Effects of defibrotide in patients with chronic deep insufficiency. The PROVEDIS study.

AIM: In the present study the effect of defibrotide, an antithrombotic and profibrinolytic agent, was investigated in patients with chronic venous insufficiency (CVI) due to deep vein obstruction and/or reflux (chronic deep vein insufficiency, CDVI). METHODS: The study was a multicenter, randomized, double blind placebo controlled trial in which only patients with CDVI confirmed by ultrasound were enrolled. All patients were treated with adequate elastic compression and randomized to receive either oral defibrotide (800 mg/die) or matching placebo for 1 year. Patients with active or previous leg ulcer were excluded. RESULTS: A total of 288 patients were randomized and 159 completed the study. At baseline ultrasound investigation, obstructive changes were found in 2/3 of all patients thus ascertaining a post-thrombotic syndrome (PTS). The primary endpoint, ankle circumference, was significantly reduced under defibrotide from day 120 throughout 360. Scores for pain and edema were improved. The number of episodes of superficial thrombophlebitis and deep vein thrombosis was significantly lower under defibrotide (n=2) than under placebo (n=10). The majority of these events occurred in the subset of patients with documented PTS. CONCLUSION: Treatment with defibrotide in addition to elastic compression in patients with objectively assessed CDVI, mostly due to PTS, resulted in clinical benefits and prevented thrombotic complications harmful to the limb conditions.

[Thoraco-abdominal aneurysms of type IV]. / Aneurismi toraco-addominali di IV tipo.

AIM OF THE STUDY: Aims of the study were: 1. to evaluate the results of surgical treatment of type IV thoraco-abdominal aneurysms (TAA), with relationship to other types, 2. to evaluate results obtained with an approach different from the traditional thoraco-phreno laparatomy, with specific attention to postoperative respiratory function. MATERIAL AND METHODS: We have retrospectively compared type IV TAA with all other types of thoraco-abdominal aneurysms electively treated between January 1st, 1994 and May 31st, 2003. Data on perioperative mortality, spinal cord ischemia and renal failure (both temporary and permanent) occurring in the first 30 postoperative days were considered. Protection from spinal cord ischemia was accomplished through liquor drainage and prostaglandin E1 (PGE1) infusion. When the aneurysm extension was limited to the celiac axis an extrapleuric access with removal of XI rib was performed. In this subgroup of patients we have considered postoperative recovery time of respiratory function (intubation time, number of days in intensive care unit, postoperative pulmonary complications) postoperative renal failure, perioperative mortality and morbidity. RESULTS: Seventy-eight TAA have been treated in the period of time of the study. Twenty cases were type IV TAA (25.6%) of which 2 due to chronic dissection. Cumulative postoperative mortality has been 19.2%. The single perioperative death in the group of type IV TAA (5%) occurred in post-operative day 15 for multiple organ failure. No spinal cord ischemia occurred in this group. Temporary renal failure occurred in 3 cases (15%) with one case requiring dialysis. In 10 cases (50%) an extrapleuric access with removal of XI rib was performed, with adequate control of the proximal aorta. Postoperative respiratory failure requiring and intubation time longer than 12 hours occurred in 2 cases (20%). In the remaining 8 cases the mean intubation time was 5.3 hours (range 4-8 hrs). Tracheostomy was not necessary in any case. Mean time of intensive care unit stay was 3.5 days (range 0-15 days). CONCLUSION: The appropriate treatment of type IV TAA leads to low mortality and morbidity with results similar to those of pararenal aneurysms rather than those of other TAA forms. Left extrapleuric access when feasible allows faster recovery of a normal respiratory function.

Ruptured pancreaticoduodenal artery aneurysm. A case report and review of the literature.

Pancreaticoduodenal artery aneurysms (PDAA) are very rare (2% of the visceral aneurysms) but characterized by a high mortality rate if ruptured. Here a case of ruptured PDAA with an atypical clinical presentation that simulated an acute hepatobiliar syndrome is reported. A 60-year-old female presented with epigastric pain, nausea, gastric vomiting, elevated levels of hepatic enzymes, normal hemoglobin and cholelithiasis on echography. With persistent pain and progressively decreasing hemoglobin, an urgent contrast computed tomography was performed and revealed a large retroperitoneal hematoma that appeared to come from a branch of the superior mesenteric artery (SMA). A selective SMA-angiography showed a small aneurysm of the antero-superior pancreaticoduodenal artery with signs of hemorrhage. The patient underwent surgical ligature of the PDAA, after superselective transcatheter arterial embolization appeared technically impossible. The postoperative period was characterized by a progressive normalization of the hepatic values and hemoglobin and a post-operative angiogram confirmed the total exclusion of the PDAA and the integrity of the posterior pancreaticoduodenal arch. The pre-operative diagnosis of PDAA is usually very difficult. Symptoms can be vague or misleading, as in our case. Angiography is the most accurate diagnostic tool to locate a ruptured PDAA. Moreover, it can be immediately used for urgent endovascular treatment. Post-operative angiography is essential to confirm the total exclusion of the PDAA and demonstrate visceral circulation.

[Immunologic problems in vascular homografts]. / Problematiche immunologiche degli omoinnesti vascolari.

Fresh arterial homografts are immunogenic, inducing in recipient a strong immune response specifically directed against the antigens of the donor graft. The initial immune response seems to be cellular (lymphocytotoxic) and the late reaction humoral (antibody), even if they are strictly correlated. Immunosuppressive therapy reduce the immune reaction, but this response is dose-related. Implanted arterial homografts induce a donor-specific response similar to chronic reaction, which occurs in the recipients of vascularized solid-organ allografts. Therefore, in arterial transplantation, ABO compatibility and negative crossmatch should be respected. Effort should be made to curb the immune response by prospective cross-matching, immunosuppressive therapy and preoperative manipulation of homografts to reduce their antigenicity.

Endovascular repair as first-choice treatment for anastomotic and true iliac aneurysms.

PURPOSE: To report our experience with the endovascular repair of iliac aneurysms secondary to aortoiliac bypass grafting. METHODS: Thirteen patients (12 men; age range 62-86 years) with histories of aortoiliac reconstructions were treated with endovascular stent-grafts for 11 false and 2 true iliac aneurysms that averaged 5.2 cm in diameter (range 3.0-7.0). Via a percutaneous access and 9-F or 12-F sheaths, Passager or Wallgraft stent-grafts were delivered to exclude the aneurysms. RESULTS: Twelve (92%) of 13 interventions were completed satisfactorily; 1 procedure for a true iliac aneurysm was converted to traditional bypass grafting. Two patients underwent additional surgical procedures. The average hospital stay for the patients with endovascular repairs only was 3 days (range 2-5). After a mean follow-up of 28 months (range 17-40), no complication or endoleak has been detected in any patient, and all endografts are patent. CONCLUSIONS: Endovascular repair is an effective treatment for secondary aneurysms arising after aortoiliac surgery. It is less invasive and involves a shorter hospital stay. Endovascular repair should be the first choice treatment for iliac aneurysms.

Immune response following fresh arterial homograft replacement for aortoiliac graft infection.

INTRODUCTION: this prospective study defines the immune response to fresh arterial homograft replacement for graft infection. MATERIALS AND METHODS: ten patients who underwent ABO-compatible homograft transplantation were studied for anti-HLA antibody production, and CD3-CD4-CD8-positive lymphocytes subset. Immunological studies were performed preoperatively, and at early (1, 3, 7 days) and late (1, 3, 6, 12, 18, 24 months) follow-up. All patients received immunosuppressive treatment with cyclosporine (1-3 mg/kg/day). Abdominal CT scans were performed postoperatively at the 1, 6, 12, 18, 24 months follow-up. RESULTS: preoperatively, antibodies could not be detected. Postoperatively, as from 1st month post-transplant, a progressive increase in % PRA was observed in all patients, up to the 12th month of follow-up. Subsequently, at 18 and 36 months, a progressive decrease in % PRA was detected. Data showed that the recipient antibodies were directed against donor-specific antigens. During the immediate postoperative period (1, 3, 7 days) CD3- and CD4-positive T lymphocytes slightly increased, whereas CD8 simultaneously decreased. Later, CD3 and CD4 progressively decreased and CD8 increased. Clinically, all patients were cured of infection at late follow-up. CT scans showed thickening of the aortic wall (range: 2.5-4.5 mm), with no signs of aneurysmal degeneration. CONCLUSIONS: fresh arterial homografts are immunogenic. Implanted homografts induce a strong anti-HLA antibody response, similar to chronic rejection, in spite of immunosuppressive treatment.

Aorta transplantation in man: clinical and immunological studies.

Aortic transplantation has progressively gained interest over the last few years and it is becoming a first choice indication in the substitution of infected prostheses. The most frequent complication in long-term vascular outcome (wall thickening, aneurysmatic dilation, stenosis), may occur through an immunological mechanism. In this study we investigated nine recipients, aged 48 to 65 years, of aorta segment replacement for anti-HLA antibody production (specificity and Ig class), CD3-CD4-CD8 T cell subpopulation dynamics and aorta wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were detected 1, 3 and 6 months after transplantation and persisted at a high concentration for at least 1 year. Furthermore, the absolute number of CD3, CD4 and CD8 positive lymphocytes increased progressively after aorta allograft. Tomography scanning showed a progressive thickness of the aorta wall. We can speculate that these anti-HLA antibodies in the recipients have the potential to harm the implant; therefore, aorta allograft should involve the induction of immunological tolerance by appropriate immunosuppressants.

Intraoperative assessment of cerebral ischaemia during carotid surgery.

BACKGROUND: This study aimed to evaluate the reliability of somatosensory evoked potentials (SEPs) in identifying clamping ischaemia during carotid surgery under general anaesthesia. METHODS: We reviewed the records of 196 consecutive carotid endarterectomies (CEA) performed under general anaesthesia, out of 1550 patients operated on between 1975 and 1993. SEPs were monitored after contralateral median nerve stimulation at the wrist in all patients. Moreover they received an intravenous bolus of 2500 IU of heparin and the stump pressure was measured. A completion angiography was performed in all patients. An intraluminal shunt was inserted when the amplitude of the N20-P25 SEPs complex decreased by more than 50% of pre-clamping value (pathologic SEPs) or when a preoperative CT-scan showed an ischaemic area in the contralateral hemisphere. In some patients the shunt was not inserted because of technical difficulties or because the pathological SEP complex decrease developed when the suture of the arteriotomy was almost complete. RESULTS AND CONCLUSIONS: As the preclamping amplitude (Ab) of N20-P25 was extremely variable, ranging from 0.9 and 7.5 microV, we adopted the ratio: deltaA=(At-Ab)/Ab (At=amplitude measured during clamping every 2 min at time t). Mean decrease of deltaA measured in the whole group ranged between 15% and 20%, but mean deltaA values in patients with pathological SEPs were around 60%. Even patients with positive CT-scans or with a back-pressure lower than 50 mmHg developed a mean deltaA decrease of about 20%. A pathological SEP was present in 50 patients, but developed in only 12 during the clamping trial. An intraluminal shunt was inserted in 22 cases; the other patients received pharmacological treatment with anaesthetic or vasoactive drugs. Among the patients with pathological SEPs, 3 presented postoperative symptoms related to carotid cross-clamping; only 1 of these was shunted but without SEPs normalisation. No patients with normal SEPs developed a postoperative neurological deficit, giving a reliability of 86.7%, a sensitivity of 100% and a specificity of 86.5%.

Mismatch-specific anti-HLA antibody production following aorta transplants.

In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.

Early and long-term results in the surgical treatment of juxtarenal and pararenal aortic aneurysms.

OBJECTIVE: Surgical treatment of juxtarenal and pararenal aortic aneurysms (JPAA) provide technical problems which may influence short- and long-term results; however few surgical series have been published on this subject. The purpose of this study is to observe predictors of results in a series of JPAA and to analyse long-term survival of these patients. DESIGN, MATERIALS AND METHODS: Patients' epidemiology and surgical technique used in all cases of JPAA were reviewed and correlated with early results through logistic regression analysis. Early results were compared with those of infrarenal aneurysms (IAA) treated in the same period. Long-term results were obtained through our surveillance protocol (3 months after surgery and yearly thereafter) and calculated by life-table analysis. RESULTS: Fifty JPAA were identified over a total of 1450 aortic aneurysms (3.4%). Surgical approach was: anterior transperitoneal in 38 cases (96%), extended retroperitoneal in one (2%) and thoracoabdominal in one (2%). Suprarenal control was obtained in all cases; at the diaphragm in seven (14%), above both renal arteries in 17 (34%) and above one renal artery in 16 cases (32%). Renal revascularisation was performed in 11 cases (22%; nine unilateral and two bilateral). Overall perioperative mortality was 12%, significantly greater than mortality of IAAs: 50/1400, 3.5% (p < 0.02). Mortality in elective cases was 3/42, 7.1% and in ruptured JPAA 3/8, 37.5%. Independent predictors of early mortality were aneurysm rupture, age > 70 years, and coronary artery disease. Gender, smoking, hypertension, diabetes mellitus, site of proximal aortic clamping, type of aortic reconstruction, visceral revascularisation, and technically difficult cases were not associated with early mortality. Three and five year survivals were 66.8% +/- 9.93 and 40.0% +/- 12.64, respectively. CONCLUSIONS: Surgical treatment of JPAAs is associated with a higher risk of early mortality compared to IAAs and reduced long-term survival. Indications for surgery in JPAAs should consider the risk/benefit ratio rather than focusing on technical aspects which do not seem to significantly influence results.

[Carotid restenosis: clinical significance and indications for reintervention]. / Le restenosi carotidee: significato clinico e indicazioni al reintervento.

Carotid restenosis is defined as a new > 50% diameter-reducing lesion present in sites of previous surgery. The clinical aspects of this complication are strongly connected with their anatomopathologic evolution: fibromuscular hyperplasia in early recurrent disease, atherosclerotic degeneration in the later lesions. Routine postendarterectomy duplex surveillance is able to detect this pathologic evolution. On 570 surgically treated carotid artery a postoperative duplex surveillance was made at 3, 6, 12 months and then yearly. Totally 42 cases of recurrent stenosis (7.3%) were present: in seven cases (16.6%) with a complicated restenosis the patients were symptomatic. In 27 cases (64.2%) restenosis was < 75%, in 8 cases (19.2%) > 75%. Indication to surgery was given for all the complicated restenosis and for high grade stenosis (> 75%). In the 27 cases of restenosis < 75% a conservative therapy together with duplex surveillance was applied: in none of these cases the restenosis increased in an average follow-up of 13.7 months. In the reoperated cases we didn't observe any mortality nor postoperative stroke. With regard to their mainly hyperplastic origin, carotid restenosis are low symptomatic and with a quite benign evolution. Surgical reintervention is to be limited to the symptomatic cases and to the asymptomatic high grade stenosis cases. A particular attention should be reserved to the morphologic characteristics of the lesion in order to detect the atherosclerotic degeneration that might cause cerebral symptoms.

Effects of ischemia on the human pancreas.

BACKGROUND & AIMS: Patients undergoing cardiac surgery frequently have pancreatic damage; several factors, including tissue hypoperfusion, have been implicated. The aim of this study is to better understand the effects of decreased blood supply on human pancreas. METHODS: Twenty-one consecutive patients undergoing surgery for thoracic or thoracoabdominal aortic aneurysm were studied. During surgery, the descending thoracic aorta was cross-clamped for a mean of 44 minutes (range, 15-85 minutes). Effects of the resultant pancreatic ischemia were assessed by examining the patients daily for evidence of acute pancreatitis for at least 20 days after surgery and by determining serum concentrations of amylase, pancreatic isoamylase, and lipase before clamping the aorta and at varying intervals after its release (1, 2, and 6 hours during the first day and once daily for the following 6 days). RESULTS: One patient died of acute necrotizing pancreatitis. None of the others had symptoms of pancreatitis postoperatively, but all showed a significant increase in serum pancreatic enzyme concentrations soon after declamping; this peaked about 24 hours later and persisted for all 7 days of the study. A significant relationship was found between the increase in pancreatic enzyme concentrations and the aortic clamping time. CONCLUSIONS: Acinar cell injury is a constant, rapidly appearing consequence of severe pancreatic ischemia, even that of brief duration; acinar cell injury is usually subclinical but may also present as severe acute pancreatitis.

Extracranial internal carotid artery aneurysms: results of a surgical series with long-term follow-up.

PURPOSE: The purpose of this study was to analyze mode of presentation, surgical treatment, and early and long-term results of a series of extracranial internal carotid artery aneurysms (EICAA). METHODS: A retrospective analysis was performed on all cases treated for EICAA in a single institution from March 1974 to March 1995. Patient follow-up was obtained by a surveillance protocol, with duplex scanning performed 3 months after surgery and yearly thereafter. RESULTS: Twenty-four EICAA in 20 patients were treated over a 21-year period. The cause was fibromuscular dysplasia in 12 cases (50%), nonspecific "atherosclerosis" in nine (37.5%), previous carotid artery surgery in two (8.3%), and trauma in one case (4.1%). Neurologic symptoms were present in a total of nine cases (37.5%) and were hemispheric in seven (29.1%) and nonhemispheric in two (8.3%). Operative techniques were performed with patients receiving general anesthetic and included aneurysm excision with internal carotid artery reanastomosis (8 cases [33.3%]) or reimplantation onto the external carotid artery (1 case [4.1%]); interposition graft (10 cases [41.6%]), 7 veins, 3 polytetrafluoroethylene) or simple aneurysmectomy and closure of the wall defect either with (3 cases [12.5%]) or without (2 cases [8.3%]) a patch. Elective surgery was performed in 22 cases, with a 0% mortality rate and 4.5% stroke rate. Emergency operations were performed in two cases of ruptured aneurysms (one spontaneous and one iatrogenic); one patient (50%) died. Cranial nerve morbidity occurred in five cases (20.8%). Mean follow-up was 96.7 +/- 88.15 months (range 4 to 240 months) and included 2 of 7 (28%) complications in saphenous vein grafts, 1 (4.1%) late transient ischemic attack, and a recurrent aneurysm after 19 years. CONCLUSIONS: Symptoms and potential complications caused by EICAA suggest a broad surgical indication. EICAA can be treated safely because of the good early and long-term results.

Prophylaxis of graft infection with rifampicin-bonded Gelseal graft: 2-year follow-up of a prospective clinical trial. Italian Investigators Group.

Between March 1991 and June 1992, 600 patients were treated with mono-, bifemoral or iliofemoral arterial graft revascularization for occlusions and/or aneurysms. The patients were divided into two groups: group A (n = 296) received a Gelseal Vascutek graft immersed for 15 min before implant in a solution containing 1 mg/ml rifampicin; group B (n = 304) received an untreated Gelseal Vascutek graft. Both groups received perioperative antibiotic treatment with cephalosporins. Clinical follow-up was performed at 1, 6, 12 and 24 months after surgery to exclude signs of graft infection. Statistical analysis (X(2)) of pre-, intra- and postoperative risk factors showed both groups to be well matched. Among 600 patients treated, the 2-year follow-up showed 12 cases of graft infection (2.0%): five in group A (1.7%) and seven in group B (2.3%) (P = n.s.). All cases of graft infection originated in the groin and Staphylococcus aureus was isolated in 50% of cases. Statistical analysis (Mann-Whitney U test) showed a significant prevalence of lymphatic complications and immediate redo surgery in patients with graft infection. Of the 12 cases with infection, one was lost to follow-up, three were treated with total graft removal, six with partial graft removal and two with conservative therapy: there were no deaths. In spite of the relatively limited series and follow-up, no statistically significant difference emerged from the clinical use of vascular grafts pretreated with antibiotics.