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The aim of this study was to evaluate the prognostic potential of a 3-parameter visual scoring (qualitative score [QS]) system for hepatobiliary phase gadoxetic acid-enhanced magnetic resonance imaging (MRI) in orthotopic liver transplant grafts.This retrospective study of 128 patients was approved by our institutional review board. Two readers independently assigned 3 QSs to T1-weighted MRI scans, 20 minutes after the administration of gadoxetic acid (hepatobiliary phase), based upon the following: (1) liver parenchymal enhancement (EnQS, 0-2); (2) biliary contrast excretion (ExQS, 0-2); and (3) signal intensity of the portal vein relative to the liver parenchyma, that is, the portal vein sign (PVsQS, 0-2). The functional liver imaging score (FLIS) was calculated as the sum score of these 3 parameters. The relative liver enhancement (RLE) was measured as well. Demographic, clinical, laboratory parameters, and imaging findings were included in univariate and multivariate statistical analyses. The primary end point was graft failure, that is, retransplantation or death from liver failure. The probability of graft survival was calculated by Kaplan-Meier estimates and Cox proportional hazards regression.In the univariate analysis, EnQS, ExQS, PVsQS, and FLIS scores, as well as RLE, were significantly associated with the 1- to 3-year probability of graft survival (P0.001). For a FLIS of (0), the 3-year probability of graft survival was 6.5%, whereas it was 51.3% for a FLIS of (1-3) and 100% for a FLIS of (4-6) (P0.001). In the multivariate survival models, EnQS, ExQS, and PVsQS, each independently outperformed the majority of clinical and laboratory parameters, and the FLIS did even better regarding the prediction of 1- to 3-year graft survival.In liver transplant recipients, gadoxetic acid-enhanced MRI-derived QSs (ie, EnQS, ExQS, and PVsQS), as well as the FLIS and RLE, can predict graft survival probability.

Endothelial deposition of the complement split product C4d is an established marker of antibody-mediated acute renal allograft rejection. A contribution of alloantibody-dependent immune reactions to chronic rejection is under discussion. In this study, the association of immunohistochemically detected endothelial C4d deposition in peritubular capillaries (PTC) with morphologic features of chronic renal allograft injury was investigated in a large study cohort. C4d deposits in PTC were detected in 73 (34%) of 213 late allograft biopsies performed in 213 patients more than 12 mo after transplantation (median, 4.9 yr) because of chronic allograft dysfunction. Endothelial C4d deposition was found to be associated with chronic transplant glomerulopathy (CG) (P < 0.0001), with basement membrane multilayering in PTC (P = 0.01), and with an accumulation of mononuclear inflammatory cells in PTC (P < 0,001). Furthermore, C4d deposits in PTC (in biopsies with normal glomerular morphology) were associated with development of CG in follow-up biopsies. Other morphologic features of chronic allograft nephropathy (with exception of tubular atrophy) were not associated with C4d deposits in PTC. Analyses of previous and follow-up biopsies revealed that C4d deposits may occur de novo and may also disappear at any time after transplantation. In conclusion, the data suggest that complement activation in renal microvasculature, indicating humoral alloreactivity, contributes to chronic rejection characterized by chronic transplant glomerulopathy and basement membrane multilayering in PTC.

A series of 74 consecutive patients (48 women, 26 men) were operated for abdominal hydatid disease between June 1949 and December 1995. The patients ranged in age from 15 to 81 years (median 49 years). In 69 cases only the liver was affected; two patients had concomitant extrahepatic disease (one spleen, one spleen and lung), and 3 had cysts in the spleen only. Cysts were multiple in 11 patients and calcified in 24. Conservative surgical procedures were used for 22 cysts in 20 patients [open partial (n = 3), open total (n = 6), closed total cystectomy (n = 9), marsupialization (n = 2), drainage (n = 2)] and radical surgical procedures for 72 cysts in 54 patients [pericystectomy (n = 41), wedge liver resection or hemihepatectomy (n = 25), splenectomy (n = 5), radical resection of a lung cyst (n = 1)]. Altogether 37 patients (50%) were given perioperative antihelmintic chemotherapy with mebendazole (18 patients) or albendazole (19 patients). Operative mortality rates were 5.0% after conservative surgery and 1.8% after radical surgery. Morbidity rates were 25.0% following conservative surgery and 24.1% following radical surgery. Antihelmintic therapy was well tolerated by all but five patients. All side effects were entirely reversible. Among the 74 patients, 60 (81.0%) were available for long-term follow-up (median 7.2 years; range 2.0-47.0 years). Recurrence of disease was seen in 9 of 60 patients at an interval of 3 months to 20 years from the first operation. The rate of recurrence was significantly lower after radical surgical procedures (p = 0.03) and after closed removal of the cyst (p = 0.04).

In a retrospective analysis of 632 orthototopic liver transplant procedures performed between 1982 and 1997, the incidence of primary dysfunction (PDF) of the liver and its influence on organ survival were studied. Graft function during the first 3 postoperative days was categorized into four groups: (1) good (GOT max1000 U/l, spontaneous PT50%, bile production100 ml/day); (2) fair (GOT 1000-2500 U/l, clotting factor support2 days, bile100 ml/day); (3) poor (GOT2500 U/l, clotting factor support2 days, bile20 ml/day); (4) primary non-function (PNF; retransplantation required within 7 days). The aim of this study was to evaluate graft survival comparing organs with PDF (poor function) and PNF vs organs with initial good or fair function. After a median follow-up of 45 months, initially good and fair function of liver grafts resulted in a significantly better long-term graft survival compared with grafts with initially poor function or primary non-function (if re-transplanted) (P0.01). The Cox model revealed primary function as a highly significant factor in the prediction of long-term graft survival (P0.0001). We conclude that these results confirm the hypothesis that primary graft function is of major importance for the long-term survival of liver transplants. Patients with a poor primary function have the worst survival prognosis, which leads to the interpretation that these patients may be candidates for early retransplantation.

In recent years, alcoholic cirrhosis has been accepted as an indication for OLT, compliance of patients suffering from alcoholic cirrhosis is still under discussion, however. 118 patients who had undergone OLT for alcoholic cirrhosis were considered for analysis. The mean follow-up time of the study population was 53.7 ± 38.9 months. Compliance was defined by 3 parameters: 1. Sobriety. Fifteen (13%) out of 118 recipients suffered an alcohol relapse during the observation period. There was no difference between the groups with or without alcohol relapse concerning compliance with medication, incidence of rejection, or adherence to checkups. 2. Drug-compliance. Nineteen recipients (16%) were not within the target range with the immunosuppressive medication. Comparison of the compliant- and non-compliant groups produced a significant difference for late acute rejection, the other parameters being similar in the subgroups. 3. Adherence to appointments. Nearly all patients in the study population (>95%) were compliant with both transplant and psychological appointments in the outpatient clinic. In conclusion, analysis of our data indicates that patients with OLT for alcoholic cirrhosis are compliant, although alcohol relapse occurs in 13% of recipients.

Early vascular occlusion is liable to cause graft failure, and differential diagnosis between this condition and primary nonfunction (PNF) caused by preservation injury may be difficult. Apoptosis has been detected in immunomediated cytotoxicity and is known to be triggered by mild ischemia. In a retrospective analysis we investigated the role of apoptosis in vascular occlusion, PNF, and acute allograft rejection to improve the differential diagnosis of early graft failure. The liver graft histology of 75 patients (46 male, 29 female) a median 47 (1–64) years of age was screened semiquantitatively for the rate of apoptosis on the hematoxylin-eosin stain (HE) and by the in situ end nick labeling technique (TUNEL). This cohort included all patients who developed PNF (n = 9) or vascular occlusion (n = 11) after orthotopic liver transplantation (OLT) in the years 1992 to 1996. Within this period of time we performed 205 OLTs on 189 patients. We further included 22 patients with early acute rejection and 11 controls. The highest rates of apoptotic hepatocytes were seen in vascular occlusion (P < 0.001). Grafts with PNF were explanted 1–3 days after OLT and showed hepatocytes that were 100 % necrotic. Cases of acute early rejection showed a significantly higher apoptotic cell count than did normal controls (P < 0.003), increasing in direct proportion to the severity of rejection. Screening biopsies for the rate of apoptosis can improve the efficacy and accuracy of differential diagnosis of early graft failure.

Post-transplant lymphoceles (LC) may lead to impaired graft function. Treatment modalities include fine-needle aspiration, percutaneous drainage, and surgical internal drainage. Recently, laparoscopic fenestration has been performed with good results, but experience is still limited. Between January 1991 and August 1996, 919 kidney transplantations were performed in 876 patients at our department. There were 745 first, 133 second, 30 third, 9 fourth, and 2 fifth operations. Sixty-three symptomatic LCs were detected in 62 patients (6.8%) after 39 +/- 31 days. In 44% of the cases, graft function was impaired; in 29% hydronephrosis was documented and in 6% infection of the LC. Forty-five of the 62 patients with LC (73%) had histologically proven rejection. Thirty-five of the 63 LCs were drained percutaneously, 20 LCs were internally drained by open surgery, and 8 LCs were drained by laparoscopy. In 14 of the 47 patients (30%) with primary percutaneous drainage, LC recurred; infection occurred in 17%. Twelve of these patients underwent surgery. One surgical redrainage was necessary after open fenestration. No conversion or complication was noted in the laparoscopy group. We conclude that surgery for post-transplant lymphoceles is safe and effective. We favor the laparoscopic technique in selected patients.

Background. 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. Methods. 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 CO levels (target: 250±50 ng/mL). Results. In the intention-to-treat analysis, 40 (45.4%) patients in the CO 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 CO 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 CO 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. Conclusion. 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 CO levels. In C2 monitored patients, C2 levels are not predictive for the incidence of early allograft rejection.

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 Transpl 2003;9:970-975.)

In recent years, alcoholic cirrhosis has been accepted as an indication for OLT, compliance of patients suffering from alcoholic cirrhosis is still under discussion, however. 118 patients who had undergone OLT for alcoholic cirrhosis were considered for analysis. The mean follow-up time of the study population was 53.7 +/- 38.9 months. Compliance was defined by 3 parameters: 1. Sobriety. Fifteen (13%) out of 118 recipients suffered an alcohol relapse during the observation period. There was no difference between the groups with or without alcohol relapse concerning compliance with medication, incidence of rejection, or adherence to check-ups. 2. Drug-compliance. Nineteen recipients (16 %) were not within the target range with the immunosuppressive medication. Comparison of the compliant- and non-compliant groups produced a significant difference for late acute rejection, the other parameters being similar in the subgroups. 3. Adherence to appointments. Nearly all patients in the study population ( > 95 %) were compliant with both transplant and psychological appointments in the outpatient clinic. In conclusion, analysis of our data indicates that patients with OLT for alcoholic cirrhosis are compliant, although alcohol relapse occurs in 13 % of recipients.

Background As significantly more patients die of infection than of rejection after liver transplantation, we have to conclude that overimmunosuppression is common. Our analysis was performed to investigate underlying disease as an appropriate parameter for individually reduced immunosuppression. Design A consecutive series of patients receiving primary liver transplantation was analyzed with regard to acute rejection. Setting Department of transplantation surgery in a university hospital. Patients and Methods From 1988 to 1995, 252 patients received liver transplantation for posthepatitic cirrhosis, alcoholic cirrhosis, cholestatic disease, or hepatoma and were analyzed in a univariate and multivariate manner. Main Outcome Measure The influence of various underlying diseases on the incidence of acute rejection. Results The estimated risk for freedom from acute rejection and analysis of cumulative rates of acute rejection stratified by group showed significant differences between the groups, except for alcoholic and posthepatitic cirrhosis. Severity of acute rejection episodes, as assessed by the need for rescue therapy, was similar in both univariate analysis and cumulative rates for alcoholic and posthepatitic cirrhosis. As expected, patients with cholestatic disease exhibited a significantly increased requirement for rescue therapy. For patients with hepatoma, a low incidence of initial and a high rate of repeated rescue therapy were observed. The varying immunological behavior within this group may have influenced both expansion of the tumor and severity of acute rejection. Multivariate analysis of potential risk factors identified underlying disease as a variable of independent prognostic significance for acute rejection and the need to receive rescue therapy. Conclusion These results indicate the importance of taking the original disease into consideration where immunosuppressive therapy is concerned.

1. OLT ist bei Lebermetastasen im Lausanne-Stadium III anderen Therapieverfahren (systemischer und lokoregionarer Chemotherapie) uberlegen. 2. Trotz nachgewiesenem Rezidiv besteht eine gute Lebensqualitat (palliativer Effekt). 3. Das synchrone Auftreten von hamatogenen Lebermetastasen stellt ein mogliches klinisches Selektionskriterium fur das Langzeituberleden dar. 4. Bedeutung einer zusatzlichen Chemotherapie unklar und weitere Sekektionskriterien zur Verbesserung der PUZ notwendig. 5. Bei neuroendokrinen Tumoren OLT bei nicht Ansprechen anderer Therapieverfahren (Embolisation, Hormon- und Immuntherapie) und bei Ausschlus extrahepataler Manifestation sinnvoll. 6. OLT ist bei nichtresezierbaren Lebermetastasen unter dem Aspekt des bestehenden Organmangels als allgemeine Therapieempfehlung abzulehnen und die Indikation im Einzelfall zu diskutieren.