Mauro Gargiulo

Postoperative course of inflammatory abdominal aortic aneurysms

Of 779 patients undergoing repair of abdominal aortic aneurysms over a 7-year period (1984–1990), 40 (5.1%) had gross features of inflammatory abdominal aortic aneurysms (IAAAs). Twenty IAAAs were assessed by CT scan preoperatively and postoperatively to evaluate the outcome of the inflammatory layer of the aneurysm in 19 cases. Complete postoperative regression was observed in nine cases (47.3%), partial regression in four (21%), and stable lesions in six (31.7%). No roentgenographic progression was found. The comparison between the roentgenologic outcome and preoperative clinical features (age, sex, erythrocyte sedimentation rate, and abdominal lumbar pain), pathologic findings, and follow-up time revealed a significant correlation (p<0.05) between the postoperative outcome and the histologic findings in the wall (cell density and cell/fibrosis ratio). Complete regression of inflammation was observed when high cell density (16±0.7 cells/2116 µm2) and a cell/fibrosis ratio >1 were found. On the contrary, little or no regression of inflammation occurred when a low cell density (3.4±0.3 cells/2116 µm2) and a cell/fibrosis ratio < 1 were found. Although it is generally thought that inflammation in IAAAs regresses after surgical repair, in our study, 31.7% of the postoperative CT scans showed no change. Histologically, the variability of morphologic aspects seemed to correlate with the relative proportions of cellular infiltrate and interstitial fibrosis in the aneurysmal wall. These proportions determine the postoperative course of the inflammation layer and, most likely, the response of the latter to steroid therapy as well.

What's next after optimal infrapopliteal angioplasty? Clinical and ultrasonographic results of a prospective single-center study.

Purpose: To evaluate arterial patency and factors influencing outcomes after successful tibial artery angioplasty in patients with critical limb ischemia (CLI). Methods: From January 2005 to August 2007, a prospective single-center study was conducted involving 80 CLI patients (56 men; mean age 71.7±8.8 years) who underwent successful tibial artery angioplasty (<30% residual stenosis) in 87 limbs. Eighty (92%) limbs showed ischemic ulcers or gangrene at baseline. In two thirds, a more proximal lesion was treated, and a secondary stent was implanted in 14 (16%). Follow-up included clinical examination for wound healing (WH), limb salvage (LS), and duplex-documented target vessel patency or restenosis at discharge and at 1, 3, 6, 9, 12, 18, and then every 6 months. Patency rates, WH, and LS were assessed with the Kaplan-Meier method, and factors influencing these outcomes were analyzed using Cox proportional hazards models. Results: Mean follow-up was 10.9 months (range 2 days — 29 months). At 12 months, the primary and assisted primary patency rates were 37.9% and 71.2%, respectively. Restenosis was significantly correlated with smoking (HR 3.58, 95% CI 1.15 to 11.18; p=0.02), infected ulcers (HR 2.04, 95% CI 1.02 to 4.09; p=0.04), and posterior tibial artery angioplasty (HR 3.76, 95% CI 1.59 to 8.87; p=0.003). Rates of LS and WH at 12 months were 92.7% and 74.9%, respectively. Peroneal angioplasty was significantly correlated with WH (HR 1.83, 95% CI 1.04 to 3.25; p=0.03), and wound healing increased with classes of age (HR 1.60, 95% CI 1.07 to 2.39; p=0.02). Conclusion: One-year restenosis after optimal tibial artery angioplasty is significant and positively correlated with smoking, infection of trophic lesions, and posterior tibial artery angioplasty. Close ultrasound surveillance provides good limb salvage after optimal infrapopliteal angioplasty in patients with CLI.

Architectural Organization and Functional Features of Early Endothelial Progenitor Cells Cultured in a Hyaluronan-Based Polymer Scaffold

Neovascularization can be improved using polymer scaffolds supporting endothelial progenitor cells (EPCs). The aim of the present study was to investigate whether human early EPCs (eEPCs) could be efficiently cultured in a hyaluronan-based non-woven mesh (HYAFF-11). eEPCs were seeded on HYAFF-11 at the density of 1 x 10(6)/cm(2) and cultured with endothelial differentiating factors for 3 weeks. After 24 h, nearly 90% of EPCs were adherent. Cell viability, evaluated by methyltetrazolium test, was greater in HYAFF-11 than on the most commonly used fibronectin-coated dishes, even if a progressive decline in viability was observed starting from approximately the second week of culture. eEPCs easily migrated to and aggregated on the scaffold. Evidence of active protein synthesis and features of endothelial differentiation, including cellular transcytotic channels and micropinocytotic vesicles, was revealed using electron microscopy, immunofluorescence, and reverse transcriptase polymerase chain reaction analysis. eEPCs cultured in the scaffold also showed a certain angiogenic activity, as demonstrated by hepatocyte growth factor transcription and vascular endothelial growth factor secretion. In conclusion, eEPCs can migrate and adhere inside HYAFF-11, maintain their pre-endothelial phenotype, and express angiogenic factors, especially within the first week of growth. These results indicate that non-woven HYAFF-11 could be a promising candidate as a vehicle for eEPCs for regenerative medicine applications.

The cellular component in the parietal infiltrate of inflammatory abdominal aortic aneurysms (IAAA)

Eight cases of inflammatory abdominal aortic aneurysm (IAAA) (group I) and a control group of ten cases of atherosclerotic abdominal aortic aneurysm (AAA) with little or no parietal inflammatory infiltrate (group II) were studied; using light microscopy, transmission electron microscopy (TEM), and immunohistochemistry. These were used to define cell composition in the inflammatory process, the degree of cell activation and alteration of connective tissue. Large numbers of B lymphocytes were present in IAAA with preservation of the T4/T8 ratio. In addition, HLA-DR and the IL2-R antigen (specific for activated cells) were widely expressed in the cell population. The interstitial matrix contained deposits of IgG, IgM and C3c together with an increase in type III collagen and a reduction in elastin which appeared fragmented and swollen. This study, therefore, characterised the cellular component of the parietal inflammatory infiltrate in IAAA. The degree of activation shown by these cell elements and the activation of complement suggest that the relevant antigen may have been localised in the aneurysm wall at the time of observation.

Content and turnover of extracellular matrix protein in human “Non-specific” and inflammatory abdominal aortic aneurysms

Inflammatory aneurysms (IAs) have peculiar macroscopic and histological aspects which make them very different from nonspecific aneurysms (NSAs). These morphological differences seem to be determined by significant modifications of the extracellular matrix. Extracellular matrix protein component concentrations were determined biochemically in infrarenal aortic biopsies from 10 NSAs, five IAs and five non-aneurysmal aortic controls. The concentration of each wall component was expressed in % w/w (relative concentration) and in mg/wall longitudinal cm (absolute concentration) with reference to total protein recovered after hydrolysis and amino acid analysis. The biochemical results were correlated with the histological and ultrastructural features of the specimens. A significant increase in total collagen was observed in the two groups of aneurysms, with respect to the controls (NSA = 285%, IA = 382%). In contrast the 80-90% decrease in the relative concentration of elastin observed in both types of aneurysm was less marked (NSA = 55%, IA = 39%). This fall was not significant when expressed in mg/cm, although elastin derived peptide (EDP) levels in the plasma of these patients was significantly higher than in age-matched controls. The concentration of the soluble collagen fraction appeared significantly higher (Mann-Whitney, p < 0.05) in the IAs with respect to the NSAs, whilst no differences were observed between the two groups regarding the concentration of insoluble elastin and of wall and plasma EDPs. As well as providing evidence of increased elastin turnover, this study emphasises the conspicuous modifications of collagen deposition in the wall of abdominal aortic aneurysms which appeared more marked in the inflammatory group.(ABSTRACT TRUNCATED AT 250 WORDS)

Commentary on: "could four dimensional contrast-enhanced ultrasounds replace computed tomography angiography during follow-up of fenestrated endografts? Results of a preliminary experience".

OBJECTIVE To evaluate four-dimensional contrast-enhanced ultrasound (4D-CEUS) as an alternative imaging method to computed tomography angiography (CTA) during follow up of fenestrated endovascular aneurysm repair (FEVAR) for juxta- and para-renal abdominal aortic aneurysms (AAA). METHODS Between October 2011 and March 2012, all consecutive patients who underwent FEVAR follow up were included in the study and evaluated with both 4D-CEUS and CTA. The interval between the two examinations was always ≤ 30 days. Endpoints were the comparison of postoperative AAA diameter, AAA volume, presence of endoleaks, revascularized visceral vessel (RVV) visualization, and patency. Comparative analysis was performed using Bland-Altman plots and McNemars Chi-square test. RESULTS Twenty-two patients (96% male, 4% female; mean age 74 ± 7 years; American Society of Anesthesiologists grade III/IV 82%/18%) were enrolled. Seventy-eight RVV (fenestrations: 60; scallops: 17; branches: 1) were analyzed. The mean AAA diameter evaluated by 4D-CEUS and CTA was 45 ± 10 mm (range 30-69 mm) and 48 ± 9 mm (range 32-70 mm), respectively. The mean difference was 3 ± 3 mm. The mean AAA volume evaluated by 4D-CEUS and CTA was 150 ± 7 cc (range 88-300 cc) and 159 ± 68 cc (range 80-310 cc), respectively. The mean difference was 7 ± 4 cc; a Bland-Altman plot revealed agreement in AAA diameter and volume evaluation (p < .01) between 4D-CEUS and CTA. The observed agreement for the detection of endoleaks was 95%. McNemars Chi-square test confirmed that 4D-CEUS and CTA were equivalent (p > .05) at detecting endoleaks. The first segment of six (8%) RVVs (four renal and two superior mesenteric arteries) was not directly visualized by 4D-CEUS owing to obesity, but the contrast enhancement into the distal part of vessel or into the relative parenchyma gave indirect information about their patency. McNemars Chi-square test demonstrated the superiority of CTA (p = .031) in visualizing RVVs. The patency of 77/78 RVVs was confirmed with both techniques. McNemars Chi-square test confirmed that 4D-CEUS and CTA were equivalent in their ability to detect visceral vessel patency. CONCLUSIONS The data suggest that 4D-CEUS is as accurate as CTA in the evaluation of postoperative AAA diameter and volume, endoleak detection, and RVV patency after FEVAR. Four-dimensional CEUS could provide hemodynamic information regarding RVVs, and reduce radiation exposure and renal impairment during follow up. Obesity limits the diagnostic accuracy of 4D-CEUS.

Follow-up outcomes of hybrid procedures for thoracoabdominal aortic pathologies with special focus on graft patency and late mortality

OBJECTIVE The purpose of this study was to analyze midterm results of bypass patency and overall and aortic-related mortality rates of hybrid aortic procedures for thoracoabdominal aortic pathologies. METHODS A retrospective study was performed considering prospectively collected data in two centers. From January 2001 to December 2012, 45 patients (33 men; mean age, 67.8 ± 7.6 years) received hybrid aortic procedures for thoracoabdominal aortic diseases (31 atherosclerotic aneurysms, 7 chronic expanding type B aortic dissections, 2 penetrating aortic ulcers, and 5 pseudoaneurysms), corresponding to 155 revascularized visceral abdominal arteries. Elective/emergency and staged/simultaneous approaches were 31 of 14 and 28 of 17, respectively. Patient demographics, clinical risk factors, and aortic morphological and procedural data were collected. End points were technical success, 30-day morbidity, reintervention and mortality, bypass graft patency, freedom from reintervention, and overall and aortic-related mortality during midterm follow-up. Mean follow-up was 2.2 ± 2.4 years. RESULTS Technical success was achieved in 86.6% (39/45) of patients. Thirty-day morbidity rate was 60% (paraplegia/paraparesis: 13.3%, stroke: 6.7%, renal failure: 31.3%, permanent dialysis: 4.4%). Thirty-day freedom from reintervention rates were 67.1% and 78.5%, respectively. Thirty-day occlusion of revascularized visceral vessels occurred in 11 (7.1%, 11/155) target arteries. In-hospital mortality rate was 24.4%. Primary graft patency after 1, 2, and 4 years was 89.7%, 85.3%, and 79%, respectively. Bypass thrombosis or stenosis developed in nine (6.8%, 9/132) vessels during follow-up. Of these, three patients required reintervention and one died. Freedom from reintervention rates after 1, 2, and 4 years were 45.6%, 45.6%, and 34.2%, respectively. Overall and aortic-related mortality rates after 1, 2, and 4 years were 32.6%, 41.4%, and 45.3% and 9.1%, 13.9%, and 13.9%, respectively. CONCLUSIONS A hybrid procedure for thoracoabdominal aortic pathologies in high-risk patient is feasible but carries a significant rate of early and midterm reintervention and death. Long-term surveillance of the visceral bypass is necessary because one-third of the patients will have bypass-related complications.

Hypertension Due to an Aneurysm of the Left Renal Artery in a Patient with Neurofibromatosis

Arterial lesions in patients with neurofibromatosis are rarely described and in most cases are stenotic. The aneurysmal changes reported in the literature are usually characterized by multiple microaneurysms due to the dysplastic lesions of the artery. We report a case of a single aneurysm of the inferior hilar branch of the left renal artery of a young female with neurofibromatosis. The patient showed hypoperfusion of the renal pole fed by this branch and was hypertensive. The aneurysm had a diameter of 4 cm and showed the histological findings typical of dysplastic lesions of neurofibromatosis. The hypertension and the renal pole hypoperfusion recovered after surgical excision of the aneurysm and end-to-end anastomosis of the hilar branch stumps.

Fenestrated and Branched Endograft after Previous Aortic Repair

BACKGROUND Para-anastomotic aneurysms (P-AAA) and proximal aortic aneurysmal degeneration after previous aortic open repair (OR) or endovascular repair (EVAR) are challenging clinical scenarios. OR is technically demanding, and standard EVAR could be impossible due to the absence of proximal landing zone. The aim of the study is to report midterm results of fenestrated and branched endografts (FB-EVAR) to treat proximal aortic lesions after previous aortic repair. METHODS Since 2010, patients that underwent FB-EVAR after previous aortic repair were prospectively enrolled. Clinical or morphologic or intraoperative or postoperative data were collected and retrospectively analyzed. Primary end points were technical success and clinical success. Secondary end points were procedure-related events (endoleaks, target visceral vessels occlusion, mortality), midterm survival and freedom from FB-EVAR-related reinterventions. RESULTS Twenty patients (Male: 98%, age: 75 ± 6 years, American Society of Anesthesiologists [ASA] ≥ III: 100%) were enrolled. Fifteen patients (75%) underwent previous aortic OR and 5 (25%) standard EVAR. The mean time since the previous treatment was 12 ± 10 years. Present aortic lesions included thoracoabdominal aneurysms 12 (60%) and juxtarenal and pararenal aneurysms 8 (40%). The mean aortic aneurysm diameter was 67 ± 15 mm. All patients were at high risk for OR and had anatomies precluding standard EVAR. Seventy-two visceral vessels (renal arteries: 34, superior mesenteric artery: 20, celiac trunk: 18) were targeted: 49 fenestrations, 19 branches, and 4 scallops. An FB-EVAR tube and trimodular endograft was planned in 17 and 3 cases, respectively. Technical success was 95%; operative target vessel perfusion was 98.5%. Thirty-day mortality was 0%. Clinical success was 80% because there was a transient renal function worsening in 4 patients (>30% of baseline). One distal type I endoleak was detected and treated at 1-month. The mean follow-up was 15 ± 11 months. There were not proximal type I endoleaks, target visceral vessel occlusions, or aneurismal-related mortality. Survival at 1 year was 85 ± 5%. One late FEVAR-related reintervention occurred. CONCLUSIONS According to the reported data, FB-EVAR for treating P-AAA or proximal aneurysmal degeneration after previous aortic OR/EVAR in high-risk patients is a safe and/or effective solution.

Dysfunctional Vasa Vasorum in Diabetic Peripheral Artery Obstructive Disease with Critical Lower Limb Ischaemia

OBJECTIVES AND DESIGN To establish whether in diabetic patients with peripheral artery obstructive disease (PAOD) vasa vasorum (vv) neoangiogenesis is altered with increased arterial damage. MATERIALS Thirty-three patients with PAOD and critical lower limb ischaemia, 22 with type II diabetes. METHODS Immunohistochemistry for endothelial cell markers (CD34 and von Willebrand Factor); real-time reverse transcription polymerase chain reaction (RT-PCR) to quantify arterial wall expression of vascular endothelial growth factor (VEGF); enzyme-linked immunosorbent assay (ELISA) to assess blood VEGF; flow cytometry to detect circulating endothelial cells (CECs). RESULTS Patients with PAOD and diabetes have a higher frequency (60% vs. 45%) of advanced atherosclerotic lesions and a significant reduction (p = 0.0003) in CD34(+) capillaries in the arterial media. Adventitial neoangiogenesis was increased equally (CD34(+) and vWF(+)) in all patients. Likewise, all patients have increased CEC and VEGF concentration in the blood as well as in-situ VEGF transcript expression. CONCLUSIONS Patients with PAOD have remarkable arterial damage despite increased in-situ and circulating expression of the pro-angiogenic VEGF; a dysfunctional vv angiogenesis was seen in diabetics which also showed a higher frequency of parietal damage; it is suggested that in diabetic arterial wall, injury is worsened by vv inability to finalise an effective VEGF-driven arterial wall neoangiogenesis.