Have we learned from our mistakes in pancreas transplantation? Chris Watson Addenbrooke’s NHS UNIVERSITY OF Cambridge University Hospitals Foundation Trust CAMBRIDGE Learning from mistakes The Pancreas Forum Annual Report on Pancreas transplantation ¡A forum for learning from the mistakes of others ¡Benchmarking centres ¡ And their good practice against their peers ¡Annual meeting, now in ¡Providing data for th National Pancreas Transplant Forum 2018 Venue: Radisson Blu Hotel, Cardiff CF10 2FL its 14 year Date: 2nd February 2018 patients PROGRAMME 9:00 Welcome 9:15 NHSBT Annual Pancreas and Islet Transplant Report 2016/17 Claire Counter 9:45 National Data on the impact of pancreas quality and retrieval logistics on the transplant outcome Claire Counter 10:00 Pancreas Discard Rate in UK – Are we all saying the same thing? Sorina Cornateanu (Edinburgh) 10:30 Discussion 10:45- 11:00 Coffee/Tea Break 11:00 Trends in pancreas transplantation – USA Raja Kandaswamy (USA) 11:40 Trends in pancreas transplantation – UK Argiris Asderakis (Cardiff) 12:00 Discussion 12:30 Lunch 13:30 Pancreas Transplantation in Type 2 DM Sanjay Sinha (Oxford) Raja Kandaswamy (USA) 14:15 Update on Immunotherapy Trials on Type 1 DM Colin Dayan (Cardiff) 14:45 Discussion 15:00-15:15 Coffee/Tea Break 15:15-16:15 Case presentations Cambridge, Edinburgh, Guys, Hammersmith, Manchester, Newcastle, Oxford, Cardiff Acknowledgements ¡Claire Counter Mistakes? ¡Questions ¡ What did we get right (if anything)? ¡ What are our mistakes? ¡ Did we learn from them? ¡Considerations ¡ Programme organisation ¡ Indications ¡ Patient Assessment ¡ Implantation techniques ¡ Immunosuppression Development of pancreas transplantation in the UK ¡National funding 250 Sol pancreas 57 Kid + Panc ¡ Scotland 2002 200 26 36 37 29 ¡ England 2004 26 53 32 39 18 17 ¡ Wales 2006 150 20 ¡ Islets 2008 100 188 188 173 173 167 6 166 162 159 159 155 151 ¡Note: 50 102 ¡ Eurotransplant activity was 75 157 transplants in 2015 0 Pancreas transplantation in UK vs elsewhere UK in Pancreas transplantation 0.5 1.5 2.5 3.5 0 1 2 3 4 USA 3.7 Austria 3.7 UK 3.1 Norway 3.1 Global Observatory on Donationon GlobalObservatory Sweden 2.8 Canada 2.1 Belgium 2.0 Germany 1.9 Czech 1.9 Spain 1.9 Switzerland 1.8 and Transplantation 2010 data data Transplantation2010and Ireland 1.7 Argentina 1.5 Australia 1.5 France 1.5 Portugal 1.4 Croatia 1.4 https:// Netherlands 1.1 Italy 0.7 reports.ont.es Poland 0.5 Finland 0.4 / caapmp.aspx Centre volume affects SPK outcomes ¡Pancreas transplants in EuroTransplant 2008-2013 Patient Survival Graft Survival ¡Centre volume Big centre ¡ Big: ≥13 per year ¡ Medium: 5-12 per year Big centre Small centre ¡ Little: <5 per year Small centre Kopp et al. Transplantation 2017;101:1247 Organisation of pancreas transplantation in the UK ¡8 centres ¡Centrally funded ¡NHSBT oversight x Edinburgh x Newcastle Manchesterx Cambridge x Oxford x Cardiff x WLRTC x x Guys Centre activity in UK 70 ¡Range 5 to 62 Solitary pancreas 60 Pancreas + kidney ¡5/8 centres in “Big” category 50 40 30 20 10 0 NHSBT Centre specific data, 2016/17 What did we learn: Solitary pancreas transplantation Pancreas graft survival Solitary pancreas transplant activity 100 2005-2010 70 90 60 80 50 70 60 40 50 30 57 40 53 % graft survival 30 20 39 36 37 N % Survival (95% CI) 32 29 20 1 Year 3 Year 5 Year 26 26 2005-2006 33 75 (56-87) 53 (35-69) 50 (32-66) 10 20 18 17 10 2007-2008 52 69 (54-80) 55 (40-67) 6 0 2009-2010 44 80 (64-90) 0 0 1 2 3 4 5 years post-transplant Data from Sue Madden & Lisa Mumford Indications for transplant ¡Type 1 ¡Insulin dependent type 2 ¡ BMI <30 ¡SPK: Renal failure ¡PTA: Hypoglycaemic unawareness https://nhsbtdbe.blob.core.windows.net/umbraco-assets- corp/6525/pol185-pancreas-transplantation-patient-selection.pdf Indications for transplant: No significant difference between type 1 and type 2 Pancreas graft survival Percentage of SPK transplants by 88% type of diabetes 84% Type 1 Type 2 Other p=0.4 Total Txs 177 141 140 145 160 157 176 151 148 150 100 2.8 2.8 3.4 3.1 4.0 4.0 4.3 6.4 4.0 8.1 95 90 96.0 97.2 97.2 96.3 96.0 96.0 Percentage 95.0 93.6 94.9 91.9 85 80 Type 2: Insulin dependent & BMI<30kg/m2 Survival by age One year graft survival following SPK Percentage of SPK transplants by age of patient transplant, 1 April 2007 to 31 March 2017 Total 0-35 36-40 41-50 51+ 89% no. txs 188 151 159 155 173 166 188 173 167 162 88% 100 85% 90 p=0.5 80 70 60 50 Percentage 40 30 20 Age group 10 0 Patient assessment Pancreas & Kidney Isolated pancreas ¡Diabetic comorbidity 18 ¡ Cardiovascular disease 16 ¡ Previous MI 14 ¡ Peripheral vascular disease 12 ¡ Previous amputations 10 ¡ Cerebrovascular disease 8 ¡ Previous TIAs/CVAs 6 4 Percentage of patients of Percentage ¡Renal failure 2 ¡ Dialysis burden 0 MI CVA Registered Major limb Digital blind amputation amputation Pre-transplant MI is associated with poorer graft survival One year graft survival following SPK transplant , 1 April 2007 to 31 March 2017, Percentage of SPK transplants where patient had an MI pre-transplant Total 88% no. txs 187 151 154 151 170 165 185 172 166 155 6 75% 5.2 p=0.007 5 4.5 4.6 4.5 4.2 4.0 4 2.7 3 2.4 2.1 1.8 2 % of transplants 1 Previous MI 0 Still significant factor for one year graft survival after adjusting for donor age, BMI, donor type and waiting time: p=0.012 Pre-transplant CVA is not associated with poorer graft survival Percentage of SPK transplants where One year graft survival following SPK transplant, 1 April 2007 to 31 March 2017 patient had a CVA pre-transplant 92% Total no. txs 187 151 152 151 171 165 181 172 167 154 87% 7 6.0 6 p=0.24 5.3 5.2 5 4.6 4.4 3.9 4 3.2 3.0 3 2.3 2.4 % of transplants 2 1 Previous CVA 0 Year Previous amputation does not affect graft survival Percentage of SPK transplants where patient had an amputation pre-transplant 88% Total Major Limb Digital no. txs 186 151 154 149 168 163 184 173 166 151 10 p=0.95 9 8 7 6 5 4 Percentage 3 2 1 0 Amputation status Financial Year Patient survival ¡One year patient survival is not affected by ¡ Previous MI (p=0.29) ¡ Previous CVA (p=0.16) ¡ Smoker (p=0.27) ¡ Limb amputation (p=0.25) Assessment summary ¡Solitary pancreas recipients have a 50% 5 year graft survival ¡The outcomes are the same for patients with type 1 and insulin-dependent type 2 diabetes ¡There is no clear difference in graft survival by recipient age ¡A history of MI is associated with poorer graft survival ¡Previous CVA or limb / digital amputation do not influence graft survival ¡ But there may be selection bias involved here Waiting for a transplant ¡Have we got this right 100 compared to USA? 90 Waiting list 80 survival 70 %survival 60 Category n 1 year 4 years 50 Wait List 12478 93.4% 58.7% SPK Tx 6995 95.0% 90.3% Months 40 0 12 24 36 48 Am J Trans 2004 Outcome following listing for a simultaneous pancreas & kidney in 2013 pancreas in the UK UK USA 100% 2 7 100% 3 7 80% 80% 60% Died 60% Removed 40% 76 40% Still waiting 64 20% 40 Transplanted 20% 37 0% 0% 1 year 3 years 1 year 3 years 7% die waiting UK figures are 4/13 to 3/14 DONOR TYPES The donors: DCD pancreases are as good as DBD pancreases SPK transplants in the UK by donor type 5 year graft survival by donor type Total no. txs 188 151 159 155 173 166 188 173 167 162 100% 15 20 22 90% 25 35 33 35 81% 44 43 78% 55 80% p=0.4 70% 60% DCD 50% 173 131 137 DBD 40% 130 138 133 153 123 119 118 30% Percentage of transplants 20% Donor type 10% 0% Year SPK transplants, 1st April 2007-31st March 2017 DCD pancreas use varies from 0 to 39% in spite of there being no difference in outcomes Proportion of DBD and DCD pancreases Median waiting time to transplant used by centres,1/4/14 to 31/3/17 2011/14 100% 600 80% DBD 500 DCD 400 60% 300 40% 200 20% 100 0% 0 Data from NHSBT annual reports Cold ischaemia affects graft survival: DBD donors One year graft survival following DBD Median cold ischaemia time for SPK transplant 1 April 2007 to 31 March 2017 SPK transplants from DBD donors 91% 2160 Median ~12 hrs 84% 192032 p=0.02 168028 1440(hours) 24 Median 1200time 20 ~10.5 hrs 96016 Cold ischaemic time 72012 — ≤ 9.5h 480ischaemic 8 — 9.5 - 11.5h 4 — 11.5 - 13.5 240 Cold — >13.5h 00 The plumbing Portal vein extension graft on the donor pancreas Percentage of SPK transplants with a Venous Extension Graft Total no. txs 170 142 143 131 141 143 170 170 152 150 25.0 23.0 20.0 17.3 15.0 11.2 10.0 8.4 7.0 5.9 5.6 6.4 % of transplants 5.0 2.3 2.9 0.0 Venous extensions are associated with poorer graft outcomes 3 month graft survival 1 year graft survival 91% 88% 83% 82% p=0.002 p=0.03 Venous extension graft Venous extension graft — No 1354 — No 1354 — Yes 135 — Yes 135 Still significant factor for one year graft survival after adjusting for donor age, BMI, donor type and waiting time: p=0.03 Is there a penalty for using a pancreas with a short portal vein? Percentage of SPK transplants where portal vein was cut short (<1cm) 88% Total no.