Jim A. Reekers

Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids: 5-year outcome from the randomized EMMY trial

BACKGROUND Since 1995 uterine artery embolization has been described as an alternative for hysterectomy in patients with symptomatic fibroids. Many studies including several randomized controlled trials established uterine artery embolization as a valuable treatment. These randomized controlled trials reported outcomes in terms of health-related quality of life, clinical outcomes, efficacy, and cost-effectiveness after 1, 2, and 5 years of follow-up. OBJECTIVE The purpose of this study was to compare clinical outcome and health-related quality of life 10 years after uterine artery embolization or hysterectomy in the treatment of heavy menstrual bleeding caused by uterine fibroids in a randomized controlled trial. STUDY DESIGN In all, 28 Dutch hospitals recruited patients with symptomatic uterine fibroids who were eligible for hysterectomy. Patients were 1:1 randomly assigned to uterine artery embolization or hysterectomy. The outcomes assessed at 10 years postintervention were reintervention rates, health-related quality of life, and patient satisfaction, which were obtained through validated questionnaires. Study outcomes were analyzed according to original treatment assignment (intention to treat). RESULTS A total of 177 patients were randomized from 2002 through 2004. Eventually 81 uterine artery embolization and 75 hysterectomy patients underwent the allocated treatment shortly after randomization. The remaining patients withdrew from the trial. The 10-year questionnaire was mailed when the last included patient had been treated 10 years earlier. The mean duration of follow-up was 133 months (SD 8.58) accompanied by a mean age of 57 years (SD 4.53). Questionnaires were received from 131 of 156 patients (84%). Ten years after treatment, 5 patients underwent secondary hysterectomy resulting in a total of 28 of 81 (35%) (24/77 [31%] after successful uterine artery embolization). Secondary hysterectomies were performed for persisting symptoms in all cases but 1 (for prolapse). After the initial treatment health-related quality of life improved significantly. After 10 years, generic health-related quality of life remained stable, without differences between both groups. The urogenital distress inventory and the defecation distress inventory showed a decrease in both groups, probably related to increasing age, without significant differences between study arms. Satisfaction in both groups remained comparable. The majority of patients declared being (very) satisfied about the received treatment: 78% of the uterine artery embolization group vs 87% in the hysterectomy group. CONCLUSION In about two thirds of uterine artery embolization-treated patients with symptomatic uterine fibroids a hysterectomy can be avoided. Health-related quality of life 10 years after uterine artery embolization or hysterectomy remained comparably stable. Uterine artery embolization is a well-documented and less invasive alternative to hysterectomy for symptomatic uterine fibroids on which eligible patients should be counseled.

Diagnostic Performance of Computed Tomography Angiography in Peripheral Arterial Disease: A Systematic Review and Meta-analysis

CONTEXT Computed tomography angiography (CTA) is an increasingly attractive imaging modality for assessing lower extremity peripheral arterial disease (PAD). OBJECTIVE To determine the accuracy of CTA compared with intra-arterial digital subtraction angiography (DSA) in differentiating extent of disease in patients with PAD. DATA SOURCES AND STUDY SELECTION Search of MEDLINE (January 1966-August 2008), EMBASE (January 1980-August 2008), and the Database of Abstracts of Reviews of Effectiveness for studies comparing CTA with intra-arterial DSA for PAD. Eligible studies compared multidetector CTA with intra-arterial DSA, included at least 10 patients with intermittent claudication or critical limb ischemia, aimed to detect more than 50% stenosis or arterial occlusion, and presented either 2 x 2 or 3 x 3 contingency tables (< or = 50% stenosis vs > 50% stenosis or occlusion), or provided data allowing their construction. DATA EXTRACTION Two reviewers screened potential studies for inclusion and independently extracted study data. Methodological quality was assessed by using the QUADAS instrument. DATA SYNTHESIS Of 909 studies identified, 20 (2.2%) met the inclusion criteria. These 20 studies had a median sample size of 33 (range, 16-279) and included 957 patients, predominantly with intermittent claudication (68%). Methodological quality was moderate. Overall, the sensitivity of CTA for detecting more than 50% stenosis or occlusion was 95% (95% confidence interval [CI], 92%-97%) and specificity was 96% (95% CI, 93%-97%). Computed tomography angiography correctly identified occlusions in 94% of segments, the presence of more than 50% stenosis in 87% of segments, and absence of significant stenosis in 96% of segments. Overstaging occurred in 8% of segments and understaging in 15%. CONCLUSION Computed tomography angiography is an accurate modality to assess presence and extent of PAD in patients with intermittent claudication; however, methodological weaknesses of examined studies prevent definitive conclusions from these data.

Endovascular repair versus open repair of ruptured abdominal aortic aneurysms: a multicenter randomized controlled trial.

Objective: Randomized comparison of endovascular repair (EVAR) with open repair (OR) in patients with a ruptured abdominal aortic aneurysm (RAAA). Background: Despite advances in operative technique and perioperative management RAAA remains fraught with a high rate of death and complications. Outcome may improve with a minimally invasive surgical technique: EVAR. Methods: All patients with a RAAA in the larger Amsterdam area were identified. Logistics for RAAA patients was changed with centralization of care in 3 trial centers. Patients both fit for EVAR and for OR were randomized to either of the treatments. Nonrandomized patients were followed in a prospective cohort. Primary endpoint of the study was the composite of death and severe complications at 30 days. Results: Between April 2004 and February 2011, we identified 520 patients with a RAAA of which 116 could be randomized. The primary endpoint rate for EVAR was 42% and for OR was 47% [absolute risk reduction (ARR) = 5.4%; 95% confidence interval (CI): −13% to +23%]. The 30-day mortality was 21% in patients assigned to EVAR compared with 25% for OR (ARR = 4.4% 95% CI: −11% to +20%). The mortality of all surgically treated patients in the nonrandomized cohort was 30% (95% CI: 26%–35%) and 26% (95% CI: 20% to 32%) in patients with unfavorable anatomy for EVAR, treated by OR at trial centers. Conclusions: This trial did not show a significant difference in combined death and severe complications between EVAR and OR. Mortality for OR both in randomized patients and in cohort patients was lower than anticipated, which may be explained by optimization of logistics, preoperative CT imaging, and centralization of care in centers of expertise.

Prospective Study of Color Duplex Ultrasonography Compared with Contrast Venography in Patients Suspected of Having Deep Venous Thrombosis of the Upper Extremities

Context Venography is the standard test for diagnosing deep venous thrombosis of the upper extremities. It is not an ideal test because it requires intravenous access and contrast media. Ultrasonography is a widely available alternative test, but how feasible and accurate is it? Contribution In 126 consecutive patients with suspected upper-extremity thrombosis, venography and ultrasonography were not feasible in 18% and fewer than 1%, respectively. When venography was used as the reference standard, the likelihood ratio for a positive result on ultrasonography was 4.5 (95% CI, 2.53 to 8.02). The likelihood ratio for a negative result was 0.2 (CI, 0.12 to 5.57). Implications Positive findings on ultrasonography are reasonably accurate for diagnosing deep venous thrombosis of the upper extremities. The Editors The exact incidence of deep venous thrombosis (DVT) of the upper extremities is unknown. A prevalence of 2 cases per 1000 hospital admissions has been reported (1). Deep venous thrombosis of the upper extremities is increasingly recognized as causing high mortality and morbidity, similar to DVT of the leg (2, 3). Deep venous thrombosis of the upper extremities is closely associated with malignant disease and the use of central venous access lines (3-11). Nevertheless, few prospective studies on diagnosis and management of DVT of the upper extremities have been published. Contrast venography is generally considered the reference method for diagnosis of DVT of the upper extremities (2, 3). However, because of its inherent problems, such as availability, use of ionizing radiation, necessity of iodinated contrast media, and technical difficulties in obtaining intravenous access, researchers have searched for more appropriate, noninvasive methods. Ultrasonography is widely available and has been used extensively for diagnosis of DVT of the lower extremities (12-18). However, only a few prospective studies have been done in limited numbers of patients to establish its role in the diagnosis of DVT of the upper extremities (3, 19-22). In addition, ultrasonography is problematic because of the anatomy of the upper extremities. The overlying bony structures and the inability to visualize the central intrathoracic venous system limit the value of compression ultrasonography. Therefore, duplex color ultrasonography has been proposed for diagnosis of DVT of the upper extremities (3, 19-24). We sought to assess the diagnostic accuracy of duplex color ultrasonography compared with contrast venography in patients suspected of having DVT of the upper extremities. Methods Study Sample From August 1996 to March 2001, 126 consecutive outpatients and inpatients with clinically suspected DVT of the upper extremities were referred for diagnostic work-up. Three of these patients were referred twice, and 2 patients were referred three times. Patients were excluded if they were pregnant, were younger than 18 years of age, had renal failure prohibiting contrast venography, had a known allergy to iodinated contrast agents, or were unable to provide informed consent. Informed consent for duplex color ultrasonography and venography was obtained at referral from all but 2 patients, and the Institutional Review Board of the Academic Medical Center, Amsterdam, approved the study. Contrast Venography Contrast venography of the symptomatic extremity was performed by using digital subtraction angiography equipment (Polytron, Siemens, Erlangen, Germany). Standardized protocol consisted of a 30-mL contrast injection in the antecubital vein or, if this was not possible, in a more distal forearm vein in the affected arm. No tourniquet was applied. Patients were studied with the examined arm extended and with little abduction of the upper arm to prevent compression of the axillary vein by soft tissues. Low osmolar nonionic contrast was used at a concentration of 300 mg of iodine per liter (Omnipaque, Nycomed-Amersham, Oslo, Norway). All injections were performed by hand. Digital subtraction images of the brachial, axillary, subclavian, and superior caval veins were obtained at a rate of one frame per second. We defined DVT of the upper extremities as the presence of an intraluminal thrombus or persistent nonfilling of a venous segment in the presence of filling of collateral vessels, as demonstrated by contrast venography. All other findings were considered inadequate for interpretation. Duplex Color Ultrasonography Duplex color ultrasonography of the affected extremity was performed with assessment of the basilic, cephalic, axillary, and subclavian veins. The jugular and innominate veins were not included; because the first is visible only on ultrasonography and the second is visible only on venography, comparison is not possible. After identification of the relevant vessels, a three-step procedure was performed. This involved compression ultrasonography of the venous segments that could be reached, assessment of intravascular thrombus by using color ultrasonography, and flow measurements during respiration to determine the outflow of the venous system by using color Doppler ultrasonography. Patients were asked to perform the Valsalva maneuver to allow assessment of changes in flow pattern. Flow patterns of the unaffected veins in the upper extremities were used only in cases of doubt. All tests were performed by senior residents and staff radiologists who had adequate experience in duplex color ultrasonography, using normal departmental practice. We used three qualified ultrasonography machines that were updated but were not changed during the study (Sonos 2000, Hewlett Packard, Andover, Massachusetts; Aloka 1700 and 2000, Aloka, Tokyo, Japan); probes ranged from 4.5 to 7.5 MHz. Duplex color ultrasonography was considered to demonstrate DVT if it showed noncompressibility of a venous segment, a visible intraluminal thrombus, or an abnormal flow pattern (absent flow or absence of phasic flow pattern indicating outflow obstruction) (3). If none of these findings were present, the results were considered normal. All other findings, lack of visualization, and performance of flow measurements were considered inadequate for interpretation. Study Design We performed a prospective comparative study in consecutive patients with clinically suspected DVT of the upper extremities. All patients underwent duplex color ultrasonography as the first test. Results were reported independently and within 4 hours before performance of the reference method, contrast digital venography. Because we followed departmental routine in our teaching hospital, a variety of qualified residents and staff personnel performed the ultrasonography and venography studies at any time during the day or evening. At all times, the radiologist who performed venography was blinded to the initial results on color duplex ultrasonography. Findings on duplex color ultrasonography were compared with those on contrast venography (the reference method). We also assessed potential factors associated with the cause of DVT of the upper extremities, such as the presence of malignant disease, indwelling catheters, or a hypercoagulable state. Statistical Analysis We calculated diagnostic accuracy (sensitivity and specificity), likelihood ratios (25), and 95% CIs for all findings except indeterminate findings on duplex color ultrasonography (because comparison with contrast venography was not possible). Patient groups in which DVT of the upper extremities was confirmed, excluded, or remained uncertain were compared by using the chi-square test. A P value less than 0.05 indicated statistical significance. Results During the inclusion period, 126 patients were eligible for study enrollment. A total of 27 patients was excluded from the analysis. Contrast venography could not be performed in 16 patients because of medical or technical reasons (failure to obtain venous access, n = 10; renal failure, n = 3; pregnancy, n = 2; and iodinated contrast allergy, n = 1). Another 5 patients were excluded because of logistic reasons, and 2 patients declined to provide informed consent. Therefore, venography could not be performed in 23 of 126 patients (18%). In 1 patient, duplex color ultrasonography was not performed because of logistic reasons. Finally, results of duplex color ultrasonography were indeterminate in 3 patients, resulting in a conclusive rate of 98%. A flow diagram of patients is provided in Figure 1. Figure 1. Flow of patients through the study. A total of 99 patients was available for evaluation after undergoing both duplex color ultrasonography and contrast venography. Forty-four patients were men, and 55 were women; the mean age of all patients was 54 years (range, 18 to 92 years). Deep venous thrombosis was demonstrated by contrast venography in 44 patients (44%). The distribution of thrombi in the veins of the right or left upper extremity on venography is shown in Figure 2. Eight patients had primary thrombosis of unknown cause, while an underlying cause could be shown in 36 patients (Table 1). Malignant disease was present in 63% of patients with proven DVT of the upper extremities and in 19 of 55 patients (35%) in whom DVT was excluded (P < 0.01). Figure 2. Distribution of 29 thrombi in the right upper-extremity veins and 33 thrombi in the left upper-extremity veins on digital subtraction venography. Table 1. Identified Causes of Proven Deep Venous Thrombosis of the Upper Extremities in 44 Patients Results on duplex color ultrasonography were compared with results on contrast venography (Table 2). Eight studies were false negative and 10 were false positive, resulting in a sensitivity and specificity of 82% (95% CI, 70% to 93%) and 82% (CI, 72% to 92%), respectively. The likelihood ratio was 4.5 (CI, 2.53 to 8.02) for a true-positive test result and 0.22 (CI, 0.12 to 0.42) for a true-negative test result. Table 2. Duplex Color Ultrasonography Compared with Contrast Venography in 99 Patients

Endovascular Thrombectomy and Thrombolysis for Severe Cerebral Sinus Thrombosis : A Prospective Study

Background and Purpose— Most patients with cerebral sinus thrombosis (CST) recover after treatment with heparin, but a subgroup has a poor prognosis. Those patients may benefit from endovascular thrombolysis. Methods— Prospective case series. Patients with sinus thrombosis were selected for thrombolysis if they had an altered mental status, coma, straight sinus thrombosis, or large space-occupying lesions. Urokinase was infused into the sinuses (bolus 120 to 600×103 U; then 100×103 U/h) via a jugular catheter, in 15 cases combined with mechanical thrombus disruption or removal. Results— We treated 20 patients (16 women), mean age 32 years. Twelve patients were comatose and 14 had hemorrhagic infarcts before thrombolysis. Twelve patients recovered (Rankin score 0 to 2), 2 survived with handicaps, and 6 died. Factors associated with a fatal outcome were leukemia (3/6 versus 0/14, P=0.02) and large hemorrhagic infarcts (4/6 versus 2/14, P=0.04). Seizures were less frequent in the fatal cases (P=0.05). Patients who died had a larger mean lesion surface than survivors (30.5 versus 13.6 cm2; P=0.03), larger midline shift (5.2 versus 1.7 mm; P=0.02), and a more rapid course (2.7 versus 8.2 days; P=0.01). Five patients who died had large hemispheric infarcts and edema before thrombolysis, causing herniation. Five patients had increased cerebral hemorrhage (3 minor, 2 major) after thrombolysis. Conclusions— Thrombolysis can be effective for severe sinus thrombosis, but patients may deteriorate because of increased cerebral hemorrhage. Patients with large infarcts and impending herniation did not benefit.

Symptomatic Uterine Fibroids: Treatment with Uterine Artery Embolization or Hysterectomy—Results from the Randomized Clinical Embolisation versus Hysterectomy (EMMY) Trial

PURPOSE To prospectively evaluate health-related quality of life (HRQOL) outcomes for uterine artery embolization (UAE) and hysterectomy up to 24 months after the intervention in terms of mental and physical health, urinary and defecatory function, and overall patient satisfaction. MATERIALS AND METHODS Ethics committee approval and informed consent were obtained for the Embolisation versus Hysterectomy Trial. Women (n = 177) with uterine fibroids and heavy menstrual bleeding who were scheduled to undergo hysterectomy were randomly assigned to undergo UAE (n = 88) or hysterectomy (n = 89). HRQOL was measured six times during a 24-month follow-up period with the following validated questionnaires: Medical Outcome Study Short Form 36 (SF-36) mental component summary (MCS) and physical component summary (PCS), Health Utilities Index Mark 3, EuroQol 5D, urogenital distress inventory (UDI), incontinence impact questionnaire, and defecation distress inventory (DDI). Satisfaction was assessed with a seven-point Likert scale. Repeated measurement analysis was performed for between-group analysis. Paired t tests were performed for within-group analysis. Satisfaction was analyzed with the Fisher exact test. RESULTS The SF-36 MCS and PCS, Health Utilities Index Mark 3, EuroQol 5D, and UDI scores were improved significantly in both groups at 6 months and afterward (P < .05). The DDI score was improved significantly in only the UAE group at 6 months and afterward (P < .05). No differences between groups were observed, with the exception of PCS scores at 6-week follow-up: Patients in the UAE group had significantly better scores than did patients in the hysterectomy group (P < .001). Improvement in PCS score at 24-month follow-up was significantly higher for patients who were employed at baseline (P = .035). At 24-month follow-up, patients in the hysterectomy group were significantly more satisfied than those in the UAE group (P = .02). CONCLUSION Both UAE and hysterectomy improved HRQOL. No differences were observed between groups regarding HRQOL at 24-month follow-up. On the basis of HRQOL results, the authors determined that UAE is a good alternative to hysterectomy.

Collapse of a stent-graft following treatment of a traumatic thoracic aortic rupture.

Purpose: To report a collapsed stent-graft used to treat a traumatic aortic rupture. Case Report: A Gore TAG stent-graft was placed in a 20-year-old man with multiple injuries. Postimplantation computed tomographic angiography (CTA) demonstrated no contrast extravasation and total exclusion of the traumatic rupture. Routine CTA 3 months after implantation revealed a collapsed stent-graft located in the outer curve of the distal aortic arch. A Talent stent-graft was placed successfully within the collapsed prosthesis. Postimplantation CTA demonstrated no contrast extravasation and good apposition of the endograft to the aortic wall. At 6 months, the repair remains secure; there is no sign of graft collapse or endoleak. Conclusions: Collapse of stent-grafts can occur after treatment for traumatic aortic ruptures; endovascular methods can be used to restore a satisfactory luminal contour.

Thrombolytic therapy for acute superior mesenteric artery occlusion

The aim of this review is to evaluate thrombolytic therapy for acute superior mesenteric artery occlusion as an alternative or adjunctive treatment modality to surgical therapy and to provide current knowledge for timely and informed decisions regarding treatment of acute mesenteric ischemia. A systematic analysis of the available literature from 1966 to 2003 regarding thrombolytic therapy for superior mesenteric artery thromboembolism was performed. A total of 20 case reports and seven small series covered 48 patients with acute superior mesenteric artery thromboembolism. In the herein reviewed series, thrombolytic therapy of acute superior mesenteric artery thromboembolism resulted in angiographic resolution of the thromboembolism in 43 patients, in clinical success without requiring additional surgical intervention in 30 patients, and in survival in 43 patients, with similar complication rates as in thrombolytic treatment of peripheral vascular occlusions. Remission of abdominal pain during the first few hours of treatment formed the most important indicator of therapeutic success. Insufficient evidence from reviewed literature is available to determine the relative effectiveness and safety of thrombolytic treatment for acute superior mesenteric artery thromboembolism; however, initial results appear to be promising. Thrombolytic therapy can be effective relatively quickly, may obviate surgery, and has the potential to resolve the clot completely. In some cases it can be used as an alternative or neo-adjunctive treatment modality to surgery. A treatment guideline for thrombolysis of acute superior mesenteric artery thromboembolism should be developed.

Feasibility, safety and clinical utility of angiography in patients with suspected pulmonary embolism

The purpose of our study was to assess feasibility, safety and clinical utility of selective pulmonary angiography in patients with suspected pulmonary embolism and a nondiagnostic lung scan. The design was a prospective, descriptive study. The subjects were consecutive patients with clinically suspected pulmonary embolism and a nondiagnostic lung scintigram in whom pulmonary angiography was considered. Angiography was withheld in cases of manifest heart failure, renal failure, mean pulmonary artery pressure above 40 mmHg, or if there were compelling clinical reasons. All patients were followed-up for 6 months. The outcome measures were successful angiography, morbidity, mortality and recurrent pulmonary embolism in patients with normal angiogram in whom anticoagulants were withheld during 6 months of follow-up. Of 487 patients, 196 (40 %) had nondiagnostic lung scan findings. In 46 patients (23 %) pulmonary angiography was withheld. Pulmonary embolism was excluded in 105 patients (70 %), and proven in 40 (27 %) patients. In 5 (3 %) patients the angiogram was inadequate for interpretation. No fatal complications were encountered [95% confidence interval (CI) 0–2.4%]. Nonfatal complications occured in 3 patients (2%; 95% CI 0–3.4%). Pulmonary angiography is safe, rules out pulmonary embolism in two thirds of patients with a nondiagnostic lung scan and can be performed in almost 80% of these patients. It is safe to withhold long-term anticoagulants if a normal angiogram is obtained in this subgroup of patients with clinically suspected pulmonary embolism.

Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis: Rationale and Design of the TO-ACT Trial

Rationale Endovascular thrombolysis, with or without mechanical clot removal, may be beneficial for a subgroup of patients with cerebral venous sinus thrombosis (CVT) who have a poor prognosis despite treatment with heparin. Published experience with endovascular thrombolysis is promising but only based on case series and not on controlled trials. Aim The objective of the Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) trial is to determine if endovascular thrombolysis improves the functional outcome of patients with a severe form of CVT. Design The TO-ACT trial is a multicenter, prospective, randomized, open-label, blinded endpoint trial. Patients are eligible if they have a radiologically proven CVT, a high probability of poor outcome (defined by presence of one or more of the following risk factors: mental status disorder, coma, intracranial hemorrhagic lesion, or thrombosis of the deep cerebral venous system), and if the responsible physician is uncertain if endovascular thrombolysis or standard anticoagulant treatment is better. One hundred sixty-four patients (82 in each treatment arm) will be included to detect a 50% relative reduction (from 40% to 20%) of poor outcomes. Study Patients will be randomized to receive either endovascular thrombolysis or standard therapy (therapeutic doses of heparin). Endovascular thrombolysis is composed of local application of rt-plasminogen activator (PA) or urokinase within the thrombosed sinuses, mechanical thrombosuction, or a combination of both. Patients randomized to endovascular thrombolysis will be treated with heparin before and after the interventional procedure, according to international guidelines. Outcomes The primary endpoint is the modified Rankin score (mRS) at 12 months, with a score ≥2 defined as poor outcome. Secondary outcomes are six-months mRS, mortality, and recanalization rate. Major intracranial and extracranial hemorrhagic complications within one-week after the intervention are the principal safety outcomes. Results will be analyzed according to the ‘intention-to-treat’ principle. Blinded assessors not involved in the treatment of the patient will assess endpoints with standardized questionnaires.