Increasing the organ supply Mr. Nigel Heaton
Overview Increasing organ donation (heart-beating donation Use of marginal grafts (quality) Cadaveric non-heart-beating donation Splitting Living donation Domino
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
Increasing the Organ Supply Spanish model Well trained transplant coordinators Systematic death Positive social atmosphere Good management of mass media relations Adequate economic investment
Increasing the Organ Supply Spanish Solution 1997 1155 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
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
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
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
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
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
Increasing the Organ Supply Non-Heart Beating Donation Controlled Haemodynamically stable Extubated in theatre / ICU Family decision Planned event Limited warm ischaemia
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
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
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% (1993-1997: 45%; 1998-2003: 85%) Eghtesad et al. Pittsburgh (abstract 20
NHBD at King s College Hospital 35 30 25 Referrals Retrievals Transplants 20 15 10 5 0 2001 2002 2003 2004
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
We wait > 60 Call renal team Withdrawal of treatment Cardiac arrest < 60 Declaration of death Stand off Tran to th
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
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 (5.2-14.3) Primary non-function: 1 Patient survival: 90%, graft survival: 87%, median 15m Acute rejection 29.7% Biliary complications 3 (8%)
Good Immediate Functio 7 h CI 14 h CI rimary Non Function
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
Liver Transplantation at King s College Hospital 250 NHBD 7 % 200 4 11 8 14 150 100 166 176 183 198 190 199 183 178 202 50 0 1996 1997 1998 1999 2000 2001 2002 2003 2004
Non-Heart Beating Donation Microvasculature Fibrinolytic agents Perfusion solution Endothelin antagonists PAF Arterial reperfusion of recipient Selection of recipients Elective transplants? Paediatric?
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
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
Ex Situ Split Liver Transplantation EARLY EUROPEAN EXPERIENCE VASCULAR COMPLICATIONS rafts RIGHT LEFT umber of grafts 161 154 arly HAT 8 % 11.7 % ortal vein thrombosis 1 % 5 % iliary complications 20 % 21 %
Ex-situ Split Liver transplantation Results or r Year Number Age group Technique Patient Graft Survival % Survival % lsch et al 1990 30 Adults Ex situ 67 55 et t al 1995 29 Mixed Ex situ 79 69 ille et al 1995 96 Mixed Ex situ 71 64 lay et al 1995 27 Mixed Ex situ 79 79 et al 1998 41 Mixed Ex situ 90 88 a et al 1998 24 Mixed Ex situ 78 68 s et al 2000 12 Paediatric Ex situ 64 45 13 Adult Ex situ 83 - lay et al 2001 34 Adult Ex situ 88 (LLS) 74 (RL) s 2001 156 Mixed Ex Situ 88.6 88
In-situ Split Liver Transplantation Results thor Year Number Age group Technique Patient Graft Survival % Survival % giers et al 1996 14 In situ 93 86 ss et al 1997 28 Mixed In situ 92 86 suttil et al 1999 72 Mixed In situ 91 81 obrial et al 2000 102 Mixed In situ 78 - ada et el2000 42 Paediatric In Situ 85 76 lledan et al 2000 34 Paediatric In Situ 81 - yes et al 2000 12 Paediatric In situ 100 83 13 Adult In situ 93 -
Ex-situ Split Liver Transplantation King s College Hospital Survival data n 1 yr 3 yr5 yr rall patient survival 256 87% 84% 84% nt survival LLS 140 90% 88% 88% nt survival RL 116 85% 81% 80%
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 50-60 per year
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.
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
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
Living Donor Left Lateral Segment Transplantation Donor complications - 2000 cases Mortality: 2 deaths Morbidity: approximately 5% Splenic injury Bile duct injury and bile leaks Subphrenic abscess Small bowel obstruction and wound infection
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
ing Related Liver Transplantation Resu in Children 40 TRANSPLANTS FOLLOW UP 2-120 months H. lc Vi a M. 1 9 9 3 PATIENT SURVIVAL 96%
Living Liver Donation Adult to Adult Transplantation Morimoto et al, Kyoto, 1994.
Graft Size and Survival raft GRWR Survival xtra small < 0.8 % 42 % mall 0.8-1 % 74 % edium 1-3 % 92 % arge > 3 % 83 % T. Kiuchi. Transplantation 1999
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
Small for Size Liver Marginal Grafts Quantity of liver mass Quality of liver (marginal) Concept of functional liver mass Influence of recipient status
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
Living Liver Donation Adult to Adult Transplantation Comparison with paediatric living donation Ethical Donor risk Recipient risk Surgical techniques Complications and outcome
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
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%)
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%)
Living Liver Donation Adult to Adult Transplantation DISADVANTAGES Recipient Smaller liver mass Increased biliary and vascular complications Graft survival comparable?
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
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
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
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
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
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
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
Increasing the Organ Supply? Medical Political Allocation of livers best use Centre size and performance Assessing and rewarding good performance Reimbursement