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ABSTRACT: The aim of the study was to analyse the incidence of benign colorectal anastomotic stenoses in consecutive patients operated on in a single institution and to assess risk factors for their development. Their impact on quality of life was also evaluated.
Patient characteristics, indications for surgery, surgical technique and postoperative complications were prospectively recorded. Stenosis was evaluated by rectoscopy at regular intervals, and patients were treated only if symptomatic. After at least 6 months following surgery, patients were asked to respond to the Short Form 36-item quality-of-life questionnaire during a telephone interview.
Of the original 211 patients considered, 195 underwent a follow-up rectoscopy and were included in the study. Benign stenosis were found in 26 (13%), and 19 (73%) symptomatic patients were treated successfully (15 with endoscopic dilatation and four with radial diathermic surgical incisions). Risk factors for anastomotic stenosis according to univariate analysis were female sex, diverticulitis, mechanical anastomosis, and anastomosis located between 8 and 12 cm from the anal verge. The significant risk factors identified by multivariate analysis were diverticulitis (OR 5, P=0.002) and mechanical anastomosis (OR 9, P=0.04). The self-perceived quality of life of patients with stenosis was significantly worse compared with controls.
Since diverticulitis and mechanical anastomosis are risk factors for anastomotic stenosis, surgeons should take this into account when they are considering what type of anastomotic technique to utilize.
Colorectal Disease 09/2011; 14(3):e124-8. · 2.93 Impact Factor
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ABSTRACT: The aim of this retrospective study was to determine the relevance of the symptom "headache" in kidney transplanted patients, since few studies have considered headache as a clinically significant complication in this condition. A total of 83 consecutive kidney transplant patients underwent to neurological examination and a detailed headache history was taken. The headache history considered the period before kidney disease, during renal failure, during dialysis treatment and after transplantation. Diagnosis was made according to International Headache Criteria (ICDH-II) (2004). Our results reveal an occurrence of headache after kidney transplantation in 44.5% of the patients, which is higher than rates reported for the general population and in the only specific comparable study on liver transplant patients. These data suggest the need for prospective studies to explore the causal mechanisms by which headache develops with frequency in kidney transplant patients, and in particular to determine the role of immunosuppressive therapy.
The Journal of Headache and Pain 09/2009; 10(6):455-60. · 2.43 Impact Factor
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BMC Geriatrics. 01/2009;
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BMC Geriatrics. 01/2009;
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ABSTRACT: Cyclophosphamide (CYP) and methotrexate (MTX) have been used as immunosuppressants in induction or maintenance protocols in a large variety of xenotransplantation models. Combining the use of transgenic porcine organs expressing human decay-accelerating factor (hDAF) with immunosuppressive therapy that included the use of CYP or MTX, survival of primate recipients of life-supporting renal xenografts has been prolonged. However, both drugs can cause significant systemic toxicity and, in particular, gastrointestinal (GI) toxicity. To date only limited data have been reported on the histopathological features deriving from the use of such agents in non-human primates.
Cyclophosphamide or MTX was used as part of the immunosuppressive regimen in 15 bilaterally nephrectomized non-human primate (Macaca fascicularis) recipients of a life-supporting hDAF porcine kidney. At post-mortem, a detailed analysis of the GI tract in animals receiving either CYP or MTX was performed. Paraffin-embedded sections of each portion of the GI tract were prepared and stained with hematoxylin and eosin (H&E). In some animals, additional investigations by immunohistochemistry (CD3, CD5, CD20, CD79 alpha cy, lambda, and kappa light chains) and by in situ hybridization for EBV encoded RNA (EBER) were undertaken.
The xenografted animals from the CYP group had a mean survival of 31 days (range: 0 to 90 days); animals from the MTX group survived a median of 14 days (range: 0 to 39 days). GI complications were the most frequent cause of euthanasia after renal failure. In CYP-treated animals GI-tract lesions were primarily characterized by diffuse, severe lymphoplasmocytic mucosal inflammatory infiltrate. Variable degrees of villi atrophy and fusion, gut-associated lymphoid tissue (GALT) and goblet cell hyperplasia were also observed. In MTX-treated primates, findings were consistent with severe villi atrophy associated with mild-to-moderate disseminated lymphoplasmocytic infiltration.
In conclusion, GI tract lesions are an early and consistent finding when CYP or MTX are used as induction agents in this model. The two compounds induce different types of GI tract damage, however, in agreement with their different mechanisms of action. Whilst CYP primarily determines inflammatory lesions, MTX leads to a degenerative type of damage. This study indicates that immunosuppressive drugs can cause severe GI tract damage in primate recipients of renal xenografts and may be responsible for life-threatening lesions.
Xenotransplantation 04/2007; 14(2):145-56. · 2.33 Impact Factor
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Arben Dedja,
Luigi Dall'Olmo, Roberto Cadrobbi,
Nicola Baldan,
Fabio Fante,
Fiorella Calabrese,
Paolo Rigotti,
Mariano Ferraresso,
Luc Delriviere,
Emanuele Cozzi,
Ermanno Ancona
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ABSTRACT: Hamster-to-rat heterotopic cardiac xenotransplantation is widely used as an experimental model to study xenograft rejection, accommodation, and tolerance, as well as in studies aimed at developing immunosuppressive strategies in xenotransplantation. Despite its widespread application, no detailed description of a surgical technique for this model has been provided in the literature. Indeed, all publications so far on the use of this species combination refer to the rat allotransplantation technique. Hence the present paper provides a detailed, up-to-date description of the surgical method adopted at our center for the hamster-to-rat heterotopic cardiac xenotransplantation model. Considerable effort went into developing a reliable, reproducible experimental model in rodents, and the description given here is enriched with "tips" that we learned in the process. The discussion of the technique also addresses several significant related issues, e.g., the anesthesia and organ preservation solution used (aspects that, in our experience, are crucial to a good surgical outcome).
Microsurgery 02/2005; 25(3):227-34. · 1.61 Impact Factor
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ABSTRACT: The use of elderly donors (ED) and dual kidney transplantation (DKT) procedures have become common in clinical practice. A correct evaluation of kidneys from ED is crucial to avoid unsuccessful transplantation or the use of DKT when a single transplant (ST) would be equally successful. The aim of this investigation was to assess the role of renal biopsy (RB) in the assessment of kidneys from ED.
A total of 84 ED aged > or = 60 yr were evaluated. In 19 cases, the kidneys were not used, mainly because of atherosclerotic vascular lesions. A histological score (HS) from 0 to 12 was awarded, considering the proportion of glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arterial and arteriolar narrowing. On the basis of the HS, 37 donors were selected for 40 ST and 21 for DKT, three were discarded. All recipients received triple-drug therapy based on calcineurin inhibitors, mycophenolate mofetil and steroids.
Primary non-function was observed in three of 40 ST and one of 21 DKT. Acute tubular necrosis occurred in 22/40 ST and in 11/21 DKT. Acute rejection occurred in 16/40 ST and four of 21 DKT. Renal function was satisfactory in both groups, with 1-yr S-Cr = 171 micromol/L and 137 micromol/L, respectively in the ST and DKT groups. One-year patient survival was 92% in ST and 100% in DKT; 1-yr graft function was 87% in ST and 95% in DKT.
The histological assessment of kidneys from ED enables a correct selection of kidneys for ST or DKT and prevents the transplantation of high-risk kidneys.
Clinical Transplantation 08/2004; 18(4):440-5. · 1.67 Impact Factor
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Nicola Baldan,
Paolo Rigotti,
Fiorella Calabrese, Roberto Cadrobbi,
Arben Dedja,
Ilaria Iacopetti,
Massimo Boldrin,
Michela Seveso,
Luigi Dall'Olmo,
Laura Frison,
Giulia De Benedictis,
Daniele Bernardini,
Gaetano Thiene,
Emanuele Cozzi,
Ermanno Ancona
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ABSTRACT: The aim of this study was to analyze the incidence of ureteral stenosis in a life-supporting human decay-accelerating factor (hDAF) transgenic pig-to-cynomolgus monkey kidney transplantation model and determine the role of possible immunological events in its pathogenesis. Thirty consecutive bi-nephrectomized cynomolgus monkeys received a kidney from hDAF transgenic pigs with or without a ureteral stent. Four monkeys were euthanized prematurely after transplantation. In the remaining 26 cases, the mean survival was 24 +/- 19 days. Except in one case, there was a close relationship between ureter and kidney in terms of type and severity of rejection. There were six ureteral stenoses; five were repaired by stent positioning and resurgery extended survival for an additional 16 +/- 10 days. The stenotic ureters showed diffuse acute humoral xenograft rejection (AHXR), while all cases with no or only focal signs of ureteral rejection never revealed ureteral obstruction. Use of a ureteral stent extends the survival of a xenografted primate, thereby helping to clarify the immunological events surrounding the onset of AHXR in kidneys in long-term xenograft recipients.
American Journal of Transplantation 05/2004; 4(4):475-81. · 6.39 Impact Factor
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Emanuele Cozzi, Roberto Cadrobbi,
Nicola Baldan,
Arben Dedja,
Fiorella Calabrese,
Massimo Castagnaro,
Fabio Fante,
Massimo Boldrin,
Ilaria Iacopetti,
Licia Ravarotto,
Paolo Carraro,
Vincenzo Bronte,
Carmela De Santo,
Roberto Busetto,
Mario Plebani,
Francesco Maria Cancellotti,
Paolo Rigotti,
Gaetano Thiene,
Ermanno Ancona
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ABSTRACT: Methotrexate (MTX) has been used successfully as an immunosuppressant in rodent xenotransplantation models, but the data generated so far with MTX in pig-to-baboon cardiac transplantation studies have been disappointing. The potential of this agent was consequently explored in a life-supporting pig-to-primate renal model using the cynomolgus monkey as the recipient species. Introductory in vitro and in vivo pharmacokinetic and pharmacodynamic studies with MTX were conducted in three cynomolgus monkeys. Subsequently, 10 cynomolgus monkey recipients of a life-supporting kidney from human decay-accelerating factor transgenic pigs were administered MTX intravenously according to three different regimens. All the animals also received cyclosporine A and steroids. In addition, mycophenolate sodium (MPS) was administered post-operatively in two of the three groups of transplanted animals. At clinically relevant concentrations, MTX is able in vitro to inhibit the mixed lymphocyte reactions (MLR) in cynomolgus monkeys. After intravenous administration, moreover, exposure of cynomolgus monkeys to MTX appeared to be higher than had been previously reported in baboons. Graft function was observed in the transplanted animals, which survived from 0 to 41 days. All but two animals revealed acute humoral rejection in the explanted graft and developed diarrhea. Diarrhea was the cause of euthanasia in five cases. It was unrelated to the administration of MPS and associated with severe histopathological signs of enteritis. This study demonstrates that the pharmacokinetic and pharmacodynamic profiles if MTX vary substantially between non-human primate species. In vitro, MTX has immunosuppressive properties in the cynomolgus monkey at clinically relevant concentrations. In vivo, MTX has a very narrow therapeutic window in cynomolgus monkeys, however, as it does in baboons. We conclude that MTX is scarcely effective as an immunosuppressant, be it for induction or maintenance, in pig-to-cynomolgus monkey renal xenotransplantation.
Xenotransplantation 12/2003; 10(6):587-95. · 2.33 Impact Factor
