Anamnese und klinischer Befund: Untersuchungen: Therapie und Verlauf: Folgerung: History and clinical findings: Investigations: Treatment and course: Conclusion:

Introduction, As we have learned, there are no golden rules of immunosuppression in solid organ transplantation, and every transplant program is using its own regimen to prevent or treat rejection. We have retrospectively analyzed the incidence and severity of acute rejection in a consecutive series of living donor liver transplants. The major objective during the whole study period was to ultimately avoid any steroids from the beginning. Methods. Twenty one adult patients and five children received 23 right, one left, and two left lateral lobe grafts from genetically or emotionally related living donors, including four ABO-incompatible pairs. The majority of patients had triple initial immunosuppression, based on tacrolimus, mycophenolate mofetil or sirolimus, and basiliximab or daclizumab. Except methylprednisolone administered before reperfusion in 13 patients, only seven had prednisolone after transplantation, and 12/26 had a completely steroid-free regimen. Results. The overall incidence of biopsy-proven acute rejection was 4/21 in adults (19%) and 4/5 in children (80%). Rejections were mild in five and moderate in three cases, respectively, and easily reversed with steroids in all patients. Different combinations of immunosuppressive drugs or ABO incompatibility did not seem to have an influence on the risk of rejection. Conclusion. Despite the small number of patients in this series, completely steroid-free triple-drug immunosuppression with tacrolimus, mycophenolate mofetil, and basiliximab is safe and efficient to prevent acute rejection in adult recipients of living donor liver transplants. At least short-term administration of prednisolone should be considered in pediatric patients.

BACKGROUND:In living donor liver transplantation (LDLTx) organ procurement is usually well controlled, and allows to assess liver preservation and graft function under standardized conditions. Because publications on histidine-tryptophan-ketoglutarate (HTK) solution are limited, we prospectively studied its safety and efficacy in a consecutive series of LDLTx.METHODS:Twenty-four patients received 22 right, 1 left, and 1 left lateral lobe graft. Liver preservation was done by gravity perfusion with HTK through portal vein, and hepatic artery, and flushing of bile ducts. Total ischemia time was 191 +/- 68 minutes.RESULTS:There was no primary nonfunction, and all partial liver grafts showed good recovery: peak aspartate aminotransferase 577 U/L, total bilirubin 15.15 mg/dL, and partial thromboplastin time 49.37 seconds. One graft was lost from parenchymal fracture secondary to portal hyperperfusion after 6 days, and the patient was salvaged with retransplantation. Thirty-day mortality, including sudden cardiac death, pancreatitis, and hepatic artery rupture, was not related to graft dysfunction. Eight of 24 recipients developed early biliary leakage. There was no late ischemic type biliary lesion.CONCLUSION:These results confirm that HTK solution is safe and effective when used in LDLTx. Potential advantages of HTK in comparison to other preservation solutions are low potassium concentration, low viscosity, no particles, in situ perfusion, no need to flush before reperfusion, improved biliary protection, better recovery of microcirculatory changes, ready to use, and lower costs. Because the risk-benefit ratio is of particular importance in LDLTx the use of HTK solution should be encouraged.

O448 Aims: Preoperative assessment and postoperative restoration of liver volume in both donors and recipients are essential prerequisites for living donor liver transplantation, indicating hepatic function and adequate regeneration. Methods: To compare the recovery of residual left lobes (LL, S.1-4) and right lobe grafts (RL, S.5-8) a consecutive series of 21 donors (age 22-69 yrs) and their corresponding recipients (age 15-61 yrs) were included in a prospective study following right hemihepatectomy and partial liver transplantation, respectively. Immunosuppression was Tacrolimus based in all cases. Serial volumetry by MR imaging was done before, 3, 7, 14, 28, 60, 90, 180 and 360 days after surgery. The following parameters were determined: calculated and actual liver volume (LV) in ml, and in relation to preoperative donor LV (defined as 100%), liver to body weight ratio (LWR, %), and regeneration rate (RR, ml/d). Results: In donors, the mean residual LL was 45 % (LV 757 ml, LWR 1 %), and increased to 50, 59, 61, 67, 69, 75, 83 and 94 % after 3, 7, 14, 28, 60, 90, 180, and 360 days, respectively. 7/21donors showed a significant initial liver volume decrease with a nadir at 3-7 days. The donor with the smallest residual liver (LV 266 ml, 21 %; LWR 0.36 %) had the fastest recovery within the first week (RR 71 ml/d). In contrast, the mean volume of RL grafts (LV 892 ml, LWR 1.18 %) increased much faster, reaching 110 % on day 7, and decreased to 98 % after one year (LWR 2.19 %). Maximum RR in recipients was 243 ml/d within 3 days. Four patients with small-for-size grafts (LWR < 0.8 %) had significantly higher morbidity and mortality. Conclusions: These data confirm the triphasic liver volume restoration after partial hepatectomy as well as transplantation with rapid early increase within 30 days, an intermediate phase, and slow adaptation to the original donor liver volume between 90 and 360 days. In contrast to previous observations we found a significant difference between the residual LL and the RL, demonstrating a 2-3-fold faster and stronger early recovery in the graft. Obviously, it takes longer than a year for both parts of the liver to regenerate to the original donor liver size. The individual liver regeneration process seems to be accelerated by small residual liver volume in the donor, and various factors including portal hypertension, hemodynamic status, immunosuppressive drugs and others in the recipient.

Background. Ischemia-reperfusion injury (IRI) can result in severe organ dys- or nonfunction. Interaction of leukocytes and endothelial cells mediated by E-selectin appears to be a key step for disturbed microcirculation. Therefore we studied gene and protein expression as well as localization of E-selectin during intestinal IRI.Methods. Intestinal tissue samples were obtained from extracorporeal perfused intestines (cold ischemia time [CIT] 2 or 20 hours, each n = 5) and additionally in intestinal transplanted pigs (CIT 2 or 20 hours, each n = 1). Mucosal damage was graded according to the Chin classification. E-selectin mRNA was determined by PCR and quantitative RT-PCR. Localization of E-selectin mRNA was performed by in situ hybridization and of the protein by immunohistochemistry.Results. Histologically, mucosal damage occurred during reperfusion and was earlier and more severe after 20 hours of CIT. E-selectin mRNA expression was detected by PCR already after laparotomy and was elevated after reperfusion. Interestingly, mRNA expression was already increased after 20 hours of CIT. E-selectin mRNA was localized to the luminal surface of muscular, submucosal, and mucosal endothelial cells and the protein was detected on submucosal arterial endothelium as early as 2 hours after reperfusion.Conclusion. Prolongation of CIT results in more severe mucosal damage during reperfusion, which is associated with protein expression of E-selection that might be used as a marker for activated endothelial cells. Increased E-selectin mRNA at end of 20 hours of CIT might indicate a preactivated state of endothelial cells potentially triggered by bacterial translocation or products.

The cardioplegic HTK-solution (Bretschneider) has not been used in human liver transplantation as yet. Herein the first results obtained from 14 patients with HTK-preserved liver grafts are presented. The suitability of HTK-solution could be shown. All grafts functioned primarily except one, where initial non-function was obviously due to donor reasons. The early postoperative peak values of transaminases as a sign of ischemic damage were average and similar to the values of other flushout solutions. Using HTK primary function could be achieved even in livers prospectively assessed as only of fair quality, and livers with poor donor function tests (MegX) functioned from the beginning. HTK-solution therefore seems to allow widening of the acceptance criteria for donor livers. It was not the aim of this trial to extend cold ischemic time, but 3 livers with 11 h and 12 h 25 showed immediate function. How far cold ischemic time can be extended is a still open question. All livers were rapidly cooled and homogeneously flushed out due to the low viscosity of HTK-solution. All livers had a soft consistency after perfusion indicating a low degree of cell edema. HTK therefore is an effective solution for liver preservation.

Background. Intestinal ischemia-reperfusion injury (IRI) represents an exaggerated inflammatory cascade with a complex pathophysiology. IL-2, IL-6, HSP70, and INF-gamma are mediators of the inflammatory process. Therefore, we investigated their kinetics and localization during intestinal IRI. Methods. Pig intestinal specimens were obtained during cold preservation (cold ischemia time 2 hours) and extracorporeal perfusion. Mucosal damage was graded according to the Chiu classification. MRNA expression was determined by Northern blot (IL-2, IL-6, IFN-gamma) or by quantitative RT-PCR (IL-6, HSP70) and localized by in situ hybridization. Results. Histologically, mucosal damge occurred during reperfusion. Expression of IL-2 mRNA was up-regulated after HTK perfusion and was highest at the start and 7 hours after reperfusion. Expression of IL-6 mRNA increased at 2 hours after reperfusion and HSP70 at 3 hours after reperfusion. IFN-gamma mRNA was expressed after HTK perfusion, with expression of this cytokine increasing to 1 hour after the start of reperfusion, and decreasing thereafter. IL-2 mRNA was localized to endothelial cells (EC) and leukocytes and in close relation to ganglion cells (GC): IL-6 mRNA in EC, smooth muscle cells (SMC), and GC: HSP70 mRNA in EC and SMC and IFN-gamma mRNA in leukocytes. Conclusion. IL-2, IL-6, HSP70, and INF-gamma are parameters of early mRNA expression during intestinal IRI. EC, SMC, leukocytes, and GC have been identified as sources of transcripts that might afford potential targets for intervention strategies to attenuate IRI.

BACKGROUND:Urine cytology, although considered a valuable diagnostic tool in the monitoring of kidney graft function, is hampered by difficulty in differentiating the nucleated non-squamous cells in urine using conventional techniques. We have now developed a method for the simple identification of urinary cell types by lectin staining.METHODS:Acetone-fixed cytopreparations of urinary sediments were incubated with the lectin combination Sophora Japonica agglutinin (SJA; rhodamine-labelled) and Erythrina cristagalli agglutinin (ECA; fluorescein isothiocyanate (FITC)-labelled) for 15 min, followed by staining of the nuclei with 4',6-diamidino-2-phenylindole (DAPI). The courses of 38 patients were serially monitored after kidney transplantation during the period in hospital.RESULTS:Nucleated urinary cell types could be easily identified from one specimen by their characteristic lectin-binding pattern using triple-immunofluorescence microscopy (FITC/rhodamine/ultra violet), permitting a differentiation between proximal (SJA+/ECA+) and distal tubules (SJA-/ECA+), collecting ducts (SJA+/ECA-) and lymphocytes (SJA-/ECA-). Stable graft function was characterized by low numbers of lymphocytes, tubular cells and urothelia. During rejection episodes, but not graft dysfunction unrelated to rejection, urinary excretion of lymphocytes as well as of distal tubular cells (from 1.0 to 6.0 and from 1.4 to 4.0 per 10 high-power fields, respectively) increased significantly up to 3 days prior to clinical diagnosis.CONCLUSIONS:Lectin staining facilitates unambiguous differentiation of the urinary cell types, in particular the various tubular epithelial cells, which are otherwise difficult to identify. This technique provides a rapid and easily applicable tool to evaluate the significance of the respective cell types in the monitoring of kidney graft function.

HistopathologyVolume 40, Issue 5 p. 485-487 Undifferentiated small cell hepatoblastoma with a chromosomal translocation t(22;22)(q11;q13) B Gunawan, B Gunawan Institute of Pathology, University of Göttingen, Göttingen, Germany,Search for more papers by this authorK-L Schäfer, K-L Schäfer Institute of Pathology, University of Münster, Münster, Germany,Search for more papers by this authorB Sattler, B Sattler Institute of Pathology, University of Göttingen, Göttingen, Germany,Search for more papers by this authorT Lorf, T Lorf Department of Surgery, University of Göttingen, Göttingen, GermanySearch for more papers by this authorB Dockhorn-Dworniczak, B Dockhorn-Dworniczak Institute of Pathology, University of Münster, Münster, Germany,Search for more papers by this authorB Ringe, B Ringe Department of Surgery, University of Göttingen, Göttingen, GermanySearch for more papers by this authorL Füzesi, L Füzesi Institute of Pathology, University of Göttingen, Göttingen, Germany,Search for more papers by this author B Gunawan, B Gunawan Institute of Pathology, University of Göttingen, Göttingen, Germany,Search for more papers by this authorK-L Schäfer, K-L Schäfer Institute of Pathology, University of Münster, Münster, Germany,Search for more papers by this authorB Sattler, B Sattler Institute of Pathology, University of Göttingen, Göttingen, Germany,Search for more papers by this authorT Lorf, T Lorf Department of Surgery, University of Göttingen, Göttingen, GermanySearch for more papers by this authorB Dockhorn-Dworniczak, B Dockhorn-Dworniczak Institute of Pathology, University of Münster, Münster, Germany,Search for more papers by this authorB Ringe, B Ringe Department of Surgery, University of Göttingen, Göttingen, GermanySearch for more papers by this authorL Füzesi, L Füzesi Institute of Pathology, University of Göttingen, Göttingen, Germany,Search for more papers by this author First published: 13 May 2002 https://doi.org/10.1046/j.1365-2559.2002.t01-2-01390.xCitations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Fletcher JA, Kozakewich HP, Pavelka K et al. Consistent cytogenetic aberrations in hepatoblastoma: a common pathway of genetic alterations in embryonal liver and skeletal muscle malignancies? Genes Chromosomes Cancer 1991; 3 ; 37–43. 2 Schneider NR, Cooley LD, Finegold MJ, Douglass EC, Tomlinson GE. The first recurring chromosome translocation in hepatoblastoma: der(4)t(1;4)(q12;q34). Genes Chromosomes Cancer 1997; 19 ; 291–294. 3 Hansen K, Bagtas J, Mark HF, Homans A, Singer DB. Undifferentiated small cell hepatoblastoma with a unique chromosomal translocation: a case report. Pediatr. Pathol. 1992; 12 ; 457–462. 4 Sattler B, Gunawan B, Lorf T, Müller D, Ringe B, Füzesi L. Undifferenziertes kleinzelliges Hepatoblastom. Pathologe 2000; 21 ; 456–459. 5 Mitelman F, ed. ISCN (1995): An international system for human cytogenetic nomenclature. Basel: S. Karger, 1995. 6 Delattre O, Zucman J, Plougastel B et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992; 359 ; 162–165. Citing Literature Volume40, Issue5May 2002Pages 485-487 ReferencesRelatedInformation