Acute limb ischemia due to ONYX 34 migration during embolization of a traumatic pseudoaneurysm of the superficial femoral artery.

Pseudo-aneurysms of the arteries of the lower limbs are a possible complication of leg trauma. Complications include rupture, infection, pain and distal embolization. This is a case of a 24-year-old man hospitalized after a car accident, in which we discovered a 1-cm large pseudo-aneurysm of the right superficial femoral artery. The pseudo-aneurysm in first place was treated by the interventional-radiologist for an endovascular repair by embolization with ONYX 34, but during the procedure the copolymer embolized in the arterial axe with complete obstruction of blood-flow in the lower limb. An urgent open surgical revascularization was then attempted by our team with the result of complete patency of the femoro-popliteal axis and of the tibial vessels. Embolization with ONYX is an effective and safe method, but it is susceptible to this type of complication for larger pseudo-aneurysms, where it is required an introduction of a larger quantity of polymer.

Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area.

Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.

A Matched Case-Control Study on Open and Endovascular Treatment of Popliteal Artery Aneurysms.

OBJECTIVE: To compare early and late results of open and endovascular management of popliteal artery aneurysm in a retrospective single-center matched case-control study Methods: From 1981 to 2015, 309 consecutive interventions for popliteal artery aneurysm were performed in our institution, in 59 cases with endovascular repair and in 250 cases with open repair. Endovascular repair was preferred in older asymptomatic patients, while open repair was offered more frequently to patients with a thrombosed popliteal artery aneurysm and a poor run-off status. A one-to-one coarsened exact matching on the basis of the baseline demographic, clinical, and anatomical covariates significantly different between the two treatment options was performed and two equivalent groups of 56 endovascular repairs and open repairs were generated. The two groups were compared in terms of perioperative results with χ2 test and of follow-up outcomes with the Kaplan-Meier curves and log-rank test. RESULTS: There were no differences between the two groups in terms of perioperative outcomes. Median duration of follow-up was 38 months. Five-year survival rates were 94% in endovascular repair group and 89.5% in open repair group (p = 0.4, log-rank 0.6). Primary patency rates at 1, 3, and 5 years were 81%, 78%, and 72% in endovascular repair group and 82.5%, 80%, and 64% in open repair group (p = 0.8, log-rank 0.01). Freedom from reintervention at 5 years was 65.5% in endovascular repair group and 76% in open repair group (p = 0.2, log-rank 1.2). Secondary patency at 1, 3, and 5 years was 94%, 86%, and 74% in endovascular repair group, and 94%, 89%, and 71% in open repair group, respectively (p = 0.9, log-rank 0.01). The rates of limb preservation at 5 years were 94% in endovascular repair group and 86.4% in open repair group (p = 0.3, log-rank 0.8). CONCLUSION: Open repair and endovascular repair of popliteal artery aneurysms provided in this retrospective single-center experience similar perioperative and follow-up results in equivalent groups of patients.

An update of the Italian Stroke Organization-Stroke Prevention Awareness Diffusion Group guidelines on carotid endarterectomy and stenting: a personalized medicine approach

Although proof-based medicine has generated much valid evidence for the drawing up of guidelines and recommendations for best clinical practice in symptomatic and asymptomatic carotid stenosis, whether and when it is better to employ endarterectomy or stenting as the intervention of choice still remain matters of debate. Moreover, guidelines have been targeted up to now to the 'representative' patient, as resulting from the statistical analyses of the studies conducted on the safety and efficacy of both interventions as well as on medical therapy alone. The Italian Stroke Organization (ISO) and Stroke Prevention and Awareness Diffusion (SPREAD) group has thus decided to update its statements for an 8th edition. To this end, a multidisciplinary team of authors representing Italian scientific societies in the neurology, neuroradiology, vascular and endovascular surgery, interventional cardiology, and general medicine fields re-examined the literature available on stroke. Analyses and considerations on patient subgroups have allowed to model the risks/benefits of endarterectomy and stenting in the individual. Accordingly, the guideline's original methodology has been revised to follow the new SIGN (Scottish Intercollegiate Guideline Network) Grade-like approach, integrating it with new considerations on Precision, or Personalized Medicine. Therefore, this guideline offers recommendations on precision medicine for the single patient, and can be followed in addition to the more standard guidelines.

Italian Percutaneous EVAR (IPER) Registry: outcomes of 2381 percutaneous femoral access sites' closure for aortic stent-graft.

AIM: The aim of this paper was to report outcomes of endovascular aneurysm repair with percutaneous femoral access (pEVAR) using Prostar XL and Proglide closure systems (Abbot Vascular, Santa Clara, CA, USA), from the multicenter Italian Percutaneous EVAR (IPER) registry. METHODS: Consecutive patients affected by aortic pathology treated by EVAR with percutaneous access (pEVAR) between January 2010 and December 2014 at seven Italian centers were enrolled in this multicenter registry. All the operators had an experience of at least 50 percutaneous femoral access procedures. Data were prospectively collected into a dedicated online database including patient's demographics, anatomical features, intra- and postoperative outcomes. A retrospective analysis was carried out to report intraoperative and 30-day technical success and access-related complication rate. Uni- and multivariate analyses were performed to identify factors potentially associated with an increased risk of percutaneous pEVAR failure. RESULTS: A total of 2381 accesses were collected in 1322 patients, 1249 (94.4%) male with a mean age of 73.5±8.3 years (range 45-97). The overall technical success rate was 96.8% (2305/2381). Major intraoperative access-related complications requiring conversion to surgical cut-down were observed in 3.2% of the cases (76/2381). One-month pEVAR failure-rate was 0.25% (6/2381). Presence of femoral artery calcifications resulted to be a significant predictor of technical failure (OR: 1.69; 95% CI: 1.03-2.77; P=0.036) at multivariate analysis. No significant association was observed with sex (P=0.28), obesity (P=0.64), CFA diameter (P=0.32), level of CFA bifurcation (P=0.94) and sheath size >18 F (P=0.24). The use of Proglide was associated with a lower failure rate compared to Prostar XL (2.5% vs. 3.3%) despite not statistically significant (P=0.33). CONCLUSION: The results of the IPER registry confirm the high technical success rate of percutaneous EVAR when performed by experienced operators, even in presence of demanding anatomies. Femoral calcification represents the only predictor of percutaneous access failure.

Proximal aortic neck angle does not affect early and late EVAR outcomes: an AnacondaTM Italian Registry analysis.

AIM: The aim of this paper was to evaluate early and 3-year results of the endovascular repair (EVAR) for abdominal aortic aneurysm (AAA) using the AnacondaTM endograft in patients with severe proximal aortic neck angle. METHODS: A retrospective analysis of the AnacondaTM Italian Registry was carried out. Two groups of patients were identified according to the presence of a severe (Group A, GA: ≥ 60°) or an absent (Group B, GB: <45°) proximal aortic neck angle. Preoperative, procedural and follow-up data were evaluated. Mortality, proximal type I endoleak, freedom from iliac leg thrombosis and conversion to open repair were analyzed at 30-day and 3-year follow-up. The results of GA and GB were compared. RESULTS: From 2005 to 2012, 1030 patients were enrolled in the Registry. Sixty-five patients (6.3%) were included in GA and 737 (71.5%) in GB. The mean age and AAA diameter were respectively 76.8 years and 62.7 mm in GA and 77.2 years and 56.5 mm in GB (P=NS). The ASA ≥ 3 was reported in the 95.3% of GA vs. 81% of GB (P=0.005). The endograft main-body was repositioned in 35% of cases in GA and 20.7% in GB (P=0.008); there were no differences in the main-body ballooning and proximal aortic cuff placement. There were no statistical differences in 30-day mortality (GA 1.5% vs. GB 1.3%), proximal type I endoleaks (GA 1.5% vs. GB 0.8%), iliac leg thrombosis (GA 1.5% vs. GB 1.4%) and conversion to open repair (GA 3% vs. GB 0.6%). The 3-year survival was 95.4% in GA and 94.7% in GB (P=NS). Freedom from proximal type I endoleak, iliac leg thrombosis and conversion to open repair were respectively 98.5%, 95.4%, and 95.4% in GA and 97.8%, 96.9%, and 98.5% in GB (P=NS). CONCLUSION: The AnacondaTM Italian Registry reports good results in terms of clinical success at 3-year follow-up. AAA with severe proximal aortic neck can be treated with similar outcomes to AAA with favorable neck anatomy. The endograft repositionability is a benefit in cases with severe neck angle.

INCRAFT® Stent-Graft System: one-year outcome of the INNOVATION Trial.

AIM: Endovascular repair has surpassed open surgical treatment as the most common procedure in patients with abdominal aortic aneurysms (AAA), yet its applicability remains limited to those with aortoiliac anatomy suitable for the introduction and deployment of the devices. The current study was performed to assess the safety and efficacy of INCRAFT® (Cordis Corporation, Bridgewater, NJ), an ultra-low-profile device for the treatment of AAA. METHODS: The INNOVATION study is a first in human prospective, multicenter trial involving 6 centers in Europe. From March 2010 to June 2011 60 patients with asymptomatic AAA were treated with the INCRAFT® bifurcated Stent-Graft System. The main inclusion criteria were a proximal aortic neck of 15 mm or more in length and up to 27 mm in diameter; iliac landing zones greater than 10 mm in length and between 9 and 18 mm in diameter; an access vessel large enough to accept the 14F outer diameter of the delivery system; and an aortic bifurcation >18 mm in diameter. The primary endpoint was technical success at one-month; one-year safety endpoints included the absence of device- or procedure-related major adverse events; absence of type I or III endoleaks; and maintenance of device integrity through one year of follow-up. RESULTS: Among 60 patients treated at six centers, the primary endpoint was met in 56 of 58 patients (97%; 95% CI, 88-100%) who came back for one month follow-up, two patients did not come back for their one month follow-up assessments but remained enrolled in the study. Fifty-six had one-year follow-up data showing 100% freedom from aneurysm enlargement with absence of type I and III endoleaks in all patients. There were two patients (3.6%) with a type Ia endoleak which was successfully treated with secondary endovascular intervention in both occasions. Core laboratory evaluation of the postoperative imaging studies documented absence of endograft migration, stent fracture, or limb occlusion. A single patient (1.8%) died within one year due to sepsis unrelated to the AAA. CONCLUSION: The results of the INNOVATION study with the INCRAFT® Stent-Graft are encouraging, with satisfactory clinical outcome and device durability through one-year of follow-up. The INCRAFT® device is a novel ultra-low-profile endograft that holds promise to broaden the patient population eligible for endovascular aneurysm repair.

Endovascular treatment of aorto-iliac aneurysms: four-year results of iliac branch endograft.

INTRODUCTION: The aim of this report was to analyse early and mid-term outcomes of endovascular treatment (endovascular aneurysm repair, EVAR) for aorto-iliac aneurysms with the use of an iliac branch device (IBD). REPORT: A total of 85 EVAR procedures with IBD were electively carried out in 81 patients between September 2007 and August 2012. Technical success was obtained in 98.7% of the cases. The mean follow-up duration was 20.4 months (SD ± 15.4). There was one IBD occlusion (1.2%). Estimated 48 months' survival, freedom from re-intervention and branch occlusion were 76.7%, 88.3% and 98%, respectively. CONCLUSIONS: EVAR for aorto-iliac aneurysms using IBD is an effective procedure with low complication and re-intervention rates at mid-term follow-up.

BRAVISSIMO: 12-month results from a large scale prospective trial.

The BRAVISSIMO study is a prospective, non-randomized, multi-center, multi-national, monitored trial, conducted at 12 hospitals in Belgium and 11 hospitals in Italy. This manuscript reports the findings up to the 12-month follow-up time point for both the TASC A&B cohort and the TASC C&D cohort. The primary endpoint of the study is primary patency at 12 months, defined as a target lesion without a hemodynamically significant stenosis on Duplex ultrasound (>50%, systolic velocity ratio no greater than 2.0) and without target lesion revascularization (TLR) within 12 months. Between July 2009 and September 2010, 190 patients with TASC A or TASC B aortoiliac lesions and 135 patients with TASC C or TASC D aortoiliac lesions were included. The demographic data were comparable for the TASC A/B cohort and the TASC C/D cohort. The number of claudicants was significantly higher in the TASC A/B cohort, The TASC C/D cohort contains more CLI patients. The primary patency rate for the total patient population was 93.1%. The primary patency rates at 12 months for the TASC A, B, C and D lesions were 94.0%, 96.5%, 91.3% and 90.2% respectively. No statistical significant difference was shown when comparing these groups. Our findings confirm that endovascular therapy, and more specifically primary stenting, is the preferred treatment for patients with TASC A, B, C and D aortoiliac lesions. We notice similar endovascular results compared to surgery, however without the invasive character of surgery.

Comparison of open and endovascular treatments of post-carotid endarterectomy restenosis.

AIM OF THE STUDY: To compare early and long term results of open and endovascular treatment of post-carotid endarterectomy (CEA) restenosis in a single centre experience. METHODS: From January 2005 to December 2011, ninety-nine consecutive interventions for primary severe post-CEA restenosis were performed: in 41 cases (41%, Group 1) open repair was carried out, whereas the remaining 58 patients (59%, group 2) underwent an endovascular treatment. Data concerning these interventions were prospectively collected in a dedicated database containing main pre, intra and postoperative variables. Early results in terms of 30-day stroke and death rates were analysed and compared with χ(2) test. Follow-up results were analysed with Kaplan Meier curves and compared with log-rank test. RESULTS: Mean time from primary CEA was 75 months in group 1 and 42 months in group 2 (p = 0.002; 95% CI 12-52). There were no differences between the two groups in terms of demographic data, comorbidities, risk factors for atherosclerosis, preoperative clinical status or degree of stenosis on the operated side. In group 1 interventions consisted of redo-CEA in 37 patients and of carotid bypass in the remaining 4; all the patients in group 2 underwent stent placement with cerebral protection device. No perioperative deaths and ipsilateral neurological events occurred in both groups. One patient in group 1 suffered from a non-fatal acute myocardial infarction. Other six patients (14.5%) experienced transient cranial nerve injuries, with complete regression at 1-month follow-up; two patients had postoperative dysphagia due to neck haematoma, which was medically managed. Neither access-related nor systemic complications were recorded in group 2. Follow-up was available in 98% of the patients with a median duration of 24 months (range 3-72). There were no differences in terms of 4-year estimated survival and stroke-free survival, whereas patients in group 1 were more likely to develop severe (>80%) secondary restenosis (28.3% and 6.5%, respectively, p = 0.01, log rank 6.3) and to undergo secondary reintervention (22% and 11%, respectively p = 0.01, log rank 6). CONCLUSIONS: despite the selection limits and bias of this study, in our experience open and endovascular surgery provided similar perioperative results in the management of post-CEA restenosis. Long term outcomes are similar, too, despite a slight increase in secondary restenosis and recurrent reinterventions among open surgery patients, warranting further studies and analysis.

A multicentric experience with open surgical repair and endovascular exclusion of popliteal artery aneurysms.

INTRODUCTION: The aim of this study was to analyse early and follow-up results of the treatment of popliteal artery aneurysms (PAAs) performed with open surgical repair or with endovascular exclusion with endografts in a multicentric retrospective registry involving seven Italian vascular centres. MATERIALS AND METHODS: We retrospectively collected data concerning 178 open surgical interventions (OR group) and 134 endovascular exclusions (ER group) for PAAs performed between January 2000 and December 2011. Early and follow-up results were analysed in terms of mortality, graft patency, reintervention and limb preservation. RESULTS: OR patients were more frequently symptomatic (64%, 115 cases) than patients in the ER group (34%, 51 cases; p < 0.001), had more frequently acute limb ischaemia (23% and 6.5%, respectively; p < 0.001) and had more frequently a run-off score <2 (39% and 26%, respectively, p = 0.03). In the OR group there were no perioperative deaths; six thromboses (3.3%) and one amputation occurred. In the ER group mortality was 1.5%; 13 thromboses (9.7%) and one amputation (0.5%) occurred. Mean duration of follow-up was 30.6 ± 27.5 months. In the OR group primary and secondary patency, freedom from reintervention and limb preservation rates at 48 months were 63.5% (standard error (SE) 0.05), 76.5% (SE 0.05), 72.5% (SE 0.06) and 89.7% (SE 0.05), respectively. The corresponding figures in the ER group were 73.4% (SE 0.04), 85% (SE 0.04), 75% (SE 0.04) and 97% (SE 0.04), respectively. CONCLUSIONS: In this large multicentric retrospective registry, open and endovascular treatment of PAAs are used in different patients with regard to clinical and anatomical characteristics. Both treatments are feasible and safe, providing satisfactory early and long-term results.

A 20-year experience with surgical management of true and false internal carotid artery aneurysms.

AIM OF THE STUDY: The aim of this study was to retrospectively analyse early and late results of surgical management of internal carotid artery (ICA) true and false aneurysms in a single-centre experience. MATERIALS AND METHODS: From January 1988 to December 2011, 50 consecutive interventions for ICA aneurismal disease were performed; interventions were performed for true ICA aneurysm in 19 cases (group 1) and for ICA post-carotid endarterectomy (CEA) pseudo-aneurysm in the remaining 31 (group 2). Early results (<30 days) were evaluated in terms of mortality, stroke and cranial nerves' injury and compared between the two groups with χ(2) test. Follow-up results (stroke free-survival, freedom from ICA thrombosis and reintervention) were analysed with Kaplan-Meier curves and compared with log-rank test. RESULTS: All the patients in group 1 had open repair of their ICA aneurysm; in group 2 open repair was performed in 30 cases, while three patients with post-CEA aneurysm without signs of infection had a covered stent placed. There were no perioperative deaths. Two major strokes occurred in group 1 and one major stroke occurred in group 2 (p = 0.1). The rates of postoperative cranial nerve injuries were 10.5% in group 1 and 13% in group 2 (p = 0.8). Median duration of follow-up was 60 months (range 1-276). Estimated 10-year stroke-free survival rates were 64% in group 1 and 37% in group 2 (p = 0.4, log rank 0.5); thrombosis-free survival at 10 years was 66% in group 1 and 34% in group 2 (p = 0.2, log rank 1.2), while the corresponding figures in terms of reintervention-free survival were 68% and 33%, respectively (p = 0.2, log rank 1.8). CONCLUSIONS: Surgical treatment of ICA aneurismal disease provided in our experience satisfactory early and long-term results, without significant differences between true and false aneurysms. In carefully selected patients with non-infected false aneurysm, the endovascular option seems to be feasible.

Alterations of haemorheological parameters in patients with peripheral arterial disease.

Peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis. Advances on the development of such vascular disease have described with a number of novel risk factors. Hyperviscosity, due to alterations of blood cells and plasma components, may play a role on the pathogenesis of the disease. Aim of this study was to evaluate the possible association between hemorheological variables and PAD. The hemorheological variables [whole blood viscosity (WBV), erythrocyte deformability index (DI), plasma viscosity (PLV)] were analyzed in 90 patients and in 180 healthy subjects. WBV and PLV were measured by a Rotational Viscosimeter and DI by a filtrometer. DI and PLV were significantly different in patients as compared to controls. To investigate the possible association between these parameters and the disease we divided the study population into tertiles. At the univariate analysis, we found a significant association between the highest tertiles of PLV, of DI and the disease. A model adjusted for traditional risk factors showed an association between highest tertiles of PLV and PAD. After adjustment for confounding parameters highest tertiles of PLV remained to be significantly associated with the disease. Our data indicate that an alteration of plasma viscosity may modulate the predisposition to PAD.

Results from an Italian multicentric registry comparing heparin-bonded ePTFE graft and autologous saphenous vein in below-knee femoro-popliteal bypasses.

AIM: The aim of this study was to evaluate early and follow-up results of below-knee bypasses performed with a bioactive heparin-treated ePTFE graft in patients with peripheral arterial obstructive disease (PAOD) in a multicentric retrospective registry involving seven Italian vascular centers and to compare them with those obtained in patients operated on with autologous saphenous vein (ASV) in the same centres in the same period of time. METHODS: Over a nine-year period, ending in 2010, a heparin bonded prosthetic graft (Propaten Gore-Tex, W.L. Gore & Associates Inc, Flagstaff, AZ, USA) was implanted in 556 patients undergoing below-knee revascularization for PAOD (HePTFE group). In the same period of time 394 below-knee bypasses with ipsilateral ASV were performed (ASV group). Data concerning these interventions were retrospectively collected in a multicenter registry with a dedicated database. Early (<30 days) results were analyzed in terms of graft patency, major amputation rates and mortality. Follow-up results were analyzed in terms of primary and secondary graft patency, limb salvage and survival. RESULTS: Among patients of HePTFE group, 413 had critical limb ischemia (74%); the corresponding figure for ASV group was 84% (332 interventions, P<0.001). Eighty-nine patients in HePTFE group (16%) and 207 patients in ASV group (52.5%; P<0.001) had distal tibial anastomosis. Patients in HePTFE group had more frequently adjunctive procedures performed at distal anastomotic sites in order to improve run-off status. Thirty-day death rate was 1.9% in HePTFE group and 0.5% in ASV group (P=0.08). The rates of perioperative thromboses and amputations were 6% and 3.5% in HePTFE group, and 5% and 1.7% in ASV group, without significant differences between the two groups. Mean duration of follow-up was 28.5±22.1 months; 921 patients (97%) had at least one postoperative clinical and ultrasonographic control. Estimated 48-month survival rates were 81% in HePTFE group and 74% in ASV group (P=0.7, log rank 0.1). Primary patency rate at 48 months was significantly better in ASV group (61%) than in HePTFE group (44.5%; P=0.004, log rank 8.1). The rates of secondary patency at 48 months were 57% in HePTFE group and 67.5% in ASV group (P=0.1, log rank 1.9); the corresponding values in terms of limb salvage in patients with critical limb ischemia were 77% and 79.5% (P=0.3, log rank 0.9), respectively. CONCLUSION: Data from this large, retrospective registry confirmed that the indexed heparin-bonded ePTFE graft provides satisfactory early and mid-term results in patients undergoing surgical below-knee revascularization. While autologous saphenous vein maintains its superiority in terms of primary patency, secondary patency and limb salvage rates are comparable.

Mitochondrial function and content in pheochromocytoma/paraganglioma of succinate dehydrogenase mutation carriers.

To date, the consequences of succinate dehydrogenase (SDH) impairment on overall mitochondrial functions are still obscure. In this study, we evaluated SDH activity and expression and mitochondrial homeostasis in 57 tissue samples of pheochromocytoma (PHEO)/paraganglioma (PGL) obtained from patients genotyped for PHEO/PGL susceptibility genes. The resulted SDH activity and content always decreased in SDH-mutated tumors, in one out of two MAX-mutated patients and in four patients resulted wild type (wt) at genetic screening. All these four wt patients were further screened for large deletions in SDH genes, TMEM127 and MAX and resulted wt but two had somatic SDHD mutations. The RT-PCR in the MAX-mutated sample suggests that the decrease in SDH depends on complex instability and not on a reduced SDHB expression. SDH mutations neither alter citrate synthase (CS) activity nor the content of voltage-dependent anion channel (VDAC) while the expression of the mitochondrial complex IV (cytochrome c oxidase (COX)) was found extremely variable in all (mutated and wt) samples suggesting an impairment of mitochondrial cristae in these tumors. In conclusion, tumors from patients with germ line SDH mutations invariably show decreased enzymatic activity and content, but an SDH impairment may also depend on SDH somatic mutations or, seemingly, on MAX mutations. The impaired SDH activity in the two wt tissues suggests mutations in other still unknown susceptibility genes. Finally, the extreme variability in COX expression levels is yet to be explained and this strongly suggests to evaluate other mitochondrial features to better understand the mitochondrial role in the pathogenesis of these tumors.

AnacondaTM: the Italian Registry. Study protocol and preliminary perioperative results.

AIM: AnacondaTM is an infrarenal stent-graft for the endovascular treatment (EVAR) of abdominal aortic aneurysms (AAA). The AnacondaTM Italian Registry is an observational multicentre registry that started in Italy on March 2009. The aim of this study is to present the registry protocol and to evaluate the interim perioperative results. METHODS: Patient data collected covered both retrospective and new cases. The case record forms are divided into preoperative data (population characteristics and clinical data), preoperative morphological data, intraoperative data, perioperative data (30-days from AnacondaTM implant) and follow-up record forms. The inclusion criteria are: AAA with a maximum sac diameter ≥ 5 cm, AAA with rapid expansion, symptomatic AAA or with a contained rupture, aorto-iliac aneurysms, proximal neck length ≥ 15 mm and diameter of the proximal aortic neck between 16 and 31.5 mm. No exclusion criteria were considered regarding aorto-iliac tortuosity, wall calcification or thrombosis and no exclusion criteria were considered regarding the patients age, comorbidities or life expectancy. Seven postoperative follow-up controls (visit and imaging) were required: at 30-days from the AnacondaTM implant, 6 months, 1 year and then annually up to 5 years. The registry is still open to new case enrollment. RESULTS: The reported results reflect the registry cases as at March 15, 2011. At this date, 787 cases were present in the database: 722 (91.7%) were male and 65 (8.3%) female. The mean patient age was 76.6 years with a range between 50 and 94 years. The ASA class was ≥ 3 in 635 patients (80.6%). The mean aneurysmal sac diameter was 55.73 ± 9.5 mm. The mean proximal aortic neck length was 26.52 ± 12.31 mm. Of the 787 patients treated, 11 cases of immediate surgical conversion were reported (1.3%). The overall 30-day mortality rate was 1.2% (10 cases): but 30-day death occurred in 0.9% of successful endograft implants and in 27.2% of surgical conversions (p<0.001). In fourteen cases (1.7%) an iliac leg thrombosis occurred and a native iliac artery thrombosis occurred in only five cases (0.5%). The 30-day overall occurrence of endoleaks was observed in 95 cases (12%): 5 cases of type I proximal endoleak (0.6%), 89 cases of type II endoleak (11.3%) and 1 case of type III endoleak (0.1%). No cases of endograft dislocation were reported. CONCLUSION: This is an interim report on the study protocol and on the preliminary early results. Presently there are no definitive conclusions, however the perioperative results show that the AnacondaTM endograft seems to be safe and effective in the treatment of AAA, even in a high risk cohort of patients. Definitive and long-term results are needed.

Urgent carotid endarterectomy in patients with recent/crescendo transient ischaemic attacks or acute stroke.

OBJECTIVES: Objective of this study was to review the results of urgent carotid endarterectomy (CEA) performed in patients with recent (< 24 h) or crescendo (at least 2 episodes in 24 h) transient ischaemic attack (TIA) or with acute stroke in a single centre experience. MATERIALS AND METHODS: From January 2000 to December 2008, 75 patients underwent urgent CEA for severe internal carotid artery stenosis and recent/crescendo TIA (51 patients, TIA group) or acute stroke (24 patients, stroke group). In patients with acute stroke the intervention was proposed on the basis of clinical and instrumental features (patient conscious, patency of middle cerebral artery, no lesions or limited brain infarction at CT scan) according to neurologists' suggestion. Data from all the interventions were prospectively collected in a dedicated database, which included main pre-, intra- and postoperative parameters. Independent neurological assessment with National Institute of Health Stroke Scale (NIHSS) score calculation was performed before the operation and within the 30th postoperative day. Early (< 30 days) results were evaluated in terms of mortality, modifications in NIHSS values and stroke and death rates. The surveillance program consisted of clinical and ultrasonographic examinations at 1, 6 and 12 months and yearly thereafter. Follow-up results (survival, occurrence of ipsilateral stroke in TIA group, recurrence of stroke in stroke group) were analysed by Kaplan-Meier curves. RESULTS: Among patients presenting with TIA, 28 had crescendo TIAs and 23 had a recent TIA; In stroke group, two patients had a stroke in evolution, eight patients had a recent major non-disabling stroke and 14 patients had a recent minor stroke. Preoperative mean value of NIHSS score in stroke group was 4.7 (SD 3.2). There were 2 perioperative (< 30 days) deaths, both in stroke group, in one case due to acute respiratory failure and to fatal stroke in the other one (preoperative NIHSS value 9, postoperative 17), with a cumulative 30-day mortality rate of 2.7%, significantly higher in stroke group (8.3%) than in TIA group (no death, p = 0.03). No postoperative cerebral haemorrhage occurred. In TIA group one postoperative major stroke occurred, with a 30-day stroke and death rate of 1.9%. In surviving patients of stroke group NIHSS value improved in 13 cases, with a mean improvement of 2 points (SD 0.9); in 8 cases the value remained unchanged, while in the remaining case it increased from 2 to 4. Mean postoperative NIHSS score in stroke group was 3.9 (SD 3.7), significantly reduced in comparison with preoperative value (p < 0.001). Mean duration of follow-up was 34 months (SD 28.1). No ipsilateral stroke in patients of TIA group occurred; in stroke group a recurrent fatal stroke at 1 postoperative month was recorded. Estimated 48-month stroke-free survival rate TIA group was 95% and 79% in stroke group (p = 0.02). CONCLUSIONS: Urgent CEA in patients with recent/crescendo TIA provided in our experience excellent results, with low rates of perioperative and late stroke. In selected patients with acute stroke early surgery seems to provide acceptable results.

Carotid artery disease: novel pathophysiological mechanisms identified by gene-expression profiling of peripheral blood.

OBJECT: The pathogenesis of carotid artery stenosis (CAS) as well as the mechanisms underlying the different localisation of the atherosclerotic lesions remains poorly understood. We used microarray technology to identify novel systemic mediators that could contribute to CAS pathogenesis. Moreover, we compared gene-expression profile of CAS with that of patients affected by abdominal aortic aneurysm (AAA), previously published by our group. METHODS AND RESULTS: By global gene-expression profiling in a pool of 10 CAS patients and 10 matched controls, we found 82 genes differentially expressed. Validation study in pools used for profiling and replication study in larger numbers of CAS patients (n = 40) and controls (n = 40) of 14 genes by real-time polymerase chain reaction (RT-PCR) confirmed microarray results. Fourteen out of 82 genes were similarly expressed in AAA patients. Gene ontology analysis identified a statistically significant enrichment in CAS of differentially expressed transcripts involved in immune response and oxygen transport. Whereas alteration of oxygen transport is a common tract of the two localisations, alteration of immune response in CAS and of lipid metabolic process in AAA represents distinctive tracts of the two atherosclerotic diseases. CONCLUSIONS: We describe the systemic gene-expression profile of CAS, which provides an extensive list of potential molecular markers.

Endovascular repair of a ruptured popliteal artery aneurysm associated with popliteal arteriovenous fistula.

Popliteal artery aneurysms (PAAs) represent the most common peripheral arterial aneurysm and are a significant cause of patient morbidity and limb loss. Complications of PAA include distal embolisation, thrombosis and, rarely, rupture. Whereas open surgical repair remains the gold standard, endovascular exclusion has been demonstrated to be a valid alternative in selected patients. We present an unusual case of ruptured PAA associated with popliteal vein arteriovenous fistula that was successfully treated with an endovascular approach. In our opinion, higher-risk patients as well as patients presenting with rupture may constitute a subgroup warranting an endovascular approach whenever possible.

Hybrid treatment of aortic arch aneurysms.

AIM: Aim of this study was to retrospectively analyze the experience of a single center in the hybrid treatment of aortic arch aneurysms. METHODS: From January 2005 to August 2008 a hybrid treatment for complex aortic aneurysms (aortic arch, thoracoabdominal aorta or thoracic and abdominal segments at the same time) was performed in 34 patients. In 11 cases a hybrid exclusion of an aortic arch aneurysm was carried out. Perioperative results in terms of morbidity and mortality were assessed. Follow-up examination consisted of computed tomography scan and chest X-ray at discharge, 6 and 12 months, and yearly thereafter. Mid-term survival and graft-related complications were analyzed. RESULTS: All the patients were males with a mean age of 74 years, range 68-81. Intraoperative technical success was achieved in all the cases. At 30 days one patient died for an acute stroke. The overall 30-day mortality rate was 9.1%. One frenic nerve paralysis and one acute re-spiratory failure with pneumonia were observed with an overall 30-day major morbidity rate of 18.2%. During follow-up (mean duration 19.3 months, range 1-36) no death, reintervention, conversion, aneurysm-related complication or graft thrombosis were recorded. CONCLUSION: Hybrid approaches to the treatment of complex aortic lesions involving the arch can be successfully used. However, perioperative complications remain still not irrelevant and long-term efficacy has to be proved.