transplantologie 18 iunie 2013 (1)
DESCRIPTION
transplantTRANSCRIPT
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Transplantul de organe
Prof. Dr. Irinel Popescu
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• Transplantul de organe şi tesuturi este rezultatul unui secol de eforturi şi progres al medicinei.
• În prezent constituie o metodă terapeutică acceptată, cu rezultate care au convins atât lumea medicală cât şi opinia publică, reuşind să salveze vieţi care se îndreptau inevitabil spre deces.
• Apariţia transplantului de organe şi ţesuturi a schimbat în mod radical faţa medicinei moderne, volumul de cunoştinţe acumulate în medicină, în general, provenind din domeniul transplantului, fiind cu adevărat uriaş.
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Momente majore în dezvoltarea transplantului mondial :
• 1902 - Alexis Carel descrie tehnica anastomozelor vasculare
• 1902 - Ullman cercetări în domeniul grefei renale
• 1905 - Florescu - transplant renal experimental la câine
• 1940 - Peter Medawar pune bazele imunologiei moderne descriind fenomenul de rejet
• 1954 - Joseph Murray efectuează primul transplant renal între doi gemeni univitelini
• 1958 - Jean Dausset descoperă sistemul antigenelor HLA
• 1963 - James Hardy efectuează primul transplant pulmonar
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• 1963- Thomas Starzl- primul transplant de ficat la om, fara supravietuirea bolnavului
• 1967 - Thomas Starzl efectuează primul transplant hepatic cu supravieţuirea bolnavului
• 1968 - Christiaan Barnard efectuează primul transplant cardiac
• 1968 - stabilirea criteriilor morţii cerebrale (Universitatea Harvard)
• 1980 - este introdusă ciclosporina• 1981 - Norman Shumway - primul transplant cord-
pulmon• 1989 – S. Raia – transplant hepatic de la donator viu
– copil
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• Thomas Starzl, probabil cea mai importanta personalitate din istoria transplantului
• Prima serie clinica de transplante renale reusite
• Primul transplant hepatic la om
• Introducerea Tacrolimusului
• Programe de transplant de pancreas si intestin subtire
• Teoria microhimerismului• Xenotransplantul
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• Începând cu anul 1980, odată cu introducerea Ciclosporinei, rezultatele s-au îmbunătăţit spectaculos. Din 1983, odată cu conferinţa de consens de la NIH (Bethesda, Maryland), transplantul de ficat a fost considerat metodă terapeutică.
• Consecinţe:– asigurările au acceptat să preia costurile– listele de aşteptare s-au mărit neîncetat deoarece
pe aceste liste au început să fie incluşi bolnavii înainte de a ajunge în stadiul final al maladiei
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• În momentul de faţă activitatea de transplant la nivel naţional se desfăşoară în cadrul unor programe şi este coordonată de un for central (de regulă o agenţie).
• Şase ţări europene (Austria, Belgia, Germania, Olanda, Luxemburg şi Slovenia) sunt coordonate de o singură agenţie care se numeşte “Eurotransplant”
• În România, potrivit legii 95/2006, activitatea de transplant este coordonată de către Agentia Nationala de Transplant
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Momente majore în dezvoltarea transplantului în România:
• 1980 - primul transplant renal de la donator viu - Prof. Eugen Proca
• 1980 - primul transplant renal de la donator cadavru Prof. Petru Dragan- Timişoara
• 1997 - se reiau prelevările de la donator cadavru: prima în februarie în Clinica Chirurgicală Fundeni (s-a prelevat numai rinichiul) şi a doua în iunie la Spitalul Clinic de Urgenţă (s-au prelevat ficatul şi rinichii).
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• 1997-primul transplant de ficat, fara supravietuirea pacientului (Prof.dr. Irinel Popescu – I. C. Fundeni)
• 1999 (octombrie) - primul transplant de cord - Dr. Şerban Brădişteanu
• 2000 (aprilie) - primul transplant de ficat cu supravieţuirea bolnavului - Prof. Dr. Irinel Popescu
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DONATOR PRIMITOR
GREFA
Principii de baza ale transplantarii:
1. Cat mai mare compatibilitate genetica (sistem ABO, sistem HLA);
2. Tehnica de prelevare si transplantare perfecta;
3. Ingrijire postoperatorie atenta.
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Clasificarea grefelor
• Origine– Autogrefa: acelasi individ– Izogrefa: gemeni monozigoti– Alogrefa: indivizivi din aceeasi specie– Xenogrefa: indivizi din specii diferite.
• Topografie– Ortotopic: regiunea anatomica obisnuita– Heterotopic: alta regiune anatomica.
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Imunologia transplantului
• Grefa – structura non-self– Raspuns imun non-specific: fagocite,
celule APC– Raspuns imun specific
• Umoral: limfocite B anticorpi• Celular
– Limfocite T citotoxicitate– Limfocite NK ADCC
REJET!
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Toleranta imuna
• Teoria microhimerismului-evidentierea celulelor dendritice in diverse organe si tesuturi
• Transplant de maduva osoasa de la donator
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Tipuri de rejet
• Hiperacut – umoral – anticorpi citotoxici cu efect nociv asupra grefei
• Acut – celular - responsiv la tratament– Acut hiperaccelerat – primitor sensibilizat
fara anticorpi circulanti
• Cronic – mecanism necunoscut (?umoral), cu deteriorarea si pierderea grefei
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Profilaxia rejetului• Pretransplant:
– Evaluarea compatibilitatii ABO– Evaluarea compatibilitatii HLA– Cross-match test (evalarea anticorpilor
preformati)• Intra – si posttransplant:
– Imunosupresia• Ciclosporina• Tacrolimus• Micofenolat (mofetil, sodic)• Corticosteroizi• Anticorpii monoclonali• Globulinele antilimfocitare/timocitare• Sirolimus• Ciclofosfamida, azatioprina
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Schema clasica de imunosupresie
• Inhibitori de calcineurina– Tacrolimus– Ciclosporina
• Antimetabolit– Micofenolat– Azatioprina
• Corticosteroizi
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Tratamentul rejetuluiTip rejetTip rejet TratamentTratament
hiperacuthiperacut PlasmaferezaPlasmafereza
CiclofosfamidaCiclofosfamida
Prostaglandina EProstaglandina E
RetransplantareRetransplantare
acutacut CorticoterapieCorticoterapie
Ac monoclonaliAc monoclonali
Ser antilimfocitarSer antilimfocitar
Retransplantare (f. Retransplantare (f. rar)rar)
croniccronic RetransplantareRetransplantare
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Tipuri de donatori
• Viu – rinichi, ficat, pancreas, intestin– Inrudit – living-related– Neinrudit – living-unrelated
• ‘Cadavru’ – decedat sau in moarte cerebrala– cu activitate cardiaca
• Criteriile de moarte cerebrala – Examen clinic:
» coma profunda, flasca, areactiva» absenta reflexelor de trunchi cerebral
– absenta ventilatiei spontane– lipsa activitatii cerebrale pe EEG
– fara activitate cardiaca – categorie inca rar folosita
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Prezervarea organelor
• Prezervarea: solutii de prezervare reci (1-4ºC)– Furnizoare de substante energetice– Antagonizeaza efectele nocive ale racirii
• Compozitia solutiei ~ mediu intracelular, izoosmotica si izo-pH
• Tipuri de solutii de prezervare– Wisconsin, Collins, Custodiol, Celsior s.a.
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Timpul de prezervare
• Ficat 12 ore• Rinichi 24 ore• Pancreas 17 ore• Cord 4 ore• Plaman 6-8 ore
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Transplantul renal
• Indicatii – afectiuni renale in stadiu terminal ‘end-stage’ – insuficienta renala cronica– Glomerulonefrite– Pionefrite– Maladii ereditare– Afectiuni metabolice– Boli sistemice
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Transplant renal - tehnica
• Anastomoze:– A renala cu a iliaca
externa/interna a primitorului
– V renala cu v iliaca externa a primitorului
– Ureter implantat in vezica urinara a primitorului
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Transplant hepatic• Indicatii
– Insuficienta hepatica acuta• Hepatite virale• Boala Wilson
– Boli hepatice in stadiu terminal• Ciroze• Colangita sclerogena primitiva• Hepatita autoimuna
– Afectiuni metabolice– Cancerul hepatic
• Hepatocarcinomul pe ciroza – criteriile Milano• Metastazele din tumori neuroendocrine (carcinoidul)
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Tehnici de Tx hepatic
• cu ficat intreg
• cu ficat redus
• cu ficat impartit
• de la donator viu
• domino
• auxiliar
de la donator in moarte cerebrala
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• Octombrie 2000 – primul transplant de la donator viu cu segmentele 2-3
• Februarie 2003 – primul transplant de la donator viu cu hemificat drept
• Martie 2012 – primul transplant cu 2 fragmente hepatice de la donatori vii (“dual-graft”)
• Octombrie 2000 – Aprilie 2013– Hemificat drept 59– Segmentele 2-3 25– Hemificat stang 5– Hemificat stang si lob caudat 2– Hemificat drept + segmente 2-3 (dual graft) 1
Transplant hepatic de la donator viuTransplant hepatic de la donator viu
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15 Aprilie 200015 Aprilie 2000 – 31 Mai 2013 – 31 Mai 2013 Centrul de Chirurgie GeneralCentrul de Chirurgie Generalăă şşi Transplant Hepatic i Transplant Hepatic
“Dan Setlacec”, Fundeni “Dan Setlacec”, Fundeni 454 transplanturi hepatice454 transplanturi hepatice la la 434 434 de pacienţi de pacienţi
((2020 retransplantări) retransplantări)
POPESCU I (sub redactia)Transplantul hepatic. Editura Academiei Romane (Bucuresti), 2011. ISBN: 978-973-27-2054-7.
342
9314 4 1
0
50
100
150
200
250
300
350 FICATINTREGTx DONATORVIUTx SPLIT
Tx FICATREDUSTx DOMINO
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TEHNICA OPERATORIE
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TEHNICA CU FICAT INTREG
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Tehnica clasica
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Anastomoza cava – tehnica “piggy-back”
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Anastomoza cava – tehnica Belghiti
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Anastomoza cava – tehnica prin triangulatie
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Anastomozele arteriala si portala
Celiac axis
Common hepatic artery
PV
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Anastomoza arteriala reconstructie vasculara
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Anastomoza biliaraE-E DUCT- TO-DUCT ANASTOMOSIS WITH /WITHOUT T-TUBE
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TEHNICI ALTERNATIVE
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1) LIVING-DONOR LT
== transplantation of one or more liver transplantation of one or more liver segments from a living donor to a child-segments from a living donor to a child-recipient (left lateral section) or to an recipient (left lateral section) or to an adult recipient adult recipient (right hemiliver)(right hemiliver)
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Liver segments harvestedfrom a living donor
transplanted liver segments
In children:the left lateral section (more frequently)the left hemiliver (segments 2, 3, 4)
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DONATOR SECTIONECTOMIE LATERALA
STANGA
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Disectia pediculului hepatic
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Disectia parenchimului
hepatic
Cavitron Ultrasonic Surgical Aspirator®
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Disectia venei hepatice
stangi
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Back-table
Flush arterial
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Back-table
Vena porta
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Back-table
Vena hepatica stanga
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RECEPTOR TRANSPLANT HEPATIC CU SEGMENTE 2-3
- VHS d – VCI r (venoplastie / triangulatie)- VPS d – VP r (termino-terminal, factor de crestere)- AHS d – AH r - Canal hepatic stang donor – canal hepatic comun
receptor
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RECEPTOR TRANSPLANT HEPATIC CU HEMIFICAT STANG SI SEGMENT 1
- VHs-m (d) (venoplastie “kilt) – VCI (r) triangulatie- VP stg (d) – VP (r) - AH stg (d) – AH (r)- 2 canale biliare (d) cu canalele hepatice stg si dr (r) protezate
pe stenturi
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Anastomoza VHs-d cu VCI-rAnastomoza VS1-d cu VCI-r
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With improvements in surgical instrumentation and techniques and progressively longer waiting times for
cadaveric livers, LDLT was extended to adult recipients, using right hemiliver grafts
In adults:the right hemiliver (segments 5-8)
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Prelevarea hemificatului drept pentru transplant
Mobilizarea hemificatului drept.Sectionarea venelor hepatice accesorii
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Mobilizarea hemificatului drept. Sectionarea ligamentului hepato-cav
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Identificarea venei hepatice drepte. Introducerea unui tub pentru efectuarea “liver hanging maneuver”
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Disectia hilara a elementelorpediculului hepatic
Clamparea temporara aarterei si portei drepte
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Modificarea culorii hemificatului drept
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Repozitionarea tubului pentru efectuarea “liver hanging maneuver”
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Repozitionarea tubului pentru efectuarea “liver hanging maneuver”
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Repozitionarea tubului pentru efectuarea “liver hanging maneuver”
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Transsectiunea parenchimului hepaticfara ligatura prealabila a pediculilor
vasculari sau biliari
Identificarea venelor tributarevenei hepatice drepte
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Ultima etapa a transsectiunii parenchimului hepatic, cu sectionarea canaluluihepatic drept intraparenchimatos
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Parenchimul hepatic complet sectionat(elementele vasculare ale hemificatului drept nu au fost inca sectionate)
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VIII VIII
VMHV LHV
RIGHT ANTERIOR SECTION VENOUS RECONSTRUCTION
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donor’s operation
recipient’s operation
Diseased liver(cirrhosis)
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DGLT overcomes the limitation encountered in single graft as the inadequate graft size and the donor risk, by
implanting two suboptimal partial grafts into one recipient – S.G. Lee
Dual graft liver transplantation
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2) SPLIT LT
In situ splitting provides two grafts of optimal quality
that can be applied to the entire spectrum of transplant
recipients: it is the method of choice for
expanding the cadaver liver donor
pool*
*Busuttil RW, Goss JA. Ann Surg. 1999;229:313-321
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SURGICAL
TECHNIQUES
EX-VIVO
IN-SITU
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SPLITTING ON THE “BACK-TABLE”SPLITTING ON THE “BACK-TABLE”
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IN-VIVO TECHNIQUEIN-VIVO TECHNIQUE
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• = transplantation of a liver from a marginal donor with hereditary metabolic disease (who receives another LT) to a marginal recipient (i.e. with cirrhosis and hepatocellular carcinoma)
•Familial amyloidotic polyneuropathy•Familial oxaluria•Familial hypercholesterolemia
3) DOMINO LT
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Patient withfamilial
hypercholesterolemia
Child with glycogenosis
Patient with hepatocellular carcinoma and
cirrhosis
domino
split
split
The liver of a patient with hereditary familial hypercholesterolemia The liver of a patient with hereditary familial hypercholesterolemia was transplanted to a was transplanted to a marginal recipientmarginal recipient with hepatocellular with hepatocellular
carcinomacarcinoma andand cirrhosis („domino transplantation”)cirrhosis („domino transplantation”)
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Transplant cardiac
• Indicatii – Cardiomiopatia idiopatica (dilatativa,
obstructiva, restrictiva);– Cardiopatia ischemica;– Valvulopatii– Defecte congenitale
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Tehnica operatorieAnastomoze:
AS donator cu AS primitor;
AD donator cu ad primitor
Aorta donator-aorta primitor
A pulmonara donator – a pulmonara primitor
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Transplantul combinat cord-pulmon
• Indicatii:– Afectiuni cardio-pulmonare terminale;– Hipertensiunea pulmonara;– Complexul Eisenemenger;– Mucoviscidoza.
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Transplantul de intestin subtire
• Indicatie:– Sindrommul de intestin scurt
• Congenital• Dobandit
Anastomoza proximala – duodenojenunala
Ileostoma terminala
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Transplantul pancreatic• Integral• Celular• Indicatia principala – diabetul zaharat tip I• Transplant
– simultan cu cel renal – dupa cel renal – singular “alone”
• Drenajul secretiei endocrine (portal)– Sistemic– Portal
• Drenaj secretiei exocrine– Enteral– vezical
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Tx de pancreas si rinichi
Drenaj exocrin enteral
Drenaj endocrin sistemic
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Tx pancreatic integral
Drenaj exocrin vezical
Drenaj endocrin sistemic
Rata “insulin-free”
- 80% la un un an
- 50% la 2 ani
- 10% la 5 ani.
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Transplantul cu insule pancreatice
• Necesita 3-4 donatori
• Injectare in vena porta
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Rezultate Tx de organe
Tip TxTip Tx SupravietuirSupravietuire 1 ane 1 an
Supravietuire 5 Supravietuire 5 aniani
rinichirinichi 80-85%80-85% 65%65%
ficatficat 85-90%85-90% 75%75%
cordcord 81%81% 69%69%
Cord-Cord-pulmonpulmon
70%70% 60%60%
Pancreas Pancreas 87%87% 56%56%