Paul G. Bannon

Systematic Review and Meta-Analysis of Randomized and Nonrandomized Trials on Safety and Efficacy of Video-Assisted Thoracic Surgery Lobectomy for Early-Stage Non–Small-Cell Lung Cancer

PURPOSE The current randomized trials comparing video-assisted thoracic surgery (VATS) lobectomy with open lobectomy for patients with early-stage non-small-cell lung cancer (NSCLC) have been of small size. We performed the present meta-analysis of the randomized and nonrandomized comparative studies in an attempt to assess the safety and efficacy of VATS lobectomy. METHODS Electronic searches identified 21 eligible comparative studies (two randomized and 19 nonrandomized) for inclusion. Two reviewers independently appraised each study. Meta-analysis was performed by combining the results of reported incidence of morbidity and mortality, recurrence, and 5-year mortality rates. The relative risk (RR) was used as a summary statistic. RESULTS There were no significant statistical differences between VATS and open lobectomy in terms of postoperative prolonged air leak (P = .71), arrhythmia (P = .86), pneumonia (P = .09), and mortality (P = .49). VATS did not demonstrate any significant difference in locoregional recurrence (P = .24), as compared with the open lobectomy arm, but the data suggested a reduced systemic recurrence rate (P = .03) and an improved 5-year mortality rate of VATS (P = .04). There was no evidence to suggest heterogeneity of trial results. Fourteen studies reported VATS to open lobectomy conversion rate ranging from 0% to 15.7% (median = 8.1%). CONCLUSION Both randomized and nonrandomized trials suggest that VATS lobectomy is an appropriate procedure for selected patients with early-stage NSCLC when compared with open surgery.

A multilayered synthetic human elastin/polycaprolactone hybrid vascular graft with tailored mechanical properties.

Small-diameter synthetic vascular graft materials fail to match the patency of human tissue conduits used in vascular bypass surgery. The foreign surface retards endothelialization and is highly thrombogenic, while the mismatch in mechanical properties induces intimal hyperplasia. Using recombinant human tropoelastin, we have developed a synthetic vascular conduit for small-diameter applications. We show that tropoelastin enhances endothelial cell attachment (threefold vs. control) and proliferation by 54.7 ± 1.1% (3 days vs. control). Tropoelastin, when presented as a monomer and when cross-linked into synthetic elastin for biomaterials applications, had low thrombogenicity. Activation of the intrinsic pathway of coagulation, measured by plasma clotting time, was reduced for tropoelastin (60.4 ± 8.2% vs. control). Platelet attachment was also reduced compared to collagen. Reductions in platelet interactions were mirrored on cross-linked synthetic elastin scaffolds. Tropoelastin was subsequently incorporated into a synthetic elastin/polycaprolactone conduit with mechanical properties optimized to mimic the human internal mammary artery, including permeability, compliance, elastic modulus and burst pressure. Further, this multilayered conduit presented a synthetic elastin internal lamina to circulating blood and demonstrated suturability and mechanical durability in a small scale rabbit carotid interposition model.

Systematic review and meta-analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis

BACKGROUND Transcatheter aortic valve implantation (TAVI) has emerged as an acceptable treatment modality for patients with severe aortic stenosis who are deemed inoperable by conventional surgical aortic valve replacement (AVR). However, the role of TAVI in patients who are potential surgical candidates remains controversial. METHODS A systematic review was conducted using five electronic databases, identifying all relevant studies with comparative data on TAVI versus AVR. The primary endpoint was all-cause mortality. A number of periprocedural outcomes were also assessed according to the Valve Academic Research Consortium endpoint definitions. RESULTS Fourteen studies were quantitatively assessed and included for meta-analysis, including two randomized controlled trials and eleven observational studies. Results indicated no significant differences between TAVI and AVR in terms of all-cause and cardiovascular related mortality, stroke, myocardial infarction or acute renal failure. A subgroup analysis of randomized controlled trials identified a higher combined incidence of stroke or transient ischemic attacks in the TAVI group compared to the AVR group. TAVI was also found to be associated with a significantly higher incidence of vascular complications, permanent pacemaker requirement and moderate or severe aortic regurgitation. However, patients who underwent AVR were more likely to experience major bleeding. Both treatment modalities appeared to effectively reduce the transvalvular mean pressure gradient. CONCLUSIONS The available data on TAVI versus AVR for patients at a higher surgical risk showed that major adverse outcomes such as mortality and stroke appeared to be similar between the two treatment modalities. Evidence on the outcomes of TAVI compared with AVR in the current literature is limited by inconsistent patient selection criteria, heterogeneous definitions of clinical endpoints and relatively short follow-up periods. The indications for TAVI should therefore be limited to inoperable surgical candidates until long-term data become available.

A Systematic Review of Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma

Introduction: The primary objective of the present systematic review was to evaluate the safety and efficacy of extrapleural pneumonectomy (EPP) for patients with malignant pleural mesothelioma. Methods: A systematic review of relevant studies identified through five online search databases was performed. Two reviewers independently appraised each study. Results: Thirty-four of 58 relevant studies from 26 institutions containing the most updated data were evaluated for survival and perioperative outcomes after EPP. The median overall survival varied from 9.4 to 27.5 months, and 1-, 2-, and 5-year survival rates ranged from 36 to 83%, 5 to 59%, and 0 to 24%, respectively. Overall perioperative mortality rates ranged from 0 to 11.8%, and the perioperative morbidity rates ranged from 22 to 82%. Quality of life assessments from three studies reported improvements in nearly all domains at 3 months postoperatively. Patients who underwent trimodality therapy involving EPP and adjuvant chemoradiotherapy had a median overall survival of 13 to 23.9 months. Discussions: The current evidence suggests that selected patients with malignant pleural mesothelioma may benefit from EPP, especially when combined with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy.

Transcatheter aortic valve implantation for high-risk patients with severe aortic stenosis: A systematic review.

OBJECTIVES The present systematic review objectively assessed the safety and clinical effectiveness of transcatheter aortic valve implantation for patients at high surgical risk with severe aortic stenosis. METHODS Electronic searches were performed in 6 databases from January 2000 to March 2009. The end points included feasibility, safety, efficacy, and durability. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS The current evidence on transcatheter aortic valve implantation for aortic stenosis is limited to short-term observational studies. The overall procedural success rates ranged from 74% to 100%. The incidence of major adverse events included 30-day mortality (0%-25%), major ventricular tachyarrhythmia (0%-4%), myocardial infarction (0%-15%), cardiac tamponade (2%-10%), stroke (0%-10%), conversion to surgery (0%-8%), moderate to major paravalvular leak (4%-35%), vascular complication (8%-17%), valve-in-valve procedure (2%-12%), and aortic dissection/perforation (0%-4%). The overall 30-day major adverse cardiovascular and cerebral events ranged from 3% to 35%. The mean aortic valve area ranged from 0.5 to 0.8 cm(2) before and 1.3 to 2.0 cm(2) after transcatheter aortic valve implantation. The mean pressure gradient ranged from 34 to 58 mm Hg before and 3 to 12 mm Hg after transcatheter aortic valve implantation. There was no significant deterioration in echocardiography measurements during the assessment period. Death rate at 6 months postprocedure ranged from 18% to 48%. No studies had adequate follow-up to reliably evaluate long-term outcomes. CONCLUSIONS The procedure has a potential for serious complications. Although short-term efficacy based on echocardiography measurements is good, there is little evidence on long-term outcomes. The use of transcatheter aortic valve implantation should be considered only within the boundaries of clinical trials.

Rare non-synonymous variations in the transcriptional activation domains of GATA5 in bicuspid aortic valve disease

Bicuspid aortic valve (BAV) is the commonest congenital heart disease and a highly heritable trait; however, only the NOTCH1 gene has been linked to limited cases of BAV in humans. Recently, the transcription factor GATA5 has been shown to have an essential role in aortic valve development, and targeted deletion of Gata5 in mice is associated with partially penetrant BAV formation. Here, we investigated the relationship between GATA5 gene variants and BAV with its associated aortopathy. One hundred unrelated individuals with confirmed BAV were prospectively recruited. Following collection of clinical information and DNA extraction, the coding regions and splice signal sequences of the GATA5 gene were screened for sequence variations. The clinical characteristics of the cohort included a male predominance (77%), mean age of diagnosis 29 ± 22 years, associated aortopathy in 59% and positive family history for BAV in 13%. Genetic analysis identified the presence of 4 rare non-synonymous variations within the GATA5 transcriptional activation domains, namely Gln3Arg, Ser19Trp, Tyr142His and Gly166Ser, occurring in one patient each. Gln3Arg and Tyr142His substitutions affect highly conserved and functionally relevant residues, and are likely to impact on the transcriptional activation of GATA5 target regions. A novel Ser19Trp variation was identified at a highly conserved amino acid residue in one patient, while the Gly166Ser variant was found in a familial case of BAV and associated aortopathy. Rare non-synonymous variations in the functionally important GATA5 transcriptional activation domains may be important in the pathogenesis of BAV disease in humans.

Animal models for the assessment of novel vascular conduits

The development of an ideal small-diameter conduit for use in vascular bypass surgery has yet to be achieved. The ongoing innovation in biomaterial design generates novel conduits that require preclinical assessment in vivo, and a number of animal models have been used for this purpose. This article examines the rationale behind animal models used in the assessment of small-diameter vascular conduits encompassing the commonly used species: baboons, sheep, pigs, dogs, rabbits, and rodents. Studies on the comparative hematology for these species relative to humans are summarized, and the hydrodynamic values for common implant locations are also compared. The large- and small-animal models are then explored, highlighting the characteristics of each that determine their relative utility in the assessment of vascular conduits. Where possible, the performance of expanded polytetrafluoroethylene is given in each animal and in each location to allow direct comparisons between species. New challenges in animal modeling are outlined for the assessment of tissue-engineered graft designs. Finally, recommendations are given for the selection of animal models for the assessment of future vascular conduits.

Extrapleural pneumonectomy for malignant pleural mesothelioma: outcomes of treatment and prognostic factors.

OBJECTIVE This study aimed to evaluate the perioperative and long-term outcomes associated with extrapleural pneumonectomy for patients with malignant pleural mesothelioma. METHODS From October 1994 to April 2008, 70 patients were selected for extrapleural pneumonectomy. Univariate analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis with entering and removing limits of P less than .10 and P greater than .05, respectively, was used. The prognostic factors included age, gender, side of disease, asbestos exposure, histology, positron emission tomography, date of surgery, neoadjuvant chemotherapy, completeness of cytoreduction, lymph node involvement, perioperative morbidity, adjuvant radiotherapy, and pemetrexed-based chemotherapy. RESULTS The mean age of patients was 55 years (standard deviation = 10). Fifty-eight patients had epithelial tumors. Six patients received neoadjuvant chemotherapy, 28 patients received adjuvant radiotherapy, and 16 patients received postoperative pemetrexed-based chemotherapy. Forty-four patients had no lymph node involvement. The perioperative morbidity and mortality were 37% and 5.7%, respectively. Complications included hemothorax (n = 7), atrial fibrillation (n = 6), empyema (n = 4), bronchopulmonary fistula (n = 3), right-sided heart failure (n = 2), pneumonia (n = 1), constrictive pericarditis (n = 1), acute pulmonary edema (n = 1), small bowel herniation (n = 1), and disseminated intravascular coagulopathy (n = 1). The median survival was 20 months, with a 3-year survival of 30%. Asbestos exposure, negative lymph node involvement, and receipt of adjuvant radiation or postoperative pemetrexed-based chemotherapy were associated with improved survival on both univariate and multivariate analyses. CONCLUSION The present study supports the use of extrapleural pneumonectomy-based multimodal therapy in carefully selected patients with malignant pleural mesothelioma.

A meta-analysis of deep hypothermic circulatory arrest versus moderate hypothermic circulatory arrest with selective antegrade cerebral perfusion

INTRODUCTION A recent concern of deep hypothermic circulatory arrest (DHCA) in aortic arch surgery has been its potential association with increased risk of coagulopathy, elevated inflammatory response and end-organ dysfunction. Recently, moderate hypothermic circulatory arrest (MHCA) with selective antegrade circulatory arrest (SACP) seeks to negate potential hypothermia-related morbidities, while maintaining adequate neuroprotection. The present meta-analysis aims to compare postoperative outcomes in arch surgery using DHCA or MHCA+SACP as neuroprotective strategies. METHODS Electronic searches were performed using six databases from their inception to January 2013. Two reviewers independently identified all relevant studies comparing DHCA with MHCA+SACP, as defined by a recent hypothermia temperature consensus. Data were extracted and meta-analyzed according to pre-defined clinical endpoints. RESULTS Nine comparative studies were identified for inclusion in the present meta-analysis. Stroke rates were significantly lower in patients undergoing MHCA+SACP (P=0.0007, I(2)=0%), while comparable results were observed with temporary neurological deficit, mortality, renal failure or bleeding. Infrequent and inconsistent reporting of systemic outcomes precluded analysis of other systemic outcomes. CONCLUSIONS The present meta-analysis indicated the superiority of MHCA+SACP in terms of stroke risk.

Coronary Artery Bypass Grafting With and Without Manipulation of the Ascending Aorta – A Meta-Analysis

BACKGROUND The main criticism of surgery in the SYNTAX trial was increased rate of stroke when compared to percutaneous coronary intervention. We aimed to determine whether avoiding aortic manipulation would decrease the rate of stroke. METHOD We performed a meta-analysis of seven studies comparing coronary artery bypass grafting (CABG) with and without manipulation of the ascending aorta. RESULTS When anaortic off-pump coronary artery bypass grafting (OPCAB) was compared with conventional CABG, the rate of stroke was 0.38% vs. 1.87% (p<0.0001). When anaortic OPCAB was compared with OPCAB using a side-clamp or proximal graft anastomosis device the rate of stroke was 0.31% vs. 1.35% (p=0.003). CONCLUSION Avoiding aortic manipulation during CABG may decrease the rate of peri-operative stroke.