The glutathione transferase Mu null genotype leads to lower 6-MMPR levels in patients treated with azathioprine but not with mercaptopurine.

The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 108 RBCs; P<0.01). In patients on MP (control group) 6-MMPR levels were comparable (6195 (1551-10712) versus 6544 (1717-11600) pmol/8 × 108 RBCs; P=0.84). The 6-TGN levels were not affected by the GSTM1 genotype. The presence of genetic variants in GSTA1 and GSTA2 was not related to the 6-MMPR and 6-TGN levels.

Risk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype.

BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial. For this analysis, patients without a variant in TPMT (*2, *3A or*3C) were included. Uni- and multivariate Cox-proportional hazard models were used to identify risk factors for leucopenia and infections. Leucopenia was defined as a white blood cell (WBC) count <3.0 × 109 /L and infections were classified according to the Common Terminology Criteria for Adverse Events. RESULTS: Sixty hundred and ninety-five patients (90.6%) included in the TOPIC-trial had no variant in TPMT, of which 45 (6.5%) developed leucopenia. Median time to leucopenia was 56 (29-112) days. Multivariate analysis showed that use of mercaptopurine compared to azathioprine was associated with leucopenia (hazard ratio [HR] 2.61 [95% CIs, 1.39-4.88; P < .01]) and a higher baseline WBC count was protective (HR 0.80 [95% CIs, 0.71-0.89; P < .01]). Risk factors for infections were older age (per 10 year; HR 2.07 [95% CIs, 1.18-3.63; P = .01]) and concomitant use of biologic drugs (HR 2.15 [95% CIs, 1.14-4.07; P = .02]). CONCLUSIONS: Low baseline WBC count and mercaptopurine, due to a relatively higher dose, were risk factors for thiopurine-induced leucopenia in patients without a TPMT variant.

Early prediction of thiopurine-induced hepatotoxicity in inflammatory bowel disease.

BACKGROUND: Hepatotoxicity, gastrointestinal complaints and general malaise are common limiting adverse reactions of azathioprine and mercaptopurine in IBD patients, often related to high steady-state 6-methylmercaptopurine ribonucleotide (6-MMPR) metabolite concentrations. AIM: To determine the predictive value of 6-MMPR concentrations 1 week after treatment initiation (T1) for the development of these adverse reactions, especially hepatotoxicity, during the first 20 weeks of treatment. METHODS: The cohort study consisted of the first 270 IBD patients starting thiopurine treatment as part of the Dutch randomised-controlled trial evaluating pre-treatment thiopurine S-methyltransferase genotype testing (ClinicalTrials.gov NCT00521950). Blood samples for metabolite assessment were collected at T1. Hepatotoxicity was defined by alanine aminotransaminase elevations >2 times the upper normal limit or a ratio of alanine aminotransaminase/alkaline phosphatase ≥5. RESULTS: Forty-seven patients (17%) presented hepatotoxicity during the first 20 weeks of thiopurine treatment. A T1 6-MMPR threshold of 3615 pmol/8 × 108 erythrocytes was defined. Analysis of patients on stable thiopurine dose (n = 174) showed that those exceeding the 6-MMPR threshold were at increased risk of hepatotoxicity: OR = 3.8 (95% CI: 1.8-8.0). Age, male gender and BMI were significant determinants. A predictive algorithm was developed based on these determinants and the 6-MMPR threshold to assess hepatotoxicity risk [AUC = 0.83 (95% CI: 0.75-0.91)]. 6-MMPR concentrations above the threshold also correlated with gastrointestinal complaints: OR = 2.4 (95% CI: 1.4-4.3), and general malaise: OR = 2.0 (95% CI: 1.1-3.7). CONCLUSIONS: In more than 80% of patients, thiopurine-induced hepatotoxicity could be explained by elevated T1 6-MMPR concentrations and the independent risk factors age, gender and BMI, allowing personalised thiopurine treatment in IBD to prevent early failure.

Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome.

BACKGROUND: The EUMDS registry is an unique prospective, longitudinal observational registry enrolling newly diagnosed patients with lower-risk myelodysplastic syndrome (MDS) from 17 European countries from both university hospitals and smaller regional hospitals. OBJECTIVE: The aim of this study was to describe the usage and clinical impact of erythropoiesis-stimulating agents (ESAs) in 1696 patients enrolled between 2008 and 2014. METHODS: The effects of ESAs on outcomes were assessed using proportional hazards models weighting observations by propensity to receive ESA treatment within a subset of anaemic patients with or without a regular transfusion need. RESULTS: ESA treatment (median duration of 27.5 months, range 0-77 months) was administered to 773 patients (45.6%). Outcomes were assessed in 897 patients (484 ESA treated and 413 untreated). ESA treatment was associated with a nonsignificant survival benefit (HR 0.82, 95% CI: 0.65-1.04, P = 0.09); this benefit was larger amongst patients without prior transfusions (P = 0.07). Amongst 539 patients for whom response to ESA treatment could be defined, median time to first post-ESA treatment transfusion was 6.1 months (IQR: 4.3-15.9 months) in those transfused before ESA treatment compared to 23.3 months (IQR: 7.0-47.8 months) in patients without prior transfusions (HR 2.4, 95% CI: 1.7-3.3, P < 0.0001). Responding patients had a better prognosis in terms of a lower risk of death (HR 0.65, 95% CI: 0.45-0.893, P = 0.018), whereas there was no significant effect on the risk of progression to acute myeloid leukaemia (HR 0.71, 95% CI: 0.39-1.29, P = 0.27). CONCLUSION: Appropriate use of ESAs can significantly delay the onset of a regular transfusion need in patients with lower-risk MDS.

Patient adherence to prescribed medication instructions for dyspepsia: the DIAMOND-study.

BACKGROUND: Insight into patient adherence is needed to enable an effect evaluation of medication for dyspepsia. OBJECTIVES: Adherence was explored by investigating two adherence outcome measures (completeness and intake fidelity) using data from the DIAMOND-study. METHODS: The DIAMOND-study is a pragmatic RCT comparing a 'step-up' with a 'step-down' treatment strategy. In step 1 participants (n =653) were instructed to use five pills/day for maximally 30 days: an antacid 4dd plus a placebo 1dd ('step-up') or a proton pump inhibitor 1dd plus a placebo 4dd ('step-down'). If the complaints persisted, step 2 was started (H(2)-receptor antagonist 2dd), and subsequently step 3 (five pills/day, placebo and verum vice versa from step 1). Completeness was assessed by pill counts, intake fidelity by patient questionnaires measuring the degree to which patients adhered to specific instructions concerning timing, frequency, dose and way of intake. RESULTS: In step 1, patients used on average 3.9 pills/day (78% of the prescribed doses), in step 2, 1.7 pills/day (85%) and in step 3, 3.6 pills/day (72%). For the four times daily pills, half of the patients used less than 80% of the prescribed pills per day. This was one third of the patients for the twice daily pills and one quarter for the once daily pills. There were no completeness differences between active or placebo medication and no differences between the study arms. As regards intake fidelity, 70% of the patients made one or more errors in the medication intake. CONCLUSION: There is room for improvement in adherence rates for dyspepsia medication.

Using CT colonography as a triage technique after a positive faecal occult blood test in colorectal cancer screening.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of CT colonography (CTC) as a triage technique in faecal occult blood test (FOBT)-positive screening participants. METHODS: Consecutive guaiac (G-FOBT) and immunochemical (I-FOBT) FOBT-positive patients scheduled for colonoscopy underwent CTC with iodine tagging bowel preparation. Each CTC was read independently by two experienced observers. Per patient sensitivity, specificity and positive and negative predictive values (PPV and NPV) were calculated based on double reading with different CTC cut-off lesion sizes using segmental unblinded colonoscopy as the reference standard. The acceptability of the technique to patients was evaluated with questionnaires. RESULTS: 302 FOBT-positive patients were included (54 G-FOBT and 248 I-FOBT). 22 FOBT-positive patients (7%) had a colorectal carcinoma and 211 (70%) had a lesion >or=6 mm. Participants considered colonoscopy more burdensome than CTC (p<0.05). Using a 6 mm CTC size cut-off, per patient sensitivity for CTC was 91% (95% CI 85% to 91%) and specificity was 69% (95% CI 60% to 89%) for the detection of colonoscopy lesions >or=6 mm. The PPV of CTC was 87% (95% CI 80% to 93%) and NPV 77% (95% CI 69% to 85%). Using CTC as a triage technique in 100 FOBT-positive patients would mean that colonoscopy could be prevented in 28 patients while missing >or=10 mm lesions in 2 patients. CONCLUSION: CTC with limited bowel preparation has reasonable predictive values in an FOBT-positive population and a higher acceptability to patients than colonoscopy. However, due to the high prevalence of clinically relevant lesions in FOBT-positive patients, CTC is unlikely to be an efficient triage technique in a first round FOBT population screening programme.

Influence of gastric mucosal status on success of stepwise acid suppressive therapy for dyspepsia.

BACKGROUND: The most effective initial treatment strategy of dyspepsia is still under debate. Individual biological characteristics, such as condition of gastric mucosa, might contribute to selection of the most appropriate acid suppression treatment strategy. AIM: To assess whether pre-treatment testing of gastric mucosal status is relevant for treatment success in an RCT comparing step-up and step-down therapies in newly diagnosed dyspepsia patients. METHODS: Baseline serum samples were collected to assess gastric mucosal status using serum levels of pepsinogens-I&II, gastrin-17, and Helicobacter pylori IgA/IgG-antibodies. The 6-month treatment success was compared between step-up and step-down for patients with serum diagnoses: normal; gastritis; corpus atrophy or antrum atrophy. RESULTS: In all, 519 patients (M/F: 249/270, age: 47 (18-85) years, 29%H. pylori+) were randomized to step-up (n = 293) or step-down (n = 226). Normal mucosa, gastritis and corpus atrophy were diagnosed serologically in 70%, 28% and 2% of the patients, evenly distributed between the strategies (P = 0.65). Treatment success was achieved in respectively, 69%, 70% and 70% for the serum diagnosis groups, and did not differ between the strategies. CONCLUSIONS: Dyspepsia treatment success could not be predicted by gastric mucosal status. Therefore, serum diagnosis of gastric mucosal status is no useful tool for patient allocation to acid suppressive treatment strategies.

Psychopathology is associated with dyspeptic symptom severity in primary care patients with a new episode of dyspepsia.

BACKGROUND: Personality and psychiatric disorders are reported to be more common in dyspeptic patients with severe complaints, but it remains unclear whether this association exists for patients with mild and moderate dyspepsia. AIM: To study the association between dyspeptic symptom severity and psychopathology, major life events and coping ability in patients with a new episode of dyspepsia. METHODS; Dyspeptic symptom severity was measured using the validated eight symptom Veldhuyzen van Zanten questionnaire. Psychopathology was measured using the Symptom Check List-90 (SCL 90). Major life events were measured with a modified version of the Social Readjustment Rating Scale (SRRS). Coping styles were measured by a short version of the Utrecht Coping Questionnaire, distinguishing six coping styles. Linear regression was used to assess the relationship between dyspepsia symptom severity and psychological factors. RESULTS: In all, 664 patients with a new episode of uninvestigated dyspepsia, aged >18 years were included. Dyspeptic symptom severity was positively correlated with the presence of depression (P < 0.01), somatization symptoms (P < 0.01), use of an active coping style (P < 0.01) and negatively correlated with age (P < 0.01). CONCLUSIONS: Primary care patients consulting with dyspepsia have higher levels of depression and somatization especially at younger age. An active coping style is associated with dyspepsia symptom severity.

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.

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.

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.

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.

The influence of team experience on outcomes of endovascular stenting of abdominal aortic aneurysms.

OBJECTIVE: To determine whether the experience of the specialist team was associated with adverse events following endovascular treatment of abdominal aortic aneurysms. METHODS: The EUROSTAR database is a voluntary registry of 2863 patients admitted to 93 hospitals in Europe with an abdominal aortic aneurysm treated with endovascular stenting. Mortality, rupture and the need for secondary interventions were the main outcomes. RESULTS: In patients who underwent endovascular stenting by the most experienced specialist teams the mortality rate was 40% lower than in those treated by the least experienced teams (adjusted hazard ratio 0.60, 95% confidence interval: 0.4-1.0; p = 0.05). Also patients treated by the most experienced specialist teams were 68% less likely to have adverse events necessitating a secondary intervention than those treated by the least experienced teams (adjusted hazard ratio 0.32, 95% confidence interval: 0.2-0.5; p < 0.001). The crude rupture rate was 0.1% among patients treated by the most experienced specialist teams and 0.8% among those treated by the least experienced teams (p = 0.74). CONCLUSIONS: Specialist teams with a high level of experience of endovascular abdominal aortic aneurysm stenting encounter lower mortality rates and fewer adverse events leading to secondary interventions.

[Endovascular therapy of aneurysms of the abdominal aorta: report of 4,291 patients of the Eurostar Register]. / Endovaskuläre Therapie von Aneurysmen der Bauchaorta: Bericht über 4291 Patienten des Eurostar-Registers.

BACKGROUND: The Eurostar project is a multicentred database of the outcome of endovascular repair of infra-renal aortic aneurysms. From 1996 to March, 2002, 113 European centres of vascular surgery have contributed. The purpose of this article is to review the medium term (up to 7 years) results of endovascular aneurysm repair as reported to Eurostar. PATIENTS AND METHODS: Patients intended for endovascular aneurysm repair were notified to the Eurostar Data Registry Centre before treatment in order to eliminate bias due to selective reporting. The following data was collected on all patients: (1) their demographic details and the anatomical characteristics of their aneurysms, (2) details of the endovascular device used, (3) procedural complications and the immediate outcome, (4) results of contrast enhanced CT imaging at 1, 3, 6, 12, 18 and 24 months after operation and at yearly intervals thereafter, (5) all adverse events. Life table analysis was performed to determine the cumulative rates of: (1) death from all causes, (2) secondary intervention. RESULTS: By March 2002, pre- and postoperative data of 4291 patients had been registered. The median duration of follow-up was 12 mo (range 0-96). Successful deployment was achieved in 97.8% of the patients with a perioperative (30 day) mortality of 2.4%. Early conversion to open repair occurred in 1.3%. Late rupture of the aneurysm occurred in 35 patients. The significant factors were endoleaks, graft migration and kinking. Late conversion to open repair occurred at an annual rate of approximately 2%. Risk factors (indications) for late conversion were endoleaks, graft migration and kinking. CONCLUSIONS: Endovascular repair of infra-renal aortic aneurysms using the first and second-generation devices that predominated in this study is associated with a risk of early or late failure of 3% per year, based upon an analysis of observed primary endpoints of rupture and conversion.

The evolving technique of endovascular stenting of abdominal aortic aneurysm; time for reappraisal.

PURPOSE: to investigate the occurrence of intra-operative device-related complications during stent-grafting for abdominal aortic aneurysm. MATERIALS AND METHODS: data on patient characteristics, vascular morphology, operative technical details, procedural and device-related complications were obtained from the European collaborators on stent-graft techniques for abdominal aortic aneurysm repair (EUROSTAR) registry. Only intra-operative device-related complications were taken into account. Potential risk factors for device-related complications were examined by logistic regression analysis. The association between these complications and conversion to open surgery and death were determined. RESULTS: between January 1994 and July 2000, 2862 patients in 90 participating hospitals underwent endovascular abdominal aortic aneurysm repair. Device-related complications occurred in 238 (8.3%) patients. Complications were associated with the age of the patient (p=0.002), gender (p=0.05), smoking habit (p=0.001), pre-operative aneurysm diameter (p=0.005), type of device implanted (p=0.0001), fitness of the patient for open surgery (p=0.002), and year of operation (p=0.001). Adjusted for risk factors, the occurrence of complications decreased between 1994 to 2000 from 21.7% to 7.3%, respectively. Patients with device-related complications were 13.6 times (95% CI; 9.2-20.1) more likely to have conversion to an open procedure and 2.4 times (95% CI; 1.4-4.0) more likely to die within 30 days of the operation. CONCLUSIONS: intra-operative device-related complications were common, although appear to be decreasing in frequency, and were significantly related to conversion and post-operative death.

Spinal cord ischaemia after stent-graft treatment for infra-renal abdominal aortic aneurysms. Analysis of the Eurostar database.

OBJECTIVES: to evaluate the prevalence and the possible causes of spinal cord ischaemia (SCI) following endovascular abdominal aneurysm repair (EVAR). Differences in the incidence of this complication between endovascular treatment and published series following conventional treatment were assessed. DESIGN: analysis of patients enrolled in the EUROSTAR collaborators registry. MATERIALS AND METHODS: 2862 patients operated between July 1994 and July 2000 were analysed. Patient characteristics, aneurysm morphology, procedure characteristics and potential causative factors with particular interference with pelvic circulation or pelvic embolisation were related to the risk of SCI. RESULTS: six patients (0.21%) were identified with postoperative symptoms of SCI: one complete spinal cord infarction (type I), two anterior spinal artery syndromes (type II) and three combinations of root lesions and centromedullary infarcts (type III). In the patients with type I or II lesions (3/6) no regression of neurological symptoms was noted, whereas the patients with type III lesions (3/6) had partial regression of symptoms in two cases and a full neurological recovery in one case. There was a significant correlation between emboli (p < 0.001) and coil embolisation of hypogastric or lumbar arteries (p < 0.029) and the development of SCI. CONCLUSIONS: SCI is equally rare following open aortic surgery or EVAR. Microembolism is the probable cause. SCI should be mentioned when taking informed consent.

Endovascular stenting of abdominal aortic aneurysm in patients unfit for elective open surgery. Eurostar group. EUROpean collaborators registry on Stent-graft Techniques for abdominal aortic Aneurysm Repair.

Endovascular aneurysm repair is useful for patients who are judged unfit for surgery. We investigated the outcome of endovascular repair of abdominal aortic aneurysm in patients fit and unfit for surgery. The 1-year cumulative survival for patients unfit for surgery and patients unfit for general anaesthesia was 20% and 23%, respectively. The overall health status of patients was an important predictor of survival after endovascular repair. The risks of endovascular aneurysm repair might, therefore, exceed that of non-operative management. Caution should be used when advising these patients about endovascular repair.