A Multidisciplinary Approach to Oncological Resections with Vascular Surgeons Improves Patient Outcomes.

OBJECTIVE: Oncological resections have become more radical in pursuit of disease free margins. Consequently, vascular structures may be injured inadvertently or purposely resected, with or without subsequent reconstruction. Thus, vascular surgeons have an increasing role in oncological surgery. The present authors sought to review their experience and examine the effect of timing of referral to a Vascular Surgeon (VS) on patient and surgical outcomes following tumour resection. METHODS: A retrospective review was conducted of a prospectively maintained database at a public hospital network in Adelaide, Australia. All cases of collaboration between a VS and other surgeons for resection of cancer or non-malignant tumour were included. Medical records and operative, pathological, and transfusion data were reviewed, with particular attention to referring team, timing of VS referral (pre- or intra-operative), and the operative role of the VS. RESULTS: Seventy-two cases were identified from January 2004 to June 2018. The most common collaborators were General Surgery and Urology. Of the cases, 86% were elective and 71% were referred to the VS pre-operatively. Pre-operative referral was associated with a predominant VS role of dissection and exposure. Pre-operative referral was associated with lower odds of vessel repair and reconstruction compared with intra-operative referral (adjusted OR = 0.20; 95% CI 0.04-0.93; p = .040) and a lower incidence of positive surgical margins (35% vs. 80%, p = .028). The rate of blood product units required was lower among pre-operative referrals relative to intra-operative referrals, but the effect of timing was not significant after adjustment for potential confounders (IRR = 0.80, 95% CI 0.26-2.44; p = .70). CONCLUSION: Pre-operative planned involvement of vascular surgery in oncological operations can improve surgical outcomes, with additional expected benefits for surgical training and cross specialty collaboration.

Lightweight Lead Aprons: The Emperor's New Clothes in the Angiography Suite?

OBJECTIVE: The aim was to determine whether lead containing and lead free composite garments in current use provide the level of radiation protection stated by manufacturers. METHODS: Fifteen garments, produced by five different manufacturers using eight different composites, were randomly selected for testing from four hospitals in South Australia. Labelling, material composition, design, and condition of the garments were assessed by direct garment examination, garment label, and product information. Garment attenuation was tested in a simulated angiography suite using a Siemens Ysio Max digital Xray machine. The front and back panels of each garment were tested under direct beam at 100 kVp. A Perspex phantom was used to simulate the density and scatter properties of the human abdomen. The front panels of each garment were tested under scattered radiation at Xray tube voltages of 50 and 70 kVp. RESULTS: Forty-seven per cent of front panels and 90% of back panels provided lower lead equivalence than claimed by the manufacturer. Twenty per cent of front panels and 62% of back panels tested did not meet the minimum International Electrotechnical Commission requirements for angiographic use. There was a 38 fold difference in front panel performance of garments to scatter radiation, which were all labelled 0.5 mm lead equivalence. 56% of garments had differences in scatter transmission of at least 49% when tested at 50 and 70 kVp. CONCLUSION: The results show that lead containing and lead free composite garments probably provide less radiation protection than manufacturer stated lead equivalence. The demonstrated wide variations in attenuation of scatter radiation are greater than previously reported. It was found that most garments failed to comply with labelling standards. The study highlights challenges in radiation shielding and the need to identify composites that consistently provide better attenuation per unit weight than lead.

Synthesis and Photophysical Study of a [NiFe] Hydrogenase Biomimetic Compound Covalently Linked to a Re-diimine Photosensitizer.

The synthesis, photophysics, and photochemistry of a linked dyad ([Re]-[NiFe2]) containing an analogue ([NiFe2]) of the active site of [NiFe] hydrogenase, covalently bound to a Re-diimine photosensitizer ([Re]), are described. Following excitation, the mechanisms of electron transfer involving the [Re] and [NiFe2] centers and the resulting decomposition were investigated. Excitation of the [Re] center results in the population of a diimine-based metal-to-ligand charge transfer excited state. Reductive quenching by NEt3 produces the radically reduced form of [Re], [Re](-) (kq = 1.4 ± 0.1 × 10(7) M(-1) s(-1)). Once formed, [Re](-) reduces the [NiFe2] center to [NiFe2](-), and this reduction was followed using time-resolved infrared spectroscopy. The concentration dependence of the electron transfer rate constants suggests that both inter- and intramolecular electron transfer pathways are involved, and the rate constants for these processes have been estimated (kinter = 5.9 ± 0.7 × 10(8) M(-1) s(-1), kintra = 1.5 ± 0.1 × 10(5) s(-1)). For the analogous bimolecular system, only intermolecular electron transfer could be observed (kinter = 3.8 ± 0.5 × 10(9) M(-1) s(-1)). Fourier transform infrared spectroscopic studies confirms that decomposition of the dyad occurs upon prolonged photolysis, and this appears to be a major factor for the low activity of the system toward H2 production in acidic conditions.

Photochemical dihydrogen production using an analogue of the active site of [NiFe] hydrogenase.

Photoproduction of dihydrogen (H2) by a low molecular weight analogue of the active site of [NiFe] hydrogenase has been investigated by reduction of the [NiFe2] cluster, 1, by a photosensitier PS (PS = [ReCl(CO)3(bpy)] or [Ru(bpy)3][PF6]2). Reductive quenching of the (3)MLCT excited state of the photosensitizer by NEt3 or N(CH2CH2OH)3 (TEOA) generates PS(•-), and subsequent intermolecular electron transfer to 1 produces the reduced anionic form of 1. Time-resolved infrared spectroscopy (TRIR) has been used to probe the intermediates throughout the reduction of 1 and subsequent photocatalytic H2 production from [HTEOA][BF4], which was monitored by gas chromatography. Two structural isomers of the reduced form of 1 (1a(•-) and 1b(•-)) were detected by Fourier transform infrared spectroscopy (FTIR) in both CH3CN and DMF (dimethylformamide), while only 1a(•-) was detected in CH2Cl2. Structures for these intermediates are proposed from the results of density functional theory calculations and FTIR spectroscopy. 1a(•-) is assigned to a similar structure to 1 with six terminal carbonyl ligands, while calculations suggest that in 1b(•-) two of the carbonyl groups bridge the Fe centers, consistent with the peak observed at 1714 cm(-1) in the FTIR spectrum for 1b(•-) in CH3CN, assigned to a ν(CO) stretching vibration. Formation of 1a(•-) and 1b(•-) and production of H2 was studied in CH3CN, DMF, and CH2Cl2. Although the more catalytically active species (1a(•-) or 1b(•-)) could not be determined, photocatalysis was observed only in CH3CN and DMF.

Update on aneurysm disease: current insights and controversies: peripheral aneurysms: when to intervene - is rupture really a danger?

Peripheral artery aneurysms are rarer than abdominal aortic aneurysms (AAA), although the true prevalence is not well known. They often coexist with aortic and other peripheral artery aneurysms. In contrast to AAA, where the principal risk is that of rupture, thromboembolism is more common, contributing a bigger risk in the more common lesions. Although rupture does occur, with incidence related to anatomical site, aneurysm diameter cannot be used to guide management with the same confidence as in AAA. In addition, the rarity of these lesions results in a paucity of evidence with which to guide intervention. Consequently they are difficult lesions to manage, and numerous aneurysm and patient factors must be considered to provide treatment individualised for each case. We discuss popliteal, femoral, carotid, subclavian, upper limb, visceral and false aneurysms, focussing on the risk of rupture and thromboembolism, and current thresholds for intervention, based on the available published literature.

Aortic aneurysms secrete interleukin-6 into the circulation.

OBJECTIVE: Circulating plasma interleukin-6 (IL-6) concentrations are elevated in patients with abdominal aortic aneurysms (AAAs) compared with controls. In vitro studies suggest that the aneurysm is the source of the IL-6. Because IL-6 is an independent risk factor for cardiovascular mortality, elevation of this cytokine may be significant in these patients, who represent a group at increased risk from cardiovascular death. The aim of this study was to directly measure in vivo aortic IL-6 concentrations, testing the hypothesis that aneurysms secrete IL-6 into the circulation. METHODS: Before endovascular aneurysm repair took place, blood was sampled from the entire length of the aorta in 27 patients with AAA and nine with thoracic aneurysms (TAs). A control group consisted of 15 patients without aneurysms undergoing angiography. Plasma IL-6 was determined using enzyme-linked immunosorbent assay, and high-sensitivity C-reactive protein (hs-CRP) was measured turbidimetrically. Aneurysm surface area was calculated from axial computed tomography scans. RESULTS: Mean IL-6 concentrations (pg/mL) were higher in the TA and AAA groups compared with controls (10.4 +/- 3.7 and 4.9 +/- 0.5 vs 2.7 +/- 0.5, P = .002). There was a significant difference in plasma IL-6 concentration corresponding to aneurysm position in the AAA (P = .002) and TA (P = .008) groups, with both patterns conforming to a linear trend. This pattern was not observed in the control group, in which no significant difference in IL-6 concentrations was found throughout the aorta. Peak IL-6 occurred earlier in TAs compared with AAAs (descending aorta vs iliac artery) corresponding to aneurysm position (P = .0007). Linear regression revealed a positive correlation between aneurysm surface area and mean plasma IL-6 (Spearman's correlation, P = .003). The mean surface areas of the TAs, at 0.07 m2 (interquartile range [IQR], 0.06 to 0.09), were higher than those of the AAAs at 0.03 m2 (IQR, 0.02 to 0.04; P = .002). High-sensitivity CRP was within normal limits, and no significant differences were found between the AAA group and the controls. CONCLUSIONS: Circulating IL-6 is elevated within the aorta in patients with aneurysms and corresponds to aneurysm position. Furthermore, aneurysm surface area and mean plasma IL-6 are correlated. In the absence of any evidence of systemic inflammation in the form of elevated hs-CRP, these data support the hypothesis that aneurysms secrete IL-6 into the circulation. This may contribute to the high cardiovascular mortality observed in patients with aneurysms.

Aortic aneurysms as a source of circulating interleukin-6.

In keeping with the inflammatory paradigm of abdominal aortic aneurysm (AAA) pathophysiology, in vitro studies suggest that aneurysms secrete the proinflammatory cytokine interleukin-6 (IL-6). Circulating IL-6 levels are higher in patients with AAA with elevated circulating IL-6 an independent risk factor for cardiovascular mortality. To investigate whether aneurysms secrete IL-6 into the circulation, arterial IL-6 was measured from within the aorta in three groups of patients undergoing endovascular procedures; 27 AAA, 10 thoracic aneurysms (TA), and 15 controls. Overall, IL-6 was higher in the aneurysm groups (P < 0.0008) with significant rises corresponding to positions downstream to the aneurysm in both AAA and TA. There were no significant differences in IL-6 with aortic position in the control group. These data support the hypothesis that aneurysms secrete IL-6 into the circulation and may account for the high cardiovascular mortality observed in patients with aneurysms.

Circulating cytokines in patients with abdominal aortic aneurysms.

Studies suggest that aneurysm-derived cytokines perpetuate the cycle of inflammation and proteolysis that is the pathological hallmark of abdominal aortic aneurysms (AAA). As interleukin (IL)-6 is an independent risk factor for cardiovascular mortality, such cytokines may also have important systemic effects. The purpose of this study was to investigate the effect of aneurysm repair on circulating levels of cytokines. Inflammatory cytokines were measured in 99 patients with AAA and 100 patients who had undergone AAA repair in the past. There was a significant reduction in IL-10 in the postoperative group, and a nonsignificant trend toward reduction in IL-6 and CRP in the postoperative group. Subgroup analysis of the postoperative group revealed significantly lower levels of IL-6 and CRP in the open group compared to endovascular aneurysm repair (EVAR). These results suggest that aneurysm repair may have an effect upon chronic levels of circulating inflammatory cytokines, and that the type of repair may exert some influence.

Endothelial progenitor cells and abdominal aortic aneurysms.

Endothelial progenitor cells (EPCs) are a population of circulating stem cells that hone in to sites of vascular injury where they undergo differentiation to become incorporated into damaged tissue. The aim of this study was to enumerate EPCs in patients with abdominal aortic aneurysms (AAA). CD133(+) peripheral blood mononuclear cells were immunomagnetically selected and CD34/CD133 was used as a marker of EPCs. EPCs were detected using flow cytometry. AAA patients had significantly higher levels of circulating EPCs than age-matched controls (2.43% vs. 1.25% of all events, P = 0.008). The role and function of EPCs in AAA remain to be determined, but their implication with angiogenesis may represent one plausible mechanism.

Pharmacotherapy of abdominal aortic aneurysms.

Aortic aneurysms account for 10,000 deaths annually in the UK, due to rupture. At present the only effective therapeutic strategy to treat abdominal aortic aneurysms is to surgically repair them; this carries an elective mortality of up to 10%. Recent advances in vascular biology have led to a greater understanding of the pathophysiological process that causes aortic aneurysms to expand and rupture. Key pathological processes include widespread aortic inflammation, proteolytic degradation of the extracellular matrix, neovascularisation and generation of reactive oxygen species. Identification of these processes has lead to pharmacological strategies to prevent aneurysm expansion and rupture. Many of these strategies have undergone proof of concept in animal models and some have now entered clinical trials. This review outlines current thinking regarding the molecular events leading to aneurysm expansion and explains how these processes may be inhibited. Experimental data on agents retarding aneurysm expansion in animal models are discussed. A significant proportion of the review details pharmacological agents that have undergone or are undergoing clinical trials. Pharmacological treatment for abdominal aneurysms is urgently required given the number of small aneurysms being diagnosed by screening programmes. This is a rapidly evolving field and one in which translation from experimental research to clinical practice is anticipated within 5 years.