Giulio Illuminati

LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism

OBJECTIVES Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. METHODS Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. RESULTS Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. CONCLUSION Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation.

Short-term results of a randomized trial examining timing of carotid endarterectomy in patients with severe asymptomatic unilateral carotid stenosis undergoing coronary artery bypass grafting

OBJECTIVE This study evaluated the timing of carotid endarterectomy (CEA) in the prevention of stroke in patients with asymptomatic carotid stenosis >70% receiving a coronary artery bypass graft (CABG). METHODS From January 2004 to December 2009, 185 patients with unilateral asymptomatic carotid artery stenosis >70%, candidates for CABG, were randomized into two groups. In group A, 94 patients received a CABG with previous or simultaneous CEA. In group B, 91 patients underwent CABG, followed by CEA. All patients underwent preoperative helical computed tomography scans, excluding significant atheroma of the ascending aorta or aortic arch. Baseline characteristics of the patients, type of coronary artery lesion, and preoperative myocardial function were comparable in the two groups. In group A, all patients underwent CEA under general anesthesia with the systematic use of a carotid shunt, and 79 patients had a combined procedure and 15 underwent CEA a few days before CABG. In group B, all patients underwent CEA, 1 to 3 months after CABG, also under general anesthesia and with systematic carotid shunting. RESULTS Two patients (one in each group) died of cardiac failure in the postoperative period. Operative mortality was 1.0% in group A and 1.1% in group B (P = .98). No strokes occurred in group A vs seven ipsilateral ischemic strokes in group B, including three immediate postoperative strokes and four late strokes, at 39, 50, 58, and 66 days, after CABG. These late strokes occurred in patients for whom CEA was further delayed due to an incomplete sternal wound healing or because of completion of a cardiac rehabilitation program. The 90-day stroke and death rate was 1.0% (one of 94) in group A and 8.8% (eight of 91) in group B (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.01-0.91; P = .02). Logistic regression analysis showed that only delayed CEA (OR, 14.2; 95% CI, 1.32-152.0; P = .03) and duration of cardiopulmonary bypass (OR, 1.06; 95% CI, 1.02-1.11; P = .004) reliably predicted stroke or death at 90 days. CONCLUSIONS This study suggests that previous or simultaneous CEA in patients with unilateral severe asymptomatic carotid stenosis undergoing CABG could prevent stroke better than delayed CEA, without increasing the overall surgical risk.

Direct Transposition of the Distal Cervical Vertebral Artery Into the Internal Carotid Artery

From January 1979 to December 1991, 92 revascularizations of the V3 segment of the vertebral artery were performed in 91 patients through a direct transposition of this artery into the internal carotid artery (ICA). These cases represented 15.1% of 610 vertebral revascularizations and 38.8% of 280 distal vertebral revascularizations performed during this period at our institution. The sex ratio of this population was 0.59, and the mean age was 59.4±13.2 years (range 14 to 82 years). Preoperative ischemic symptoms were vertebrobasilar in 87 (94.6%) cases, exclusively hemispheric in one (1.1%), and absent in the remaining four (4.3%). One of these four patients had asymptomatic severe multivessel occlusive disease and three others underwent resection of a spinal tumor involving the vertebral foraminal canal. In 31 (33.7%) cases significant carotid occlusive disease was also present. The distal V3 segment of the artery was directly transposed into the ICA in all cases in this series. In 24 (26.1%) cases the ICA was endarterectomized during the same operation. There were no deaths or strokes in this series but there were two (2.2%) transient ischemic attacks-one vertebrobasilar and the other hemispheric. However, eight (8.7%) transposed vertebral arteries were totally occluded at early follow-up. At 1 month, among the 87 patients with vertebrobasilar insufficiency, 44 (50.6%) were cured, 31 (35.6%) were improved, and 12 (13.8%) remained unchanged. Among the 12 who were unchanged, eight (66.7%) had occlusion or stenosis of the distal transposition at the time of discharge. At 5 years, the primary patency rate in the series was 89.1%±7.2%. At the time of the last follow-up, among the 87 patients with vertebrobasilar insufficiency, 50 (57.5%) were cured, 25 (28.7%) were improved, two (2.3%) had remained unchanged since the operation, two (2.3%) suffered a relapse, and eight (9.2%) exhibited vertebrobasilar symptoms of varying severity and therefore could not be considered improved. Direct transposition of the V3 segment of the vertebral artery into the ICA is a simple, safe, and reliable technique for revascularization of the distal cervical vertebral artery.

The surgical treatment of chronic intestinal ischemia: Results of a recent series

Abstract Due to the rarity of the condition, large and prospective series defining the optimal method of digestive arteries revascularization, for the treatment of chronic intestinal ischemia, are lacking. The aim of this consecutive sample clinical study was to test the hypotesis that flexible application of different revascularization methods, according to individual cases, will yield the best results in the management of chronic intestinal ischemia. Eleven patients, of a mean age of 56 years, underwent revascularization of 11 digestive arteries for symptomatic chronic mesenteric occlusive disease. Eleven superior mesenteric arteries and one celiac axis were revascularized. The revascularization techniques included retrograde bypass grafting in 7 cases, antegrade bypass grafting in 2, percutaneous arterial angioplasty in 1, and arterial reimplantation in one case. The donor axis for either reimplantation or bypass grafting was the infrarenal aorta in 4 cases, an infrarenal Dacron graft in 4, and the celiac aorta in one case. Grafting materials included 5 polytetrafluoroethylene (PTFE) and 3 Dacron grafts. Concomitant procedures included 3 aorto-ilio-femoral grafts and one renal artery revascularization. Mean follow-up duration was 31 months. There was no operative mortality. Cumulative survival rate was 88,9% at 36 months (SE 12,1%). Primary patency rate was 90% at 36 months (SE 11,6%). The symptom free rate was 90% at 36 months (SE 11.6%). Direct reimplantation, antegrade and retrograde bypass grafting, all allow good mid-term results: the choice of the optimal method depends on the anatomic and general patient’s status. Associated infrarenal and renal arterial lesions can be safely treated in the same time of digestive revascularization. Angioplasty alone yields poor results and should be limited to patients at poor risk for surgery.

Results of a pancreatectomy with a limited venous resection for pancreatic cancer

PurposeThe indications for a pancreatectomy with a partial resection of the portal or superior mesenteric vein for pancreatic cancer, when the vein is involved by the tumor, remain controversial. It can be assumed that when such involvement is not extensive, resection of the tumor and the involved venous segment, followed by venous reconstruction will extend the potential benefits of this resection to a larger number of patients. The further hypothesis of this study is that whenever involvement of the vein by the tumor does not exceed 2 cm in length, this involvement is more likely due to the location of the tumor being close to the vein rather than because of its aggressive biological behavior. Consequently, in these instances a pancreatectomy with a resection of the involved segment of portal or superior mesenteric vein for pancreatic cancer is indicated, as it will yield results that are superposable to those of a pancreatectomy for cancer without vascular involvement.MethodsTwenty-nine patients with carcinoma of the pancreas involving the portal or superior mesenteric vein over a length of 2 cm or less underwent a macroscopically curative resection of the pancreas en bloc with the involved segment of the vein. The venous reconstruction procedures included a tangential resection/lateral suture in 15 cases, a resection/end-to-end anastomosis in 11, and a resection/patch closure in 3.ResultsPostoperative mortality was 3.4%; morbidity was 21%. Local recurrence was 14%. Cumulative (standard error) survival rate was 17% (9%) at 3 years.ConclusionA pancreatectomy combined with a resection of the portal or superior mesenteric vein for cancer with venous involvement not exceeding 2 cm is indicated in order to extend the potential benefits of a curative resection.

Outpatient repair for inguinal hernia in elderly patients: Still a challenge?

BACKGROUND Elective inguinal hernia repair as a day case is a safe and suitable procedure, with well-recognized feasibility. The increasing number of elderly patients requiring inguinal hernia repair leads clinicians to admit a growing number of outpatients. The aim of the current study was to analyze the outcomes (feasibility and safety) of day case treatment in elderly patients. METHODS Eighty patients >80 years of age and 80 patients ≤55 years of age underwent elective inguinal hernia repairs under local anesthesia. RESULTS There were no mortalities or major complications in the elderly undergoing inguinal herniorraphies as outpatients, and only one unanticipated admission occurred in the younger age group. CONCLUSIONS Elective inguinal hernia repair in the elderly has a good outcome, and age alone should not be a drawback to day case treatment.

Prosthetic bypass for restenosis after endarterectomy or stenting of the carotid artery

Objective: The objective of this study was to evaluate the results of prosthetic carotid bypass (PCB) with polytetrafluoroethylene (PTFE) grafts as an alternative to carotid endarterectomy (CEA) in treatment of restenosis after CEA or carotid artery stenting (CAS). Methods: From January 2000 to December 2014, 66 patients (57 men and 9 women; mean age, 71 years) presenting with recurrent carotid artery stenosis ≥70% (North American Symptomatic Carotid Endarterectomy Trial [NASCET] criteria) were enrolled in a prospective study in three centers. The study was approved by an Institutional Review Board. Informed consent was obtained from all patients. During the same period, a total of 4321 CEAs were completed in the three centers. In these 66 patients, the primary treatment of the initial carotid artery stenosis was CEA in 57 patients (86%) and CAS in nine patients (14%). The median delay between primary and redo revascularization was 32 months. Carotid restenosis was symptomatic in 38 patients (58%) with transient ischemic attack (n = 20) or stroke (n = 18). In this series, all patients received statins; 28 patients (42%) received dual antiplatelet therapy, and 38 patients (58%) received single antiplatelet therapy. All PCBs were performed under general anesthesia. No shunt was used in this series. Nasal intubation to improve distal control of the internal carotid artery was performed in 33 patients (50%), including those with intrastent restenosis. A PTFE graft of 6 or 7 mm in diameter was used in 6 and 60 patients, respectively. Distal anastomosis was end to end in 22 patients and end to side with a clip distal to the atherosclerotic lesions in 44 patients. Completion angiography was performed in all cases. The patients were discharged under statin and antiplatelet treatment. After discharge, all of the patients underwent clinical and Doppler ultrasound follow‐up every 6 months. Median length of follow‐up was 5 years. Results: No patient died, sustained a stroke, or presented with a cervical hematoma during the postoperative period. One transient facial nerve palsy and two transient recurrent nerve palsies occurred. Two late strokes in relation to two PCB occlusions occurred at 2 years and 4 years; no other graft stenosis or infection was observed. At 5 years, overall actuarial survival was 81% ± 7%, and the actuarial stroke‐free rate was 93% ± 2%. There were no fatal strokes. Conclusions: PCB with PTFE grafts is a safe and durable alternative to CEA in patients with carotid restenosis after CEA or CAS in situations in which CEA is deemed either hazardous or inadvisable.

Results of axillofemoral by-passes for aorto-iliac occlusive disease

The purpose of this study was to review our results with axillofemoral by-passes performed for aortoiliac occlusive disease. Fifty patients receiving 51 axillofemoral by-passes from January 1989 to December 1994 were retrospectively reviewed. The 30-day post-operative mortality was 4%. Seven patients (14%) presented graft-related local complications and all but one required reoperation. Five patients were lost to follow-up, the mean length of which was 36 months (16–74 months). Forty-nine per cent of the patients died during the follow-up period. At 36 months, the primary patency rate was 51%, the secondary patency rate was 69%, and limb valvage rate was 87%. A statistical difference was seen in the secondary patency rate between axillobifemoral by-pass (87%) and axillo-unifemoral by-pass (56%) at 36 months (P<0.01), but no difference was seen in the limb salvage rate at 36 months between the two configurations of the by-pass (94% vs 81 %) (P=NS). Twenty patients (40%) operated upon for acute ischemia had a significantly higher post-operative mortality rate (10% vs 0), a significantly higher amputation rate (20% vs 6.6%) and a significantly lower patency rate of by-pass (26% vs 63%) (P<0.01), than the 30 patients (60%) operated on for claudication, rest pain or trophic ulcers. Our findings indicate that the results of axillofemoral by-pass are significantly influenced by the selection of patients for operation, namely the clinical status of ischaemic symptoms, and that since the overall results of axillofemoral by-pass are inferior to those of aortofemoral by-pass, this treatment should be restricted to patients at high risk of aortic clamping.ZusammenfassungEs wurden 51 axillofemorale By-passoperationen aus dem Zeitraum Januar 1989 bis Dezember 1994 retrospektiv analysiert. Die postoperative Mortalitätsrate (nach 30 Tagen) betrug 4%. Bei 7 Patienten (14%) traten am Graft Komplikationen ein, so daß 6 von ihnen reoperiert werden mußten. In die Nachuntersuchung (mittleres Follow-up: 36 Monate, Spanne: 16–74 Monate) konnten 5 Patienten nicht einbezogen werden. Während der Follow-up-Periode verstarben 49% der Patienten. Nach 36 Monaten betrug die primäre Durchflußwiederherstellungsrate 51%, die sekundäre 69%, die Sanierungsrate im betroffenen Glied 87%. Statistisch gab es nach 36 Monaten bei der sekundären Durchflußwiederherstellungsrate einen Unterschied zwischen axillo-bifemoralen (87%) und axillo-uni-femoralem Bypass (56%) (p<0,01), aber hinsichtlich der Heilungsrate gab es zu diesem Zeitpunkt zwischen den beiden Bypass-Arten keinen signifikanten Unterschied (94% vs. 81%). Die postoperative Mortalitätsrate war bei 20 Patienten (40%), die wegen akuter Ischämie operiert worden waren, signifikant höher (10% vs. 0%); ebenso die Amputationsrate (20% vs. 6,6%); signifikant niedriger hingegen war die Durchflußwiederherstellungsrate nach Bypass (26% vs. 63%) (p<0,01) —im Vergleich zu 30 Patienten (60%), die wegen Claudicatio, Ruheschmerz oder trophischen Ulzera operiert worden waren. Nach unseren Untersuchungen sind die Ergebnisse bei axillofemoralen Bypassoperationen entscheidend abhängig von der Auswahl der Patienten gemäß klinischem Zustand und ischämischen Symptomen. Die Gesamtergebnisse nach axillofemoralem Bypass sind schlechter als nach aortofemoralem Bypass, und darum sollte die erstgenannte Operation nur bei Patienten angewendet werden, bei denen die Abklemmung der Aorta ein hohes Risiko darstellen würde.

Management of Carotid Dacron Patch Infection: A Case Report Using Median Sternotomy for Proximal Common Carotid Artery Control and In Situ Polytetrafluoroethylene Grafting

We report on a 58-year-old male who presented with an enlarging cervical hematoma 3 months following carotid endarterectomy with Dacron patch repair, due to septic disruption of the Dacron patch secondary to presumed infection. The essential features of this case are the control of the proximal common carotid artery gained through a median sternotomy, because the patient was markedly obese with minimal thyromental distance, and the treatment consisting of in situ polytetrafluoroethylene bypass grafting, due to the absence of a suitable autogenous saphenous vein. Median sternotomy is rarely required in case of reintervention for septic false aneurysms and hematomas following carotid endarterectomy but should be considered whenever difficult control of the common carotid artery, when entering the previous cervicotomy, is anticipated. In situ polytetrafluoroethylene grafting can be considered if autogenous vein material is lacking.

Hemangiopericytoma of the spleen

INTRODUCTION Hemangiopericytoma of the spleen is a very rare tumor, with 14 isolated reports. It was our aim to review our experience and compare it with all the reported cases in an attempt to standardize surgical treatment, adjuvant treatment and follow-up protocol of this infrequent condition. METHODS A consecutive case series study, with a mean follow-up of 44 months. Five patients (mean age, 49 years) underwent simple splenectomy for hemangiopericytoma limited to the spleen followed by adriamycin-based chemotherapy in one patient. RESULTS All the patients are alive and free from disease. CONCLUSIONS For tumors confined to the spleen, simple splenectomy can be considered curative, without any need for further adjuvant treatment. On review of the medical literature, cure can still be achieved with complete resection of recurrences, when feasible, with adjuvant chemotherapy being also indicated. The slow-growing pattern of the tumor suggests a 10-year follow-up.