G Kirste

University of Freiburg, Freiburg, Baden-Württemberg, Germany

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Publications (100)318.87 Total impact

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    ABSTRACT: Background In the Eurotransplant Senior Programme (ESP), kidneys from donors aged ≥65 years are preferentially allocated locally and transplanted into patients aged ≥65 years on dialysis. The purpose of this study was to analyse whether the results of transplantation in the ESP can be improved by preservation of organs by hypothermic machine perfusion (MP) compared with simple cold storage (CS).Methods Overall, 85 deceased heart-beating donors ≥65 years of age were included in this analysis with follow-up until 1 year post-transplant. For each donor, one kidney was randomly assigned to preservation by CS and the contralateral kidney to MP from organ procurement until transplantation. Delayed graft function (DGF), primary non-function (PNF) and 1-year patient and graft survival rates were evaluated as primary and secondary endpoints.ResultsThe median recipient age was 66 years in both groups and the median cold ischaemia time was 11 h for MP and 10.5 h for CS (P = 0.69). The DGF rate was 29.4% for MP and 34.1% for CS (P = 0.58). Only extended duration of cold ischaemia time was an independent risk factor for the development of DGF (odds ratio 1.2, P < 0.0001). PNF was significantly reduced (3.5% MP versus 12.9% CS, P = 0.02). The 1-year patient and graft survival rates were similar for MP and CS (94% versus 95% and 89 versus 81%, P > 0.05). The 1-year graft survival rate was significantly improved after MP in recipients who developed DGF (84% MP versus 48% CS, P = 0.01).Conclusions Continuous pulsatile hypothermic MP for kidneys from donors aged ≥65 years can reduce the rate of never-functioning kidneys and improve the 1-year graft survival rate of kidneys with DGF. In this small cohort, the known advantage of MP for the reduction of DGF could not be confirmed, possibly due to relatively short cold ischaemia times.
    Nephrology Dialysis Transplantation 07/2012; · 3.37 Impact Factor
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    ABSTRACT: The critical pathway of deceased donation provides a systematic approach to the organ donation process, considering both donation after cardiac death than donation after brain death. The pathway provides a tool for assessing the potential of deceased donation and for the prospective identification and referral of possible deceased donors.
    Transplant International 04/2011; 24(4):373-8. · 3.16 Impact Factor
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    ABSTRACT: The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heart-beating deceased ECDs--defined according to the United Network of Organ Sharing definition--were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P=0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) (P=0.04). One-year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P=0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1-year graft survival and function in ECD kidneys. (Current Controlled Trials number: ISRCTN83876362).
    Transplant International 02/2011; 24(6):548-54. · 3.16 Impact Factor
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    ABSTRACT: Retrospective evidence suggests that lactate dehydrogenase, aspartate aminotransferase, total glutathione-S-transferase (GST), alanine-aminopeptidase, N-acetyl-β-D-glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) measured during kidney machine perfusion (MP) could have predictive value for posttransplant outcome. However, these data may be biased due to organ discard based on biomarker measurements, and previous analyses were not adjusted for likely confounding factors. No reliable prospective evidence has been available so far. Nevertheless, some centers already use these biomarkers to aid decisions on accepting or discarding a donor kidney. From 306 deceased-donor kidneys donated after brain death or controlled cardiac death and included in an international randomized controlled trial, these six biomarkers were measured in the MP perfusate. In this unselected prospective data set, we tested whether concentrations were associated with delayed graft function, primary nonfunction, and graft survival. Multivariate regression models investigated whether the biomarkers remained independent predictors when adjusted for relevant confounding factors. GST, NAG, and H-FABP were independent predictors of delayed graft function but not of primary nonfunction and graft survival. Lactate dehydrogenase, aspartate aminotransferase, and alanine-aminopeptidase had no independent prognostic potential for any of the endpoints. Perfusate biomarker concentrations had no relevant correlation with cold ischemic time or renal vascular resistance on the pump. Increased GST, NAG, or H-FABP concentrations during MP are an indication to adjust posttransplant recipient management. However, this study shows for the first time that perfusate biomarker measurements should not lead to kidney discard.
    Transplantation 11/2010; 90(9):966-73. · 3.78 Impact Factor
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    ABSTRACT: Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility. In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival. Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P=0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion. Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)
    New England Journal of Medicine 02/2009; 360(1):7-19. · 51.66 Impact Factor
  • Transplantation 01/2008; 86. · 3.78 Impact Factor
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    ABSTRACT: Quality assessment of renal grafts via (31)P magnetic resonance spectroscopy (MRS) has been investigated since 1986. As ATP concentrations decay rapidly during cold ischemia, the ratio of phosphomonoesters (PME) to inorganic phosphate (Pi(O)) within the organ (PME/Pi(O)) is commonly used as a quality marker and is considered to be the most reliable parameter. MRS did not lead to any delay in the transplantation procedure since it was performed during the time necessary for immunological matching (cross-match). Differences in the time period until transplantation call for extrapolation of the measured ratio to the end of cold ischemia before correlating with graft performance after transplantation. Therefore, quantitative determination of PME/Pi(O) kinetics is essential. As a model for metabolite decay in human renal grafts, pig kidneys obtained from a slaughterhouse were monitored for up to 80 h via (31)P MRS at 2 T. By employing chemical shift imaging (CSI) with a spatial resolution of approximately 1 x 1 x 4 cm(3), it was possible to reduce partial volume effects significantly. The improved spectral resolution gained through CSI enabled reliable PME/Pi(O) ratios to be determined only from those voxels containing renal tissue. Spectra were fitted automatically using the magnetic resonance user interface (MRUI), with prior knowledge obtained from unlocalized spectra when necessary. A monoexponential time dependence of PME/Pi(O) for histidine-tryptophane-alpha-ketoglutarate (HTK)-perfused kidneys during cold ischemia was observed, and the determined value of the decay constant alpha was 0.0099 +/- 0.0012 h(-1). In University of Wisconsin solution (UW)-perfused kidneys, an alpha of 0.0183 +/- 0.0053 h(-1) was determined. Determination of the decay constant enables a usable extrapolation of PME/Pi(O) for quality assessment of UW perfusion and a reliable extrapolation for HTK-perfused human renal grafts.
    NMR in Biomedicine 12/2007; 20(7):652-7. · 3.45 Impact Factor
  • Transplantation 05/2007; 83(8 Suppl):S1-22. · 3.78 Impact Factor
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    ABSTRACT: Mycophenolate mofetil (MMF) based immunosuppression after renal transplantation has proven to be safe and beneficial for children and adolescents. However, long-term analysis, in particular of pediatric patients, is scarce. Data of 140 patients receiving MMF versus azathioprine (AZA) in combination with cyclosporine A (CsA) and prednisone without induction were analyzed with a main focus on survival and renal function in long-term follow-up. After 5 years of follow-up, 44 MMF and 20 AZA patients were still on study. Graft survival of intent to treat (ITT) groups was 90.7% for MMF and 68.5% for AZA patients (P<0.001). Cumulative rejection free survival was 51.2% in MMF versus 37.0% in AZA patients (P<0.05). In association with early acute rejections (ARE), projected half-life was 14.4/4.5 years in patients with and 18.7/14.5 years without rejection in the MMF/AZA group, respectively. MMF based protocols improved long-term graft survival without an increase in side effects. Early ARE were associated with worse half-life of the graft, although more stressed in the AZA group. Thus, to improve quality of life in children for very long-term outcome, ARE should be further decreased and renal function should be better preserved.
    Transplantation 04/2007; 83(7):900-5. · 3.78 Impact Factor
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    ABSTRACT: The objective of this study was to determine outcome after living-donor kidney transplantation in a single-center institution in Germany. From 1976 to May 2005, a total of 298 living-donor kidney transplants were performed at the University of Freiburg. Most recipients (78.8%) were placed on cyclosporine, mycophenolate mofetil, and corticosteroids maintenance immunosuppression. Cox proportional hazard model was applied to analyze predictors for patient and graft survival. Mean follow-up was 5.3 years. According to Kaplan-Meier calculation, 1-, 5-, and 10-year patient survival was 98.6, 92.7, and 86.8%, respectively. Kidney function rate was 95.5, 82.8, and 67.9%, respectively. A 5-year graft function rate continued to increase from 79.5% in patients transplanted before 1996 to 83.6% in patients transplanted thereafter. In a Cox regression model recipient age above 50 years, duration of dialysis above 2 years and preexisting type 1 diabetes mellitus were associated with a decreased patient survival. Graft survival was mostly influenced by the type of immunosuppression and preexisting hypertension of the recipient. Our results demonstrate that living-donor kidney transplantation is a highly effective therapy for patients with end stage renal failure. Updates in immunosuppression, recipient selection, and operative technique may have contributed to the improved graft survival over the past three decades.
    Langenbeck s Archives of Surgery 02/2007; 392(1):23-33. · 1.89 Impact Factor
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    ABSTRACT: Mycophenolate mofetil (MMF) was introduced in pediatric renal transplantation almost 10 years ago. In several pediatric studies, MMF has been associated with improved graft survival and improved renal function with standard immunosuppression of steroids and calcineurin inhibitors (CNI). Both drugs are associated with significant negative effects including influence on growth, blood pressure, glucose metabolism, and also cosmetic side effects. Reduction of CNI was possible with MMF without increased rejection, improving blood pressure and renal function. Information is accumulating that steroid-sparing protocols including CNI are also associated with clinical improvement. Recent reports are positive in the pediatric population using the combination of induction with interleukin-2-receptor antagonists and mTOR inhibitors to spare steroids and CNI. Therefore MMF remains a mainstay of immunosuppressive protocols in the pediatric renal transplantation.
    Transplantation Proceedings 10/2006; 38(7):2038-40. · 0.95 Impact Factor
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    ABSTRACT: For years ABO-incompatible kidney transplantations were preferentially performed in Japanese centers. In order to overcome the increased risk of humoral rejections, patients were treated with multiple sessions of plasmapheresis, intensified immunosuppressive therapy and splenectomy before transplantation. Despite good long-term results regarding patient and organ survival rates, increased morbidity during the early post-transplant period prevented a broad application of this method. Recently, a new protocol including the anti-CD20-antibody (Ab) rituximab and blood group-specific immunoadsorption instead of splenectomy and plasmapheresis was published with excellent short-term results. From April 2004 to September 2005, 11 patients were prepared for ABO-incompatible transplantation. All patients received 375 mg/m2 rituximab intravenous 3 to 4 weeks before transplantation. Immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and prednisone and was started at least 7 days before transplantation. Intravenous immunoglobulins (0.5 g/kg) were administered the day before transplantation. Immunoglobulin G (IgG)-anti-A or -B Ab titers before starting immunoadsorption treatment ranged between 1 : 4 and 1 : 1024. Immunoadsorption treatment was started in parallel with immunosuppressive medication and was continued until the anti-A or anti -B Ab titers (IgG and IgM) were lowered to the aimed pre-transplant threshold of <1 : 8. During the early postoperative period, additional immunoadsorption treatments were performed, if the titers increased again above 1 : 8 (days 0 to 7) or 1 : 16 (days 8 to 14), respectively. Transplantation could be conducted in eight of 11 patients (two females, six males, mean recipient age 52+/-11 yr). The mean follow-up was 7.0 months (range 4 to 17). The blood group constellation was A1 to 0 in four cases, A2 to 0 in two cases, B to A in one case, and A1 to B in another case, respectively. On average, each patient received seven immunoadsorption treatments. All transplants showed primary function and no humoral rejections occurred. Three of our 11 patients showed rapid increases of isoagglutinin titers after each immunoadsorption treatment and thus could not be transplanted. One patient died 4 months after transplantation with a functioning graft due to sepsis secondary to pseudomembranous enterocolitis. The mean creatinine value of the remaining seven patients now is 1.6 mg/dl. The use of antigen-specific immunoadsorption and an immunosuppressive regimen consisting of a conventional triple immunosuppressive therapy has shown excellent short-term results. The immunoadsorption treatment using antigen-specific columns is highly effective and even patients with high isoagglutinin titers can be transplanted. This protocol is an option for end-stage renal disease patients who have no blood group-compatible donor.
    Xenotransplantation 04/2006; 13(2):108-10. · 2.57 Impact Factor
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    ABSTRACT: We sought to determine the impact of kidney transplantation with simultaneous unilateral nephrectomy on perioperative morbidity and patient and graft survival. From January 1990 to May 2004, 75 kidney transplantations with simultaneous unilateral nephrectomy (group NE+) were performed at the University of Freiburg. Of these, 49 had polycystic kidney disease. Patients of group NE+ were matched with 75 kidney transplants without nephrectomy (group NE-). Immunosuppressive maintenance therapy in both groups was based on cyclosporine A, mycophenolate mofetil or azathioprine, and prednisone. Mean follow up was 4.1 yrs (range 0.3-11.7 yrs). Patient survival rate at 1 and 5 yrs was 95% and 84% versus 95% and 93% in group NE+ and NE-, resp. (P=0.56). Accordingly, kidney function rate was 85% and 74% in group NE+ versus 89% and 79% in group NE- (P=0.89). Perioperative (90 days) mortality rate in group NE+ was 1.3% and 2.7% in group NE- (P=0.56). Perioperative surgical complications were similar in both groups. Kidney transplantation with concomitant unilateral nephrectomy has no negative impact on patient or graft survival and is associated with a reasonable morbidity rate.
    Transplantation 04/2006; 81(6):874-80. · 3.78 Impact Factor
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    ABSTRACT: The human cytomegalovirus (CMV) is a major cause of morbidity and mortality in transplant patients. In this study, we compared the diagnostic value of pp65 antigen test, qualitative nested polymerase chain reaction (PCR), and quantitative Taqman PCR in predicting the clinical outcome of CMV infection. A total of 169 samples derived from 59 organ-transplant recipients (kidney n= 46, liver n= 11, kidney and pancreas n= 2) were analyzed. Peripheral blood leukocytes (PBL) were isolated using dextran gradient centrifugation, and 2 x 10 cells were analyzed for pp65 antigen by immunofluorescence. A crude DNA extract obtained from the same number of cells was used for qualitative nested PCR and quantitative Taqman PCR analysis. RESULTS.: The correlation coefficient of pp65 antigen test and Taqman PCR was R= 0.699 (P = 0.001). With cut-off values for pp65 antigen test set at greater than 10 positive nuclei per 2 x 10 PBL, sensitivity was 91%, and positive predictive value (PPV) was 70%. When the corresponding cut-off value for Taqman PCR was applied (>125000 genome copies per 2 x 10 PBL), a sensitivity of 83% and a PPV of 68% were found. Both assays allowed for the monitoring of successful antiviral therapy. Although qualitative nested PCR was highly sensitive (95%), it was less useful in predicting CMV disease (PPV 47%) and in therapy control. Our data show that pp65 antigen test and Taqman PCR are almost equivalent in the monitoring of CMV infection and disease when identical cell numbers are used for both assays.
    Transplantation 06/2004; 77(11):1692-8. · 3.78 Impact Factor
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    ABSTRACT: Phosphorus-31 (P) magnetic resonance spectroscopy (MRS) has been evaluated in several studies for pretransplant assessment of renal viability. As an indicator of graft quality, the ratio of phosphomonoesters (PME) to an organ's inorganic phosphate (Pio) is the parameter of choice. However, exact calculation of the PME/Pio ratio is disturbed by interference from the signal of phosphorus contained in the preservation solution (Pip). In this article, the authors present an improvement attained by using volume selective P-MRS using chemical shift imaging (CSI) enabling reduction in the disturbing influence of Pip. Sixteen renal grafts were investigated using a 2.0-T whole-body scanner and a cross-coil setting with an active decoupled receiver coil. P-CSI was used to measure two-dimensional spectra of a 4-cm slice of the graft in a 12 x 12 matrix. Peaks of each spectrum were fitted with magnetic resonance user interface-MatLab software using VarPro and the mean PME/Pio ratio was calculated. Significant correlation between the PME/ Pio ratio and clinical kidney function was found. In comparison to former trials using PME/Pio ratios calculated from non-volume-selective spectra, the correlation outcome improved significantly. Furthermore, overlay of CSI-spectra matrix and corresponding slice image of the kidney illustrates the origin of different signals in the spectra. The authors' work demonstrates that the PME/Pio ratio calculated from CSI spectra is a reliable indicator of viability of renal grafts. Early knowledge of graft quality may allow therapy to be adapted to the conditions of the organ, for example, by initial withholding of nephrotoxic calcineurin-inhibitors in kidneys with high risk of delayed graft function.
    Transplantation 05/2004; 77(7):1041-5. · 3.78 Impact Factor
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    ABSTRACT: In the liver, efficacy of cryosurgical ablation of tumors located near the retrohepatic vena cava is impaired by the heat-sink effect. This could be overcome by total vascular exclusion (TVE) of the liver. In this study, the effect of TVE on cryosurgical ablation of liver tissue close to the retrohepatic vena cava was investigated with regard to the extent of the cryolesion and complications arising from necrosis of the caval wall. Of a total of 28 pigs, 14 underwent cryotherapy with TVE compared to 14 without TVE, both involving the vena cava. 7 animals in each group were subjected to one freeze cycle and 7 in each group to two freeze cycles. Temperatures in the cryolesion were monitored and cryolesions were documented sonographically. Laboratory parameters were determined pre- and postoperatively. Follow-up was 14 days. Morphology, extent of the cryolesion, damage to the vena cava and complications were assessed after autopsy. With TVE, freezing rates were increased and cryolesions were significantly larger than without TVE. Transmural necroses of the vena cava with complete necrosis of the intima occurred significantly more frequently after TVE. Macro- and microscopically, the damage to the caval wall was considerably more marked after cryotherapy under TVE but in all cases the continuity of the vessel wall remained intact. There were no ruptures, thrombosis, or strictures of the vena cava. The combination of cryotherapy and TVE increases the effectiveness of cryoablation in the liver involving the retrohepatic vena cava without any severe vascular complications occurring in the pig.
    Journal of Surgical Research 02/2004; 116(1):32-41. · 2.02 Impact Factor
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    ABSTRACT: BACKGROUND: The human cytomegalovirus (CMV) is a major cause of morbidity and mortality in transplant patients. In this study, we compared the diagnostic value of pp65 antigen test, qualitative nested polymerase chain reaction (PCR), and quantitative Taqman PCR in predicting the clinical outcome of CMV infection. METHODS: A total of 169 samples derived from 59 organ-transplant recipients (kidney n= 46, liver n= 11, kidney and pancreas n= 2) were analyzed. Peripheral blood leukocytes (PBL) were isolated using dextran gradient centrifugation, and 2 x 10 cells were analyzed for pp65 antigen by immunofluorescence. A crude DNA extract obtained from the same number of cells was used for qualitative nested PCR and quantitative Taqman PCR analysis. RESULTS.: The correlation coefficient of pp65 antigen test and Taqman PCR was R= 0.699 (P = 0.001). With cut-off values for pp65 antigen test set at greater than 10 positive nuclei per 2 x 10 PBL, sensitivity was 91%, and positive predictive value (PPV) was 70%. When the corresponding cut-off value for Taqman PCR was applied (>125000 genome copies per 2 x 10 PBL), a sensitivity of 83% and a PPV of 68% were found. Both assays allowed for the monitoring of successful antiviral therapy. Although qualitative nested PCR was highly sensitive (95%), it was less useful in predicting CMV disease (PPV 47%) and in therapy control. CONCLUSION: Our data show that pp65 antigen test and Taqman PCR are almost equivalent in the monitoring of CMV infection and disease when identical cell numbers are used for both assays.
    Transplantation. 01/2004; 77(11):1692-8.
  • Transplantation Proceedings 06/2003; 35(3):944-5. · 0.95 Impact Factor
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    ABSTRACT: Mycophenolate mofetil (MMF)-based immunosuppression has reduced the acute rejection rate in adults and in children in the early posttransplantation period. Three-year posttransplantation results have been reported for adults but not for children thus far. In the present open-labeled study, patients 18 years old and younger were evaluated prospectively for up to 3 years after renal transplantation (RTX). Eighty-six patients receiving MMF in combination with cyclosporine and prednisone without induction were evaluated for patient survival, transplant survival, renal function, arterial blood pressure, adverse events, and opportunistic infections. These patients were compared with a historic control group (n=54) receiving azathioprine (AZA) instead of MMF. Patient survival after 3 years was 98.8% in the MMF group and 94.4% in the AZA group (NS). Intent-to-treat analysis of graft survival demonstrated superiority for MMF (98% vs. 80%; P<0.001). Cumulative acute rejection episodes occurred in 47% of patients in the MMF group versus 61% in the AZA group (P<0.05). Renal function was not significantly different, neither after 3 years nor in the long-term calculation. Antihypertensive medication was administered to 73% to 84% of patients, similar in both groups. Opportunistic infections were recorded only for MMF. Infection rates were comparable to those reported in adults. These results suggest that MMF is safe and beneficial as a longer term maintenance immunosuppressive drug in children and adolescents.
    Transplantation 02/2003; 75(4):454-61. · 3.78 Impact Factor
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    ABSTRACT: Liver tumors located near the retrohepatic vena cava are often considered nonresectable. For these patients cryoablation could be a therapeutic option. In this study the safety and efficacy of hepatic cryosurgery involving the retrohepatic vena cava were investigated. Cryolesions involving the vena cava were created in 26 pigs. Follow-up was 24 h and 14 days. The extent of the cryolesion, damage to the vena cava and complications were assessed after autopsy. The cyronecrosis extended into the wall of the vena cava in 81&percnt; of the animals. All animals had an uneventful recovery without any complications such as ruptures of the vessel, thrombosis or pulmonary embolism. Microscopically elastic and collagenous fibers of the cava wall remained intact. The continuity of the vessel wall was conserved. In conclusion, the safety and efficacy of cryosurgical treatment involving the retrohepatic vena cava were shown in a pig model.
    European Surgical Research - EUR SURG RES. 01/2003; 35(2):67-74.