Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM).

BACKGROUND: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date. PATIENTS AND METHODS: In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions). RESULTS: Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1. CONCLUSIONS: Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.

Reprinted article "Realistic expectations for patients with stent-graft treatment of abdominal aortic aneurysms. Results of a European multicentre registry".

OBJECTIVE: The outcomes for patients after endovascular treatment of abdominal aortic aneurysm (AAA) are determined primarily by the endpoints of death and endoleaks, the latter representing continued risk of rupture. The data of a multicentre registry were analysed with regard to the early outcome of stent-graft procedures for AAA and the complications associated with this treatment. In addition, the results during follow-up were analysed by determining mortality and endoleak development as separate endpoints and as a combined endpoint defined as endoleak-free survival. SETTING: 38 European institutions of Vascular Surgery collaborating in a multicentre registry project. PATIENTS AND METHODS: 899 patients with AAA underwent between May 1994 and March 1998 elective endovascular repair (818 men and 81 women; mean age 69 years). 80 (8.9%) of the patients had medical conditions that excluded them from open repair. 818 (91%) of patients had a bifurcated device, 63 (7%) had a straight tube graft, and only 18 (2%) had an aorto-uni-iliac device. Clinical examination and contrast-enhanced computed tomography was performed at fixed follow-up intervals to assess increase or decrease of the maximum transverse diameter (MTD). Endoleaks observed at follow-up were discriminated into persistent endoleak and temporary endoleak. The latter is defined as single time observed endoleaks or with two or more negative imaging studies between observed endoleaks. Life-table analyses were used to calculate the rates of freedom-from-endoleak (no endoleak at any time), freedom-from-persistent endoleak (no persistent endoleak), patient survival, and persistent-endoleak-free-survival. RESULTS: The median follow-up of this patient series was 6.2 months. The ratio between observed and expected follow-up data was 82% for the overall follow-up period. However, at 18 months of follow-up this rate was only 45%. The number of patients followed during this period was sufficient to allow statistically meaningful assessment. The MTD in patients with temporary endoleaks demonstrated a significant decrease at 6 to 12 months compared to preoperative values (mean 57 and 53 respectively, p = 0.004). In patients with persistent endoleaks there was no change between the preoperative and 6-month MTD (mean 57 and 60 mm respectively). At 6 and 18 months freedom-from-endoleak was 83% and 74% and freedom-from-persistent endoleak was 93% and 90%, respectively. The 18-month cumulative patient survival was 88% and the main outcome measure, the persistent endoleak-free-survival was 79%. CONCLUSIONS: The MTD decreases in patients with temporary endoleak, but not in patients with persistent endoleak. Therefore, the use of the rate of freedom-from-persistent endoleak, reflecting absence of persisting endoleaks to estimate the prognosis with regard to the AAA, is justified. Determining persistent endoleak-free survival appears a rational approach to provide a realistic outlook for patients with stent-grafted AAA. The observed 18-month endoleak-free survival reflects a satisfactory mid-term result.

Validation of the chronic venous insufficiency quality of life questionnaire in Dutch patients treated for varicose veins.

BACKGROUND: The Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ) is a disease-specific instrument to measure the impact of chronic venous insufficiency (CVI) on patients' lives. The objective of this study is to test the psychometric properties of the CIVIQ, and to validate the use of the questionnaire translated into the Dutch language. METHODS: A standardised questionnaire, including CIVIQ and Short Form (36) Health Survey (SF-36), was obtained before and 1 month after treatment to all new patients with varicose veins. The feasibility was tested by missing responses and response distribution. CIVIQ scores were compared to the SF-36 scores and between different levels of severity of varicose veins. The CIVIQ's reliability was assessed using Cronbach's alpha and test-retest reliability. The structure was studied using factor analysis. The scores before and after therapy were compared to assess responsiveness. RESULTS: There was a response rate of 93.5%. None of 20 items missed < 10% of responses, but three showed ceiling effect. The CIVIQ correlated well with the physical and moderately with the mental MCS of the SF-36, suggesting a good construct validity of the CIVIQ. The median CIVIQ scores increased significantly with the severity of varicose veins. The CIVIQ showed an excellent internal consistency and an excellent test-retest reliability. The CIVIQ score decreased in 76% of patients after treatment. The results were in accordance with the Norman's rule and showed a median effect size. CONCLUSION: This study confirms the feasibility, validity, reliability and responsiveness of the CIVIQ in patients with varicose veins. The psychometric properties of the Dutch CIVIQ were comparable to the original French version.

Importance of initial stress for abdominal aortic aneurysm wall motion: dynamic MRI validated finite element analysis.

Currently the transverse diameter is the primary decision criterion to assess rupture risk in patients with an abdominal aortic aneurysm (AAA). To obtain a measure for more patient-specific risk assessment, aneurysm wall stress, calculated using finite element analysis (FEA), has been evaluated in literature. In many cases, initial stress, present in the AAA wall during image acquisition, is not taken into account. In the current study the effect of initial stress incorporation (ISI) is determined by directly comparing wall displacements extracted from FEA and dynamic MRI. Ten patients with an aneurysm diameter >5.5 cm were scanned with cardiac triggered MRI. Semi-automatic segmentation of the AAA was performed on the diastolic phase. The segmented in-slice contours were propagated through the remaining cardiac phases using an active contour model as to track wall displacements on MRI. Consequently, FEA with and without ISI (no-ISI) was performed using the diastolic geometry with simultaneously measured intra-aneurysm pressure values as boundary condition. Contours extracted from FEA were compared with MRI contours at corresponding cardiac phases by distance and relative area differences. The wall displacements from FEA with ISI show significant better correspondence with wall motion from MRI data in comparison with the no-ISI FEA (deviation in wall displacement 1.7% vs. 12.4%; p<0.001). Based on these results it can be concluded that incorporation of initial stress significantly improves wall displacement accuracy of FEA and therefore it should be incorporated in future analyses.

Initial stress and nonlinear material behavior in patient-specific AAA wall stress analysis.

Rupture risk estimation of abdominal aortic aneurysms (AAA) is currently based on the maximum diameter of the AAA. A more critical approach is based on AAA wall stress analysis. For that, in most cases, the AAA geometry is obtained from CT-data and treated as a stress free geometry. However, during CT imaging, the AAA is subjected to a time-averaged blood pressure and is therefore not stress free. The aim of this study is to evaluate the effect of neglecting these initial stresses (IS) on the patient-specific AAA wall stress as computed by finite element analysis. Additionally, the contribution of the nonlinear material behavior of the AAA wall is evaluated. Thirty patients with maximum AAA diameters below the current surgery criterion were scanned with contrast-enhanced CT and the AAA's were segmented from the image data. The mean arterial blood pressure (MAP) was measured immediately after the CT-scan and used to compute the IS corresponding with the CT geometry and MAP. Comparisons were made between wall stress obtained with and without IS and with linear and nonlinear material properties. On average, AAA wall stresses as computed with IS were higher than without IS. This was also the case for the stresses computed with the nonlinear material model compared to the linear material model. However, omitting initial stress and material nonlinearity in AAA wall stress computations leads to different effects in the resulting wall stress for each AAA. Therefore, provided that other assumptions made are not predominant, IS cannot be discarded and a nonlinear material model should be used in future patient-specific AAA wall stress analyses.

Patient-specific AAA wall stress analysis: 99-percentile versus peak stress.

OBJECTIVE: Biomechanically, rupture of an Abdominal Aortic Aneurysm (AAA) occurs when the stress acting on the wall due to the blood pressure, exceeds the strength of the wall. Peak wall stress estimations, based on CT reconstruction, may be prone to observer variation. This study focuses on the robustness and reproducibility of AAA wall stress assessment and the relation with geometrical features of the AAA. METHODS: The AAAs of twenty patients were reconstructed by three operators. Both the peak and 99-percentile stress were used for intra- and inter-operator variability using the intraclass correlation coefficient (ICC). A regression analysis was performed to relate the stress parameters with the maximum diameter. Outliers were analyzed by their geometrical characteristics. RESULTS: The intra-operator ICC was 0.73-0.79 for the peak stress and 0.94 for the 99-percentile stress. The inter-operator ICC was 0.71 for the peak stress and 0.95 for the 99-percentile stress. A significant linear relation with the diameter was found only for the 99-percentile stress. CONCLUSIONS: The 99-percentile stress is more reproducible than peak wall stress. A significant relation between wall stress and diameter was found. Other geometrical features had no statistical relation with high stress.

Towards patient-specific risk assessment of abdominal aortic aneurysm.

Diagnosis of vascular disease and selection and planning of therapy are to a large extent based on the geometry of the diseased vessel. Treatment of a particular vascular disease is usually considered if the geometrical parameter that characterizes the severity of the disease, e.g. % vessel narrowing, exceeds a threshold. The thresholds that are used in clinical practice are based on epidemiological knowledge, which has been obtained by clinical studies including large numbers of patients. They may apply "on average", but they can be sub-optimal for individual patients. To realize more patient-specific treatment decision criteria, more detailed knowledge may be required about the vascular hemodynamics, i.e. the blood flow and pressure in the diseased vessel and the biomechanical reaction of the vessel wall to this flow and pressure. Over the last decade, a substantial number of publications have appeared on hemodynamic modeling. Some studies have provided first evidence that this modeling may indeed be used to support therapeutic decisions. The goal of the research reported in this paper is to go one step further, namely to investigate the feasibility of a patient-specific hemodynamic modeling methodology that is not only effective (improves therapeutic decisions), but that is also efficient (easy to use, fast, as much as possible automatic) and robust (insensitive to variation in the quality of the input data, same outcome for different users). A review is presented of our research performed during the last 5 years and the results that were achieved. This research focused on the risk assessment for one particular disease, namely abdominal aortic aneurysm, a life-threatening dilatation of the abdominal aorta.

Impact of study design on outcome after endovascular abdominal aortic aneurysm repair. A comparison between the randomized controlled DREAM-trial and the observational EUROSTAR-registry.

BACKGROUND: Patients with abdominal aortic aneurysm (AAA) can be treated by transfemoral endovascular intervention and by conventional open surgery. Level-one evidence of the safety and efficacy of one treatment mode over the other is only provided by a randomised controlled trial (RCT). Results reported by voluntary registries are considered less valid than data from RCTs. On the other hand the outcome of a RCT may not be generalisable to the common practice because of vigorous selection of patients and institutions. PURPOSE: The outcomes reported by the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial were compared with the results of the EURopean collaborators on Stent-graft techniques for AAA Repair (EUROSTAR) registry. METHODS: To obtain comparable study groups with regard to risk factors equal proportions of ASA I, II and III patients as observed in the endovascular arm of the DREAMtrial were selected at random from the EUROSTAR-registry. All patients had an aneurysm of at least 50mm. Only patients, who had been enrolled into the registry from 1999, were selected to avoid the influence of first generation endografts which are not longer in use. Patient characteristics and outcomes of endovascular AAA repair (EVAR) of EUROSTAR and DREAM-trial participants were compared. Differences in early findings between study groups were assessed by Chi-Square tests for discrete variables and by Wilcoxon rank sum tests for continuous variables. Follow-up variables were analysed by Kaplan-Meier and Cox proportional hazard models. RESULTS: Data of 177 patients of the DREAM trial with randomization to EVAR and 856 patients selected in the EUROSTAR-registry were compared. Baseline characteristics were comparable between the EUROSTAR-cohort and EVAR-arm of the DREAM-trial. The 36-month survival-rate was 87.6% for EVAR-arm in the DREAM-trial similar to the 86.8% found in this EUROSTAR-study population. The freedom of secondary procedures reached after 3 years 85.7%, and 86.9% in the DREAM and EUROSTAR-cohort, respectively. CONCLUSION: We found comparable characteristics and outcomes between patients of comparable risk class of the EUROSTAR-registry and the EVAR-cohort of the DREAM-trial. This demonstrates the following: first, the EUROSTAR-data provide reliable information, and further comparisons of registry data with patients treated by conventional AAA surgery may be justified. Secondly, the various outcomes of the randomised DREAM trial appear generalisable, as it agrees with observations in a broad common practice derived database.

Impact of renal dysfunction on operative mortality following endovascular abdominal aortic aneurysm surgery.

BACKGROUND: Preoperative renal dysfunction is a significant risk factor for death after open abdominal aortic aneurysm repair. The aim of this study was to determine whether renal dysfunction also affected mortality after endovascular aneurysm repair. METHODS: Patients from the EUROSTAR registry were stratified into two groups: 4198 with normal renal function (creatinine less than 133 micromol/ml) and 969 with renal dysfunction (serum creatinine more than 133 micromol/ml). Patient characteristics and postoperative complications in the two groups were compared and the effect of renal dysfunction on operative mortality was analysed by multivariable regression models. RESULTS: Patients with renal dysfunction had significantly more co-morbidities, including cardiac and pulmonary impairment. Thirty-day mortality was significantly higher in the group with renal dysfunction (6.2 versus 2.0 per cent; P<0.001). A significant increase in mortality (5.5 per cent) was also seen in patients with moderate renal dysfunction (serum creatinine 133-265 micromol/ml). After adjustment for age and other risk factors, renal dysfunction was still an independent risk factor for 30-day mortality (odds ratio 2.3, 95 per cent confidence interval 1.6 to 3.3; P<0.001). CONCLUSION: Renal dysfunction was a significant and independent risk factor for death after endovascular aneurysm repair.

[Endarterectomy is a good treatment option in patients with asymptomatic carotid stenosis]. / Endarteriëctomie goede behandeloptie bij patiënten met een asymptomatische carotisstenose.

Among patients with substantial carotid artery stenosis without neurological symptoms, the benefit of carotid endarterectomy had been unclear until this issue was addressed in two randomised trials. The incidence of stroke during follow-up was reduced by approximately one-half after endarterectomy. In appropriate patients, endarterectomy ofa significant asymptomatic carotid stenosis is certainly a treatment option.

Adjuvant procedures performed during endovascular repair of abdominal aortic aneurysm. does it influence outcome?

OBJECTIVE: The purpose of this study was to assess whether there is a difference in outcome of endovascular repair in patients with and without intraoperative adjuvant procedures. METHODS: Demographic, anatomic and operative details were assessed in patients undergoing endovascular repair using the EUROSTAR registry and correlated with morbidity and mortality rates. Three groups of adjuvant procedures: (A) endovascular, (B) surgical peripheral arterial and (C) surgical abdominal arterial were compared with a group of patients without an adjuvant procedure (D). Logistic regression and Cox proportional hazards model were used for statistical analysis. RESULTS: Of 4631 endovascular repairs, 1353 patients (29.2%) required adjuvant procedures. Additional endovascular procedures were performed in 1057 (78.1%), surgical peripheral arterial in 193 (14.3%) and surgical abdominal arterial in 103 (7.6%). The 30-day mortality rate was significantly higher in categories with peripheral arterial surgical (6.7%) and abdominal surgical procedures (7.8%) compared to patients without adjuvant procedures (1.5%, p = .001 and p = .004, respectively). Life-table-analysis demonstrated that late mortality, conversion or rupture rates were not increased in patients with an adjuvant procedure. CONCLUSION: Adjuvant surgical procedures were associated with increased 30-day mortality. Because of this higher risk, endovascular repair should be recommended with caution when surgical adjuvant procedures are anticipated.

Results of endovascular repair of inflammatory abdominal aortic aneurysms. A report from the EUROSTAR database.

OBJECTIVES: To investigate the results following endovascular treatment of patients with inflammatory abdominal aortic aneurysms (IAAA). DESIGN: Retrospective study based on the EUROSTAR registry. MATERIAL AND METHODS: Patients included in the EUROSTAR registry with IAAA (n=52, 1.4%) were compared to those having aneurysms without aortic fibrosis (n=3613, 98.6%). The mean follow-up period in patients with IAAA was 23 months (range 1-60). In 11 of the patients detailed information on the effect of endovascular repair and perianeurysmal fibrosis and ureteral entrapment was obtained by a dedicated questionnaire. RESULTS: Twelve patients (23%) with IAAA had preoperative impairment of renal function and five had known hydronephrosis. Variables that were significantly associated with IAAA included younger age (p<.0001, mean difference 5.9, CI 3.7-7.9) and lower pulmonary risks score (OR 0.38, CI 0.19-0.74). At completion of the endovascular procedure, device stenosis was more frequently observed in patients with IAAA (OR 18.1, CI 3.52-93.0). There were no differences with regard to the rates of mortality, rupture or conversion in patients with IAAA and controls. In the majority, the aneurysm size regressed irrespective of nature of aneurysm. Of the 11 patients with a detailed assessment three had deterioration of renal function and three still had ureteral entrapment during follow-up. CONCLUSION: Despite persistence of perianeurysmal inflammation in a proportion of patients operative and midterm results of endovascular repair were comparable in the patients with inflammatory and standard AAA.

The multicenter experience with a third-generation endovascular device for abdominal aortic aneurysm repair. A report from the EUROSTAR database.

AIM: The purpose of this study was to evaluate the effect of the preoperative diameter of abdominal aortic aneurysms (AAA) upon the midterm outcome obtained by endovascular AAA repair, using a third-generation endovascular device, the Excluder bifurcated endoprosthesis (W. L. Gore & Associates, Inc. Sunnyvale, CA, USA). METHODS: The data of 676 patients, who had undergone endovascular aneurysm repair (EVAR) were analysed. Patients were enrolled over a 6-year period to April 2004 in the EUROSTAR database. Outcomes were compared between 2 groups defined by the preoperative diameter of the aneurysm: group A (n=300), smaller than 5.5 cm; group B (n=376), 5.5 cm or larger. Patient characteristics, details of aorto-iliac anatomy, operative procedure and postoperative complications in the 2 patient groups were compared. Outcome events included aneurysm-related death, overall death, conversion, and late rupture of the aneurysm. Life table analyses and log rank tests were used to compare outcome in the study groups. Multivariate Cox models were used to determine whether baseline and follow-up variables were independently associated with adverse outcomes. RESULTS: Patients in group B were significantly older than patients in group A (73 years vs 71 years respectively; p=0.006), and more frequently were at higher operative risk (ASA-classification >3; 44% vs 59%; p<0.0001). Anatomic differences included a higher incidence of aorto-iliac angulation, a wider and shorter infrarenal neck in group B. Risk factors that were more frequently observed in group B included hypertension, carotid disease and pulmonary disorders. Additional operative events including device migration occurred more frequently in group B (0% vs 2%; p=0.03). Device-related (type I and III combined) endoleaks were more frequently observed at completion arteriography in group B compared to group A (2% vs 4%; p=n.s.). Thirty-day mortality was comparable between the 2 study groups. However, the overall death rate after 3 years of follow-up was significantly higher in patients with larger aneurysms, group B (4% vs 14%; p=0.0025). Similarly, aneurysm-related death was significantly higher in group B (after 3 years 0.3% vs 3%; p=0.02). Aneurysm growth after EVAR was modest low in both study groups (after 2 years 6% vs 8%; non-significant). There was no correlation between growth of the sac and aneurysm-related death. CONCLUSIONS: The midterm outcome after endovascular repair by Excluder devices was satisfactory in patients with small and large AAAs. A higher rate in all-cause deaths and aneurysm-related deaths in patients with larger aneurysms was observed. Post-EVAR aneurysm growth was observed in a small percentage of patients but this did not contribute to aneurysm-related death.

Impact of smoking on endovascular abdominal aortic aneurysm surgery outcome.

OBJECTIVE: Smoking plays a major role in deficiencies of the vascular system, and seems to have consequences for the treatment of cardiovascular diseases. We hypothesized that smokers have a higher mortality and more complications after endovascular abdominal aortic aneurysm surgery than non-smokers. METHODS: We assessed mortality and complications of 3270 patients who underwent endovascular abdominal aortic aneurysm surgery in Europe between January 1994 and July 2001. Survival and (post) operative complications were assessed by smoking status. RESULTS: Mortality did not significantly differ between smokers and non-smokers. Smokers had a higher number of intra-operative additional procedures, but a lower number of late endoleaks in comparison to non-smokers. In addition, smokers had a reduced risk of late type II endoleaks in comparison with non-smokers. CONCLUSION: There seems to be no significant difference in endovascular abdominal aortic aneurysm surgery outcome between smokers and non-smokers, although there were significant differences in intra-operative additional procedures and late endoleaks.

Endograft treatment in ruptured abdominal aortic aneurysms using the Talent AUI stentgraft system. Design of a feasibility study.

OBJECTIVES: To study the outcome of patients with ruptured AAA treated by EVAR using the Talent AUI stentgraft system. DESIGN: A multicenter prospective consecutive patient cohort of 100 patients. MATERIALS: Consecutive patients with ruptured AAA will be screened for treatment by EVAR. All patients screened, including those excluded from EVAR, will be clustered and called the study group. The study group will be compared with a historical group of patients with ruptured AAA derived from literature. The New ERA study started February 2003. OUTCOME: Main outcome events are applicability rate and operative mortality rate of the study group. CONCLUSION: The study rationale and design are reported here.

Is a type II endoleak after EVAR a harbinger of risk? Causes and outcome of open conversion and aneurysm rupture during follow-up.

OBJECTIVE: There is still debate whether type II endoleaks represent a risk for the patient after EVAR. Treatment policies vary from fairly conservative to active intervention. In this analysis risk factors for type II endoleak and adverse events during follow-up were assessed. In addition, risk factors and causes for conversion to open repair and for rupture post-EVAR were studied. METHODS: The data of 3595 patients, who underwent operation between 1996 and 2002 in 114 European institutions that collaborated in the EUROSTAR Registry, were assessed. To accurately assess the influence of type II endoleaks patients with type I, III and combined endoleaks were excluded from the present study cohort. RESULTS: A combined adverse outcome event consisting of aneurysmal growth, transfemoral reintervention, and transabdominal secondary procedures (including laparoscopic branch vessel clipping) occurred in 55% in patients with type II endoleak at 3 years, compared to 15% in patients without any endoleak (p<0.0001). Conversion to open repair or post-EVAR rupture was not significantly associated with type II endoleaks. An independent association of device migration and expansion of the aneurysm with late conversion was observed. The cumulative incidence of aneurysm rupture at 3 years of follow-up was 1.2% for an annual rate of 0.4%. Variables that significantly and independently correlated with rupture were size of the aneurysm at preoperative measurement and device migration during follow-up. CONCLUSION: Endoleak type II may not be harmless as it was more frequently associated with enlargement of the aneurysm and reinterventions. Large aneurysms and migration of the device were the main risk factors for rupture. The clinical implications of these findings may involve more frequent surveillance visits for patients with type II endoleak. Aneurysm expansion is a clear indication for reintervention. Patients with large aneurysms, 65 mm or larger, may also benefit from a more comprehensive surveillance schedule.

Endoleaks during follow-up after endovascular repair of abdominal aortic aneurysm. Are they all dangerous?

AIM: Development of endovascular abdominal aortic aneurysm repair (EVAR) has been accompanied by previously unencoutered complications. The most challenging but least understood of these complications is incomplete seal of the endovascular graft (endoleak), a phenomenon which has a variety of causes. An important consequence of endoleakage may be persistent pressurisation of the aneurysm sac, which may ultimately lead to post-EVAR rupture. METHODS: Data of 110 European centers were recorded in a central database (EUROSTAR). Patient, anatomic characteristics and operative and device details were correlated with the occurrence of different types of endoleaks. Outcome events during follow-up, notably expansion of the aneurysm, incidence of conversion to open repair and post-EVAR rupture were assessed in the different categories of endoleaks and in a group of patients without any endoleak. RESULTS: Type I and III endoleak were associated with an increased frequency of open conversions or risk of rupture of the aneurysm. Device-related endoleaks also correlated with an increased need for secondary interventions. These types of endoleak need to be treated without delay, and when no other possibilities are present, an open conversion to avert the risk of rupture should be considered. Endoleaks type II do not pose an indication for urgent treatment. However, they may not be harmless, as there was a frequent association with enlargement of aneurysm and reinterventions. CONCLUSION: Our findings suggest that more frequent surveillance examinations are indicated than in patients without collateral endoleak. The indication for intervention is primarily dictated by documented expansion of the aneurysm.

Rupture of infra-renal aortic aneurysm after endovascular repair: a series from EUROSTAR registry.

OBJECTIVES: Although small, the risk of rupture after EVAR remains a major concern. The aim of this study was to identify mechanisms of late aneurysm rupture after endovascular repair. METHODS: Patients who suffered a proven aneurysm rupture after EVAR were identified from the EUROSTAR (European Collaborators on Stent-graft Techniques for Abdominal Aortic Aneurysm Repair) registry. Complications preceding rupture were studied to identify common patterns and possible mechanisms of late rupture. RESULTS: A rupture was documented in 34 patients resulting in death of 21 (62%). Adverse events documented during previous follow-up in these patients included endoleak (30%), migration (18%), limb occlusion (12%) and kinking (12%). The findings at time of rupture were documented in 24 patients and including endoleak: Type III (10), Type I (9), Type II (1); stent-graft disintegration (2) and migration (3). Aneurysm diameter changes could be ascertained in 24 patients and had increased in only seven. CONCLUSION: The importance of graft-related endoleak, stent-graft disintegration and migration in the causation of aneurysm rupture was confirmed. Poor compliance with follow-up schedule was also identified as a common feature. However, the absence of complications in some patients, who attended regularly for follow-up, highlights the difficulty of predicting rupture after EVAR.

Emergency treatment of acute symptomatic or ruptured abdominal aortic aneurysm. Outcome of a prospective intent-to-treat by EVAR protocol.

OBJECTIVE: Outcome of treatment of patients with ruptured or symptomatic non-ruptured aneurysm (rAAA and snrAAA), preferentially treated by emergency endovascular repair was assessed. The outcome was compared with a historical group of patients treated by open repair. PATIENTS AND METHODS: Two groups of patients presenting with acute symptomatic AAA were compared. Group I (study group) consisted of 40 consecutive prospectively enrolled patients from May 2001 until June 2002, in whom emergency endovascular abdominal aortic aneurysm repair (e-EVAR) was the preferential management. Short or wide neck or profound hypovolemic shock were exclusion criteria for e-EVAR. Group II (control group) consisted of 28 patients, retrospectively analysed, all treated by conventional surgical repair between January 1999 and May 2001. In group I, 26 patients had rAAA and in group II 22 patients. The other patients had snrAAA. RESULTS: In group I, 14 patients were treated by open repair. Unsuitable anatomy or profound hypovolemia was the cause of open repair in eight patients, while logistic reasons were the reasons for use of open repair in six patients (off-protocol use of open surgery). Thus, in this prospective series the feasibility of EVAR was 80% (32/40). Patient characteristics, proportion rAAA or hemodynamically unstable patients were comparable in group I and II. Volume of blood loss and need for fluid transfusion were significantly less in group I compared to group II. The perioperative mortality in group I was significantly less than in group II (20% vs. 43%, respectively, p = 0.04). If patients with rAAA were considered the mortality was 31% in group I and 50% in group II, which difference did not reach the level of statistical significance. CONCLUSION: e-EVAR was a feasible treatment in the majority of patients with rAAA and snrAAA. Blood loss and the requirements of fluid transfusion were significantly decreased. Most importantly in this institutional series significantly lower first-month mortality was observed in the group with preferential e-EVAR compared to a control group. A multi-center study assessing the outcome of preferential use of e-EVAR in patients with acute symptomatic AAA is required.