MicroRNA-1247 inhibits the viability and metastasis of osteosarcoma cells via targeting NRP1 and mediating Wnt/ß-catenin pathway.

OBJECTIVE: Osteosarcoma (OS) is a common malignant bone tumor that poses a serious threat to the health of adolescents or children. A large number of studies have proposed the role of microRNAs (miRNAs) in OS, except for miR-1247. Therefore, this research was designed to explore the molecular mechanism of miR-1247 in OS. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) or Western blot analysis was used to measure the expressions of miR-1247 and genes. The function of miR-1247 was investigated using Cell Counting Kit-8 (CCK-8) and transwell assays. The Dual-Luciferase reporter assay was used to explore the relationship between miR-1247 and neuropilin-1 (NRP1). RESULTS: MiR-1247 was downregulated in OS, which was related to the aggressive behavior of OS patients. Moreover, miR-1247 inhibited cell viability and metastasis in OS. At the same time, miR-1247 promoted apoptosis and inactivated the Wnt/ß-catenin pathway in OS. Furthermore, it was confirmed that NRP1 was a direct target of miR-1247. Upregulation of NRP1 attenuated the inhibitory effect of miR-1247 in OS. CONCLUSIONS: MiR-1247 played a suppressive role in OS by suppressing cell viability and metastasis.

Morphometric analysis of the popliteal artery for endovascular treatment.

This study intended to determine the precise diameter of the popliteal artery in patients at risk for popliteal aneurysms. Accurate sizing is necessary to develop devices for endovascular treatment of popliteal aneurysms. Fifty-four patients with abdominal aortic aneurysms (AAAs) had computed tomography (CT) scans of the popliteal arteries. Age- and gender-matched control subjects were measured by ultrasound. NIH Image was used to measure the minor diameter at the adductor hiatus (proximal) and femoral condyles (midpopliteal artery). There were 4 unsuspected popliteal aneurysms (7.4%). The proximal popliteal artery was ectatic in these patients: 13.4 +/- 5.2 mm. Proximal and midpopliteal arteries were significantly larger in the other patients with AAAs compared with controls: 9.6 +/- 1.8 mm vs 7.9 +/- 1.1 mm at the hiatus (p<0.001) and 10.2 +/- 2 mm vs 7.9 +/- 0.9 mm at the condyles (p<0.001). The popliteal artery was focally larger in patients with AAAs without popliteal aneurysms. The popliteal artery was larger in men compared with women; 9.8 +/- 1.8 mm vs 8.8 +/- 1.9 mm at the hiatus (p=0.024) and 10.5 +/- 1.9 mm vs 9.0 +/- 2.4 mm at the condyles (p=0.005). The proximal popliteal artery was 2 mm larger in patients at risk for popliteal aneurysms and 5 mm larger in patients with popliteal aneurysms compared to controls. Focal ectasia of the midpopliteal artery was common. Planning for endovascular treatment of popliteal aneurysms must incorporate this striking enlargement.

Is bilateral ultrasound scanning of the legs necessary for patients with unilateral symptoms of deep vein thrombosis?

PURPOSE: The purpose of this study was to determine the necessity of bilateral lower-extremity venous duplex ultrasound scanning in patients with unilateral symptoms of deep vein thrombosis (DVT). PATIENTS AND METHODS: A retrospective review of 1080 bilateral venous duplex scans was performed. Patients were randomly selected from a total of 7922 studied between May 1998 and May 2000. Data on patient age, sex, comorbidity, and the reason for ultrasound scan were compiled. Forty percent (435/1080) of patients presented with unilateral symptoms of lower-extremity DVT. This group was further analyzed according to their status as inpatients or outpatients. RESULTS: DVT was diagnosed in 26.9% (117/435) of the patients. Of the inpatients found to have DVT, the thrombus was confined to the symptomatic leg in 23.8% (38/159), thrombus was present just in the asymptomatic leg in 8/159 (5.0%), and thrombus was found in both legs in 8/159 (5.0%). In the outpatient group, thrombus was confined to the symptomatic leg in 21.0% (58/276) and found in both legs in 1.8% (5/276). None of the 276 outpatients had DVT isolated in the asymptomatic leg. CONCLUSION: Routine bilateral lower-extremity venous duplex studies are not necessary in outpatients presenting with unilateral symptoms. In many outpatients, a single-limb study will suffice. If a patient is found to have a DVT on the symptomatic side, then we believe that a bilateral study is indicated. We do believe that routine bilateral scanning of inpatients remains justified. This algorithm may save technician time and increase vascular laboratory efficiency.

Mesenteric venous thrombosis: a changing clinical entity.

OBJECTIVE: Mesenteric venous thrombosis (MVT) and its clinical spectrum have become better defined following improvements in diagnostic imaging. Historically, MVT has been described as a morbid clinical entity, but this may not necessarily be true. Often, an underlying disease process that predisposes a patient to MVT can be found and potentially treated. This study was designed to evaluate the diagnostics and management of MVT and to review long-term results of treatment. PATIENTS: Thirty-one patients in whom MVT was diagnosed between 1985 and 1999 were retrospectively reviewed. Survivors were contacted for follow-up. There were 15 men and 16 women. Ages ranged from 22 to 80 years (mean, 49.1 years). Thirteen patients had documented hypercoagulability, 10 had a history of previous abdominal surgery, 6 had a prior thrombotic episode, and 4 had a history of cancer. MVT presented as abdominal pain (84%), diarrhea (42%), and nausea/vomiting (32%). Computed tomography (CT) was considered diagnostic in 18 (90%) of 20 patients who underwent the test. CT diagnosed MVT in 15 (100%) of 15 patients presenting with vague abdominal pain or diarrhea. Angiography demonstrated MVT in only five (55.5%) of nine patients. RESULTS: Seven of 31 patients died within 30 days (< 30-day mortality rate, 23%). Twenty-two patients (72%) were initially treated with heparin. Nine patients were not heparinized: four of them died, and two were later given warfarin sodium (Coumadin). Of the 31 patients, only one received lytic therapy. Three patients became symptom free without anticoagulation. Ten patients (32%) underwent bowel resection. Overall, 19 (79%) of 24 survivors were treated with long-term warfarin therapy. Long-term follow-up was obtained in 24 patients (mean, 57.7 months). Twenty-one (88%) of 24 survived in follow-up. CONCLUSION: The diagnosis of MVT should be suspected when acute abdominal symptoms develop in patients with prior thrombotic episodes or a documented coagulopathy. CT scanning appears to be the primary diagnostic test of choice. Anticoagulation is recommended. If diagnosed and treated early, MVT is not likely to progress to gangrenous bowel. Recent mortality rates for MVT are lower than previously published, perhaps because of earlier diagnosis and aggressive treatment or possibly because we now readily diagnose a more benign form of the disease, which is due to widespread use of CT scanning.

Staged embolization and operative treatment of multiple visceral aneurysms in a patient with fibromuscular dysplasia--a case report.

The importance of following a prioritized sequential approach to patients with complex multianeurysm disease cannot be overemphasized. The following patient with multiple visceral aneurysms first had coil embolization of bilateral renal artery aneurysms and then operative excision of her remaining splenic artery aneurysms to minimize the potential morbidity of a larger operation. This case also demonstrates the potential for following levels of specific degradative enzymes associated with aneurysmal disease (matrix metalloproteinase-9 (MMP-9) in this case) preoperatively and postoperatively and in long-term follow-up to monitor for disease recurrence.

Incidental asymptomatic cerebral aneurysms in patients with extracranial cerebrovascular disease: is this a case against carotid endarterectomy without arteriography?

As less arteriography is performed before carotid surgery, concern arises about missing occult cerebral aneurysms and possible adverse outcomes. A study was conducted by the divisions of vascular surgery and neurosurgery of Northwestern University Medical School to evaluate the frequency of incidental cerebral aneurysms and outcomes of patients with extracranial cerebrovascular disease and asymptomatic cerebral aneurysms. From October 1995, through March 1997, 200 patients underwent intracranial and extracranial cerebrovascular angiography for evaluation of extracranial disease. Demographic data, symptoms, data of vascular lesions, surgical treatment and outcomes of stroke and death were recorded prospectively. Two patients (1%) had asymptomatic cerebral aneurysms found on angiography. Six more patients were referred with a known asymptomatic cerebral aneurysm with extracranial disease during this same period. Of these eight patients, five underwent extracranial vascular reconstruction surgery and seven received treatment for their aneurysms. There were two stroke complications, both occurred after treatment of a basilar artery aneurysm. One of these patients died. No aneurysms ruptured following 203 extracranial revascularizations during this same period. On the basis of the low prevalence of diagnosing coincidental cerebral aneurysms during work-up of extracranial disease, as well as the lack of evidence that carotid surgery predisposes to aneurysm rupture in these patients in both our study and the literature review, it is concluded that coexisting extracranial disease and asymptomatic cerebral aneurysms do not pose a case against carotid surgery without routine arteriography. However, arteriography should be considered in selected groups of patients where the yield of intracranial aneurysms is high; these include patients with a familial history of cerebral aneurysms, autosomal dominant polycystic kidney disease, extracranial internal carotid artery medial fibrodysplasia, Takayasu's arteritis, alpha1-antitripsin deficiency and atypical clinical presentations, including headache.

Reoperative aortic surgery.

The presentation of long-term complications after conventional aortic surgery and the treatment of patients that have had reoperative aortic operations are reviewed. Ninety-seven consecutive patients that had 102 subsequent aortic operations at a tertiary referral center were studied. Presenting symptoms, demographics, risk factors, indications for initial and second procedures, operative techniques and outcomes were recorded in a computerized database. There were 70 men and 27 women studied, with an average age of 64 years. First operations were performed primarily for aneurysm (56%) and occlusive disease (44%). The interval between procedures ranged up to 23 years, with a mean of 6 years. Indications for reoperation were subsequent aneurysm (65), graft occlusions (25) and/or infections (24). Seventy-three percent of the subsequent aneurysms were true metachronous aneurysms; the others were associated with the graft or an anastomosis. Para-anastomotic aneurysms may be more common with a primary end-to-side graft configuration. One-third of subsequent aneurysms were not palpable and asymptomatic. Graft occlusion can be treated safely with elective repeat bypass (mortality 0%). Graft infections that require total graft removal remain a challenging problem (mortality 17%). Although surgical approach for reoperations utilized more extensive exposure and proximal clamping, 59 elective aneurysm cases had a 5.1% mortality rate; eight emergent procedures for ruptured aneurysms resulted in 88% mortality. Reoperation for graft occlusion or infection showed a similar high mortality rate with emergent cases. In this referral practice, graft occlusion and infection are relatively less frequent, whereas metachronous aneurysm formation is now the most common indication for reoperation. These aneurysms often remain undetected until symptoms occur; frank rupture is usually lethal. As elective repair with modern reoperative techniques can be safely performed, routine computed tomographic examination is advisable at least every 5 years after aortic operations.

Natural history of composite sequential bypass: ten years' experience.

BACKGROUND: We previously reported 48-month patency rates of composite sequential bypass (CSB) approaching 60%. Yet, extended patency and limb salvage rates are unknown. HYPOTHESIS: Long-term patency and limb salvage rates of CSB are affected by sex, bypass configuration, and warfarin therapy. DESIGN: Medical records of all patients who underwent CSB during a 10-year period were retrospectively reviewed. SETTING: A referral center for the Chicago, Ill, region. PATIENTS: One hundred consecutive patients (mean age, 68.8 years; 57% were men and 49% had diabetes) undergoing 102 CSBs for limb salvage (ulcer, 43%; rest pain, 39%; and gangrene, 18%) from January 1986 to January 1996 were identified. INTERVENTIONS: Warfarin was used after surgery by 72% of patients and aspirin was used by the remainder of them. MAIN OUTCOME MEASURES: Life table primary patency and limb salvage rates were compared for sex, diabetes mellitus status, location of distal prosthetic anastomosis (above knee vs. below knee), and anticoagulation drug therapy (warfarin sodium vs aspirin) with log-rank statistics. RESULTS: Primary patency of CSB was 56% at 24 months, 29% at 48 months, and 20% at 84 months (SE <10%; mean follow-up, 19.6 months [range, 1.0-110.0 months]). Limb salvage rates were 64% at 24 months, 30% at 48 months, and 23% at 84 months (SE <10%); 66% and 90% of patients had failed grafts requiring amputation by 3 months and 1 year, respectively. CONCLUSIONS: Composite sequential bypass for limb salvage provides reasonable 2-year patency. However, patency rates steadily declined from year 2 to year 5. After CSB failure, limb salvage rates are poor, with 90% of patients progressing to amputation within 1 year.

Upper extremity ischemia in athletes.

Arterial injury is infrequent in the thoracic outlet syndrome but must be identified to prevent these younger patients from being dramatically disabled. This requires thorough interview and clinical examination, and then pursuit with a workup including complete bilateral arteriography with positional views. Helical computed tomography (CT) provides precise localization of arterial trauma with correlation to specific compressive elements. Unique features in athletes include a greater role of soft tissue hypertrophy and overuse in pathogenesis of arterial injury, more frequent compression of the axillary artery and its branches, and possible hand ischemia from direct trauma. In addition, these prospective or established professionals require optimum arm function to sustain their careers. Because of the desire to continue provocative arm use, decompression is performed early, and arm "claudication" is surgically treated. Operations are customized to achieve adequate decompression without compromising function. Surgical management consists of targeted resection of compressing structures, which is most often a cervical rib; arterial reconstruction to eliminate stenosis and the source of emboli; and improvement of distal perfusion with selection from an arsenal that includes catheter embolectomy, thrombolysis, and bypass grafting. Familiarization with the many unique diagnostic aspects and therapeutic options in arterial thoracic outlet syndrome produces excellent results in all but the most advanced cases.

Carotid plaque morphology correlates with presenting symptomatology.

PURPOSE: In carotid artery disease, correlation of carotid plaque morphology with the patient's presenting symptoms has drawn conflicting conclusions. The purpose of this series was to correlate carotid plaque characteristics with the presenting symptoms from a large cohort of patients who underwent operation for carotid artery disease. METHODS: From a series of 1252 consecutive patients who underwent carotid endarterectomy, presenting symptoms were divided into three groups: transiently symptomatic (transient ischemic attack [TIA] or amaurosis fugax), prior stroke, and asymptomatic. Plaque characteristics, including ulceration, intraplaque hemorrhage, and degree of stenosis, were recorded prospectively for 1008 procedures. All endarterectomy specimens were inspected during the procedure, and plaque characteristics were recorded immediately after operation. RESULTS: There was a higher incidence of plaque ulceration in the transiently symptomatic and prior stroke groups (391 of 508 [77%] and 91 of 115 [79%]) than in the asymptomatic cohort (231 of 385 [60%]; p < 0.0001, chi2 test). There was no significant difference in the incidence of plaque hemorrhage between the transiently symptomatic and prior stroke patients compared with the asymptomatic patients. There was no statistical difference for ulcerated plaque or plaque hemorrhage between the transiently symptomatic and prior stroke group. Intraplaque hemorrhage occurred more frequently in patients with high-grade stenosis (90% to 99%) than in those with less than 90% stenosis (202 of 299 [68%] versus 97 of 299 [32%]; p = 0.01, chi2 test). CONCLUSIONS: On gross examination of the carotid specimen in the operating room, plaque ulceration correlates with an initial presentation of amaurosis fugax, TIA, or prior stroke compared with patients operated on for asymptomatic disease. The presence of intraplaque hemorrhage is associated with more advanced stenosis of the internal carotid artery. These findings suggest that plaque morphology does play an important role in the presentation of carotid artery disease.

Helical computed tomography of the normal thoracic outlet.

PURPOSE: This study was performed to determine the detailed anatomy of the thoracic outlet in normal subjects using helical computed tomography (CT), with particular attention to vascular compression with arm movement. METHODS: Ten volunteers underwent detailed clinical evaluation and helical CT scanning of the upper thorax and neck with the arm in a neutral position and with the arm abducted 90 degrees or greater and externally rotated. Anterior scalene-clavicle distance (SC), costoclavicular distance (CC), and vessel diameters were measured with electronic calipers in each position. Comparisons were made with Student's t test. RESULTS: With abduction the SC decreased from 18.4 +/- 3.9 mm to 5.2 +/- 2.4 mm (p < 0.001), and the CC decreased from 12.6 +/- 2.7 mm to 6.3 +/- 3.3 mm (p = 0.005). At these same anatomic planes, the vein diameter decreased from 11.0 +/- 1.6 mm at the neutral position to 5.1 +/- 1.5 mm (p < 0.001) and from 16.1 +/- 3.0 mm to 7.4 +/- 2.6 mm with the arm abducted (p < 0.001). The artery diameter changed from 6.6 +/- 0.8 mm to 6.2 +/- 0.5 mm (p = 0.08) and from 7.2 +/- 0.8 mm to 6.0 +/- 0.5 mm (p = 0.001) with arm movement. CONCLUSIONS: Both the distances between the anterior scalene muscle and the clavicle and between the clavicle and the first rib are significantly reduced with abduction of the upper extremity. Venous compression is universal at both the SC and CC spaces in normal subjects with this maneuver. Arterial narrowing occurs less frequently and appears to be minor. Minor changes in these thoracic outlet dimensions (SC/CC) may produce venous compression without movement.

Treatment of venous malformations by direct injection with ethanol.

PURPOSE: Venous malformations (VMs) may be discrete or extensive, and larger lesions may be difficult to remove with surgery. Incompletely removed lesions have a tendency to recur. We report our experience with ethanol ablation of VMs. METHODS: All 12 patients (seven women; mean age, 37 years) were evaluated with magnetic resonance imaging before treatment. A total of 19 prior surgical excisions had been performed for seven of the patients. Symptoms were present in all 12 patients and included bleeding, pain, swelling, and limitation of exercise. The VMs were present in the lower extremities of seven patients, in the upper extremities of three patients, and in the flank and buttocks in two patients. RESULTS: The 12 patients have undergone 30 injection procedures, with six patients requiring one, three patients requiring two, two patients requiring three, and one patient having undergone 12 treatments. General anesthesia was used in 11 patients. Blood loss was minimal for all procedures, and 28 of the 30 procedures were technically successful. Skin ulceration was seen in approximately half of the treated VMs, all of which healed with local wound care. Focal VMs were injected in six patients and resolved with a single treatment in five patients. Patients were free of symptoms at a mean follow-up of 10 months. Extensive VMs were injected for discrete, symptomatic areas in five patients. These lesions all regressed and were asymptomatic at a mean follow-up of 23 months in all but one patient. However, these lesions required multiple treatments as additional areas became problematic. CONCLUSIONS: Ethanol sclerosis is a well-tolerated, safe, and effective adjunct to the management of VMs. Advantages of ethanol injection include the ability to treat a very localized area without an incision. Conversely, extensive lesions may be palliated as symptoms occur.