Santi Cosmo e Damiano
Erano entrambi medici, nati
in Arabia nel III secolo
d.c.
L’iconografia eccelsiastica li
rende protagonisti del
tentativo di trapiantare la
gamba di un moro a un
cristiano
1831
Mary Shelley Publishes
Frankenstein
…describes a morally and physically superior creature
constructed with parts from graveyards; this creature
turns to violence only when his fictional creator rejects
him. This is the first positive and negative depiction in
literature of the
use of organs and parts from dead people.
1902, the French surgeon Alexis Carrel, Nobel Prize for
medicine in 1912, develops the
technique of vascular anastomosis for the suture of blood
vessels.
Joseph Murray and the medical team at Boston's Peter
Bent Brigham Hospital perform the first long-term
successful organ (kidney) transplant,
Dec 23 1954. Richard Herrick received a kidney from his
identical twin.
T.E. Starzl performed in Denver, Co, USA
the first successful liver transplant procedure
1963
Christiaan Barnard performed the first human heart
transplant, in Cape TownSouth Africa
Dec. 3, 1967
TRASPLANTS IN THE WORD
KIDNEY
PANCREAS
KIDNEY-PANCREAS
LIVER
LRLT
HEART
CUORE-LUNG
LUNG
BONE MARROW
447.182
19.695
8.823
112.299
3.291
49.829
2.266
8.842
82.780
UNOS 2004
LONGEST SURVIVAL WITH
WORKING TRANSPLANT
KIDNEY
LIVER
BONE MARROW
HEART
PANCREAS
KIDNEY-PANCREAS
HEART-LUNG
LUNG
35 anni
28 anni
29 anni
23 anni
15 anni
16 anni
13 anni
13 anni
UNOS 2004
DEFINITION
OF DEATH
THE DEATH OF AN INDIVIDUAL
IS IDENTIFIED BY THE
IRREVERSIBLE CESSATION OF
ALL THE ENCEPHALIC
FUNCTIONS
(CORTEX AND TRUNK)
(art. 1 Legge 23/12/93 n. 578)
POTENTIAL
DONOR
PRIMARY BRAIN PATHOLOGIES
WITH POSSIBLE FATAL
OUTCOME
• Cerebro-vascular accidents
• Cranioencephalic traumas
• Post-anoxia cerebral damages
Intensive
Care
DEATH
DIAGNOSIS
CONVOCATION OF THE MEDICAL
COLLEGE
(Art. 5 D.M. 409/1977)
• Forensic expert/ pathologist or a doctor
commisioned by Direzione Sanitaria
• Anesthesist / Intensive Care expert
• EEG expert neurologist/ neurosurgeon
DEATH
DIAGNOSIS
INSTRUMENT CHECKS
(D.M. 22/8/94 n. 582)
• 30’ EEG is required every 2 h for 3 times
( absence of electric activity, spontaneous or
induced)
• X-ray brain angiography ( abcence of flux)
DEATH
DIAGNOSIS
OBSERVATION TIME
(D.M. 22/8/94 n. 582)
• Adults and children > 5 anni 6 hours
• Chidren 1 - 5 years
12 hours
• Children < 1 year
24 hours
ACTUAL
DONOR
TWO PREREQUISITE
CONDITIONS
• Not opposition/ consent of the family
• Overall and specific organ suitability
REALTIONSHIP
WITH THE FAMILY
THE PROPOSAL FOR DONATION
IS MADE AFTER THE
COMMUNICATION OF DEATH
• The family cannot interfere in the
course of death verification
• The will of the deceased and the will of
the family must be made clear
• The talk must explain clearly the
timing and procedure of consent or
opposition
RELATIONSHIP
WITH THE FAMILY
The Intensive Care expert must
safeguard the relationship with the
family as much as possible, supply all
the information as clearly as possible
and explain the possibility of donation
without influencing the family
discretionary power.
THE NEW TRANSPLANT
LAW
(Legge n.91, 1-3-99)
ANONIMITY
• The donor’s and the recipient’s personal
data must remain anonymous
• The harvest must be performed with the
due respect for the deceased
THE NEW
TRANSPLANT LAW
(Legge n.91, 1-3-99)
PENALTIEA FOR TRAFFICKERS
• Arrest and heavy fines for organ
traffickers. Disqualification from the
medical profession for the doctors
ORGANIZATIONAL
ASPECTS
(donor-recipient)
–
–
–
–
–
Suitability of the donor:
Tests for the evaluation of organ functionality
Serology ( transmissible diseases)
Instrument exams (exclusion of tumors in the
donor)
Specialistic counselling
Possible biopsies for the organ evaluation
(liver, marginal kidneys)
Managment of the recipient ( call, transport)
Transplants in Italy
CNT (Roma)
NITp
AIRT
OCST
SICILIA
TRANSPLANT
OPERATIVE SCHEDULE
Repert about donor from I.C. to NITp
Alert of transplant center
Selection and call of the recipient
Transport activation: harvest team and recipient
Harvest and conservation of the organs
Transplant (within ~ 10 hours from report)
Heart
6h
LIver
12 h
Pancreas
20 h
Kidney
36 h
Donation & Transplantation Process
Society
Potential
Donor
Detection
Brain Death
Confirmation
Org. Proc.
Experts
Transplant
Family
Consent
Organ
Storage
Organ
Removal
Legal
Confirmation
Brain Death
Transplant
Teams
Organizational
Aspects
Donor
Management
Legal
Consent
Donor
Evaluation
Safety-Quality Network
T.I.
Interregional Reference
Centers
Regional Reference
Centers
Componenti
CNT
Database
Experts ( couselling during
harvesting procedure)
Video
Conferenza
National Transplant Center
Istituto Superiore di Sanità
*Dati preliminari al 31 luglio 2009
Confronto Donatori Utilizzati PMP 2008 vs 2009*
Anno 2008
19,2
+ 6,77%
Anno 2009*
20,5
FONTE DATI: Dati Reports CIR
*Dati preliminari al 31 luglio 2009
Confronto Numero Donatori Utilizzati 2008 vs 2009*
Anno 2008
1094
+11,7%**
**Il maggiore aumento % riscontrato sul numero assoluto delle
donazioni rispetto all’incremento % del PMP è dovuto all’adozione della nuova popolazione
Anno 2009*
1222
*Dati preliminari al 31 luglio 2009
Attività donazione per regione – Anno 2009*
% Opposizioni alla donazione
REGIONE
2009*
2008*
diff
Prov. Auton. Bolzano
0,0%
0,0%
0,0%
Prov. Auton. Trento
0,0%
0,0%
0,0%
Friuli Venezia Giulia
12,5%
25,0%
-12,5%
Umbria
20,0%
22,2%
-2,2%
Lombardia
21,2%
25,5%
-4,2%
Sardegna
23,1%
34,7%
-11,6%
Basilicata
25,0%
47,6%
-22,6%
Emilia Romagna
25,9%
33,3%
-7,4%
Toscana
27,3%
31,9%
-4,6%
Marche
28,6%
36,2%
-7,6%
ITALIA
29,2%
32,6%
-3,4%
Veneto
30,1%
21,6%
8,5%
Puglia
30,3%
35,0%
-4,7%
Lazio
30,3%
27,8%
2,5%
Liguria
31,0%
28,0%
3,0%
Campania
33,6%
46,8%
-13,1%
Piemonte - Valle d'Aosta
35,9%
28,6%
7,3%
Sicilia
46,3%
51,8%
-5,5%
Calabria
47,1%
38,3%
8,7%
Abruzzo - Molise
56,0%
44,6%
11,4%
FONTE DATI: Dati Reports CIR
Donatori % opposizione – Anni 2002/2008
29,9
27,7
29,4
29,4
31,0
32,7
27,5
473
558
601
575
574
683
749
2002
2003
2004
2005
2006
2007
2008
FONTE DATI: Dati Reports CIR
Incremento percentuale delle opposizioni ultimo
triennio
32,7
+ 11,2 %
29,4
2005
2008
Incremento percentuale trapianti eseguiti ultimo
triennio
3177
- 8,2 %
2005
2916
2008
Incremento percentuale pazienti iscritti in lista ultimo
triennio
9790
8988
2005
+ 8,9 %
2008
*Dati SIT 17 Febbraio 2009
Liste di Attesa al 31 Dicembre 2008*
Incluse tutte le
combinazioni
Rene
Fegato
Cuore
9.175
7.069
Pazienti
Tempo medio di attesa
dei pazienti in lista
% mortalità in lista
Iscrizioni
1.544
1.535
Pazienti
Iscrizioni
731
738
Pazienti
Iscrizioni
3,11 anni
2,04 anni
2,19 anni
1,53 %
6,18 %
9,72%
FONTE DATI: Dati Sistema Informativo Trapianti
*Dati definitivi al 31 Dicembre 2008
Trapianto di FEGATO – Attività per centro trapianti
Incluse tutte le
combinazioni
2008*
100
75
50
25
Torino
Pisa
Bologna
Pa ISMETT
Padova
Bergamo
Modena
Milano-Ni
Na Cardarelli
Milano-Pol
Genova S. Mart.
Ancona
Udine
Milano Tumori
Rm S. Camillo
Rm Cattolica
Cagliari
Rm Sapienza
Rm S.Eugenio
Bari
Verona
Rm B. Gesù
136
105
82
73
70
60
59
50
44
37
34
30
30
27
27
25
25
24
23
19
13
3
FONTE DATI: Dati Reports CIR
OLTx
Università degli Studi di Udine
Clinica chirurgica
Centro Nazionale Trapianti
Sopravvivenza dei pazienti trapiantati
100
Sopravvivenza %
p = 0,0001
80
74 %
60
40
20
0
0
1
2
3
4
Anni
5
Centro Nazionale Trapianti
Sopravvivenza dei pazienti entrati
in lista d’attesa e non trapiantati
100
Sopravvivenza %
80
60
p = 0,0001
31,2 %
40
20
0
0
3
6
9
12
15
18
21
24
27
30
33
Mesi
36
SOPRAVVIVENZA TRAPIANTI DI
FEGATO
Udine vs registro Europeo
Udine
ELTR
1 anno
80%
79%
5 anni
70%
69%
18 Ottobre 2003
TRAPIANTI:A GENOVA IMPIANTATO
FEGATO DA DONATRICE DI 97 ANNI
(ANSA) - GENOVA, 18 OTT - Il fegato di una paziente di 97, morta giovedi scorso
in seguito ad un incidente stradale a Savona, e' stato impiantato in una donna di
64 anni. L' intervento, della durata di 8 ore, e' stato eseguito a Genova presso il
Centro Trapianti d' Organo dell' Ospedale San Martino nella notte tra il 16 e il 17
ottobre. La donatrice, una genovese di 97 anni, risulta essere il donatore piu'
anziano segnalato dalla letteratura internazionale.
CONDIZIONI DEL PAZIENTE
TRAPIANTATO DI FEGATO A 5 ANNI
Scadente
9,2 %
Eccellente
90,8 %
Organ procurement
Organ procurement
Organ procurement
Liver Transplantation in Europe
Indications in 33845 Cirrhosis
01/1988 - 12/2005
Primary Biliary : 3761
11%
Unknown causes : 2689
8%
Others : 439
1%
Virus related :
13973
41%
Secondary Biliary :
378
1%
> 60% HCV
Autoimmune : 1462
4%
Alcoholic : 11143
33%
ELTR
12/2005
Primary Indications of Liver Transplantation
in 14359 Virus related Cirrhosis in Europe
01/1988 - 06/2006
Virus BCD : 117
Other virus : 102
1%
Virus BC : 590
1%
4%
Virus B : 3469
Virus BD : 974
24%
7%
Virus C : 9107
63%
ELTR
12/2005
Liver Transplantation in Europe
Indications in 7318 Hepato-Biliary Cancers
01/1988 - 12/2005
Cholangiocellular
carcinoma : 227
3%
Metastases : 403
6%
Carcinoma biliary tract : 209
3%
Others : 508
7%
Hepatocellular carcinoma : 5971
82%
ELTR
Indications of Liver Transplantation in 177912/2005
Other liver diseases in Europe
01/1988 - 12/2005
Polycystic diseases :
424
24%
Other liver diseases
(unspecified): 523
29%
Budd Chiari : 567
32%
Parasitic
diseases : 54
3%
Benign liver tumors :
211
12%
Emergency
•
•
•
•
•
Fulminating Hepatitis
PNF within 10 days since OLTx
Hepatectomy for trauma with complete loss of function
Acute deficiency in Wilson’s disease
HAT within 15 days since OLTx
UNOS Priority Criteria
Accepted indications for liver trasplant
Emergency
Not emergency
Hepatic trauma
Advancfed liver chronic disease
Fulminating hepatitis
Hereditary mataboic liver disease
Primary non function
Primary liver tumors
Fulminating Wilson
Benign tumors or polycystic liver
Keeffe EB. In: Transplantation of the liver. Lippincott Williams & Wilkins Ed 2001, mod.
Controindications for liver transplant
Relative
Absolute
alcohol or drugs abuse
Extraepatic tumors
Portal thrombosis
Out of control infections
Previous biliary surgery
Advanced cardiopulmonary diseases
Old age ( > 65 aa)
Major psychiatric diseases
Keeffe EB. In: Transplantation of the liver. Lippincott Williams & Wilkins Ed 2001, mod.
MILAN CRITERIA
Solitary lesion < 5 cm or < 3 lesions with
diameter < 3 cm, no major vessel invasion and
no extrahepatic involvement
NEWS
CRITERI MINIMI PER INDIRIZZARE IL
PAZIENTE AL CENTRO TRAPIANTI
1. Sopravvivenza stimata senza trapianto ad 1 anno
90%
2. MELD score >15
3. Child-Pugh score 7 (Child-Pugh class B or C)
4. Sanguinamento da varici esofagee o singolo episodio
di PBS indipendentemente dal punteggio di ChildPugh
Lucey et al. Liver Transpl Surg, 1997
PUNTEGGIO DI CHILD-PUGH
Punti:
1
2
3
Albumina, g/l
>35
28-35
<28
Prolung. PT, sec
<3’’
4-6’’
>6’’
Bilirubina, mg/dl
<2
2-3
>3
Encefalopatia PS
assente
I-II
III-IV
Ascite
assente
+
++
Il candidato ideale per OLT ha CP-score 8-10
Pugh et al. Br J Surg 1973
Il modello MELD
c
l
i
c
c
a
s
u
l
p
u
l
s
a
n
t
e
p
e
r
c
a
l
c
o
Il MELD (Mayo End stage Liver Disease) è un particolare sistema a
punteggio che è stato proposto dalla Mayo Clinic (Rochester,
Minnesota, USA) per valutare la sopravvivenza dei pazienti con la
cirrosi ed un'insufficienza epatica terminale.
Si basa sulla determinazione dei valori di bilirubina, di INR (indice
della coagulazione del paziente) e di creatinina (indice della funzione
dei reni).
Tanto più alto è il punteggio ottenuto, tanto più gravi sono le
condizioni cliniche del paziente.
La formula per il calcolo è:
3.8*loge(bilirubina [mg/dL]) + 11.2*loge(INR) +
9.6*loge(creatinina [mg/dL])
Liver transplantation in HIV-infected recipients in
HAART era in Italy:
inclusion criteria
“Eligible” subjects:
– No history of AIDS defining illness in the previous
two years
– CD4 >200 or >100 if intolerant to ARVs
– HIV RNA undetectable, or intolerant to ARVs but
post-transplant HIV suppression is expected
“Ineligible” subjects:
– Did not meet 1 or more criteria above
UDINE, (2004-2009)
26/418 OLT
17% of the overall activity of the center
Traditional types of liver transplant in
adults and children
Cadarveric donor
Whole liver
Living donor
Split liver
Classic split
Enlarged split
Split liver
OLTx Surgical Incision
Traditional technique
Piggy-Back technique
Split sinistro
pediatrico
Split destro
adulto
Trapianto di fegato da donatore vivente
LRLT
Trapianto di fegato da donatore vivente
INDICAZIONI ADULTO
LRLT
4%
8%
FHF
P=0.05
58%
60%
Cirrosi
HCC
ReOLT
22%
10%
0.8%
P< 0.0001
LRLT
P< 0.0001
10%
Intero da cadavere
15%
13%
Altre
0%
20%
40%
60%
Patient Survival according to the
Year of Liver Transplantation
(%)
100
88
85
80
77
82
65
60
61
64
52
46
40
34
20
0
21
0
1
2
<85 : 513
95-99 : 18044
3
4
5
18
6
7
85-89 : 4117
2000-2004 : 22573
8
9
10 Yrs
90-94 : 11984
>2004 : 6157
ELTR
Evolution of Recipient Age
12/2005
05/1968 - 12/2005
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
6880
82
84
86
0 to 2 : 2633
88
90
92
2 to 15 : 3598
45 to 60 : 27864
94
96
98
2000
15 to 45 : 17860
>= 60 : 9561
2002
2004
Patient Survival according to Adult
Recipient Age
01/1988 - 06/2006
100 (%)
81
80
74
70
78
69
60
63
59
62
52
45
40
< 60 yrs : 45262
20
p Log Rank = 0.001
>=60 yrs : 9867
0
0
1
2
3
4
5
6
7
8
9
10 Yrs
ELTR
Soppravvivenza SPLIT versus LRLT e OLT
(%)
100
79
80
75
77
65
60
66
64
58
54
49
40
Intero da cadavere
Living donor
Split liver
20
0
0
1
2
3
4
5
6
7
8
9
10
anni
ELTR
Graft Survival according to Donor
Age in Europe
12/2005
01/1988 - 12/2005
(%)
100
Total Log Rank test p = 0.0001
<55 years : 46061
55-65 years : 7607
75
80
>=65 years : 4763
68
72
60
64
57
57
61
53
48
53
41
40
41
32
20
0
0
1
2
3
4
5
6
7
8
9
10 Yrs
AFTER OLTx
Immunological
complications
Rejection
Infections
...
Immunosuppression
Surgical
complications
Hypertension
Diabetes
Dyslilipidemia
Obesity
Osteoporosis
“De novo” tumors
...
Vascular
Biliary
...
Relapse
Infectious complications
Bacterial
Viral
Mycotic
•
•
•
•
Bacterial infections of the biliary tract
Cholangitis
Peritonitis
Abdominal absidations
Medical complications
•
•
•
•
•
•
•
•
D.M.
Iperlipemia
Obesity
Osteoporosis
Cardiovascular complications
Neuropsychiatric complications
IRA
IRC
REJECTION
ACUTE REJECTION
Within 5 days to 6 weeks after OLTx
Inflammatory process involving the biliary
ducts and the vascular endothelium
•
•
•
•
•
•
•
fever
jaundice
Hepatomegalia
low bile production
pale bile
increase of ALT, AST, GGT, bilirubine
increase WBC and eosinophily
•
•
•
BIOPSY
RAI SCORE
STEROIDS
CRONIC REJECTION
60-90 days after OLTx or later
After an acute rejection not solved
After recurrent episodes of acute rejection
Without acute episodes, probably related
to an inadeguate immunosuppressive
therapy
•
Not specific symptoms vs cholestasis
HAT or HAS!!!
Duttopenia
•
•
IMMUNOSUPPRESSIVE THERAPY
Re OLTx
De novo tumors after liver
transplantation
The risk of malignancy is a well recognized
event in transplanmt recipients.
Besides skin cancer, Kaposi’s sarcoma and
lymphoproliferative disorder, in close contact
with immunosuppression, many cancers of
solid organ are described
Causes of death after organ transplant
N. = 321 (autopsies)
10%
8%
12%
6%
64%
Infections
Hepatic insuff.
MOF
Respiratory insuff
Cardiovascular
Torbenson et al. Mod Pathol; 1998