what makes a pancreas allograft marginal? peter j friend university of oxford
TRANSCRIPT
What makes a pancreas allograft marginal?
Peter J FriendUniversity of Oxford
• Do we need marginal grafts?• What is a marginal graft – conventionally?• What is a marginal graft – evidence-based?• How can we use marginal grafts safely?• The future
Pancreas transplantation in the UK – the current situation
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1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Year
Nu
mb
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Donors
Transplants
Active Transplant list
Pancreas transplantation (UK) 1999 - 2009 Donor BMI criterion introduced August 2008
Year All HB donors
HB donors aged 8-60 % Offered
% Retrieved if offered
% Transplanted if retrieved
Conversion rate*
2009 613 491 88 70 60 37
2008 620 499 88 66 64 37
2007 607 498 85 68 76 44
2006 633 521 64 60 77 30
2005 630 540 53 55 74 21
Pancreas transplantation from DBD – UKAge range 8 to 60 years
* Percent of HB donors aged 8 to 60 resulting in transplant
• Donors aged 8 to 60 years - decreasing
• Expanding age criteria - offers and retrievals have increased
• Transplant conversion rate -declined by 7 percentage points
Year All HB donors
HB donors aged 8-60 BMI ≤ 30 % Offered
% Retrieved if offered
% Transplanted if retrieved
Conversion rate*
2009 613 409 90 72 60 43
2008 620 422 90 69 67 42
2007 607 428 85 71 78 47
2006 633 441 67 63 81 34
2005 630 464 54 58 78 24
Pancreas transplantation from DBD – UKInclude BMI less than 30
* Percent of HB donors aged 8 to 60 with a BMI ≤ 30 resulting in transplant
• Donors within age & BMI criteria - decreasing
• Including age and BMI criteria, conversion rate still below 50%
Donor age group
HB donors aged 8-60 BMI ≤30 % Offered
% Retrieved if offered
% Transplanted if retrieved
Conversion rate*
0 to <8 6 67 75 100 50
8 to <18 22 86 84 81 59
18 to <30 75 91 87 83 65
30 to <40 72 93 75 78 54
40 to <50 107 89 66 63 37
50 to <60 133 89 66 45 26
Over 60 87 28 42 30 3
Pancreas transplantation from DBD (2009)The influence of age
* Percent of HB donors aged 8 to 60 with a BMI ≤ 30 resulting in transplant
• Highest conversion rate - donors aged 18 to < 30 years
• Very low conversion rates - donors aged over 50 years
BMI group HB donors aged 8-60 % Offered
% Retrieved if offered
% Transplanted if retrieved
Conversion rate*
≤20 34 94 84 78 62
21 to ≤23 80 93 74 76 53
24 to ≤26 153 89 73 67 44
27 to ≤30 142 90 68 55 34
Pancreas transplantation from DBD (2009)The influence of BMI
* Percent of HB donors aged 8 to 60 with a BMI ≤ 30 resulting in transplant
• Lower BMI associated with higher conversion rates
What factors make a graft marginal?
Uncontrollable factors:AgeObesityCardiovascular diseaseAlcohol Amylase
Controllable factors:Inotropes(Warm ischaemia)Cold ischaemiaRewarming timeRetrieval technique
‘Standard’ criteria vs. ‘Extended’ criteria
University of Minnesota 1994-2003
• 937 transplants– 327 SPK– 399 PAK– 211 PTA
• 624 functioning (66.5%) - mean follow-up 45 months• 123 (13%) lost due to ‘technical’ complications -
– 52% thrombosis 6.5% leaks– 19% sepsis 2.4% bleeding– 20% pancreatitis
Humar et al Transplantation 2004
Risk factors for technical failure
Recipient BMI >30 2.42Preservation time >24 hr. 1.87Donor death Non-trauma 1.58Drainage Enteric 1.68Donor BMI >30 1.66
Humar et al Transplantation 2004
The extended criteria donor - results
Oxford data
• Single centre retrospective analysis• Extended criteria
• Age less than 12, more than 45 years• Non-heart-beating donors
• All pancreas transplant recipients 2004 – 2009• End points:
– Graft & patient survival– Delayed graft function– Complications (re-admissions, re-operations)
Muthusamy et al
Patients & Methods
• 265 transplants (261 pts)– 155 male, 106 female– 176 SCD, 89 ECD– Enteric-systemic drainage of grafts
• Immunosuppression:– Campath / Tac / MMF (n = 249)– (ATG n=8, Basiliximab n=4) / Tac/MMF/Steroids
(all SCD)
Clinical detailsSCD ECD P value
Creatinine – donor 85 ± 31 85 ± 28 NS
Cause of death: vascular 43% 66% 0.0006
Cause of Death: head injury 30% 16% 0.013
Donor Body Mass Index 24 ± 3 25 ± 9 NS
Recipient age (years) 42±7 46±8 <0.0001
Recipient Body mass index 24±4 26 ± 4 0.03
Recipient ethnicity %Caucasian/Asian/Afro-Caribbean
90/ 7 /3 94 / 6 / 0 NS
HLA (median) 4 4 NS
Cold Ischemia (mins) 692±159 717±177 NS
Hospital stay (days) 19 ±12 20 14 NS
Median F/U (months) 23 16 0.0043
Results - Outcomes
SCD ECD P value
DGF - kidney 11% 19% 0.13
DGF - pancreas 1.7% 6.7% 0.06
PNF - kidney 0 0 NS
PNF - pancreas 0 1.5% NS
Re-operation 25% 25% NS
Re-admission 20% 33% 0.03
Rejection episodes 15% 10% NS
Patient & graft survival: SCD vs ECD
Graft function SCD vs. ECD
Conclusions – the expanded criteria donor pancreas
• Equivalent graft and patient survival
• Equivalent pancreatic & renal graft function at 3 months
• Higher risk of delayed graft function of kidney & pancreas
• Greater morbidity related to pancreatitis
• Feasible source to expand the organ pool
Pre-procurement pancreas suitability score (P-PASS) - Eurotransplant
Vinkers et al 2008
P-PASS predicts organ acceptance, not viability
But – more complications and longer hospital stay
Bochum, Germany
Analysis of 24,703 donors 2000 – 2004 (OPTN)44,529 kidney transplants21,079 liver transplants5521 solid organ pancreas transplants1041 pancreases used for islets
Reasons for non-retrieval of pancreas in 64% multi-organ donors
Poor organ function 33%Donor medical history 12%No recipient 7%Intra-operative evaluation 6%Hepatitis serology 6%Anatomical anomaly 3%Unstable haemodynamics 3%Time constraints 2%Other 28%
Stegall et al 2007
Effect of donor age
Age PAK SPK
Less than 50 79.7 85.6*
More than 50 66.7 75.5
* p=0.05
Stegall et al 2007
1 year graft survival
Effect of donor BMI
BMI PAK SPK
Less than 30 79.6 85.7*
More than 30 78.1 82.7
*p=0.06
1 year graft survival
Stegall et al 2007
Effect of cold ischaemia time
Cold ischaemia (hrs)
PAK SPK
0 – 12 79.7 86.7
12 – 18 79.3 85.2
18 – 24 75.7 85.8
24 + 79.3 76.2
Stegall et al 2007
(UK results show significant effect of cold ischaemia time at 3 months)
The effect of donor age
OPTN data Salvalaggio et al (St Louis) 2007
Increased complications of older donors (+/- 45 years) more than compensated by reduced morbidity whilst waiting longer
Paediatric donors
• University of Wisconsin 1986 – 2001• 680 SPK including 142 paediatric donors
– 47 aged 3 to 12 years– 95 aged 12 – 17 years
• 10 year survival and function better in paediatric donors
• No difference between smaller and larger cohorts
Fernandez et al 2004
(Concerns about islet mass & technical complications)
Pancreas graft survival
Fernandez et al 2004
Kidney graft survival
Fernandez et al 2004
Pancreas transplantation from NHB donors
• Salvalaggio et al 2006• Analysis of UNOS data 1993 to 2003
– 57 NHBD (47 SPK, 10 PA)– 4038 HBD (2431 SPK, 1607 PA)
• Equivalent patient & graft survival rates• Shorter time on waiting list• Longer hospital stay• More pancreas thrombosis (12.8% vs. 6.1%)• More renal DGF (28.2% vs. 7.6%)
Kidney graft survival
Pancreas graft survival
Patient survival
Salvalaggio et al 2006
Higher-risk transplants
Postoperativemortality
Waiting listmortality
Mortality on Tx waiting list
Mortality after pancreas Tx
IPTR, UNOS data Gruessner et al 2004
The future
• Improved method of assessment needed– Objective rather than subjective
• Improved graft protection needed– Prevent ischaemia-reperfusion
• Minimise cold ischaemia• Free radical scavenging; Haemoxygenase-1;
Complement inhibition etc.• Machine perfusion +/- normothermia
Conclusions
• Pancreas donor organs poorly utilised• Marginal donor organs are the reality• Published data are inconsistent• Risk-benefit analysis favours early transplant• Innovative preservation and viability
assessment methods needed