The long-term fate of renal and visceral vessel reconstruction after open thoracoabdominal aortic aneurysm repair.

OBJECTIVES: In the ever-advancing era of endovascular thoracoabdominal aneurysm (TAAA) repair, understanding long-term patency of renovisceral reconstructions after open TAAA repair provides important benchmarks. METHODS: Institutional open TAAA repair patient data were queried. Patients dying during index admission or with incomplete operative detail were excluded. Visceral and renal reconstructions were categorized as bypass, incorporation into a proximal or distal beveled aortic anastomosis, inclusion button, Carrel patch, or hybrid stent along with endarterectomy/stent adjuncts. Axial imaging or angiography determined long-term patency. Vessel event was defined as new occlusion or reintervention after repair. Overall time-to-event analysis was performed as well as separate analyses for each vessel (celiac, superior mesenteric artery [SMA], right renal, left renal) by reconstruction type utilizing Kaplan-Meier methods. Log-rank testing was employed to compare reconstructive strategies. RESULTS: Over 28 years, 604 repairs (type I, 106 [18%]; type II, 73 [12%]; type III, 195 [32%]; and type IV, 230 [38%]) were identified. Follow-up (median, 500 days) was available in 410/570 (72%) celiac, 406/573 (71%) SMA, 379/532 (71.2%) right renal, and 370/515 (72%) left renal reconstructions. There were five celiac, one SMA, eight right renal, and 10 left renal events. No type of reconstruction or adjunct was significantly associated with event. Overall 5-year patency of all renal/visceral reconstructions was 94% (95% confidence interval, 90%-96%). Estimated 5-year patency of the celiac, SMA, left renal, and right renal were similar, and were 99%, 100%, 97%, and 96%, respectively (P = .09). CONCLUSIONS: Visceral and renal long-term patency after open TAAA repair is excellent regardless of reconstructive technique. No differences are appreciated even when target vessel disease is addressed at the time of reconstruction. These findings continue to substantiate the effective long-term durability of open TAAA repair and are particularly germane to the ongoing evolution of endovascular strategies.

Haplotype Analysis of Vitamin D Receptor (VDR) Gene in Breast Cancer Patients.

BACKGROUND: The aim of the study was to evaluate the role of well-characterized vitamin D receptor (VDR) gene polymorphisms, BsmI (rs 1544410), ApaI (rs 7975232), TaqI (rs 731236), and FokI (rs 10735810) and their haplotypes in the pathogenesis of breast cancer in Turkish women. METHODS: The subjects consisted of women including 331 breast cancer patients and 345 healthy controls. After conventional DNA isolation genotyping was done by a PCR-RFLP method, haplotype analysis was performed using Haploview 4.2. RESULTS: Haplotype analysis in different combinations revealed that frequencies of Fbt, fbt, bAt, and bt haplotypes are significantly higher in breast cancer patients than controls (χ2 = 6.862, p = 0.0088; χ2 = 4.176, p = 0.041; χ2 = 4.184, p = 0.0408; χ2 = 8.409, p = 0.0037 respectively). However, no statistically significant difference between genotypes of cases and controls were found when analyzed separately. CONCLUSIONS: All these data support the hypothesis that it is crucial to evaluate VDR gene polymorphism by haplotype analysis in order to understand how changes in VDR sequence influence the function of the VDR gene and how this variability affects the risk of breast cancer.

Multispecialty surgical management of carotid body tumors in the modern era.

OBJECTIVE: The objective of this study was to assess the perioperative and long-term outcomes of carotid body tumor (CBT) resection with a multispecialty (head and neck surgery/vascular surgery) approach. METHODS: Our institutional data registry was queried for Current Procedural Terminology codes (60600, 60605) pertaining to CBT excision. These patient records and operative reports were individually reviewed to determine laterality, preoperative tumor embolization, operative time, estimated blood loss, need for intraoperative transfusion, intraoperative electroencephalogram changes, intraoperative division of the external carotid artery, carotid artery repair, resection of the carotid bifurcation, tumor volume, final pathology, cranial nerve injury, stroke, death, and clinical or radiographic evidence of recurrence. RESULTS: From 1996 to 2018, 74 CBT resections were identified in 68 patients (41 [60%] females; mean age, 50.83 years). The mean tumor volume was 9.92 ± 14.26 cm3 (range, 0.0250-71.0627 cm3). Embolization was performed by a neurointerventional specialist in 27 CBT resections (36%) based on size (embolization 14.27 ± 16.84 cm3 vs 7.17 ± 11.86 cm3; P = .063) and superior extension. This practice resulted in one asymptomatic vertebral dissection, which postponed the surgery. There was a trend toward greater blood loss in the embolization group (embolization 437 ± 545 mL vs 262 ± 222 mL; P = .17); however, no transfusions were required in any patient. The mean operative time was also significantly longer in the embolization group (198.33 ± 61.13 minutes vs 161.5 ± 55.56 minutes; P = .03). Three resections had reversible intraoperative electroencephalogram changes, one of which occurred during carotid clamping. These changes resolved with shunting. Eight external carotid resections (11%) and 6 carotid reconstructions (8.1%; two primary, two patch, and two primary anastomosis) were required. Malignancy was identified in four tumors (5.4%), accounting for four of the six carotid reconstructions. There were no postoperative cranial nerve injuries, no strokes, no reexplorations, and no deaths. One patient developed transient dysphagia from pharyngeal tumor infiltration. Long-term follow-up (mean, 43 ± 54 months), available in 61 of the 68 patients (89.7%), revealed three (4.4%) recurrences. CONCLUSIONS: This large, single-institution series demonstrates that a multispecialty team combining two surgical skill sets for the treatment of this rare, challenging condition yields unparalleled low complication rates with short operative times. This approach, including long-term surveillance for recurrent disease, should be considered to optimize outcomes of CBT resection.

Evaluation of vitamin D receptor gene polymorphisms in patients with differentiated thyroid carcinomas and nodular goiter.

BACKGROUND: The role of vitamin D has previously been determined in autoimmune and malignant thyroid diseases. We aimed to identify the haplotype distribution of single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene, which has been suggested to play a role in the pathogenesis of differentiated thyroid cancers and benign thyroid diseases. METHODS: Two hundred and sixteen patients, 113 with benign and 103 with differentiated thyroid cancers, together with the same number of healthy controls, were included in the study. FokI, BsmI, ApaI, and TaqI SNPs in VDR were analyzed in all participants using the PCR-RFLP method. RESULTS: When the patients with differentiated thyroid cancers or the patients with nodular goiter and control cases were compared for BsmI, ApaI or TaqI polymorphisms, three genotype distributions (BB, Bb, bb; AA, Aa, aa; TT, Tt, tt) were found to not differ significantly. When the patients with differentiated thyroid cancers and control cases were compared for the FokI polymorphism in the VDR gene, the three genotype distributions (FF, Ff, ff) did not differ. However, in patients with nodular goiter, the FF genotype in the FokI polymorphism of the VDR gene was found to be statistically significantly higher (P=0.033). CONCLUSIONS: This is the first study in the literature evaluating the role of VDR gene SNPs in nodular goiter. We can suggest that SNP distribution in the VDR gene is not associated with malignancy but may cause some alterations in thyrocyte morphology and functions.

Nigella sativa and Cancer: A Review Focusing on Breast Cancer, Inhibition of Metastasis and Enhancement of Natural Killer Cell Cytotoxicity.

BACKGROUND: In the last decade, there have been accumulating data that the use of medicinal plants could bring additional benefits to the supportive treatment of various diseases. Nigella sativa (N. sativa, family Ranunculaceae) is one of these plants that has attracted considerable interest. The extracts and seeds of N. sativa and its active component thymoquinone have been studied extensively and the results suggest that N. sativa might carry some therapeutic potential for many diseases, including cancer. METHODS: The selection criteria for references were applied through Pubmed with "N. sativa and cancer", "N. sativa and breast cancer", "N. sativa and metastasis", "N. sativa and cytotoxicity of natural killer cells". The pathway analysis was performed using the PANTHER tool by using five randomly selected N. sativa affected genes (Cyclin D1, P53, p21 protein (Cdc42/Rac) activated kinase 1 (PAK1), B-cell lymphoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF)) in order to elucidate further potentially affected signaling pathways. RESULTS: The aim of this review was to summarize studies regarding the effects of N. sativa in cancer generally, with a focus on breast cancer, its anti-metastatic effects, and how N. sativa modulates the cytotoxicity of Natural Killer cells that play a crucial role in tumor surveillance. CONCLUSION: In summary, the data suggest that N. sativa might be used for its anti-cancer and antimetastatic properties and as an immune system activator against cancer.

Presentation, surgical intervention, and long-term survival in patients with Marfan syndrome.

OBJECTIVE: Patients with Marfan syndrome (MFS) often present with acute catastrophic aortic events at a young age and have a shortened life span. This study examines the impact of presentation and demographics on late survival in patients with MFS. METHODS: Adults with confirmed MFS in our thoracic aortic center dataset were identified and statistical analysis performed to identify the incidence and predictors of aortic interventions and late mortality. RESULTS: We identified 301 patients with a MFS initial diagnosis at age 17 years (interquartile range, 4-30 years) with presentation into our thoracic aortic center at 21 years (interquartile range, 8-34 years). The average follow-up in our center was 10 ± 10 years. Clinical features were 41% male, 86% white race, coronary artery disease 28%, hypertension 40%, peripheral vascular disease 19%, and anti-impulse agent in 51% (ß-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, calcium channel blocker). Distribution of operative aortic pathology was isolated to the ascending aorta (70%) and descending aorta (8%). One hundred seventy-eight patients (59%) required primary aortic surgery (36% emergent). Primary procedures were cardiac (aortic valve/root) in nature in 94%. Seventy-four patients (42%) required multiple aortic procedures at a mean of 9.2 ± 6.9 years, involving the thoracoabdominal aorta in 65%, thoracic aorta in 37%, and abdominal aorta in 21%. Patients who required multiple aortic procedures were more likely (P < .05) to have coronary artery disease (50% vs 30%), and peripheral vascular disease (43% vs 18%). Multiple aortic procedures were also more likely (P < .05) in patients who developed de novo distal dissection (14% vs 0%), had prior dissection (47% vs 18%), or unknown MFS at the time of the initial procedure (27% vs 63%). Multivariable analysis identified prior dissection as an independent predictor of need for emergent surgery (odds ratio, 13.20; 95% confidence interval, 4.64-37.30; P < .05), as well as additional aortic surgery (odds ratio, 4.42; 95% confidence interval, 1.87-10.50; P < .05). Kaplan-Meier analysis showed similar 10-year survival with or without aortic interventions (82% with vs 89% without; P = .08). Late survival was decreased in patients undergoing emergent initial procedures (66% vs 89%; P < .01), as well as those undergoing multiple operations (74% vs 86%; P = .03). CONCLUSIONS: These data indicate that, in the modern era, the mode of presentation and need for multiple procedures have a detrimental impact on late survival. Additionally, the presence of acute or chronic dissection predicts the need for additional aortic procedures during follow-up.

Association of Serum Paraoxonase 1 Activities, Polymorphisms and Oxidative Stress in Breast Cancer Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The aim of the study was to investigate the association of paraoxonase 1 (PON1) polymorphism, PON1/arylesterase (ARE) activity and oxidative stress index (OSI) in breast cancer (BC) patients with type 2 diabetes (DM). METHODS: Our study group consisted of 30 healthy women (HV group) and 66 female BC patients. The BC patients were divided into two groups: those with (n=37) and without DM (n=29) (BDM and NBDM group). Genotyping of PON1 Q192R and L55M polymorphisms were done by polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) method. Serum PON1/ARE enzyme activities, total oxidant status (TOS) and total antioxidant status (TAS) were analysed by spectrophotometric method. The ratio of TOS to TAS was accepted as the oxidative stress index (OSI). RESULTS: PON1 Q192R genotype frequency distribution was significantly different in the BDM group compared to the NBDM group (p=0.021). When alleles distribution was examined, R and L alleles were significantly lower, Q and M alleles were significantly higher in the BDM group than in the NBDM group (p<0.001). TOS and OSI were statistically higher in BC patients than HV group (p<0.001). CONCLUSIONS: Our results suggest that PON1 gene Q and M alleles may be the risk factors predisposing formation of BC due to increased oxidant damage seen in DM. However, these statements require further confirmation with screening PON1 polymorphism in a greater number of patients with DM, and also wide range follow-up studies are necessary for the same purpose.

The Relationship Between Urothelial Type Bladder Cancer, Plasma 25-Hydroxyvitamin D Levels, and Vitamin D Receptor ApaI BsmI FokI, and TaqI Polymorphisms.

BACKGROUND: Bladder cancer is an important health problem which ranks 4th among most frequently seen cancer types in men. In our study we aimed to investigate the correlations among urothelial type bladder cancer polymorphisms, ApaI, BsmI, FokI, and TaqI, prevalently observed in the vitamin D receptor (VDR) gene and plasma vitamin D levels in a Turkish population. METHODS: Our study included 101 patients and 109 control subjects. Plasma 25(OH)D levels were determined using a HPLC method and VDR gene polymorphisms with PCR-RFLP method. RESULTS: A statistically significant intergroup difference was not observed with regard to age, gender, and BMIs of the patients. Median (min - max) 25(OH)D levels in the patient and the control groups were determined as 11.9 ng/dL (1.9 - 33.0 ng/dL) and 9.7 ng/dL (2.1 - 39.5 ng/dL), respectively. A statistically significant intergroup difference was not observed with regard to 25(OH)D levels (p = 0.402). A statistically significant intergroup differ-ence was not observed with regard to genotype distribution of ApaI, BsmI, and TaqI polymorphisms and allele frequencies. Control and urothelial type bladder cancer groups showed a statistically significant difference with respect to genotype distribution of FokI polymorphism (p = 0.048). However in a binary logistic regression model, when corrected OR values were estimated by including smoking history in the model, the correlation detected be-tween the presence of FF and increased risk of disease was not statistically significant (ORadj = 1.64, 95% CI = 0.89 - 3.02, p = 0.114). CONCLUSIONS: In the light of the data concerning Turkish population a statistically significant correlation could not be demonstrated between plasma vitamin D levels, ApaI, BsmI, FokI, and TaqI polymorphisms, and urothelial type bladder cancers. Since literature data are limited in number, further studies should be conducted in larger patient groups.

Contralateral Occlusion and Concomitant Procedures Drive Risk of Non-ipsilateral Stroke After Carotid Endarterectomy.

OBJECTIVES: Stroke after carotid endarterectomy (CEA) has been assessed widely. However, factors enhancing non-ipsilateral stroke risk are poorly defined. The aim of this study was to identify drivers of 30 day non-ipsilateral stroke after CEA in the Vascular Quality Initiative (VQI) and assess long-term survival based on laterality of post-operative stroke. METHODS: The VQI was queried between April 1, 2003, and March 31, 2017, for all CEA. Bilateral carotid procedures within 30 days were excluded. Thirty day non-ipsilateral strokes were identified. Factors were examined to discriminate between patients with and without non-ipsilateral stroke. Univariable analysis followed by multivariable logistic regression was performed. Kaplan-Meier and log rank methods were used to estimate and compare survival. RESULTS: During this 14 year period, 80,230 CEA in 74,928 patients met the criteria. The average age was 70.3 ± 9.3 years. Most were male (48,506; 60%), Caucasian (73,967; 92%), smokers (60,543; 76%), and asymptomatic (43,074; 54%). Contralateral stenosis ≥70% was present in 8033 (10%) with 2239 (3%) having contralateral occlusion. In 491 (0.6%) patients, peri-operative non-ipsilateral stroke occurred. After characterising univariable associations, logistic regression identified independent drivers of non-ipsilateral stroke after CEA. Operative urgency (p = .001), symptomatic disease (p < .001) and contralateral occlusion (p = .001) were pre-operative drivers. Operative predictors included shunt use (p = .008), CEA with cardiac surgery (p = .013), and CEA with concomitant proximal ipsilateral endovascular intervention (p = .01). Use of dextran (p = .005) and anti-angiotensin therapy (p = .03) were protective. Reperfusion syndrome (p < .001), re-exploration (p < .001), myocardial infarction (p < .001), and intravenous treatment of hypotension (p < .001) or hypertension (p < .001) were post-operative correlates. Non-ipsilateral stroke 30 day mortality was less than ipsilateral stroke (6.1% vs. 10.3%; p = .007). Five year survival after non-ipsilateral stroke was 73%, and no different from ipsilateral stroke 76% (p = .16). Both were worse than without stroke (88%; p < .001). CONCLUSION: Non-ipsilateral stroke after CEA is rare. Features driving risk surround global disease burden, combined procedures, and haemodynamic fluctuations. Contralateral occlusion independently increases non-ipsilateral stroke risk. Regardless of laterality or location, effects of stroke after CEA on long-term survival are similar.

The effect of combining coronary bypass with carotid endarterectomy in patients with unrevascularized severe coronary disease.

OBJECTIVE: Management of significant carotid stenosis in those with symptomatic coronary disease remains controversial. Staged and combined carotid endarterectomy (CEA) with coronary artery bypass grafting has been described. Yet, an understanding of the additive risks of these approaches is poor. This study sought to assess outcomes in patients with clinically relevant coronary disease undergoing either isolated CEA (ICEA) or combined CEA and coronary artery bypass (concurrent coronary artery bypass [CCAB]). METHODS: All CEAs in the Vascular Quality Initiative from 2003 to 2017 were reviewed. CCABs were identified, as were ICEAs in patients with unrevascularized stable angina, unstable angina, or myocardial infarction (MI) within 6 months of operation. CCABs were compared with ICEAs as well as with a risk-matched cohort of ICEAs. Primary outcomes included perioperative stroke, all-cause death, MI, and these as composite (SDM). Univariate analysis and logistic regression were performed. RESULTS: There were 4042 patients identified, including 2582 ICEA patients (64%) and 1460 CCAB patients (36%); 61% were male, 91% were white, and 39% had symptomatic carotid disease. Overall stroke was 3.5%, death 1.8%, and SDM 6.0%. ICEA had higher rates of postoperative MI (1.9% vs 0.9%; P = .01) but lower rates of stroke (2.8% vs 4.7%; P = .002), death (1.0% vs 3.0%; P < .001), and SDM (5.1% vs 7.5%; P = .002). After regression, predictors of SDM were congestive heart failure (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.4; P < .001), urgent operation (OR, 1.6; 95% CI, 1.2-2.2; P = .001), and CCAB (OR, 1.3; 95% CI, 1.01-1.7; P = .04). After propensity matching, ICEA continued to have higher rates of perioperative MI (2.6% vs 1.0%; P = .01) and lower rates of death (1.0% vs 3.0%; P = .001). However, there were no longer differences in stroke (3.2% vs 4.6%; P = .10) or SDM (6.3% vs 7.8%; P = .18). Within the matched cohort, predictors of SDM included chronic obstructive pulmonary disease (OR, 1.6; 95% CI, 1.1-2.2; P = .01), congestive heart failure (OR, 1.7; 95% CI, 1.1-2.5; P = .01), and symptomatic carotid disease (OR, 1.5; 95% CI, 1.03-2.1; P = .03). CCAB was not significant (OR, 1.3; 95% CI, 0.9-1.8; P = .18). CONCLUSIONS: In patients with unrevascularized, clinically relevant coronary disease, CCAB reduces operative MI but increases risk of stroke and death. After risk adjustment, MI remains higher in ICEA, but differences in 30-day stroke and SDM between ICEA and CCAB are no longer appreciated. These data suggest that CEA risk undertaken in patients with unrevascularized coronary disease is not inconsequential, and outcomes are similar to those of CCAB.

Regional variation in use and outcomes of combined carotid endarterectomy and coronary artery bypass.

OBJECTIVE: In treating concomitant carotid and coronary disease, some recommend staged carotid endarterectomy (CEA) and coronary artery bypass grafting, whereas others favor the combined approach (CCAB). Pressure to reduce surgical variation and to improve quality is real, yet little is known about how geographic practice differences affect outcomes. Using the Vascular Quality Initiative (VQI), this study evaluated regional variation in use and outcomes of CCAB. METHODS: All CCAB procedures in the VQI from 2003 to 2017 were reviewed and stratified into four regions, as defined by the United States Census Bureau. Primary outcomes included perioperative stroke, death, myocardial infarction (MI), and these as composite (SDM). A χ2 analysis was performed. RESULTS: There were 1495 CCAB procedures identified, representing 1.8% of the VQI CEAs. Regions included the following: Midwest (MW), 32%; Northeast (NE), 39%; South (S), 25%; and West (W), 4%. Most were male (70%) and white (92%). There was significant regional variation in proportional volume of CCABs to all CEAs (0.7% [W] to 2.5% [MW]; P < .001). Regional variation in patch use (78% [W] to 93% [MW]; P < .001), shunting (29% [W] to 71% [MW]; P < .001), and electroencephalography monitoring (13% [W] to 52% [NE]; P < .001) was also significant. Overall perioperative stroke was 3.6%; death, 3.0%; and SDM, 6.8%. No regional difference was seen in outcomes of mortality (1.5% [MW] to 4.2% [NE]; P = .05), stroke (2.8% [NE] to 4.4% [MW]; P = .52), and MI (0.6% [MW] to 1.8% [W]; P = .62). When the Bonferroni correction was used, there remained no difference in stroke, MI, or SDM across regions, but mortality became significant. Using the Society for Vascular Surgery guidelines for consideration of CCAB, the minority of patients fell within the symptomatic carotid stenosis (SYMP, 15%; n = 218) or severe (≥70%) asymptomatic bilateral carotid disease (BIL, 18%; n = 267) categories. The most common indication was asymptomatic unilateral severe carotid stenosis (UNI, 37%; n = 552). There were no differences in regional outcomes stratified by indication (SYMP, BIL, UNI). Overall, when SYMP and BIL were compared with UNI, UNI had lower rates of stroke (2.4% vs 4.9%; P = .03) but similar MI (0.7% vs 1.2%; P = .40) and mortality (2.2% vs 2.5%; P = .75). CONCLUSIONS: Significant variation exists across VQI centers in the use of CCAB. Despite differences in volume and practices, regional perioperative outcomes are similar. UNI is the most commonly used indication and has lower stroke rates relative to SYMP and BIL. CCAB is performed well across the United States, but most patients fall outside of Society for Vascular Surgery guidelines.

Durability of open surgical repair of type I-III thoracoabdominal aortic aneurysm.

OBJECTIVE: Early outcomes and late mortality after open repair of extent I to III thoracoabdominal aortic aneurysms (TAAAs) are described, but late graft and aortic events are seldom detailed. This study investigated long-term aortic and graft outcomes as these data are increasingly important as endovascular repair matures. METHODS: During 28 years, 516 patients underwent repair (type I, n = 177 [34%]; type II, n = 100 [20%]; type III, n = 239 [46%]). Patients were monitored for late events. Late aortic events were defined as native aortic disease leading to death or further intervention. Planned secondary procedures were excluded. Graft complications included anastomotic aneurysm, graft infection, and branch occlusions. Variables were assessed for association with end points using log-rank methods and Cox proportional hazards regression. Time-to-event analysis was performed using Kaplan-Meier methods. RESULTS: In-hospital death occurred in 40 patients (8%), leaving 476 for surveillance. Mean age was 69.8 ± 10.5 years. Mean follow-up was 4.9 ± 4.6 years. Repair conduct included distal aortic perfusion and motor evoked potential monitoring (n = 169 [35.5%]), clamp and sew (n = 307 [64.5%]), and selectively applied in-line mesenteric shunting (n = 172 [36.1%]). At the time of repair, 117 patients (24.6%) had 122 synchronous, noncontiguous aortic aneurysms. There were 98 late aortic and graft events in 89 patients (18.7%); 62 aortic-related events occurred in 56 patients (12%; elective repair, n = 47; emergent repair, n = 14; type A dissection, n = 1) at a mean of 4.4 ± 4.2 years after repair. Variables independently predictive of an aortic event were aortic clamp time (hazard ratio [HR], 1.02/min; P = .001), type III extent (HR, 2.5; P = .008), and expansion of retained aorta (HR, 10.4; P < .0005). There were 33 patients (7%) who experienced 36 graft-related events (anastomotic aneurysm, n = 14 [3% of cohort; aortic, n = 7; visceral patch, n = 6; side graft, n = 1]; graft infection, n = 12; renovisceral occlusion/repair, n = 9 [1.9%; side-arm graft, n = 8; native, n = 1]; and anastomotic stricture, n = 1) occurring at 4.7 ± 4.5 years. Variables predictive of graft-related complication were type II extent (HR, 3.4; P = .002) and distal aortic perfusion and motor evoked potential monitoring (HR, 3.6; P = .02). Freedom from aortic- or graft-related event was 80% at 5 years. Freedom from any aortic or graft reintervention was 84% at 5 years. Aortic-related mortality after discharge was 2.7% and estimated to be 3.1% at 5 years. Overall survival was 67% and 44% at 5 and 10 years, respectively. CONCLUSIONS: After type I-III TAAA repair, late aortic and graft-related events occur in 19% of patients. Native aortic disease sequelae are more common than graft complication. Aortic events are predicted by complex operation and degree of remaining aorta. Extensive reconstruction drives graft-related events. Ultimately, reintervention is rare and aorta-related mortality low. These findings verify durability of extensive TAAA repair, serving as benchmarks for endovascular repair.

Durability of open surgical repair of type IV thoracoabdominal aortic aneurysm.

OBJECTIVE: Perioperative outcomes and late mortality after open type IV thoracoabdominal aortic aneurysm (TAAA) repair are known, yet risk of late graft and subsequent aortic events is infrequently described. Such data are increasingly important as endovascular repair becomes an option and are the subject of this study. METHODS: During a 27-year interval, 233 patients underwent open surgical repair of type IV TAAA. Surviving patients were monitored for late aortic or graft-related events. Late aortic events were defined as native aortic disease unrelated to the prior reconstruction leading to death or further intervention. Graft-related complications included anastomotic aneurysm, graft infection, and branch occlusion. Variables were assessed for association with study end points using univariate log-rank methods and Cox proportional hazards regression. Time-to-event analysis was performed using Kaplan-Meier techniques. RESULTS: In-hospital mortality occurred in 7 patients (3%), leaving 226 available for surveillance. Mean age was 72 ± 9 years; 50 patients (21%) had 52 synchronous, noncontiguous aortic aneurysms at time of repair (n = 11 ascending aorta/arch; n = 41 descending thoracic aorta). Mean follow-up was 4.3 ± 3.7 years (median, 3.5 years; interquartile range, 5 years). Aortic events (n = 19 [8%]) included elective aortic repair (n = 15), emergent repair (n = 2), and atheroembolic embolization (n = 2) at a mean of 2.6 ± 2.2 years after type IV TAAA repair. There were 17 patients (8%) who experienced graft-related events (renovisceral occlusion [n = 10; 4% of cohort], anastomotic aneurysm repair [n = 5], graft infection [n = 1], and graft-caval fistula [n = 1]) occurring at 1.7 ± 1.9 years after repair. Variables independently predictive of an aortic event were initial rupture (hazard ratio, 5.6; P = .02) and native aortic expansion during surveillance (hazard ratio, 3.9; P = .04). No independent predictors of graft-related complication were identified. Freedom from an aortic or graft-related event was 93% at 1 year and 66% at 5 years. Freedom from graft or aortic reintervention was 86% at 5 years. Aortic-related mortality in follow-up was 2% and estimated to be 5% at 5 years after type IV TAAA repair. Overall survival was 92% and 66% at 1 year and 5 years, respectively. CONCLUSIONS: After open type IV TAAA repair, late aortic and graft-related events are uncommon. Native aortic disease sequelae and graft complications occur with equal frequency and with similar temporal relation to repair. Need for reintervention is infrequent, and aortic-related mortality is low. These findings verify durability of open type IV TAAA repair and serve as long-term comparative results for endovascular repair.

A Regional Experience with Carotid Endarterectomy in Patients with a History of Neck Radiation.

BACKGROUND: Historically, a history of neck radiation has been considered as an anatomic risk factor for poor outcomes after carotid endarterectomy (CEA). However, this is based on small and primarily single institution reports with few comparative series. This study uses a regional quality database to compare perioperative outcomes of CEA in patients with and without a history of neck radiation (RAD and NORAD, respectively). METHODS: The Vascular Study Group of New England database was queried for all CEA from 2003 to 2017. The RAD group included a history of neck radiation. Primary end points included perioperative stroke (30-day), myocardial infarction (MI) (in-hospital), death (30-day), a composite end point including major adverse events (MAEs: stroke, MI, and death), and long-term survival. RESULTS: Overall, 18,832 patients underwent CEA (18,551 NORAD, 281 RAD). Baseline demographics differed in the following: the RAD group more frequently had a history of contralateral carotid artery stenting (1.4% vs. 0.3%, P = 0.009), anatomic high risk features (12.8% vs. 1.3%, P < 0.001), and contralateral carotid occlusion (5.3% vs. 2.4%, P = 0.005). The NORAD cohort comprised mostly women (38.9% vs. 29.5%, P < 0.001), had American Society of Anesthesiologists class 4 or 5 (8.0% vs. 4.6%, P = 0.035), had higher body mass index (28.3 ± 5.6 vs. 27.1 ± 5.4, P < 0.001), on a beta blocker preoperatively (68.0% vs. 62.3%, P = 0.042), and had major cardiovascular comorbidities including coronary artery disease (29.6% vs. 22.1%, P = 0.006). There were no differences in the percent stenosis, proportion symptomatic (37.4% vs. 34.2%, P = 0.259), use of preoperative antiplatelet agents or statins. Electroencephalography monitoring was more frequently used in RAD (54.5% vs. 46.0%, P = 0.005). There was no difference in perioperative complications, including stroke (RAD 0.4% vs. NORAD 0.7%, P > 0.999), MI (0.4% vs. 0.9%, P = 0.736), death (0.7% vs. 0.6%, P = 0.683), MAE (2.1% vs. 2.2%, P > 0.999), or long-term survival (79.9% vs. 85.0%, P = 0.357). When only symptomatic or asymptomatic stenosis was considered, there remained no difference in primary end points. However, perioperative neurologic events (transient ischemic attack or stroke) was higher in symptomatic RAD versus symptomatic NORAD (6.7% vs. 2.6%, P = 0.020). CONCLUSIONS: This regional experience with CEA in RAD patients shows similar perioperative morbidity, mortality, and long-term survival when compared with CEA for standard surgical patients (NORAD). Symptomatic presentation was associated with higher perioperative neurologic events, but this was not reflected in stroke rates. RAD is not always a contraindication to CEA and select patients can expect outcomes comparable to standard surgical patients.

Addition of proximal intervention to carotid endarterectomy increases risk of stroke and death.

OBJECTIVE: Adding ipsilateral, proximal endovascular (IPE) intervention to carotid endarterectomy (CEA) for the treatment of tandem bifurcation and supra-aortic trunk disease is controversial. Some suggest that this combined strategy (CEA + IPE) confers no risk over isolated CEA (ICEA). Others disagree, reserving CEA + IPE for symptomatic patients. Using the Vascular Quality Initiative (VQI), this study assessed the effect of adding IPE to CEA on stroke and death risk. We further weighed CEA + IPE outcomes in the context of symptomatic status and Society for Vascular Surgery guidelines. METHODS: All CEAs in the VQI database from 2003 to 2017 were reviewed. Urgent and redo CEAs were excluded. CEA + IPE procedures were identified. To isolate the effect of IPE, patients undergoing other concurrent procedures were removed, providing an ICEA cohort. Primary end points were perioperative (30-day) stroke and death. Univariate and logistic regression analyses were performed. RESULTS: After exclusion and identification of CEA + IPE, 66,519 procedures were available for analysis. Of these, 66,115 represented ICEA and 404 represented CEA + IPE. Most patients (60%) were male, 93% were white, and 41% were symptomatic. Average age was 70 ± 9 years. Those undergoing CEA + IPE were more likely to be female (50% vs 40%; P < .001) and smokers (87% vs 76%; P < .001), and they were more likely to have coronary artery disease (32% vs 27%; P = .04), congestive heart failure (14% vs 10%; P = .01), and chronic obstructive pulmonary disease (30% vs 22%; P < .001). ICEA patients were more likely to have severe ipsilateral stenosis (86% vs 80%; P = .002) and to undergo intraoperative shunting (53% vs 49%; P = .05). There was no difference in 30-day mortality between cohorts (1% vs 1%; P = .23). However, CEA + IPE had higher rates of perioperative stroke (3.0% vs 1.4%; P = .01) and combined 30-day stroke and death (3.5% vs 1.8%; P = .02). When patients were stratified by symptomatic status, there were no differences in primary end points between cohorts in asymptomatic patients. In symptomatic patients, CEA + IPE carried significantly higher stroke (4.9% vs 1.9%; P = .002) and stroke and death risk (6.0% vs 2.4%; P = .002). After risk adjustment, predictors of stroke and death were diabetes (odds ratio [OR], 1.2; P = .001), symptomatic status (OR, 1.7; P < .001), and CEA + IPE (OR, 1.9; P = .02). CONCLUSIONS: The addition of IPE to CEA confers increased stroke and death risk over ICEA. Risk is largely in symptomatic patients. Although CEA + IPE increases risk compared with ICEA, overall risk remains low. Based on this VQI analysis, CEA + IPE outcomes for asymptomatic patients fall within Society for Vascular Surgery guidelines for ICEA. Those for symptomatic patients do not, and consideration should be given to other surgical bypass, cerebral protection, and staged strategies.

Risk factor profile and anatomic features of previously asymptomatic patients presenting with carotid-related stroke.

OBJECTIVE: Although carotid atherosclerotic-mediated stroke remains a major cause of morbidity and mortality, some have suggested intervention in carotid stenosis should be limited to symptomatic patients given the advances in medical therapy. The present study was conducted to assess the atherosclerotic risk factor profiles, anatomic features, and clinical outcomes of previously asymptomatic patients admitted with stroke of carotid etiology. METHODS: We reviewed the data from 3382 patients admitted to a tertiary referral center with an ischemic stroke during 2005 to 2015. We focused on patients admitted with a radiographically confirmed infarct ipsilateral to a documented carotid artery stenosis ≥50%, with the admitting neurology team adjudicating the stroke etiology as carotid related. Patients were excluded if they had had a previous transient ischemic attack, previous infarct ipsilateral to any carotid lesion, or previous carotid revascularization, intracranial hemorrhage, or malignancy. Patient demographic data, medical treatments before stroke, stroke admission carotid imaging, and stroke treatments and outcomes were assessed. RESULTS: A total of 219 carotid stroke patients (7% of all strokes) were identified, of whom 61% were white and 66% were men, with a mean age of 68 ± 12 years. Hypertension (79%) and smoking (33% current; 29% former) were predominant risk factors. On admission, 50% were receiving antiplatelet therapy (aspirin, n = 92 [41%]; clopidogrel, n = 9 [4%]; dual therapy, n = 11 [5%]) and 55% were receiving lipid-lowering agents (statin, n = 115 [53%]; other, n = 6 [2%]); 77 patients (35%) were receiving both antiplatelet and lipid-lowering therapy. Of the 219 patients, 156 (71%) presented with a moderate or severe stroke (National Institutes of Health stroke scale ≥5 at admission), 54 (25%) received lytic therapy, 96 (43%) presented with an occluded ipsilateral internal carotid artery, and 117 (53%) ultimately underwent carotid revascularization at a median of 4 days. Individuals receiving both antiplatelet and lipid-lowering therapy were significantly less likely to experience a moderate or severe stroke (44% vs 78%; P = .006). CONCLUSIONS: Internal carotid artery occlusion is the culprit lesion in 43% of carotid-related strokes in those without previous symptoms. Previously asymptomatic patients not receiving combined antiplatelet and lipid-lowering medical therapy presenting with carotid-related stroke are significantly more likely to experience a severe, debilitating stroke. However, those receiving appropriate risk-reduction medical therapy are still at risk of carotid-mediated stroke. These results suggest medical therapy alone is unlikely to be sufficient stroke prevention for patients with significant carotid stenosis.

Use of extracorporeal bypass is associated with improved outcomes in open thoracic and thoracoabdominal aortic aneurysm repair.

OBJECTIVE: There is no consensus on the use or benefit of extracorporeal circulation (EC) during aneurysm repair of the descending thoracic aorta (DTA) or thoracoabdominal aorta (TAA). We evaluated the role of EC during DTA or TAA aneurysm repair using U.S. Medicare data. METHODS: Medicare (2004-2007) patients undergoing open repair of nonruptured DTA or TAA aneurysm were identified by International Classification of Diseases, Ninth Revision code. Specific exclusions included ascending aortic or arch repairs, concomitant cardiac procedures, and procedures employing deep hypothermic circulatory arrest. The impact of EC (code 3961) on early and late outcomes was analyzed using univariate analysis and multivariable regression. Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards regression models. RESULTS: There were 4230 patients who had repair of intact DTA or TAA aneurysms, 2433 (57%) of which employed EC. Differences in baseline clinical features of EC and non-EC patients showed that patients undergoing aortic reconstruction with EC were older (73 ± 1 years vs 72 ± 1 years; P = .002), were more likely to be female (53% vs 47%; P < .001), and had more hypertension (56% vs 53%; P = .02); they had less chronic obstructive pulmonary disease (28% vs 34%; P < .0001), peripheral vascular disease (5.7% vs 11.3%; P < .001), and chronic kidney disease (7.7% vs 5.5%; P = .003). The 30-day mortality (9.7% for EC vs 12.2%; P = .02) and any major complication (49% for EC vs 58%; P < .001) were significantly reduced with EC use. EC use was associated with a shorter length of stay (13.5 ± 13 days vs 17.2 ± 18 days; P < .01) and lower total hospital charges ($151,000 ± 140,000 vs $180,000 ± 190,000; P < .01) compared with non-EC patients. EC patients were more likely to be discharged home instead of to an extended care facility (67% vs 56%; P < .01). Multivariable regression modeling to adjust for baseline clinical differences showed EC to independently reduce the risk of operative mortality (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.65-0.97; P = .02), any complication (OR, 0.67; 95% CI, 0.59-0.76; P < .01), pulmonary complications (OR, 0.68; 95% CI, 0.59-0.79; P < .01), and acute renal failure (OR, 0.52; 95% CI, 0.44-0.61; P < .01). Long-term survival was higher (log-rank, P < .01) in EC patients at 1 year (81% ± 0.8% vs 73% ± 1%) and 5 years (67% ± 1% vs 52% ± 1%). Risk-adjusted Cox proportional hazards regression also showed that EC was independently associated with improved long-term survival (hazard ratio, 0.69; 95% CI, 0.63-0.74; P < .01). CONCLUSIONS: Although important clinical variables such as DTA or TAA aneurysm extent and spinal cord ischemic complications cannot be assessed with the Medicare database, EC use during open DTA and TAA aneurysm repair is associated with improved late survival and a significant reduction in operative mortality, morbidity, and procedural costs. These data indicate that EC should be a more widely applied adjunct in open DTA or TAA aneurysm repair.

Risk and outcome profile of carotid endarterectomy with proximal intervention is concerning in multi-institutional assessment.

OBJECTIVE: Approaching tandem bifurcation and brachiocephalic disease using carotid endarterectomy (CEA) with ipsilateral proximal endovascular intervention (IPE) has been promulgated as safe and durable. There have been recent concerns about neurologic risk with this technique. The goal of this study was to define stroke and perioperative risk with this uncommon procedure across multiple centers. METHODS: Between August 2002 and July 2016, patients who underwent CEA + IPE were identified by operative records at three institutions. Primary end points were perioperative stroke and death, restenosis, freedom from neurologic event, and need for reintervention. Factors related to these end points were analyzed. RESULTS: There were 62 patients who underwent CEA + IPE. The average age was 69 ± 9 years. Most were female 34 (55%); 56 (90%) were taking a statin and at least one antiplatelet agent. Bilateral internal carotid stenosis (>50%) was present in 32 (52%); 26 (42%) patients were symptomatic and 12 (19%) had undergone prior ipsilateral CEA. Bifurcation operations included longitudinal CEA/patch (38 [61%]), eversion CEA (20 [32%]), bypass graft (3 [5%]), and CEA/primary repair (1 [2%]). CEA was performed first in 53 (85%). All IPEs included stenting, with a single stent used in 58 (94%). Balloon-expandable stents were placed in the majority of patients (51 [82%]). Proximal arteries treated included the innominate (20 [32%]), left common carotid (32 [52%]), right common carotid (8 [13%]) and both innominate and right common carotid (2 [3%]). IPE was protected by carotid cross-clamp in 48 (77%). Shunting occurred in 14 (23%). There were four (6.5%) perioperative ipsilateral strokes and two hyperperfusion events. There were three (4.8%) operative deaths, one from stroke and two cardiovascular. Combined stroke and death rate was 11.3% and was not different between centers. Mean clinical follow-up was 6 ± 4 years. Mean imaging follow-up was 3 ± 4 years. Restenosis ≥50% at either intervention occurred in 20 (34%). Reintervention was performed for five proximal and three bifurcation failures (14%). Symptomatic status, redo operation, carotid clamp protection, multiple stents, and procedural order were not associated with operative stroke. Carotid clamp protection was associated with less restenosis (P = .003). Redo operation (P = .04) and hyperlipidemia (P = .05) were associated with reintervention. The 5-year actuarial survival was 81%, whereas freedom from stroke and reintervention were 94% and 81%, respectively. CONCLUSIONS: Perioperative stroke and death with CEA + IPE are substantial and consistent across centers. It is strikingly different from isolated CEA or CEA added to open brachiocephalic reconstruction. Restenosis is frequent, and reintervention at either the proximal stent or bifurcation is common. This technical strategy should be used cautiously and selectively reserved for those who are symptomatic with hemodynamically relevant tandem lesions and unfit for open revascularization.

Aneurysm sac expansion is independently associated with late mortality in patients treated with endovascular aneurysm repair.

BACKGROUND: Patients undergoing endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms can exhibit variations in sac behavior ranging from complete regression to expansion. We evaluated the impact of sac behavior at 1-year follow-up on late survival. METHODS: We used the Vascular Study Group of New England (VSGNE) registry from 2003 to 2011 to identify EVAR patients with 1-year computed tomography follow-up. Aneurysm sac enlargement ≥5 mm (sac expansion) and decrease ≥5 mm (sac regression) were defined per Society for Vascular Surgery guidelines. Predictors of change in sac diameter and impact of sac behavior on long-term mortality were assessed by multivariable methods. RESULTS: Of 2437 patients who underwent EVAR, 1802 (74%) had complete 1-year follow-up data and were included in the study. At 1 year, 162 (9%) experienced sac expansion, 709 (39%) had a stable sac, and 931 (52%) experienced sac regression. Sac expansion was associated with preoperative renal insufficiency (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.5-8.0; P < .01), urgent repair (OR, 2.7; 95% CI, 1.4-5.1; P < .01), hypogastric coverage (OR, 1.7; 95% CI, 1.1-2.7; P = .02), and type I/III (OR, 16.8; 95% CI, 7.3-39.0; P < .001) or type II (OR, 2.9; 95% CI, 2.0-4.3; P < .001) endoleak at follow-up, and sac expansion was inversely associated with smoking (OR, 0.6; 95% CI, 0.4-0.96; P = .03) and baseline aneurysm diameter (OR, 0.7; 95% CI, 0.6-0.9; P < .001). Sac regression (vs expansion or stable sac) was associated with female gender (OR, 1.8; 95% CI, 1.4-2.4; P < .001) and larger baseline aneurysm diameter (OR, 1.4; 95% CI, 1.2-1.5; P < .001) and inversely associated with type I/III (OR, 0.2; 95% CI, 0.1-0.5; P < .01) or type II endoleak at follow-up (OR, 0.2; 95% CI, 0.2-0.3; P < .001). After risk-adjusted Cox regression, sac expansion was independently associated with late mortality (hazard ratio, 1.5; 95% CI, 1.1-2.0; P = .01), even with adjustment for reinterventions and endoleak during follow-up. Sac regression was associated with lower late mortality (hazard ratio, 0.6; 95% CI, 0.5-0.7; P < .001). Long-term survival was lower (log-rank, P < .001) in patients with sac expansion (98% 1-year and 68% 5-year survival) compared with all others (99% 1-year and 83% 5-year survival). CONCLUSIONS: These data suggest that an abdominal aortic aneurysm sac diameter increase of at least 5 mm at 1 year, although infrequent, is independently associated with late mortality regardless of the presence or absence of endoleak and warrants close observation and perhaps early intervention.