Marie-Hélène Delbouille

Organ Procurement After Euthanasia: Belgian Experience

Euthanasia was legalized in Belgium in 2002 for adults under strict conditions. The patient must be in a medically futile condition and of constant and unbearable physical or mental suffering that cannot be alleviated, resulting from a serious and incurable disorder caused by illness or accident. Between 2005 and 2007, 4 patients (3 in Antwerp and 1 in Liège) expressed their will for organ donation after their request for euthanasia was granted. Patients were aged 43 to 50 years and had a debilitating neurologic disease, either after severe cerebrovascular accident or primary progressive multiple sclerosis. Ethical boards requested complete written scenario with informed consent of donor and relatives, clear separation between euthanasia and organ procurement procedure, and all procedures to be performed by senior staff members and nursing staff on a voluntary basis. The euthanasia procedure was performed by three independent physicians in the operating room. After clinical diagnosis of cardiac death, organ procurement was performed by femoral vessel cannulation or quick laparotomy. In 2 patients, the liver, both kidneys, and pancreatic islets (one case) were procured and transplanted; in the other 2 patients, there was additional lung procurement and transplantation. Transplant centers were informed of the nature of the case and the elements of organ procurement. There was primary function of all organs. The involved physicians and transplant teams had the well-discussed opinion that this strong request for organ donation after euthanasia could not be waived. A clear separation between the euthanasia request, the euthanasia procedure, and the organ procurement procedure is necessary.

Liver transplant donation after cardiac death : experience at the University of Liège

OBJECTIVE Donation after cardiac death (DCD) has been proposed to overcome in part the organ donor shortage. In liver transplantation, the additional warm ischemia time associated with DCD procurement may promote higher rates of primary nonfunction and ischemic biliary lesions. We reviewed the results of liver transplantation from DCD. PATIENTS AND METHODS From 2003 to 2007, we consecutively performed 13 controlled DCD liver transplantations. The medical records of all donors and recipients were retrospectively reviewed, evaluating in particular the outcome and occurrence of biliary complications. Mean follow-up was 25 months. RESULTS Mean donor age was 51 years, and mean intensive care unit stay was 5.4 days. Mean time between ventilation arrest and cardiac arrest was 9.3 minutes. Mean time between cardiac arrest and arterial flushing was 7.7 minutes. No-touch period was 2 to 5 minutes. Mean graft cold ischemia time was 295 minutes, and mean suture warm ischemia time was 38 minutes. Postoperatively, there was no primary nonfunction. Mean peak transaminase level was 2546 UI/mL. Patient and graft survival was 100% at 1 year. Two of 13 patients (15%) developed main bile duct stenosis and underwent endoscopic management of the graft. No patient developed symptomatic intrahepatic bile duct strictures or needed a second transplantation. CONCLUSIONS Our experience confirms that controlled DCD donors may be a valuable source of transplantable liver grafts in cases of short warm ischemia at procurement and minimal cold ischemia time.

End of life care in the operating room for non-heart-beating donors: organization at the University Hospital of Liège.

Non-heart-beating (NHB) organ donation has become an alternative source to increase organ supply for transplantation. A NHB donation program was implemented in our institution in 2002. As in many institutions the end of life care of the NHB donor (NHBD) is terminated in the operating room (OR) to reduce warm ischemia time. Herein we have described the organization of end of life care for these patients in our institution, including the problems addressed, the solution proposed, and the remaining issues. Emphasis is given to our protocol elaborated with the different contributors of the chain of the NHB donation program. This protocol specifies the information mandatory in the medical records, the end of life care procedure, the determination of death, and the issue of organ preservation measures before NHBD death. The persisting malaise associated with NHB donation reported by OR nurses is finally documented using an anonymous questionnaire.

Contribution of Donors After Cardiac Death to the Deceased Donor Pool: 2002 to 2009 University of Liege Experience

OBJECTIVE In this study, we have evaluated the organ procurement and transplantation activity from donors after cardiac death (DCD) at our institution over an 8-year period. Our aim was to determine whether this program influenced transplantation programs, or donation after brain death (DBD) activity. METHODS We prospectively collected our procurement and transplantation statistics in a database for retrospective review. RESULTS We observed an increasing trend in potential and actual DCD number. The mean conversion rate turning potential into effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD) pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3-79). Among the effective donors, 63.3% (n = 31) came from the transplant center and 36.7% (n = 18) were referred from collaborative hospitals. All donors were Maastricht III category. The number of kidney and liver transplants using DCD sources tended to increase. DCD kidney transplants represented 10.8% of the DD kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8 years. The DBD program activity increased in the same time period. In 2009, 17 DCD and 33 DBD procurements were performed in a region with a little >1 million inhabitants. CONCLUSION The establishment of a DCD program in our institution enlarged the donor pool and did not compromise the development of the DBD program. In our experience, DCD are a valuable source for abdominal organ transplantation.

Fulminant Hepatic Failure Induced by Venlafaxine and Trazodone Therapy: A Case Report

Although acute hepatitis may be a side effect of many medications, most cases are reversible after treatment interruption, and fulminant hepatic failure (FHF) is rare. Venlafaxine and trazodone are 2 popular antidepressant agents. Alteration of liver enzyme levels has been reported as a side effect of these drugs at normal doses. Herein we have reported the case of a 48-year-old woman without any previous history of liver disease, who developed fulminant liver failure after 4 months of venlafaxine and trazodone therapy. She required liver transplantation, a procedure that was successful with full patient recovery. The first 5 years of follow-up were uneventful. This case documented that venlafaxine and trazodone at normal doses can produce severe liver toxicity. Liver tests should be monitored regularly in patients who receive this therapy.

A More Than 20% Increase in Deceased-Donor Organ Procurement and Transplantation Activity After the Use of Donation After Circulatory Death

BACKGROUND Organ procurement and transplant activity from controlled donation after circulatory death (DCD) was evaluated over an 11-year period to determine whether this program influenced the transplant and donation after brain death (DBD) activities. MATERIAL AND METHODS Deceased donor (DD) procurement and transplant data were prospectively collected in a local database for retrospective review. RESULTS There was an increasing trend in the potential and actual DCD numbers over time. DCD accounted for 21.9% of the DD pool over 11 years, representing 23.7% and 24.2% of the DD kidney and liver pool, respectively. The DBD retrieval and transplant activity increased during the same time period. Mean conversion rate turning potential into effective DCD donors was 47.3%. Mean DCD donor age was 54.6 years (range, 3-83). Donors ≥60 years old made up 44.1% of the DCD pool. Among referred donors, reasons for nondonation were medical contraindications (33.7%) and family refusals (19%). Mean organ yield per DCD donor was 2.3 organs. Mean total procurement warm ischemia time was 19.5 minutes (range, 6-39). In 2012, 17 DCD and 37 DBD procurements were performed in the Liege region, which has slightly >1 million inhabitants. CONCLUSIONS This DCD program implementation enlarged the DD pool and did not compromise the development of DBD programs. The potential DCD pool might be underused and seems to be a valuable organ donor source.

Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.

BACKGROUND & AIMS Mesenchymal stromal cell (MSC) infusion could be a means to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase I study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients. METHODS Ten liver transplant recipients under standard immunosuppression received 1.5-3×106/kg third-party unrelated MSCs on postoperative day 3±2, and were prospectively compared to a control group of ten liver transplant recipients. As primary endpoints, MSC infusion toxicity was evaluated, and infectious and cancerous complications were prospectively recorded until month 12 in both groups. As secondary endpoints, rejection rate, month-6 graft biopsies, and peripheral blood lymphocyte phenotyping were compared. Progressive immunosuppression weaning was attempted from month 6 to 12 in MSC recipients. RESULTS No variation in vital parameters or cytokine release syndrome could be detected during and after MSC infusion. No patient developed impairment of organ functions (including liver graft function) following MSC infusion. No increased rate of opportunistic infection or de novo cancer was detected. As secondary endpoints, there was no difference in overall rates of rejection or graft survival. Month-6 biopsies did not demonstrate a difference between groups in the evaluation of rejection according to the Banff criteria, in the fibrosis score or in immunohistochemistry (including Tregs). No difference in peripheral blood lymphocyte typing could be detected. The immunosuppression weaning in MSC recipients was not successful. CONCLUSIONS No side effect of MSC infusion at day 3 after liver transplant could be detected, but this infusion did not promote tolerance. This study opens the way for further MSC or Treg-based trials in liver transplant recipients. LAY SUMMARY Therapy with mesenchymal stromal cells (MSCs) has been proposed as a means to improve results of solid organ transplantation. One of the potential MSC role could be to induce tolerance after liver transplantation, i.e. allowing the cessation of several medications with severe side effects. This study is the first-in-man use of MSC therapy in ten liver transplant recipients. This study did not show toxicity after a single MSC infusion but it was not sufficient to allow withdrawal of immunosuppression. CLINICAL TRIAL REGISTRATION NUMBER Eudract: # 2011-001822-81, ClinicalTrials.gov: # NCT 01429038.

An 11-Year Overview of the Belgian Donor and Transplant Statistics Based on a Consecutive Yearly Data Follow-up and Comparing Two Periods: 1997 to 2005 Versus 2006 to 2007.

BACKGROUND The Belgian Transplant Coordinators Section is responsible for the yearly data follow-up concerning donor and transplantation statistics in Belgium and presents herein a 10-year overview. METHODS The procurement and transplant statistics were compared between 2 periods: Period 1 (P1, 1997-2005) versus Period 2 (P2, 2006-2007). RESULTS The kidney and liver waiting lists (P1 vs P2) showed an overall decrease for a period of 2 consecutive years in P2; kidney (-170 patients; -18%), and liver (-83 patients; -34%). All other waiting lists (heart, lung, pancreas) remained stable. Mean ED further increased (P1 vs P2); 229 (P1) versus 280 (P2, +22.27%). Non-heart-beating donors were significantly (+288%) more often procured in P2. Mean donor age was 37.9 +/- 17.8 years (P1) versus 46.5 +/- 19.9 years (P2), and mean organ yield per donor was 3.48 +/- 1.7 (P1) versus 3.38 +/- 1.8 (P2). Overall transplant activity per million inhabitants increased 21.1%. CONCLUSION For 2 consecutive years, the Belgian statistics showed significantly increased donor activity with an impact on waiting list dynamics and transplantation. The mean organ yield per donor was not influenced despite an increased average age and change in reason for death.

Cardiac transplantation beyond 55 years of age

Between January 1985 and December 1988, 20 pateints over the age of 55 years (extremes 56–63 years; 15 men and 5 women) underwent cardiac transplantation. The cause of cardiopathy was ischemic in 70% of the cases. The immunosuppressive regimen consisted of cyclosporin A, corticoids, and azathioprine. Rejection episodes were monitored by endomyocardial biopsies and treated by pulses of corticoids or monoclonal antibodies (OKT3). The operative mortality was 10% (n=2). The 1-year survival rate was 70%. The 1-year incidence of infection and/or rejection episodes was 1 and 1.53 episodes/patient, respectively. One patient was successfully retransplanted after 9 months because of intractable rejection. Age beyond 55 years is no longer a contraindication to cardiac transplantation. This change in recipient selection policy should lead to parallel changes in donor selection criteria.

[150] CADAVERIC WHOLE LIVER TRANSPLANTATION FOR NON-ACETAMINOPHEN FULMINANT HEPATIC FAILURE: A 20-YEAR EXPERIENCE

AIM: To investigate the long-term results of liver transplantation (LT) for non-acetaminophen fulminant hepatic failure (FHF). METHODS: Over a 20-year period, 29 FHF patients underwent cadaveric whole LT. Most frequent causes of FHF were hepatitis B virus and drug-related (not acetaminophen) liver failure. All surviving patients were regularly controlled at the out-patient clinic and none was lost to follow-up. Mean follow-up was 101 mo. RESULTS: One month, one-, fi ve- and ten-year patient survival was 79%, 72%, 68% and 68%, respectively. One month, one-, fi ve- and ten-year graft survival was 69%, 65%, 51% and 38%, respectively. Six patients needed early (< 2 mo) retransplantation, four for primary non-function, one for early acute refractory rejection because of ABO blood group incompatibility, and one for a malignant tumor found in the donor. Two patients with hepatitis B FHF developed cerebral lesions peri-transplantion: one developed irreversible and extensive brain damage leading to death, and one suffered from deep defi cits leading to continuous medical care in a specialized institution.