Influence of genetic and environmental factors in peripheral arterial disease natural history: Analysis from six years follow up.

BACKGROUND: Peripheral arterial disease (PAD) is a disease affecting million of patients worldwide. Though traditional cardiovascular risk factors have been associated with the development of PAD, the possible existence of an inherited genetic predisposition to PAD has been investigated in few familial aggregation studies. A link between genetics and PAD may open new avenues for the prevention of this morbid and mortal disorder. AIM: The aim of this study is to investigate a possible role of some genetic determinant involving into coagulation and homocysteine metabolism in the progression of PAD. MATERIALS AND METHODS: We follow one-hundred patients affected by PAD for six years. We evaluated Ankle-Brachial Index (ABI) two times; first at the time of recruitment and then after six years, in order to assess the progression of disease. Genotypes for the genes of Factor V Leiden, Prothrombin or Factor II G20210A, Cystathionine Beta-Synthase 844ins68bp and Methylenetetrahydrofolate Reductase C677T was ascertained after taking blood samples. Chi-square test was performed to determinate the possible correlation of these genes and the most common environmental factors in the progression of PAD. RESULTS: Genetic disorders resulting in high level of homocysteina or thrombophilic phenotype are not so frequent. None among the genetic factors we considered were correlated with PAD. CONCLUSION: PAD is a chronic disease whose course can be slowed down especially with the control of environmental risk factors. Genetic analyses are not useful to determine the disease progression or its tendency to remain stable.

[Results of elective open surgery for juxtarenal aortic aneurysms]. / I risultati del trattamento elettivo in open surgery degli aneurismi juxtarenali dell'aorta.

Review of the most significant surveys (data base: Pub Med on September 2003) of elective open surgery for Juxtarenal aneurysms and personal results of 106 cases (9.3% of AAA consecutively operated in the last 11 yrs.) are reported. Mortality and morbidity are discussed related to: technique of aortic cross-clamping; protective measures on splanchnic and renal perfusion; risks from previous CAD and chronic renal failure. Over all, the main predictive factor is the accuracy of the selected technique, without any difference among different approaches, and the same results of infrarenal aneurysms can be obtained.

Experience with cyclosporine.

Six hundred thirty-eight cadaveric kidney transplant patients between 1983 and 2001 were treated with cyclosporine (CsA) for 87 +/- 58 months. Among 571 patients with follow-up greater than 12 months, the 15-year renal function was investigated to assess the probability of a >30% increase in serum creatinine (sCr) above the month-6 value (baseline) and the impact on graft survival. At 15 years, patient and graft survival rates were 82.7% and 56.1%, respectively, with a 19.5-year half-life (censored for deaths). The main causes of graft loss were chronic rejection (33.0%) and patient death (24%). Cardiovascular disease and neoplasms were the main causes of death. Renal function remained stable in 266 patients (46.6%) with excellent sCr values observed even after a 15-year treatment period. An increased sCr was observed in 305 patients (53.4%) with a 15-year probability of 74%. In 178 patients (59.3%) it was self-limited; their grafts are still functioning well. One hundred three patients (32.8%) lost their graft which was more likely when the sCr had increased >45%. Twenty-four patients (7.9%) died with a functioning graft. Multivariate analysis showed the progression of graft deterioration to be related to proteinuria (P<.0001), a late acute rejection episode (P<.002), or the extent of sCr increase (P<.008). In conclusion, the long-term use of CsA has allowed us to achieve excellent long-term patient and transplant survival rates. Our data indicate a high 15-year probability of an increased sCr, but the rate of progression is slow.

[Distal pancreatic resection with splenic preservation for metastasis of renal carcinoma diagnosed 24 years later from the nephrectomy]. / Pancreasectomia distale con preservazione della milza per metastasi di carcinoma renale diagnosticato a 24 anni di distanza dalla nefrectomia.

Renal cell carcinoma is a malignant tumor with a singular biological behaviour, presenting in some reported cases very late metastases. This report describes a case of solitary pancreatic metastasis from kidney carcinoma, operated on 24 years before, that appears exceptional because of the long disease-free period after nephrectomy and the unusual metastatic site. The 73-year-old woman concluded the follow-up several years before; she presented aspecific abdominal pain and ultrasonographic examination and CT-scan revealed the presence of a mass in the pancreatic istmus. The mass was excised with splenic preservation and was diagnosed to be a pancreatic metastasis from clear cell renal carcinoma. We discuss the diagnostic and therapeutic features of this tumors. It appears important to obtain the diagnosis preoperatively, because good results may be obtained with surgery, justifying an aggressive surgical approach.

Combined surgical approach for carotid and coronary stenosis. Sixty-four patients and review of literature.

BACKGROUND: The proper role of combined carotid endarterectomy (CEA) and coronary bypass (CABG) is still controversial. We contribute to the discussion through the critical evaluation of 64 consecutive patients, whose data have been collected in a prospective way. METHODS: Between 1990 and 1999, 64 patients presenting a critical coronary disease (unemendable by PTA) associated with severe carotid stenosis (= or >70% if symptomatic, = or >80% if asymptomatic), underwent combined CEA-CABG. Cardiological symptoms were evident in 90.6% of cases. Thirty-five patients (54.7%) had a three-vessel coronaropathy, 18 (28.1%) a two-vessel disease and 11 (17.2%) severe stenosis of the common trunk; furthermore 7 patients (10.9%) had a low ejection fraction (<50%). A positive neurologic history was present in 22 (44%) patients. Thirty-four patients (55%) had a carotid stenosis >90%; a significant disease of the contralateral carotid axis was observed in 53% of cases: stenosis >50% in 30 patients and thrombosis in 4. CEA was performed with somato-sensorial evoked potential monitoring. RESULTS: The hospital mortality rate was 6.2% (4 patients). The cause of death was cardiac in 2 cases (1 early bypass thrombosis and 1 irreversible coronary spasm) and related to a multiorgan failure in 2. The neurologic morbidity rate was 0%. CONCLUSIONS: Our data highlight that in these high-risk patients the combined approach dramatically reduces the stroke risk although the mortality rate is still higher than that observed after CEA or CABG.

Is there an association between Helicobacter pylori cytotoxin Cag A seropositivity and risk for gastric cancer?

BACKGROUND: Since discovered in 1990, Cag A, a protein expressed by specific strains of Helicobacter pylori, was thought able to explain why only a few Helicobacter infected patients develop peptic diseases and gastric cancer. However, clinical trials provide discordant results. MATERIALS AND METHODS: In this study we evaluate Helicobacter pylori and Cag A seropositivity in 35 cancer affected patients, in 36 gastritis affected patients and in 40 healthy blood donors by means of two commercially available fluorescence enzyme-immunoessay (ELISA). RESULTS: Odds ratios determination strongly suggests that Cag A bearer Helicobacter strains play a pathogenetic role in gastric diseases (OR 4.23, 95% CI 3.22-5.24 for cancer versus healthy volunteers, OR 3.2, 95% CI 2.19-4.21 for gastritis versus asymptomatic patients), but is unable to demonstrate a direct carcinogenic activity (cancer-gastritis difference is not significant: OR 1.32, 95% CI 0.39-1.25). CONCLUSIONS: Cag A seropositivity can be considered a risk factor for peptic disease, and only indirectly for gastric carcinoma. The paper also discuss some sampling, laboratory and statistical bias that can explain a wide eterogenity of the results reported in the literature.

Right subclavian artery aneurysms of fibrodysplastic origin: two case reports and review of literature.

Right subclavian aneurysms involving the intrathoracic portion of the artery are rare and those of fibrodysplastic origin are mentioned in literature only as sporadic cases. In this article, we present two cases of this uncommon pathologic condition and discuss problems concerning diagnostic tools and technical choices. The two patients underwent a successful vascular graft substitution; an echo-Doppler scan revealed that they had no disease 1 and 2 years after the operation.

Suprarenal aortic cross-clamping in elective abdominal aortic aneurysm surgery.

INTRODUCTION: this retrospective study was undertaken to evaluate whether suprarenal aortic cross-clamping increased the perioperative mortality and morbidity as compared to infrarenal clamping, in order to create the rationale for a more extensive application of this apparently more traumatic manoeuvre. MATERIALS AND METHODS: in a series of 734 elective aortic substitutions for abdominal aneurysm (AA), performed consecutively from January 1992 to June 1999, aortic cross-clamping was performed at a suprarenal level in 56 juxtarenal aneurysms, i.e. aneurysms extending to the lower edge of the renal arteries (8%, Group 1), and at an infrarenal level in 634 subrenal aneurysms (92%, Group 2). When analysing preoperative data, the diameter of aneurysms was larger in Group 1 than in Group 2 (p<0. 005). No significant differences were found between the two groups as regards age, sex, postinfarction cardiomyopathy, chronic obstructive pulmonary disease, chronic renal insufficiency and ASA classification of operative risks. RESULTS: the average time of renal exclusion in the juxtarenal aneurysms was 20 min (range 12-35 min). There is no difference between the two groups as regards the time of aortic clamping (mean 50 vs. 60 min) or the need for homologous blood transfusion (7% vs. 11% of patients). Perioperative (30 days) mortality did not differ: 3.6% vs. 1.9% (n.s.); nor did the incidence of acute myocardial infarction (3.6% vs. 2.3%). Renal function deteriorated in 8 (14%) vs. 0 (0%) (p<0.001) and 1 patient (2%) required permanent dialysis, as compared to 0% in Group 2. The incidence of ischaemic colitis was also significantly higher in Group 1 (7%) than in Group 2 (2%, p<0.01). CONCLUSION: this data shows that suprarenal clamping, which is necessary for the radical treatment of juxtarenal aortic aneurysms, can be performed with a low risk.

A prospective randomized trial on azathioprine addition to cyclosporine versus cyclosporine monotherapy at steroid withdrawal, 6 months after renal transplantation.

BACKGROUND: Many attempts have been made to withdraw steroid therapy in renal transplant patients in order to avoid its many side effects. Results have been, so far, controversial. In this randomized prospective study, we compare the efficacy of azathioprine adjuncts to cyclosporine at the time of steroid withdrawal, 6 months after transplantation, versus Cyclosporine monotherapy, in preventing acute rejection. METHODS: One hundred and sixteen kidney transplant patients with good and stable renal function (creatininemia <2 mg/dl) received, in the first 6 months, cyclosporine + steroid. They were then randomized into two groups (A and B), and steroid therapy was withdrawn over 2 months. Group A (58 patients) continued on cyclosporine monotherapy, whereas group B (58 patients) added azathioprine (1 mg/kg/day) at the beginning of randomization and continued on cyclosporine + azathioprine. In both groups, patients resumed steroid therapy at the first episode of acute rejection. Follow-up after randomization was 5.3+/-1.6 years. RESULTS: After 5 years, the incidence of steroid resumption was 57% in group A and 29% in group B (P<0.02); of those, 68% and 88% of them were within 6 months from randomization. Anti-rejection therapy was always successful. Five-year patient and graft survival rates were 90% and 88% in group A and 100% and 91% in group B. Creatininemia did not differ, at follow-up. Side effects differed only for mild and reversible leukopenia caused by azathioprine in group B. CONCLUSION: Cyclosporine plus azathioprine is more effective than cyclosporine monotherapy in reducing the incidence of acute rejection after steroid withdrawal. Graft loss as a result of chronic rejection, mild in both groups, did not differ. Steroid withdrawal is feasible and advantageous, and the addition of azathioprine allowed 71% of our selected patients to remain steroid-free.

Limb salvage in lower-extremity sarcomas and technical details about vascular reconstruction.

Vascular surgery may allow limb salvage when a sarcoma of the lower limb involves the main vascular bundle. We present our experience and describe the techniques which have been employed for such surgery. From October 1995 to April 1999, vascular surgery procedures were employed in seven patients with sarcomas of the thigh: two complete subadventitia dissections of the main vascular trunks, four artery replacements (two polytetrafluoroethylene [PTFE] grafts and two autologous saphenous grafts), and five venous reconstructions (all with autogenous saphenous graft: three substitutions; two distal transpositions with one external rigid support at the anastomosis). Clinical and instrumental (sonogram, computed tomography [CT] scan, echodoppler) follow-up was carried out at 3, 6, and then every 12 months after surgery (mean, 25 months; range, 6-53 months). Operative mortality and morbidity were nil. All the grafts were patent (one arterial thrombosis was successfully treated on the first postoperative day). The functional result was good in six patients and fair in one. Two patients died, 24 and 13 months after surgery, with disseminated disease, but had no local recurrence. Five patients are alive and disease-free. Vascular techniques allow limb salvage with en-bloc resection of sarcomas of the thigh involving the main vessels. Venous reconstructions are indicated after removal of both the superficial and deep femoral veins. We suggest limiting the number of anastomoses (two transpositions in our series) and using external rigid support in those patients with a small saphenous vein graft (one patient in our series).

Complete in vitro prosthesis endothelialization induced by artificial extracellular matrix.

This report presents our research on the conditions necessary to substain optimal in vitro prosthetic endothelialization using human endothelium cultures. Human vein endothelial cells were seeded at a concentration of 3 x 10(5)/cm2 in a gelatinized Dacron patch graft coated with a commercial collagen film, using a solution of fibrin glue. Endothelium adhesion, proliferation, and survival were measured by [3H]thymidine incorporation, after 7 days of incubation. Finally, the morphology of prosthetic endothelialization was analyzed by scanning electron microscopy. We observed that the Dacron patch grafts coated with collagen film were able to promote endothelialization better than the prostheses coated with highly concentrated collagen solution or gelatin. We therefore concluded that the collagen film that supports endothelial cell adhesion and proliferation uniformly covers the entire synthetic endoluminal surface of the Dacron graft, thus preventing endothelial cell alterations induced by direct contact with the synthetic prosthetic surface.

Phenotypic and functional characteristics of tumour-derived microvascular endothelial cells.

We recently developed a method for the isolation and purification of tumour-derived endothelium. In this study the phenotypic and functional properties of human tumour-derived microvascular endothelial cells (TdMEC) were examined. Endothelium obtained from human adrenal gland specimens (HAMEC) was used as a reference microvascular endothelial cell population. TdMEC formed a confluent monolayer with the typical morphological appearance of endothelium and were positive for endothelial markers such as Ulex-1 lectin, CD31 antigen, von Willebrand Factor and VE-cadherin. The addition of acidic Fibroblast Growth Factor (aFGF), basic FGF (bFGF) or Vascular Endothelial Growth Factor (VEGF) substantially improved proliferation of TdMEC; and kidney carcinoma derived endothelial cells were more responsive to FGFs, whereas glioblastoma derived endothelial cells greatly responded to VEGF TdMEC expressed high levels of the VEGF receptors, KDR/flk-1 and Flt-1, as shown by northern blot analysis. TdMEC expressed the adhesion molecules ICAM-1, VCAM-1 and E-selectin that could be further increased by exposing TdMEC culture to interleukin-1. All the TdMEC expressed interleukin-8 mRNA. These findings show that TdMEC in vitro maintain several of the features described for microvasculature. Thus, TdMEC represent a useful tool to study markers for tumor vasculature.

[Splanchnic aneurysms: 10 treated cases and review of the literature]. / Gli aneurismi splancnici: 10 casi trattati e revisione della letteratura.

The splanchnic aneurysms, which are complicated by rupture in 25% of cases with a mortality of 25-70%, are usually a surprise during diagnostic tests for other abdominal pathologies or emergency laparotomies. 10 cases treated (8 in elective and 2 in emergency surgery) are presented here: the aneurysm was in celiac trunk (1 patient), common hepatic artery (1 pt.), hepatic artery (2 pts.), gastroduodenal artery (1 pt.), superior mesenteric artery (1 pt.), inferior pancreaticoduodenal artery (1 pt.), right colic artery (1 pt.) and inferior mesenteric artery (1 pt.). There were 1 case of Marfan syndrome and 9 cases of atherosclerosis, 4 of which arteries presenting hyperdynamic flow consequent to occlusions of the superior mesenteric artery and/or the celiac trunk. The 2 cases operated on for hemoperitoneum underwent aneurysmectomy and ligation of the inflow vessels (1 death from pulmonary embolism on 5th postoperative day), whereas the 8 cases electively treated (with no deaths and I case of transient diarrhoeal syndrome) underwent 4 aneurysmal resections with end-to-end arterial reconstruction, 3 PTFE-graft substitutions and 1 autologous saphenous vein substitution. At follow-up (12-74 months; mean 30.6) all the reconstructions resulted successful. These data confirm the consistent indications of the recent Literature suggesting the indication to the surgical treatment of the incidental aneurysms in the splanchnic area.

[Carotid endarterectomy in patients with neurological non-side related (NSRS) symptoms]. / La endoarterectomia della carotide in pazienti con sintomi neurologici non lateralizzati (NSRS).

Out of 970 carotid endarterectomies (CE) performed for high-grade (> 80%) stenosis of the internal carotid artery (ICA) until 1995, 147 patients with neurological non side-related symptoms (NSRS) and without any cardiac, ocular or vestibular significant pathology have been evaluated, analyzing the medium and long-term functional results (mean follow-up 37.6 months) related to the morphological status of the ICA contralateral and the vertebral arteries. NSRS disappeared in 126 pts (85.71%): contralateral ICA was non-stenotic in 32 cases (25.39%), stenotic < 75% in 68 cases (53.96%), stenotic > 75% in 7 cases (5.55%) and occluded in 19 cases (15.09%); vertebral arteries were pathological in only 6 cases (4.75%), among which 4 were on the same side and 2 on the opposite side of CE. NSRS persisted in 20 pts (13.6%): contralateral ICA was non-stenotic in 5 cases (25%), with a stenosis < 75% in 11 cases (55%) and with stenosis > 75% in 4 cases (20%); vertebral obliterative lesions were 3 (15.78%), among which 1 on the same and 2 on the opposite side of CE. No one statistical comparison among the groups of cases obtained on the ground of the status of ICA and vertebral arteries were significant (p always > 0.05 at chi-square analysis). Authors' data confirmed that high grade stenoses of ICA can cause NSRS and that CE--always performed at the aim to prevent major neurological attacks--can relieve also these functional disorders in the most of cases, independently from the status of the contralateral ICA and the vertebral arteries.

[Total pancreatectomy. Which indications?]. / Pancreatectomia totale. Quali indicazioni?

This a review of the different topics held by literature for and against total pancreatectomy (TP) for adenocarcinoma of the pancreas. Technical and oncological aspects are discussed as are the metabolic effects of TP; metabolic data of our series of 6 TP are also referred. Postoperative mortality and morbidity decreased to less than 5% during the last decade both for TP and the Whipple procedure; long term survival is also similar for the two procedures. Even if the metabolic consequences of both exocrine and endocrine function deprivation are generally well compensated, they can still threaten the patient's life; furthermore their long term effects are only partially known. These are the reasons that force most authors to choose TP only in selected patients in which a multifocal neoplasia is demonstrated or whose pancreatic remnant is particularly soft and friable with high risk of pancreatojejunostomy complication. A pancreatic remnant in fact grants the hormonal milieu that makes easy the pharmacological control of any pancreatic function deficiency.

Temporary axillo-femoral bypass graft for renal transplant protection during aortic aneurysm repair.

Aortic surgery in renal transplant recipients requires a method of maintaining intraoperative graft perfusion. Here we present a case in which temporary axillo-femoral bypass was used to perfuse a renal transplant during the aortic aneurysm repair; the rationale of inserting the temporary axillo-femoral bypass on transverse arteriotomies is pointed out. Other methods of renal graft perfusion are discussed.