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Cadaveric Liver
Transplantation - Where do
‘we’ stand Today
Dr. Rajasekhar Perumalla
MS, FRCS
Senior Consultant Transplant Surgeon
SIMS (SRM Institute of Medical Sciences)
Vadapalani
Chennai
Important milestones in transplantation
Dr.Thomas Starzl
1963- Denver, Colarado,US
• INTRODUCTION OF CYCLOSPORINE
A –
JEAN BOREL
• SIR ROY CALNE – CAMBRIDGE
UNIVERSITY
Initial results
130 LTX by 1970, 12 alive in 1976
Scope for improvement
Transplant scenario in India
 Brain Death and deceased donor organ donation is
legal - Human Organ transplantation Act 1994
 Liver transplant - First DDLT - 1998
First LDLT - 1999 (Paediatric)
First LDLT - 2000 (Adult)
Transplants Oct 2008 to Jan
2015
 Donors From TN 587
 Heart 116
 Lung 50
 Liver 542
 Kidney 1052
 Pancreas 4
 Small Bowel 1
 Total Major organs 1765
 Heart Valve 566
 Cornea 886
 Skin 13

Total Organs 3231
Liver transplant - survival
 1 year survival - 88- 90%
 2 year survival - 80- 85%
 5 Year survival - 70- 75%
Complication rate – 10- 15%
Artery, Bile duct, Infection, rejection
Improved outcomes
 Patient selection
 Organ preservation
 Refined surgery & anaesthesia
 Immunosuppression
 Early recognition of complications &
management
Prognostic Models
 CTP Score
 MELD score
Importance of HCC screening in Cirrhotics
6 monthly AFP and Ultrasound
Deceased Donor Vs Living Donor
– Which to offer and when?
 Time available for the Recipient -
Stable – Can wait
Stable – not ideal to wait
Unstable
Donor
 Deceased donor
1. Brain Dead Donor
2. DCD (Donation after cardiac death)
 Organ preservation time
Liver – 12 -24 hrs
 Whole organ / Reduced graft / Split
Organ harvesting /Procurement
 Laparotomy/Asessment
 Aortic cannulation
 Portal cannulation
 Goal: Cool the organs and perfuse with
preservative solution (HTK (Custodial)
UW (Belzer) while exsanguinating the
organs
Cold Ischemia Time
 Retrieval of liver following clamping the Aorta
 Packaging and Transport
 Recipient Hepatectomy
 Implantation of New Liver –
 Vena Caval anastomosis,
 Portal Vein Anastomosis,
 Reperfusion
TOTAL TIME 6 – 12 hrs.
Always a race against Time!
Selection
 Selection of transplant type depends on
 Organ availability
 ABO match
 Physical size (HT, WT, Abdominal girth)
 Medical condition - MELD, CTP score)
 Age match – Donor / Recipient
 DDLT preferred in a recipient
 High BMI
 Portal vein thrombosis
 Re-transplantation
 Sick recipients
 In India: organ shortage
DDLT- Is there a need for
Speed?
 Keys to a safe and quick transplant
 Prepare well - Know your patient, review the case
history, diagnosis & Lab values.
 Review the CT scan & Know the anatomy
 Start slowly, progress gradually with careful
mobilisation of liver & no traction
 Ensure haemostasis at every step
 DDLT is usually faster
 Implantation is less complex & quicker
 DDLT  Emergency - Race against time to CIT
Recipient hepatectomy
Level of dissection
High ligation of the hilar
structures: Arteries and bile
ducts
Beware of vascular intimal
dissection
LDLT- High ligation of
structures
Cava preserving hepatectomy
 Preferred
technique
 Avoids caval
clamping
 Could be avoided
in select DDLT
cases.
Veno venous bypass
Difficult hepatectomy
Caudate lobe hypertrophy
Severe portal hypertension
Volume overload- Tissue oedema
Retransplantation
Previous upper abdominal surgery
Abdominal cocoon
Temporary porto caval shunt
Belghiti et al
Difficult recipient
hepatectomy
Training period
No portal hypertension
 Acute liver failure
 Non cirrhotic
Implantation - Classic technique
Hepatic vein implantation
DDLT
 Piggyback technique
 Preferred
 Single cava anastamosis
 Cavacavoplasty
 Side to side cavo-caval
 Caval replacement
 Budd chiari syndrome
 Massive caudate lobe
 Retransplantation
LDLT
 Multiple veins to be
drained
 RHV in right lobe grafts
 Seg 5/8/ IRHV
reconstruction
Caval anastomosis –
“pyggy-back” technique
Caval anastomosis –
Belghiti technique
Final aspect of anastomoses
1. Hepatectomy – can sometimes be the toughest
2. Anhepatic Phase – Major role for Anesthesiologist
3. Reperfusion – “ Anesthesia- watch for Toxin release to
the heart , Surgeons - Watch for golden bile”
Good graft function
 Haemodynamic stability
 Awakening from anesthesia
 Clearence of lactate
 Resolution of hypoglycemia
 Normalisation of coagulation profile
 Resolution of elevated transaminases
 Bile (Golden) production on the table
Uncomplicated post op period
 Stable Haemodynamics- Minimum to no
inotropes
 Patient wakes up - 1- 2 hrs.
 Acid base balance
 Extubation – 4-6 hrs.
 Doppler – day 1
 Out of ICU to wards
 Diet – NE feeds 6 hrs. to 12 hrs.
 OUT OF HOSPITAL – 10 -14 days
Factors? : Immediate outcome
 Graft selection / Graft quality
 Organ preservation
 Warm & cold ischaemia times
 Donor – Recipient matching
 Surgical & Medical problems
Post Op Care –
MULTI-FACETED APPROACH
 FLUID AND
ELECTROLYTE BALANCE
 RESPIRATORY STATUS
 RENAL FUNCTION – RRT
 INFECTION CONTROL
 IMMUNO-SUPPRESSION
 IMAGING ALL THE
‘PLUMBING’
Early complications
 Primary Non Function of Graft (2%)
 Delayed Graft Function
 Technical (Arterial, bile duct) 10- 12%
 Acute Rejection
 Infection
Post Transplant Phase - PNF
 Age
 Electrolyte imbalance
 Inotropes
 Prolonged ICU stay
 CIT
 PNF Prevention
 Careful management of donor
Long Term Complications
 Recurrence of primary disease
 Metabolic complications –
 Hypertension
 Renal failure
 Dyslipidemia
 PTDM (Immunosuppression related)
 Malignancy- PTLD, Skin tumors
Care of Transplant Patient
Primary Care physician
Hepatologist
Transplant Team
Expansion of the Organ Donor
Pool
 Improving results
 Increasing demand
 Scanty resource
 Decrease the waiting list mortality
 Efforts are on to expand the pool
Future?
 ORGAN SUPPLY – “Political”
 Opting out system (Spanish model)
 Infrastructure? ITU beds
 ORGAN SUPPLY – Surgical
 Using marginal grafts
 Resuscitation of grafts

Ischaemic preconditioning

Avoidance of cold ischaemia
 Fewer technical complications
 Split liver for 2 adults
Future?
The First Split & Auxiliary Liver Transplant in India was performed by Prof Mohamed Rela and
his team to save the lives of two different individuals.
Ms. Himani Koshala and Ms. Kamala Bulledulla
1919thth
September 2009September 2009
Split the liver graft for 2 adult recipients
Ex-situ Split Liver Transplantation
King’s College Hospital – Survival data
n 1 yr 3 yr 5 yr
 Overall patient survival 256 87% 84% 84%
 Patient survival – LLS 140 90% 88% 88%
 Patient survival – RL 116 85% 81% 80%
Results of Ex-situ
Split Liver Transplantation
Author Year Number Age group Technique Patient Graft
Survival % Survival %
Broelsch et al 1990 30 Adults Ex situ 67 55
Otte et al 1995 29 Mixed Ex situ 79 69
De Ville et al 1995 96 Mixed Ex situ 71 64
Azoulay et al 1995 27 Mixed Ex situ 79 79
Rela et al 1998 41 Mixed Ex situ 90 88
Mirza et al 1998 24 Mixed Ex situ 78 68
Reyes et al 2000 12 Paediatric Ex situ 64 45
13 Adult Ex situ 83 -
Azoulay et al 2001 34 Adult Ex situ 88 (LLS) 74 (RL)
Kings 2001 156 Mixed Ex Situ 88.6 88
Biliary anatomy of Caudate Lobe
Marginal Donor
 Definition
 Organs considered unsuitable for
transplantation are currently being used.
 New Terminology
 “Marginal” donor,
 “Expanded” donor
 “Extended criteria” donor
Marginal Donor
 Older donors
 Diabetes mellitus
 Hypertension
 Renal insufficiency
 Selected cases

Hepatitis B & C

HIV
Marginal Donor-
Disadvantages
 risk of delayed graft function
 Primary non function (PNF)
Assessment Extended Criteria Donor
 Donor age and history
 Donor haemodynamics
 Donor Anatomy
 Donor liver Biopsy
 Pump parameters
 Recipient selection important
Steatotic graft
 Western population: steatosis is prevalent in
30 to 70% of people
 Most common type of ‘‘extended criteria’’
organs
 Problems – depending on severity of steatosis
  Primary/delayed function
 Post transplant complications
 Poor long-term outcomes ??
Nocito A, et al. J Hepatol 2006;45:494–499
Steatotic Graft - Assessment
 Assessment
 Visual inspection and palpation
 Biopsy – Two cores from the right and left liver were
regarded to best predict overall liver histological
characteristics
 Frozen section may overestimate
Hepatic Steatosis
 Quantitative evaluation - based on the
percentage of hepatocytes containing cytoplasmic
fat inclusions
 Mild - ≥ 30%
 Moderate - 30 -60%,
 Severe - > 60%
 Fatty infiltration - Two categories
 Macrosteatosis
 Microsteatosis
1
.
Donor Risk Index
 May be acceptable to transplant with up to 60% steatosis
in the graft
McCormack L, et al. Journal of Hepatology 2011; 54: 1055–1062
 Cold ischemic time  5hrs. for grafts with steatosis
 Consider donor < 40 year
 Recipient MELD:
Those with low MELD seem to tolerate steatotic grafts better
Best scenario would be use this for low MELD score recipients
with urgency such as those with HCC
Long term outcome
 Steatotic Graft show a dramatic decrease in fatty
infiltration after LT
 Mechanism – not fully understood
 Factors that negatively affect this reversal of steatosis - donor age
(>50 years) and prolonged cold ischemia time (>12 h)
 Severe macrosteatosis :  Biliary complications
 Steatosis in the liver graft – negative prognostic factor
for HCV recurrence
 Literature is divided on the effect of donor graft steatosis as a
facilitator or stimulator of fibrosis on patients with post-LT HCV
recurrence
Baccarani U, et al. Clin Transplant 2009.
Li J, et al. Transplant Proc 2009;41: 3560–3563.
Future Challenges Ongoing work by the Pioneers
Long Term Complications IMMUNE Tolerance
Ever Increasing Demand Xenotransplantation
LIVER TX– TEAM EFFORT
TX SURGEONS
ANESTHESIOLOGIST
HEPATOLOGIST
INTENSIVIST
SCRUB NURSE
PERFUSIONIST
DIALYSIS TECHNICIANS
BLOOD BANK
PATHOLOGIST
LAB PERSONNEL
TX COORDINATORS
Don’t take your Organs to heaven,
heaven knows we need them here.
Thank you

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Isg chennai march 2015 rajasekar

  • 1. Cadaveric Liver Transplantation - Where do ‘we’ stand Today Dr. Rajasekhar Perumalla MS, FRCS Senior Consultant Transplant Surgeon SIMS (SRM Institute of Medical Sciences) Vadapalani Chennai
  • 2. Important milestones in transplantation Dr.Thomas Starzl 1963- Denver, Colarado,US • INTRODUCTION OF CYCLOSPORINE A – JEAN BOREL • SIR ROY CALNE – CAMBRIDGE UNIVERSITY Initial results 130 LTX by 1970, 12 alive in 1976 Scope for improvement
  • 3. Transplant scenario in India  Brain Death and deceased donor organ donation is legal - Human Organ transplantation Act 1994  Liver transplant - First DDLT - 1998 First LDLT - 1999 (Paediatric) First LDLT - 2000 (Adult)
  • 4. Transplants Oct 2008 to Jan 2015  Donors From TN 587  Heart 116  Lung 50  Liver 542  Kidney 1052  Pancreas 4  Small Bowel 1  Total Major organs 1765  Heart Valve 566  Cornea 886  Skin 13  Total Organs 3231
  • 5. Liver transplant - survival  1 year survival - 88- 90%  2 year survival - 80- 85%  5 Year survival - 70- 75% Complication rate – 10- 15% Artery, Bile duct, Infection, rejection
  • 6. Improved outcomes  Patient selection  Organ preservation  Refined surgery & anaesthesia  Immunosuppression  Early recognition of complications & management
  • 7. Prognostic Models  CTP Score  MELD score
  • 8.
  • 9.
  • 10. Importance of HCC screening in Cirrhotics 6 monthly AFP and Ultrasound
  • 11.
  • 12.
  • 13. Deceased Donor Vs Living Donor – Which to offer and when?  Time available for the Recipient - Stable – Can wait Stable – not ideal to wait Unstable
  • 14. Donor  Deceased donor 1. Brain Dead Donor 2. DCD (Donation after cardiac death)  Organ preservation time Liver – 12 -24 hrs  Whole organ / Reduced graft / Split
  • 15. Organ harvesting /Procurement  Laparotomy/Asessment  Aortic cannulation  Portal cannulation  Goal: Cool the organs and perfuse with preservative solution (HTK (Custodial) UW (Belzer) while exsanguinating the organs
  • 16. Cold Ischemia Time  Retrieval of liver following clamping the Aorta  Packaging and Transport  Recipient Hepatectomy  Implantation of New Liver –  Vena Caval anastomosis,  Portal Vein Anastomosis,  Reperfusion TOTAL TIME 6 – 12 hrs. Always a race against Time!
  • 17. Selection  Selection of transplant type depends on  Organ availability  ABO match  Physical size (HT, WT, Abdominal girth)  Medical condition - MELD, CTP score)  Age match – Donor / Recipient  DDLT preferred in a recipient  High BMI  Portal vein thrombosis  Re-transplantation  Sick recipients  In India: organ shortage
  • 18. DDLT- Is there a need for Speed?  Keys to a safe and quick transplant  Prepare well - Know your patient, review the case history, diagnosis & Lab values.  Review the CT scan & Know the anatomy  Start slowly, progress gradually with careful mobilisation of liver & no traction  Ensure haemostasis at every step  DDLT is usually faster  Implantation is less complex & quicker  DDLT  Emergency - Race against time to CIT
  • 19. Recipient hepatectomy Level of dissection High ligation of the hilar structures: Arteries and bile ducts Beware of vascular intimal dissection LDLT- High ligation of structures
  • 20. Cava preserving hepatectomy  Preferred technique  Avoids caval clamping  Could be avoided in select DDLT cases.
  • 22. Difficult hepatectomy Caudate lobe hypertrophy Severe portal hypertension Volume overload- Tissue oedema Retransplantation Previous upper abdominal surgery Abdominal cocoon
  • 23. Temporary porto caval shunt Belghiti et al Difficult recipient hepatectomy Training period No portal hypertension  Acute liver failure  Non cirrhotic
  • 25. Hepatic vein implantation DDLT  Piggyback technique  Preferred  Single cava anastamosis  Cavacavoplasty  Side to side cavo-caval  Caval replacement  Budd chiari syndrome  Massive caudate lobe  Retransplantation LDLT  Multiple veins to be drained  RHV in right lobe grafts  Seg 5/8/ IRHV reconstruction
  • 28. Final aspect of anastomoses
  • 29. 1. Hepatectomy – can sometimes be the toughest 2. Anhepatic Phase – Major role for Anesthesiologist 3. Reperfusion – “ Anesthesia- watch for Toxin release to the heart , Surgeons - Watch for golden bile”
  • 30. Good graft function  Haemodynamic stability  Awakening from anesthesia  Clearence of lactate  Resolution of hypoglycemia  Normalisation of coagulation profile  Resolution of elevated transaminases  Bile (Golden) production on the table
  • 31. Uncomplicated post op period  Stable Haemodynamics- Minimum to no inotropes  Patient wakes up - 1- 2 hrs.  Acid base balance  Extubation – 4-6 hrs.  Doppler – day 1  Out of ICU to wards  Diet – NE feeds 6 hrs. to 12 hrs.  OUT OF HOSPITAL – 10 -14 days
  • 32. Factors? : Immediate outcome  Graft selection / Graft quality  Organ preservation  Warm & cold ischaemia times  Donor – Recipient matching  Surgical & Medical problems
  • 33. Post Op Care – MULTI-FACETED APPROACH  FLUID AND ELECTROLYTE BALANCE  RESPIRATORY STATUS  RENAL FUNCTION – RRT  INFECTION CONTROL  IMMUNO-SUPPRESSION  IMAGING ALL THE ‘PLUMBING’
  • 34. Early complications  Primary Non Function of Graft (2%)  Delayed Graft Function  Technical (Arterial, bile duct) 10- 12%  Acute Rejection  Infection
  • 35. Post Transplant Phase - PNF  Age  Electrolyte imbalance  Inotropes  Prolonged ICU stay  CIT  PNF Prevention  Careful management of donor
  • 36. Long Term Complications  Recurrence of primary disease  Metabolic complications –  Hypertension  Renal failure  Dyslipidemia  PTDM (Immunosuppression related)  Malignancy- PTLD, Skin tumors
  • 37. Care of Transplant Patient Primary Care physician Hepatologist Transplant Team
  • 38. Expansion of the Organ Donor Pool  Improving results  Increasing demand  Scanty resource  Decrease the waiting list mortality  Efforts are on to expand the pool
  • 39. Future?  ORGAN SUPPLY – “Political”  Opting out system (Spanish model)  Infrastructure? ITU beds
  • 40.  ORGAN SUPPLY – Surgical  Using marginal grafts  Resuscitation of grafts  Ischaemic preconditioning  Avoidance of cold ischaemia  Fewer technical complications  Split liver for 2 adults Future?
  • 41. The First Split & Auxiliary Liver Transplant in India was performed by Prof Mohamed Rela and his team to save the lives of two different individuals. Ms. Himani Koshala and Ms. Kamala Bulledulla 1919thth September 2009September 2009
  • 42. Split the liver graft for 2 adult recipients
  • 43.
  • 44.
  • 45.
  • 46.
  • 47. Ex-situ Split Liver Transplantation King’s College Hospital – Survival data n 1 yr 3 yr 5 yr  Overall patient survival 256 87% 84% 84%  Patient survival – LLS 140 90% 88% 88%  Patient survival – RL 116 85% 81% 80%
  • 48. Results of Ex-situ Split Liver Transplantation Author Year Number Age group Technique Patient Graft Survival % Survival % Broelsch et al 1990 30 Adults Ex situ 67 55 Otte et al 1995 29 Mixed Ex situ 79 69 De Ville et al 1995 96 Mixed Ex situ 71 64 Azoulay et al 1995 27 Mixed Ex situ 79 79 Rela et al 1998 41 Mixed Ex situ 90 88 Mirza et al 1998 24 Mixed Ex situ 78 68 Reyes et al 2000 12 Paediatric Ex situ 64 45 13 Adult Ex situ 83 - Azoulay et al 2001 34 Adult Ex situ 88 (LLS) 74 (RL) Kings 2001 156 Mixed Ex Situ 88.6 88
  • 49.
  • 50. Biliary anatomy of Caudate Lobe
  • 51.
  • 52.
  • 53. Marginal Donor  Definition  Organs considered unsuitable for transplantation are currently being used.  New Terminology  “Marginal” donor,  “Expanded” donor  “Extended criteria” donor
  • 54. Marginal Donor  Older donors  Diabetes mellitus  Hypertension  Renal insufficiency  Selected cases  Hepatitis B & C  HIV
  • 55. Marginal Donor- Disadvantages  risk of delayed graft function  Primary non function (PNF)
  • 56. Assessment Extended Criteria Donor  Donor age and history  Donor haemodynamics  Donor Anatomy  Donor liver Biopsy  Pump parameters  Recipient selection important
  • 57.
  • 58.
  • 59. Steatotic graft  Western population: steatosis is prevalent in 30 to 70% of people  Most common type of ‘‘extended criteria’’ organs  Problems – depending on severity of steatosis   Primary/delayed function  Post transplant complications  Poor long-term outcomes ?? Nocito A, et al. J Hepatol 2006;45:494–499
  • 60. Steatotic Graft - Assessment  Assessment  Visual inspection and palpation  Biopsy – Two cores from the right and left liver were regarded to best predict overall liver histological characteristics  Frozen section may overestimate
  • 61. Hepatic Steatosis  Quantitative evaluation - based on the percentage of hepatocytes containing cytoplasmic fat inclusions  Mild - ≥ 30%  Moderate - 30 -60%,  Severe - > 60%  Fatty infiltration - Two categories  Macrosteatosis  Microsteatosis 1 .
  • 62. Donor Risk Index  May be acceptable to transplant with up to 60% steatosis in the graft McCormack L, et al. Journal of Hepatology 2011; 54: 1055–1062  Cold ischemic time  5hrs. for grafts with steatosis  Consider donor < 40 year  Recipient MELD: Those with low MELD seem to tolerate steatotic grafts better Best scenario would be use this for low MELD score recipients with urgency such as those with HCC
  • 63. Long term outcome  Steatotic Graft show a dramatic decrease in fatty infiltration after LT  Mechanism – not fully understood  Factors that negatively affect this reversal of steatosis - donor age (>50 years) and prolonged cold ischemia time (>12 h)  Severe macrosteatosis :  Biliary complications  Steatosis in the liver graft – negative prognostic factor for HCV recurrence  Literature is divided on the effect of donor graft steatosis as a facilitator or stimulator of fibrosis on patients with post-LT HCV recurrence Baccarani U, et al. Clin Transplant 2009. Li J, et al. Transplant Proc 2009;41: 3560–3563.
  • 64.
  • 65. Future Challenges Ongoing work by the Pioneers Long Term Complications IMMUNE Tolerance Ever Increasing Demand Xenotransplantation
  • 66. LIVER TX– TEAM EFFORT TX SURGEONS ANESTHESIOLOGIST HEPATOLOGIST INTENSIVIST SCRUB NURSE PERFUSIONIST DIALYSIS TECHNICIANS BLOOD BANK PATHOLOGIST LAB PERSONNEL TX COORDINATORS
  • 67. Don’t take your Organs to heaven, heaven knows we need them here. Thank you

Editor's Notes

  1. Good Morning, Respected Chair Persons, Faculty and my dear friends, It gives me great privilege to be amongst such august presence. I sincerely thank the organisers Prof. Mohd. Ali &amp; Dr. Prem Kumar for giving me this opurtunity.
  2. Conventional LTx with total hepatectomy and resection of the recipient retrohepatic inferior vena cava (IVC) and interposition of the donor IVC attached to the new graft was described by Starzl et al. in 1963. In this procedure, during the anhepatic phase, there is a sub- stantial decrease in venous backflow to the heart, causing hemodynamic instability, metabolic alterations, and reduction in renal flow.3
  3. Calne and Williams4 in 1968 reported a technique that was popularized in 1989 by Tzakis et al.5 as the so-called piggyback (PB) technique. This technique includes hepatectomy with preservation of the recipient retrohepatic vena cava to maintain the venous return to the heart, preventing hemodynamic alterations.4,5
  4. n 1992, Belghiti et al.12 developed the modified pig- gyback (MPB) technique, in which, besides the preser- vation of the caval flow by partial IVC clamping during the anhepatic phase, outflow obstruction can be mini- mized by doing a side-to-side cavocaval anastomosis at the anterior face of the recipient IVC. Thereafter, they modified their technique specifically by adding a tem- porary portocaval shunt (PCS) to preserve the portal venous flow in order to reduce the intestinal congestion during the anhepatic phase.15