Raffaele Pulli

Surgical treatment of visceral artery aneurysms: A 25-year experience

OBJECTIVE The aim of this study was to analyze our 25-year experience with surgical treatment of visceral artery aneurysms (VAAs), with particular attention paid to early and long-term results. MATERIALS AND METHODS From January 1982 to September 2007, 55 patients (32 males, 58%, and 23 females, 42%) underwent surgical treatment of 59 VAAs. Only one patient was treated with an endovascular procedure. Mean patient age was 59.3 years (range, 36-78 years). The site of aneurysmal disease was splenic artery in 30 (50.8%) cases, renal artery in nine (15.2%) cases, common hepatic artery in seven (11.9%) cases, pancreaticoduodenal artery in four (6.8%) cases, celiac trunk in three (5.1%) cases, superior mesenteric artery in two (3.4%) cases, and gastroduodenal, inferior mesenteric, middle colic and right gastroepiploic in one (1.7%) case for each artery. Two (3.6%) patients had multiple VAAs. In five (9.1%) patients, an abdominal aortic aneurysm coexisted. Early results in terms of mortality and major complications were assessed. Follow-up consisted of clinical and ultrasound examinations at 1 and 12 months, and yearly thereafter. Long-term results in terms of survival and aneurysm-related complications were analyzed. RESULTS In all but two cases, elective intervention in asymptomatic patients was performed. Two (3.6%) patients had a ruptured aneurysm (one pancreaticoduodenal artery and one middle colic artery). The one perioperative death was due to an acute pancreatitis in a patient operated on for a giant inflammatory splenic artery aneurysm, yielding a perioperative mortality rate of 1.8%. Two major complications (retroperitoneal hematoma and acute pancreatitis) were recorded. Mean duration of follow-up was 82.1 months (range, 0-324 months). Estimated 10-year survival rate was 79.5%. During follow-up two aneurysm-related complications occurred, with an estimated 10-year, aneurysm-related, complication-free survival rate of 75.2%. CONCLUSION In the era of minimally invasive therapeutic approaches, elective open surgical treatment of visceral artery aneurysms is safe and effective, and offers satisfactory early and long-term results.

High levels of homocysteine, lipoprotein (a) and plasminogen activator inhibitor-1 are present in patients with abdominal aortic aneurysm

Over the last few years,there has been increasing interest in the investigation of the pathogenesis of AAA, and a role for some novel risk factors, in particular thrombophilic risk factors, has been suggested. The aim of this study was to evaluate a number of thrombophilic parameters in a large group of patients with AAA. In 438 patients with AAA, and in 438 healthy subjects, selected to be comparable for age and gender with patients and without instrumental evidence of AAA, a pattern of thrombophilic parameters [homocysteine (Hcy), lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), anticardiolipin antibodies (ACA), MTHFR C677T polymorphism, prothrombin gene G20210A variant and FactorV Leiden mutation] has been evaluated. A significant difference for Hcy, PAI-1 and Lp(a) plasma levels has been observed between patients and controls. After adjustment for the traditional cardiovascular risk factors, a significant increased risk of having AAA has been observed for high levels of Hcy (OR: 7.8; p<0.0001), Lp(a) (OR: 2.4; p<0.0001) and PAI-1 (OR: 3.2; p<0.0001). The association has been confirmed after exclusion of patients with other localization of atherosclerosis. Moreover, a significant association between larger abdominal aortic diameters and the number of thrombophilic parameters has been reported (r = 0.13; p = 0.005). In conclusion, a significant association between abnormal levels of some metabolic parameters related to thrombosis such as Hcy, Lp(a) and PAI-1 and AAA has been observed.

Genetic analysis of 56 polymorphisms in 17 genes involved in methionine metabolism in patients with abdominal aortic aneurysm

Background: Previous studies suggested an association between abdominal aortic aneurysm (AAA) and hyperhomocysteinaemia, a complex trait determined by genetic and environmental factors. Our hypothesis was that polymorphisms in genes directly or indirectly involved in methionine metabolism may contribute to AAA susceptibility. Method: We studied 56 polymorphisms in MTHFR, MTR, MTRR, CBS, MTHFD1, SLC19A1, NNMT, TCN2, AHCY, BHMT, BHMT2, FOLH1, TYMS, ENOSF1, SHMT1, PON1, PON2 genes according to their demonstrated/putative function, localisation in promoter or regulatory and coding regions and/or heterozygosity values >0.300. Polymorphisms were evaluated by using a primer extension based microarray technology in 423 AAA patients and 423 matched controls. Results: All polymorphisms resulted in Hardy–Weinberg equilibrium in patients and controls. At the multiple logistic regression analysis adjusted for traditional cardiovascular risk factors (sex, age, hypertension, smoking habit, dyslipidaemia, diabetes) and chronic obstructive pulmonary disease (COPD), rs8003379 MTHFD1 (odds ratio (OR) 0.41, 95% confidence interval (CI) 0.26 to 0.65) and rs326118 MTRR (OR 0.47, 95% CI 0.29 to 0.77) polymorphisms resulted in independent susceptibility factor for AAA. Conclusions: After haplotype reconstruction, logistic regression analyses adjusted for traditional risk factors and COPD showed a significant association among AAA and AHCY, FOLH1, MTHFD1, MTR, NNMT, PON1 and TYMS haplotypes. Our findings offer new insights into the pathogenesis of AAA.

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 multicenter comparison between autologous saphenous vein and heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft in the treatment of critical limb ischemia in diabetics

OBJECTIVES The aim of this study was to evaluate early and follow-up results of below-knee bypasses performed using a bioactive heparin-treated expanded polytetrafluoroethylene (ePTFE) graft in diabetic patients with critical limb ischemia (CLI) in a multicenter 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 centers in the same period of time. METHODS Over an 8-year period, ending in 2009, a heparin-bonded prosthetic graft (Propaten Gore-Tex; W. L. Gore & Associates Inc, Flagstaff, Ariz) was implanted in 180 diabetic patients undergoing below-knee revascularization for CLI in seven Italian hospitals (group 1). In the same period in these seven centers, 133 below-knee bypasses with ipsilateral ASV in diabetics with CLI were performed (group 2). 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 The interventions consisted of below-knee bypasses in 132 cases in group 1 (73%) and in 45 cases in group 2 (33%; P < .001); 48 patients in group 1 (27%) and 88 patients in group 2 (67%; P < .001) had distal tibial anastomosis. Patients in group 1 had more frequently adjunctive procedures performed at distal anastomotic sites to improve run-off status. Postoperative and long-term medical treatment consisted of single antiplatelet therapy in 93 cases (52%) in group 1 and in 64 cases (48%, P = ns) in group 2, of double antiplatelet therapy in 18 cases (10%) in group 1 and in four cases (3%; P = .05) in group 2 and of oral anticoagulants in 69 patients in group 1 (38%) and in 65 (49%; P = .02) in group 2. Mean duration of follow-up was 28.3 ± 21.4 months; 308 patients (98%) had at least one postoperative clinical and ultrasonographic examination and 228 (72%) reached at least a 1-year follow-up. Estimated 48-month survival rates were 76.6% in group 1 and 72.7% in group 2 (P = > .9, log-rank 0.08). Primary patency rate at 48 months was significantly better in group 2 (63.5%) than in group 1 (46.3%; P = .03, log-rank 4.1). Assisted primary patency rates at 48 months were 47.3% (SE 0.05) in group 1 and 69% (SE 0.05) in group 2 (P = .01, log-rank 6.3). The rates of secondary patency at 48 months were 57.5% in group 1 and 69.6% in group 2 (P = .1, log-rank 2.3); the corresponding values in terms of limb salvage and amputation free-survival rates were 75.4% and 82.4% (P = .3, log-rank 1), and 59.9% and 64.4% (P = .3, log-rank 0.9), respectively. CONCLUSIONS Data from this large, retrospective registry confirmed that the indexed heparin-bonded ePTFE graft provides satisfactory early and midterm results in diabetic patients undergoing surgical treatment of CLI. While autologous saphenous vein maintains its superiority in terms of primary patency, secondary patency rates are not statistically different, even in the presence of a trend for improved secondary patency with vein graft; and also limb salvage rates are comparable.

Midterm results from a multicenter registry on the treatment of infrainguinal critical limb ischemia using a heparin-bonded ePTFE graft

OBJECTIVES To report midterm results of infrainguinal bypasses performed with a heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft in patients presenting with critical limb ischemia. METHODS Over a 7-year period ending in 2008, 425 patients presenting with critical limb ischemia underwent infrainguinal revascularization using a heparin-bonded ePTFE graft in seven Italian vascular centers. Preoperative, intraoperative, and follow-up data were collected in a multicenter registry. Patients were predominantly male (79%) with a mean age of 73.5 years. Mean preoperative ankle brachial index (ABI) was 0.35 and 192 of the patients (45%) were diabetic. Intervention consisted of a femoral to below-knee bypass in 324 patients (76%), whereas the remaining 101 patients had a femoral to above-knee bypass. In patients with below-knee bypass, distal target vessels were the popliteal artery in 238 cases, the tibioperoneal trunk in 38 cases, and a tibial vessel in the remaining 48 cases (anterior tibial artery in 20 cases, posterior tibial artery in 23 cases, and peroneal artery in 5). Follow-up consisted of clinical and duplex scanning examinations within 3 months from the intervention and yearly thereafter. Early (<30 day) results were analyzed in terms of deaths, graft thromboses, and amputations with univariate and multivariate (stepwise logistic regression) analysis. Follow-up results were evaluated in terms of primary and secondary graft patency, limb salvage, and survival rate with univariate and multivariate (Cox regression) analysis. RESULTS Thirteen perioperative deaths occurred (3.1%). Thirty-day primary graft patency was 92.5% and limb salvage was 95.8%. Follow-up was available in 98% of patients with a median duration of 25.5 months (SD, 17.6; range, 1-72). Cumulative estimated 36-month primary and secondary patency, limb salvage, and survival rates were 61%, 70%, 83%, and 83%, respectively. At univariate analysis, the factors associated with poorer limb salvage rates during follow-up were the presence of ischemic ulcers or gangrene (log-rank, 8.4; P = .004; 95% confidence interval [CI] 1.2-3.5; odds ratio [OR], 2.1), the presence of only one patent tibial vessel (log-rank, 41.3; P < .001; 95% CI, 3.1-10.8, OR, 5.8), redo surgery (log-rank, 12.4; P < .001; 95% CI, 1.4-4; OR, 2.4) and the postoperative treatment with antiplatelet therapy in comparison to oral anticoagulants (log-rank, 5.1; P = .02; 95% CI, 1.0-3.4; OR, 1.8). At multivariate analysis redo surgery (P = .02; 95% CI, 1.1-3.1; OR, 1.8), poor runoff score (P < .001; 95% CI, 2.5-9.1; OR, 4.7) and preoperative clinical status (P = .02; 95% CI, 1.1-3.1; OR, 1.8) were independently associated with decreased limb salvage rates. CONCLUSION The use of a heparin-bonded ePTFE graft provides good early and midterm results, with low rates of late amputations. Primary and secondary patency made this graft an excellent alternative to autologous saphenous vein when it is absent, unsuitable, or of poor quality.

Early and long-term results of surgical treatment of splenic artery aneurysms

BACKGROUND This retrospective study was conducted to describe the presentation, surgical treatment, and follow-up of patients with splenic artery aneurysms. METHODS From 1982 to 2000, 1,952 patients with abdominal aneurysms were referred to our department; 15 had splenic artery aneurysms. None had ruptured. All were operated on. RESULTS Fourteen complete and 1 partial aneurysmectomies were carried out. Arterial continuity was restored in 10, by end-to-end anastomosis, and 4 had splenectomies. In 1 patient the spleen was preserved without arterial reconstruction. There were no deaths. Morbidity was restricted to 1 patient with a limited, asymptomatic splenic infarction. Eleven patients were followed up for a mean 19.7 months. No deaths or major complications were recorded. Reconstructed splenic arteries were patent in all cases without atrophy or new cases of splenic infarction. CONCLUSIONS Elective surgery for splenic artery aneurysms is safe. Arterial reconstruction allows good early and long-term results. In some cases splenectomy may be unavoidable.

Endovascular Aortic Aneurysm Repair with the Endurant Stent-graft: Early and 1-year Results from a European Multicenter Experience

PURPOSE To assess preliminary results of the Endurant stent-graft, which was developed to treat patients with abdominal aortic aneurysms (AAAs) and challenging aortoiliac anatomy. MATERIALS AND METHODS From November 2007 to October 2008, 45 patients with AAAs were treated with the Endurant stent-graft in three European vascular centers. Thirty-eight of the 45 patients (84%) had a hostile anatomy of the proximal neck. Early (30 days), early midterm (6 months), and late midterm (1 year) results were analyzed in terms of technical success, clinical success, morbidity, and mortality. RESULTS Intraoperative immediate technical and clinical success was achieved in all cases. At completion angiography, a type II endoleak was detected in seven of the 45 patients (16%) and an iliac limb stenosis was diagnosed and successfully treated in five (11%). At discharge, computed tomography demonstrated a type I endoleak in one of the 45 patients (2.2%). At 30 days, a graft limb thrombosis was diagnosed (2.2%) and successfully treated. The 30-day overall technical and clinical success rates were 97.8% (44/45 cases) and 95.6% (43/45 cases), respectively. During follow-up (mean duration, 8 months; range, 5-16 months), the type I endoleak was successfully treated with an aortic extension. Estimated freedom from type I or III endoleak and repeat intervention at 1 year was 97.8% (44/45 cases) and 93.3% (42/45 cases), respectively. CONCLUSIONS The initial experience shows that the Endurant stent-graft appears to be effective in endovascular repair of AAAs in patients with hostile aortoiliac anatomy. This graft permits a broader group of patients to be treated with endovascular aneurysm repair; however, further studies are needed to evaluate the long-term results.

Early and long-term comparison of endovascular treatment of iliac artery occlusions and stenosis

OBJECTIVES This study evaluated early and long-term results of endovascular treatment of iliac artery occlusions and compared these outcomes with those in patients treated for stenotic lesions. METHODS During a 10-year period ending in January 2010, 223 endovascular procedures to treat aortoiliac occlusive disease (PAD) were performed. All patients were prospectively enrolled in a dedicated database. The intervention was performed for iliac occlusion in 109 patients (group 1) and for iliac stenosis in 114 (group 2). Early results were analyzed and compared by χ² and Fisher exact tests. Follow-up consisted of clinical examination and duplex scanning at discharge, ≤ 3 months, at 6 and 12 months, and yearly thereafter. Follow-up results were analyzed with Kaplan-Meier curves and compared with the log-rank test. RESULTS The two groups had similar risk factors for atherosclerosis and comorbidities. Critical limb ischemia was more common in group 1 (20.5%) than in group 2 (8.5%; P = .01). Intraoperative technical details were similar, except for a higher percentage of brachial and contralateral femoral access and more frequent use of nitinol stents in group 1. Two immediate technical failures occurred, one in both groups, requiring immediate conversion to surgical bypass. Four intraoperative iliac ruptures occurred, two in each group; all were successfully treated with covered stents. An additional 10 immediate complications occurred (8 in group 1; 2 in group 2), one of which required conversion to open surgical bypass. The cumulative rate of perioperative complications was 9% in group 1 and 3.5% in group 2 (P = .08). Primary patency at 30 days was 97.3% and 98.7%, respectively. Mean duration of follow-up was 28.4 months; 203 patients (91%) had a regular postoperative follow-up visit. At 60 months, primary patency in group 1 vs group 2 was 82.4% vs 77.7% (P = .9), assisted primary patency was 90.6% vs 85.5% (P = .4), and estimated secondary patency was 93.1% vs 92.8% (P = .3). The cumulative rate of reintervention during follow-up (excluding reinterventions performed in the perioperative period) was 2.5% in group 1 and 12.5% in group 2 at 60 months (P = .09). Univariate analysis in group 1 failed to find any of the examined risk factors significantly affected long-term primary patency rates. CONCLUSIONS In our experience, endovascular treatment of iliac occlusions provides excellent early and long-term results, similar to those obtained in the treatment of stenotic lesions.

Gene expression profiling of peripheral blood in patients with abdominal aortic aneurysm.

OBJECT Abdominal aortic aneurysm (AAA) pathogenesis remains poorly understood. This study investigated the gene expression profile of peripheral blood from patients with AAA using microarray technology. METHODS AND RESULTS We determined gene expression profiles in pooled RNA from 10 AAA patients and 10 matched controls with arrays representing 14,000 transcripts. Microarray data for selected genes were confirmed by real-time PCR in two different AAA (n=36) and control (n=36) populations and integrated with biochemical data. We identified 91 genes which were differentially expressed in AAA patients. Gene Ontology analysis indicated a significant alteration of oxygen transport (increased hemoglobin gene expression) and lipid metabolism [including monoglyceride lipase and low density lipoprotein receptor-related protein 5 (LRP5) gene]. LRP5 expression was associated inversely with serum lipoprotein(a) [Lp(a)] concentration. CONCLUSIONS Increased expression of hemoglobin chain genes as well as of genes involved in erythrocyte mechanical stability were observed in the AAA RNA pools. The association between low levels of LRP5 gene expression and increased levels of Lp(a) in AAA patients suggests a potential role of LRP5 in Lp(a) catabolism. Our data underline the power of microarrays in identifying further molecular perturbations associated with AAA.