Siamo pronti per nuovi programmi nazionali e a quali benefici potrebbero portare? Prof. A.D. Pinna

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1 Siamo pronti per nuovi programmi nazionali e a quali benefici potrebbero portare? Prof. A.D. Pinna Department of General Surgery and Transplantation Policlinico Sant Orsola Malpighi University of Bologna, Italy

2 Organ allocation: match among graft, recipient and (surgeon)

3 Prospective may be different

4 But common principles among different organ allocation policies - Equity - Clear and common rules - Patients benefit

5 Equity among HCC and non-hcc Centers adapt their strategy according to: - rate of HCC on list - median waiting time for LT - drop-out on list of all recipients - type of donor

6 Which strategy to transplant HCC? Priority according AFP Priority with LDLT Extended criteria donor Priority according tumor stage Priority according response to treatments Liver Transpl. 2011; 17: Ann Surg Oncol. 2010;17: Transplantation ; 81: Transplantation. 2011; 92: Priority according waiting time Am J Transplant. 2006; 6: Liver Transpl. 2007; 13: Am J Transplant. 2010; 10: Hepatology 2011;53: Hepatogastroenterology 2012;59: Oncology 2011;81:

7 Lancet 2012; 379: ; J Hepatol ; 56(4):

8 Liver Resection Bologna policy for HCC on cirrhosis -Single nodule any size - Child A and MELD < Cirrhosis with or without portal hypertension but PLT > and no high risk oesophageal varices - LTs in case of HCC recurrence or liver decompensation after LR Grazi et al. Annals of Surgery 2001 Ravaioli et al. American Journal of Transplantation 2006 Cucchetti et al. Liver Transplantation 2006 Del Gaudio et al. American Journal of Transplantation 2008 Cescon et al. Archives of Surgery 2009

9 Liver resection for HCC before Liver Transplantation WHY NOT? -Pts not suitable for LT after LR due to: HCC recurrence out of conventional criteria Age limit Clinical condition - LTs more complex after LR Come prevedere i pz FREGATI dalla resezione?

10 How to predict variables for transplantability? Problems with Bologna data Liver resection for HCC on cirrhosis transplantable 94 HCC > 3 cm 78 HCC > 3 cm and with m.v.i. or poor differentiated Microscopic vascular invasion Poorly differentiated tumor Tumor size > 3 cm Satellite nodules Liver cirrhosis 36% LR on waiting list for LT without evidence of recurrence Hepatology 2012; 55:

11 Equity among old and young recipient for KT Il numero annuale di donatori cadavere in US rimane costante tra 18 e 55 anni con due picchi di incidenza a 21 anni (trauma) ed a 50 anni (cause cardiovascolari). Al contrario l età dei riceventi è spostata verso i anni. Pertanto i riceventi anziani hanno una relativa maggiore probabilità di ricevere un rene da donatore giovane rispetto ai riceventi giovani. Recipient age Age (years) Donor age Ross FL. Equal Opportunity Supplemented by Fair Innings: Equity and Efficiency in Allocating Deceased Donor Kidneys. Am J Transplant. 2012

12 EQUAL OPPORTUNITY: garantire uguale opportunità ai candidati di ricevere un donatore di simile età allocando i reni, ad ogni specifica categoria, proporzionalmente al numero di candidati in lista per quella categoria. 0,14 0,12 0,1 0,08 0,06 0,04 0,02 0 Probabilities of receive transplant Current US policy Ideal allocation policy Category recipient age group

13 FAIR INNINGS FAIR INNINGS: è una considerazione etica che si basa sul prudential life-span equity. Riceventi giovani ed anziani devono avere le stesse probabilità di vita, o aspettativa di vita, in relazione alla propria età. Da questo punto di vista appare etico allocare i reni giovani a pazienti giovani ed i reni ECD a pazienti anziani. STEP 1: determinare la proporzione dei riceventi in lista per gruppi di età Età No. Candidati (UNOS data) No. Donatori richiesti per soddisfare l equal opportunity % % % % %

14 Equity among old and young recipient for KT STEP 2: determinare la proporzione dei donatori in rapporto alla loro età e calcolare la probabilità di ogni classe di candidati di ricevere il trapianto matchato per età Età del donatore Età candidato STEP 3: Allocare il rene alla classe di candidati della stessa classe di età, qualora non ci sia un match, offrire il rene alla classe di età più vicina.

15 Clear and common rules

16 Clear and common rules

17 Clear and common rules Ravaioli et al. American Journal of Transplantation 2006

18 Clear and common rules Ravaioli et al. American Journal of Transplantation 2006

19 Patients Benefit? Too sick recipient Planning a liver transplantation: Dialysis MARS Transfusions I.C.U. Stay LIFE GAINED Planning a discharge at home to die LIFE LOST Ask for another center?

20 Patients Benefit? Marginal graft MELD Recipient Selective criteria MELD era Pre-MELD era Quality transplant programs

21 Patients Benefit? MELD >30 we would not generally recommend to restrict OLT to pts with MELD <30

22 Bologna experience MELD > cases 1-year 76% 5-year 60% Intention to-treat survival 90 days since on waiting list No-LT 4% (46 pts) Vs. LT 85% (94 pts)

23 Patients Benefit? How to improve results? Do not forget the starting point to find particular things

24 Patients Benefit? How to improve results? related living unrelated Gjertson and Cecka, Kidney Int, 2006 Collaborative Transplant Study

25 Patients Benefit? How to improve results? Lodhi SA, NDT 2011

26 Patients Benefit? How to improve results? Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation; NEJM 2009

27 Liver transplantation strategies from Kidney experience 1-3 hours Liver biopsy Expert pathologists on liver disease available 24 hours per day at our hospital Donor aorta clamped Recipient on the operating room Decision to accept the liver: senior surgeons considers the histological assessment and the macroscopic aspect as depicted by the harvesting surgeon 30 minutes Histo-pathological report by telephone

28 Liver transplantation strategies from Kidney experience Dissection Hepatectomy Transplantation Increased graft ischemia

29 Liver transplantation strategies from Kidney experience Dissection Hepatectomy Transplantation Short graft ischemia

30 Liver transplantation strategies from Kidney experience Ravaioli et al.transplant International 2009

31 Liver transplantation strategies Transplant survival benefit: the expected lifetime with a transplant is longer than the expected lifetime without the transplant. Example: patient with a predicted 1-year survival rate of 60% without a transplant on the waiting list and 70% with a transplant net transplant survival benefit Merion et al. Liver Transplantation 2004

32 Liver transplantation strategies Merion et al. Liver Transplantation 2004 Merion et al. American Journal of Transplantation 2005

33 Liver transplantation strategies Ravaioli et al Transplantation 2009

34 Allocation according to transplant benefit Prospective

35 Prospective TRANSPLANT BENEFIT = SOPRAVVIVENZA ATTESA DOPO TRAPIANTO SOPRAVVIVENZA ATTESA SENZA TRAPIANTO STIMATORE DELLA SOPRAVVIVENZA ATTESA SENZA TRAPIANTO: Candidato senza HCC, Model for End-stage Liver Disease (MELD): Wiesner RH, McDiarmid SV, Kamath PS.MELD and PELD: application of survival models to liver allocation, Liver Transpl 2001;7: Include: Bilirubina, INR, Creatinina Non include le caratteristiche dell epatocarcinoma per cui bisogna usare una formula specifica: Candidato con HCC, HCC-MELD: Freeman RB, Edwards EB, Harper AM. Waiting list removal rates among patients with chronic and malignant liver diseases. Am J Transplant. 2006;6: Include: MELD, Diametro tumore ed AFP

36 TRANSPLANT BENEFIT = SOPRAVVIVENZA ATTESA DOPO TRAPIANTO SOPRAVVIVENZA ATTESA SENZA TRAPIANTO STIMATORE DELLA SOPRAVVIVENZA ATTESA DOPO TRAPIANTO: Italian Donor Model for End-stage Liver Disease (MELD): Avolio AW, Cillo U, Salizzoni M. Balancing donor and recipient risk factors in liver transplantation: the value of D-MELD with particular reference to HCV recipients.am J Transplant. 2011;11: Include: MELD Età ricevente HBV, HCV status Presenza di trombosi portale Ritrapianto come indicazione Non include le caratteristiche dell epatocarcinoma (che venivano non significative alla regressione di Cox) ma non ci sono altri scores predittivi inclusivi di tutta la popolazione trapiantata (con e senza HCC)

37 TRANSPLANT BENEFIT = SOPRAVVIVENZA ATTESA DOPO TRAPIANTO SOPRAVVIVENZA ATTESA SENZA TRAPIANTO

38 TRANSPLANT BENEFIT = SOPRAVVIVENZA ATTESA DOPO TRAPIANTO SOPRAVVIVENZA ATTESA SENZA TRAPIANTO Esempio in caso di donatore di 65 anni. Tutti i riceventi non hanno trombosi portale e sono in lista per il primo trapianto. La lista è ordinata per MELD reale. Pz Età HCC HCV MELD Transplant Benefit (over 3-years) 1 45 No Pos anni 2 63 No Pos anni 3 54 Max 3cm, AFP 60 Neg anni 4 62 Max 2cm, AFP 20 Pos anni 5 60 No Pos anni 6 39 No Neg anni 7 58 Max 3cm, AFP 50 Pos anni 8 64 Max 4cm, AFP 30 Neg anni 9 60 Max 3cm, AFP 60 Pos anni

39 TRANSPLANT BENEFIT = SOPRAVVIVENZA ATTESA DOPO TRAPIANTO SOPRAVVIVENZA ATTESA SENZA TRAPIANTO Esempio in caso di donatore di 65 anni. Tutti i riceventi non hanno trombosi portale e sono in lista per il primo trapianto. La lista è ordinata per MELD reale. Pz Età HCC HCV MELD Transplant Benefit (over 3-years) 3 54 Max 3cm, AFP 60 Neg anni 1 45 No Pos anni 6 39 No Neg anni 2 63 No Pos anni 4 62 Max 2cm, AFP 20 Pos anni 8 64 Max 4cm, AFP 30 Neg anni 7 58 Max 3cm, AFP 50 Pos anni 9 60 Max 3cm, AFP 60 Pos anni 5 60 No Pos anni

40 Prospective

41 Transplant centers with low performance assessments are stimulated to be more conservative

44 Transplant centers with low performance assessments are stimulated to be more conservative In summary, findings of this study indicate a significant association between low performance evaluations of kidney transplant centers and a reduction in transplant volume Results highlight a potential unintended impact of regulatory oversight on center practice that may deleteriously impact access to care for transplant candidates Continued growth of national kidney transplant volume is of critical importance to the end-stage renal disease population and ongoing efforts to identify barriers to this growth should be a priority of the transplant community

45 Conclusions: support donation and living donors