Cutting Edge Members' Abstracts

Below are a selection of abstracts that have been successfully published or presented by Cutting Edge Members whilst at Medical School.

The Carotid Endarterectomy: Is it Time to Change Approach?


AuthorsM.A. Bailey, R.G. Tunstall, M.J. Gough & D.J.A. Scott
JournalAnnals of The Royal College of Surgeons of England, 2007; 89: 646-648.
BackgroundMild carotid stenosis is highly prevalent in the general population owing to the unique haemodynamics of the carotid bifurcation (CB). Worsening stenosis increases the risk of plaque rupture and ischaemic stroke. Carotid endarterectomy (CEA) is the gold standard intervention for patients with high grade stenosis. Stroke-death rates have improved dramatically over the last decade and are now extremely low however the incidence of local complications such as cranial nerve injury has changed little over this period. The recently proposed retrojugular approach to CEA is quick, simple and safe. Studies to-date suggest it provides superior exposure whilst imparting protection to local structures and may offer a favourable modification to routine surgical practice.
Materials & MethodsThe anterior triangle of the neck was dissected in four 4.0% formaldehyde fixed human cadavers to present local structures. Objective measurements were taken using electronic digital callipers of the CB height, relationship of the hypoglossal nerve (HN) to the CB and the extent of exposure with both the retrojugular and traditional approaches.
ResultsHN was found within 6mm of high CB, directly obstructing antejugular approach to the carotid artery. The retrojugular approach provided enhanced arterial exposure in all cases with an average increase of 12.9±7.6mm compared to antejugular dissection. The HN was swept out of the surgical field with this approach, regardless of its relationship to the CB but the vagus nerve (VN) was located superficially at risk of damage during dissection. The accessory nerve (AN) ran anterior to the internal jugular vein (IJV) in all cases at risk of stretch during anterior mobilisation of the IJV.
ConclusionsHN damage and voice changes are the most commonly reported complications following antejugular CEA. Whilst the retrojugular approach confers protection to the HN, it puts both the VN and AN in jeopardy. The superior exposure is irrefutable, however appropriately designed randomized trials are necessary to fully evaluate the relative risk of nerve damage with this approach before a decision to alter surgical practice can be made. Until then its use should be reserved for patients where HN protection is of paramount importance.
Other DetailsPresented at the Yorkshire Vascular Forum (November 2006); Winner, Registrars' Prize Section

Characterisation of Fractalkine and Fractalkine Receptor Expression in Abdominal Aortic Aneurysm Disease


AuthorsA. Patel, V.P. Jagadesham, K.E. Porter, S.R. Carding & D.J.A. Scott
BackgroundAbdominal aortic aneurysms (AAA) exhibit histological features of a chronic inflammatory disease. It is unclear how the inflammation is initiated and propagated. The CX3C chemokine, fractalkine (CX3CL1) is expressed on both vascular smooth muscle cells (vSMC) & endothelial cells (vEC) and promotes adhesion and extravasation of leucocytes through interactions with fractalkine receptor (CX3CR1), which is expressed on CD56+/CD16+ NK-cells and CD8+ T-cells. This study aims to analyse expression of CX3CL1 and CX3CR1 in AAA disease.
Materials & MethodsImmunohistochemistry (IHC) was used to define expression of CX3CR1 in AAA tissue. The cellular infiltrate was graded for CX3CR1 staining using a three plus scoring system. Multi-parametric flow cytometry (FC) was used to determine CX3CR1 expression on T-cells (CD3+) and NK cells (CD56+) from AAA tissue and peripheral blood mononuclear cells (PBMCs) of AAA patients and healthy controls. Primary vEC and vSMC prepared using the explant techniques were stimulated with the pro-inflammatory cytokine TNFa, and CX3CL1 expression was assessed with FC. Percentage median values were calculated with interquartile ranges.
ResultsCX3CR1+ cells were detected in 21/31 AAA tissue samples and predominately localised in the adventitia. PBMCs from patients with AAA demonstrated higher percentages of CX3CR1+ NK cells (72.9, 46.9 - 87.7%) and T cells (12, 6.9 – 38.9%) compared with healthy controls. Furthermore, the frequency of CX3CR1+ NK cells (91%) and T cells (94%) in inflammatory AAA tissue were higher than in atherosclerotic AAA tissue. The pro-inflammatory cytokine TNFa increased expression of fractalkine by vEC and vSMC by 14.8 fold and 1.5 fold respectively.
ConclusionsCX3CL1+ and CX3CR1+ cells are present in AAA disease and their interaction may contribute to the recruitment of inflammatory cells seen in AAA tissue.
Other DetailsPresented at The Annual Meeting of the European Society for Vascular Surgery, Madrid, Spain (September 2007) & The Yorkshire Vascular Forum (November 2007)

Tumour Metabolism in Colorectal Cancer and Liver Metastases: A Revisitation of the Warburg Effect


AuthorsI.A. Insari, R. Rajaganeshan, N. Scott, I. Ansari, P.J. Guillou & D.G. Jayne
JournalBritish Journal of Surgery, 94: 1-31.
BackgroundA link between mitochondrial dysfunction and tumour glycolysis was first proposed by Warburg in the 1930’s. The current study aims to study further this association with specific reference to mitochondrial cytochrome c oxidase (COX).
Materials & MethodsTissue microarray immunohistochemistry was used to investigate the expression of mitochondrial DNA-encoded subunit II and nuclear DNA-encoded subunit IV of COX in parallel with markers of glucose uptake and glycolysis (GLUT-1, hexokinase II and LDH 5) in 79 colorectal cancers and 53 liver metastases.
ResultsA large variation in COX subunit expression was observed. In 44/79 (56%) primary cancers, COX II and IV expression was moderate-strong, with a selective suppression of COX II in 22/79 (28%) cancers (p <0.0001). Intense expression of markers of glycolysis was evident in 83% of tumours with moderate-strong expression of both COX subunits, compared to only 40% in COX II-suppressed tumours (p=0.001). At the invasive margin, COX II and IV expression were found to positively correlate with hexokinase II (p=0.02 and p=0.016) and LDH 5 (p><0.0001 and p=0.001). Kaplan Meier analysis of time to recurrence, showed that increased COX II activity was significantly associated with liver metastasis formation [mean (95% CI) high COX II: 43.9(32.9-54.9) vs. low COX II: 67.4(54.21-80.51); Log rank p=0.026].
ConclusionsSelective suppression of COX II is associated with reduced glycolytic marker expression and reduced metastatic potential. The observed relationship between mitochondrial and glycolytic activity is in direct contrast to that proposed by Warburg and raises important questions concerning the control of tumour metabolism.
Other DetailsPresented at The European Society for Surgical Research, Rotterdam, Amsterdam (2007), The Society for Academic and Research Surgery, Cambridge (2007) and The Student Research Symposium at The Royal College of Surgeons of Edinburgh (2006); Winner best oral presentation.

Lateral External Carotid Artery: Implications for the Vascular Surgeon


AuthorsM.A. Bailey, D.J.A. Scott, R.G. Tunstall & M.J. Gough
JournalThe European Journal of Vascular & Endovascular Surgery Extra, 2007; 14: 22-24.
AbstractThe internal carotid artery (ICA) usually lies posterolaterally to the external carotid artery (ECA) beyond the carotid bifurcation. Unusual conformations of these arteries have received little attention in the literature. Two cases of lateral ECA (LECA) were identified during cadaveric dissection which would have limited access to the ICA during carotid endarterectomy (CEA). ICA exposure during CEA in cases of LECA is challenging requiring care to avoid hypoglossal or internal laryngeal nerve injury. Circumferential dissection and medial mobilisation of the ECA provides suitable exposure for CEA.