Rainer Lück

Indications for and outcomes after combined lung and liver transplantation: a single-center experience on 13 consecutive cases.

Background. Combined lung and liver transplantation (Lu-LTx) is a therapeutic option for selected patients with coexisting lung and liver disease. For several reasons, Lu-LTx is performed in few centers and information about the technical issues, posttransplant management and long-term outcomes associated with this procedure is limited. Methods. We analyzed data from 13 consecutive patients who underwent combined Lu-LTx at Hannover Medical School (Hannover, Germany) between April 1999 and December 2003. The main indications were cystic fibrosis, &agr;1-proteinase inhibitor deficiency and portopulmonary hypertension. All patients had advanced cirrhosis and severe pulmonary disease manifestation. Results. Ten patients received a sequential double Lu-LTx, one patient received a single Lu-LTx, one received a double lung and split liver transplantation, and one received an en-bloc heart-lung and liver translantation. Immunosuppression was based on cyclosporine in a triple/quadruple regimen. Postoperative surgical complications occurred in eight patients. There were two perioperative deaths; two patients died during the first year on day 67 and 354, respectively, and one patient died at month 53. The overall patient survival rates at 1, 3, and 5 years were 69%, 62%, and 49%, respectively. Conclusion. Combined Lu-LTx is a therapeutic option for highly selected patients with end-stage lung and liver disease with acceptable long-term outcome.

Outcome and quality of life in patients with polycystic liver disease after liver or combined liver‐kidney transplantation

In advanced stages of polycystic liver disease, often associated with polycystic kidney disease, a curative therapy is liver or combined liver‐kidney transplantation. However, little is known about long‐term outcome and quality of life. Between 1990 and 2003, 36 patients (32 female, 4 male) with polycystic liver or combined liver‐kidney disease underwent liver (n = 21) or liver‐kidney (n = 15) transplantation at our center. Main indications for liver transplantation were cachexia, muscle atrophy, loss of weight, recurrent cyst infections, portal hypertension, and ascites. Apart from clinical parameters, 2 anonymous questionnaires (standard short form 36 and self‐designed) addressing quality of life and social status were evaluated. Five patients (14 %) died due to sepsis or myocardial infarction with pneumonia, all within 61 days after transplantation. The follow‐up time of the remaining 31 patients ranged from 5 to 156 months, with a mean of 62 months. Of the 23 (74%) answered the questionnaires, 91% of patients felt “much better” or “better,” only 9% felt “worse” than before, and 52% of patients participated in sports regularly. Fatigue, physical fitness, loss of appetite, and vomiting improved significantly after transplantation. Physical attractiveness and interest in sex increased as well. Professional occupation did not change for 71% of patients. Family situation before and after transplantation changed in 1 case only. Finally, 78% of patients said they would opt for transplantation again, while 17% were undecided; 1 patient would not repeat transplantation. In conclusion, patients with advanced polycystic liver or polycystic liver‐kidney disease have an excellent survival rate and an improved quality of life after liver or combined liver‐kidney transplantation. Liver Transpl 12:1268‐1277, 2006.

Progressive Deterioration of Endocrine Function After Intraportal but Not Kidney Subcapsular Rat Islet Transplantation

In inbred streptozocin-induced diabetic rats, the long-term function of different endocrine pancreatic isografts was compared. Isolated islets transplanted into the portal vein showed a progressive deterioration of function over time. In contrast, islets under the kidney capsule sustained a constant long-term function controlling all clinical signs of diabetes. Recipients of kidney subcapsular islets displayed normal growth rate, peripheral serum glucose and insulin levels, and metabolic parameters. However, their functional reserve was markedly reduced as revealed by diminished glucose tolerance and reduced insulin-secreting capacity after an intravenous glucose challenge. Vascularized whole-organ pancreatic grafts with portal venous drainage led to complete normalization of all parameters determined in this study. This study showed that the long-term function of islets transplanted under the kidney capsule is superior compared with islets transplanted into the portal vein.

Use of Neoral C2 monitoring: a European consensus

Large‐scale clinical trials using C2 monitoring of cyclosporine (CsA) microemulsion (Neoral) in renal transplant recipients have demonstrated low acute rejection rates and good tolerability with a low adverse event profile in a variety of settings: with or without routine induction therapy; in combination with mycophenolate mofetil; with standard‐exposure or low‐exposure Neoral; and in patients with immediate or delayed graft function. In liver transplantation, C2 monitoring significantly reduces the severity and incidence of acute rejection compared with C0 monitoring, without adverse consequences in terms of renal function or tolerability. Different C2 targets are appropriate depending on adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk of renal toxicity and time since transplantation. CsA absorption may increase substantially in most patients during the first 1–2 weeks post‐transplant, and this should be taken into account to avoid overshooting C2 target range. A patient with a low C2 value may be either a low or a delayed absorber of CsA, or be a normal absorber who is receiving too low a dose of Neoral. C2 monitoring alone is insufficient to differentiate between these types of patients, and measurement of additional timepoints is recommended. Adopting C2 monitoring in maintenance transplant patients identifies those who are overexposed to CsA. In summary, randomized, prospective, multicenter studies and single‐center trials have evaluated Neoral C2 monitoring within a range of regimens in different organ types, providing a robust evidence base for the benefits of this sensitive monitoring technique.

Successful Outcome Of Acute Graft-versus-host Disease In A Liver Allograft Recipient By Withdrawal Of Immunosuppression

BACKGROUND Graft-versus-host disease (GVHD) after liver transplantation is uncommon, and the outcome is almost always fatal. Since 1987, about 30 cases have been described, and patient survival is mostly exceptional. METHODS A 29-year-old man underwent retransplantation due to chronic cholestatic syndrome, 5 years after his first liver transplantation. Indication for the first liver transplantation was acute liver failure caused by exsiccosis. After the second transplantation, the patient had an initially uneventful course, developing thrombocytopenia at day 21 followed by skin rash and septic complications. Diagnosis of acute GVHD was made by using serological techniques for HLA-A and HLA-DRB and subsequently by fluorogenic sequence-specific primed polymerase chain reaction. In addition, donor lymphocytes were marked by immunohistochemical methods via biopsies of the skin. Immunosuppressive therapy was withdrawn to allow the patients own immune system to eliminate donor cells. RESULTS By withdrawing the immunosuppressive therapy, clinical and morphological signs of GVHD vanished. The patient is doing well without recurrence 13 months after transplantation. CONCLUSION Withdrawal of immunosuppressive therapy is a promising approach in the treatment of acute GVHD to allow the patients immune system to reconstitute itself, reject offending lymphocytes, and avoid lethal septic complications.

Hepatic reticuloendothelial function during parenteral nutrition including an MCT/LCT or LCT emulsion after liver transplantation – a double‐blind study

Abstract.It has been demonstrated that total parenteral nutrition (TPN) modulates the function of the hepatic reticuloendothelial system (RES). The objective of this study was to evaluate the impact of two different TPN lipid emulsions on the recovery of allograft RES function after orthotopic liver transplantation (OLTx). In a prospective, double-blind study, OLTx patients were randomly assigned to two treatment groups. Group I (n=13) received a TPN regimen that included long-chain triglycerides (LCT). Group II (n=9) received a TPN regimen that included a fat emulsion consisting of both medium-chain triglycerides (MCT) and LCT. At baseline, i.e., on days 2 or 3 after OLTx (t1), before lipids for TPN were started, hepatic RES function was determined using the human serum albumin millimicrosphere technique (K-value, 1/min). A second measurement (t2) was obtained after 7 days of TPN, including one of the studys two fat emulsions. The mean (± SD) K-value (1/min) was 0.48±0.16 in the LCT group and 0.55±0.28 in the MCT/LCT group at t1, and it improved to 0.62±0.21 in the LCT group and to 0.86±0.32 in the MCT/LCT group at t2. RES function recovery was significantly better in the MCT/LCT group (P≤0.05). MCT/LCT emulsion appears to be the TPN fat emulsion of choice after OLTx as it seems to have less impact on hepatic RES recovery.

Quality of life following living donor nephrectomy comparing classical flank incision and anterior vertical mini-incision

In this study we focused on the quality of life and satisfaction of living kidney donors comparing traditional lumbar (LDN) and mini-incision donor nephrectomy (MIDN). From May 1996 to December 2002, 174 donor nephrectomies including 127 cases of LDN and 47 cases of MIDN were performed. Donors were evaluated using the SF-36 quality-of-life survey as well as a questionnaire dealing with donors‘ attitude towards kidney donation, financial burdens, pain, cosmetic satisfaction and duration of sick leave. Our donors achieved comparable or even higher scores in all the SF-36 categories in comparison to the general US population. Following MIDN, quality of life tended to be superior compared to that of LDN donors; however, statistical significance was reached only in one of the eight categories. Duration of sick leave following surgery was in favor of MIDN compared to LDN donors. Statistically significant differences favoring MIDN were observed regarding postoperative hospital stay and cosmetic satisfaction. The procedure would be again undergone by 94 of LDN and 97% of MIDN donors. Open-donor nephrectomy is a safe and cost-effective procedure. Introduction of the here-described MIDN has led to comparable or even improved results compared to LDN.

Significance of portal venous drainage after whole-organ pancreas transplantation for endocrine graft function and prevention of diabetic nephropathy.

The significance of portal venous drainage after whole-pancreas transplantation both for metabolic control and development of diabetic nephropathy was investigated. Streptozotocin-diabetic inbred LEW rats received a duct-ligated pancreas graft with either systemic or portal venous drainage and were followed for up to one year. Normal and untreated diabete rats (n=18 in each group) served as controls. Irrespective of the route of venous drainage pancreas transplants normalized the diabetic polyuria, polyphagia, and polydipsia. Growth rates and general health did not differ from normal rats. Pancreas transplantation with portal venous drainage furthermore aormalized nonfasting blood glucose and peripheral insulin levels, and intravenous glucose tolerance. Pancreas transplantation with systemic venous drainage, however, was associated with peripheral hyperinsulinemia, slightly elevated nonfasting blood glucose levels, and suprauormal K-values in intravenous glucose tolerance tests. Though portal venous drainage was associated with better metabolic control than systemic vanous drainage, both techniques of pancreas transplantation proved equally effective to prevent the development of diabetic glomerular membrane thick-ening determined 6 and 12 months posttransplant.

Achieving adequate cyclosporine exposure in liver transplant recipients: A novel strategy for monitoring and dosing using intravenous therapy

It has been demonstrated that achieving therapeutic levels of cyclosporine (CsA) exposure in the first days posttransplant is critical for effective prevention of rejection. In patients receiving oral CsA, it has been shown that C2‐monitoring is superior to trough (trough level [C0]) measurement. Intravenous administration may overcome the problem of CsA absorption dysfunction seen in some patients. Currently, little evidence is available concerning CsA exposure after intravenous application. Twenty de novo liver transplant recipients were given twice‐daily 4‐hour infusions of intravenous CsA, with full pharmacokinetic profiles undertaken during the first postoperative week. The greatest CsA exposure occurred during the period 2 to 4 hours after the start of infusion. The correlation between C0 and area under the curve (AUC0–12) was r2 = 0.18; the correlation between C2 and AUC0–12 was r2 = 0.82. The best 2‐point predictive model included both C2 and C4 (r2 = 0.90). There was a poor correlation between CsA dose per kilogram of body weight and AUC0–12 (r2 = 0.19); total CsA dose also showed a weak relationship to exposure (r2 = 0.37). When patients were divided according to initial or delayed graft function, there was good correlation between total CsA dose and AUC0–12 (initial function, r2 = 0.71; delayed function, r2 = 0.86). In conclusion, previous discouraging results with intravenous CsA in liver transplant patients may have been due to a limited understanding of CsA pharmacokinetics. Our results show that C2‐monitoring during 4 hour infusion provides a reliable indication of CsA exposure. Calculation of starting dose based on initial graft function is more precise than use of body weight. Using C2‐monitoring to individualize dosing and function‐based calculations of starting dose could be expected to improve clinical outcomes in patients receiving intravenous CsA. (Liver Transpl 2004;10:686–691.)

Genetic control of rat heart allograft rejection: effect of different MHC and non-MHC incompatibilities.

We investigated the genetic control of heterotopic heart allograft rejection using a family of standard inbred, major histocompatibility complex (MHC)-congenic, and intra-MHC recombinant rat strains. Gene products of the various regions within the rat MHC differed markedly in their capacity to induce rejection. Isolated incompatibility at class I antigens encoded by theRT1. A andRT1. C regions failed to induce rejection within the observation period of 100 days, whereas class II antigens encoded by theRT1.B/D region provoked rapid rejection within 10 days. By comparison of the rejection times of isolated and combined incompatibilities a number of functional interactions could be demonstrated between individual MHC regions which either prolonged or shortened allograft survival. In contrast to rapid rejection of MHC-mismatched heart allografts, differences at non-MHC histocompatibility antigens were associated with graft survival beyond 100 days, although chronic rejection of variable severity was detected histologically. Disparity at non-MHC plus class I antigens, however, provoked acute heart allograft rejection.