Top 10 candidate aortic disease trials.

Aortic pathologies such as aneurysm, dissection and trauma are relatively common and potentially fatal diseases. Over the past two decades, we have experienced unprecedented technical and medical developments in the field. Despite this, there is a great need, and great opportunities, to further explore the area. In this review, we have identified important areas that need to be further studied and selected priority aortic disease trials. There is a pressing need to update the AAA natural history and the role for endovascular AAA repair as well as to define biomarkers and genetic risk factors as well as influence of gender for development and progression of aortic disease. A key limitation of contemporary treatment strategies of AAA is the lack of therapy directed at small AAA, to prevent AAA expansion and need for surgical repair, as well as to reduce the risk for aortic rupture. Currently, the most promising potential drug candidate to slow AAA growth is metformin, and RCTs to verify or reject this hypothesis are warranted. In addition, the role of endovascular treatment for ascending pathologies and for uncomplicated type B aortic dissection needs to be clarified.

Cerebral embolization, silent cerebral infarction and neurocognitive decline after thoracic endovascular aortic repair.

BACKGROUND: Silent cerebral infarction is brain injury detected incidentally on imaging; it can be associated with cognitive decline and future stroke. This study investigated cerebral embolization, silent cerebral infarction and neurocognitive decline following thoracic endovascular aortic repair (TEVAR). METHODS: Patients undergoing elective or emergency TEVAR at Imperial College Healthcare NHS Trust and Guy's and St Thomas' NHS Foundation Trust between January 2012 and April 2015 were recruited. Aortic atheroma graded from 1 (normal) to 5 (mobile atheroma) was evaluated by preoperative CT. Patients underwent intraoperative transcranial Doppler imaging (TCD), preoperative and postoperative cerebral MRI, and neurocognitive assessment. RESULTS: Fifty-two patients underwent TEVAR. Higher rates of TCD-detected embolization were observed with greater aortic atheroma (median 207 for grade 4-5 versus 100 for grade 1-3; P = 0·042), more proximal landing zones (median 450 for zone 0-1 versus 72 for zone 3-4; P = 0·001), and during stent-graft deployment and contrast injection (P = 0·001). In univariable analysis, left subclavian artery bypass (ß coefficient 0·423, s.e. 132·62, P = 0·005), proximal landing zone 0-1 (ß coefficient 0·504, s.e. 170·57, P = 0·001) and arch hybrid procedure (ß coefficient 0·514, s.e. 182·96, P < 0·001) were predictors of cerebral emboli. Cerebral infarction was detected in 25 of 31 patients (81 per cent) who underwent MRI: 21 (68 per cent) silent and four (13 per cent) clinical strokes. Neurocognitive decline was seen in six of seven domains assessed in 15 patients with silent cerebral infarction, with age a significant predictor of decline. CONCLUSION: This study demonstrates a high rate of cerebral embolization and neurocognitive decline affecting patients following TEVAR. Brain injury after TEVAR is more common than previously recognized, with cerebral infarction in more than 80 per cent of patients.

Mid-term Outcomes of Renal Branches Versus Renal Fenestrations for Thoraco-abdominal Aneurysm Repair.

OBJECTIVE/BACKGROUND: The objective was to investigate renal outcomes following endovascular repair of thoraco-abdominal aortic aneurysms (TAAA) comparing fenestrations with branches for the renal arteries. METHODS: Renal outcomes following TAAA endovascular repair performed with renal branches were collected from five high volume European centers and compared with renal outcomes following TAAA endovascular repair performed with renal fenestrations at one center. Renal re-intervention and occlusion rates, and freedom from any renal outcome and death were analyzed by patient and target vessel. Estimated glomerular filtration rate (eGFR) was calculated and collected pre-operatively and at the last available follow up. RESULTS: In total, 449 patients were included in this retrospective study (235 treated with branched devices [BEVAR] and 214 with fenestrated devices [FEVAR]). Altogether, 856 renal vessels were analyzed (445 perfused by branches and 411 by fenestrations). Both groups were comparable except for sex and smoking habits. Technical success rates were 95% and 99%, respectively. Mean ± SD follow up was 19 ± 18 months after BEVAR and 24 ± 20 months after FEVAR. During follow up, renal re-intervention rates were similar in both groups (4.7% vs. 5.2%). The renal occlusion rate was significantly higher following BEVAR (9.6% vs. 2.3%; p < .01), and the 2 year freedom for renal occlusion rate was 90.4% (SE 85.8-95.3%) following BEVAR and 97.1% (SE 94.6-99.7%) following FEVAR (p < .01). During follow up, a 12% median decrease in eGFR was observed following BEVAR versus 9% following FEVAR (non-significant). The 2 year survival rates were 73.4% (SE 66.6-80.9%) and 81.8% (SE 76.1-87.9%) following BEVAR and FEVAR, respectively. CONCLUSION: Mid-term renal outcomes following endovascular repair of TAAA are satisfactory. Endograft designs incorporating renal fenestrations rather than renal branches are associated with significantly lower occlusion rates. A prospective trial is now required to confirm these results.

Editor's Choice - Effect of Branch Stent Choice on Branch-related Outcomes in Complex Aortic Repair.

OBJECTIVES: The use of branched stent grafts for the treatment of thoracoabdominal aneurysms [TAAA] is increasing, but mating stent graft choice has not been studied. This study combined experience of five high volume centres to assess a preferred mating stent. METHODS: Data from five centres were retrospectively combined. Patients were included if they underwent stent graft for treatment of TAAA that used only branches to mate with visceral and renal vessels. All patients with fenestrations in their device were excluded. Perioperative details, reintervention, occlusion, and death were recorded. Outcome of occlusion or reintervention, as well as a composite outcome of any death, occlusion, or reintervention was planned using a per-patient, and per-branch analysis. RESULTS: In 235 included patients, there were 940 vessels available for placement of mating stent. The average age of included patients was 70 years (SD 7.9), and 179 of the 235 were male. Medical comorbidities included diabetes in 29/234 (12.4%), current smoker in 81/233 (34.8%), and COPD in 77/234 (32.9%). The primary stent deployed was self-expanding in 556 branches, balloon expandable in 231 branches, and was unknown in 92 branches. After a mean of 20.7 months (SD 25) follow-up, there have been 44 incidents of occlusion or reintervention, of which 40 culprit stents are known. Where the stent placed is known, the event rate in renal branches (35/437, 8%) is higher than that of visceral branches (8/443, 1.8%). There is no difference in occlusion or reintervention between self-expanding and balloon expandable stents (HR 0.95, p = .91) but there is a statistically significant difference between renal and visceral artery occlusions (HR 3.51, p = 0.001). CONCLUSION: There appears to be no difference in occlusion or reintervention rate for branch vessels mated with balloon expandable compared with self-expanding stents. Renal events appear to outnumber visceral events in this population.

Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC).

OBJECTIVE/BACKGROUND: The management of aortic graft infection (AGI) is highly complex and in the absence of a universally accepted case definition and evidence-based guidelines, clinical approaches and outcomes vary widely. The objective was to define precise criteria for diagnosing AGI. METHODS: A process of expert review and consensus, involving formal collaboration between vascular surgeons, infection specialists, and radiologists from several English National Health Service hospital Trusts with large vascular services (Management of Aortic Graft Infection Collaboration [MAGIC]), produced the definition. RESULTS: Diagnostic criteria from three categories were classified as major or minor. It is proposed that AGI should be suspected if a single major criterion or two or more minor criteria from different categories are present. AGI is diagnosed if there is one major plus any criterion (major or minor) from another category. (i) Clinical/surgical major criteria comprise intraoperative identification of pus around a graft and situations where direct communication between the prosthesis and a nonsterile site exists, including fistulae, exposed grafts in open wounds, and deployment of an endovascular stent-graft into an infected field (e.g., mycotic aneurysm); minor criteria are localized AGI features or fever ≥38°C, where AGI is the most likely cause. (ii) Radiological major criteria comprise increasing perigraft gas volume on serial computed tomography (CT) imaging or perigraft gas or fluid (≥7 weeks and ≥3 months, respectively) postimplantation; minor criteria include other CT features or evidence from alternative imaging techniques. (iii) Laboratory major criteria comprise isolation of microorganisms from percutaneous aspirates of perigraft fluid, explanted grafts, and other intraoperative specimens; minor criteria are positive blood cultures or elevated inflammatory indices with no alternative source. CONCLUSION: This AGI definition potentially offers a practical and consistent diagnostic standard, essential for comparing clinical management strategies, trial design, and developing evidence-based guidelines. It requires validation that is planned in a multicenter, clinical service database supported by the Vascular Society of Great Britain & Ireland.

Atherosclerotic Plaque Analysis: A Pilot Study to Assess a Novel Tool to Predict Outcome Following Lower Limb Endovascular Intervention.

INTRODUCTION: Atherosclerotic plaque analysis using computed tomography angiography (CTA) has been found to be accurate and reproducible in the coronary and carotid arteries. The aim of our study was to assess the utility of this technique in predicting outcome following lower limb endovascular interventions. METHODS: Pre-procedural CTA was retrospectively analysed in 50 patients who had undergone femoropopliteal (F-P) angioplasty (and/or stenting). Plaque analysis was performed using TeraRecon workstation by two observers blinded to the long-term outcome. Using the Hounsfield units (HU) scale atherosclerotic plaque composition was subdivided into volumes of soft (-100-100 HU) fibrocalcific (101-300 HU) or calcified (300-1000 HU) components. The relationship between plaque composition, clinical and procedural variables, and the study end points (vessel patency, binary restenosis rate, and Amputation-Free Survival [AFS]) were assessed using multivariate analysis. RESULTS: The technical success rate of the endovascular procedure was 98%, with 48% of patients receiving F-P stents. The AFS was 90%, primary patency 84%, assisted primary patency 88%, and binary restenosis 44% all at 1 year. A significantly greater total volume of calcified plaque (1.1 [.01-3.2] cm(3) vs. .11 [0-1.86] cm(3), p < .001) was found in patients developing restenosis (>50%) compared with those who did not. Patients with a calcified plaque volume greater than 1.1 cm(3) had a significantly worse AFS than those with a volume less than 1.1 cm(3) (p = .0038). Multivariate analysis showed that the percentage calcified plaque (p = .003, HR 11.4, 95% CI 1.45-37.29) was an independent predictor of binary restenosis at 12 months, and that absolute volume of calcified plaque (p = .001, HR 3.56, 95% CI 1.64-7.7) was independently associated with AFS. CONCLUSIONS: The burden of calcified plaque, but not soft or fibrocalcific plaque is related to restenosis, reintervention, and AFS. Computed tomography plaque analysis may form an important non-invasive tool for risk stratification in patients undergoing F-P endovascular procedures.

Neuroprotective Strategies Can Prevent Permanent Paraplegia in the Majority of Patients Who Develop Spinal Cord Ischaemia After Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

OBJECTIVES: Spinal cord ischaemia (SCI) following endovascular thoracoabdominal aortic aneurysm (TAAA) repair is a devastating and unpredictable complication. This study describes a single unit's experience of SCI in patients who have had endovascular TAAA repair. METHODS: A prospectively maintained database of patients having endovascular TAAA repair using branched and fenestrated stent grafts between 2008 and 2014 at a single high volume centre was reviewed. Patients who developed neurological symptoms and signs related to SCI were identified and factors associated with onset and recovery of neurology were analysed. RESULTS: Sixty-nine patients (median age 73 years, 52 male; Crawford classification type I [n = 4], type II [n = 11], type III [n = 33], type IV [n = 14], type V [n = 7]) underwent endovascular TAAA repair. Twelve patients developed neurological symptoms/signs related to SCI but this was successfully reversed in eight patients, leaving four (5.8%) with permanent paraplegia. The median length of aorta covered was not significantly different in the 12 patients who developed SCI compared with the cohort that did not. Eleven of the patients who developed SCI had an intraoperative mean arterial pressure (MAP) below 80 mmHg. Cutaneous atheroemboli were noted in half of the patients in the SCI group compared with 11% of the non-SCI group (p < .05). Strategies used to reverse SCI included raising MAP, cerebrospinal fluid drainage, angioplasty of stenosed internal iliac arteries, and restoring perfusion to the aneurysm sac. CONCLUSIONS: This series highlights some of the risk factors associated with the development of SCI after endovascular repair of TAAAs. It also illustrates the importance of a dedicated institutional protocol aimed at ensuring the early diagnosis of SCI and prompt intervention to reverse permanent paraplegia in the majority of cases.

Editor's choice--Angulation of the C-arm during complex endovascular aortic procedures increases radiation exposure to the head.

OBJECTIVES/BACKGROUND: The increased complexity of endovascular aortic repair necessitates longer procedural time and higher radiation exposure to the operator, particularly to exposed body parts. The aims were to measure directly exposure to radiation of the bodies and heads of the operating team during endovascular repair of thoracoabdominal aortic aneurysms (TAAA), and to identify factors that may increase exposure. METHODS: This was a single-centre prospective study. Between October 2013 and July 2014, consecutive elective branched and fenestrated TAAA repairs performed in a hybrid operating room were studied. Electronic dosimeters were used to measure directly radiation exposure to the primary (PO) and assistant (AO) operator in three different areas (under-lead, over-lead, and head). Fluoroscopy and digital subtraction angiography (DSA) acquisition times, C-arm angulation, and PO/AO height were recorded. RESULTS: Seventeen cases were analysed (Crawford II-IV), with a median operating time of 280 minutes (interquartile range 200-330 minutes). Median age was 76 years (range 71-81 years); median body mass index was 28 kg/m(2) (25-32 kg/m(2)). Stent-grafts incorporated branches only, fenestrations only, or a mixture of branches and fenestrations. A total of 21 branches and 38 fenestrations were cannulated and stented. Head dose was significantly higher in the PO compared with the AO (median 54 µSv [range 24-130 µSv] vs. 15 µSv [range 7-43 µSv], respectively; p = .022), as was over-lead body dose (median 80 µSv [range 37-163 µSv] vs. 32 µSv [range 6-48 µSv], respectively; p = .003). Corresponding under-lead doses were similar between operators (median 4 µSv [range 1-17 µSv] vs. 1 µSv [range 1-3 µSv], respectively; p = .222). Primary operator height, DSA acquisition time in left anterior oblique (LAO) position, and degrees of LAO angulation were independent predictors of PO head dose (p < .05). CONCLUSIONS: The head is an unprotected area receiving a significant radiation dose during complex endovascular aortic repair. The deleterious effects of exposure to this area are not fully understood. Vascular interventionalists should be cognisant of head exposure increasing with C-arm angulation, and limit this manoeuvre.

A novel reverse thermosensitive polymer to achieve temporary atraumatic vessel occlusion in infra-popliteal bypasses.

OBJECTIVE: The study aims to assess a novel thermosensitive polymer (LeGoo(®)) for distal vessel control during infra-popliteal (crural/pedal) bypass surgery in severe leg ischaemia. METHOD: Retrospective analysis of all distal bypasses from October 2009 to February 2012. Technical success, patency, limb salvage and amputation-free survival rates were analysed. RESULTS: Fifty-four infra-popliteal bypasses using the polymer were performed in 46 patients. The distal anastomosis was at the anterior tibial (n = 15, 28%), posterior tibial (n = 12, 22%), peroneal (n = 8, 15%), tibio-peroneal trunk (n = 8, 15%) and dorsalis pedis arteries (n = 11, 20%). Technical success was achieved in 51/54 (94.4%; failures: two inadequate haemostasis, one un-dissolved polymer). In-hospital duplex of the distal anastomosis showed a significant stenosis in two cases (4.3%). Outflow angioplasty was performed in three cases (two distal anastomotic, one run-off vessel, 5.6%). The 1-year patency rate was 76.2% (standard error (SE) 6.7%), limb salvage rate 79.3% (SE 6.7%). Amputation-free survival was 93.5% at 30 days (SE 3.6%) and 67.5% at 1 year (SE 7.5%). CONCLUSION: This thermosensitive polymer is a potentially safe and useful atraumatic device to achieve a blood-less distal anastomotic field in infra-popliteal bypasses. The technique avoids other potentially traumatic methods of vessel control, which may be particularly important in patients with calcified distal vessels.

Occupational radiation exposure during endovascular aortic procedures.

OBJECTIVES: To measure the radiation exposure of the operating team during endovascular aortic procedures, and to determine factors that predict high exposures. MATERIALS AND METHODS: Electronic dosimeters placed over and under protective lead garments, were used to prospectively record radiation exposure during endovascular aortic repairs performed in a designated interventional radiology suite. Univariate and multivariate linear regression analyses of predictors of radiation exposure were performed. RESULTS: A total of 26 infra-renal and 10 thoracic endovascular cases were studied. Median (IQR) patient age and body mass index were 76.0 (70.0-81.8) years and 26.2 (23.9-28.9) kg/m(2) respectively. Over-lead exposure to the operator was higher for thoracic than for infra-renal procedures (421.0 [233.8-597.8] µSv vs. 52.5 [27.8-179.8] µSv, p = .0003), reflecting a significant exposure to unprotected parts of the body. Under-lead exposures for operator and assistant were 5.5 (2.0-14.2) µSv and 1.0 (0.0-2.3) µSv respectively, which for an average caseload would comply with total body effective dose limits. Type of case and percentage of digital subtraction angiography (DSA) time in left anterior oblique angulations predicted dose to the operator (p < .0001). CONCLUSIONS: Thoracic procedures, DSA runs and obliquity of the C-arm are strong predictors of radiation exposure during endovascular aortic repairs. Understanding scatter radiation dynamics and instigating measures to minimise radiation exposure should be mandatory.

Risk of radiation exposure during endovascular aortic repair.

OBJECTIVE: Exposure to radiation doses above 2 Gray (Gy) can cause skin burns. There is also a lifetime cancer risk of ≈5.5% for every Sievert (Sv) of radiation. We assessed the radiation burden associated with endovascular treatment of the aorta. METHOD: Thoracic (TEVAR), Infra-renal (IEVAR) and branched/fenestrated (BEVAR/FEVAR) endovascular aortic repairs were studied. The prospectively recorded dosimetric parameters included: fluoroscopy time and dose area product (DAP). Exposure films, placed underneath 10 patients intra-operatively, recorded skin dose and were used to calculate skin (Gy) and tissue (Sv) doses. RESULTS: The TEVAR cohort (n = 232) were younger (p < 0.0001) than BEVAR/FEVAR (n = 53) and IEVAR (n = 630). The median DAP was higher (p = 0.004) in the BEVAR/FEVAR group compared with IEVAR and TEVAR: 32,060 cGy cm(2) (17,207-213,322) vs 17,300 cGy cm(2) (10,940-33,4340) vs 19,440 cGy cm2 (11,284-35,101), respectively. The equivalent skin doses were BEVAR/FEVAR: 1.3 Gy (0.71-8.75); IEVR: 0.71 Gy (0.44-13.7); TEVAR: 0.8 Gy (0.46-1.44). The whole body effective doses were BEVAR/FEVAR: 0.096 Sv (0.052-0.64); IEVR: 0.053 Sv (0.033-1.00); TEVAR: 0.058 Sv (0.034-0.11). CONCLUSIONS: The radiation exposure during endovascular aortic surgery is relatively low for the majority but some patients are exposed to very high doses. Efforts to minimise intra-operative exposure and graft surveillance methods that do not use radiation may reduce the cumulative lifetime malignancy risk.

Total endovascular repair of thoracoabdominal aortic aneurysms.

BACKGROUND: Endovascular graft designs incorporating sidebranches, fenestrations and scallops offer a minimally-invasive alternative to open surgery and hybrid approaches for thoracoabdominal aortic aneurysms (TAAA). Our unit has offered total endovascular TAAA repair to selected higher-risk patients since 2008. We report the largest UK series to date of total endovascular TAAA repair. METHODS: Retrospective analysis of a prospectively-maintained operative database. RESULTS: 31 patients (21 male, 10 female) median age 71 years (range 58-84), with TAAA (12 Crawford type I, 13 type III, 6 type IV), median diameter 6.4 (4.3 (mycotic)- 9.9) underwent endovascular TAAA repair (total 48 sidebranches, 26 fenestrations, 13 scallops) between July 2008 and January 2011. Median operating time 225 min (65-540 min), X-ray screening time 58 min (4-212 min), contrast dose 175 ml (70-500 ml), blood loss 325 ml (100-400 ml). Median post-operative length of hospital stay 6 days (2-22 days). Three patients (3/31, 9.7%) died within 30 days of operation: multisystem organ failure (1) acute renal failure and paraplegia (1) and paraplegia (1). There were no other cases of in-hospital organ failure, paraplegia or major complications. The median change in pre-discharge from pre-operative renal function was 3.4% deterioration in eGFR (range: 32.7% deterioration to 73.0% improvement) One patient presented with late-onset paraparesis, a second developed acute renal failure 8 months after repair. One early high-pressure endoleak (type 3) required correction. Three patients had died by median follow-up 12 months (1-36), 2 from heart disease and one from haemopericardium secondary to acute dissection of the ascending aorta (the dissection did not involve, nor extend close to, the endovascular graft). CONCLUSIONS: Total endovascular repair of TAAA offers patients a minimally-invasive alternative to open surgery with early results at least comparable to those seen with open or hybrid surgical approaches.

Quality improvement framework for major amputation: are we getting it right?

INTRODUCTION: The quality improvement framework for major amputation was developed with the aim of improving outcomes and reducing the perioperartive mortality to less than 5% by 2015. The aim of the study was to assess our compliance with the framework guidelines and look for the reasons for non-compliance. METHOD: All major amputations performed between 2008 and 2010 were included. The following data were collected: presence of infection ± tissue loss, status of arterial supply, revascularisation attempts, time to surgery, type of amputation, morbidity and mortality. RESULTS: A total of 81 patients were included (42 BKAs, 39 AKAs). Ninety percentage had formal preoperative arterial investigations and 84% had an attempted revascularisation procedure. Patients who were transferred late from non-vascular units (n = 12) had a 30-day mortality of 50% whereas patients who presented directly to our unit had a 30-day mortality of 7.2%. The number of amputations has decreased over the last 3 years from 34 to 21 per year, coinciding with the doubling of crural revascularisation procedures performed (from 60 to 120 per year). Ten patients underwent a revision from BKA to AKA because of an inadequate profunda femoris artery (PFA), whereas all those with a healed BKA stump either had a good PFA or a named crural vessel. CONCLUSION: The overall number of amputations is decreasing from year to year. By doubling our crural revascularisation procedures we are saving more limbs. Thirty-day mortality is higher than expected, particularly in patients who present late. Expeditious referral may potentially improve the mortality rate among this group of patients.

Techniques of assessing hypoxia at the bench and bedside.

Tissues require an adequate supply of oxygen in order to maintain normal cell function. Low oxygen tension (hypoxia) is characteristic of a number of conditions, including cancer, atherosclerosis, rheumatoid arthritis, critical limb ischaemia, peripheral vascular disease, and ischaemic heart disease. Tissue hypoxia is found in tumours, atherosclerotic plaque, and ischaemic myocardium. There is a growing interest in methods to detect and assess hypoxia, given that hypoxia is important in the progression of these diseases. Hypoxia can be assessed at the level of the whole organ, tissue, or cell, using both invasive and non-invasive methods, and by a range of immunohistochemical, biochemical, or imaging techniques. This review describes and critiques current methods of assessing hypoxia that are used at the bench and in clinical practice.

Predictors of stroke and paraplegia in thoracic aortic endovascular intervention.

BACKGROUND: Endoluminal repair of thoracic aortic pathology has become established in clinical practice, but is associated with significant neurological complications. The aim of this study was to identify factors that were predictive of stroke and paraplegia. METHODS: Prospective data was collected for a cohort of 293 consecutive patients having thoracic aortic endovascular repair between August 1997 and September 2009. Patient and procedural characteristics were related to the incidence of stroke and paraplegia using multivariate logistic regression analysis. RESULTS: The median age was 68 years (18-87), there were 191 men and 102 women. Mortality was 5.1% for 195 elective and 13.4% for 98 urgent patients. Stroke affected 16 (5.5%) patients: 11 affected the anterior and 5 the posterior circulation. Coverage of the left subclavian artery with no revascularisation was the only significant factor predictive of stroke (OR 5.34 (1.42-20.40) P = 0.01). Paraplegia affected 16 patients (5.5%) but no independent risk factor was identified: 12 were identified perioperatively and 4 were delayed by up to 6 months. CONCLUSION: Covering the left subclavian artery without revascularisation increases the risk of stroke following endoluminal repair of thoracic pathology. Paraplegia appears to be more complex and no independent precipitating factor was identified.

Quality of life after surgical reduction for severe primary lymphoedema of the limbs and genitalia.

BACKGROUND: The aim was to assess the quality of life (QoL) of patients who had surgery for primary lymphoedema. METHODS: A QoL questionnaire was administered to patients who had surgery between 1981 and 2003 (retrospective group) and between 2003 and 2006 (prospective group). RESULTS: The response rate was 70.3 per cent (109 of 155 patients): 88 patients had limb reduction (78, retrospective; ten, prospective) and 21 had genital reduction (13, retrospective; eight, prospective). Forty-nine patients (63 per cent) who had limb reduction studied retrospectively reported satisfaction with the procedure and most of these would opt for surgery again. In the prospectively studied group, nine of ten patients reported improved limbs, and seven would opt for surgery again. Nineteen of 21 patients who had genital reduction would choose to have surgery again if needed (11 of the retrospectively assessed group and all of the prospective group). Patients' perception that surgery was worthwhile was greater in both of the prospectively assessed groups (P = 0.013). CONCLUSION: Surgery for severe lymphoedema improved QoL at early assessment. This, however, may not be sustained. Genital reduction appeared to provide greater benefit than limb reduction.

Adenovirus-mediated VEGF gene therapy enhances venous thrombus recanalization and resolution.

OBJECTIVE: Rapid thrombus recanalization reduces the incidence of post-thrombotic complications. This study aimed to discover whether adenovirus-mediated transfection of the vascular endothelial growth factor gene (ad.VEGF) enhanced thrombus recanalization and resolution. METHODS AND RESULTS: In rats, thrombi were directly injected with either ad.VEGF (n=40) or ad.GFP (n=37). Thrombi in SCID mice (n=12) were injected with human macrophages transfected with ad.VEGF or ad.GFP. Thrombi were analyzed at 1 to 14 days. GFP was found mainly in the vein wall and adventitia by 3 days, but was predominantly found in cells within the body of thrombus by day 7. VEGF levels peaked at 4 days (376+/-299 pg/mg protein). Ad.VEGF treatment reduced thrombus size by >50% (47.7+/-5.1 mm(2) to 22.0+/-4.0 mm(2), P=0.0003) and increased recanalization by >3-fold (3.9+/-0.69% to 13.6+/-4.1%, P=0.024) compared with controls. Ad.VEGF treatment increased macrophage recruitment into the thrombus by more than 50% (P=0.002). Ad.VEGF-transfected macrophages reduced thrombus size by 30% compared with controls (12.3+/-0.89 mm(2) to 8.7+/-1.4 mm(2), P=0.04) and enhanced vein lumen recanalization (3.39+/-0.34% to 5.07+/-0.57%, P=0.02). CONCLUSIONS: Treatment with ad.VEGF enhanced thrombus recanalization and resolution, probably as a consequence of an increase in macrophage recruitment.

Endoscopic transanal resection of rectal adenomas using the urological resectoscope.

OBJECTIVE: Large sessile rectal adenomas are often difficult to excise and several different techniques have been described. This study evaluates the results of adenoma excision by endoscopic transanal resection using the urological resectoscope by a single surgeon in a UK district general hospital. METHOD: Between January 1989 and November 2004, data on all patients treated by endoscopic transanal resection of benign rectal tumours using a urological resectoscope (ETAR) were prospectively collected and analysed. RESULTS: Forty patients (50% male, median age 72 years) underwent a total of 81 endoscopic transanal resections. The tumour characteristics were: size > 2 cm (83%), location in lower 2/3 of rectum (83%) and extensive circumferential carpet-like appearances (13%). Fifty percent of the patients required only one procedure to achieve clearance. Mean operative time was 26 min (range 10-65 min). Seventy-eight percent of the patients were discharged home within 24 h. Postoperative morbidity was 8% and in-hospital mortality was zero. Histology revealed severe dysplasia in 48% of the tumours and five patients were incidentally found to have foci of rectal adenocarcinoma. With a median follow-up of 47 months (range 2-162 months), local recurrences occurred in 13% (n = 5) of patients. All, except one, were treated successfully with further endoscopic transanal resections. CONCLUSION: ETAR is simple and safe for managing rectal adenomas.

Inhibition of prolyl hydroxylase domain proteins selectively enhances venous thrombus neovascularisation.

BACKGROUND: Hypoxia within acute venous thrombi is thought to drive resolution through stabilisation of hypoxia inducible factor 1 alpha (HIF1α). Prolyl hydroxylase domain (PHD) isoforms are critical regulators of HIF1α stability. Non-selective inhibition of PHD isoforms with l-mimosine has been shown to increase HIF1α stabilisation and promote thrombus resolution. OBJECTIVE: The aim of this study was to investigate the therapeutic potential of PHD inhibition in venous thrombus resolution. METHODS: Thrombosis was induced in the inferior vena cava of mice using a combination of flow restriction and endothelial activation. Gene and protein expression of PHD isoforms in the resolving thrombus was measured by RT-PCR and immunohistochemistry. Thrombus resolution was quantified in mice treated with pan PHD inhibitors AKB-4924 and JNJ-42041935 or inducible all-cell Phd2 knockouts by micro-computed tomography, 3D high frequency ultrasound or endpoint histology. RESULTS: Resolving venous thrombi demonstrated significant temporal gene expression profiles for PHD2 and PHD3 (P < 0.05), but not for PHD1. PHD isoform protein expression was localised to early and late inflammatory cell infiltrates. Treatment with selective pan PHD inhibitors, AKB-4924 and JNJ-42041935, enhanced thrombus neovascularisation (P < 0.05), but had no significant effect on overall thrombus resolution. Thrombus resolution or its markers, macrophage accumulation and neovascularisation, did not differ significantly in inducible all-cell homozygous Phd2 knockouts compared with littermate controls (P > 0.05). CONCLUSIONS: This data suggests that PHD-mediated thrombus neovascularisation has a limited role in the resolution of venous thrombi. Directly targeting angiogenesis alone may not be a viable therapeutic strategy to enhance venous thrombus resolution.