Attrition rates in integrated vascular and cardiothoracic surgery residency and fellowship programs.

BACKGROUND: Attrition in surgical programs remains a significant problem resulting in trainee dissatisfaction and wasted time and educational dollars. Attrition rates in general surgery training programs approximate 5% per year (30% cumulative). Attrition rates in cardiovascular surgery training for the traditional vascular surgery fellowship (VSF), the vascular surgery residency (VSR), and the corresponding programs in cardiothoracic surgery have yet to be described, although they are assumed to be similar to those associated with general surgery training. METHODS: A retrospective review of the Association of American Medical Colleges Annual Physician Specialty Data Book was performed. Data from consecutive academic years 2007-2008 to 2013-2014 were analyzed. The number of total residents, the number who did not complete their training, and those who successfully completed the program were recorded. Attrition rates were then calculated for VSF, VSR, general surgery residency (GSR), cardiothoracic surgery fellowship (CTF), and cardiothoracic surgery integrated residency (CTR). RESULTS: Annually, between 2007-2008 and 2013-2014, there were zero to two vascular surgery residents who failed to complete the program (0%-5.9%). In the last 4 years of the study, whereas the absolute number of residents who failed to complete the program remained constant at 1 or 2 per year, the attrition rate decreased to 1 of 171 trainees (0.6%) in 2013-2014 as the total number of programs (and numbers of vascular surgery residents) significantly increased. During the same 7-year period, the number of vascular surgery fellows who did not complete their training ranged from one to six annually (0.4%-2.5%). Compared with the VSF, the VSR data show a relatively low and constant rate of attrition. In contrast, the number of general surgery residents who did not complete their program during the study period varied from 255 to 388 residents annually (3.3%-5.2%). During its first 3 years of inception, the CTR program had an attrition rate of 0%, and it was not until 2012-2013 that trainees failed to complete the program, resulting in an annual attrition rate of 1.2% to 3.2% from that point on. The annual attrition rate of CTF training programs ranged from 7 to 15 fellows (2.9%-6.8%) during the study period. CONCLUSIONS: The inception of VSR and CTR programs dramatically changed the paradigms for training in these highly specialized surgical fields. Comparisons of attrition rates between these two programs and the traditional VSF and CTR as well as GSR suggests lesser rates of attrition in the integrated programs. These data may prove reassuring to VSR and CTR program directors, whose significantly smaller programs are more vulnerable to the loss of even a single trainee than general surgery training programs are. In addition, the VSF program has stable and lower attrition rates compared with the CTF and GSR programs.

Predictors of 30-day postoperative major adverse clinical events after carotid artery stenting: An analysis of the procedure-targeted American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: Information about carotid artery stenting (CAS) is largely derived from clinical trials, consensus statements, and outcomes comparisons between CAS and carotid endarterectomy. Given these limitations, the goal of this study was to identify risk factors for adverse outcomes after CAS among hospitals participating in the CAS-targeted American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). METHODS: Our study sample consisted of patients from the 2012 to 2015 CAS-targeted ACS NSQIP data set. The primary outcome variable was 30-day postoperative incidence of major adverse clinical events (MACEs; death, myocardial infarction/arrhythmia, ipsilateral stroke/transient ischemic attack). Univariable and multivariable analyses were performed to identify patient and procedural characteristics associated with MACEs. RESULTS: A total of 448 patients undergoing CAS for carotid artery stenosis were identified in the 2012 to 2015 CAS-targeted ACS NSQIP data set as eligible for analysis. The incidence of postoperative MACEs was 8.4% for symptomatic patients and 5.4% for asymptomatic patients. On multivariable analysis, independent predictors of MACEs included age ≥80 years, female sex, black race, presence of chronic obstructive pulmonary disease, active tobacco use (protective), and use of more than one stent. CONCLUSIONS: The rate of major postoperative events in preoperatively asymptomatic patients is higher than the threshold recommended by the American Heart Association guidelines. Elderly patients (≥80 years), female patients, and black patients as well as those receiving more than one stent are at increased risk of negative outcome after CAS.

A comparison of open surgery versus endovascular repair of unstable ruptured abdominal aortic aneurysms.

OBJECTIVE: Two randomized trials to date have compared open surgery (OS) and endovascular (EVAR) repair for ruptured abdominal aortic aneurysm (rAAA); however, neither addressed optimal management of unstable patients. Single-center reports have produced conflicting data regarding the superiority of one vs the other, with the lack of statistical power due to low patient numbers. Furthermore, previous studies have not delineated between the outcomes of stable patients with a contained rupture vs those patients with instability. Our objective was to compare 30-day outcomes in patients undergoing OS vs EVAR for all rAAAs, focusing specifically on patients with instability. METHODS: Patients who underwent repair of rAAA were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database (2005 to 2010). Unstable patients with rupture were identified as those who were American Society of Anesthesiologists Physical Status Classification 4 or 5 requiring emergency repair with at least one of the following: preoperative shock, preoperative transfusion of >4 units, preoperative intubation, or preoperative coma or impaired sensorium. Univariable and multivariable logistic regression analyses were performed. RESULTS: Of the 1447 patients with rAAA, 65.5% underwent OS and 34.5% EVAR. Forty-five percent were unstable, and for these patients, OS was performed in 71.3% and EVAR in 28.7%. The 30-day mortality rate was 47.9% (OS, 52.8%; EVAR, 35.6%; P < .0001) for unstable rAAAs and was 22.4% for stable rAAAs (OS, 26.3%; EVAR, 16.4%; P = .001). Amongst patients with unstable rAAA, 26% had a myocardial infarction or cardiac arrest ≤ 30 days (OS, 29.0%; EVAR, 19.1%; P = .006), and 17% needed postoperative dialysis (OS, 18.7%; EVAR, 12.8%; P = .04). Amongst patients with stable rAAA, 13.6% had a myocardial infarction or cardiac arrest ≤ 30 days (OS, 14.9%; EVAR, 11.6%; P = .20), and 11.5% needed postoperative dialysis (OS, 13.3%; EVAR, 8.7%; P = .047). Multivariable analyses showed OS was a predictor of 30-day mortality for unstable rAAA (odds ratio, 1.74; 95% confidence interval, 1.16-2.62) and stable rAAA (odds ratio, 1.64; 95% confidence interval, 1.10-2.43). CONCLUSIONS: Approximately one-third of patients treated for rAAA undergo EVAR in NSQIP participating hospitals. Not surprisingly, unstable patients have less favorable outcomes. In both stable and unstable rAAA patients, EVAR is associated with a diminished 30-day mortality and morbidity.

Postdischarge outcomes after endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Perioperative outcomes after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) have been rigorously studied; however, inpatient and postdischarge outcomes have not been separately analyzed. The objective of this study was to examine postdischarge 30-day outcomes after elective EVAR. METHODS: Patients who underwent an elective EVAR for AAA (n = 11,229) were identified from the American College of Surgeons 2005-2010 National Surgical Quality Improvement Project database. Univariable and multivariable logistic regression analyses were performed. RESULTS: The median length of hospital stay was 2 days (interquartile range, 1-3 days). Overall 30-day mortality was 1.0% (n = 117), with 31% (n = 36) of the patients dying after discharge. Overall 30-day morbidity was 10.7% (n = 1204), with 40% (n = 500) of the morbidities being postdischarge. The median time of death and complication was 9 and 3 days, respectively, after surgery. Eighty-eight percent of the wound infections (n = 205 of 234), 33% of pneumonia (n = 44 of 133), and 55% of venous thromboembolism (n = 36 of 65) were postdischarge. Multivariable analyses showed age, congestive heart failure, admission from nursing facility, postoperative pneumonia, myocardial infarction, and renal failure were independently associated with postdischarge mortality, and peripheral arterial disease, female gender, previous cardiac surgery, age, smoking, and diabetes with postdischarge morbidity (P < .05 for all). CONCLUSIONS: Patient characteristics associated with a higher risk for postdischarge adverse events after EVAR were identified. Whether improved predischarge surveillance and close postdischarge follow-up of identified high-risk patients will further improve 30-day outcomes after EVAR needs to be prospectively studied.

Venous thromboembolic disease.

Venous thromboembolic disease is extremely common. Conventional treatment with anticoagulation alone aims to impede the progression of thrombus, and prevent recurrence and the development of pulmonary embolism. This is appropriate for most patients. However, in certain patient populations, this alone does not address the long-term complications of venous thromboembolic disease. Surgeons should be familiar with the surgical techniques that have been demonstrated to improve outcomes with low risk. Recent studies of catheter-directed thrombolysis have demonstrated its safety, efficacy, and possibly the superiority over standard treatment alone.

The effect of warfarin therapy on endoleak development after endovascular aneurysm repair (EVAR) of the abdominal aorta.

OBJECTIVES: The presence of an endoleak after endovascular abdominal aortic aneurysm (AAA) repair (EVAR) may predispose to sac expansion and potential sac rupture. The incidence of endoleak after AAA repair can be as high as 20% to 30%. We investigated whether warfarin anticoagulation was an independent risk factor for endoleak after EVAR for AAA. METHODS: All AAA patients who underwent elective EVAR were prospectively followed-up. Data for demographics, clinical comorbidities, outcomes, EVAR devices, and anticoagulation methods were recorded. All patients underwent routine follow-up at 1, 6, and 12 months and annually thereafter. Computed tomography angiography (CTA) with 3-dimensional (3D) volumetric analysis was also completed. RESULTS: During a 7-year period, 127 consecutive patients with infrarenal AAAs who underwent EVAR were monitored for a mean of 2.14 years. The average age at the time of EVAR was 73.8 years. Warfarin therapy alone was administered to 24 patients, and anticoagulation with antiplatelet therapy alone was administered to 103. During the study period, 38 (29.9%) endoleaks were documented. The overall endoleak rate was 13 of 24 in the warfarin group and 25 of 103 in the antiplatelet group (P = .004). CTA 3D volumetric aneurysm sac analysis showed an increase of 16.09% in the warfarin study group and a reduction of 9.71% in the antiplatelet group (P = .04). CONCLUSIONS: Anticoagulation with warfarin appears to be linked to an increased risk for the development of endoleak after EVAR, specifically type II. Volumetric analysis showed warfarin therapy also contributed to persistent aneurysm sac expansion. These data suggest that patients who require warfarin anticoagulation for other indications should be advised that they might be at an increased risk for the development of endoleaks, subsequent secondary interventions, persistent sac expansion, and possible delayed sac rupture.

Effect of early plasma transfusion on mortality in patients with ruptured abdominal aortic aneurysm.

BACKGROUND: The ratio of red blood cell (PRBC) transfusion to plasma (FFP) transfusion (PRBC:FFP ratio) has been shown to impact survival in trauma patients with massive hemorrhage. The purpose of this study was to determine the effect of the PRBC:FFP ratio on mortality for patients with massive hemorrhage after ruptured abdominal aortic aneurysm (RAAA). METHODS: A retrospective review was performed of patients undergoing emergent open RAAA repair from January 1987 to December 2007. Patients with massive hemorrhage (≥10 units of blood products transfused prior to conclusion of the operation) were included. The effects of patient demographics, admission vital signs, laboratory values, peri-operative variables, amount of blood products transfused, and the PRBC:FFP ratio on 30-day mortality were analyzed by multivariate analysis. RESULTS: One hundred and twenty-eight of the 168 (76%) patients undergoing repair for RAAA received at least 10 units of blood products within the peri-operative period. Mean age was 73.1 ± 9.1 years, and 109 (85%) were men. Thirty-day mortality was 22.6% (29/128), including 11 intra-operative deaths. By multivariate analysis, 30-day mortality was markedly lower (15% vs 39%; P < .03) for patients transfused at a PRBC:FFP ratio ≤2:1 (HIGH FFP group) compared with those transfused at a ratio of >2:1 (LOW FFP), and the likelihood of death was more than 4-fold greater in the LOW FFP group (odds ratio 4.23; 95% confidence interval, 1.2-14.49). Patients in the HIGH FFP group had a significantly lower incidence of colon ischemia than those in the LOW FFP group (22.4% vs 41.1%; P = .004). CONCLUSION: For RAAA patients requiring massive transfusion, more equivalent transfusion of PRBC to FFP (HIGH FFP) was independently associated with lower 30-day mortality. The lower incidence of colonic ischemia in the HIGH FFP group may suggest an additional benefit of early plasma transfusion that could translate into further mortality reduction. Analysis from this study suggests the potential feasibility for a more standardized protocol of initial resuscitation for these patients, and prospective studies are warranted to determine the optimum PRBC:FFP ratio in RAAA patients.

Complications of spinal fluid drainage in thoracoabdominal aortic aneurysm repair: a report of 486 patients treated from 1987 to 2008.

OBJECTIVE: Spinal fluid drainage reduces paraplegia risk in thoracic (TAA) and thoracoabdominal (TAAA) aortic aneurysm repair. There has not been a comprehensive study of the risks of spinal fluid drainage and how these risks can be reduced. Here we report complications of spinal fluid drainage in patients undergoing TAA/TAAA repair. METHODS: The study comprised 648 patients who had TAA or TAAA repair from 1987 to 2008. Spinal drains were used in 486 patients. Spinal fluid pressure was measured continuously, except when draining fluid, and was reduced to <6 mm Hg during thoracic aortic occlusion and reperfusion. After surgery, spinal fluid pressure was kept <10 mm Hg until patients were awake with normal leg lift. Drains were removed 48 hours after surgery. Spinal and head computed tomography (CT) scans were performed in patients with bloody spinal fluid or neurologic deficit. We studied the incidence of headache treated with epidural blood patch, infection, bloody spinal fluid, intracranial and spinal bleeding on CT, as well as the clinical consequences. RESULTS: Twenty-four patients (5%) had bloody spinal fluid. CT exams showed seven had no evidence of intracranial hemorrhage, 14 (2.9%) had intracranial blood without neurologic deficit, and three with intracranial bleeding and cerebral atrophy had neurologic deficits (1 died, 1 had permanent hemiparesis, and 1 with transient ataxia recovered fully). Two patients without bloody spinal fluid or neurologic deficit after surgery presented with neurologic deficits 5 days postoperatively and died from acute on chronic subdural hematoma. Neurologic deficits occurred after spinal fluid drainage in 5 of 482 patients (1%), and 3 died. The mortality from spinal fluid drainage complications was 0.6% (3 of 482). By univariate and multivariate analysis, larger volume of spinal fluid drainage (mean, 178 mL vs 124 mL, P < .0001) and higher central venous pressure before thoracic aortic occlusion (mean, 16 mm Hg vs 13 mm Hg, P < .0012) correlated with bloody spinal fluid. CONCLUSION: Strategies that reduce the volume of spinal fluid drainage but still control spinal fluid pressure are helpful in reducing serious complications. Patients with cerebral atrophy are at increased risk for complications of spinal fluid drainage.

A new intercostal artery management strategy for thoracoabdominal aortic aneurysm repair.

OBJECTIVE: The purpose of this study is to describe a new approach for addressing the intraoperative management of intercostal arteries during thoracoabdominal aortic aneurysm (TAAA) repair, using preoperative spinal MRA for detection of intercostal arteries supplying the anterior spinal artery. METHODS: Patients undergoing TAAA repair from August 2005 to September 2007 were included. Spinal artery MRA was performed to identify the anterior spinal artery, the artery of Adamkiewicz, and its major intercostal source artery (SA-AAK). Intraoperative spinal cord protection was carried out using standard techniques. Important intercostal arteries were either preserved or reimplanted as a button patch after removing aortic clamps. Demographic and perioperative data were collected for review. Analysis was performed with Fisher's exact test or Student's t-test, where applicable, using SAS ver. 8.0 (Cary, NC). RESULTS: Spinal artery MRA was performed in 27 patients. The SA-AAK was identified in 85% of preoperative studies. Open or endovascular repair was performed in 74% and 26% of patients, respectively. The SA-AAK was preserved or reimplanted in 13 (65%) of patients who underwent open repair. A mean of 1.67 (range 1-3) intercostal arteries were reimplanted. All patients undergoing endovascular repair necessitated coverage of the SA-AAK. No patient developed immediate or delayed paraplegia. Longer mean operative times in the reimplanted cohort were not statistically significant (330 versus 245 min, P = 0.1). CONCLUSION: The SA-AAK identified by MRA can be preserved or safely reimplanted after TAAA repair. Further study is warranted to determine if selective intercostal reimplantation can reduce the risk of immediate or delayed paraplegia.

A quantitative assessment of the impact of intercostal artery reimplantation on paralysis risk in thoracoabdominal aortic aneurysm repair.

OBJECTIVES: We previously demonstrated an 80% reduction in paraplegia risk using hypothermia, naloxone, steroids, spinal fluid drainage, intercostal ligation, and optimizing hemodynamic parameters. This report demonstrates that intercostal revascularization for the last 3 years further reduced our paraplegia risk index by 75%. METHODS: We evaluated 655 patients who had thoracic or thoracoabdominal aneurysm repair for factors that affected paraplegia risk including aneurysm extent, acuity, cardiac function, blood pressure mean arterial pressure, and spinal fluid drainage with naloxone (SFDN). Eighteen patients died during or shortly after surgery leaving 637 patients for analysis of paralysis. We evaluated the effect of intercostal reimplantation (IRP) using a highly accurate (r(2) > 0.88) paraplegia risk index we developed and published previously. RESULTS: Fifty-eight percent of patients were male with a mean age of 67. Thirty-three percent were acute with rupture, acute dissection, mycotic aortitis, and trauma. Eighty (12%) had dissections. Thirty-five patients had paraplegia or paraparesis (5.4%). Significant factors by univariate analysis (P < 0.05) were Crawford type 2, acuity, SFDN, cardiac index after unclamping, mean arterial pressure during crossclamping, and IRP. In multivariate modeling, aneurysm extent, SFDN, acuity, and IRP remained significant (P < 0.02). The paraplegia risk index declined from 0.20 to 0.05 (P < 0.03). CONCLUSIONS: The incidence of paralysis after TAAA repair decreased from 4.83% to 0.88% and paralysis risk index decreased from 0.26 to 0.05 when intercostal artery reimplantation was added to neuroprotective strategies that had already substantially reduced paralysis risk. These findings suggest that factors that affect collateral blood flow and metabolism account for approximately 80% of paraplegia risk and intercostal blood flow accounts for 20% of risk. This suggests a limit to paraplegia risk reduction in thoracoabdominal endograft patients. Early results in this emerging field support this prediction of high paraplegia risk with thoracoabdominal branched endografts with extensive aortic coverage.

Outcomes after endarterectomy for chronic mesenteric ischemia.

OBJECTIVES: A retrospective study was performed to identify optimal factors affecting outcomes after open revascularization for chronic mesenteric ischemia. METHODS: All patients who underwent open surgery for chronic mesenteric ischemia from 1987 to 2006 were reviewed. Patients with acute mesenteric ischemia or median arcuate ligament syndrome were excluded. Mortality, recurrent stenosis, and symptomatic recurrence were analyzed using logistic regression, and univariate and multivariate analysis. RESULTS: We identified 80 patients (69% women, 31% men). Mean age was 64 years (range, 31-86 years). Acute-on-chronic symptoms were present in 26%. Presenting symptoms included postprandial pain (91%), weight loss (69%), and food fear and diarrhea (25%). Preoperative imaging demonstrated severe (>70%) stenosis of the superior mesenteric artery in 75 patients (24 occluded), the celiac axis in 63 (20 occluded), and the inferior mesenteric artery in 53 (20 occluded). Multivessel disease was present in 72 patients (90%), and 40 (50%) underwent multivessel reconstruction. Revascularization was achieved by endarterectomy in 37 patients, mesenteric bypass in 29, and combined procedures in 14. Concurrent aortic reconstruction was required in 13 patients (16%). Three hospital deaths occurred (3.8%). Mean follow-up was 3.8 years (range, 0-17.2 years). One- and 5-year survival was 92.2% and 64.5%. Mortality was associated with age (P = .019) and renal insufficiency (P = .007), but not by clinical presentation. Symptom-free survival was 89.7% and 82.1% at 1 and 5 years, respectively. Symptoms requiring reintervention occurred in nine patients (11%) at a mean of 29 months (range, 5-127 months). Multivariate analysis showed that freedom from recurrent symptoms correlated with endarterectomy for revascularization (5.2% vs 27.6%; hazard ratio, 0.20; 95% confidence interval, 0.04-0.92; P = .02). CONCLUSION: For open surgical candidates, endarterectomy appears to provide the most durable long-term symptom relief in patients with chronic mesenteric ischemia.

Antisense to transforming growth factor-beta(1) facilitates the apoptosis of macrophages in rat vein grafts.

BACKGROUND: The success of peripheral vein grafts is limited by intimal hyperplasia. Transforming growth factor (TGF)-beta(1) has effects on cell proliferation, apoptosis and extracellular matrix synthesis. We have previously observed positive changes in vessel healing with antisense to TGF-beta(1). METHODS: Adenovirus was used to transduce rat femoral artery vein grafts with antisense to TGF-beta(1) (Ad-AST) or the sequence encoding the bioactive form of TGF-beta(1) (Ad-BAT). Grafts were harvested at 1, 2, 4 and 12 weeks and formalin fixed for immunohistochemical studies of the cell markers proliferating cellular nuclear antigen (proliferation) and active caspase 3 (apoptosis). In situ DNA fragmentation assays were also performed to confirm active caspase 3 results. RESULTS: Ad-AST treatment significantly (p = 0.05) increased apoptosis of macrophages inside the internal elastic lamina. In addition, Ad-AST treatment significantly increased the cellularity of the graft at early time points and reduced it at later time points (p = 0.01). CONCLUSION: The low levels of TGF-beta(1) in Ad-AST treatment promote apoptosis of macrophages and provide an environment that is more conducive to the proliferation or infiltration of cells that contribute to healthy vessels.

Effectiveness of intensive medical therapy in type B aortic dissection: a single-center experience.

OBJECTIVE: Although the mainstay of managing acute descending thoracic aortic dissection (ADTAD) remains medical, certain patients will require emergency surgery for complications of rupture or ischemia. This study evaluates factors that affect outcome and determines which patients previously treated surgically would have been eligible for endovascular repair. METHODS: A single-institution retrospective study was conducted of patients who presented with clinical signs of ADTAD that was confirmed by magnetic resonance angiography (MRA) or computed tomography (CT). All patients were admitted to the intensive care unit (ICU) and medically managed to maintain systolic blood pressure<120 mm Hg and heart rate<70 beats/min. Two treatment groups were identified: group 1 received medical treatment only; group 2 received medical treatment plus emergency surgery. Patient demographic and clinical data were correlated with 30-day group mortality and morbidity and need for emergency surgery. The MRA and CT scan images of group 2 were retrospectively reviewed to determine if currently available endovascular treatment could have been done. The Fisher exact test was used to compare between the groups, and P<.05 was considered significant. RESULTS: Between 1991 and 2005, 83 patients (55 men) were treated for ADTAD. The mean age was 67 years (range, 38 to 85). Sixty-eight patients (82%) had hypertension, three (3.6%) had Marfan syndrome, and 51 (62%) were smokers. Twenty-five (32%) of the patients were receiving beta-blocker therapy before the onset of their symptoms. Back pain was the most common initial symptom (72.2%). Emergency surgery was required in 19 patients (23%): 12 for rupture or impending rupture, four for mesenteric ischemia, and three for lower extremity ischemia. The need for emergency surgery was significantly higher in smokers (P=.03), in patients>70 years old (P=.035), and in patients who were not receiving beta-blocker therapy before the onset of symptoms (P=.023). The combined overall morbidity rate was 33%, and the mortality rate was 9.6%. Morbidity in group 2 was 64% and significantly higher than the 23% in group 1 (P=.00227). The mortality rate was also higher in group 2 at 31.5% compared with group 1 at 1.6% (P=.0004). Factors affecting the overall mortality included age>70 years (P=.057), previous abdominal aortic aneurysm repair (P=.018), tobacco use (P=.039), and the presence of leg pain at initial presentation (P=.013). As determined from the review of radiologic data, 11 of 13 patients with scans available for review in group 2 could have been treated with currently available endovascular grafts. CONCLUSIONS: Intensive medical therapies are effective in preventing early mortality associated with ADTAD. Predictably, the need for emergency surgery carries a high morbidity and mortality rate. Most patients in this series requiring emergency surgery could have been candidates for endovascular therapy had it been available.

Transforming growth factor-beta1 antisense treatment of rat vein grafts reduces the accumulation of collagen and increases the accumulation of h-caldesmon.

BACKGROUND: The main cause of occlusion and vein graft failure after peripheral and coronary arterial reconstruction is intimal hyperplasia. Transforming growth factor beta-1 (TGF-beta1) is a pleiotropic cytokine known to have powerful effects on cell growth, apoptosis, cell differentiation, and extracellular matrix synthesis. METHODS: To investigate the role of TGF-beta1 in intimal hyperplasia, we used adenovirus to deliver to superficial epigastric vein messenger RNA (mRNA) antisense to TGF-beta1 (Ad-AST) or the sequence encoding the bioactive form of TGF-beta1 (Ad-BAT). Infection with "empty" virus was used as a control (Ad-CMVpLpA). The treated vein was then used for an interposition graft into rat femoral artery. Grafts were harvested at 1, 2, 4, and 12 weeks and formalin-fixed for histologic studies or placed in liquid nitrogen for mRNA studies. RESULTS: Ad-AST treatment resulted in an overall reduction of TGF-beta1 expression (P = .001), and Ad-BAT treatment resulted in an overall increase in TGF-beta1 expression (P = .007). Histologic analysis showed Ad-AST caused reduced collagen build up in the neointima at 12 weeks (P = .0001). Immunohistochemical staining for h-caldesmon at 12 weeks indicated Ad-AST increased smooth muscle cells throughout the vessel wall compared with Ad-CMVpLpA (P = .0024) or Ad-BAT (P = .04). Ad-AST also resulted in reduced CD68-positive cells in the media/adventitia (P = .005 vs Ad-CMVpLpA, P = .01 vs Ad-BAT). To further understand how Ad-AST was influencing the build up of collagen, we performed quantitative polymerase chain reaction on complimentary DNA (cDNA) from homogenates of the vein grafts. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) was increased at 1 week by Ad-BAT (P = .048 vs Ad-CMVpLpA) and decreased by Ad-AST at all time points (P

Antisense to transforming growth factor-beta1 messenger RNA reduces vein graft intimal hyperplasia and monocyte chemotactic protein 1.

BACKGROUND: Autogenous vein grafts are commonly used for arterial reconstructive procedures. Their success is limited by the development of intimal hyperplasia (IH), a fibroproliferative disease that predisposes the grafts to occlusive stenosis. Mesenchymal cell proliferation and the deposition of an extracellular matrix characterize neointimal development. Increasing evidence suggests that, regardless of blood vessel type, IH results from complex interactions among vessel wall cells, infiltrating leukocytes, and cytokines. Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine with powerful effects on inflammatory cell chemotaxis; smooth muscle cell, fibroblast, and endothelial cell proliferation; and extracellular matrix synthesis. METHODS: Epigastric vein to common femoral artery interposition grafts were placed in male Lewis rats and harvested at 1, 2, 4, and 12 weeks after surgery. We used replication-defective adenoviruses to deliver a control reporter gene for the enzyme beta-galactosidase (Ad-GAL), empty virus (Ad-CMVpLpA), or the sequence encoding the antisense strand of TGF-beta1 (Ad-AST). The vein graft was transduced passively in medium containing 10 7 plaque-forming units per milliliter of Ad-GAL, Ad-CMVpLpA, or Ad-AST for 20 minutes at room temperature. The adenovirus-treated grafts were compared with grafts treated with medium without virus (sham). RESULTS: The Ad-GAL control grafts showed beta-galactosidase activity from 3 days to 4 weeks. Twenty percent of cells were positive out to 2 weeks, at which time the number of cells positive for beta-galactosidase activity began to decline. Treatment with Ad-AST resulted in a significant reduction vs sham, Ad-CMVpLpA, and Ad-GAL in TGF-beta1 messenger RNA, total TGF-beta1 protein, and bioactive TGF-beta1 protein. Neointimal area was significantly reduced in the Ad-AST group vs Ad-GAL at 4 weeks, vs Ad-CMVpLpA at 4 and 12 weeks, and vs sham at 2 and 4 weeks. The medial/adventitial layer was significantly thicker in the Ad-AST group than the Ad-GAL group at 12 weeks. In addition, we studied the effect of Ad-AST on monocyte chemotactic protein 1 (MCP-1). Although the reduction in TGF-beta1 resulted in a reduction of MCP-1 messenger RNA in whole-graft homogenates and MCP-1 protein-positive staining in histologic sections from the perianastomotic region, no reduction in the number of ED1-positive cells (monocytes and macrophages) was observed. CONCLUSIONS: Perioperative antisense TGF-beta1 treatment of the vein to be used in arterial reconstructions resulted in a prolonged diminution of IH; this emphasizes the importance of TGF-beta1 in neointimal thickening and indicates that ex vivo gene therapy can reduce the vessel's predisposition to IH. CLINICAL RELEVANCE: The main cause of occlusion and graft failure after peripheral and cardiac arterial reconstruction is IH. The study of the mechanisms and mediators of IH, including TGF-beta1, should lead to future gene therapies to prevent or limit IH. The clinical effect of such treatments would be enormous, because they would increase graft longevity, thereby enhancing quality of life and enabling patients to live without the threat of limb loss or recurrent heart attack.

Is coil embolization of hypogastric artery necessary during endovascular treatment of aortoiliac aneurysms?

The aim of this study was to evaluate the safety and efficacy of stent graft coverage of hypogastric artery in the management of aortoiliac aneurysms. Between January 2000 and December 2002, 98 patients underwent endovascular repair of aortoiliac aneurysms (EVAR). Of these, 24 (24.5%) required occlusion of one hypogastric artery to facilitate the endovascular repair. Based on the method of hypogastric artery occlusion, patients were divided in to two groups. Group A (13/24 = 54%) underwent standard coil embolization followed by hypogastric artery orifice coverage whereas group B (11/24 = 46) underwent hypogastric artery orifice coverage without coil embolization. Post-EVAR computed tomographic angiography (CTA) was used to determine occurrence of endoleaks from the hypogastric artery orifice and patency of superior gluteal artery in both groups. These findings were further correlated with presence or absence of gluteal claudication. There was no difference in age (p < 0.38) or iliac aneurysm size (p < 0.3). In group A (13 patients), occlusion of superior gluteal artery was seen in 6 (46%). Four of six (66%) patients developed severe gluteal claudication. Patients in group A were likely to require more than one intervention (p < 0.00036). No patients in group B developed occlusion of the superior gluteal artery (p < 0.04) or gluteal claudication (p < 0.046). No endoleaks were seen from the origins of hypogastric artery in either group. The follow-up period ranged from 2 to 35 months. Hypogastric artery orifice coverage without coil embolization effectively prevented retrograde endoleak without the occurrence of disabling gluteal claudication. Coil embolization of the hypogastric artery may be unnecessary during treatment of aortoiliac aneurysm.

Macrophage depletion reduces monocyte chemotactic protein-1 and transforming growth factor-beta1 in healing rat vein grafts.

OBJECTIVE: We previously showed that treatment with liposomally encapsulated dichloromethylene bisphosphonate reduces intimal hyperplasia development and macrophage accumulation in a rat epigastric vein to femoral artery model of intimal hyperplasia. Our objective in this study was to determine the effect of liposomally encapsulated dichloromethylene bisphosphonate on the expression of two cytokines essential to neointimal development, monocyte chemotactic protein-1 (MCP-1) and transforming growth factor-beta1 (TGF-beta). METHODS: We injected rats both 2 days preoperatively and 2 weeks postoperatively with liposomally encapsulated dichloromethylene bisphosphonate (Lip-Clod), liposomally encapsulated phosphate-buffered saline solution (Vector), or phosphate-buffered saline solution (PBS), and harvested the grafts at 1 and 4 weeks. In the perianastomotic region, MCP-1 and TGF-beta protein expression in the total graft cross-section and in the neointima was determined with immunohistochemistry. In whole-graft lysates, MCP-1 and TGF-beta protein were determined with an enzyme-linked immunosorbent assay, and messenger RNA expression was determined with reverse transcription quantitative polymerase chain reaction. RESULTS: Lip-Clod treatment reduced intimal hyperplasia when compared with Vector or PBS treatment. These reductions were significant (P<.05) at both time points. When compared with the PBS treatment, at 1 week but not at 4 weeks Lip-Clod reduced both MCP-1 and TGF-beta protein (P< or =.01 and P< or =.006) in the perianastomotic region of vein grafts. In whole-graft lysates, no significant difference was seen in MCP-1 protein at either time point; however, TGF-beta protein expression was significantly reduced at both 1 and 4 weeks (P=.02 and P=.004). Message analysis in whole-graft lysates at 1 week showed that MCP-1 message expression increased in the Lip-Clod group compared with the PBS group (P=.02), but no significant differences among groups for TGF-beta message levels. Results with Vector were often intermediate to results with Lip-Clod and PBS. CONCLUSION: The major effect of Lip-Clod treatment on TGF-beta and MCP-1 protein levels in the perianastomotic region is observed at 1 week, and macrophage depletion with Lip-Clod inhibits graft neointimal hyperplasia and TGF-beta protein expression in whole-graft lysates at 1 and 4 weeks. These results support the concept that the infiltrating macrophages contribute a significant portion of the cytokines that facilitate intimal hyperplasia and that reducing these cytokines early after grafting influences the development of intimal hyperplasia at later time points. CLINICAL RELEVANCE: All vascular surgeons have patients who have undergone a technically satisfying vein graft, only to have the bypass fail during the first year due to perianastomotic intimal hyperplasia (IH). We hypothesize that vein graft IH is analogous to aberrant wound healing. Central to wound healing is the recruitment of macrophages with their cytokines. This work raises the question whether clinical strategies designed to either decrease macrophages or the cytokines released by macrophages at the time of vein graft placement will be efficacious for limiting the development of IH.

Beta-galactosidase-tagged adventitial myofibroblasts tracked to the neointima in healing rat vein grafts.

OBJECTIVE: Myofibroblasts are present transiently in normal healing wounds. However, they have been found to persist in the stroma of neoplasms, fibrotic conditions and other pathological settings. In rat vein grafts, we have observed the prolonged presence of myofibroblasts. Our aim was to determine the origin of myofibroblasts in vein grafts. METHODS: Epigastric vein to femoral artery grafts were microsurgically placed in male Lewis rats and harvested. Neointimal development, cellular death and proliferation, and cell phenotypes were analyzed using immunohistochemistry and light and electron microscopy. To follow cellular movement in the vessel wall, vein grafts were transfected with replication-defective adenovirus containing the gene encoding beta-galactosidase (n = 50), and harvested at 1, 2, 3, 4, 5, 6, 7, 14 and 28 days. Grafts were analyzed after X-gal staining. RESULTS: Myofibroblasts were detected in the outer adventitia at 4 days, in the media at 1 week and in the developing neointima at 2 weeks. Cells tagged using adenoviral beta-galactosidase demonstrated adventitia to neointima cell migration. CONCLUSIONS: Although there may be other sources of myofibroblasts in this model, the adventitia has been shown to be an origin of myofibroblasts which subsequently migrate through the vessel wall to the neointima during graft remodeling and contribute to neointimal formation.

Minimal incision aortic surgery (MIAS).

This study evaluates the clinical and economic impact of using less extensive minimal invasive aortic surgery (MIAS) for elective treatment of infrarenal aortic aneurysms (AAA) and aortoiliac occlusive disease (AIOD) in two independent surgical departments. Surgeons from two institutions conducted a prospective consecutive, nonrandomized analysis of MIAS electively performed in 80 patients. MIAS outcomes were compared with 80 consecutive elective standard open aortic procedures (40 from each institution), which were performed during the same time period. Cost analyses for MIAS and standard open repair were performed at each institution. Our results indicated that MIAS is as safe as standard open repair, is more cost-effective, and has significantly shorter hospital stays than with standard open repair.