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Biomedical subjects

F Muehlbacher

Publications and source records attributed to F Muehlbacher.

18 recordsLinked to original sources

Influence of cumulative number of marginal donor criteria on primary organ dysfunction in liver recipients.

BACKGROUND: The aim of this cohort study was to assess the cumulative effect of marginal donor criteria on initial graft function and patient survival after liver transplantation. METHODS: We included 734 consecutive patients who underwent orthotopic liver transplantation at the Vienna General Hospital between January 1993 and December 2003. We employed the local registry of the Department of Transplant Surgery, where variables of all patients are routinely and prospectively recorded. Primary outcome was initial graft function, secondary outcome was patient survival. RESULTS: Cumulative number of marginal donor criteria was significantly and linearly associated with an increased rate of primary dysfunction (PDF; p = 0.005). In patients with more than three cumulative marginal donor criteria the rate of PDF was 36%. Patient survival was not influenced by the cumulative number of donor criteria (log-rank test, p = 0.81). Independent marginal donor criteria to predict PDF were cold ischemia time >10 h [odds ratio (OR) 0.56; 95% CI 0.32-0.98] and donor peak serum sodium >155 mEq/L (OR 0.44; 95% CI 0.26-0.77), as assessed in a multivariate regression model. CONCLUSIONS: The use of marginal liver donors with more than three marginal donor criteria shows deleterious effects on initial graft function. Noteworthy, patient survival was not associated with marginal donor criteria, which may be explained by early and successful retransplantation of liver recipients with primary non-function.

Cohort Studies↗

Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma.

We performed a pilot-study on pegylated liposomal doxorubicin (PLD) for advanced hepatocellular carcinoma. Seventeen patients received 40 mg/m(2) PLD intravenously every 4 weeks. A clinical benefit response was achieved in 50% (complete remission 7%, minor remission 7%, stable disease 36%). Toxicities were moderate. In view of these encouraging findings, further studies appear warranted.

Adult↗

Post-transplant acute myeloid leukemia (PT-AML).

Acute myeloid leukemia following organ transplantation (PT-AML) is a rare event with only a few published cases in the literature. We present three patients who developed AML (FAB M1, M5, M4) after renal, double lung or liver transplantation. Molecular analysis detected a t(9;11) in one patient and documented the recipient origin of AML in a second patient. All patients were treated with chemotherapy. Immunosuppression was reduced to cyclosporin A (CsA) and prednisone in two patients and to prednisone alone in one patient. Two patients achieved a complete remission (CR), with a remission duration of 4.6 months in one patient, the other patient died from septicemia after 15.2 months in CR. One patient was refractory to chemotherapy and died from septicemia. This report together with the documented cases in the literature suggests that PT-AML (1) develops after a median interval of 5 years after transplantation with variable latency (range, <1-17 years); (2) is heterogeneous with respect to FAB classification; (3) shows chromosomal and molecular changes typical of therapy-related AML (t-AML: -7, +8, 11q23, inv16, t(15;17)); (4) standard chemotherapy is feasible after reduction of immunosuppression and produces a CR rate of 56% with a median remission duration of 4.6 months and an overall survival of 2.6 months; (5) the major complications are early death (25%), gram-negative septicemia, progressive disease or relapse. This review provides diagnostic and therapeutic experiences and guidelines for the management of this increasing group of post-transplant patients.

Acute Disease↗

Prediction of graft dysfunction by analysis of liver biopsies after cold storage.

Failure of the hepatic allograft continues to be a serious life-threatening risk for the recipient. Because no effective method of extracorporeal support is available for these patients, early retransplantation is the only alternative that offers the potential for survival. The aim of this prospective analysis was to search for a predictor of primary non-function of hepatic allografts before reperfusion. From March to June 1993 we investigated 19 liver biopsies which were obtained during the preparation of the donor liver in the back table bath immediately before the implantation of the organ. All organs were preserved by UW solution. Biopsies were stored at -80 degrees C, the working-up process was started by dividing the biopsy into several portions for the determination of fat (petrol-ether extraction), water (weighing before thawing and after drying) and free amino acids (OPA-HPLC method). Graft function was categorized into three groups: (1) good function; (2) fair function; (3) primary non-function (PNF). In addition to known risk factors for delayed graft function such as a long stay of the donor in intensive care and a prolonged anhepatic period of the recipient, we were able to demonstrate that organs with malfunction had a higher fat and water content. Donor livers developing PNF showed a trend towards higher total and subdivided amino acids, which could be explained by the incapacity of the liver to utilize available substrates for gluconeogenesis.

Biopsy↗

Tumor recurrence after oLTX.

Although early survival following transplantation for primary hepatic cancer is excellent, previously reported high recurrence rates have generally discouraged liver replacement for this condition. The aim of this retrospective analysis was to examine the influence of risk factors on the development of early tumor recurrence. Between December 1982 and June 1995, 480 liver transplantations were performed at a single institution. Out of these, 103 patients had unresectable primary hepatic cancer (88 hepatocellular cancer; HCCA; 20%) and 15 had cholangiocellular cancer (CHCA; 4%). The influence of the following tumor-associated risk factors was assessed: tumor size, tumor distribution within the liver, grading, pseudocapsular formation, vascular invasion, lymph node metastasis, and cirrhotic alteration. The diagnosis of tumor recurrence was made using various radiological imaging techniques, reelevation of serum alphafetoprotein, or autopsy. For patient survival and disease-free period, data analysis was performed by the method of Kaplan-Meier. The Cox model was used for multivariate analysis; a P-value of less than 0.05 was considered to be significant. The mean age of the 103 patients was 54 years (range 15-63a). There were 22 female and 81 male patients. The follow-up period ranged between 4 and 108 months. Twenty-nine patients (50%) died during the follow-up period due to recurrence of disease. The survival rates of the 88 patients with HCCA were 57%, 34%, and 26% at 1, 3, and 5 years, respectively, after orthotopic liver transplantation (oLTX; follow-up 36 month). Of the 15 pts with CHCA the rates were 53%, 33%, and 33%, respectively, with a median follow-up of 60 months. The influence of the risk factors studied showed a significantly longer disease-free period for the following tumor characteristics: grading below or equal 2 (P = 0.009) and absence of vascular invasion (P = 0.04). Regarding a median survival rate of 2-4 months for patients with unresectable malignant liver tumors, these results confirmed the indication for oLTX, especially if the patient does not compete with someone on the waiting list for benign liver disease.

Adolescent↗

Immunological risk factors are solely responsible for primary non-function of renal allografts.

Primary non-function (PNF) of renal allografts has been attributed to various risk factors, among them immunological ones, as well as unfavourable preservation conditions. To investigate the impact of these risk factory on the occurrence of PNF, 1335 consecutive kidney transplants performed at a single centre over a 10-year period were analysed. All patients received immunosuppression based on cyclosporine. As the method of analysis a conditional stepwise logistic regression model was chosen, comparing each graft suffering PNF with its partner kidney retrieved from the same donor. Thus, all donor-related variables could be omitted from the analysis, as they are the same in every pair of grafts. Risk factors analysed included panel-reactive antibodies, number of pretransplant transfusions, pregnancies, number of prior transplants, cold and second warm ischaemia time, mismatches on HLA loci A, B and DR and recipient age. The overall incidence of PNF was 87 grafts (6.5%). One patient suffered immediate rejection due to transplantation of an ABO incompatible graft. This case was excluded from further analysis. PNF occurred three times in recipients of living related grafts, twice in recipients of en-bloc grafts and four times in grafts, in which the paired kidney was either not transplanted or shipped outside the Eurotransplant region, so that no paired graft was available for matched case-control analysis. Of the remaining 77 pairs, twice both organs of one donor failed immediately. The remaining 73 complete pairs were analysed. Two of the investigated risk factors have independently a significant impact on the occurrence of PNF. Increasing the number of pretransplant transfusions raises the relative risk of graft failure up to six fold (P=0.02), while a history of prior transplants bears a relative risk of 0.21E05 (P=0.005). Ischaemia has no significant impact on the occurrence of PNF. Our data strongly suggest that immunological rather than donor risk factors are responsible for the non-function of kidney grafts.

ABO Blood-Group System↗

Reasons for 50% reduction in the number of organ donors within 2 years--opinion poll amongst all ICUs of a transplant centre.

To detect the reasons for a massive decrease in the annual number of organ donors and as a means of evaluating the effectiveness of our information programme, a questionnaire was designed and sent to all intensive care units (ICUs) in our catchment area. We wished to obtain information about medical, organizational and capacity problems and negative occurrences that had happend during past retrievals. Although 60% of the answers we reiceved (87% feedback rate) mentioned the additional workload involved in treating an organ donor (and 88% had serious problems because of the shortage of nurses), less than 16% remembered a "lost" donor because of capacity problems. Eighty-six percent recognized our efforts to support them in any respect and were satisfied with the amount of "service" provided by the transplantation (TX) centre. About 45% remembered negative occurrences. More than 85% of all replies asked for more and continuing information related to organ donation and transplantation. We think that the key to a successful TX programme is a system of active care for the ICU staff in all peripheral hospitals; repeated mailing of updated information brochures, annual lectures about new developments, letters of thanks after each reported donor (including information on the fate of the organs), visiting donor ICU's accompanied by successfully transplanted recipients, etc.... The downwards trend of donor rates in our area clearly shows that it takes more than a stable legal situation to ensure the necessary amount of donor organs, even a very successful TX centre has to work hard to maintain a certain standard of knowledge, information and motivation amongst the staff of the peripheral hospitals. Moreover, the high turnover rate of ICU personnel requires a steady "flow of information" and cooperation between the "transplant people" and their coworkers outside to guarantee a permanent state of awareness concerning organ donation and transplantation. In fact, awareness seems to be the key issue: the activity of sending out the questionnaires was enough to raise the number of reported donors from 72 (estimated in July) to 96 (31 December 1992).

Austria↗

A reliable and safe way of shortening cadaver kidney ischemia time: prenephrectomy tissue typing using donor lymph node cells.

The purpose of this study was to investigate the impact of prenephrectomy donor tissue typing on tissue typing quality and transplantation outcome in human kidney transplantation. We report on 680 consecutive kidney transplantations performed at the Vienna Transplantation Center from 1986 to June 1991. In 343 of them, HLA typing was performed using donor lymph node cells obtained in a small surgical procedure several hours before organ retrieval. The mean cold ischemia time (CIT) could be reduced to 17.7 h in these patients compared with 21.9 h in the control group (n = 337, conventional tissue typing using spleen lymphocytes obtained during the organ removal, P = 0.0001). There was a trend towards better initial and long-term function in the lymph node group; however, this did not reach statistical significance. The clarity of tissue typing results was significantly better when lymph nodes were used as the lymphocyte source. We conclude that prenephrectomy tissue typing is a feasable and inexpensive method of shortening CIT in renal transplantation and favors HLA typing, both likely to benefit transplantation outcome particularly within organ exchange programs.

Cadaver↗

Orthotopic liver transplantation in the management of end stage liver disease: the University of Vienna experience.

Two hundred and eight orthotopic liver transplantations (OLT) were performed in 191 patients at the I Department of Surgery, University of Vienna from 1982-1990. The most frequent indications were hepatocellular carcinoma, alcoholic cirrhosis, posthepatic cirrhosis, primary biliary cirrhosis, and fulminant hepatic failure. Patients with malignancy constituted 33.8% of cases. The overall results showed a 64% one-year and 58% two-year survival; best results were seen in patients with primary biliary cirrhosis and the poorest long-term results were in malignancy. There were 23 postoperative deaths (11%). Primary non-function was seen in 14 (7%) cases; acute rejection episodes were seen in 62% of patients. The presence of a well organised cadaver organ procurement system in eastern Austria with upto 41 donors per million population per year ensures that the 57% growth rate in OLT achieved in 1990 will be maintained with even better results.

Austria↗

The advantage of allocating kidneys from old cadaveric donors to old recipients: a single-center experience.

BACKGROUND: In January 1999 a new kidney allocation program was launched by the Eurotransplant Foundation, the 'Eurotransplant Senior Program' (ESP). Cadaveric donors above the age of 65 yr are allocated to kidney transplant recipients of the same age group. METHODS: Using a single-center database, 91 patients who underwent first renal transplantation at the age of 65 yr and older in the years 1999-2002 were identified. Fifty-six patients were transplanted through ESP allocation (study group) and 35 patients (control group) via normal Eurotransplant Kidney Allocation System (ETKAS) procedure. RESULTS: Age, sex and comorbid conditions did not differ by group. The rate of acute rejection episodes, primary non-function, delayed graft function, perioperative mortality did not differ by group. Serum creatinine was significantly lower in the ETKAS group (1.3 vs. 1.9 mg/dL; p=0.015) from six months after the transplantation on. Overall graft survival at six yr was 56% in the ETKAS group and 52% in the ESP group. With 73% in the ETKAS group and 71% in the ESP group, cumulative patient survival according to the Kaplan-Meier estimation was not statistically different at five yr. CONCLUSIONS: We did not find a relevant difference in the outcome between young and old kidney transplants in old recipients after this long observation period.

Aged↗