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 They were then randomized into two groups (A and B), and steroid therapy was withdrawn over 2 months.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.

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.

Surgery for obstructive lesions of the main trunk of the renal artery. A review of the literature and personal experience of 41 operated patients.

Today, surgical revascularization of the renal artery seems to maintain interest in the therapy of renovascular hypertension and chronic ischemic nephropathy because both medical therapy and angioplasty show limits and inconveniences. The authors present here their experience of 45 revascularized renal arteries in 41 patients and they discuss early and late morphological and functional results related to isolated arterial renal pathology (Group 1 of 23 patients) and associated to aorto-iliac pathology (Group 2 of 18 patients). Mortality related to arterial renal reconstruction was nil. There were 3/45 arteries (6.6%) with early thromboses and 4/32 (9.3%) with late thromboses. Early functional results, with respect to renovascular hypertension and/or chronic ischaemic renal insufficiency, showed 16/41 (39%) healed patients, 16/41 (39%) improved patients and 9/41 (22%) unvariated patients. Late results among 28 observed patients (average follow up at 49 months, range from 18 to 144 months) showed 14/28 (50%) healed patients, 11/28 (39%) improved patients and 3/28 (11%) unvariated patients. Results of the Group I were significantly better than results of Group 2 with regards to healed patients (p < 0.01) but not summarizing healed and improved cases. These data have been discussed in comparison with the Literature review of 46 references.

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.

[Bifocal lesion of striated muscle (hamartoma or focal myositis) in the course of Proteus syndrome]. / Lésion musculaire striée bifocale (hamartome ou myosite focale) au cours d'un syndrome de Protée.

We report a case of bifocal recurrent lesion developed in muscles of the left thigh in a 5 year-old-girl with Proteus syndrome (rare congenital hamartomatous disorder). We discuss the diagnosis of focal myositis versus hamartoma. The clinical and morphological features favour the second hypothesis.

[Extra-cardiac rhabdomyoma of the fetal type]. / Rhabdomyome extra-cardiaque de type foetal.

Rhabdomyomas are benign tumors of striated muscle. They are distinguished by topographic data: cardiac or genital and by histological criteria: foetal or adult type. The foetal type is the most heterogeneous, with either a majority of immature cells or a mixture of maturing elements. This diversity has led to distinguish immature (or standard) foetal Rhabdomyomas from intermediate foetal Rhabdomyomas. One observation of this last type is reported. The authors highlight the essential characteristics of foetal Rhabdomyomas, however the exact meaning remains unclear: an anomaly in the differentiation of the striated muscle? or a true tumoral process through genetic anomaly?

Early and long-term prognostic factors after liver resection for HCC.

The Authors discuss the principal early and long term predictive factors after liver resection in patients with hepatocellular carcinoma (HCC). The Authors report (131 cases) early mortality as 7.6%, entirely confined in the group, numerically prevalent and affected by cirrhosis. None of the 50 patients with chronic hepatitis (29 cases) or normal liver (21 cases) died after hepatic resection. Mortality is higher in Child B patients (20.7%) and in cases in which a massive haemotransfusion was given (p < 0.05), apart from the width of resection and from the number of hepatic resections. None of 41 cirrhotic Child A patients undergoing a limited hepatic resection (< or = 1 segment) died during the perioperative period. In the group of patients which survived to the resection, global survival at 5 years was 45%. The most important prognostic factor is local recurrence while cirrhosis and the degree of liver failure are not statistically significant. No feature can identify a subgroup of patients with a higher risk of recurrence, which is observed in 52% of patients with a follow up observation after more than 1 year. Among the 29 patients alive after more than 4 years from liver resection, only 11 didn't have local recurrence. The others were treated with iterative hepatic resections or with radiological techniques. In conclusion, the present experience suggests that, in selected cases, hepatic resection could be a low risk therapy (in cirrhotic patients as well). The long term results could improve with an aggressive attitude towards recurrence.

[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.

[Indications and short and medium time results of crossover bypasses in the treatment of obstructive arteriopathies of the lower limbs]. / Indicazioni e risultati a breve e medio termine dei pontaggi cross-over nel trattamento della arteriopatia ostruttiva degli arti inferiori.

The authors evaluate the indications, the hemodynamical aspects, the short and medium term results over their track record of 49 crossover bypass (44 dacron and 5 PTFE grafts) performed between 1981 and 1993. Crossover bypass grafts were mainly inserted for unilateral iliac arterial disease in order to avoid aortic manipulation. This procedure was particularly selected when in presence of: young patients (< 60 years old), high surgical risk, poor run-off, high risk of prosthetic infection, thrombosis and/or infection of orthotopic grafts. 3 ilio-iliac, 27 iliofemoral, 18 femorofemoral and 1 femoropopliteal bypass have been performed. The postoperative resting pressure Index increase was highly significant in recipient limbs. There wasn't perioperative mortality; during the follow up (mean 24.4 months) no amputation of recipient limb was observed. 4 patients died of A.M.I. and 1 of neoplastic disease. Late cumulative patency rate was 81% at 2 years and 67.3% at 3 years. These values rise to 97.2% and 86.1% respectively when considering patients with "ideal" indication (excluding 7 patients operated on for complications of previous bypass grafts and 6 with extremely poor run-off). An accurate evaluation of the lesion topography and haemodynamic pattern of donor and recipient iliofemoral districts are stressed as key points for a correct surgical indication.

[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.

[Nephronogenic nephroma: a benign kidney tumor in adults. Two case reports]. / Le néphrome néphronogène: tumeur bénigne du rein de l'adulte. A propos de 2 cas.

The authors report 2 cases of a benign and uncommon type of renal tumour in adult, the nephronogenic nephroma. The pathology is discussed and compared to other groups of solid renal tumour. The confusion with malign tumour is usual. According to radiological investigations and pathological analysis, aspects of surgical treatment are presented and discussed.

Hydatid disease of the liver: long term results of surgical treatment.

Many surgical techniques have been used in the management of the hydatid disease of the liver. The aim of the treatment should be to minimize the high risks of complication and recurrence. The Authors reviewed the records of 33 consecutive cases of hydatid disease of the liver surgically treated during a 6 year period (1974-1979) to determine complications and long term results (10 years) of the different surgical procedures applied. Partial pericystectomy with tube drainage was the most common treatment (30/49 cysts) followed by total pericystectomy (15/49) and partial liver resection (4 cases). Complication rates were 13.3%, 6.6% and 0% respectively. There was no perioperative mortality. In 1989 all patients were investigated for cystic recurrence: it was possible to study by CT scan or abdominal US 23 patients. Only three of them showed an asymptomatic recurrent disease. They had undergone partial pericystectomy in 1974 (2 cases) and 1977 (1 case) for recurrent hydatid disease of the right hepatic lobe and, in one case, even of the rectus muscle. Complication and recurrence rates seem to be higher with conservative surgical procedures compared to more radical treatment, but indiscriminate application of total pericystectomy or major liver resection may be followed by a higher incidence of major postoperative complications and mortality. Therefore, total pericystectomy or wedge resection were performed only for peripheral cysts since we believe liver resection for hydatid cyst is a very radical approach taking into account the type of disease.

[Splenic autografts in omental and subcutaneous pouches. An experimental study]. / Autoinnesti splenici in tasche omentali e sottocutanee. Studio sperimentale.

An accurate morphological study has been done on splenic grafts in rats after 7-15-30 days from their implant in omental or subcutaneous pouches. Observation after 7 days confirmed the necrosis of all the central portion of the implants. Anyway, marginal parts of the graft survived to ischaemia and showed to be supplied by vessels, coming from the contiguous tissues. In these parts the rigenerative process had begun from the structures of red residual pulp, by reticular cells proliferating so to rigenerate the capsula limiting the place of the central necrotic area. After 15 days the neocapsula was completed and from it neoformed trabecolae departed accompanied with chords, sinus capillary, venular and arteriolar vessels which reformed the structure of red pulp both in peripheral and central area, now undistinguishable. After 30 days lymphocytes aggregating around the neoformed vessels promoted a rudimental reconstruction of the white pulp too. In conclusion, splenic implants are able to get over the ischaemic phase and after 30 days the red pulp is morphologically reconstructed and probably functioning, while the white pulp is still primordial.

[The role of magnetic resonance in the follow-up of aortofemoral prosthetic reconstructions]. / Ruolo della risonanza magnetica nel follow-up delle ricostruzioni protesiche aorto-femorali.

The authors report their experience with the use of Magnetic Resonance (MR) in the follow-up of patients undergone aortofemoral bypass or substitution procedures for aneurysmal and/or steno-occlusive lesions of the aortoiliofemoral vascular bed. Twenty-eight patients, at least 2 years from aorto-bifemoral revascularization were evaluated by means of coronal and parasagittal MR planes (mean follow up 78.9 months). One exam over 28 was found to be not diagnostic; whereas the technique showed great usefulness in the morphological and haemodynamic evaluation of each of the graft sites explored (proximal anastomosis, graft body and limbs, femoral anastomosis and periprosthetic tissues) in the remaining 27 cases. The use of this method, in spite of some setting up problems peculiar to the type of examination, according to the authors is very promising because of the chance to obtain morphological and functional data at once and because of the interesting current and future developments of this diagnostic device.

[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.

[Carotid thromboendarterectomy in old age]. / La TEA carotidea nell'età avanzata.

Data obtained in 323 carotid bifurcation endarterectomies and in 77 patients affected by extracranial internal carotid artery stenosis not operated, have been analyzed in relation to patients' age: Group 1 less than or equal to 69 years old (268 cases operated on and 59 not operated), and Group 2 greater than or equal to 70 years old (55 cases operated on and 18 not operated). Among the operated patients, the most important anaesthetic risk factors, the type of neurological symptoms, and the diameter of the lesion did not turn out significantly different between the two age groups, except for the patients operated on because of stenoses less than or equal to 50% of carotid lumen reduction (42 cases in Group 1 and 1 case in Group 2, p less than 0.001). The overall operative mortality rate was 1.8% (6/323 carotid endarterectomies): 1.5% in Group 1 (4/268 cases, 2 due to stroke and 2 to heart disease), and 3.6% in Group 2 (2/55 cases, both due to stroke) (N.S.). The overall neurological morbidity was 0.6%, owing to 2 strokes both found in Group 2 (3.6% of patients greater than or equal to 70 years). Therefore, the overall incidence of fatal and non fatal stroke was 1.8% (6/323 carotid endarterectomies): 0.7% (2 cases) in Group 1, and 7.3% (4 cases) in Group 2 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Penetration of aztreonam into pleural exudate following rapid intravenous bolus or constant infusion.

A study on the effects of the mode of administration on aztreonam (AZ) concentrations in pleural fluid was performed in human subjects. The same dose of AZ was given as an intravenous bolus injection to one group and as a drip infusion to another group of patients. Serum and pleural fluid samples were collected at different times after drug administration, and the antibiotic concentrations were measured by using a microbiological method. The highest serum and pleural exudate concentrations and area under the curve values were obtained after drip infusion. These results indicate that drip infusion gives higher concentrations of AZ in pleural effusion.