Martin Bodingbauer

Medical University of Vienna, Wien, Vienna, Austria

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Publications (16)72.07 Total impact

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    ABSTRACT: The assessment of donor-derived damage of transplanted kidneys might be instrumental for estimating donor organ quality and for predicting short- and long-term organ outcome. In the present study, we report a new standardized method for obtaining pre-transplant kidney biopsy specimens. Instead of taking wedge biopsies (WBs), a skin punch biopsy (PB) tool was utilized to obtain standardized biopsy samples that also represented deeper cortical zones. We compared 147 PB specimens and 114 WBs with respect to the number of glomeruli and arterial vessels they contained. The performance of the two biopsy methods in detecting glomerular damage, interstitial fibrosis/tubular atrophy (IF/TA) and arteriosclerosis was determined by evaluation of subsequent transplant core biopsies of the patients. Statistical comparison employed Kruskal-Wallis and kappa (κ) tests. Significantly more PB samples (89%) than WBs (66%) were diagnostically adequate according to the Banff criteria. Despite a higher number of glomeruli in WBs (34.6 versus 21.7 in punch biopsies), arteries were present in only 68% of WBs but could be found in 93% of punch biopsies. The comparison of findings in pre-transplant biopsies with lesions in corresponding post-transplant core biopsies revealed a superior diagnostic concordance for IF/TA and arteriosclerosis for punch biopsies than for WBs, reaching kappa values of 0.823 versus 0.729 and 0.661 versus 0.516, respectively. The use of skin PB tools for obtaining baseline biopsies from transplanted kidneys is a safe and effective method for assessment of donor-derived damage of the organ.
    Nephrology Dialysis Transplantation 04/2012; 27(8):3241-8. · 3.37 Impact Factor
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    ABSTRACT: Brain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function, which might be counterbalanced by steroid pretreatment of the organ donor. The aim of this randomized controlled trial was to elucidate whether steroid pretreatment of liver donors improves early liver allograft function, prevents rejection and prolongs survival. A placebo-controlled blinded randomized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008. Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6h before recovery of organs. The primary end point was the concentration slope of transaminases within the first week. The secondary end point included survival and biopsy-confirmed acute rejection (BCAR) within 3 years after transplantation. Of the 90 randomized donors, 83 recipients were eligible for study. The trajectories of ALT and AST were not different between treatments (p=0.40 and p=0.13, respectively). Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment (RR=0.63 95% CI [0.29,1.36], p=0.31). Eleven recipients experienced biopsy-confirmed rejection (BCAR) in the steroid and 11 in the placebo group (RR=1.02 95% CI [0.50,2.10], p=1.00). No effect modification could be identified in the predefined strata of donor age, sex, cold ischemic time, and cause of donor death. Steroid pretreatment of organ donors did not improve outcomes after liver transplantation.
    Journal of Hepatology 02/2012; 56(6):1305-9. · 9.86 Impact Factor
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    ABSTRACT: For patients with colorectal liver metastasis (CLM), the presence of concomitant perihepatic/para-aortic lymph node metastasis (LNM) is considered a contraindication to liver resection. We sought to determine the benefits of liver resection among patients with CLM + LNM by examining long-term outcomes among a large cohort of patients. Between October 1996 and December 2007, 61 patients with CLM and pathologically proven LNM were identified from an international multi-institutional database of 1629 patients. The effect of LNM, as well as other prognostic factors, on recurrence-free and overall survival was analyzed. Median overall survival was 32 months, and 1-, 3-, and 5-year overall survival were 86, 35, and 18%, respectively. Five patients were alive and disease-free at last follow-up. Survival was associated with location of LNM. Specifically, 5-year overall survival was 30% among patients with LNM along the hepatoduodenal ligament/retropancreatic area (area 1), 14% among patients with LNM along the common hepatic artery/celiac axis (area 2), and there was only one long-term survivor who experienced recurrent disease among patients who had CLM + para-aortic LNM (area 3) (P = 0.004). On multivariate analyses, overall margin status (hazard ratio [HR] = 2.0), treated number of metastases >6 (HR = 2.3) and para-aortic lymph node involvement (HR = 2.6) each remained significantly associated with increased risk of death (all P < 0.05). Although overall survival in the setting of LNM is only 18%, certain subsets of patients with LNM can benefit from surgical resection. Specifically, patients with CLM + LNM isolated to area 1 had a 5-year survival of approximately 30%, while long-term survival among patients with para-aortic LNM was rare.
    Annals of Surgical Oncology 07/2011; 19(2):435-42. · 4.12 Impact Factor
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    ABSTRACT: The increased use of older and/or marginal donor organs in liver transplantation over the last decade calls for strategies to minimize ischaemic reperfusion (I/R) injury to prevent early graft failure. Tacrolimus, a very potent and effective calcineurin inhibitor, was selected because of its ability to ameliorate I/R injury. A randomized, blinded, controlled single-centre trial of 26 liver transplant recipients was performed between February 2008 and December 2009. Donor organs were randomized to be perfused intraportally during liver transplantation with 1.5 l 5% albumin infusion containing either 20 ng/ml tacrolimus or placebo. The primary end point was liver function as assessed by aspartate transaminase (AST) or alanine transaminase (ALT) levels 6 days after transplantation. Treatment effectiveness was tested by transcriptome-wide analysis of biopsies. There was no difference in the primary end point, i.e. AST (IU/l) and ALT (IU/l) at day 6 after transplantation between groups. Furthermore, choleastatic parameters as well as parameters of liver synthesis were not different between groups. However, tacrolimus treatment suppressed inflammation and immune response in the transplanted liver on a genome-wide basis. Intrahepatic administration of tacrolimus did not result in a reduction of AST and ALT within the first week after transplantation.
    Transplant International 06/2011; 24(9):912-9. · 3.16 Impact Factor
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    ABSTRACT: Background: The rate at which radioactive albumin particles clear from the bloodstream is used to measure reticuloendothelial capacity. Traditionally, iodine radioisotopes have been used. Non-active albumin particles mixed with the technetium-99 m labelled particles of the readily available radiopharmaceutical 99 mTc Albumin Nanocolloid (ANC) would be more convenient. Aim: To prepare human albumin nanospheres (HAN) with a diameter similar to 99 mTc-ANC and to investigate their stability. Experimental: HAN were prepared by heating 30 g/l albumin solution pH 10 at 70°C for 20 min then 75°C for 17.5 min, adjusting to pH 7.5 and sterilizing by filtration. Seven batches were prepared. The HAN diameter was measured by photon correlation spectroscopy at 0–3 months. Various measures of stability were performed. Results: The mean diameter of the HAN was 3.9 ± 1.9, 4.0 ± 1.5, 4.4 ± 1.6 and 4.2 ± 2.0 nm at 0, 1, 2 and 3 months. After mixing HAN and 99 mTc-ANC, no changes in particle size or radiolabelling of ANC were detected. Conclusions: HAN with a diameter comparable to the particles in 99 mTc-ANC were prepared successfully. The diameter of HAN does not change over 3 months or after mixing with 99 mTc-ANC. The particle size and labelling efficiency of 99 mTc-ANC are not affected by the addition of HAN. Copyright © 2011 John Wiley & Sons, Ltd.
    Journal of Labelled Compounds 02/2011; 54(5):252 - 255.
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    ABSTRACT: Hepatic resection for colorectal liver metastasis (CLM) with concomitant extrahepatic disease (EHD) is a controversial topic. We sought to evaluate the long-term outcome of patients undergoing liver resection for CLM in presence of EHD and identify factors associated with prognosis. From 1996 to 2007, a total of 1629 patients who underwent resection of CLM were identified from an international multi-institutional database. One hundred seventy-one patients (10.4%) underwent resection of EHD. Clinicopathologic and outcome data were collected and analyzed by univariate and multivariate analyses. Median number of treated CLM was 2 (range, 1-18); most patients had solitary EHD (n = 114; 66.6%) a single anatomic site of EHD (n = 153; 89.4%). The 5-year survival for patients with EHD was 26% compared with 58% for those without EHD (P < 0.001). Recurrence was common (84%). Among patients with EHD, R1 margin status, multiple EHD sites, and location of EHD were associated with worse survival (all P < 0.05). Patients with multiple EHD sites or aortocaval lymph node metastasis had a 5-year survival of 14% and 7%, respectively. When survival was stratified by the total number of metastases treated, the presence of EHD still had a prognostic impact, but the relative impact of EHD diminished as the total number of metastases treated increased. Concurrent resection of hepatic and EHD in well-selected patients may provide the possibility of long-term survival. The risk of recurrence, however, remains high, and a worse outcome is associated with both number of metastases and location of EHD.
    Annals of Surgical Oncology 12/2010; 18(5):1380-8. · 4.12 Impact Factor
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    ABSTRACT: Microarray data showed that osteopontin overexpression predicts early HCC-recurrence after liver resection. Osteopontin (OPN) expression could serve as a predictor of HCC-recurrence after OLT. Osteopontin expression was investigated immunohistochemically in a unique population of 125 HCC-patients undergoing OLT between 1982 and 2002, including 81 patients (65%) outside the Milan criteria. Multivariate analysis of factors associated with median overall survival (OS) and time to recurrence (TTR) was performed. Osteopontin was expressed in 40/125 (32%) of the HCCs. Overall survival post-OLT at 1, 2, 3, 5 years was 77%, 62%, 52%, and 43% (median survival 37 months). Overall survival was significantly longer without expression of OPN (p < 0.05; (median OS: 56 vs. 23 months). The same was true for median TTR (p = 0.008). Outside Milan criteria, patients without OPN-expression had better prognosis (median OS: 37.8 vs. 19.2 months, p = 0.003). Tumor recurrence in patients transplanted outside Milan criteria occurred in 43% (23 of 54) of patients without and 70% (19 of 27, p = 0.018) of patients with OPN-expression after a median TTR of 83.5 vs. 13.9 months. On multivariate analysis, vascular invasion and OPN-expression were independently associated with OS and TTR in HCC-patients after OLT. Immunohistochemically detectable Osteopontin in HCC is an independent predictor of tumor recurrence and survival in patients beyond Milan criteria undergoing OLT.
    Journal of Hepatology 08/2010; 54(1):89-97. · 9.86 Impact Factor
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    ABSTRACT: During the last two decades, resection of colorectal liver metastases (CLM) in selected patients has become the standard of care, with 5-year survival rates of 25-58%. Although a substantial number of actual 5-year survivors are reported after resection, 5-year survival rates may be inadequate to evaluate surgical outcomes because a significant number of patients experience a recurrence at some point. This study aimed to analyse longterm results and prognostic factors in liver resection for CLM in patients with complete 10-year follow-up data. A total of 369 patients who underwent liver resection for CLM between 1985 and 1998 were identified from a bi-institutional database. Postoperative deaths and patients with extrahepatic disease were excluded. Clinicopathological prognostic factors were analysed using univariate and multivariate analyses. The sample included 309 consecutive patients with complete 10-year follow-up data. Five- and 10-year overall survival rates were 32% and 23%, respectively. Overall, 93% of recurrences occurred within the first 5 years of follow-up, but 11% of patients who were disease-free at 5 years developed later recurrence. Multivariate analysis demonstrated four independent negative prognostic factors for survival: more than three metastases; a positive surgical margin; tumour size >5 cm, and a clinical risk score >2. Five-year survival rates are not adequate to evaluate surgical outcomes of patients with CLM. Approximately one-third of actual 5-year survivors suffer cancer-related death, whereas patients who survive 10 years appear to be cured of disease.
    HPB 05/2010; 12(4):244-9. · 1.94 Impact Factor
  • Transplant International 08/2009; 23(1):118-20. · 3.16 Impact Factor
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    ABSTRACT: The KiSS-1 gene has been reported to play an important role as a metastasis suppressor gene in various human malignancies. However, there is little information about its possible role in hepatocellular carcinoma (HCC). In this study, we evaluated the prognostic significance of the expression of KiSS-1 and its receptor AXOR12 in 142 HCC tissue specimens by immunohistochemistry. By using a cutoff level of 50%, immunoreactivity of KiSS-1 and AXOR12 was found in 6 (4%) and 11 (8%) HCCs. The expression of KiSS-1 and AXOR12 in HCC correlated with each other (r = 0.42, p < 0.0001) and with the expression in corresponding, surrounding liver tissue (both r = 0.35, p < 0.0001). Positive AXOR12 immunoreactivity in HCC correlated with advanced pT-stage of tumors and low tumor grading (r = 0.18, p = 0.032; r = -0.18, p = 0.029). High KiSS-1 expression in HCC had a statistically significant influence on diminished disease-free and overall survival in uni- (p = 0.006 and p = 0.002) and multivariate analysis (r = 2.874, p = 0.027 and r = 2.913, p = 0.026). In this study, we report for the first time that elevated KiSS-1 expression level in HCC correlates with worsened clinical outcome, as an independent prognostic marker for the aggressiveness of HCC.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2007; 450(2):143-9. · 2.68 Impact Factor
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    ABSTRACT: Recently, the anti-apoptotic Mcl-1 protein has been reported as a resistance factor in various types of cancer. Here we investigated the presence of Mcl-1 protein in hepatocellular carcinoma (HCC) tissues and its potential role as a molecular drug target for HCC therapy. HCC specimens of 149 patients were examined by immunohistochemistry for Mcl-1 expression. Antisense oligonucleotides (ASO) targeting Mcl-1 were evaluated as monotherapy and in combination with cisplatin in the HCC cell lines HepG2 and Snu398. Protein regulation, cell viability, and apoptosis were assessed by western blotting, cell counting, and FACS analysis. Mcl-1 protein is overexpressed in 51% of all cases irrespective of underlying disease. Targeting Mcl-1 by ASO specifically downregulated Mcl-1 protein expression and led to significant dose and time dependent single agent activity in HCC cells characterized by increased apoptosis and decreased cell viability. No significant target regulation or cell death was observed for control oligonucleotide treatment. Upon combination with cisplatin, Mcl-1 ASO revealed a significant chemosensitizing effect. Mcl-1 is overexpressed in half of HCC-tissues. ASO targeting Mcl-1 revealed a prominent single agent and chemosensitizing activity against HCC in vitro. Targeting Mcl-1 might qualify as a promising novel approach in HCC therapy.
    Journal of Hepatology 02/2006; 44(1):151-7. · 9.86 Impact Factor
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    ABSTRACT: The Eurotransplant Senior Program (ESP) was launched in 1999, targeted to increase the supply of donor kidneys to the elderly. This program requires local allocation of kidneys from cadaveric donors >65 years to recipients >65 years. Of all patients >65 years who received a kidney transplant in 1999-2002 at our center, 59 patients were transplanted through the ESP protocol (ESP group), and 44 patients received a transplant from a younger donor (EuroTransplant Kidney Allocation System, ETKAS group). Recipients were followed for up to 5.3 years using the Austrian Dialysis and Transplant Registry. Outcomes studied included all-cause mortality and allograft loss. Age, sex, and comorbid conditions did not differ by group. Donor age was higher (69 vs. 36 years; P < 0.001) and cold ischemia time shorter in the ESP group (10 vs. 15 hr; P < 0.001). Number of HLA mismatches was greater in the ESP group (3.8 vs. 3.0; P = 0.003). ESP patients were more likely to receive induction therapy and less likely to receive cyclosporine A. Primary nonfunction, delayed graft function, operative mortality, rate of acute rejection episodes, and length of stay did not differ by group. Although serum creatinine at discharge was higher in ESP patients (1.7 vs. 1.4 mg/dL; P < 0.001), 4-year mortality (hazard ratio [HR] = 0.68; 95% CI: 0.31-1.49) and graft loss (HR = 0.61; 95% CI: 0.29-1.28) tended to be less. Long-term patient and graft survival were comparable between elderly patients who received their organ via the ESP and the regular ETKAS algorithm.
    Transplantation 10/2005; 80(5):582-9. · 3.78 Impact Factor
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    ABSTRACT: Monitoring immunosuppression with cyclosporine microemulsion formulation (CsA-MEF) by using 2-hour CsA blood levels (C2) has been strongly recommended after kidney transplantation. The aim of our study was to evaluate the impact of C2 monitoring on the clinical outcome early after transplantation in a single-center setting. Nonsensitized, consecutive, de novo cadaveric kidney-transplant recipients were treated with CsA-MEF, mycophenolate mofetil, and steroids. Patients receiving transplants after January 2002 (n=89) were prospectively monitored by C2 levels (target: 1,500+/-200 ng/mL [fluorescence-polarization immunoassay]). They were retrospectively compared with the patients receiving transplants during 2001 (n=88) who had been monitored by C0 levels (target: 250+/-50 ng/mL). In the intention-to-treat analysis, 40 (45.4%) patients in the C0 group and 25 (28.1%) patients in the C2 group received treatment for rejection (P=0.017). The incidence of histologically verified rejection of Banff grade I or higher was 20.45% in the C0 group and 13.48% in the C2 group (P=0.235). In the per-protocol analysis, incidence of treated rejection was 24.7%, and incidence of histologically verified rejection of Banff grade I or higher was 12.35% in the C2 group (P=0.004 and 0.160, respectively, vs. C0). Mean CsA-MEF doses were 1.7 to 2 times higher in the C2 group than in the C0 group throughout follow-up (P=0.019). In the C2 group, target C2 levels were achieved on average 4 days after transplantation, and there was no significant difference in C2 levels between patients who rejected and patients who did not reject. Kidney-transplant recipients monitored by C2 levels receive significantly higher doses of CsA-MEF and have a lower incidence of early acute allograft rejection than patients monitored by C0 levels. In C2 monitored patients, C2 levels are not predictive for the incidence of early allograft rejection.
    Transplantation 01/2005; 78(12):1787-91. · 3.78 Impact Factor
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    ABSTRACT: Sufficient assessment of potential candidates for orthotopic liver transplantation (OLT) is the most important factor for a low alcohol relapse rate after transplantation in patients suffering from alcoholic cirrhosis. In the current study the efficiency of pretransplant screening with carbohydrate-deficient transferrin (CDT) was analysed in patients on the waiting list for OLT. A prospective study was performed in 44 patients who had undergone OLT for alcoholic cirrhosis. All patients had had pretransplant assessment by a specialist psychologist and were found to have no problems with alcohol. Pre- and post-transplant CDT monitoring was performed. Overall, 790 CDT values were measured in the study population. The median observation period was 2.1 months before and 41.2 months after transplantation, respectively. In 35 patients (80%) pretransplant CDT values were found to be above the reference value, but only one patient suffered an alcohol relapse after transplantation. Of the nine patients (20%) who demonstrated normal CDT before transplantation, two suffered an alcohol relapse after transplantation. CDT is a very useful marker for the monitoring of an alcohol relapse in patients following OLT for alcoholic cirrhosis, as has been previously indicated. However, CDT does not appear to be useful as a pretransplant screening marker for selection of potential transplant candidates suffering from alcoholic cirrhosis.
    Transplant International 12/2004; 17(10):617-21. · 3.16 Impact Factor
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    ABSTRACT: It is unknown whether continuation of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II (ATII) blocker therapy after kidney transplantation has an influence on early kidney graft function. We compared early postoperative graft function between 260 cadaveric kidney transplant recipients, either with or without peritransplantation ACE inhibitor/ATII blocker therapy. Regression analysis was used to show the influence of variables interfering with posttransplantation serum creatinine levels. The effect of different variables on the occurrence of delayed graft function (DGF) was analyzed by means of stepwise logistic regression. Improvement in kidney function during the first week after transplantation was compared between groups by means of Kaplan-Meier survival analysis. Intake of an ACE inhibitor or ATII blocker did not influence immediate posttransplantation graft function or the occurrence of DGF. Conversely, serum creatinine levels decreased significantly faster in patients administered an ACE inhibitor/ATII blocker than in those without therapy (P < 0.01). The only variables delaying graft function were number of previous transplantations, cold ischemia time, and male sex. Among patients with DGF, those with ACE inhibitor/ATII blocker therapy had significantly faster graft recovery (P < 0.001). Our results suggest that intake of an ACE inhibitor or ATII blocker during the immediate posttransplantation course is safe and does not impair graft function. Additionally, patients with DGF might profit from blockade of the renin-angiotensin-aldosterone system, which possibly shortens the time to graft recovery.
    American Journal of Kidney Diseases 06/2004; 43(6):1065-70. · 5.29 Impact Factor
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    ABSTRACT: The goal of this study was to analyze the influence of multiple anastomosis on outcome in orthotopic liver transplantation (OLT) and its implications for split-liver and living related liver transplantation programs. In a retrospective study, 683 first OLTs in adults were analyzed. Complex hepatic artery reconstruction was defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries. OLT was performed in a standard manner. All patients had daily ultrasound examination. In this series we found 72 grafts (10.5%) with anatomic arterial variations that required complex hepatic artery reconstruction. There was no difference in primary organ function and demographic data compared with patients with simple arterial reconstruction. However, hepatic artery thrombosis (HAT) occurred in 9.7% of patients (7 of 72) with complex reconstruction in contrast to 2.0% in the control group (12 of 638; P <.001). Statistical analysis identified multiple anastomoses (P <.002) and primary nonfunction (P <.02) as significant risk factors for HAT. Three patients underwent successful thrombectomy for HAT, all others had to undergo retransplantation. Although in the group with complex arterial reconstruction increased graft loss caused by HAT was found early postoperatively, the overall 5-year patient and graft survival was not different for both groups. Although complex reconstruction is a risk factor for HAT, early diagnosis of HAT by daily ultrasound and early repeat OLT can provide similar 5-year survival as for patients with simple reconstruction. We conclude that complex hepatic artery reconstruction challenges conventional OLT as well as split-liver and living related liver transplantation, but does not necessarily affect its long-term outcome.
    Liver Transplantation 09/2003; 9(9):970-5. · 3.94 Impact Factor