I want to be a Paediatric Liver Transplant surgeonpaedhpb.org/2017/Friday/I want to be a Paediatric...
Transcript of I want to be a Paediatric Liver Transplant surgeonpaedhpb.org/2017/Friday/I want to be a Paediatric...
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I want to be
a
Paediatric
Liver Transplant surgeon
Dr. Beelke D’hondt
MD ( Belgium), FRC Paed Surg (RSA)
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Overview 1. Historical Steps
2. Knowledge
3. Skills
4. Passion
5. Aim for perfection
6. Outcomes
7. Future perspectives
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Historical Steps • 1963 : Thomas Starzl : first liver transplantation
• 1967 : Thomas Starzl : first successful liver transplantation
• 1968 : Roy Calne : first successful liver transplantation in Europe (DDLT)
• 1979 : FDA approves cyclosporine
• 1983 : National Institutes of Health : consensus conference declares liver
transplantation a valid therapy for ESLD
• 1984 : first reduced-size liver transplantation
• 1987 : UW solution
• 1988 : First split-liver transplant
• 1989 : Tacrolimus introduced into clinical trials
• 1990 : First successful living-related liver transplantation
• 2003 : IGL-1 solution : to replace UW solution
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Recent progress
• Technical development
• Progress in pre-operative management
• Progress in peri- and postoperative management
• Progress in immunosuppression
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Recent progress : pre-operative management
1. Multidisciplinary approach of the sick child
2. Nutritional support
3. Enteral feedings
4. Control of bleeding esophageal varices
5. Correction of ascites
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Recent progress : peri- and postoperative management
1. Anesthesiological expertise of dealing with
extreme sick babies/infants/children
2. Surgeons trained in paediatric surgery
3. Paediatric intensivists with expertise in liver
failure, renal dialysis
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Recent Progress in
immunosuppression
• 1st break through : cyclosporin A + steroids : doubled the 1y patient survival rate
• FK 506 (tacrolimus) with small dosage of prednisolone
• FK 506 + anti-IL-2 receptor monoclonal antibodies: no need for steroids , low incidence of acute rejection
• AIM : prope tolerance, steroid free post PLTX evolution
• Downside: increased risk for infections, malignancies
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KNOWLEDGE
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Indications & Contraindications
of PLTX • Indications
• Relative contra-indications 1. An advanced or partially treated systemic infection 2. Advanced hepatic encephalopathy (grade IV) 3. Severe psychosocial abnormalities. 4. Portal venous thrombosis extending throughout the mesenteric venous system.
• Absolute contra-indications 1. HIV (+) 2. non-resectable extrahepatic malignancy. 3. Uncontrolled systemic sepsis. 4. Irreversible neurological injury 5. Concomitant end-stage organ failure that cannot be corrected by a combined Transplantation
1. Extra-hepatic cholestasis: Biliary atresia
2. Intra-hepatic cholestatic disease : sclerosing cholangitis, Alagille, PFIC
3. Metabolic disease : Cystic fibrosis, a1- anti trypsine deficiency , Wilson’s disease, Crigler-Najjar syndrome,
disorders of the urea cycle, tyrosinemia, inborn errors of the bile acid metabolism, organic acidemia, acid
Lipase defect, oxaluria type I
4. Fulminant hepatic failure
5. Irresectable hepatic malignancy : hepatoblastoma, HCC
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Evaluation of the
transplant patient 1. Confirm indication for PLTX
2. Determine the severity of the disease
3. Consider alternative treatments to Tx
4. Exclude contra-indications to Tx
5. Identify active infections and assess Immunological status of the
child
6. Rule out cardiac malformations that might need to be corrected
before Tx
7. Establish a pre-transplant therapeutic plan : immunizations,
nutritional support, dental care, prevention of drug-induced side
effects
8. Inform parents, and patient, on the transplantation procedure and
the post-transplantation period
9. Evaluate social status and logistic issues
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Teamwork
The Key to success
Is
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Team of Specialists The hospital in which the liver transplant center will be established should have the following departments :
1. Gastro-enterology with endoscopy facility
2. Pediatric/ adult anesthesiology
3. Pediatric/ adult surgery
4. Pediatric/ adult ICU facility
5. Tropical disease
6. Radiology
7. Hematology and blood bank.
8. Pathology.
9. Biochemistry laboratory.
10. Nephrology with hemodialysis and peritoneal dialysis unit.
11. Cardiology
12. Immunology
• Crossmatch
• Monitoring drug level
• Screening antibodies for patients in waiting list
• HLA typing
•
13. Pneumology
14. Psychiatry
15. Physiotherapy
16. Microbiology laboratory
• PCR- EBV
• CMV Antigen
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HOLISTIC APPROACH
Mens sana in corpore sano
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Child = sick kid
• Kiddie with a (congenital) disease
• Malnourished
• Unhappy miserable desperate
• Family member
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Prioritization
• Early 80ies : patient stratification based on
severity of illness & waiting time
• Late 80ies: waiting time no relationship with
mortality, EXCEPT for fulminant liver failure
• need for objective medical criteria score
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PELD score
Pediatric end-stage liver disease score
• Albumin
• Total bilirubin
• INR
• Growth failure
• age (<1y)
• PELD = 4.80[Ln serum bilirubin (mg/dL)] + 18.57[Ln INR] - 6.87[Ln albumin (g/dL)] + 4.36(<1 year old) + 6.67(growth failure)
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PELD score
• Additional PED points for specific risk factors:
hepatopulmonary syndrome, metabolic diseases,
liver tumors
• Unfortunately : PELD score is not a successful
predictor of post-transplant outcome
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SKILLS
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The transplant operation
• Until early 80ies : whole liver transplantation of
donor with weight close to the recipient’s weight
• 50 % mortality due to waiting for the ideal donor
• Development of new techniques changed this
high mortality to a current overall survival rate of
> 90%
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Technical developments
1. Split liver (80ies)
2. Living related liver transplantation : segment 2-
3 in pediatric LTX
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Donor surgery in LDLT
• Standardized technique of segmentectomy
S2&3
• Ethical concern :
• mortality : 1/1000 LD
• Morbidity : 10%
• Strict selection criteria
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Anatomy of the liver
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Recipient surgery
1. Hepatectomy
2. Anhepatic phase
3. Implantation:
1. piggyback anastomosis of the VCI
2. End-to-end running anastomosis of the PV ( portoplasty )
3. End-to-end interrupted anastomosis of the HA
4. Biliairy anastomosis : hepaticojejunostomy
4. 2 abdominal drains
5. Abdominal patch if GRBWR >4M
Check perop patency
with
Duplex-doppler
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Recipient surgery
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Hepatic Dupplex doppler Per- and postoperative hepatic duplex doppler will help in detecting :
- Venous kinking/thrombosis
- Arterial flow problems (RI) : tardus-parvus wave pattern
- Biliairy stricture
Normal = - PV : continuous flow pattern towards the liver w/ mild
velocity variations due to respiration
- IVC & hepatic veins: phasic flow pattern
- Arterial : rapidly systolic upstroke with continuous diastolic flow
- Bile ducts should not be visible
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PASSION
Nothing great in the world has ever
been accomplished without
passion
Georg Wilhelm Friedrich Hegel
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Passion
• Every patient is different, every transplantation is
as starting from scratch
• Teamwork supplies everyone’s fuel
• “Fight” for every patient and their course, with or
without complications
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Early postoperative course
- Primary non-function (rare)
- Vascular complications:
- HAT : 5-18%,
- PVT: 5-10%
- Biliairy complications : 24%
- lateral vs terminal leaks
- Biliary strictures
- calculi
Possible technical complications
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Early postoperative course
• Hyperacte rejection :
• Rare after PLtX
• Minutes to days post PLTX
• Mediated by ABO or preformed anti-HLA AB
• Intravascular thrombosis, intestinal haemorraghe
• Acute rejection : • 20-50 % during first week post PLTX
• T ceel dependent
• May be cell-mediated, antibody-mediated or both
• No imaging modality sensitive or specific to diagnose rejection
• Symptoms : fever, lethargy, anorexia, increased liver enzymes
• Usually reversible with steroids (sliding scale)
Bacterial/viral infections
Rejection
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Late complications
• Most common cause of long-term alograft loss
• Occurs over months/years
• Incidence : 5-10%
• Risk factors :
- previous episode(s) of acute rejection
- poor HLA match
- long warm ischaemia time
- CMV infection
- raised blood lipids
- inadequate immunosuppression
• 2 subtypes: - vanishing bile duct syndrome R/ change IS or re-TX if non-responsive
- progressive ischemic injury of the bile duct re Tx
Chronic rejection
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Post transplant
malignancies
• 4-5% of LDLT recipients will develop a malignant
tumor
• 4-fold increased risk for lymphoma ( non-Hodgkin
lymphoma) compared to normal population
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Drugs
The following drugs must be permanently available in the center :
• Immunosuppressive drugs (Medrol, Solumedrol, Prograf,
Neoral, Cellcept, Rapamune, Zenapax or Simulect)
• Drugs used to treat acute rejection episodes such as
methylprednisolone
• Wisconsin University solution
• Drugs to treat bacterial, viral, and fungal or parasitic infections.
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AIM FOR EXCELLENCE
“ Nothing we had done in advance would
have prepared us for the enormity of the task Thomas Starzl, the puzzle people
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3D bioprinting technology
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Outcome after PLTX • European liver transplantation Registry (1988-2005):
• UNOS :
• SPLIT : 1y patient survival 88%
1y alograft survival 82%
4y patient survival 83%
4y alograft survival 74%
< 2Y old > 2y old
1y patient survival 81% 84%
1y alograft survival 71% 73%
10y patient survival 74% 75%
10 alograft survival 60% 61%
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Outcome after PLTX
• Role of age :
• Survival for infants <1y or <10kg : 65% and 80%--> improved due to technical innovations, better graft preparations
• Role of diagnosis :
• Similar survival rate if metabolic or cholestatic liver disease
• Early survival in acute liver failure and liver tumor group is worse, Long-term survival is similar to those of oter recipients
• PELD score of >20 or deterioration of PELD score before PLTX
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Outcome after PLTX
• Graft-related outcome:
• Inferior when donor age : < 6mo or >60y
• Graft type (whole, reduced, split, LD) : less clear
• In experienced centres : no difference
• In lower volume centres : older patients with LDLT : less favourable outcome
• Severity of patient’s illness @ Tx : most important prognostic factor : PELD>20, severe growth retardation, acute liver failure : significant lower overall survival
• Long-term survival : influenced by consequences of prolonged IS like infection, PTLD, renal inufficiency, hypertension, DM, coronary artery disease.
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Future perspectives
• Hepatocyte stem cell transplantation
• Genetic therapy
• Bio Artificial liver systems
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Conclusion
• Success of liver transplantation is directly related to the strength of the team
• As a surgeon, not only technical skills, but also a broad knowledge of immunosuppression, pathology and psychological insight are of critical value in the holistic approach of the child with ESLD
• A transplant patient is a patient for life, but being allowed a +/- normal life throughout
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THANK YOU