sarcoma in a patient who complained of the symptoms of typical intestinal angina. We diagnosed an aortic sarcoma preoperatively but failed to resect the tumor on thoracolaparotomy because of the tumor extension to marginal arteries of the whole small intestine. We recommend preoperative laparoscopy for evaluation of tumor extension to marginal arteries of the small intestine in a patient having aortic sarcoma and intestinal angina if the patient is considered to be a surgical candidate.

Experience of an abdominal aortic aneurysm in a patient having crossed ectopia with fusion anomaly of the kidney.

We report a case of surgically treated abdominal aortic aneurysm (AAA) in a patient having crossed ectopia with fusion anomaly of the kidney. One artery from the abdominal aorta above the aneurysm supplies the right kidney while three renal arteries (two from the aneurysm itself and one from the left common iliac artery) supply the crossed ectopic kidney. Preoperative imaging to define the arterial and collecting systems along with a detailed planning of the operation is essential to prevent ischemic renal injury as well as ureteral injury during AAA repair.

Relationship between circle of Willis morphology on 3D time-of-flight MR angiograms and transient ischemia during vascular clamping of the internal carotid artery during carotid endarterectomy.

BACKGROUND AND PURPOSE: A potential source of complication at carotid endarterectomy (CEA) is cerebral ischemia caused by hypoperfusion during clamping of the carotid artery. Configuration of primary collateral pathways may be a major risk factor for development of transient cerebral ischemia during clamping. We investigated whether circle of Willis morphology on 3D time-of-flight (TOF) MR angiograms can reliably predict transient ischemia during vascular clamping of the internal carotid artery (ICA) in patients undergoing CEA. METHODS: Three-dimensional TOF MR angiography and CEA were performed in 117 patients. Patients had unilateral stenosis (n = 86), unilateral stenosis with contralateral occlusion (n = 21), or bilateral severe stenosis (n = 10) of the ICA. Circle of Willis morphology on preoperative 3D TOF MR angiograms was analyzed and correlated with intraoperative history of ischemia during vascular clamping of the ICA. RESULTS: Patients with unilateral stenosis or bilateral severe stenosis experienced transient ischemia during clamping of ICA at a low rate (11 [11%] of 96). In these groups, we found no specific circle of Willis patterns associated with development of intraoperative ischemia. However, patients with contralateral ICA occlusion experienced ischemia frequently during clamping of the ICA (12 [57%] of 21). In this group, incompleteness of the circle of Willis was significantly related to the risk of intraoperative ischemia (P =.005). CONCLUSION: In patients without contralateral ICA occlusion, circle of Willis morphology on 3D TOF MR angiograms cannot predict the development of intraoperative ischemia. However, in patients with contralateral ICA occlusion, incompleteness of the posterior part of the circle of Willis is a significant risk factor for development of ischemia during vascular clamping of the ICA.

Spontaneous rupture of the left external iliac vein.

Recently, we have experienced a case of spontaneous rupture of the left iliac vein in a 62-year-old woman, who had been suffering from hemiparesis and chronic constipation. An urgent laparotomy was performed for massive hemoperitoneum without knowing the bleeding point, and laceration on the left external iliac vein was repaired. Spontaneous rupture of the iliac vein is extremely rare. However, it should be included in differential diagnoses of the patient with massive hemoperitoneum who have no known pathology or any evidence of blunt trauma.

Large vessel injury following operation for a herniated lumbar disc.

Major vascular injury can occur during an operation for a herniated lumbar disc due to the intimate anatomical relation between the lumbar vertebrae and major vessels. Although occurrence is infrequent, it is associated with high morbidity and mortality. Diagnosis is suspected when early signs of retroperitoneal hemorrhage appear, but may often be delayed for weeks or years. Formation of a pseudoaneurysm or an arteriovenous (A-V) fistula may be of gradual onset and produce initially only a few symptoms. We report here six cases of large vessel injury, which consisted of active bleeding from an injured common iliac artery, or a pseudoaneurysm of the common iliac artery with or without an A-V fistula that occurred following an operation for a herniated lumbar disc and was successfully treated by radiologic intervention and/or surgery. Angiography with the intention of intervention is considered the first step of treatment for a large vessel injury following an operation for a herniated lumbar disc at the level between fourth and fifth lumbar or between fifth lumbar and first sacral intervertebral space.

Ruptured abdominal aortic aneurysms due to Salmonella, not of typhi species.

Ruptured aortic aneurysms due to Salmonella not of typhi species are rare and associated with high morbidity and mortality. We present three patients with Salmonella-infected ruptured aortic aneurysms successfully treated with an in situ prosthetic bypass graft. One patient had a saccular aneurysm at the infrarenal aorta and two patients had fusiform aneurysms at the aortic bifurcation. All the patients were treated with wide debridement of the infected aortic tissue followed by in situ graft replacement and long-term systemic antibiotic therapy. The method of revascularization, in situ bypass or extraanatomic bypass, remains controversial. On the basis of our clinical experience and recent literature focusing on more than 10 cases, in situ bypass reconstruction may be a feasible surgical technique for Salmonella-infected ruptured aortic aneurysm.

Ruptured renal artery stump aneurysm in a renal autotransplanted Behçet's disease patient.

A recurrent aneurysm at the anastomosis site or the remaining artery frequently occurs after the operative treatment of an aneurysm in Behçet's disease despite anti-inflammatory medication. Herein, a ruptured left renal artery stump aneurysm in a patient with Behçet's disease, who received a left nephrectomy, aorto-biiliac bypass and heterotopic autotransplantation of the right kidney for the treatment of an abdominal aortic aneurysm and renal hypertension one year prior to this admission, is reported. An aneurysm and rupture occurred despite the administration of anti-inflammatory medications while monitoring of the clinical findings, such as skin manifestations, erythrocyte segmentation rate (ESR) and C-reactive protein (CRP). Although there is no definite proven treatment modality to prevent recurrent aneurysms at the anastomosis site or a remote artery, close follow-up with anti-inflammatory medications, and surveillance with regular intervals are the only current methods for the prevention and/or to treatment of an arterial complication in patients with Behçet's disease.

Pararenal leiomyosarcoma of the inferior vena cava.

A complete surgical resection is the only proven therapeutic modality that prolongs the survival in patients with leiomyosarcoma of the inferior vena cava (IVC). Reconstruction of the IVC is not always necessary but is often required to facilitate venous drainage of the kidney for the tumors at the pararenal area of the IVC. Controversy exists in postoperative adjuvant therapy. Recently, we experienced four cases of pararenal leiomyosarcoma of the IVC, of which treatment consisted of a complete resection of the tumor, ringed polytetrafluoroethylene (PTFE) graft interposition, and bilateral renal vein reconstructions in all patients. Postoperative radiation therapy was instituted in 3 of 4 patients. One patient who did not receive the postoperative radiation therapy was treated with adjuvant chemotherapy. The kidneys were preserved in all patients and no deep vein thrombosis (DVT) or venous insufficiency of the lower extremity veins developed. Distant metastasis to the lung was noted in one patient at 18 months after surgery, who was not received the postoperative radiation therapy but chemotherapy. In conclusion, a complete resection of the tumor, IVC reconstruction, and bilateral renal vein reconstruction followed by adjuvant radiation therapy is recommended for the treatment of pararenal leiomyosarcoma of the IVC.

Inflammatory pseudotumor of the carotid artery: radiologic findings.

The radiologic appearance of inflammatory pseudotumor in the two cases presented was a fusiform mass surrounding the carotid bifurcation. The masses showed an avascular mass with focal narrowing of the carotid bifurcation on carotid arteriography, a homogeneous hypoechoic mass on ultrasound, less enhancement on contrast-enhanced computed tomography, and relatively intense enhancement on magnetic resonance imaging.

Metabolic changes after revascularization in a patient with innominate artery occlusion by localized in vivo proton magnetic resonance spectroscopy.

Localized in vivo proton magnetic resonance spectroscopy ((1)H-MRS) has been used to measure the metabolic status of the human brain in a non-invasive manner; thus, it is often called "a non-invasive biochemical assay". MRS is more sensitive than magnetic resonance imaging (MRI) in detecting ischemic damage by measuring the metabolic changes that occur prior to the anatomic changes. We report a patient who presented with innominate artery occlusion and symptoms of posterior circulation insufficiency and showed favorable metabolic changes by (1)H-MRS after revascularization. He showed no visible lesion in brain MRI, but in (1)H-MRS, decreased N-acetylaspartate (NAA) signal was noted in a resting state. After revascularization, both symptomatic improvement and recovery of NAA signal were observed. (1)H-MRS may provide valuable clinical information in diagnosis and management of cerebral hypoperfusion at a much earlier stage prior to the anatomic changes.

Mesenteric Buerger's disease.

A young male patient with a history of heavy smoking and low-extremity Buerger's disease was operated on because of small bowel infarction. The postoperative histopathological diagnosis was mesenteric involvement of Buerger's disease. Mesenteric Buerger's disease is extremely rare, the early diagnosis is difficult, and the prognosis is poor. Considering the difficulty in diagnosis and the poor prognosis, patients with Buerger's disease presenting with gastrointestinal manifestations should be carefully evaluated, and early surgical intervention is recommended.

Mesenchymal chondrosarcoma originating from the femoral vein.

Mesenchymal chondrosarcoma is a rare variant of chondrosarcomas characterized by a bimorphic pattern with areas of the undifferentiated malignant small cells and well differentiated cartilaginous islands.(1) It occurs most commonly in the bone but can also occur in the extraskeletal soft tissues, the brain, and the meninges. This type of tumor has also been described in the eyelids, parapharyngeal space, mediastinum, and the kidney.(1-5) An origin from the large vessels has not been reported in the medical literature. The authors report a case of mesenchymal chondrosarcoma originating from the femoral vein in a 28-year-old female patient, treated by the wide-margin resection.

Can carotid endarterectomy improve metabolic status in patients with asymptomatic internal carotid artery flow lesion? Studies with localized in vivo proton magnetic resonance spectroscopy.

PURPOSE: Carotid endarterectomy (CEA) has proven to be effective in the prevention of stroke in patients with significant internal carotid artery (ICA) stenosis. However, whether increased cerebral blood flow after CEA improves the cerebral metabolism in patients with asymptomatic ICA flow lesions is unknown. Localized in vivo proton magnetic resonance spectroscopy ((1)H-MRS) has been used to measure the metabolic status of the human brain in a totally noninvasive manner. The aim of this study was to investigate the cerebral metabolism after CEA in patients with asymptomatic ICA flow lesions and no visible infarction on magnetic resonance imaging (MRI). MATERIALS AND METHODS: We designed a prospective study to investigate the metabolic changes in the middle cerebral artery (MCA) territory with (1)H-MRS for 18 consecutive patients with asymptomatic severe stenosis of the ICA (>70% reduction in diameter) and for 16 healthy control subjects. The 18 patients with ICA flow lesion and no visible infarction on MRI who underwent CEA were evaluated before and 7 days after surgery (CEA group). The 16 control subjects had never had a cerebral event, and brain MRI and carotid duplex scan study results were normal in all (control group). RESULTS: Preoperative ICA volume flow was severely decreased to less than 150 mL/min in all 18 patients, in comparison with our laboratory normal value of matched age group of 250 to 300 mL/min. After CEA, ICA volume flow was increased to greater than 300 mL/min in all patients (P =.00). For patients in the CEA group, preoperative N-acetylaspartate/creatine and choline/creatine ratios in the MCA territory were slightly decreased compared with the healthy subjects in the control group but were within normal limits. However, the postoperative values of N-acetylaspartate/creatine and choline/creatine ratios in the ipsilateral MCA territory were significantly increased as compared with the preoperative values (P <.05). In the contralateral side, the postoperative increase of choline/creatine ratio and the decrease of myo-inositol/creatine ratio were statistically significant as compared with the preoperative values (P <.05). CONCLUSION: CEA seems to improve the cerebral metabolic status in patients with asymptomatic ICA flow lesions and no visible infarction on MRI.