Research

Haemolysis during sample preparation alters microRNA content of plasma

Kirschner MB, Kao SC, Edelman JJ, Armstrong NJ, Vallely MP, van Zandwijk N, Reid G

PLoS ONE 2011;6(9):e24145

PMID: 21909417

Abstract

The presence of cell-free microRNAs (miRNAs) has been detected in a range of body fluids. The miRNA content of plasma/serum in particular has been proposed as a potential source of novel biomarkers for a number of diseases. Nevertheless, the quantification of miRNAs from plasma or serum is made difficult due to inefficient isolation and lack of consensus regarding the optimal reference miRNA. The effect of haemolysis on the quantification and normalisation of miRNAs in plasma has not been investigated in great detail. We found that levels of miR-16, a commonly used reference gene, showed little variation when measured in plasma samples from healthy volunteers or patients with malignant mesothelioma or coronary artery disease. Including samples with evidence of haemolysis led to variation in miR-16 levels and consequently decreased its ability to serve as a reference. The levels of miR-16 and miR-451, both present in significant levels in red blood cells, were proportional to the degree of haemolysis. Measurements of the level of these miRNAs in whole blood, plasma, red blood cells and peripheral blood mononuclear cells revealed that the miRNA content of red blood cells represents the major source of variation in miR-16 and miR-451 levels measured in plasma. Adding lysed red blood cells to non-haemolysed plasma allowed a cut-off level of free haemoglobin to be determined, below which miR-16 and miR-451 levels displayed little variation between individuals. In conclusion, increases in plasma miR-16 and miR-451 are caused by haemolysis. In the absence of haemolysis the levels of both miR-16 and miR-451 are sufficiently constant to serve as normalisers.

Aortic valve-sparing operations in aortic root aneurysms: remodeling or reimplantation?

Rahnavardi M, Yan TD, Bannon PG, Wilson MK

Interact Cardiovasc Thorac Surg 2011 Aug;13(2):189-97

PMID: 21571910

Abstract

A best evidence topic was written according to a structured protocol. The question addressed was whether the reimplantation (David) technique or the remodeling (Yacoub) technique provides the optimum event free survival in patients with an aortic root aneurysm suitable for an aortic valve-sparing operation. In total, 392 papers were found using the reported search criteria, of which 14 papers provided the best evidence to answer the clinical question. A total of 1338 patients (Yacoub technique in 606 and David technique in 732) from 13 centres were included. In most series, cardiopulmonary bypass time and aortic cross-clamp time were longer for the David technique compared to the Yacoub technique. Early mortality was comparable between the two techniques (0-6.9% for the Yacoub technique and 0-6% for the David technique). There is a tendency for a higher freedom from significant long-term aortic insufficiency in the David group than the Yacoub group, which does not necessarily result in a higher reoperation rate in the Yacoub group. In the largest series reported, freedom from a moderate-to-severe aortic insufficiency at 12 years was 82.6 ± 6.2% in the Yacoub and 91.0 ± 3.8% in the David group (P=0.035). Freedom from reoperation at the same time point was 90.4 ± 4.7% in the Yacoub group and 97.4 ± 2.2% in the David group (P=0.09). In another series, freedom from reoperation at a follow-up time of about four years was 89 ± 4% in the Yacoub group and 98 ± 2% in the David group. Although some authors merely preferred the Yacoub technique for a bicuspid aortic valve, the accumulated evidence in the current review indicates comparable results for both techniques in a bicuspid aortic valve. Current evidence is in favour of the David rather than the Yacoub technique in pathologies such as Marfan syndrome, acute type A aortic dissection, and excessive annular dilatation that may impair aortic root integrity. Careful selection of patients for each technique and successful restoration of normal cusp geometry are the keys to success in aortic valve-sparing operations.

Total percutaneous cardiopulmonary bypass with Perclose ProGlide

Ramponi F, Yan TD, Vallely MP, Wilson MK

Interact Cardiovasc Thorac Surg 2011 Jul;13(1):86-8

PMID: 21482577

Abstract

Suture-mediated closure devices have been previously described as an interesting alternative to femoral cutdown during endovascular aortic procedures. The insertion of two or three devices before the cannulation (preclose technique) permits successful percutaneous access also with a large sheath up to 24 Fr diameter. The main benefit of percutaneous access is a lower rate of complication at the groin. The same technique can be applied to cardiac procedures where femoral cannulation for cardiopulmonary bypass (CPB) is required. We report a series of 12 patients in whom total percutaneous CPB was successfully established using a Perclose ProGlide for the arterial access.

Improving survival results after surgical management of malignant pleural mesothelioma: an Australian institution experience

Yan TD, Cao CQ, Boyer M, Tin MM, Kennedy C, McLean J, Bannon PG, McCaughan BC

Ann Thorac Cardiovasc Surg 2011;17(3):243-9

PMID: 21697784

Abstract

BACKGROUND: There has been an evolving role of surgery for malignant pleural mesothelioma (MPM) over the past 25 years. The objective of this study was to investigate whether the survival results for MPM patients after surgery have improved within this time period by an analysis of a prospective cohort of 540 patients.

METHODS: Five hundred and forty consecutive patients with MPM were treated by a thoracic surgical team. These patients were categorized into two groups: Group I (before September 1999, n = 270) and Group II (after September 1999, n = 270). The two groups were compared for clinicopathologic data and survival results. The statistical analyses of all prognostic parameters used overall survival as the endpoint.

RESULTS: Group II had higher proportions of epithelial tumors and patients who had preoperative PET scan, extrapleural pneumonectomy (EPP), postoperative radiotherapy and pemetrexed chemotherapy. The overall survival results were significantly better in Group II compared with Group I (p = 0.004). Four factors were found to be independently associated with an improved survival in multivariate analysis: epithelial subtype (p 100 cases (p = 0.006), patients who underwent EPP (p = 0.001) and those who received pemetrexed chemotherapy (p = 0.016). The median survival for patients selected for EPP was 20 months, as compared to 9 months for pleurodesis/decortication and pleurodesis.

CONCLUSIONS: Significant improvement of overall survival results has been achieved in the more recent 270 MPM patients through accumulated experience in a specialist treatment center.

Transapical wire-assisted endovascular repair of thoracic aortic dissection

Ramponi F, Vallely MP, Stephen MS, Bannon PG, Bayfield MS, White GH

J. Endovasc. Ther. 2011 Jun;18(3):350-4

PMID: 21679073

Abstract

PURPOSE: To describe a technique for transapical wire-assisted endograft deployment under rapid ventricular pacing for a type B dissection involving the proximal left subclavian artery and extending to the aortic bifurcation.

CASE REPORT: A 58-year-old man presented with a symptomatic thoracic aneurysm as a complication of a chronic type B dissection, with a short proximal neck in zone 1. After arch vessel debranching, the patient underwent endoluminal repair with deployment of a closed web, tapered Valiant thoracic endograft over a through-and-through wire from the left groin to the apex of the left ventricle, using rapid ventricular pacing to reduce cardiac output. The remaining dissected aorta was covered with a second Valiant endograft down to the distal third of the descending thoracic aorta and bare Z stents down to the aortic bifurcation to re-expand the true lumen. A freeflow Valiant endograft was deployed as a proximal extension to treat a proximal type I endoleak. The recovery was complicated by retrograde type A aortic dissection, considered secondary to the bare stent. The complication was repaired surgically; postoperative computed tomography after recovery was unremarkable.

CONCLUSION: Transapical wire-assisted deployment with rapid ventricular pacing is feasible and may provide improved stability for stenting within the aortic arch. The use of a stent-graft with a proximal bare stent is associated with a higher risk of retrograde extension of the dissection and warrants lifelong imaging follow-up.

Thoracic endovascular aortic repair–indications and evidence

Cao CQ, Bannon PG, Shee R, Yan TD

Ann Thorac Cardiovasc Surg 2011;17(1):1-6

PMID: 21587120

Abstract

PURPOSE: Since its introduction more than a decade ago, thoracic endovascular aortic repair (TEVAR) has shown promising results for patients with various thoracic aortic diseases. The aim of the current review is to assess the current literature to evaluate the safety and efficacy of TEVAR.

METHODS: A thorough search of the existing literature on TEVAR was conducted on electronic databases, including Medline, Pubmed, EMBASE and Database of Abstracts of Review of Effectiveness. The most recent results were categorized according to the indications of performing TEVAR.

RESULTS: A number of case-series studies and reviews have shown reduced early morbidity and mortality rates in a range of thoracic aortic diseases for TEVAR in comparison to open surgical repair. However, there is a lack of robust clinical data to suggest any improvement in long-term overall survival.

CONCLUSION: Despite numerous encouraging results from a large number of publications in recent years, there remains a lack of level 1 evidence to support an improvement of long-term overall survival for patients who underwent TEVAR when compared with traditional treatment modalities. There appears to be an urgent need to conduct well-designed randomized-controlled trials in this rapidly expanding intervention.

Familial aortic aneurysm and dissection due to transforming growth factor-beta receptor 2 mutation

Edelman JJ, Ramponi F, Bannon PG, Jeremy R

Interact Cardiovasc Thorac Surg 2011 May;12(5):863-5

PMID: 21324918

Abstract

This report describes the clinical course and management of a patient with Loeys-Dietz syndrome (LDS) type 2. In 2003, a 31-year-old male was diagnosed with acute aortic dissection type B; in the following six years he underwent multiple surgical and endovascular aortic procedures at different thoracic and abdominal levels secondary to progressive enlargement of both the non-dissected thoracic aorta and the false lumen distal to the left subclavian artery. LDS is characterized by arterial tortuosity and aneurysms as a result of heterozygous mutations in genes encoding transforming growth factor-β receptor 1 and 2. Further studies are required to establish the proper surgical management.

Staging of patients after extrapleural pneumonectomy for malignant pleural mesothelioma–institutional review and current update

Cao C, Krog Andvik SK, Yan TD, Kennedy C, Bannon PG, McCaughan BC

Interact Cardiovasc Thorac Surg 2011 May;12(5):754-7

PMID: 21303872

Abstract

Extrapleural pneumonectomy (EPP) has been established as a viable surgical option in the treatment of malignant pleural mesothelioma (MPM) for selected patients. A number of pathological staging systems have been developed to prognosticate survival outcomes. We assessed 91 patients with MPM who underwent EPP in our institution and evaluated the applicability of the most updated staging systems in the current literature. After a mean follow-up of 20 months, the median overall survival was 27.6 months. Postoperative pathological staging according to the International Mesothelioma Interest Group criteria (P = 0.026) and the Brigham and Women’s Hospital criteria (P = 0.039) were both found to be significant prognostic factors. Adjuvant chemotherapy (P = 0.022) and radiotherapy (P = 0.008) were associated with improved survival outcomes. These findings are consistent with previous reports that demonstrated the usefulness of pathological staging systems as a prognostic tool in patients with MPM after undergoing EPP. However, preoperative clinical staging systems need to be developed to facilitate the patient selection process prior to surgery.

Coronary artery bypass grafting with and without manipulation of the ascending aorta–a meta-analysis

Edelman JJ, Yan TD, Bannon PG, Wilson MK, Vallely MP

Heart Lung Circ 2011 May;20(5):318-24

PMID: 21511187

Abstract

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.

A novel tumor-node-metastasis (TNM) staging system of diffuse malignant peritoneal mesothelioma using outcome analysis of a multi-institutional database*

Yan TD, Deraco M, Elias D, Glehen O, Levine EA, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH,

Cancer 2011 May;117(9):1855-63

PMID: 21509762

Abstract

BACKGROUND: Currently, no tumor-node-metastasis (TNM) staging system exists for patients with diffuse malignant peritoneal mesothelioma (DMPM). The primary objective was to formulate a clinicopathological staging system through the identification of significant prognostic parameters.

METHODS: Eight international institutions with prospectively collected data on patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy contributed to the registry. Two hundred ninety-four patients had complete clinicopathological data and formed the basis of this staging project.

RESULTS: Peritoneal cancer index (PCI) was categorized into T(1) (PCI 1-10), T(2) (PCI 11-20), T(3) (PCI 21-30), and T(4) (PCI 30-39). Twenty-two patients had positive lymph nodes (N(1) ) and 12 patients had extra-abdominal metastases (M(1) ). The survival for patients with T(1) (PCI 1-10) N(0) M(0) was significantly superior to the other patients. This group of patients is therefore designated as Stage I. The survival of patients with T(2) (PCI 11-20) and T(3) (PCI 21-30), in absence of N(1) or M(1) disease, was similar. This group of patients was categorized as Stage II. The survival of patients with T(4) (PCI 30-39), N(1,) and/or M(1) was similarly poor. This group of patients was therefore categorized as Stage III. Three prognostic factors were independently associated with survival in the multivariate analysis: histological subtype, completeness of cytoreduction, and the proposed TNM staging. The 5-year survival associated with Stage I, II, and III disease was 87%, 53%, and 29%, respectively.

CONCLUSIONS: The proposed TNM staging system resulted in significant stratification of survival by stage when applied to the current multi-institutional registry data.

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