F. Muehlbacher

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/m2 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.

Tumor recurrence after oLTX

Abstractu2002 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 hepato‐cellular 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, reelavation of serum al‐phafetoprotein, 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 15–63 a). 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.

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

Abstract 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‐ix 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 ICUs 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).

Immunological risk factors are solely responsible for primary non‐funetion of renal allografts

Abstract 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 felative 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.

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.