Overview Increasing organ donation (heart-beating donation Use of marginal grafts (quality) Cadaveric non-heart-beating donation Splitting Living dona
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1 Increasing the organ supply Mr. Nigel Heaton
2 Overview Increasing organ donation (heart-beating donation Use of marginal grafts (quality) Cadaveric non-heart-beating donation Splitting Living donation Domino
3 Increasing the Organ Supply Legislation (Opting out) Spanish model 1989 to 1999 Donation 14.3 to 33.7 pmp Mainly in 45 year age group (30% of donors) USA similar utilisation increased donation by 40% (21.5 pm Chang et al, Am J Transpl 2003; 3: 1189
4 Increasing the Organ Supply Spanish model Well trained transplant coordinators Systematic death Positive social atmosphere Good management of mass media relations Adequate economic investment
5 Increasing the Organ Supply Spanish Solution donors (29 pmp; pop 40 mill) Multi-organ donation in 80% 27% older than 60 years Progressive decrease in family refusal (23%) Kidney transplantation live donors 20 / 1861
6 Increasing the Organ Supply Spanish Solution 40% of donors lost Healthcare personnel 20% Poor donor care 23% Family refusal 23% Cases no reported 4% Medically not suitable 30% Still opportunities for improvement
7 Overview Reduce graft loss Early technical, graft dysfunction Late disease recurrence, compliance, Increased use of marginal grafts (quality or quantity New or rediscovered surgical techniques Managing small for size liver syndrome
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10 Use of Marginal Grafts Preserving Liver Function Donor management Technical competence for retrieval and transplant Ameliorating ischaemia / reperfusion Ischaemic preconditioning Preserving the microcirculation Avoiding early rejection and infection
11 Managing Marginal Grafts Surgical intervention Implantation technique Short cold ischaemia time Early temporary porto-caval shunt Arterial then portal venous reperfusion Ligation of splenic artery Use of portosystemic shunt porto- or meso-caval banded pressure / flow
12 Increasing the Organ Supply ON-HEART BEATING DONATION Unsuccessful resuscitation Dead on arrival Awaiting cardiac arrest-ventilator switch off Cardiac arrest while brain-dead Uncontrolled Uncontrolled Contro Contr First International Workshop on NHBD, Maastricht, 1994
13 Increasing the Organ Supply Non-Heart Beating Donation Controlled Haemodynamically stable Extubated in theatre / ICU Family decision Planned event Limited warm ischaemia
14 Increasing the Organ Supply Non-Heart Beating Donation Uncontrolled Largest pool of potential donors Issues Ethical Legal Logistical Only legal form of NHBD in Spain
15 utcome of Non-Heart Beating Liver Transplants (UNOS data) Graft survival 1 year 3 years NHBD 70.2% 63.3% HBD 80.4% 72.1% Patient survival 1 year 3 years NHBD 79.9% 72.1% HBD 85% 77.4% Abt et al. Ann Surg 2004; 239: 87
16 on-heart Beating Donation in USA 55 NHBD (4-68 years) transplanted 26 livers discarded Primary non-function 11% Hepatic artery thrombosis 11% Biliary strictures 18% 1 year graft survival 69% 1 year patient survival 78% ( : 45%; : 85%) Eghtesad et al. Pittsburgh (abstract 20
17 NHBD at King s College Hospital Referrals Retrievals Transplants
18 NHBD at King s College Hospital 72 NHBD 37 used 38 LT (1 split) 1 exported 2 imported + 1 usable no recipient 81.6% Patient Survival 18 months follow up 79% Graft Survival 18 months follow up 7 children, 100% patient and graft survival, 14 months follow up
19 We wait > 60 Call renal team Withdrawal of treatment Cardiac arrest < 60 Declaration of death Stand off Tran to th
20 Super Rapid Technique Cannulation of aorta Perfusion with Marshall s with added heparin Topical cooling Thoracotomy aortic clamping drainage IVC Cannulation of SMV Perfusion with UW with added heparin Look for aberrant vessels A. Casavilla, Pittsburgh, 1995
21 Non-Heart Beating Donation King s College Hospital NHBD Programme 38 liver transplants Median age: recipient 42 y (0.7-72), donor 37 y (10-67) Warm ischaemia time:14 minutes (7-31) Cold ischaemia time: 8.5 hours ( ) Primary non-function: 1 Patient survival: 90%, graft survival: 87%, median 15m Acute rejection 29.7% Biliary complications 3 (8%)
22 Good Immediate Functio 7 h CI 14 h CI rimary Non Function
23 Non-Heart Beating Donation NHBD recipients 30% risk of early graft failure Primary non-function Retransplantation Cold ischaemia time >8 hours 30.4% graft failure >12 hours 58.3% < 8 hours 10.8% Donor age Donors > 60 years (n=12) Early graft failure 25% Warm ischaemia > 30 minutes Abt et al. Ann Surg 2004; 239: 87
24 Liver Transplantation at King s College Hospital 250 NHBD 7 %
25 Non-Heart Beating Donation Microvasculature Fibrinolytic agents Perfusion solution Endothelin antagonists PAF Arterial reperfusion of recipient Selection of recipients Elective transplants? Paediatric?
26 Non-Heart Beating Donation Results of liver transplantation are improving Controlled vs uncontrolled Potential to increase organ supply (10-20%) Resources required - development and education Careful donor selection and short cold ischaemia Long term results -? cholangiopathy
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31 entres performing more than 30 spli liver transplants Home HospitalITU Graft R 76 % 63 % 15 % Survival L 64 % 54 % 41 % Patient R 82 % 67 % 21 % Survival L 82 % 80 % 53 % Median follow up for all 3 groups > 1 year
32 Ex Situ Split Liver Transplantation EARLY EUROPEAN EXPERIENCE VASCULAR COMPLICATIONS rafts RIGHT LEFT umber of grafts arly HAT 8 % 11.7 % ortal vein thrombosis 1 % 5 % iliary complications 20 % 21 %
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34 Ex-situ Split Liver transplantation Results or r Year Number Age group Technique Patient Graft Survival % Survival % lsch et al Adults Ex situ et t al Mixed Ex situ ille et al Mixed Ex situ lay et al Mixed Ex situ et al Mixed Ex situ a et al Mixed Ex situ s et al Paediatric Ex situ Adult Ex situ 83 - lay et al Adult Ex situ 88 (LLS) 74 (RL) s Mixed Ex Situ
35 In-situ Split Liver Transplantation Results thor Year Number Age group Technique Patient Graft Survival % Survival % giers et al In situ ss et al Mixed In situ suttil et al Mixed In situ obrial et al Mixed In situ 78 - ada et el Paediatric In Situ lledan et al Paediatric In Situ 81 - yes et al Paediatric In situ Adult In situ 93 -
36 Ex-situ Split Liver Transplantation King s College Hospital Survival data n 1 yr 3 yr5 yr rall patient survival % 84% 84% nt survival LLS % 88% 88% nt survival RL % 81% 80%
37 Paediatric Split Liver Transplantation Current status - Established (ex-vivo vs. in-situ) Infrastructure requirements Matching graft function / recipient requirement Anatomy understood Marginal graft and small for size Potential for splitting limited by recipient numbers UK probably per year
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39 Adult Split Liver Transplantation Paul Brousse Hospital - Paris: 17 splits, 30 transplanted, 4 exported PNF in 3 cases (GBWR <1% - small for size) Complications (24% - 8 cases) Biliary stenosis (4), biliary leak (2), PV thrombosis (2), HA stenosis (2), subphrenic abscess (1), haemoperitoneum (1) Graft loss (3), Death (2) Graft survival 1 y (R-L): 72%-76% Patient survival 1 y (R-L): 72%-87% Adam et al, 2002.
40 Adult Split Liver Transplantation Learning curve for donor and recipient procedures Avoid high risk Complex surgical cases Advanced / decompensated liver disease Outcome less good than whole liver transplantation Graft survival 70% Vascular complications 5-10% Biliary complications / small for size 20%? Increase donor graft availability
41 Adult Split Liver Transplantation Current status - Experimental (ex- vs. in-situ) Infrastructure requirements Matching graft function / recipient requirement Technical excellence and understanding new anatomy Marginal graft and small for size Potential for splitting 25% of livers
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44 Living Donor Left Lateral Segment Transplantation Donor complications cases Mortality: 2 deaths Morbidity: approximately 5% Splenic injury Bile duct injury and bile leaks Subphrenic abscess Small bowel obstruction and wound infection
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46 Advantages of Living Related Liver Transplantation (Paediatric) Reduced pretransplant waiting time Elective procedure before deterioration Improved survival rates Shorter recuperation times Reduced hospitalisation Uniformly good graft quality Reduced blood product utilisation? Immunological advantage
47 ing Related Liver Transplantation Resu in Children 40 TRANSPLANTS FOLLOW UP months H. lc Vi a M PATIENT SURVIVAL 96%
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49 Living Liver Donation Adult to Adult Transplantation Morimoto et al, Kyoto, 1994.
50 Graft Size and Survival raft GRWR Survival xtra small < 0.8 % 42 % mall % 74 % edium 1-3 % 92 % arge > 3 % 83 % T. Kiuchi. Transplantation 1999
51 Small for Size Liver Syndrome Primary graft dysfunction Prolonged cholestasis and INR Early ischaemia and regeneration Susceptibility to infection Late mortality 4-6 weeks Poor long term graft survival
52 Small for Size Liver Marginal Grafts Quantity of liver mass Quality of liver (marginal) Concept of functional liver mass Influence of recipient status
53 Small for Size Liver Graft Recipient Factors Severity of liver disease Portal hypertension Previous surgery / infection Graft vascular inflow Graft vascular outflow Problems often covert
54 Living Liver Donation Adult to Adult Transplantation Comparison with paediatric living donation Ethical Donor risk Recipient risk Surgical techniques Complications and outcome
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58 Adult Living Liver Donation 1158 adult living related liver transplants in USA Donor complications 10-20% Three deaths Bile leak 6% Non autologous blood transfusion 5% Reoperation 4.5% Infection 1% Pressure sores
59 Living Liver Donation Adult to Adult Transplantation Recipient outcome 3 year patient survival 70-90% Graft survival 50-70% Vascular complications 12% Biliary complications 15-33% Main cause of death : Sepsis (50%)
60 Living Liver Donation Adult to Adult Transplantation DISADVANTAGES Donor Full risks unknown No long term follow up data Safety and ethics of right lobe donation Surgical complications (23%)
61 Living Liver Donation Adult to Adult Transplantation DISADVANTAGES Recipient Smaller liver mass Increased biliary and vascular complications Graft survival comparable?
62 Living Liver Donation Adult to Adult Transplantation 100 potential recipients 49 suitable 51 rejected 24 no donor 25 donor for evaluation 10 unacceptable donor 15 suitable donor 15 LRLT
63 Adult Living Donation in USA 449 adult-to-adult transplants in 42 centres 80% performed in 10 centres Large volume centres Paediatric transplantation Hepatobiliary surgery
64 Adult Living Liver Donation ECIPIENTS Learning curve for donor and recipient procedures Avoid high risk Complex surgical cases / decompensated liver disease Outcome less good than whole liver transplantation Graft survival 70% Vascular complications 5-10% Biliary complications 20%? Expand current indications for liver transplantation
65 Domino FAP Liver Transplantation y man transplanted for HCV / HCC (8cm) Domino liver from FAP Met 30 TTR donor 8y post-transplant no HCV / HCC recurrence Peripheral and autonomic neuropathy Retransplantation First documented recurrence Donor age Recipient age Disease pattern
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67 Hepatocyte Transplantation for Urea Cycle Defect One day old male (3 kg) Severe OTC deficiency (antenatal diagnosis) One sibling died of same disorder Umbilical vein catheter (selective right portal vein cannula) Infused with ~1.8 billion hepatocytes
68 creasing the Organ Supply - Politica Legislation (Opting out) Spanish model (money and commitment) Permanent network of trained medical staff Specific budget Responsible staff, accountable for performance Required referral Intensive care capacity Incentives or enthusiasm
69 creasing the Organ Supply Surgica Use of marginal grafts (quality and quantity) Use of non-heart-beating donors Living donation and splitting Fewer technical complications USE OF LEFT LOBE GRAFTS
70 Increasing the Organ Supply? Medical Political Allocation of livers best use Centre size and performance Assessing and rewarding good performance Reimbursement
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