N Selzner

Publications (8)69.41 Total impact

• Article: Routine induction therapy in living donor liver transplantation prevents rejection but may promote recurrence of hepatitis C.

  A Ghanekar, A Kashfi, M Cattral, N Selzner, I McGilvray, M Selzner, E Renner, L Lilly, G Levy, D Grant, P Greig
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  ABSTRACT: Routine induction therapy in living donor liver transplantation (LDLT) has not been well described. We reviewed outcomes of induction therapy with rabbit antithymocyte globulin (rATG) or basiliximab within 1 year of LDLT. Between 2002 and 2007, 184 adults underwent LDLT and received induction therapy in addition to standard immunosuppression. Acute cellular rejection (ACR) developed in 17 of 130 patients (13.1%) who received rATG and 13 of 54 patients (24.1%) who received basiliximab (P = .066). The interval between transplantation and rejection as well as rejection severity was similar in patients who received rATG and those who received basiliximab. Hepatitis C (HCV) recurrence requiring initiation of antiviral therapy was more common in patients who received rATG compared with basiliximab (34.5% vs 8.7%; P = .021), and in those who received induction combined with tacrolimus as opposed to cyclosporine (38.5% vs 3.9%; P = .001). rATG and basiliximab were associated with excellent patient and graft survivals well as low rates of opportunistic infections and malignancies. Induction with rATG or basiliximab was well tolerated and highly effective at preventing ACR within 1 year of LDLT, but may be associated with a higher risk of clinically significant HCV recurrence in some patients.
  Transplantation Proceedings 06/2012; 44(5):1351-6. · 1.00 Impact Factor
• Article: The prothrombinase activity of FGL2 contributes to the pathogenesis of experimental arthritis.

  M C Melnyk, I Shalev, J Zhang, A Bartczak, R M Gorczynski, N Selzner, R Inman, P A Marsden, M J Phillips, D A Clark, G A Levy
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  ABSTRACT: Fibrin deposition is integral to the pathogenesis of collagen-induced arthritis (CIA), an experimental model of rheumatoid arthritis (RA). Membrane-associated fibrinogen-like protein 2 (mFGL2), a novel inducible prothrombinase, generates fibrin by an alternate pathway and has been reported to be involved in the pathogenesis of a number of immune-mediated diseases. We hypothesized that expression of mFGL2 in inflamed synovium contributes to the fibrin deposition and subsequent inflammation in arthritis. DBA/1 mice were immunized with 100 µg bovine collagen type II (CII) emulsified in complete Freund's adjuvant (CFA) followed by lipopolysaccharide (LPS) injection. Expression of mFGL2 prothrombinase in association with fibrin deposition was examined in mice with CIA and CD200-treated mice following induction of CIA. To directly assess the contribution of mFGL2, fgl2(-/-) mice were injected with antibody to CII (anti-CII). Levels of fgl2 mRNA transcripts and mFGL2 protein were markedly up-regulated in joints of mice that developed CIA. Fibrin deposition was prominent within the synovial lining and articular joint space associated with expression of mFGL2. Inhibition of CIA by the immunosuppressant CD200 was associated with decreased expression of fgl2 mRNA and mFGL2 protein and absence of fibrin deposition. Following injection of anti-CII, all fgl2(+/+) mice developed severe arthritis with clinical and histological manifestations characteristic of RA, whereas fgl2(-/-) mice failed to develop any clinical manifestation or histological evidence of arthritis. This study demonstrates that the prothrombinase activity of mFGL2 contributes to the pathogenesis of experimental arthritis. These studies may have therapeutic implications for patients with RA.
  Scandinavian journal of rheumatology 04/2011; 40(4):269-78. · 2.51 Impact Factor
• Article: Adult living liver donors have excellent long-term medical outcomes: the University of Toronto liver transplant experience.

  L Adcock, C Macleod, D Dubay, P D Greig, M S Cattral, I McGilvray, L Lilly, N Girgrah, E L Renner, M Selzner, N Selzner, A Kashfi, R Smith, S Holtzman, S Abbey, D R Grant, G A Levy, G Therapondos
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  ABSTRACT: Right lobe living donor liver transplantation is an effective treatment for selected individuals with end-stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow-up of 12 months (range 12-96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 +/- 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long-term follow-up may contribute to favorable donor outcomes.
  American Journal of Transplantation 02/2010; 10(2):364-71. · 6.39 Impact Factor
• Article: 13C-methacetin breath test as a quantitative liver function test in patients with chronic hepatitis C infection: continuous automatic molecular correlation spectroscopy compared to isotopic ratio mass spectrometry.

  O Goetze, N Selzner, H Fruehauf, M Fried, T Gerlach, B Mullhaupt
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  ABSTRACT: The (13)C-methacetin breath test (MBT) has been proposed for the non-invasive evaluation of hepatic microsomal activity. To test a new continuous breath analysis system (BreathID) in comparison with gold-standard isotopic ratio mass spectrometry (IRMS) in patients with chronic hepatitis C infection and to assess the diagnostic performance of these validation data compared with liver biopsy for the quantification of liver fibrosis. Fifty patients at different METAVIR stages received 75 mg of (13)C-methacetin. Breath isotopic ratio was analysed over 90 min by BreathID (one sample/3 min; BreathID) and IRMS (one sample/10 min). Results were expressed as delta over baseline [DOB (%)] at each time interval and maximal DOB [DOB(max)(%)]. A high linear association between both methods was observed (R(2) = 0.95, P < 0.001). For all DOB and DOB(max), the limits of agreement by Bland-Altman analysis were within the predefined maximal width of s.d. <2.5%. MBT parameters in patients with high-grade fibrosis were different from patients with low-grade fibrosis (P < 0.001). The MBT obtained by an easy to operate, automated BreathID provides results comparable with standard IRMS and differentiates fibrosis grades in patients with chronic hepatitis C infection.
  Alimentary Pharmacology & Therapeutics 07/2007; 26(2):305-11. · 3.77 Impact Factor
• Article: Downstaging colorectal liver metastases by concomitant unilateral portal vein ligation and selective intra-arterial chemotherapy.

  N Selzner, B C Pestalozzi, Z Kadry, M Selzner, S Wildermuth, P-A Clavien
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  ABSTRACT: Although selective intrahepatic arterial chemotherapy successfully downstaged irresectable colorectal liver metastases in a previous study, curative resection was rarely possible, as the remnant healthy liver volume was inadequate. This pilot study evaluated the efficacy of concomitant unilateral portal vein ligation and selective intrahepatic arterial chemotherapy in downstaging such tumours. The study included 11 patients with irresectable colorectal liver metastases. Selective intrahepatic arterial chemotherapy was delivered using a subcutaneous pump, and each patient underwent concomitant unilateral portal vein ligation of the hemiliver judged to have the higher tumour load. Chemotherapy involved serial administration of floxuridine for 2 weeks every 4 weeks. All patients developed significant atrophy of the hemiliver subjected to portal vein ligation and contralateral hypertrophy. There was no increase in tumour load within 6 months of therapy, and the load decreased by 60 per cent in the hemiliver ipsilateral to the ligated vein. At 3 months, six of 11 patients showed a significant response to chemotherapy. In four patients, downstaging allowed curative resection after only three cycles of chemotherapy. These patients survived at least 20 months afterwards. Combined unilateral portal vein ligation and selective intrahepatic arterial chemotherapy produced substantial atrophy of the ipsilateral hemiliver along with contralateral hypertrophy, without increased tumour growth in the regenerating hemiliver.
  British Journal of Surgery 06/2006; 93(5):587-92. · 4.61 Impact Factor
• Article: Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding.

  N Selzner, M Selzner, R Graf, U Ungethuem, J G Fitz, P-A Clavien
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  ABSTRACT: Although exposure of cells to extreme hypotonic stress appears to be a purely experimental set up, it has found an application in clinical routine. For years, surgeons have washed the abdominal cavity with distilled water to lyse isolated cancer cells left after surgery. No data are available supporting this practice or evaluating the potential mechanisms of cell injury under these circumstances. Recent evidence indicates that increases in cell volume stimulate release of adenosine triphosphate and autocrine stimulation of purinergic (P2) receptors in the plasma membrane of certain epithelial cell types. Under physiological conditions, purigenic stimulation can contribute to cell volume recovery through activation of solute efflux. In addition, adenosine triphosphate-P2 receptor binding might trigger other mechanisms affecting cell viability after profound hypotonic stress. This study demonstrates a novel pathway of cell death by apoptosis in human colon cancer cells following a short hypotonic stress. This pathway is induced by transitory cell swelling which leads to extracellular release of adenosine triphosphate (ATP) and specific binding of ATP to P2 receptors (probably P2X7). Extracellular ATP induced activation of caspases 3 and 8, annexin V, release of cytochrome c, and eventually cell death. The effect of ATP can be blocked by addition of (i) apyrase to hydrolyse extracellular ATP and (ii) suramin, a P2 receptor antagonist. Finally, (iii) gadolinium pretreatment, a blocker of ATP release, reduces sensitivity of the cells to hypotonic stress. The adenosine triphosphate-P2 receptor cell death pathway suggests that autocrine/paracrine signaling may contribute to regulation of viability in certain cancer cells disclosed with this pathway.
  Cell Death and Differentiation 01/2005; 11 Suppl 2:S172-80. · 8.85 Impact Factor
• Article: Hepatic artery chemotherapy and colorectal liver mestastases.

  P A Clavien, F Dahm, N Selzner, M Selzner
  The Lancet 06/2003; 361(9370):1742-3; author reply 1743. · 38.28 Impact Factor
• Article: Conversion from cyclosporine to FK506 in adult liver transplant recipients: a combined North American and European experience.

  N Selzner, F Durand, J Bernuau, M A Heneghan, J E Tuttle-Newhall, J Belghiti, P A Clavien
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  ABSTRACT: Although cyclosporine (CsA) made clinical liver transplantation possible, side effects and development of rejection have limited its use. In some patients, conversion to tacrolimus has been necessary to abrogate side effects and to preserve allograft function. The results of conversion from CsA to tacrolimus were studied retrospectively in 94 liver allograft recipients from a North American and a European transplant center (Duke University Medical Center, Durham, NC, and Hopital Beaujon, Clichy, France). Forty-seven of 94 patients (50%) were converted for steroid-resistant acute rejection. Conversion was successful in 91% of these patients, whereas 9% of patients developed chronic rejection. A further nine patients were converted for chronic allograft rejection with positive results in eight of nine grafts. Mean serum bilirubin in these nine patients was 8.7 mg/dl before conversion and 2.1 mg/dl 6 months after conversion (P=0.02). Nine patients were converted due to inability to wean steroid. Of these, six patients remains steroid free 1 year after conversion. Twenty-three patients (24%) were converted for nephrotoxicity with a reduction in serum creatinine from 167+/-36 mmol/L to 119+/-28 mmol/L 1 year after conversion (P=0.006). Eight of 11 patients converted for neurotoxicity improved after conversion. Conversion to tacrolimus had no effect on seizure frequency or memory loss. These results suggest that conversion to tacrolimus from CsA is an appropriate paradigm for graft rescue and treatment of a variety of side effects after liver transplant. However, some situations such as memory loss and hypertension may require other strategies.
  Transplantation 10/2001; 72(6):1061-5. · 4.00 Impact Factor