Edward Y. Woo

Cutting Edge: Regulatory T Cells from Lung Cancer Patients Directly Inhibit Autologous T Cell Proliferation

Active suppression by T regulatory cells plays an important role in the down-regulation of T cell responses to foreign and self-Ags. Thus far, the potential role of CD4+CD25+ T cells in human tumors has not been reported. In this work we show that lung tumors contain large numbers of these cells and that they have constitutive high-level expression of CD152 (CTLA-4). Furthermore, the CD4+CD25+ T cells mediate potent inhibition of autologous T cell proliferation. Finally, regulatory T cells from patient tumors failed to inhibit the proliferation of allogeneic T cells. Together these results suggest that the CD4+CD25+ T cells found in lung tumors selectively inhibit the host immune response and therefore could contribute to the progression of lung cancer.

Results of a New Surgical Paradigm: Endovascular Repair for Acute Complicated Type B Aortic Dissection

BACKGROUND Conventional open repair of acute complicated type B aortic dissection is associated with significant morbidity and mortality. This study examined the results of thoracic endovascular aortic repair (TEVAR) in acute type B aortic dissection complicated with rupture or malperfusion syndrome. METHODS From 2004 through 2007, 35 patients (22 men) with acute complicated type B aortic dissection were treated with TEVAR. Indications included rupture in 18 (51.4%) and malperfusion syndrome in 17 (48.6%; mesenteric or renal, 5;lower extremities, 3; both, 9). Three types of endograft devices were used (mean per patient, 1.9 devices). Intravascular ultrasound imaging was used in 15 patients (42.8%). In patients with malperfusion syndrome, distal adjunct procedures to expand the true lumen included infrarenal aortic stents in 4, mesenteric/renal stents in 4, and iliofemoral stents in 7. Follow-up was 93.9% during a period of 18.3 months (range, 3 to 47 months). RESULTS The mean age was 58.6 +/- 13.4 years. Technical success (coverage of the primary tear site) was achieved in 34 patients (97.1%). Coverage of the left subclavian artery was required in 25 patients (71.4%). Thirty-day mortality was 2.8%. One-year survival was 93.4% +/- 4.6%. Complications included permanent renal failure (2.8%), stroke (2.8%), spinal cord ischemia (transient [5.7%], permanent [(2.8%]), and vascular access (14.2%). The mean intensive care unit and hospital stay were 4.7 +/- 2.6 and 16.7 +/- 12.0 days, respectively. CONCLUSIONS Endovascular repair of acute complicated type B aortic dissection is associated with low morbidity and mortality and has emerged as the surgical therapy of choice.

Risk factors, outcomes, and clinical manifestations of spinal cord ischemia following thoracic endovascular aortic repair

OBJECTIVE The purpose of this study was to assess the incidence, risk factors, and clinical manifestations of spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR). METHODS A retrospective review of a prospectively collected database was performed for all patients undergoing TEVAR at a single academic institution between July 2002 and June 2010. Preoperative demographics, procedure-related variables, and clinical details related to SCI were examined. Logistic regression analysis was performed to identify risk factors for the development of SCI. RESULTS Of the 424 patients who underwent TEVAR during the study period, 12 patients (2.8%) developed SCI. Mean age of this cohort with SCI was 69.6 years (range, 44-84 years), and 7 were women. One-half of these patients had prior open or endovascular aortic repair. Indication for surgery was either degenerative aneurysm (n = 8) or dissection (n = 4). Six TEVARs were performed electively, with the remaining done either urgently or emergently due to contained rupture (n = 2), dissection with malperfusion (n = 2), or severe back pain (n = 2). All 12 patients underwent extent C endovascular coverage. Multivariate regression analysis demonstrated chronic renal insufficiency to be independently associated with SCI (odds ratio [OR], 4.39; 95% confidence interval [CI], 1.2-16.6; P = .029). Onset of SCI occurred at a median of 10.6 hours (range, 0-229 hours) postprocedure and was delayed in 83% (n = 10) of patients. Clinical manifestations of SCI included lower extremity paraparesis in 9 patients and paraplegia in 3 patients. At SCI onset, average mean arterial pressure (MAP) and lumbar cerebrospinal fluid (CSF) pressure was 77 mm Hg and 10 mm Hg, respectively. Therapeutic interventions increased blood pressure to a significantly higher average MAP of 99 mm Hg (P = .001) and decreased lumbar CSF pressure to a mean of 7 mm Hg (P = .30) at the time of neurologic recovery. Thirty-day mortality was 8% (1 of 12 patients). The single patient who expired, never recovered any lower extremity neurologic function. All patients surviving to discharge experienced either complete (n = 9) or incomplete (n = 2) neurologic recovery. At mean follow-up of 49 months, 7 of 9 patients currently alive continued to exhibit complete, sustained neurologic recovery. CONCLUSION Spinal cord ischemia after TEVAR is an uncommon, but important complication. Preoperative renal insufficiency was identified as a risk factor for the development of SCI. Early detection and treatment of SCI with blood pressure augmentation alone or in combination with CSF drainage was effective in most patients, with the majority achieving complete, long-term neurologic recovery.

Presentation, complications, and natural history of penetrating atherosclerotic ulcer disease

OBJECTIVES Increased utilization of computed tomography angiography (CTA) has increased the radiologic diagnosis of penetrating atherosclerotic ulcers (PAUs), which are defined as the ulceration of atherosclerotic plaque through the internal elastic lamina into the aortic media. However, the presentation, treatment indications, and natural history of this disease process remain unclear. METHODS The radiology database at a single university hospital was searched retrospectively for the CTA diagnosis of PAU from January 2003 to June 2009. All scans were interpreted by a cardiovascular radiologist. Information on PAU characteristics and need for surgical repair due to PAU disease was collected. PAU stability or progression was assessed by follow-up CTA, if available. Only PAUs in the aortic arch, descending thoracic aorta, and abdominal aorta were included. RESULTS Three hundred eighty-eight PAUs were diagnosed by CTA interpretation. PAU location was in the aortic arch in 27 (6.8%) cases, the descending thoracic aorta in 243 (61.2%) cases, and the abdominal aorta in 118 (29.7%) cases. Two hundred twenty-four (57.7%) PAUs were isolated (without saccular aneurysm or intramural hematoma); 108 (27.8%) PAUs had associated saccular aneurysms; and 56 (14.4%) PAUs had associated intramural hematoma. Rupture was present in 16 (4.1%) cases. Fifty (12.9%) PAUs underwent repair with thoracic endovascular aortic repair (TEVAR) (n = 30), endovascular aneurysm repair (EVAR) (n = 10), or open surgery (n = 10); primary indications for repair were saccular aneurysm (n = 26), rupture (n = 16), and persistent or recurrent symptoms (n = 8). Even if initially treated conservatively with resolution of pain, symptomatic PAU disease was more likely to require repair than asymptomatic PAU disease (36.2% vs 7.8%, P < .001). Follow-up CTA was available for 87 PAUs, 20 (23.0%) of which demonstrated radiographic disease progression at a mean follow-up of 8.4 ± 10.3 months. Symptomatic PAU disease was more likely to progress than asymptomatic disease (42.9% vs 16.7%, P = .029). CONCLUSIONS For PAUs diagnosed on CTA at a single institution, 4.1% were ruptured and 12.9% underwent repair. Close follow-up imaging appears to be indicated for PAUs, particularly in the case of symptomatic disease, which is more likely to require repair and to undergo radiographic progression.

Thoracic endovascular aortic repair for acute complicated type B aortic dissection: superiority relative to conventional open surgical and medical therapy.

OBJECTIVE This study compared outcomes between thoracic endovascular aortic repair and conventional open surgical and medical therapies for acute complicated type B aortic dissection. METHODS From 2002 to 2010, a total of 170 patients with type B aortic dissections were retrospectively identified from the University of Pennsylvania aortic database. Of these 170 patients, 147 had acute type B aortic dissections (uncomplicated 70, complicated 77). For patients with acute complicated type B aortic dissections, management included thoracic endovascular aortic repair (group A) or conventional open surgical and medical therapies (group B). RESULTS In the 77 patients with acute complicated type B aortic dissections, thoracic endovascular aortic repair (group A) was performed in 45 patients (59%). In group B, 20 patients (26%) underwent open surgical repair and 12 (15%) had their conditions managed with medical therapy. Thoracic endovascular aortic repair was associated with lower in-hospital or 30-day mortality (n = 2, 4%) than conventional therapy (open surgical repair n = 8, 40%, medical therapy, n = 4, 33%, P = .006). Patients in group A (thoracic endovascular aortic repair) continued to show significantly improved survival at 1, 3, and 5 years (group A: 82%, 79%, and 79% vs group B: 58%, 52%, and 44%, P = .008). CONCLUSIONS Thoracic endovascular aortic repair for acute complicated type B dissection is associated with superior early outcome and improved midterm survival relative to conventional therapy. Longer follow-up demonstrating survival benefit is needed before definitive conclusion can be made.

Limb Ischemia During Femoral Cannulation for Cardiopulmonary Support

OBJECTIVES Extracorporeal membrane oxygenation and extracorporeal cardiopulmonary support (ECMO/CPS) are potentially life-saving techniques for patients with cardiopulmonary collapse. Complications include lower extremity ischemia from femoral artery cannulation. We examined the outcomes of patients placed on ECMO/CPS, including the rate of limb ischemia. METHODS All instances of ECMO/CPS over a 3-year period (2006-2009) at a single university hospital were examined retrospectively for cannulation strategy, perfusion strategy, mortality, and limb ischemia. Potential predictors of limb ischemia with femoral artery cannulation were age, gender, body surface area (BSA), body mass index (BMI), and arterial cannula size. RESULTS Fifty-eight patients were placed on ECMO/CPS. Of these, 43 patients (74%) had femoral arterial cannulation. In 10 patients, the superficial femoral artery (SFA) was cannulated prophylactically (without antecedent limb ischemia) and perfused in the antegrade direction from a branch of the ECMO/CPS circuit. In 7 of the remaining 33 patients (21%), limb ischemia developed requiring decannulation with fasciotomy (n = 4) or additional cannulation of the SFA with branching of the ECMO/CPS circuit (n = 3). One patient with ipsilateral leg ischemia required eventual amputation. Patients with limb ischemia were significantly younger than those who did not develop limb ischemia (P = .001). BSA, BMI, and cannula size did not predict limb ischemia. Overall 30-day mortality following the initiation of ECMO/CPS was 79%. There was no correlation between limb ischemia and mortality. CONCLUSIONS Younger patients may be at increased risk for lower extremity arterial insufficiency with femoral cannulation for ECMO/CPS. Prophylactic or expectant SFA cannulation are reasonable approaches.

Left subclavian artery coverage during thoracic endovascular aortic repair : A single-center experience

OBJECTIVE This study was conducted to determine the results of left subclavian artery (LSA) coverage during thoracic endovascular aortic repair (TEVAR). METHODS We retrospectively reviewed the results of 308 patients who underwent TEVAR from 1999 to 2007. The LSA was completely covered in 70 patients (53 men, 13 women), with a mean age of 67 years (range 41-89). Elective revascularization of the LSA was performed in 42 cases, consisting of transposition (n = 5), bypass and ligation (n = 3), or bypass and coil embolization (n = 34). Mean follow-up was 11 months (range, 1-48 months). The chi(2) test was used for statistical analysis. RESULTS Indications for treatment included aneurysm in 47, dissection in 16, transection in 4, pseudoaneurysm in 2, and right subclavian aneurysm in 1, with 47 elective and 23 emergency operations. Aortic coverage extended from the left common carotid artery (LCCA) to the distal arch (n = 29), middle thoracic aorta (n = 9), or celiac artery (n = 32). Operative success was 99%. The 30-day mortality was 4% (intraoperative myocardial infarction, 1; traumatic injuries, 1; visceral infarction, 1). No paraplegia developed. The stroke rate was 8.6%; no strokes were related to LSA coverage because there were no posterior strokes. Stroke rates between the revascularization (7%) and non-revascularization (11%) groups were not significantly different (P = .6). All but one patient fully recovered by 6 months. No left arm symptoms developed in patients with LSA revascularization. All bypasses remained patent throughout follow-up. One complication (2%) resulted in an asymptomatic persistently elevated left hemidiaphragm, likely related to phrenic nerve traction. Left upper extremity symptoms developed in five (18%) patients without LSA revascularization. Two required LSA revascularization, one of which was for acute limb-threatening ischemia. No permanent left upper extremity dysfunction or ischemia developed in any patient. CONCLUSION Zone 2 TEVAR with LSA coverage can be accomplished safely in both elective and emergency settings and with and without revascularization (with the exception of a patent LIMA-LAD bypass). Nevertheless, overall stroke rates are higher compared with all-zone TEVAR. Staged LSA revascularization and even urgent revascularization may be necessary but can be performed without long-term detriment to the left arm.

Long-term comparison of thoracic endovascular aortic repair (TEVAR) to open surgery for the treatment of thoracic aortic aneurysms

OBJECTIVE Thoracic endovascular aortic repair (TEVAR) has become a widely established treatment for a variety of thoracic aortic pathologic diseases despite limited long-term data to support its use. We compared the long-term outcomes of TEVAR with the 3 commercially available stents grafts for thoracic aortic aneurysms to results in control subjects undergoing open surgery. METHODS Demographic, clinical radiographic parameters were collected prospectively on patients enrolled in trials assessing the Gore TAG (55), Medtronic Talent (36) and Cook TX2 (15) devices. Outcomes were compared with 45 contemporaneous open controls. Detailed clinical and radiographic information was available for analysis. Standard univariate, survival, and regression methods were used. RESULTS During the study period (1995-2007) 106 patients were enrolled in TEVAR trials and there were 45 open controls. TEVAR patients were older and had significantly more comorbidities including diabetes and renal failure. TEVAR patients had 2.3 ± 1.3 devices implanted. Mortality (2.6% TEVAR, 6.7% open; P = .1), paralysis/paraparesis (3.9% TEVAR, 7.1% open; P = .2), and prolonged intubation more than 24 hours (9% TEVAR, 24% open; P = .02) tended to be more common in the open controls. Overall survival at 10 years was similar between groups (log rank P = .5). Multivariate predictors of late mortality included age, chronic obstructive pulmonary disease, diabetes, and chronic renal failure. Use of TEVAR versus open surgery did not influence mortality (hazard ratio, 0.9 95% confidence interval, 0.4-1.6). Over 5 years of radiographic follow-up in the TEVAR group, mean aortic diameter decreased from 61 to 55 mm. Freedom from reintervention on the treated segment was 85% in TEVAR patients at 10 years. CONCLUSIONS TEVAR is a safe and effective procedure to treat thoracic aortic aneurysms with improved perioperative and similar long-term results as open thoracic aortic repair. TEVAR-treated aneurysm diameters initially decrease and then stabilize over time.

Barriers to Endovascular Aortic Aneurysm Repair: Past Experience and Implications for Future Device Development:

Despite improvements in endovascular aortic aneurysm repair (EVAR) devices and techniques, significant anatomic constraints still preclude successful EVAR in a large number of patients. The authors sought to identify the current barriers to EVAR and examine their evolution over time. Patients were evaluated for potential endovascular repair by computed tomography angiography (CTA) with or without supplemental conventional arteriograms. The patient population was separated into 2 groups (A and B) based on early and late time periods in the experience with EVAR, corresponding to the availability of various devices. Group A (early) consisted of the Guidant Ancure, Medtronic Talent, and AneuRx devices and comprised patients presenting between April 1997 through June 2000. Group B (late) consisted of the Medtronic AneuRx, Cook Zenith, Edwards Lifepath, Gore Excluder, and Endologix PowerLink devices and comprised patients presenting between July 2000 and December 2003. Patient demographics and anatomic reasons for rejection were recorded in a database for statistical analysis. In total, 547 patients were evaluated (463 men, 84 women). Of these, 346 patients (63%; 312 men, 34 women) were deemed suitable candidates for EVAR and 201 (37%; 151 men, 50 women) were rejected. There was no significant difference in the overall rate of rejection in the early vs the late time period (34% A, 41% B, p= 0.08), but the number of exclusion criteria per patient decreased over time; patients rejected for EVAR had an overall average of 1.6 exclusion criteria (Group A, 1.9; Group B, 1.2). The reasons for rejection did significantly change over time. Specifically, rejection on the basis of inadequate arterial access, presence of extensive iliac artery aneurysms, or an inadequate proximal neck decreased. A disproportionate number of women were excluded throughout the study: Group A, 56% of women compared to 30% of men (p= 0.0003); Group B, 63% of women compared to 36% of men (p= 0.0022). Women were more likely than men to have inadequate arterial access routes. In addition, patients with high operative risk were also more likely to be excluded from EVAR, a finding that persisted over time. Anatomic constraints continue to pose significant challenges to aortic endografting. Progress has been made in that technological advances have conquered some of the previous anatomic challenges, chiefly those of arterial access and treatment of concomitant iliac aneurysm disease. However, the overall rate of rejection for EVAR remains the same. The chief anatomic barriers continue to be the difficult aortic neck and management of branched vascular segments.

Low rehospitalization rate for vascular surgery patients

OBJECTIVES Reducing rehospitalization rates has been proposed to improve care, reduce costs, and as a pay-for-performance criterion. Recent review of Medicare claims data indicates that vascular surgery patients have among the highest rates of 30-day rehospitalization at 23.9%. METHODS We retrospectively examined all live patient discharges (n = 799) from the vascular surgery service at a single university hospital over 12 months. Planned and unplanned 30-day rehospitalizations were distinguished, and predictors of unplanned 30-day rehospitalization were determined. To identify whether patients were readmitted to other hospitals, a prospective study of patient discharges (n = 66) over 1 month was also performed. RESULTS Ninety-five (11.9%) of the 799 patient discharges from the vascular surgery service were rehospitalized within 30 days. Of these, 71 were unplanned; therefore, the unplanned rehospitalization rate was 8.9%. The most common causes of unplanned 30-day rehospitalization were related to wound complications. Diabetes (P = .039) predicted unplanned 30-day rehospitalization by multivariate analysis. Patients with the diagnosis of critical limb ischemia (14.9%) and patients undergoing open lower extremity revascularization (14.6%) had the highest rates of unplanned 30-day rehospitalization. In the prospective portion of this study, no patient was readmitted to any other hospital. CONCLUSIONS Relatively low 30-day rehospitalization was accomplished in vascular surgery patients at a single university hospital. Moreover, planned rehospitalizations accounted for approximately 25% of readmissions in vascular surgery patients. Strategies designed to reduce rehospitalization in diabetics may be warranted.